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  • WCLC 2018

    19th World Conference on Lung Cancer

    Access to all presentations that occur during the 19th World Conference on Lung Cancer in Toronto, ON

    Presentation Date(s):  
    • Sept 23 - 26, 2018
    • Total Presentations: 2384

    To review abstracts of the presentations below, narrow down your search by using the Filter options below, and then select the session listing of your choice. Click the "+" for a presentation to expand & view the corresponding Abstract details.

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    PL02 - Presidential Symposium - Top 5 Abstracts (ID 850)

    • Type: Plenary Session
    • Track: Advanced NSCLC
    • Presentations: 11
    • Moderators:
    • Coordinates: 9/25/2018, 08:15 - 09:45, Plenary Hall
      • Abstract
      • Presentation
      • Slides

      Background

      In the global, Phase 3 PACIFIC study (Antonia 2017; NCT02125461), durvalumab significantly improved progression-free survival (PFS) versus placebo in Stage III, unresectable NSCLC patients without progression after chemoradiotherapy (CRT) (stratified HR, 0.52; 95% CI, 0.42–0.65; P<0.001). This was the first major advance in this disease setting for many years. Here we report the second primary endpoint overall survival (OS) for PACIFIC.

      Patients with WHO PS 0/1 (any PD-L1 tumor status) who received ≥2 cycles of platinum-based CRT were randomized (2:1) 1–42 days post-CRT to durvalumab 10 mg/kg IV Q2W or placebo up to 12 months, stratified by age, sex, and smoking history. Primary endpoints were PFS from randomization (blinded independent central review; RECIST v1.1) and OS (interim analysis reported). Secondary endpoints included time to death or distant metastasis (TTDM) and PFS2 (time to second progression) from randomization and safety. Time to first/second subsequent therapy or death (TFST/TSST) were supportive assessments for PFS/PFS2.

      Between May 2014 and April 2016, 713 patients were randomized of whom 709 received treatment (durvalumab, n=473; placebo, n=236). As of March 22, 2018 (data cutoff), median follow-up duration was 25.2 months (range, 0.2–43.1). After discontinuation, 41.0% and 54.0% in the durvalumab and placebo groups received subsequent anticancer therapy; overall, 8.0% and 22.4% received additional immunotherapy. Durvalumab significantly improved OS versus placebo (stratified HR 0.68, 99.73% CI, 0.469–0.997; P=0.00251), with the median not reached (NR; 95% CI, 34.7 months–NR) and 28.7 months (95% CI, 22.9–NR), respectively. Durvalumab improved OS in all pre-specified subgroups. Updated PFS remained similar (stratified HR 0.51, 95% CI, 0.41–0.63), with medians of 17.2 and 5.6 months with durvalumab and placebo, respectively. Durvalumab improved the updated TTDM (stratified HR 0.53, 95% CI, 0.41–0.68), as well as PFS2 (stratified HR 0.58, 95% CI, 0.46–0.73), TFST (stratified HR 0.58, 95% CI, 0.47–0.72) and TSST (stratified HR 0.63, 95% CI, 0.50–0.79). Within the durvalumab and placebo groups, 30.5% and 26.1% had grade 3/4 any-causality AEs, 15.4% and 9.8% discontinued due to AEs, and no new safety signals were identified.

      Durvalumab demonstrated statistically significant and clinically meaningful improvement in OS compared with placebo, supported by secondary endpoints such as PFS2. PACIFIC is the first study to show a survival advantage following CRT in this population, providing compelling evidence for the unprecedented benefit of durvalumab treatment as the standard of care.

      a9ded1e5ce5d75814730bb4caaf49419

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      PL02.02 - Discussant - PL02.01 (ID 14736)

      08:25 - 08:30  |  Presenting Author(s): Everett E Vokes

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      • Abstract
      • Presentation
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      Background

      Brigatinib has robust efficacy in crizotinib-resistant ALK+ NSCLC, exhibiting median progression-free survival (mPFS) of 16.7 months. We report results of the first interim analysis from the ALTA-1L study of brigatinib vs crizotinib in ALK TKI-naive, ALK+ NSCLC (NCT02737501).

      This open-label, multicenter study enrolled patients with stage IIIB/IV ALK+ NSCLC based on local ALK testing (FDA approved/other). Eligible patients had ECOG PS 0–2, ≤1 prior systemic therapy for locally advanced/metastatic NSCLC, and no prior ALK inhibitor. Asymptomatic CNS metastases were allowed. All patients had systematic CNS imaging. Patients were randomized 1:1 to brigatinib 180 mg QD with 7-day lead-in at 90 mg or crizotinib 250 mg BID. Primary endpoint: blinded independent review committee (BIRC)-assessed PFS (RECIST v1.1). Secondary efficacy endpoints included BIRC-assessed objective response rate (ORR), intracranial ORR (iORR), and intracranial PFS (iPFS). Interim analyses were planned at 50% and 75% of planned PFS events (n=198).

      275 patients were randomized (brigatinib/crizotinib, n=137/138); median age (years) 58/60. 26%/27% received prior chemotherapy for advanced disease, and 29%/30% had baseline brain metastases. At data cut-off (19 February 2018), median follow-up brigatinib/crizotinib: 11.0/9.25 months; with 99 PFS events, brigatinib met the prespecified threshold for statistical superiority vs crizotinib in the primary endpoint, BIRC-assessed PFS (HR 0.49, 95% CI 0.33–0.74, log-rank P=0.0007); brigatinib mPFS was not reached (95% CI NR–NR) vs crizotinib 9.8 months (95% CI 9.0–12.9). Investigator-assessed PFS HR 0.45 (95% CI 0.30–0.68), log-rank P=0.0001. Table shows additional efficacy data. Most common treatment-emergent AEs grade ≥3: brigatinib: increased CPK (16.2%), increased lipase (13.2%), hypertension (9.6%); crizotinib: increased ALT (9.5%), AST (5.8%), and lipase (5.1%). Any grade ILD/pneumonitis: brigatinib, 3.7%; crizotinib, 2.2%. Discontinuations due to AE (brigatinib/crizotinib): 11.8%/8.8%.

      Brigatinib showed a statistically and clinically significant improvement in PFS compared with crizotinib in ALK inhibitor–naive ALK+ NSCLC.

      BIRC-Assessed Endpoint, %

      Brigatinib

      (n=137)

      Crizotinib

      (n=138)

      P-Value
      All patients
      ORRa 76 (68–83b) 73 (65–80b)
      Confirmed ORR 71 (62–78b) 60 (51–68b) 0.0678
      With any intracranial CNS metastases
      (n=43) (n=47)
      iORRa 79 (64–90b) 23 (12–38b)
      Confirmed iORR 67 (51–81b) 17 (8–31b) <0.0001
      Median iPFS, months NR (11–NRb) 6 (4–9b)
      1-year iPFS 67 (47–80b) 21 (6–42b)
      HR 0.27 (0.13–0.54) <0.0001c
      With measurable intracranial CNS metastases
      (n=18) (n=21)
      iORRa 83 (59–96b) 33 (15–57b)
      Confirmed iORR 78 (52–94b) 29 (11–52b) 0.0028
      aResponse, ≥1 assessment; b95% CI; cLog-rank.

      a9ded1e5ce5d75814730bb4caaf49419

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      PL02.04 - Discussant - PL02.03 (ID 14737)

      08:40 - 08:45  |  Presenting Author(s): Fiona Blackhall

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PL02.05 - Effects of Volume CT Lung Cancer Screening: Mortality Results of the NELSON Randomised-Controlled Population Based Trial (ID 14722)

      08:45 - 08:55  |  Presenting Author(s): Harry J De Koning  |  Author(s): Carlijn M. Van Der Aalst, Kevin ten Haaf, Matthijs Oudkerk

      • Abstract
      • Presentation
      • Slides

      Abstract

      The NELSON-trial is a population-based RCT using nodule volume management for referral, initiated to show a 25% LC mortality reduction in males at 10-years of follow-up.

      606,409 persons, aged 50-74, in the Netherlands and Leuven were sent a general questionnaire about risk factors, leading to 150,920 responders. 30,959 responders were eligible and invited to participate, of which 15,822 gave informed consent and were randomized (1:1). CT-screening was offered to study arm participants at baseline and 1, 3 and 5.5 years after randomization, whereas no screening was offered to control arm participants. Participant’s records were linked to national registries with 100% coverage regarding cancer diagnosis (Netherlands Cancer Registry), date of death (Centre for Genealogy) and cause of death (Statistics Netherlands). Medical files for deceased lung cancer patients up to 2013 were reviewed by an expert panel (blinded to study arm); cause of death reported by Statistics Netherlands was used thereafter. Follow up to 31.12.2015 comprised a minimum duration of 10 years for 98.7% enrolled (unless deceased). A pre-determined 9-year analysis was also considered due to dilution effects by screening design given growth rate of LC.

      CT screening compliance was 94% on average, leading to a total of 29,736 scans. In 9.1% of the participants additional CT scans within 2 months were performed to estimate nodule Volume Doubling Time, leading to an overall referral rate of 2.1% for suspicious nodules. Detection rates across the rounds varied between 0.8-1.0%, and 69% of screen-detected LC were detected at stage IA or B. 261 lung cancers (52 interval cancers) were detected before the 4th round. In a subset of analyzed patients, surgical treatment was 3 times significantly more prevalent in study LC patients than in control arm patients (67.7% versus 24.5%, p<0,001). In total 934 participants have died in the control arm (NL), versus 904 in the study arm (NL). In the Dutch female enrolled participants, the rate-ratio of dying from lung cancer was 0.73 at 10-years, and 0.58 at 9-years FU.

      The minimum 10-year FU for NELSON has been realized, and full data on incidence, mortality and cause of death are equally available for both arms. A (non- significant) 41.8% lung cancer mortality reduction has been achieved in the small subset of 2,382 Dutch women. Post-hoc analysis shows a 51.4% (p=0.04) LC mortality reduction at 8 years of FU. Data for the full cohort will be presented on behalf of NELSON-investigators.

      e353dbe42c8654f33588d4da0b517469

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      PL02.06 - Discussant - PL02.05 (ID 14738)

      08:55 - 09:00  |  Presenting Author(s): John Kirkpatrick Field

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PL02.07 - IMpower 133: Primary PFS, OS and Safety in a PH1/3 Study of 1L Atezolizumab + Carboplatin + Etoposide in Extensive-Stage SCLC (ID 12892)

      09:00 - 09:10  |  Presenting Author(s): Stephen V Liu  |  Author(s): Aaron S. Mansfield, Aleksandra Szczesna, Libor Havel, Maciej Krzakowski, Maximilian Johannes Hochmair, Florian Huemer, Gyorgy Losonczy, Melissa L. Johnson, Makoto Nishio, Martin Reck, Tony S. Mok, Sivuonthanh Lam, David S. Shames, Juan Liu, Beiying Ding, Fairooz Kabbinavar, Wei Lin, Alan Sandler, Leora Horn

      • Abstract
      • Presentation
      • Slides

      Background

      First-line (1L) standard-of-care treatment for extensive-stage small cell lung cancer (ES-SCLC) is platinum (carboplatin or cisplatin) with etoposide. Despite high initial response rates, there has been limited progress in the last two decades and outcomes remain poor with a median overall survival (OS) of ~10 months. IMpower133 (NCT02763579), a global Phase 1/3, double-blind, randomized, placebo-controlled trial evaluated efficacy and safety of adding atezolizumab, a humanized monoclonal anti–PD-L1 antibody, or placebo to 1L carboplatin and etoposide in ES-SCLC.

      Patients with measurable (RECIST v1.1) ES-SCLC, ECOG performance status 0 or 1, who had not received prior systemic treatment for ES-SCLC were enrolled. PD-L1 immunohistochemical testing was not required. Patients were randomized 1:1 to receive four 21-day cycles of carboplatin (AUC 5 mg/mL/min IV, Day 1) plus etoposide (100 mg/m2 IV, Days 1-3) with either atezolizumab (1200 mg IV, Day 1) or placebo, followed by maintenance therapy with atezolizumab or placebo until intolerable toxicity or progressive disease per RECIST v1.1. Patients meeting predefined criteria could receive treatment beyond progression. Co-primary endpoints were OS and investigator-assessed progression-free survival (PFS). Adverse events (AEs) were graded per NCI-CTCAE v4.0. Blood-based tumor mutation burden (bTMB) was assessed using prespecified cutoffs of ≥16 vs. <16 and ≥10 vs. <10 mutations/Mb.

      In total, 201 patients were randomized to the atezolizumab group, and 202 to the placebo group. Median follow-up was 13.9 months. Median OS was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio [HR] 0.70 [95% confidence interval (CI): 0.54, 0.91; P=0.0069]). Median PFS was 5.2 months and 4.3 months, respectively (HR 0.77 [95% CI: 0.62, 0.96; P=0.017]). OS and PFS benefits were consistent across key patient subgroups. Investigator-assessed confirmed objective response rates were 60.2% and 64.4% in the atezolizumab and placebo groups, respectively; median duration of response, 4.2 and 3.9 months. Exploratory analyses showed OS survival benefits in subgroups above and below prespecified bTMB cutoffs. Grade 3-4 treatment-related AEs were reported in 56.6% vs. 56.1% patients in atezolizumab vs. placebo groups, respectively; serious treatment-related AEs occurred in 22.7% and 18.9% patients, respectively.

      Addition of atezolizumab to carboplatin and etoposide provided a significant improvement in OS and PFS in 1L ES-SCLC in an all-comer patient population. No unexpected safety signals were identified. Atezolizumab plus carboplatin and etoposide may represent a new standard regimen for patients with untreated ES-SCLC.

      a9ded1e5ce5d75814730bb4caaf49419

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      PL02.08 - Discussant - PL02.07 (ID 14739)

      09:10 - 09:15  |  Presenting Author(s): Natasha B Leighl

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      PL02.09 - Nintedanib + Pemetrexed/Cisplatin in Patients with Unresectable MPM: Phase III Results from the LUME-Meso Trial (ID 11192)

      09:15 - 09:25  |  Presenting Author(s): Giorgio Vittorio Scagliotti  |  Author(s): Rabab Gaafar, Anna K. Nowak, Takashi Nakano, Jan Van Meerbeeck, Sanjay Popat, Nicholas Vogelzang, Federica Grosso, Rasha Aboelhassan, Marko Jakopovic, Giovanni L Ceresoli, Paul Taylor, Francisco Orlandi, Dean A Fennell, Silvia Novello, Arnaud Scherpereel, Ute Von Wangenheim, Miyoung Kim, José Barrueco, Anne S. Tsao

      • Abstract
      • Presentation
      • Slides

      Background

      Nintedanib targets VEGFR 1–3, PDGFR α/β, FGFR 1–3, Src and Abl kinases, all implicated in malignant pleural mesothelioma (MPM) pathophysiology. This global Phase II/III, randomised, double-blind study investigated pemetrexed/cisplatin in combination with nintedanib or pemetrexed/cisplatin in combination with placebo, followed by nintedanib or placebo maintenance, in patients with unresectable MPM. In the double-blind, randomised Phase II part, nintedanib plus pemetrexed/cisplatin improved PFS vs placebo (HR=0.56; 95% CI: 0.34–0.91; p=0.017; median 9.4 vs 5.7 months).

      In Phase III, chemotherapy-naïve patients with epithelioid MPM (ECOG PS 0–1) were randomised 1:1 to receive up to six cycles of pemetrexed (500 mg/m2)/cisplatin (75 mg/m2) on Day 1, plus nintedanib (200 mg bid) or matched placebo on Days 2–21. After combination treatment, patients without disease progression received nintedanib or placebo maintenance. The primary endpoint (PFS by investigator assessment) and key secondary endpoint (OS) were planned to be analysed by hierarchical testing, with an interim OS analysis at the time of the primary PFS analysis. PFS was also assessed by independent central review. Based on the assumed treatment effect (HR=0.63), the study had 90% power to detect a statistically significant and clinically meaningful improvement in PFS.

      In total, 458 patients were randomised. Baseline patient characteristics and oncological history were similar between treatment arms. Median duration of nintedanib or placebo administration was 5.3 and 5.1 months, respectively. After 250 events, there was no difference in PFS between nintedanib and placebo arms (HR=1.01; 95% CI: 0.79–1.30; p=0.91; median 6.8 vs 7.0 months, respectively). PFS by central independent review was similar (242 events; HR=0.99; 95% CI: 0.77–1.28; p=0.96; median 6.8 months in each arm). In the interim OS analysis (127 deaths [28% of events]), median OS was 14.4 vs 16.1 months (nintedanib vs placebo; HR=1.12; 95% CI: 0.79–1.58; p=0.54). There were no unexpected safety findings. The proportion of patients with Grade ≥3 AEs was higher with nintedanib than with placebo (72% vs 62%). The most frequently reported Grade ≥3 AE by medical concept in both treatment arms was neutropenia (nintedanib: 32%; placebo: 24%). The proportion of deaths due to serious AEs was 4.0% (nintedanib) and 7.5% (placebo).

      The primary endpoint of the Phase III part of LUME-Meso was not met ‒ Phase II findings were not confirmed. The reported safety profile was consistent with the known safety profiles of nintedanib and pemetrexed/cisplatin.

      a9ded1e5ce5d75814730bb4caaf49419

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      PL02.10 - Discussant - PL02.09 (ID 14740)

      09:25 - 09:30  |  Presenting Author(s): Ross Soo

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    PR02 - Press Conference (ID 1000)

    • Type: Press Conference
    • Track:
    • Presentations: 0
    • Moderators:
    • Coordinates: 9/25/2018, 09:45 - 10:30, Plenary Hall
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    ES02 - Quality Care in Lung Cancer (ID 770)

    • Type: Educational Session
    • Track: Nursing and Allied Professionals
    • Presentations: 6
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 206 BD
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      ES02.01 - Expanding PROs in Daily Practice (ID 11356)

      10:30 - 10:45  |  Presenting Author(s): Kahren White

      • Abstract

      Abstract not provided

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      ES02.02 - PRO: To Medicate: Managing Breathlessness (ID 11357)

      10:45 - 11:00  |  Presenting Author(s): Alexandre Chan

      • Abstract

      Abstract not provided

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      ES02.03 - CON: Not to Medicate: Managing Breathlessness (ID 11358)

      11:00 - 11:15  |  Presenting Author(s): Catherine L Granger

      • Abstract

      Abstract not provided

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      ES02.04 - Molecular Testing 101 for Nurses (ID 11359)

      11:15 - 11:30  |  Presenting Author(s): Beth Eaby-Sandy

      • Abstract

      Abstract not provided

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      ES02.05 - Structured Approach For Developing and Implementing and Advanced Practice Nursing Role in Lung Cancer (ID 11360)

      11:30 - 11:45  |  Presenting Author(s): Andrea Serena  |  Author(s): Solange Peters, Manuela Eicher

      • Abstract

      Abstract not provided

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    GR01 - Thymic Malignancies Tumor Board (ID 777)

    • Type: Grand Rounds Session
    • Track: Thymoma/Other Thoracic Malignancies
    • Presentations: 6
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 206 F
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      GR01.01 - Pathology (ID 11386)

      10:30 - 10:45  |  Presenting Author(s): Anja C Roden

      • Abstract

      Abstract not provided

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      GR01.02 - Surgical Oncology (ID 11387)

      10:45 - 11:00  |  Presenting Author(s): Pier Luigi Filosso  |  Author(s): Enrico Ruffini, Francesco Guerrera, Paolo Olivo Lausi, Paraskevas Lyberis, Alberto Oliaro

      • Abstract

      Abstract not provided

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      GR01.03 - Surgical Oncology (ID 11388)

      11:00 - 11:15  |  Presenting Author(s): David Waller

      • Abstract

      Abstract not provided

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      GR01.04 - Medical Oncology (ID 11389)

      11:15 - 11:30  |  Presenting Author(s): Nicolas Girard

      • Abstract

      Abstract not provided

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      GR01.05 - Radiation Oncology (ID 11390)

      11:30 - 11:45  |  Presenting Author(s): Anthony Brade

      • Abstract

      Abstract not provided

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    MA10 - Considerations in Immunotherapy / Real World (ID 911)

    • Type: Mini Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 12
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 105
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      MA10.01 - Antibiotic Use and PD-1 Inhibitors: Shorter Survival in Lung Cancer, Especially When Given Intravenously. Type of Infection Also Matters (ID 13542)

      10:30 - 10:35  |  Presenting Author(s): Xabier Mielgo-Rubio  |  Author(s): Luis Enrique Chara, Miguel Jhonatan Sotelo-Lezama, Rafael Lopez Castro, Judit Rubio-Martínez, Alejandro Velastegui, Clara Olier-Garate, Sandra Falagan, Isabel Gómez-Barreda, Pilar Bautista-Sanz, Jorge Silva-Ruiz, Juan Moreno Rubio, Cynthia López, Ana Cardeña-Gutiérrez, Elia Pérez-Fernández, María Sereno Moyano

      • Abstract
      • Presentation
      • Slides

      Background

      Some studies found that cancer patients treated with PD-1 immune checkpoint inhibitors (ICI) who receive antibiotics (ATB) had worse efficacy outcomes because ATB can dysregulate gut microbiota. AvaiIable data in NSCLC are contradictory. In addition it’s unknow whether route of administration, type of the ATB and reason for its use, can affect survival outcomes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a multicenter retrospective study. We included consecutive patients with advanced non-small-cell lung cancer (NSCLC) treated with nivolumab or pembrolizumab in second line or beyond between March 2015 and April 2018, from 7 hospitals in Spain. The aim of the study was to evaluate if patients taking ATB 2 months before or within the first month after starting ICI had worse OS, and if OS was affected by the route of administration, type of ATB, and the reason for its use.

      4c3880bb027f159e801041b1021e88e8 Result

      168 patients were evaluated. Median age was 65 years (39-85). 134(79,8%) were male and 121 (72%) had PS>=1. Predominant histologies were adenocarcinoma (50%) and squamous-cell carcinoma (42,9%). 92,3% received nivolumab and 7,7% pembrolizumab. The median number of prior lines was 1 (1-5), median number of cycles 11 (1-68). Median follow: 6,3m. Most were current or former smokers (94,6%). Only 2,9% had driver mutations. PD-L1 was available in 25% (<1%: 36,6%; 1-49%: 39%; >=50%: 24,4%). Response rate (RR) was 30,4%. 47,9% received ATB, 30% of them intravenously and 70% orally. Median PFS and OS were 5,6 months (m) (95%CI, 3,9-7,3) and 11,4 m (95%CI, 9,4-13,5). Patients who received ATB had shorter OS (8,1m (95%CI, 3,6-12,5) vs 11,9m (95%CI 9,1-14,7); p=0,026) and PFS (5m (95%CI,3,1-6,9) vs 7,3m (95%CI,2-12);p=0,028). Those patients receiving ATB intravenously had shorter OS than orally (2,9m (95%CI, 1,6-4,1) vs 14,2m (95%CI, 7,9-20,6); p=0,0001) and shorter PFS (2,2m (95%CI,0,6-3,7) vs 5,9m (95%CI,3,9-8); p=0,001). Patients treated for a lower respiratory tract infection (LRTI) and urinary infection had significantly shorter OS (6m (95%CI2,2-9,7) vs 26m (95%CI, 7,9-44); p=0,006).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results suggest that use of antibiotics (mainly intravenously) has a negative impact on survival outcomes in patients with pretreated advanced NSCLC receiving ICI. To our knowledge, this is the biggest retrospective study evaluating the impact of ATB on the efficacy of ICI in NSCLC patients and the first one evaluating route of administration of ATB. We also found worse outcomes when ATB were administered for low respiratory or urinary tract infection.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA10.02 - Impact of Antibiotics on Outcome of Metastatic Non Small Cell Lung Cancer Patients Treated with Immunotherapy (ID 14021)

      10:35 - 10:40  |  Presenting Author(s): Giulia Galli  |  Author(s): Marta Poggi, Giovanni Fucà, Martina Imbimbo, Claudia Proto, Diego Signorelli, Milena Vitali, Nicoletta Zilembo, Monica Ganzinelli, Filippo De Braud, Marina Chiara Garassino, Giuseppe Lo Russo

      • Abstract
      • Presentation
      • Slides

      Background

      Immunotherapy (IO) is effective against metastatic non small cell lung cancer (mNSCLC). Gut microbioma has a strong impact on immune functions and its imbalance due to antibiotics (atbs) may impair the efficacy of IO. Recent works on other malignancies supported this evidence, but data are still lacking. We studied this topic in a case series of mNSCLC patients (pts) treated with IO.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Data about all consecutive pts with mNSCLC treated with IO at Istituto Nazionale dei Tumori, Milan, Italy, between 04/2013 and 01/2018 were retrospectively collected. Pts were stratified according to atb use between 1 month (mo) before and 3 mos after the beginning of IO, and to atb exposure (AEx) defined as the ratio “days under atb/days under IO”. Survival was estimated with Kaplan-Meier method. Log-rank test was used to compare curves. Multivariate analysis was performed with Cox proportional model.

      4c3880bb027f159e801041b1021e88e8 Result

      One hundred fifty-seven pts were analyzed, for a median follow-up of 28.6 mos. IO consisted in an anti-PD1 agent in 62.4% of cases, in an anti-PDL1 agent in 32.5% of cases, in a combination anti-PDL1+anti-CTLA4 in 5.1% of cases. First-line IO was administered in 25 cases, second-line IO in 66 cases, third- or more advanced-line IO in 66 cases. Twenty-seven pts received atbs. The 3 most commonly used atbs were levofloxacin (55.6%), amoxicillin/clavulanate (25.9%), and ceftriaxone (14.8%). No differences in either response rate, progression free survival (PFS) and overall survival (OS) were observed between the subgroups defined by atb use (p .14, .18 and .24, respectively). Median AEx of the treated pts was 5%. The pts with an AEx longer than the median one had significantly worse PFS (2.2 vs 7.7 mos, p<.0001) and OS (4.9 vs 16.3 mos, p .0004) than the others. This result maintained significance after correction for IO line (p .0003) and performance status (p .0002), which were the only other variables influencing PFS and OS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Though no differences in outcome could be observed in our population according to simple atb use, a significant disadvantage in PFS and OS became evident for pts with a higher AEx. If confirmed, these data may suggest to carefully weigh the prescription of atbs to mNSCLC pts treated with IO.

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      MA10.03 - Plasmatic Evaluation of the Intestinal Barrier and Blood Microbiota, and Antibiotic Use in Non-Small Cell Lung Cancer Patients Treated with Nivolumab (ID 13863)

      10:40 - 10:45  |  Presenting Author(s): Etienne Giroux Leprieur  |  Author(s): Julia Ouaknine, Pierre Helly De Tauriers, Coraline Dumenil, Nathalie Neveux, Jennifer Dumoulin, Violaine Giraud, Sylvie Labrune, Julie Tisserand, Jean-François Emile, Thierry Chinet

      • Abstract
      • Presentation
      • Slides

      Background

      Recent data suggest that gut microbiota and antibiotic use affect the efficacy of immune checkpoint inhibitors. We aimed to evaluate the predictive role of blood microbiota, plasma citrulline (marker of the intestinal barrier), and the impact of early (from 2 months before until 1 month after beginning of nivolumab) and late (after 1 month of nivolumab) antibiotic use on nivolumab efficacy in NSCLC patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We included consecutive patients with advanced NSCLC treated with nivolumab between July 2014 and December 2017. Plasma tests were taken prospectively during treatment. The microbial population present in the plasma samples was determined using sequencing of variable regions of the 16S rRNA bacterial gene at M0. Plasma citrulline concentrations were evaluated by ion exchange chromatography at month (M) 0, M2, M4 and M6 of nivolumab.

      4c3880bb027f159e801041b1021e88e8 Result

      Seventy-two patients were included (male: 62%; smokers: 87%; adenocarcinoma: 63%). Early use of antibiotics (EUA) (n=28/72) was associated with poor overall survival (OS) (median 5.1 months, versus 13.4 months without EUA, p=0.03), whereas later use of antibiotic during treatment had no significant effect. Thirty-six patients (50%) had serial plasma samples available for analyses. The composition of blood microbiota at M0 was associated with tumor response and long-term benefit of nivolumab, with a significant impact of Paludibacilum, Gemmatimonadaceae and Nocardioides. Patients with long-term benefit of nivolumab had significantly higher plasma citrulline concentrations than other patients, at M0, M2 and M4, and maintained high citrulline concentrations at M6. Median progression-free survival (PFS) and OS for patients with citrulline ≥20µM at M0 were 7.9 months and not reached, versus 1.6 months (p<0.0001) and 2.2 months (p<0.0001) for patients with citrulline <20µM, respectively. Patients with EUA had lower median citrulline concentrations at M0 (17µM [IQR 15-30] versus 31µM [IQR 21.3-40.5]; p=0.06).

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study confirms the negative impact of EUA during nivolumab treatment, and suggests that plasma evaluation of the intestinal barrier and blood microbiota may help to predict the outcome of NSCLC patients treated with nivolumab.

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      MA10.04 - Discussant - MA 10.01, MA 10.02, MA 10.03 (ID 14611)

      10:45 - 11:00  |  Presenting Author(s): Bertrand Routy

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA10.05 - Effect of Early Steroids use in Advanced NSCLC Patients Treated with Immunotherapy (ID 14163)

      11:00 - 11:05  |  Presenting Author(s): Giovanni Fucà  |  Author(s): Marta Poggi, Giulia Galli, Martina Imbimbo, Giuseppe Lo Russo, Claudia Proto, Milena Vitali, Monica Ganzinelli, Nicoletta Zilembo, Filippo De Braud, Marina Chiara Garassino, Diego Signorelli

      • Abstract
      • Presentation
      • Slides

      Background

      Immunotherapy (IO) radically improved patients (pts) outcomes in advanced non-small cell lung cancer (NSCLC). Because of their immunosuppressive activity, the use of steroids as supportive care medications or for mild adverse events, even if at anti-inflammatory dosage, is debatable. In this study we assessed the effect of early steroids use on clinical outcomes of pts with advanced NSCLC treated with IO.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively collected demographics, clinical and pathological data of pts with advanced NSCLC treated with IO at our institution with at least one instrumental response assessment. Early use of steroids was defined as the use of a daily prednisone-equivalent dose 10 mg for at least 1 day within 28 days from the start of IO. Chi-square test or Fisher's exact test were used to analyze the association of early use of steroids with pts’ characteristics. The Kaplan-Meier method and the Cox proportional-hazards model were used for survival analyses while the reverse Kaplan-Meier method was used for follow-up quantification.

      4c3880bb027f159e801041b1021e88e8 Result

      We included 151 pts, 35 (23 %) of whom recurred to an early use of steroids. Six pts (4%) received combinatorial PD-L1+CTLA-4 blockade while 145 (96%) received single agent anti PD-1/PD-L1. Early use of steroids was positively associated with ≥2 metastatic sites (OR 3,08, 95% CI 1.33-7.89; P = .01) and ECOG PS 2 (OR 4.57; 95% CI 1.10-20.37; P = .03) and negatively associated with disease control (OR 0,32; 95% CI 0.14-0.71, P = .006). With a median follow-up of 28.61 months, early use of steroids characterized a poorer median OS (4.86 vs 15.14 months; HR 2.60; 95% CI 1.70-4.10; P < .0001). In the multivariable model including the only other covariate significantly associated with survival (ECOG PS), the early use of steroids was confirmed to independently worsen OS (HR 2.38; 95% CI 1.49-3.81; P = .0003). Early use of steroids was also associated with a poorer median progression-free survival (PFS) (1.98 vs 3.94 months; HR 1.80; 95% CI 1.20-2.80; P = .003).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In our analysis, the early use of steroids significantly affected disease control, PFS and OS in advanced NSCLC patients treated with IO. If our findings will be further prospectively confirmed, early use of steroids should be avoided in this setting.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA10.06 - Impact of Immune-Related Adverse Events on Survival in Patients with Advanced Non-Small Cell Lung Cancer Treated with Nivolumab (ID 13039)

      11:05 - 11:10  |  Presenting Author(s): Biagio Ricciuti  |  Author(s): Carlo Genova, Andrea De Giglio, Marta Brambilla, Maria Bassanelli, Maria Giovanna Dal Bello, Sara Baglivo, Giulio Metro, Francesco Grossi, Rita Chiari

      • Abstract
      • Presentation
      • Slides

      Background

      Anti PD1 and anti PD-L1 monoclonal antibodies represent the standard of care for platinum-pretreated advanced non-small cell lung cancer (NSCLC) patients, having shown to prolong survival compared to chemotherapy in second-line setting in phase III clinical trials. Patients treated with these drugs not infrequently experience immune-related adverse events (irAEs), which we hypothesize might reflect antitumor response. In this study we investigated whether the development of irAEs was associated with nivolumab efficacy in patients with advanced NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a multicenter retrospective study of patients with advanced NSCLC treated with nivolumab between October 2013 and September 2017. IrAEs were defined as AEs having immunological basis that required intensive monitoring and interventions. We evaluated nivolumab efficacy according to the development of irAEs.

      4c3880bb027f159e801041b1021e88e8 Result

      Among 195 patients (median [range] age, 63 [30-40] years; 128 men [65.6%], 67 women [34.4%]), irAEs were observed in 85 patients (43.6%), including 15 patients (7.6%) with grade 3 or 4 events. Median PFS was 5.7 months in patients with irAEs compared to 2 months of those without irAEs (P < 0.0001). Median OS was 17.8 months compared to 4.04 months of no-irAEs group (P < 0.0001). The survival benefit of irAEs was consistent also in 12- and 6-weeks landmark analysis. Patients who developed ≥ 2 irAEs (n: 37) had a significantly longer median PFS and OS compared to those with one AE (n: 48) or none (n: 110) (PFS: 8.5 months vs. 4.6 vs. 2, P < 0.0001; OS: 26.8 months vs. 11.9 vs. 4, P < 0.0001). Multivariable analysis revealed that irAEs were positively associated with survival outcome, with hazard ratios of 0.48 (95%CI, 0.34-0.77; P < 0.0001) for PFS and 0.38 (95%CI, 0.26-0.56; P < 0.0001) for OS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This is the largest study conducted to date aimed to evaluate whether the development of irAEs is predictive of nivolumab efficacy in pre-treated NSCLC patients. In this study we confirmed that the development of irAEs was a strong predictor of survival outcomes in NSCLC patients who had received nivolumab in ≥ 2 line setting. This data was consistent in the 12- and 6-weeks landmark analysis, suggesting that an early onset of irAEs might be predictive of durable clinical benefit in NSCLC patients treated with nivolumab. Moreover, patients who experienced ≥ 2 irAEs had a more pronounced survival benefit compared to those with 1 irAE. Further studies are required to investigate the molecular mechanisms underlying this association.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA10.07 - Discussant - MA 10.05, MA 10.06 (ID 14614)

      11:10 - 11:25  |  Presenting Author(s): Kenneth O’byrne

      • Abstract
      • Presentation
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      Abstract not provided

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      MA10.08 - Choice of Taxane and Outcomes in the KEYNOTE-407 Study of Pembrolizumab Plus Chemotherapy for Metastatic Squamous NSCLC (ID 14698)

      11:25 - 11:30  |  Presenting Author(s): Balazs Halmos  |  Author(s): Alexander V Luft, Margarita Majem, Rina Hui, Romain Corre, Mahmut Gümüş, Konstantin Laktionov, Barbara Hermes, İrfan Çiçin, Andrew G Robinson, Terufumi Kato, Ying Cheng, Dariusz Kowalski, Xiaodong Li, Gregory M Lubiniecki, Bilal Piperdi, Luis Paz-Ares

      • Abstract
      • Presentation
      • Slides

      Background

      In the randomized, double-blind, phase 3 KEYNOTE-407 study (NCT02775435), pembrolizumab plus chemotherapy with carboplatin and paclitaxel or nab-paclitaxel significantly prolonged OS (HR 0.64, 95% CI 0.49-0.85, P=0.0008) and PFS (HR 0.56, 95% CI 0.45-0.70, P<0.0001) compared with placebo plus chemotherapy in patients with previously untreated, metastatic squamous NSCLC. The benefit of pembrolizumab plus chemotherapy was observed irrespective of PD-L1 TPS. Pembrolizumab plus chemotherapy also had a manageable safety profile. We performed an exploratory analysis of outcomes by investigator’s choice of paclitaxel or nab-paclitaxel, which was a randomization stratification factor.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      559 eligible patients were randomized 1:1 to pembrolizumab 200 mg or placebo Q3W for up to 35 cycles plus 4 cycles of carboplatin AUC 6 mg/mL/min Q3W and investigator’s choice of paclitaxel 200 mg/m2 Q3W or nab-paclitaxel 100 mg/m2 QW. Primary end points were OS and PFS; ORR and safety were secondary.

      4c3880bb027f159e801041b1021e88e8 Result

      Paclitaxel was the chosen taxane in 60% of patients. The addition of pembrolizumab to chemotherapy improved OS, PFS, and ORR regardless of choice of carboplatin and paclitaxel or carboplatin and nab-paclitaxel (Table). Incidence of grade 3-5 AEs in the pembrolizumab plus chemotherapy arm vs placebo plus chemotherapy arm was 63.9% vs 59.3% in paclitaxel recipients and 78.9% vs 81.4% in nab-paclitaxel recipients. AEs led to discontinuation of all treatment in 13.6% vs 8.4% of paclitaxel recipients and 12.8% vs 3.5% of nab-paclitaxel recipients and led to discontinuation of any treatment in 19.5% vs 13.2% and 29.4% vs 9.7%, respectively. Immune-mediated AEs occurred in 29.6% vs 9.6% of paclitaxel recipients and 27.5% vs 7.1% of nab-paclitaxel recipients.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Adding pembrolizumab to chemotherapy with carboplatin and a taxane improved efficacy and was generally tolerable compared with chemotherapy alone as first-line therapy in patients with metastatic squamous NSCLC regardless of whether paclitaxel or nab-paclitaxel was the chosen taxane.

      Carboplatin plus Paclitaxel Carboplatin plus Nab-Paclitaxel

      Pembrolizumab + Chemotherapy

      N = 169

      Placebo + Chemotherapy

      N = 167

      Pembrolizumab + Chemotherapy

      N = 109

      Placebo + Chemotherapy

      N = 114

      OS, median

      (95% CI), mo

      14.0 (12.6-16.6) 10.3 (8.2-14.8) NR (NE-NE) 12.6 (9.6-NE)
      HR (95% CI)a 0.67 (0.48-0.93) 0.59 (0.36-0.98)

      PFS, median

      (95% CI), mo

      6.4 (6.0-8.3) 4.4 (4.2-5.1) 6.5 (6.2-8.5) 5.9 (4.4-6.9)
      HR (95% CI)a 0.52 (0.40-0.68) 0.65 (0.45-0.94)
      ORR, % (95% CI) 57.4 (49.6-65.0) 37.7 (30.4-45.5) 58.7 (48.9-68.1) 39.5 (30.4-49.1)
      aBased on a Cox regression model with treatment as a covariate.

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      MA10.09 - NECPAL 2: A Multicentre Descriptive Study of Primary and Continuous Attention in Palliative Care in Argentina: Lung Cancer Cohort (ID 12928)

      11:30 - 11:35  |  Presenting Author(s): Carolina Gabay  |  Author(s): Mara Bonet, Monica Castro, Romina Tranier, Sol Sandijian, Silvina De Lellis, Alvaro Sauri, Vilma Tripodoro, Gustavo De Simone

      • Abstract
      • Presentation
      • Slides

      Background

      In Argentina Lung cancer is the most deadly neoplasm (9230 annuals death). Early identification of palliative care (PC) needs has proven benefits in terms of quality of life, survival, and decision making in Lung cancer patients. The NECPAL CCOMS-ICO© tool is face and content-validated instrument to identify patients likely in need of PC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      To implement and evaluate a demonstration multicenter program for early and continuous PC for Lung cancer patients in Buenos Aires using the NECPAL-CCOMS-ICO© tool (multifactorial assessment) in every level of attention. We reported the results of one University Cancer center lung cancer cohort (2016-2018).

      We categorized patients as surprise question positive (SQ+), (Would you be surprised if this patient were to die in the next 12 month?). If the healthcare professional answered ‘NO’, the patient was considered SQ+ and they were also considered NECPAL+ when they presented at least one additional parameter from the NECPAL tool. All patients classified as NECPAL+ were considered to be in need of PC. Then using a Cox regression model analyzed predictors for overall survival (OS).

      4c3880bb027f159e801041b1021e88e8 Result

      82 patients out of 206 were SQ+ and NECPAL +. Median age 64 (35-82). 46 % had stage IVB (8th ) ,18 % IVA , 19.5% locally advanced, and 7 ptes early stage. 6 ptes presented SCLC . Male were 59%. 78 ptes were analyzed for overall survival; n=4 were excluded due lost of follow up. 56% had died with a Median OS of 11 months (7.2-14.7). 5/82 ptes did not receive any kind of oncology treatment due ECOG, comorbidities or patients’ choice. Median OS was 17 months (10.5-23.4) for men and 10 months (3.7-16.2) for females (p=0.08).

      In the univariate analyses, only metastasis in vital organs (nervous central system, liver, massive lung) was predicted of survival (17 vs 8 months; p=0.035). The other NECPAL indicators did not met the criteria for significance.

      The multivariate analysis, did not find a statistically significant combination of predictors for overall survival except metastasis in vital organs. It was noted an small number of low PPS score (11/78), as well as nutritional (14/78) or severe functional deterioration (5/78), in spite of the majority of the cohort had advanced disease.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This Program adds a prospective direct method of measuring prevalence of PC needs including a Palliative approach. The results presented support consideration of the NECPAL tool as a prognostic tool in our setting.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA10.10 - Lung Cancer Stigma: A Ten-Year View of Patient, Provider, and Public Attitudes About Lung Cancer. (ID 13413)

      11:35 - 11:40  |  Presenting Author(s): Jennifer C King  |  Author(s): Maureen Rigney, Lisa Carter-Harris

      • Abstract
      • Presentation
      • Slides

      Background

      The presence of lung cancer stigma is well documented (Chapple, 2004; Chambers, 2012; Marlow, 2015) and impacts the care and treatment of lung cancer survivors (Tod, 2008; Carter-Harris, 2014). In 2008, a large survey of patients, oncologists, and general public revealed that most participants felt lung cancer was principally caused by external factors, was preventable, and lung cancer patients were partly to blame for their illness (Weiss 2014; 2017). We replicated the survey to understand whether perceptions have changed over the last decade.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      1001 members of the general public, 208 lung cancer patients, and 205 oncologists who treat lung cancer were surveyed with the identical instrument as 2008 plus 3-11 questions at the end including Cataldo Lung Cancer Stigma Scale (Cataldo, 2011) strongest-loaded items for the patient survey. The survey was administered by phone and online during summer 2018.

      4c3880bb027f159e801041b1021e88e8 Result

      General lung cancer awareness has significantly improved in a decade with 94% of the public reporting familiarity with lung cancer, every segment reporting increased media visibility (65%, 78%, 85% for public, patients, and oncologists, respectively), and patients reporting significantly increased use of advocacy organizations (39% vs 18%, p<.05). Additionally, significantly more oncologists reported having adequate treatment options to prolong patients’ lives (52% vs 31%, p<.05) and most patients reported satisfaction with medical care (87%) and treatment options (71%).

      Despite these advances, stigma remains a critical problem. In 2018, significantly more of the public believed lung cancer patients are viewed/treated differently than other cancer patients (37% vs 31%, p<.05) and a similar proportion (56%) felt patients are partly to blame for their illness. Oncologists continue to believe there is stigma associated with lung cancer (68%) although more felt stigma was lower for never-smokers. More oncologists indicated patients blame themselves (67% vs 57%). Patients reported significant increases (p<.05) in presence of stigma associated with lung cancer (70% vs. 54%), lung cancer patients being treated differently by society (63% vs. 45%), having personally been treated different by society (43% vs 25%), and loved ones would be more supportive if they had a different type of cancer (25% vs. 11%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      After a decade of lung cancer research progress, results indicate considerably elevated awareness. Unfortunately, disease stigma remains. Interestingly, stigma is reported more frequently by lung cancer patients and may be felt more acutely, perhaps due to increased awareness and empowerment. This work underscores the need to address stigma with proactive multilevel approaches (Hamann, 2018).

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA10.11 - Discussant - MA 10.08, MA 10.09, MA 10.10 (ID 14616)

      11:40 - 11:55  |  Presenting Author(s): Antoinette Wozniak

      • Abstract
      • Presentation
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      Abstract not provided

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    MA11 - Biomarkers of IO Response (ID 912)

    • Type: Mini Oral Abstract Session
    • Track: Immunooncology
    • Presentations: 12
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 203 BD
    • +

      MA11.01 - Comparative Efficacy of T-Cell Intrinsic Versus Extrinsic PD-1 Blockade to Overcome PD-L1+ Tumor-Mediated Exhaustion (ID 14194)

      10:30 - 10:35  |  Presenting Author(s): Jordan Dozier  |  Author(s): Nan Chen, Jasmeen Saini, Navin Chintala, Prasad S. Adusumilli

      • Abstract
      • Presentation
      • Slides

      Background

      Anti-PD-1 agents are effective in overcoming PD-L1+ mediated T-cell exhaustion. Effective therapeutic regimens include multiple, long-term administration. We hypothesized that a single dose of T-cell intrinsic PD-1 blockade by expression of a dominant negative receptor (PD1-DNR) can be equally effective as multiple doses of anti-PD-1 agent administration in the treatment of PD-L1 overexpressing thoracic cancers.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Human T cells engineered to target the cancer-antigen mesothelin (MSLN) by expression of a chimeric antigen receptor (CAR) with or without co-transduction with a PD1-DNR underwent repeated antigen stress with cancer cells with constitutive overexpression of PD-L1. For comparative efficacy evaluation, anti-PD-1 antibody was co-administered with CAR T cells (CARs). In vitro efficacy was evaluated by cytotoxicity (chromium-51 release assay). In vivo, mice with established pleural tumor were treated with either a single dose of MSLN CARs (with and without anti-PD-1 agent) or MSLN PD1-DNR CARs. Tumor burden regression by bioluminescence imaging and median survival were evaluated.

      4c3880bb027f159e801041b1021e88e8 Result

      In vitro, constitutive PD-L1 overexpression (Fig. A) inhibits MSLN CAR effector function as evidenced by a decrease in cytotoxicity following repeated stimulation with MSLN+PD-L1hi tumor cells (Fig B). MSLN PD1-DNR CARs had increased cytotoxicity when compared to MSLN CARs with or without high frequency anti-PD-1 antibody supplementation. In vivo, mice treated with MSLN CAR (with or without anti-PD-1 antibody) or MSLN PD1-DNR CARs demonstrated enhanced tumor regression (Fig C) and prolonged median survival (Fig D) compared to MSLN CARs alone. Furthermore, a single low dose of MSLN PD1-DNR CARs shows equal anti-tumor efficacy compared to MSLN CARs with multiple doses of anti-PD-1 antibody.

      dozier_figure 1.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results demonstrate that CAR T cells engineered to express a cell-intrinsic PD-1 dominant negative receptor overcome PD-L1 mediated T-cell inhibition equally compared to multiple doses of anti-PD-1 antibody administration. A clinical trial with MSLN CAR PD1-DNR CAR T cells is being initiated.

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      MA11.02 - Increased CD3+ TIL Infiltration and Low FOXP3+/CD8+ TIL Ratio Can Predict Anti-PD-1 Therapeutic Response in Non-Small Cell Lung Cancer Patients (ID 12553)

      10:35 - 10:40  |  Presenting Author(s): Hyojin Kim  |  Author(s): Hyun Jung Kwon, Yeon Bi Han, Soo Young Park, Eun Sun Kim, Jin-Haeng Chung

      • Abstract
      • Presentation
      • Slides

      Background

      To determine whether distinct tumor microenvironments differentially affect the clinical response to anti-PD-1 therapy in non-small cell lung cancer (NSCLC), we investigated the expression level of PD-L1 and tumor infiltrating lymphocytes (TILs) and elucidate their predictive role.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Forty pretreated specimens (including 21 resected and 19 biopsied tissues) from 36 advanced, treatment-refractory NSCLC patients who underwent PD-1 blockade therapy were analyzed. PD-L1 expression by tumor cells and the distribution of CD3, CD8, CD4, FOXP3 and PD-1 positive TILs were immunohistochemically assessed. The mean number of cells positive for each marker in covered total fields was expressed in density per mm2 using digital image analyzer. In addition, CD8+/CD3+, CD8+/CD4+, FOXP3+/CD8+, and PD-1+/CD8+ ratios were calculated for each specimen using the mean number of total fields.

      4c3880bb027f159e801041b1021e88e8 Result

      CD3+ and CD8+ TILs were distributed more in PD-L1 positive group compared to PD-L1 negative group. Inversely, EGFR mutant group showed fewer CD3+ TILs than EGFR-naïve group. The patients in the clinical benefit group with PD-1 blockade showed a higher number of CD3+, CD8+ TILs and a higher CD8+/CD3+ TIL ratio (p=0.003, p=0.001, and p =0.042) and a lower FOXP3+/CD8+ TIL ratio compared to non-responders (p=0.001). We analyzed the effects of TIL, PD-L1 and clinicopathologic factors in PD-1 blockade therapeutic response using logistic regression. In multivariate analysis, increased CD3+ TIL infiltration and low FOXP3+/CD8+ TIL ratio were found to be independent predictors of clinical benefit with PD-1 blockade. (p=0.014 and p=0.03, respectively). Using receiver operating characteristic curves, levels of CD3+ TIL and FOXP3+/CD8+ TIL ratio that provide the best distinguishing point between responder versus non-responder to PD-1 blockade were 617.5/mm2 and 25%, respectively (p=0.007 and p=0.003). Considering that 1 mm2 is about 5 high power fields (HPF), a good response to the PD-1 blockade can be expected when CD3 + TIL is observed in 120 per 1 HPF and CD8 + TIL : FOXP3 + TIL are greater than 4 : 1. In addition, there were no difference between sample acquisition method (resection vs. biopsy) and duration (3, 6, and 12 months before PD-1 blockade treatment), and TIL expression.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Based on our results, TIL is an independent predictive factor of response to PD-1 blockade and we suggested a cutoff value of TIL to predict responder group. In addition, properly sampled small biopsy tissue and well preserved archival specimens are feasible to evaluate TIL status.

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      MA11.03 - Interaction of Tumor Infiltrating Lymphocytes and Cancer Nuclei Predicts Response to Nivolumab in Non-Small Cell Lung Cancer (NSCLC) (ID 14143)

      10:40 - 10:45  |  Presenting Author(s): Xiangxue Wang  |  Author(s): Cristian Barrera, Cheng Lu, Vamsidhar Velcheti, Anant Madabhushi

      • Abstract
      • Presentation
      • Slides

      Background

      Immune checkpoint inhibitors, particularly drugs targeting the Programmed death-1 (PD-1) pathway, are promising agents in NSCLC. These drugs however are effective in only a small subset of patients. Programmed death Ligand-1 (PDL1) expression in the tumor predicts response to these agents but is not an optimal biomarker because of spatial and temporal heterogeneity associated with PDL1. PD-L1 is upregulated in response to inflammation in the tumor and strongly correlates with Tumor-infiltrating lymphocytes (TILs). In this work, we evaluated whether quantitative measurements relating to the spatial interplay and arrangement of TILs and cancer nuclei from diagnostic biopsy tissue slide images (H&E) was predictive of response to Nivolumab.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Tumor biopsies of total 82 NSCLC patients previously treated with Nivolumab from two different institutions were employed in this study. The RECIST criteria was used to define response. [vv1] The 492 features characterizing the global interaction of TILs and cancer cells through graph interplay metrics are extracted from tumor regions delineated by two expert pathologists to interrogate the difference of phenotypes. Top 5 features were learnt on learning set by random forest classifier from one institution (n=32) and independently validated on patients from a second site (n=50).

      4c3880bb027f159e801041b1021e88e8 Result

      The most predictive features comprised of difference of characteristic path length between lymphocyte graph and cancer nuclei graph and cosine similarity between lymphocyte node and cancer nuclei node based on their node centrality index. The random forest classifier yielded an area under the receiver operating characteristic curve (AUC) of 0.76 on the training cohort and 0.68 on the validation set (Figure 1).til40.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results showed that quantitative measurements relating to the spatial interplay and arrangement of lymphocyte and cancer nuclei from H&E slide images were predictive of response to Nivolumab in NSCLC. Additional independent multi-site validation of these features is needed.

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      MA11.04 - Discussant - MA 11.01, MA 11.02, MA 11.03 (ID 14619)

      10:45 - 11:00  |  Presenting Author(s): Donald Morris

      • Abstract
      • Presentation
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      Abstract not provided

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      MA11.05 - Indoleamine 2,3-Dioxygenase Expression in Non-Small-Cell Lung Cancer: Analyses of Prevalence, Clinical Correlations and Prognostic Impact (ID 13309)

      11:00 - 11:05  |  Presenting Author(s): Francesco Agustoni  |  Author(s): Hui Yu, Kim Ellison, Derek Smith, Paul Mitchell, Gareth Rivalland, Rafal Dziadziuszko, Dexiang Gao, Kenichi Suda, Shengxiang Ren, Christopher J. Rivard, Charles Caldwell Jr, Leslie Rozeboom, Kristine Brovsky, Diego Cortinovis, Paolo Bidoli, Fred R. Hirsch

      • Abstract
      • Presentation
      • Slides

      Background

      Indoleamine 2,3-dioxygenase-1 (IDO-1) is a cytosolic enzyme involved in the catabolism of tryptophan; IDO-1-related immune suppression is due to decreased tryptophan availability and to the generation of tryptophan metabolites, culminating in substantial suppression of T-lymphocytes. Here we investigate IDO-1 expression in a cohort of non-small-cell lung cancer (NSCLC) specimens, both in tumor cells and in immune infiltrate, with correlation of IDO-1 to PD-L1 expression, clinical patient demographics and outcomes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A cohort of 1.200 NSCLC samples were obtained from 437 patients who underwent surgical lung resections at Austin Health, Melbourne, Australia. IDO-1 expression was evaluated by immunohistochemistry. Correlations were assessed using Spearman and Kendall tests. A Cox proportional hazards (PH) model was used to assess if overall survival (OS) was associated with IDO-1 positivity in univariate and multivariable settings.

      4c3880bb027f159e801041b1021e88e8 Result

      Samples from 437 patients were analyzed for IDO-1 expression, with 111 (25.4%) determined as positive (H-Score 1) and 326 patients (74.6%) as negative (H-Score: 0). IDO-1 expression was determined to be greater in tumor immune infiltrate, with 406 patients (93.8%) determined as positive, while just 27 (6.2%) were IDO-1 negative. There was a significant positive correlation between IDO-1 positive tumor cells and immune cells (0.2167, p < 0.001). Both continuous and binary versions of tumor H-Score showed a significant positive correlation with the amount of tumor immune infiltrate (0.1806 and 0.1698, p < 0.0001, respectively). None of the analyzed variables (age, sex, histology, stage, EGFR, KRAS and PD-L1 status) were found to display a significant correlation with IDO-1 positivity in tumor and immune cells. IDO-1 positivity in tumor cells was found to be significantly associated with OS in the univariate setting and in the multivariable model where variables age, sex, histology, stage, EGFR, KRAS and PD-L1 status were included [P-value = 0.009 and 0.021, respectively; HR: 0.72 (95% CI: 0.55-0.95)]. IDO-1 positivity in immune cells was found to be significantly associated with OS in the univariate setting and was borderline significant in the multivariable model [P-value = 0.006 and 0.053, respectively; HR: 0.798 (95% CI: 0.635-1.003)].

      8eea62084ca7e541d918e823422bd82e Conclusion

      To our knowledge, this is the most extensive analysis of IDO-1 expression in NSCLC patients reported in the literature. Our results suggest the possible prognostic role of IDO-1 expression in tumor and immune cells, highlighting the relevance of IDO-1 detection in tumor tissue. Since new compounds targeting IDO-1 are actually under investigation, the identification of potential prognostic and predictive biomarkers will be needed.

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      MA11.06 - Prognostic Value of Complement System in NSCLC and its Association with PD-1 and PD-L1 Expression (ID 12372)

      11:05 - 11:10  |  Presenting Author(s): Luis M Montuenga  |  Author(s): Daniel Ajona, María José Pajares, Javier Freire, Javier Gomez-Roman, Elena Martinez-Terroba, Sergio Ortiz-Espinosa, Ana Lledo, Elisabeth Arenas-Lazaro, Jackeline Agorreta, Fernando Lecanda, Ruben Pio

      • Abstract
      • Presentation
      • Slides

      Background

      Recent research has unveiled novel molecular mechanisms linking imbalanced complement activation and cancer progression. In this context, complement inhibition has emerged as a treatment option for maximizing the clinical efficacy of current immunotherapies that target the PD-1/PD-L1 immune checkpoint.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Lung cancer tissues were obtained from 140 patients treated by surgery at the Clinica Universidad de Navarra. Inclusion criteria were: NSCLC histology, complete resection of the primary tumor, absence of cancer within the five years previous to the lung cancer surgery, and no treatment with chemo- or radiotherapy prior to surgery. Resected primary lung tumors were fixed in formalin and embedded in paraffin. After antigen retrieval samples were incubated with anti-human C4d, C5aR1, C1q, PD-1 and anti-PD-L1 followed by detection with the Envision system (Dako). Peroxidase activity was visualized with 3,3’-diaminobenzidine. Sections were slightly counterstained with hematoxylin. Two independent and blinded observers calculated an H -score based on intensity and extension of the staining. Survival curves were generated using the Kaplan–Meier method, and statistically significant differences were analyzed with the log rank test.

      4c3880bb027f159e801041b1021e88e8 Result

      Immunohistochemistry of complement proteins in NSCLC was performed for C1q, the target recognition of the complement pathway in NSCLC, C4d, a split product of complement activation, and C5aR1, the complement C5a anaphylatoxin receptor. Immunohistochemical analysis showed positive staining for all these proteins, indicating complement activation in primary lung tumor cells. Importantly, high levels of C1q, C4d, and C5aR1 predict poor disease-free survival (P=0.004; P=0.044; and P=0.02; respectively) and poor overall survival (P=0.031; P=0.022; and P=0.048; respectively) in NSCLC patients. A significant association between PD-1 expression levels in immune cells and disease-free survival was found (P=0.002) but this association was not significant for overall survival. PD-L1 expression levels in both immune cells and tumor cells were not associated with prognosis in NSCLC patients. Interestingly, those patients with high levels of C4d presented a significant decrease of PD-L1 expression in tumor cells (P<0.001) suggesting a link between complement activation and the immune homeostasis of the tumor microenvironment.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Complement activity in primary NSCLC tumors predicts poor prognosis. C4d, a marker of complement activation, is associated with low levels of PD-L1 expression in tumor cells. Harnessing complement system as therapeutic target may enhance PD-1/PD-L1 immune checkpoint-based immunotherapies.

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      MA11.07 - Expression of LAG-3 and NY-ESO-1 In Tumor Cells is Promising Biomarker Predicting Durable Clinical Benefit of PD-1 Blockade in Advanced NSCLC (ID 12403)

      11:10 - 11:15  |  Presenting Author(s): Hee Ryeong Jang  |  Author(s): Se Hyun Kim, Kyoung Jin Suh, Yu Jung Kim, Mi So Kim, Bhumsuk Keam, Tae Min Kim, Jin-Haeng Chung, Dong-Wan Kim, Dae Seog Heo, Jong-Seok Lee

      • Abstract
      • Presentation
      • Slides

      Background

      Anti-PD-1 antibodies are currently used in treating advanced non-small cell lung cancer (NSCLC). PD-L1 expression in tumor cell or immune cell is the only available predictive biomarker in the clinic. Lymphocyte activation gene-3 (LAG-3) is an inhibitory checkpoint in immune cells and NY-ESO-1 is an antigen expressed in tumor cells. We investigated LAG-3 and NY-ESO-1 protein expression and its relationship to response to anti-PD-1 therapy in NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed the medical records of 38 patients with advanced NSCLC who were enrolled in prospective clinical trials of nivolumab or pembrolizumab monotherapy (NCT01295827, NCT01905657, and NCT02175017) between October 2013 and April 2016 at Seoul National University Hospital and Seoul National University Bundang Hospital. Immunohistochemial staining (IHC) of NY-ESO-1(E978, Invitrogen), and PD-L1 (22C3, Dako) in tumor cell and LAG-3(EPR4392, Abcam) in immune cell was performed to determine protein expression.

      4c3880bb027f159e801041b1021e88e8 Result

      LAG-3 and NY-ESO-1 protein expression were assessed in 38 patients. LAG-3, NY-ESO-1 and PD-L1 were expressed in 76.3% (29/38), 50% (19/38) and 18.5% (7/36, 50% cut-off value), respectively. Sixteen patients with durable clinical benefit (DCB, anti-PD-1 therapy more than 6-month) were grouped as responder. NY-ESO-1 expression (DCB 11/19 vs 5/19, p= .05) and LAG-3 expression (DCB 16/29 vs 0/9, p= .003) were significantly correlated with the DCB to Anti-PD-1 therapy, while PD-L1 expression was identified in 5 patients with DCB (5/7 vs 11/29, p= .12). Patients with both NY-ESO-1 and LAG-3 expression had high rate of DCB (73.3%, 11/15 pts). With the results of the interaction with DCB, the calculation of positive predictive value and negative predictive value about durable clinical benefit is assessed and the significance of each measurement was proven by Fisher’s exact test. As a result, NPV of LAG-3 expression in tumor cell was 100% and PPV of each protein expression was LAG-3 (55.17%), NY-ESO-1(57.89%) and PD-L1 (71.43%) respectively. In survival analysis, LAG-3 expression was a significant predictor for PFS (HR 0.170; CI 0.066-0.437; p< .0001) and OS (HR 0.250; CI 0.140-0.599; p= .002).

      8eea62084ca7e541d918e823422bd82e Conclusion

      NY-ESO-1 expression on tumor tissue and LAG-3 expression on tumor microenvironment may be useful for identifying advanced NSCLC patients for the treatment of anti-PD-1 therapy. These protein markers seem quite promising and warrant further investigation in large sample size.

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      MA11.08 - Discussant - MA 11.05, MA 11.06, MA 11.07 (ID 14620)

      11:15 - 11:30  |  Presenting Author(s): Erin Schenk

      • Abstract
      • Presentation
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      Abstract not provided

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      MA11.09 - Single-Cell Characterization of the Immunologic Microenvironment in Advanced-Stage, Oncogene-Driven NSCLC (ID 12122)

      11:30 - 11:35  |  Presenting Author(s): Julia Rotow  |  Author(s): Caroline McCoach, Ashley Maynard, David Naeger, Yaron Gesthalter, K Pallav Kolli, Spyros Darmanis, Trever G Bivona, Collin Blakely, Jonathan Weissman

      • Abstract
      • Presentation
      • Slides

      Background

      The immunologic microenvironment in oncogene-driven non-small cell lung cancer (NSCLC) is poorly understood. Despite high initial response rates to tyrosine kinase inhibitors (TKIs) in patients with oncogene-driven NSCLC, responses are incomplete and transient. Furthermore, response rates to subsequent checkpoint inhibitor immunotherapies are very low. Understanding the immunologic microenvironment may facilitate understanding treatment resistance in this population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      From October 2016 to March 2018 we performed single-cell sequencing on 35 tissue samples from 28 patients with NSCLC. Fresh tissue samples were obtained at time of standard of care biopsies and as research sample collections. Single-cell level whole transcriptome RNA sequencing was performed using SmartSeq2. Cells were clustered into distinct cell states on a multi-dimensional gene expression space and visualized using t-distributed stochastic neighbor embedding (t-SNE) for further dimensionality reduction. Cellular identities for each cluster were established by examining the enrichment of known cell-type specific genes across all distinct clusters.

      4c3880bb027f159e801041b1021e88e8 Result

      Tumor samples were obtained from predominantly stage IV lung adenocarcinoma (90.6%) harboring an oncogenic driver (EGFR-mutant 50%, ALK-rearranged 21.9%, BRAF V600E 9.4%, ROS1-rearranged 9.4%, MET exon 14 skipping 6.3%, and KRAS-mutant 3.1%). Samples were collected prior to treatment (21.9%), during treatment (46.9%), and at disease progression on therapy (31.3%). All patients with a targetable oncogenic driver received a standard of care TKI and the KRAS-mutant patient received pembrolizumab monotherapy. A total of 6048 cells were isolated, including 3457 immune cells, with an average of one million reads and 2500 genes per cell. The immunologic microenvironment (average 108 immune cells/sample) included macrophages/monocytes (33% of cells), T cells (31.9%), and B cells (11.6%), as well as a smaller fraction (<10%) of dendritic cells, Langerhans cells, mast cells, neutrophils, and NK cells. Unbiased gene expression-based subclustering of T cells identified 7 distinct T cell populations, including naïve (22.6%), cytotoxic and/or memory T cells (44.1%), and T regulatory cells (5.6%), as well as 6 tumor-associated macrophage populations with distinct gene expression patterns.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Single-cell RNA sequencing to identify immune cell populations is feasible in advanced-stage NSCLC biopsy specimens across multiple time points during treatment. Here, we describe the heterogeneity of infiltrating immune cell phenotypes including T cell and macrophage subtypes. An improved understanding of the immunologic microenvironment in oncogene-driven NSCLC may facilitate patient selection for immunotherapy treatment and aid in the rational design of alternative or combination immunotherapy strategies for a patient population rarely responsive to current immunotherapeutic agents.

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      MA11.10 - Identification of Mismatch Repair Deficient Lung Adenocarcinomas Using Targeted Next-Generation Sequencing (ID 12439)

      11:35 - 11:40  |  Presenting Author(s): Navin Rajput Mahadevan  |  Author(s): Priyanka Shivadasani, Jonathan Nowak, Mark M. Awad, Lynette M Sholl

      • Abstract
      • Presentation
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      Background

      Mismatch repair (MMR) deficiency/microsatellite instability (MSI) results from the inactivation of DNA mismatch repair proteins. Due to the defect in DNA repair, MMR-deficient (D) tumors display an elevated tumor mutation burden (TMB) and a characteristic increase in small insertions/deletions within homopolymer tracts (“homopolymer indels”), a signature that can be detected using next generation sequencing methods. MMR-D/MSI predicts response to immune oncology (IO) agents (Le et al., 2017) and is an approved biomarker for pembrolizumab therapy in the relapse setting irrespective of histologic diagnosis. In this study, we retrospectively analyzed a large cohort of non-small cell lung carcinomas using targeted next generation sequencing to examine the prevalence and clinicopathologic associations of MMR-D in this tumor type.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      TMB and MSI status was derived from a 309-447 gene targeted next generation sequencing panel (OncoPanel) using an internally validated method (Nowak et al., 2017), that relies on an empirically defined homopolymer indel cutoff of >=1.52/Mb to identify candidate MMR-D tumors. MMR/MSI status was confirmed using MSI PCR (5 marker panel) and/or immunohistochemistry (IHC) for MLH1, PMS2, MSH2, and MSH6. When indicated, MLH1 promoter methylation status was evaluated by methylation-specific PCR.

      4c3880bb027f159e801041b1021e88e8 Result

      2242 lung tumors, including 1835 non-squamous non-small cell lung carcinomas (NSCLC), were interrogated. A total of three lung tumors (all adenocarcinoma) with confirmed MSI/MMR-D by orthogonal methods were identified, for a prevalence of 0.1% of all lung tumors and 0.2% of non-squamous NSCLC. The TMB of these tumors averaged 42.5 mutations/Mb with 7-10 homopolymer indels /Mb. All three tumors showed loss of MLH1 and PMS2 staining by IHC; two cases had somatic loss-of-function MLH1 variants and one showed MLH1 promoter methylation. All were from female patients whose mean age was 68 years (range: 53-83). All showed a poorly-differentiated histology with moderate to brisk lymphoid infiltrates. One patient was a never-smoker; her tumor had a concomitant EML4-ALK rearrangement. The other two patients had moderate/heavy smoking histories (12.5-80 pack-years) both showed RASA1 and NF1 inactivating mutations. One tumor evolved in the context of usual interstitial pneumonia.

      8eea62084ca7e541d918e823422bd82e Conclusion

      MMR-D is very rare in lung tumors, where it appears to arise as somatic event and is enriched in adenocarcinoma. MMR-D may coexist with other relatively uncommon driver alterations, including those not traditionally associated with IO response. Additional investigation is needed to determine if MMR-D confers sensitivity to IO in lung carcinomas.

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      MA11.11 - Discrepancy of Tumor Neoantigen Burden Between Primary Lesions and Matched Metastases in Lung Cancer (ID 12289)

      11:40 - 11:45  |  Presenting Author(s): Tao Jiang  |  Author(s): Caicun Zhou

      • Abstract
      • Presentation
      • Slides

      Background

      Personalized vaccine based on tumor neoantigens showed the striking antitumor effect on several solid tumors, suggesting its significant and potential role in curing cancer. However, whether tumor neoantigens identified from primary lesions were similar to their matched metastases remain unknown. Here, we aimed to compare the tumor neoantigen burden (TNB) between primary lesions and matched metastases in lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Primary lung cancers, matched metastatic sites and peripheral blood (10 mL, EDTA) were collected before any systemic therapy as part of the standard clinical care. Genomic DNA was extracted from all included samples. The matched peripheral blood leukocytes were used as the source for germline DNA control. DNA libraries were subjected to whole-exome capture and then sequenced on an Illumina HiSeq X-TEN platform. The criteria for tumor neoantigen identification were tumor specific mutations (missense, frameshift, inframe insertion or deletions), fold change > 10, high predicted affinity (IC50 < 500 nM) and predicted peptide of 9-10 amino acids in length.

      4c3880bb027f159e801041b1021e88e8 Result

      Totally, 14 cases with matched lung primary lesions and metastases were enrolled, including 10 patients with liver metastases and 4 with brain metastases. A wide range of TNB were identified in both primary lesions (median 157, range 21-1156) and metastases (median 135, range 35-1902). We observed a large discrepancy of TNB between primary lesions and matched metastases, with a median unique percentage of 82.20% (74.03%-95.24%) in primary lesions and 84.50% (77.45%-97.14%) in metastases. In patients with brain metastases, primary lesions had a percentage of 90.98% (79.57%-95.24%) unique tumor neoantigens, while metastases had 86.03% (77.45%-97.14%). For those with liver metastases, the median unique percentage of tumor neoantigens was 80.58% (74.03%-88.66%) in primary lesions and 83.35% (78.49%-91.14%) in metastases. Smoking history and histological types had no impact on the discrepancy of TNB (P > 0.05, P > 0.05; respectively). TNB of primary lesions was similar to matched metastases (P = 0.733). However, primary lesions of brain metastases had a significantly higher percentage of unique tumor neoantigen than that of liver metastases (P = 0.025).

      8eea62084ca7e541d918e823422bd82e Conclusion

      There is a large percentage of different tumor neoantigens between primary lesions and matched metastases in lung cancer. Whether this discrepancy could affect the efficacy of following personalized vaccine on primary lesions or matched metastases need further investigation.

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      MA11.12 - Discussant - MA 11.09, MA 11.10, MA 11.11 (ID 14621)

      11:45 - 12:00  |  Presenting Author(s): Ignacio Gil-Bazo

      • Abstract
      • Presentation
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      Abstract not provided

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    MA12 - Mesothelioma Surgery and Novel Targets for Prognosis and Therapy (ID 913)

    • Type: Mini Oral Abstract Session
    • Track: Mesothelioma
    • Presentations: 12
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 202 BD
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      MA12.01 - The Information Pathway to Randomisation: Patients Experience of the Mesothelioma and Radical Surgery (MARS2) Feasibility Trial (ID 11200)

      10:30 - 10:35  |  Presenting Author(s): Angela Mary Tod  |  Author(s): Clare Warnock, Karen Lord, Liz Darlison

      • Abstract
      • Presentation
      • Slides

      Background

      The Mesothelioma and Radical Surgery 2 (MARS 2) trial was established in the UK to evaluate the role of radical surgery, (Pleurectomy decortication), for the treatment of malignant pleural mesothelioma (MPM). It compares chemotherapy and surgery to chemotherapy alone. The feasibility trial included a nested qualitative sub-study. The sub study aimed to 1) understand the patient experience of MARS2 trial process and interventions and 2) Identify any information and support needs required by patients. We present here the results related to MARS2 participant’s information experiences and needs at the point of randomisation. Implications for information provision to enhance patient experience and overcome recruitment barriers1 within MPM trials are considered.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      41 in-depth longitudinal qualitative methods were used with 15 participants following randomisation. 9 participants received chemotherapy and surgery and 6 received chemotherapy alone. Interviews were conducted following randomisation, and at 6 and 12 months after the initial interviews. Participants randomised to surgery also had an interview after post-operative discharge. Data was collected between August 2015 and March 2017 and analysed using Framework analysis2

      4c3880bb027f159e801041b1021e88e8 Result

      The findings provide insight into the challenging context within which potential participants have to assimilate knowledge about a trial such as MARS2. Prior to hearing about the trial participants had encountered a diverse range of new and concerning experiences. These included worrying symptoms, diagnostic tests, investigations and the drainage of litres of fluid from the lung. They had to absorb an array of life-changing facts in a short time including that they had a rare incurable cancer with a poor prognosis; their illness was an occupational disease with legal and financial implications due to asbestos exposure. Participants attended their trial consultation soon after this challenging diagnostic information provision. The study reveals variations in understanding of the trial procedures, specifically decision-making regarding treatments, equipoise and the process of randomisation. Motivations for participating in the trial were identified along with preferences for information formats.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study provides unique insight into the information pathway of MPM trail participants, from diagnosis to randomisation. Results suggest that improvements in presentation of trial information and the development of formats that can be tailored to individual needs and preferred ways of learning, many enhance experience of and recruitment to MPM trials. Working with patients to co-produce information that communicates challenging concepts effectively, (such as randomisation and equipoise), may be a useful approach to meeting this challenge.

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      MA12.02 - Quality of Life Following Pleurectomy Decortication and Extrapleural Pneumonectomy for Pleural Malignant Mesothelioma (ID 12983)

      10:35 - 10:40  |  Presenting Author(s): Wil Lieberman-Cribbin  |  Author(s): Andrea Wolf, Rebecca Schwartz, Raja Flores, Emanuela Taioli

      • Abstract
      • Presentation
      • Slides

      Background

      Few studies have focused on quality of life (QoL) after treatment of malignant pleural mesothelioma (MPM). Questions remain as to which surgical procedure, extrapleural pneumonectomy (EPP) or pleurectomy (P/D), is most effective and results in better outcomes for survival and involves fewer complications. A comprehensive review was conducted on MPM patients to assess differences in QoL following P/D and EPP.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Original research studies on QoL after mesothelioma surgery were identified through May 2018: 17 articles, 14 datasets encompassing 659 patients, were retrieved. Measures of lung function (FEV, FVC) and EORTC QLQ-C30 were compared 6 months following surgery with preoperative values.

      4c3880bb027f159e801041b1021e88e8 Result

      QoL data was available for 102 EPP patients and 432 P/D patients. Two studies directly compared QoL between the two techniques. While QoL was still compromised 6 months following surgery, P/D patients fared better than EPP patients across all QoL measures. Physical function, social function, global health and dyspnea were higher at follow-up for PD than for EPP, while other indicators such as pain and cough were similar. FEV and FVC were higher at follow-up for P/D compared to EPP, although only one study reported FEV and FVC following EPP.

      8eea62084ca7e541d918e823422bd82e Conclusion

      QoL is better for patients undergoing P/D compared to EPP for an extended period following surgery. Given the need for multimodality therapy and the aggressive nature of MPM, QoL outcomes should be strongly considered when choosing type of surgery for MPM.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA12.03 - The Impact of Malignant Pleural Mesothelioma Histology on the Use of Surgery and Survival in a Population-Based Analysis (ID 14406)

      10:40 - 10:45  |  Presenting Author(s): Chi-Fu Jeffrey Yang  |  Author(s): Nicholas Mayne, John Z Deng, Sarah J Commander, Thomas A. D'Amico, Mark Berry

      • Abstract
      • Presentation
      • Slides

      Background

      Histologic subtype for malignant pleural mesothelioma (MPM) is known to be an important determinant of both treatment and survival. This study aimed to quantify the impact of MPM histology on the use of surgery and survival in a population-based analysis.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Overall survival (OS) of patients with stage I-III epithelioid, sarcomatoid, and biphasic MPM in the National Cancer Database from 2004 to 2015 was evaluated using Kaplan-Meier survival analysis and multivariable Cox proportional hazard models.

      4c3880bb027f159e801041b1021e88e8 Result

      Of the 3,346 patients who met inclusion criteria, the histologic subtype was epithelioid in 2,326 patients (70%), biphasic in 482 patients (14%), and sarcomatoid in 538 patients (16%). Median survival was 16.2 [95% CI: 15.3 – 17.2] months in the epithelioid group, 10.9 [95% CI: 9.8 – 11.9] months in the biphasic group, and 5.3 [95% CI: 4.7 – 6.0] months in the sarcomatoid group (p<0.001). Cancer-directed surgery was utilized more often in epithelioid (31%, n=718) and biphasic patients (38%, n=181) compared to sarcomatoid patients (17%, n=91) (p<0.001). Among patients who underwent surgery, median survival was significantly better for epithelioid (22.6 [95% CI: 21.2 – 24.8] months) and biphasic (14.7 [95% CI: 12.6 – 17.3] months) histologies compared to sarcomatoid histology (7.7 [95% CI: 6.4 – 8.6] months) (p<0.001). Surgery was associated with better survival in multivariable analysis for epithelioid (HR 0.81; [95% CI: 0.72 – 0.93], p=0.002) and biphasic histologies (HR 0.69; [95% CI: 0.53 – 0.89], p=0.004), but not for sarcomatoid type mesothelioma (HR 0.87; [95% CI: 0.65 – 1.16, p=0.34). Further, the absolute difference in median survival between surgical and non-surgical therapy was more clinically significant for the epithelioid (22.6 vs 15.8 months; p <0.001 and biphasic (14.7 vs 10.4 months; p=0.001) patients compared to the sarcomatoid (7.7 vs 7.2 months; p=0.13).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In this U.S. national analysis of patients with malignant pleural mesothelioma, surgery was most commonly used for epithelioid and biphasic histologies and was associated with a median survival of nearly 2 years and over 1 year, respectively. However, surgery was also used in almost 1 in 5 patients with sarcomatoid mesothelioma but was associated with a median survival of less than 8 months. These results suggest that the specific mesothelioma histology should be firmly established before surgery, and it is reasonable to aggressively treat select patients with epitheloid and biphasic mesothelioma with surgery, but that surgery should not be performed for most patients with sarcomatoid mesothelioma.

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      MA12.04 - Discussant - MA 12.01, MA 12.02, MA 12.03 (ID 14623)

      10:45 - 11:00  |  Presenting Author(s): Marc De Perrot

      • Abstract
      • Presentation
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      Abstract not provided

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      MA12.05 - Phase 1 Study of HSP90 Inhibitor Ganetespib with Pemetrexed and Cisplatin/Carboplatin Chemotherapy for Pleural Mesothelioma (ID 11921)

      11:00 - 11:05  |  Presenting Author(s): Dean A Fennell  |  Author(s): Sarah Danson, Martin Forster, Denis Talbot, Penella Woll, Jennifer Child, Yenting Ngai, Laura Farrelly, Allan Hackshaw, Annabel Sharkey, Sara Busacca, Robert Hastings, Dan Barnes, Marianne Nicolson, Paul Taylor, Samreen Ahmed, Graham Mark Wheeler

      • Abstract
      • Presentation
      • Slides

      Background

      There have been no new licenced therapies for mesothelioma in over a decade. Ganetespib is a small-molecule heat-shock protein 90 (Hsp90) inhibitor, with significant activity for down-regulating Hsp90 client protein levels. Prior evidence indicates efficacy for ganetespib in mesothelioma through critical survival pathways and synergies with antifolates and platinum chemotherapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a dose-escalation study of ganetespib in patients with pleural malignant mesothelioma and ECOG 0-1. Ganetespib was combined with standard pemetrexed/platinum therapy, using either cisplatin (GCisP), or carboplatin (GCarbP). Three ganetespib cohorts were: 100, 150 & 200mg/m2 given days 1 and 15, every 21 days. GCisP was evaluated using a 3+3 design. GCarbP followed an accelerated titration run-in using single patients, switching to a 3+3 design after one dose limiting toxicity (DLT). DLT was assessed during cycles 1-2 for GCisP and cycle 1 for GCarbP. Genomic instability was inferred by array-based analysis of somatic copy number.

      4c3880bb027f159e801041b1021e88e8 Result

      27 patients were treated (GCisP, n=16; GCarbP, n=11). Median age 66 (range 37-76), 6 PS-0/21 PS-1, and 25 male. Only 3 patients experienced DLTs, all at 200mg/m2: grade 3 nausea (GCisP, n=1; GCarbP, n=1); grade 2 infusion-related reaction (GCarbP, n=1). This dose was the maximum tolerated dose. Partial tumour response rate was 61% (14/23 evaluable patients); 7 patients had tumour burden reduction of >50% (Figure). PFS was better using 200mg/m2 versus 100mg/m2 (hazard ratio 0.32, 95%CI 0.11-0.95, p=0.04). One patient remains progression-free even after 37 months. Total loss of heterozygosity (LOH) was correlated with increased tumour burden (n=7, correlation=0.7, p=0.078).

      meso02abstract_bestresponse.png

      Figure. Best tumour response (% change in tumour burden from baseline)

      8eea62084ca7e541d918e823422bd82e Conclusion

      Ganetespib plus pemetrexed and platinum chemotherapy was well-tolerated in patients with pleural mesothelioma, with evidence of activity, particularly at the recommended dose of 200mg/m2. LOH correlated with poorer response to this triplet combination.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA12.06 - STELLAR – Final Results of a Phase 2 Trial of TTFields with Chemotherapy for First-Line Treatment of Malignant Pleural Mesothelioma (ID 13806)

      11:05 - 11:10  |  Presenting Author(s): Giovanni L Ceresoli  |  Author(s): Joachim G.J.V. Aerts, Jaroslaw Madrzak, Rafal Dziadziuszko, Rodryg Ramlau, Susana Cedres, Birgitta Hiddinga, Jan P Van Meerbeeck, Manlio Mencoboni, David Planchard, Antonio Chella, Lucio Crinò, Maciej Krzakowski, Federica Grosso

      • Abstract
      • Presentation
      • Slides

      Background

      Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable, medical device. In-vitro, human mesothelioma cells were highly susceptible to TTFields. TTFields have been shown to significantly extend survival of patients with glioblastoma when added to chemotherapy.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The trial accrued 80 patients with unresectable, previously untreated mesothelioma. Patients were treated with continuous 150 kHz TTFields (>18h/day) in combination with pemetrexed and cisplatin or carboplatin (at standard dosing). Inclusion criteria included ECOG PS of 0-1, pathologically proven mesothelioma and at least one measurable lesion according to modified RECIST criteria. Patients were followed q3w (CT scan q6w) until disease progression. The primary endpoint was overall survival (OS) and secondary endpoints were response rate, progression free survival (PFS) and toxicity. This prospective, single arm study assumed an historical control with a median survival of 12.1 months (Vogelzang et al. 2003). The sample size provides 80% power with a two-sided alpha of 0.05 to detect an increase in median OS of 5.5 months.

      4c3880bb027f159e801041b1021e88e8 Result

      All 80 patients were enrolled between 2016 and 2017, with a minimum follow up of 12 months. Median age was 67 (range 27-78), 84% were male and 56% smokers. 16% (13 patients) had metastatic disease and 44% (35 patients) had an ECOG PS of 1. 66% (53 patients) had epithelioid histology. Compliance with TTFields was 68% (16.3 hours/day) during the first 3 months of therapy and 63% (50 patients) received carboplatin.

      Median OS was 18.2 months (95% CI 12.1-25.8) compared to 12.1 months in the historical control. Median PFS was 7.6 months (95% CI 6.7-8.6) compared to 5.7 months in the historical control. Partial responses were seen in 40.3% of patients and clinical benefit (PR+SD) was seen in 97.2% of patients. No device-related serious adverse events (AEs) were reported. Expected TTFields-related dermatitis was reported in 46% (37 patients). Only 4 patients (5%) had grade 3 dermatitis. The following grade 3-4 systemic AEs were reported in >3% of patients: hematological AEs (15%) and fatigue (4%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The study met its primary endpoint of significant extension of survival for previously untreated mesothelioma patients. Secondary efficacy endpoints were also improved compared to historical control. The study demonstrated no safety concerns for the combination of TTFields to the thorax together with standard chemotherapy. These results support the addition of TTFields to standard chemotherapy in the treatment of first-line malignant pleural mesothelioma.

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      MA12.07 - gC1qR Expression is Independently Prognostic for Survival Benefit Following Chemotherapy in Mesothelioma (ID 13284)

      11:10 - 11:15  |  Presenting Author(s): Xiaoyu Li  |  Author(s): Takashi Eguchi, Rania G Aly, Navin Chintala, Kay See Tan, John Messinger, Marjorie G. Zauderer, Berhane Ghebrehiwet, Prasad S. Adusumilli, Ellinor I.B. Peerschke

      • Abstract
      • Presentation
      • Slides

      Background

      Overexpression of gC1qR, a multicompartmental and multifunctional cellular protein, has been shown to promote chemotherapy-induced apoptosis in cancer cells, but compromise CD4 T-cell proliferation in viral infections. The goal of this study was to investigate the overexpression of gC1qR, and its prognostic association with chemotherapy and CD4 T-cell infiltration in malignant pleural mesothelioma (MPM).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Tissue microarrays comprising 6 tumoral and 3 stromal cores from 265 patients with MPM (216 epitheloid, 26 biphasic, and 23sarcomatoid, 1989-2010) were investigated by immunohistochemistry for gC1qR expression (intensity and distribution by H-score, range 0-300), and CD4 T-cell infiltration. Overall survival (OS) was analyzed by the Kaplan-Meier method (high versus low gC1qR expression delineated by median score). Multi-variable analysis included clinical, pathological factors and stage (T, N).

      4c3880bb027f159e801041b1021e88e8 Result

      In comparison to benign and reactive mesothelial cells (median H-score 30), gC1qR is overexpressed (median H-score 155) in all histological types of MPMs (263/265, 99.2%). In epithelioid MPM patients – 1) among patients who received neoadjuvant chemotherapy (NAC), high gC1qR was associated with better median OS (25 vs.11 months, Fig1A), 2) among patients without NAC, high gC1qR was associated with better survival, survival benefit is pronounced in patients who received postoperative chemotherapy (median OS 38 vs.19 months, Fig1B), and 3) in multivariate analysis, high gC1qR was an independent factor for better OS. gC1qR expression did not correlate with CD4 T cell infiltration. However, among patients without NAC, high CD4+ T cell infiltration-high gC1qR expression was associated with better OS (26 vs 18,12, and11 months, Fig1C).

      gc1qr.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      gC1qR is overexpressed on MPM cells. MPM patients with high gC1qR expression have a significant survival benefit particularly following chemotherapy; or in the presence of high CD4 T-cell infiltration.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA12.08 - Discussant - MA 12.05, MA 12.06, MA 12.07 (ID 14625)

      11:15 - 11:30  |  Presenting Author(s): Quincy Chu

      • Abstract
      • Presentation
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      Abstract not provided

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      MA12.09 - Preclinical Investigations of Folate Receptor Targeted Nanoparticles for Photodynamic Therapy of Malignant Pleural Mesothelioma (ID 11277)

      11:30 - 11:35  |  Presenting Author(s): Tatsuya Kato  |  Author(s): Cheng S Jin, Hideki Ujiie, Kosuke Fujino, Daiyoon Lee, Hironobu Wada, Hsin-pei Hu, Licun Wu, Rober A Weersink, Juan Chen, Hiromi Kanno, Yutaka Hatanaka, Kanako C Hatanaka, Yoshihiro Matsuno, Marc De Perrot, Brian C Wilson, Gang Zheng, Kazuhiro Yasufuku

      • Abstract
      • Presentation
      • Slides

      Background

      Photodynamic therapy (PDT) following lung-sparing extended pleurectomy (EPD) for malignant pleural mesothelioma (MPM) has been investigated as a potential means to kill residual microscopic cells. High expression of folate receptor 1 (FOLR1) has been reported in MPM, and targeting the FOLR1 has been considered as a new potential strategy. We have developed FOLR1-targeting porphyrin-lipid nanoparticles (folate-porphysomes; FP) for PDT. The inhibition of survival pathways of activated epidermal growth factor (EGFR) also enhance the PDT efficacy. Here, we have combined these approaches by using FP based PDT together with an EGFR-tyrosine kinase inhibitor (EGFR-TKI).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The frequency of FOLR1 and EGFR expression in MPM was analyzed using tissue microarrays. Confocal microscopy and a cell viability assay were performed to confirm the specificity of FOLR1-targeting cellular uptake and photocytotoxicity in vitro. In vivo fluorescence activation and the therapeutic efficacy were then examined. The effect of EGFR-TKI was assessed in vitro. The in vivo combined anti-tumor effect of EGFR-TKI and FP-PDT was then evaluated.

      4c3880bb027f159e801041b1021e88e8 Result

      FOLR1 and EGFR were expressed in 79 % and 89 % of the MPM samples, respectively. The intracellular uptake of FP corresponded well with FOLR1 expression. When MPM cells were incubated in FP and then irradiated at 671 nm, there was significant in vitro cell kill, which was inhibited in the presence of free folic acid, suggesting the specificity of FPs. FOLR1 targeting resulted in disassembly of the porphysomes and subsequent fluorescence activation in intrathoracic disseminated MPM tumors, as demonstrated by ex vivo tissue imaging. FP-PDT resulted in significant cellular damage and apoptosis in vivo. Furthermore, the combination of pre-treatment with EGFR-TKI plus FP-PDT showed further marked improvement of treatment responses.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Folate-porphysome based PDT shows selective destruction of MPM cells based on FOLR1 targeting, and pre-treatment with EGFR-TKI further enhances the therapeutic response.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA12.10 - Long-Term Impact of Radiotherapy Before Surgery for Mesothelioma on the Distribution of Memory T Cell Subsets (ID 12728)

      11:35 - 11:40  |  Presenting Author(s): Junichi Murakami  |  Author(s): Licun Wu, Mikihiro Kohno, Mei-Lin Chan, Yidan Zhao, Zhihong Yun, Marc De Perrot

      • Abstract
      • Presentation
      • Slides

      Background

      Postoperative recurrence remains one of the critical issues in treatments for mesothelioma. We previously reported that non-ablative, hypo-fractionated radiation before surgery generated an antigen-specific activation of the immune system and could provide an in situ vaccination with long-term protection against mesothelioma in our murine model. An effective immunological protection depends on memory T cell subset diversification. However, limited work has been done to address the distribution of memory T cell subsets and its effects on the immune system after radiotherapy followed by surgery for mesothelioma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      C57BL/6 mice bearing AE17-OVA tumor were treated with local radiotherapy (LRT). LRT 5Gy was delivered on days 10, 11 and 12. We performed radical tumor resection 7 days after LRT. The mice were re-challenged under the skin or into thoracic cavity with AE17-OVA 28 days after surgery and defined as immunological protective memory model if the tumors were completely rejected. Memory model received subcutaneous tumor inoculation once again (second rechallenge), samples were harvested on day 0, 3, 10. We investigated memory T cell subsets using flow cytometry. In addition, the harvested total splenocytes (effector) were co-cultured with CFSE-labeled AE17-OVA (target) for three days. Each of their cytotoxic potential was analyzed by evaluating a number of AE17-OVA and its early or late apoptosis.

      4c3880bb027f159e801041b1021e88e8 Result

      8 out of 10 mice completely rejected the subcutaneous tumor in mice treated with LRT and surgery after re-challenged. We observed significantly better survival in the memory model re-challenged into the thoracic cavity compared with no treatment mice. After subcutaneous tumor inoculation, central memory T cells (CD44[+]CD62L[+]KLRG1[-]) on day 0, effector memory T cells (CD44[+]CD62L[-]KLRG1[-]) and terminal effector T cells (CD44[+]CD62L[-]KLRG1[+]) on day 0, 3, 10 increased significantly in CD8[+] splenocytes of memory model compared with no treatment mice. This observation was also seen in draining and non-draining lymph nodes. The MFI of CFSE reflecting a number of AE17-OVA cells decreased, whereas the proportion of early (Annexin V[+]FVD[low]) or late (Annexin V[+]FVD[high]) apoptotic cells in CFSE[+] cells increased, depending on time passage and effector/target ratio after tumor inoculation in both memory model and naïve mice. However, during time passage, memory model always had a stronger cytotoxicity (even at Day 0) as compared to naïve mice.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our data raise an important possibility that non-ablative, hypo-fractionated radiotherapy followed by surgery for mesothelioma contributes to the development and long-term maintenance of memory T cell subsets, which could remain poised to rapidly recall effector functions upon antigen re-exposure.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA12.11 - Analysis of Angiogenic and Stromal Biomarkers in a Large Malignant Mesothelioma Cohort (ID 12234)

      11:40 - 11:45  |  Presenting Author(s): Puey Ling Chia  |  Author(s): Prudence Russell, Khashayar Asadi, Carmel Murone, Marzena Walkiewicz, Ulf Eriksson, Andrew Scott, Thomas John

      • Abstract
      • Presentation
      • Slides

      Background

      Malignant mesothelioma (MM) is an aggressive malignancy of the pleura and other mesothelium membranes. Agents targeting vascular endothelial growth factor (VEGF) receptor such as bevacizumab; and multi-kinase inhibitors like nintedanib [angiokinase inhibitor of VEGF, platelet-derived growth factor (PDGF) receptor and fibroblast growth factor receptor (FGFR)] have recently demonstrated efficacy in MM. In the setting of these new therapies, it is important to evaluate angiogenic and stromal markers in MM to assess their associated prognostic implications.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Tissue microarrays (TMAs) were created from formalin-fixed, paraffin-embedded tissue samples obtained from 326 patients who underwent surgical resection or biopsy for MM between 1988 and 2014. PDGF-CC, FGFR-1, VEGF and CD31 expression were analysed by immunohistochemical (IHC) staining. The H-score method assigned a score of 0–300 to each sample, based on the percentage of cells stained at different intensities. The discriminatory threshold was set for each IHC stain (usually the median score) and samples were classified as low (below median) or high expression (above median). CD31 was evaluated via Chalkley’s method to evaluate microvessel density. We evaluated the association between expression of the biomarkers, clinicopathological factors and outcomes, in patients with MM.

      4c3880bb027f159e801041b1021e88e8 Result

      The histological subtypes comprised of 203/325 (62.5%) epithelioid; 72/325 (22.2%) biphasic; 42/325 (12.9%) sarcomatoid, or indeterminate. The median age was 67 (range 24-88) with Male: Female ratio of 266: 53.

      CD31 high (≥5) was seen in only 31/302 (10.3%) irrespective of histology (13/31 (42%) epithelioid; 10/31 (32%) sarcomatoid; 7/31 (23%) biphasic; 1/31 indeterminate).

      PDGF-CC high (≥150) was seen in 203/310 (65%) of all samples but was higher in epithelioid subtype [129/203 (64%)]. VEGF high (≥80) was seen in 219/322 (68%) of all MM with 143/209 (68%) of epithelioid histology.

      FGFR-1 high (≥40) was seen in 127/310 (41%) of all MM and 73/127 (57.5%) are of epithelioid histology.

      There was no association of VEGF and FGFR-1 IHC with survival nor differences between histological subtypes.

      There was a non-significant trend towards poorer survival in epithelioid tumours with increased PDGF-CC expression (OS 18.5 vs 13.2 months; HR 0.7928; 95%CI 0.5958 to 1.055, P=0.1110).

      High CD31 score was associated with significantly poorer survival (OS 12 vs 8.6 months; HR 0.48; 95%CI 0.2873 to 0.7941, P=0.0044). Of the 31 patients with high CD31 scores; 23/31 (74%) were also high for PDGF-CC and 20/31 (64%) with high VEGF scores.

      8eea62084ca7e541d918e823422bd82e Conclusion

      High PDGF-CC expression and CD31 scores are associated with poor survival in MM. Abrogating these pathways may have prognostic implications.

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      MA12.12 - Discussant - MA 12.09, MA 12.10, MA 12.11 (ID 14627)

      11:45 - 12:00  |  Presenting Author(s): Masaki Anraku

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MA13 - Interventional Pulmonology (ID 914)

    • Type: Mini Oral Abstract Session
    • Track: Interventional Diagnostics/Pulmonology
    • Presentations: 12
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 206 AC
    • +

      MA13.01 - CT-Guided Transthoracic Needle Biopsy for Evaluation of PD-L1 Expression: Comparison of 22C3 and SP263 Assays (ID 11312)

      10:30 - 10:35  |  Presenting Author(s): Kyongmin Sarah Beck  |  Author(s): Kyo Young Lee, Su Jin Hong

      • Abstract
      • Presentation
      • Slides

      Background

      Although there are a few studies about concordance of different assays testing PD-L1 expression using surgical specimens, there hasn’t been any such concordance study using real-world biopsy specimens. However, many of the patients requiring immunotherapy and thus PD-L1 testing have unresectable lung cancer and have to rely on small biopsy results. Although phase 2 of Blueprint phase 2 does include core biopsy specimens, they are mixed with bronchial biopsy specimens and the absolute number is very small (n=20). We sought to evaluate the concordance of 22C3 and SP263 assays in a larger number CT-guided transthoracic needle biopsy (TNB) specimens.

      The purpose of this study was to assess the concordance of two commercially available diagnostic assays (22C3 and SP263) in evaluating programmed cell death ligand-1 (PD-L1) expression using specimens from CT-guided TNB in a routine clinical setting.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This retrospective analysis reviewed 202 non-small cell lung cancer (NSCLC) patients who underwent CT-guided TNB at our institution from April 2017 to February 2018. Among these, biopsy specimens tested with both 22C3 and SP263 assays were included for review. Concordance of PD-L1 expression levels determined by the two assays was assessed using intraclass correlation coefficient, and the agreement of dichotomized values at various cut-offs (1%, 25%, and 50%) were assessed using Cohen’s κ coefficient of agreement. Clinical characteristics and biopsy-related factors were also assessed for the association of concordance of PD-L1 expression detected by different assays

      4c3880bb027f159e801041b1021e88e8 Result

      In total, 80 patients (M:F =47:33, mean age: 68.0 years) were included in the study. Concordance of PD-L1 expression levels was high (intraclass coefficient: 0.892) between 22C3 and SP263 assays. Agreements at cut-off levels of 1%, 25%, and 50% were also good, with κ values of 0.878, 0.698, and 0.790 respectively. Positive percent agreement was 93.2%, 100.0%, and 95.2% for agreements at 1%, 25%, and 50%. At multivariate analysis, the presence of emphysema was significantly related to discordant PD-L1 results (odds ratio: 0.059, p= 0.005).

      8eea62084ca7e541d918e823422bd82e Conclusion

      There is a high concordance of PD-L1 expression evaluated with 22C3 and SP263 assays using CT-guided TNB specimens.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.02 - PD-L1 Expression in EBUS-Guided Cytology Specimens of Non-Small Cell Lung Cancer is Not Affected by Type of Fixation: A Study of Matched Pairs (ID 11867)

      10:35 - 10:40  |  Presenting Author(s): Alexander Haragan  |  Author(s): John Roy Gosney, Claire Chadwick, Tom Giles, Seamus Grundy, Victoria Tippett, Krishna Gumparthy, Andrew Wight, Hock Tan

      • Abstract
      • Presentation
      • Slides

      Background

      No previous trials of immune modulators (IMs) to treat non-small cell lung cancer (NSCLC) have included ‘cytology’ specimens, dispersed cells aspirated from a tumour deposit or body cavity, for immunochemical assessment of PD-L1, a useful complementary or compulsory companion diagnostic test. This has led to the widely-held view that, in the absence of such ‘validation’, cytology specimens cannot be used to assess it. In many centres, endobronchial ultrasound (EBUS)-guided aspiration of the tumour or intra-thoracic lymph nodes is the preferred means of diagnosis and staging of NSCLC and such specimens account for the majority received for analysis. Failure to asses them has serious implications for appropriate management and might deny patients effective therapy. Much of this reluctance centres on the alleged effect of fixation in alcohol-based fixatives, the preferred method of cytopathologists, rather than formalin, the standard fixation medium for tissue specimens, on the expression of PD-L1 on the cell surface.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We compared expression of PD-L1 in 50 paired specimens of NSCLC, one fixed in an alcohol-based fixative and one in neutral-buffered formalin, taken from the same tumour deposit or lymph node during the same procedure. All were spun down and formed into a cell block before assessment for PD-L1 expression, which was by two appropriately-trained pathologists with extensive experience in its interpretation.

      4c3880bb027f159e801041b1021e88e8 Result

      In none of the 50 pairs studied was there any significant difference, qualitative or quantitative, in the pattern or extent of PD-L1 expression and, in the great majority, it was identical irrespective of fixation.

      8eea62084ca7e541d918e823422bd82e Conclusion

      There is no evidence from this study that the use of alcohol-based fixatives has any effect on the expression of PD-L1 or its interpretation. Notwithstanding the general challenges in accurately assessing such expression, which are common to specimens of tissue as well as dispersed cells, pathologists should feel able to interpret cytology specimens with confidence and clinicians able to rely on the results.

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      MA13.03 - Heterogeneity Analysis of EBUS-TBNA-Derived Specimens for Evaluation of PD-L1 Expression and Copy Number Alterations in Patients with NSCLC (ID 12664)

      10:40 - 10:45  |  Presenting Author(s): Katsuhiro Yoshimura  |  Author(s): Yusuke Inoue, Kazuo Tsuchiya, Masato Karayama, Yuji Iwashita, Tomoaki Kahyo, Akikazu Kawase, Masayuki Tanahashi, Hiroshi Ogawa, Koshi Yokomura, Naoki Inui, Kazuhito Funai, Kazuya Shinmura, Hiroshi Niwa, Takafumi Suda, Haruhiko Sugimura

      • Abstract
      • Presentation
      • Slides

      Background

      Most patients with non-small cell lung cancer (NSCLC) are diagnosed at advanced stages and only small biopsy specimens are available for diagnosis in the majority of the patients. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a useful diagnostic modality and is becoming more relevant and essential procedure in the real-world clinical setting. However, it is poorly elucidated whether EBUS-TBNA-derived small specimens are suitable for evaluation of biomarkers such as PD-L1 alterations, because heterogeneity of PD-L1 expression limits the power as a guide to select patients who are likely to benefit from the PD-1/PD-L1 blockade therapy. In addition, PD-L1 copy number alterations (CNAs) have been proposed to potentially complement the predictive performance of PD-L1 expression. We here evaluated the utility of EBUS-TBNA-derived specimens in the assessment of PD-L1 protein and CNAs focusing on the heterogeneity with other biopsy/resected samples.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      PD-L1 protein expression and CNAs in 71 EBUS-TBNA specimens of NSCLC were assessed. Corresponding 68 transbronchial biopsy (TBB) specimens, 13 resected primary tumors, and 6 resected metastases were comparatively analyzed. PD-L1 expression on tumor cells was assessed by immunohistochemistry (E1L3N). Positivity of ≥1% was used as the cut-off. PD-L1 CNAs were assessed with fluorescent in situ hybridization, and were classified into three categories: amplification, polysomy, and disomy. Concordance between EBUS-TBNA and other specimens were calculated.

      4c3880bb027f159e801041b1021e88e8 Result

      The median age was 68 years (38-90 years). The cohort comprised 48 men (67.6%), 15 never-smokers (21.1%), and 39 adenocarcinomas (54.9%). The concordance of PD-L1 positivity between EBUS and the other specimens was moderate; κ=0.63 for EBUS vs TBB, κ=0.68 for EBUS vs the resected primary tumors, and κ=1.00 for EBUS vs the resected metastases. The concordance of PD-L1 CNA statuses was comparable with that of PD-L1 expression: κ=0.60 for EBUS vs TBB, and κ=0.74 for EBUS vs the resected primary tumors. When the PD-L1 copy number was assessed as a continuous variable, the correlation was also good/moderate: ρ=0.60 for EBUS vs TBB specimens, ρ=0.56 for EBUS vs the resected primary tumors, and ρ=0.80 for EBUS vs the resected metastases. Intratumorally, PD-L1 expression was significantly heterogeneous in whole sections of resected tumors, but PD-L1 CNAs was less heterogeneous than protein expression.

      8eea62084ca7e541d918e823422bd82e Conclusion

      EBUS-TBNA-derived specimens can be used for the assessment of PD-L1 alterations including CNAs. The concordance of PD-L1 CNAs between EBUS-TBNA and TBB/resected specimens were comparable with that of PD-L1 expression. However, spatial heterogeneity should be taken into account to interpret both PD-L1 protein expression and CNAs.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.04 - Discussant - MA 13.01, MA 13.02, MA 13.03 (ID 14629)

      10:45 - 11:00  |  Presenting Author(s): John Roy Gosney

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA13.05 - The Canada Lymph Node Sonographic Score: National Validation of a Sonographic Score to Determine Mediastinal Lymph Node Malignancy (ID 12084)

      11:00 - 11:05  |  Presenting Author(s): Danielle Alexandria Hylton  |  Author(s): Julie Huang, Simon Turner, Daniel French, Chuck Wen, James Masters, Biniam Kidane, Jonathan David Spicer, Jenelle Taylor, Christian Finley, Yaron Shargall, Christine Fahim, Forough Farrokhyar, Kazuhiro Yasufuku, John Agzarian, Waël C. Hanna

      • Abstract
      • Presentation
      • Slides

      Background

      At the time of endobronchial ultrasound (EBUS) staging for Non-Small Cell Lung Cancer (NSCLC), 6 ultrasonic criteria (Fig. 1) are used to assign a Lymph Node Sonographic Score (LNSS) that is predictive of malignancy. The LNSS has not gained widespread use due to lack of research demonstrating its validity and reliability among endoscopists. We hypothesized that LNSS correlates well with the probability of malignancy, potentially guiding decisions for lymph node (LN) biopsy.

      iaslc abstract lnss - figure 1_jpg.jpg

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We conducted a prospective study to assess the validity and reliability of the LNSS. The validation cohort comprised LN that were video-recorded from patients with NSCLC, and assigned a LNSS by an experienced endoscopist. Videos were then circulated to thoracic surgeons and interventional respirologists across Canada, who were asked to assign a score to each LN. All raters had demonstrated proficiency using our online education module, were blinded to staging information, and to each other. Each LN was scored by at least 3 independent raters. Pathological specimens were used as the gold standard for determination of malignancy. Regression, receiver operator curve (ROC), and Gwet’s AC1 analyses were used to test LNSS score performance, discriminatory capacity, and inter-rater reliability.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 300 LNs (18% malignant) from 140 patients were analyzed by 11 endoscopists across 7 Canadian centres. LNSS=0 was strongly predictive of benign LN (NPV= 95.69%, OR=49.2, p=0.001). LNSS ≤2.5 (OR=44, p=0.001) was determined as the cutoff for malignancy based on ROC analysis (c= 0.7757, 95%CI: 0.70281-0.84853). Inter-rater reliability for LNSS=0 was 0.8553 (95%CI:0.8158-0.8947, p=0.0001) and 0.46 for LNSS ≤2.5 (95%CI=0.3521-0.5012, p=0.0001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The Canada LNSS shows excellent performance in identifying benign LN at the time of EBUS. A cutoff ≤2.5 has the potential to inform decision-making regarding biopsy or repeat biopsy/mediastinoscopy if the initial results are inconclusive. Further teaching and education are required to improve inter-rater reliability.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.06 - Endosonography with Lymph Nodes Sampling for Restaging the Mediastinum in Lung Cancer: A Systematic Review and Pooled-Data Analysis (ID 11918)

      11:05 - 11:10  |  Presenting Author(s): Long Jiang  |  Author(s): Jun Liu, Wenlong Shao, Kassem Harris, Lonny Yarmus, Weizhe Huang, Jianxing He

      • Abstract
      • Presentation
      • Slides

      Background

      Mediastinal restaging after induction treatment is still a difficult and controversial issue. We aimed to investigate the diagnostic accuracy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for restaging the mediastinum after induction treatment in patients with lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Embase and PubMed databases were searched from conception to July 2017. Data from relevant studies were analyzed to assess sensitivity and specificity of EBUS-TBNA and EUS-FNA, and to fit the Hierarchical Summary Receiver-Operating Characteristic curves.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of nine studies consisting of 542 patients fulfilled the inclusion criteria. All patients were restaged by EBUS-TBNA, EUS-FNA or both. Negative results were confirmed by subsequent surgical approaches. There were no complications reported during any endosonography approaches reviewed. The pooled sensitivities of EBUS-TBNA and EUS-FNA were 66%(95% CI, 60%-72%) and 73%(95% CI, 52%-87%), respectively; and specificities were 100%(95% CI, 98%-100%) and 99%(95% CI, 90%-100%), respectively. The area under the HSROC curves(AUC) were 0.84(95% CI, 0.81-0.87) for EBUS-TBNA and 0.99(95% CI, 0.98-1) for EUS-FNA. Moreover, for patients who received chemotherapy alone, the pooled sensitivity of endosonography with lymph node sampling for restaging was 69% (95% CI, 63%-75%), and specificity was 100% (95% CI, 97%-100%); and for patients who received chemoradiotherapy, the results seemed similar with sensitivity of 65% (95% CI, 50%-78%) and specificity of 100% (95% CI, 96%-100%).

      Variables

      No. of patients

      Pooled sensitivity (95% CI)

      Pooled specificity (95% CI)

      Negative Likelihood Ratio

      AUC

      In all mediastinal stations

      Overall

      543

      0.70 (0.65-0.75)

      1.00 (0.98-1.00)

      0.30 (0.21-0.43)

      0.93 (0.91-0.95)

      EBUS-TBNA

      424

      0.66 (0.60-0.72)

      1.00 (0.98-1.00)

      0.38 (0.26-0.54)

      0.84 (0.81-0.87)

      EUS-FNA

      226

      0.73 (0.52-0.87)

      0.99 (0.90-1.00)

      0.27 (0.14-0.53)

      0.99 (0.90-1.00)

      Combine

      106

      0.67 (0.53–0.79)

      0.96 (0.86–0.99)

      N/A

      0.81 (0.73–0.87)

      Subgroup analysis

      Chemo alone

      365

      0.69 (0.63-0.75)

      1.00 (0.97-1.00)

      0.35 (0.26-0.48)

      0.90 (0.88-0.94)

      Chemo radiotherapy

      130

      0.65 (0.50-0.78)

      1.00 (0.96-1.00)

      0.25 (0.06-1.02)

      0.97 (0.95-0.98)

      If negative Likelihood Ratio(LR-) is smaller: essentially a definite diagnosis when negative result.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Endosonography with lymph node sampling is an accurate and safe technique for mediastinal restaging of lung cancer. For nondiagnostic results, a further more invasive approach should be thoroughly considered.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.07 - Diagnostic Yield of N3 Hilar Staging by Endobronchial Ultrasonography (EBUS) in Lung Cancer (ID 12565)

      11:10 - 11:15  |  Presenting Author(s): Antoni Rosell  |  Author(s): Jaume Bordas Martinez, Jose Luis Vercher Conejero, Guillermo Rodriguez Gonzalez, Cristina Martin Cabeza, Noelia Cubero De Frutos, Rosa-Maria Lopez Lisbona, Marta Diez Ferrer, Paula Notta, Roger Llatjos Sanuy, Jordi Dorca Sargatal

      • Abstract
      • Presentation
      • Slides

      Background

      Systematic lung cancer staging with EBUS has proven to be equivalent to cervical mediastinoscopy. Nevertheless, in the daily practice it is common to explore and sample negative PET-CT hilar N3 lymph nodes (LN). This study aims to explore if there is enough evidence to support this clinical practice.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Retrospective study from our database including 1,013 explorations over the last 5 years. Including criteria were patients with lung cancer staged by PET-CT and EBUS-TBNA. Mediastinal and hilar N3 LN with a short axis ≥ 5 mm were sampled with a 21G needle and assessed by rapid on site evaluation (ROSE). A single nuclear medicine expert reviewed blindly all PET-CT scans and determined the SUVmax of every LN. Those that were ≥ 5 SUVmax by PET-CT and/or ≥ 10mm in short axis by EBUS were considered abnormal.

      4c3880bb027f159e801041b1021e88e8 Result

      87 patients were included, of which 87% were male with a mean age of 66 years (SD 12.6). The final histopathology diagnoses were adenocarcinoma (46%), squamous cell carcinoma (39%) and other histology (14%). EBUS-TBNA was performed 30 days (SD 16.9) after PET-CT. None of the 61 normal hilar and normal mediastinum N3 LN, and none of the 7 normal N3 hilar LN with abnormal mediastinal LN (3 by PET-CT, 3 by EBUS and 1 for both) resulted positive for lung cancer. Of the 19 patients with abnormal N3 hilar LN (6 by PET-CT, 8 by EBUS and 6 for both) malignancy was found in 16.7% , 25% and 60% for both techniques, respectively.ryywawmo--450186-1-any.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      In absence of abnormal N3 hilar LN (PET: SUVmax<5; EBUS<10mm in short axis) it seems there is not enough evidence to sample them, regardless of N3 mediastinal status.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA13.08 - Discussant - MA 13.05, MA 13.06, MA 13.07 (ID 14631)

      11:15 - 11:30  |  Presenting Author(s): Nicole Bouchard

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA13.09 - Electromagnetic Navigation Bronchoscopy as an Integrated Approach to Aid in Diagnosis and Treatment of Pulmonary Lesions (ID 12623)

      11:30 - 11:35  |  Presenting Author(s): Sandeep Khandhar  |  Author(s): Septimiu Murgu, Kyle Hogarth, William Krimsky, Javier Flandes, Otis Rickman, Momen Wahidi, Eric Sztejman, Philip Linden, Sadia Benzaquen, Sandeep Bansal, Erik Folch

      • Abstract
      • Presentation
      • Slides

      Background

      Electromagnetic navigation bronchoscopy (ENB) is an image-guided localization approach to guide endoscopic tools to lung targets. In a single procedure, ENB aids in localizing lung lesions for biopsy or molecular profiling, fiducial placement for stereotactic body radiation therapy (SBRT), or dye marking for surgical resection. The multidisciplinary utility of ENB in a large, prospective, multicenter study is unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      NAVIGATE (clinicaltrials.gov, NCT02410837) is a prospective, multicenter, observational cohort study of ENB using the superDimension™ navigation system. From April 2015 to August 2016, 1,215 consecutive subjects were enrolled at 29 United States sites. Two-year follow-up is ongoing. A prespecified 1-year interim analysis is presented.

      4c3880bb027f159e801041b1021e88e8 Result

      ENB was used to aid in lung lesion biopsy (n=1157 subjects), fiducial placement (n=258), pleural dye marking (n=23), and/or lymph node biopsy (n=30). EBUS-guided lymph node staging was conducted in the same procedure in 448 subjects. The median lesion-to-pleura distance was 9mm. The median lesion size was 20mm; most were in the middle (30%) and peripheral (67%) thirds of the lung. Pathology results were malignant in 44.3% (484/1092) (54.1% Stage I, 11.1% Stage II, 17.0% Stage III, 17.7% Stage IV). Molecular testing was attempted in 30.7% (80/261) of adenocarcinoma or NSCLC-not-otherwise-specified cases overall and 57.9% (33/57) of Stage IIIB/IV cases. Tissue was adequate in 87.5% (70/80) of cases. EGFR mutations (14.7%) and ALK translocations (4%) were the most frequently observed genetic alterations. The ENB procedure was well-tolerated; 2.9% of subjects had procedure-related pneumothorax requiring hospitalization or intervention, lower than published rates for CT-guided core biopsy (25%) and CT-guided fine needle aspiration (19%). Subject-reported impact of ENB on daily activities was 0.9 out of 10 (0 = no impact).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In the largest prospective, multicenter study to date, ENB aided in lesion biopsy in the middle and periphery of the lung and tissue collection for molecular testing, with a very low morbidity. ENB facilitates a multidimensional approach to lung biopsy and mediastinal/hilar staging, offering the opportunity for multiple sites/tissues to be safely sampled in one anesthetic event.

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      MA13.10 - Comparison of Pulmonary Nodule Location Between Preprocedural CT and Intra-Procedural Cone-Beam CT During Guided Bronchoscopy (ID 14216)

      11:35 - 11:40  |  Presenting Author(s): Michael A. Pritchett

      • Abstract
      • Presentation
      • Slides

      Background

      Electromagnetic navigation bronchoscopy relies on pre-procedural CT scans to create a virtual airway reconstruction that is used as a roadmap during bronchoscopy. These systems assume similarity between the position of the nodule during bronchoscopy and the pre-procedure CT scan. However, there are multiple factors that suggest that such assumption maybe inaccurate. These include differences in positioning, breathing motion, and the presence of atelectasis. In this study, we evaluated the lung nodule position between pre-procedural CT to interprocedural cone-beam CT (CBCT). In addition, we assessed the ability of a novel augmented endobronchial fluoroscopic guidance system (LungVision, Body Vision Medical Ltd, Israel) to overcome those differences in real-time.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This was a prospective study of 21 patients with 23 peripheral pulmonary nodules. CT scans were imported into the planning software and the physician identified the nodule and navigation pathway. CBCT (Philips Allura Xper FD20) was used to scan the patient during the procedure. LungVision was used for real-time navigation and guidance during biopsy. The divergence in nodule location between the pre-procedural CT and the interprocedural CBCT was measured.

      4c3880bb027f159e801041b1021e88e8 Result

      The average patient age was 69 ± 8.6, median nodule size was 18mm with 74% of the nodules in the upper lobes. The average divergence of the nodule was 14.11 ± 9.9mm. Successful navigation was verified by CBCT in 91% of cases. Malignancy was diagnosed in 20 of 23 nodules for a diagnostic yield of 87%. No adverse events were reported.

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study demonstrates a significant divergence in lesion location between pre-procedural CT and intra-procedural CBCT during guided bronchoscopy. This finding indicates that the change in nodule position between the CT and bronchoscopy could have a great impact on the diagnostic success of the procedure. This movement, sometimes greater than the size of the nodule itself, can lead to an inaccurate localization when relying solely on virtual bronchoscopic or electromagnetic navigation.

      CT to patient divergence does not appear to influence the accuracy of this novel navigation platform. The system is capable of tracking the nodules dynamically and can compensate for changes in patient positioning and respiratory motion during both navigation and biopsy which leads to a high diagnostic yield.

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      MA13.11 - Photodynamic Therapy for Peripheral-Type Lung Cancer in a Multi-Center Clinical Trial (ID 13691)

      11:40 - 11:45  |  Presenting Author(s): Jitsuo Usuda

      • Abstract
      • Presentation
      • Slides

      Background

      Photodynanic therapy (PDT), is a treatment modality for many cancers, and uses a tumor-specific photosensitizer and laser irradiation. Recently, we have developed a new minimally invasive laser device using a 1.0 mm in diameter composite-type optical fiberscope (COF), which could transmit laser energy and images for observation in parallel.In this study, we aimed to develop a new endobronchial treatment for peripheral cancer using PDT and a COF, and we evaluated the feasibility of PDT using COF for peripheral lung cancer.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This phase I study enrolled 3 patients with peripheral lung cancers (primary tumor< 20 mm, stage IA), which were definitively diagnosed by bronchoscopic modalities such as EBUS-GS and brocnhoscopic navigation system. We conducted irradiation using a diode laser (664 nm) and a COF 4 hours after the administration of NPe6 40 mg/m2. We evaluated the tumor lesions using EBUS, and then we introduced the COF into the peripheral lung cancer, and irradiated of red light 664 nm (120 mW, 50 J/cm2 or 100J/cm2). 

      4c3880bb027f159e801041b1021e88e8 Result

      We performed PDT for 3 patients with c-stage IA peripheral lung cancer, using a laser dose (120mW, 50J/cm2), and confirmed the feasibility of the dose. We escalated the laser dose and performed 4 patients using a laser dose (120mW, 100J/cm2).

      Seven patients met our criteria, and 5 cases were adenocarcinoma and 2 case squamous cell carcinoma. We were able to observe the cancer lesions at the peripheral lung by the COF, and feasibly irradiated. Two weeks and 3 months after NPe6-PDT, complications such as pneumonia and pneumothorax were not found, but one mildly found light skin-photosensitivity. Six months later, we found CR in 3 cases and SD in 4 cases.

      8eea62084ca7e541d918e823422bd82e Conclusion

      The 1.0 mm COF was a very useful device of NPe6-PDT for peripheral lung cancers, and PDT was a feasible and non-invasive treatment for a peripheral type early lung cancer. In the future, for non-invasive adenocarcinoma such as AIS, NPe6-PDT will become a treatment modality.

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      MA13.12 - Discussant - MA 13.09, MA 13.10, MA 13.11 (ID 14632)

      11:45 - 12:00  |  Presenting Author(s): Antoni Rosell

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MA14 - Survivorship, Socioeconomic and End-of-Life Considerations (ID 915)

    • Type: Mini Oral Abstract Session
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 12
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 205 BD
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      MA14.01 - Life Sustaining Procedures, Palliative Care and Hospital Cost Trends in Dying Lung Cancer Patients in U.S. Hospitals: 2005-2014 (ID 14134)

      10:30 - 10:35  |  Presenting Author(s): Jinwook Hwang  |  Author(s): Ji won Yoo, Jay Shen, Sun Jung Kim, Sung Youn Chun

      • Abstract
      • Presentation
      • Slides

      Background

      Little is known about the extent to which dying patients with lung cancer receive life-sustaining treatments and palliative care services at the end-of-life in U.S. hospitals. We examine hospital cost trends and the impact of palliative care utilization on the use of life-sustaining procedures in this population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Retrospective nationwide cohort analysiswas performed using National Inpatient Sample (NIS) data from 2005 and 2014. We examined the receipt of both palliative care and life-sustaining procedures, defined as systemic procedures, local procedures, or surgeries using the International Classification of Diseases, 9th revision (ICD-9-CM).

      4c3880bb027f159e801041b1021e88e8 Result

      Figure 1.

      스크린샷 2018-05-05 05.44.27.png

      We used compound annual growth rates (CAGR) to determine temporal trends and multilevel multivariate regressions to identify factors associated with hospital cost. Among 77,394,755 hospitalizations, 120,144 patients were examined. During 10 years, the CAGR of hospital cost was 7.05% (p<.0001). In contrast, the CAGR of hospital lengths of stay was -3.77% (p<.0001). The CAGRs of palliative care was over ten percentage (13.30 %, p<.0001). However, the CAGRs of systemic procedures, local procedures, and surgeries were less than around one percentage (-1.13%, -1.07% and 1.42%, each p<.0001). Systemic procedures, local procedures and surgeries were associated with increased hospital cost and lengths of stay by 50.6%, 74.4%, 68.5%, and 7.4%, 50.6%, 4.6% respectively (each p<.001). Palliative care was associated with decreased hospital cost and length of stay by 28.6% and 4.6% (each, p<.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      The volume of life-sustaining treatments is the biggest driver of cost increase although there is a cost-saving effect from greater palliative care utilization at the end-of-life in dying lung cancer patients.

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      MA14.02 - Use and Impact of A Systematic Advanced Care Planning in Hospitalized Lung Cancer Patients: A Prospective Study. (ID 13997)

      10:35 - 10:40  |  Presenting Author(s): Anne Claire Toffart  |  Author(s): Natacha Denis, Matteo Giaj Levra, Linda Sakhri, Michaël Duruisseaux, Julian Pinsolle, Léonie Ferrer, Denis Moro-Sibilot, Jean-François Timsit

      • Abstract
      • Presentation
      • Slides

      Background

      End-of-life communication is crucial, particularly for cancer patients. In usual practice, advanced care planning discussions with the patients are uncommon and rarely documented. The aim of this study was to investigate the impact of advanced care planning on intensity of care in cases of organ failure in lung cancer patients.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This prospective study was performed at the Grenoble University Hospital in France. Consecutive patients hospitalized in thoracic oncology unit between 01/28/2014 and 03/31/2016 were included and followed up to 12/31/2016. At each hospital admission, lung cancer patients benefited from advanced care planning. We defined 3 intensities of care: intensive care, maximal medical care and exclusive palliative care. The propositions of care could be modified during the hospitalization. Patients’ wishes should be received.

      4c3880bb027f159e801041b1021e88e8 Result

      Data of 715 hospitalizations corresponding to 473 patients were studied. Hundred fifty nine patients had a second hospitalization and 69 a third. At first admission, 247 (52%) patients had a performance status of 0 to 2, 186 (39%) were not yet treated for the cancer and 165 (35%) in progression. Main reasons of admission were an acute disease (n=208, 44%) and supportive care of cancer symptoms (n=167, 35%).

      During the three first admissions, 173 (25%) patients developed an organ failure. Among them, 56 (32%) had intensive care proposition, 104 (61%) maximal medical care, and 13 (7%) exclusive palliative care. Median time between admission and organ failure was 9 days [IQR 25%-75%, 3-13]. All patients benefited from intensity of care equal or lower than the proposed intensity of care. Among patients planed for intensive care, 17 (30%) patients received intensive care, 22 (39%) maximal medical care and 17 (30%) exclusive palliative care. Thirteen of the 39 patients not admitted in ICU despite organ failure and previous proposition of intensive care were considered too well by the oncologist. Patients’ wishes were recorded for 158 (91%) patients, and a discussion about end of life conditions was led with 116 (73%) patients or families.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In case of organ failure, an advanced care planning appears helpful to provide reasonable intensity of care. The proposition of care seems to be adapted to the patient’s general condition and cancer characteristics. 3/4 of the patients with an organ failure benefited from a discussion about end of life conditions.

      ClinicalTrials.gov Identifier: NCT02852629

      Funding from the publicly funded nonprofit organization Cancéropole Lyon Auvergne Rhône-Alpes (CLARA).

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      MA14.03 - Aggressiveness of Cares on the Month Before Death of Patients with Lung Cancer: A French National Database Survey (ID 12005)

      10:40 - 10:45  |  Presenting Author(s): Olivier Bylicki  |  Author(s): Charlène Tournier, florence Canoui-Poitrine, Cecile Blein, Christos Chouaid

      • Abstract
      • Presentation
      • Slides

      Background

      Prior studies have demonstrated that high-intensity end of life (EOL) cares improves neither survival nor quality of life for cancer patients. The National Quality Forum endorses markers of poor EOL care for cancer patients but there is little data’s concerning lung cancer patients (1). The aim of this study was to assess, the quality of management during the last month of life of lung cancer patients managed in France and factors associated EOL aggressiveness.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Using a French hospital discharge database (PMSI, Programme de Médicalisation des Systèmes d’Information), all patients with lung cancer who died between January 1, 2010 and December 31, 2011 (cohort 1) and between January 1, 2015 and December 31, 2016 (cohort 2) were identified through the International Classification of Diseases 10th version (ICD-10). Aggressiveness of EOL cares was assessed by the following criteria’s 1) chemotherapy administrated within last 14 days of life (DOL); 2) > 1 hospitalization within 30 DOL; 3) ICU admission within 30 DOL; and 4) Palliative care < 3 days before death. Multivariate analysis was performed to identify individual determinants EOL aggressiveness.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 90,827 incident adult patients were identified (cohort 1: 43,862, cohort 2: 46,965): men: 74%, median age: 67 years], metastatic at diagnosis: 70%; 57% have at least one marker of aggressiveness of EOL cares (repeated hospitalizations: 49%, ICU admissions: 12%, chemotherapy within 14 DOL: 9%, palliative care < 3 days before death: 5%). A significant increase was observed between 2010/2011 and 2015/2016 for repeated hospitalizations (48% vs 51%, p<.001) and ICU admissions (11% vs 13%, p<.001); the two other markers have remained stable. In multivariate analysis of cohort 2, the risk of aggressiveness of care in EOL was increased by the presence of COPD (OR: 1.08, 95%CI: 1.02-1.14) and a management in an anti-cancer center (OR: 2.32,95%CI 2.05-2.61) while advanced age (OR: 0.51, 95%CI 0.47-0.55), female sex (OR: 0.86 95%CI: 0.82-0.90), malnutrition (OR: 0.72, 95%CI:0.68-0.76) were protective factors for EOL aggressiveness of cares.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Despite growing focus on providing appropriate EOL cares, in this analysis 57% of deceased lung cancer patients in France received aggressive EOL cares. Research must be undertaken to better identify patients at risk of aggressive EOL cares and to improve the quality of cares of last days of life these patients.

      1.McNiff KK, . Measuring supportive care in medical oncology practice: lessons learned from the quality oncology practice initiative. JCO 2008;

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      MA14.04 - Discussant - MA 14.01, MA 14.02, MA 14.03 (ID 14636)

      10:45 - 11:00  |  Presenting Author(s): Gouri Shankar Bhattacharyya

      • Abstract
      • Presentation
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      Abstract not provided

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      MA14.05 - Social Isolation Increases Psychological Distress in Patients With NSCLC (ID 11959)

      11:00 - 11:05  |  Presenting Author(s): Cheryl Ho  |  Author(s): Bonnie Leung, Jonn Wu, Janessa Laskin, Heather Rennie, Alan Bates

      • Abstract
      • Presentation
      • Slides

      Background

      The Psychosocial Screen for Cancer (PSSCAN-R) questionnaire is a validated screening tool used to identify the psychosocial needs of patients with cancer. The questionnaire assesses patients’ perceived social supports and identifies patients at risk for developing psychological distress. The study goal was to examine patients with NSCLC who reported risk factors for social isolation and their risk for developing psychological distress.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      All patients with NSCLC referred to BC Cancer from 2011-2015 who completed a prospective PSSCAN-R questionnaire at the time of first visit were included in the study. Perceived social support questions include: if patients live alone, lost a life partner recently, have no help with IADLs, have no regular contact with friends and family or have no emotional support from others. Demographics were collected retrospectively. Chi-squared test and logistical regression were used to compare patient groups based on age, gender and perceived social support factors.

      4c3880bb027f159e801041b1021e88e8 Result

      The study cohort was comprised of 4428 patients who completed the PSSCAN-R questionnaire. Female 50%, patients ≥65 years 69%, live alone 29%, lost life partner 13%, no help with IADLs 9%, no regular contact 3% and no emotional support 5%.table1.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      Female patients and patients younger than 65 are more at risk for developing moderate to severe anxiety and depression. Lack of perceived social support also contributes to the risk of developing psychological distress. In addition to developing gender and age-based resources for patients addressing their psychosocial needs, greater efforts in assessing patients’ perceived social supports and allocating community and institutional resources to isolated patients should also become an important part of the patients’ comprehensive and holistic care.

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      MA14.06 - Predictors of Financial Toxicity, an Under-Recognized Patient-Reported Outcome (ID 13571)

      11:05 - 11:10  |  Presenting Author(s): Doreen Anuli Ezeife  |  Author(s): Josh Morganstein, Sally C Lau, Jennifer Law, Lisa Le, Penelope Bradbury, Geoffrey Liu, Frances A Shepherd, Natasha B Leighl

      • Abstract
      • Presentation
      • Slides

      Background

      In contemporary cancer care, financial distress has been established as a clinically relevant patient-reported outcome (PRO) associated with worse mortality and quality of life, but remains under-recognized by health care providers. Our goal was to define predictors of patient financial toxicity (FT) in a public healthcare system.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with advanced lung cancer were recruited from outpatient clinics at the Princess Margaret Cancer Centre (Toronto, Canada). FT was measured with the validated Comprehensive Score for Financial Toxicity (COST) instrument, an 11-item survey scored from 0-44 with lower scores reflecting worse financial well-being. Data on patient and treatment characteristics, total out-of-pocket costs (OOP) and extended insurance coverage (EIC) were collected. Associations between variables and COST score were evaluated using multivariable regression analyses.

      4c3880bb027f159e801041b1021e88e8 Result

      Of 249 patients approached, 200 (80%) participated. Median age of the cohort was 65 years; 44% were male, 36% immigrants, 67% employed or on pension, with median OOP between $1000-5000 CAD. Median COST score was 21 (range 0-44). FT was associated with age, with patients <65 years reporting greater FT than older patients (COST 18 vs. 25; P<0.0001). Employed patients or those receiving pension income reported less FT than unemployed patients (22 vs. 19; P=0.01). Less FT occurred in patients with EIC compared to those without (23 vs. 19; P=0.03). Patients with higher OOP reported more FT (P<0.0001). Patients on clinical trials reported less FT than others (25 vs. 20; P=0.04). In multivariable linear regression, younger age was a predictor of higher FT, when adjusting for income, employment status, OOP and EIC (P<0.0001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Age is a predictor of FT in the Canadian (Ontario) public healthcare system, with younger lung cancer patients reporting greater financial distress. This study highlights priority patient populations where FT should be routinely assessed and appropriate resources for support offered.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA14.07 - The Impact of Socioeconomic Status and Geographic Location on Palliative Chemotherapy Uptake in Patients with Metastatic NSCLC  (ID 13098)

      11:10 - 11:15  |  Presenting Author(s): Zamzam Salam Al-Hashami  |  Author(s): Bonnie Leung, Janessa Laskin, Jonn Wu, Heather Rennie, Alan Bates, Cheryl Ho

      • Abstract
      • Presentation
      • Slides

      Background

      Socioeconomic status (SES) and geographic factors may impact patient treatment choices. Canada has a publically funded health care system and in BC, there are 35 community oncology network sites that delivery treatment in patients’ local communities. We studied the impact between SES and geographic location upon delivery of chemotherapy/survival in metastatic NSCLC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      All patients with metastatic NSCLC referred to BC Cancer centres from 2011-2015, who completed a prospective Canadian Problem Checklist questionnaire at the time of their first visit and for which chemotherapy data was available were included in the study. The CPC assesses patient distress in 6 domains including practical aspects of cancer care. The Postal Code Conversion File Plus uses data from Statistics Canada 2011 census to determine population size and income quintiles. Baseline characteristics and chemotherapy treatments were collected retrospectively. Univariate analysis using the Chi-squared test and Fisher’s exact test were used for analysis.

      4c3880bb027f159e801041b1021e88e8 Result

      1113 patients were included with median age of 69 years, 54% female and 77% were former/current smoker and 47% received palliative chemotherapy. Uptake of chemotherapy did not differ between lowest + mid-lowest 44%, middle 51% /mid-highest + highest 49% income quintiles (p=0.18). Chemotherapy use was also similar between patients reporting financial concerns 50% versus none 47% (p=0.51). Uptake of chemotherapy was lower in patients who lived in rural communities population<10 37% (P 0.00), 10K-1.5M 41%, >1.5 million 53% (p<0.001). Chemotherapy use was lower for patients with concerns about getting to appointments (39% vs 49%, p=0.008) or accommodations (33% vs 48%, p=0.012).

      8eea62084ca7e541d918e823422bd82e Conclusion

      This dataset provide evidence that patients from rural communities were less likely to receive palliative chemotherapy treatment for metastatic NSCLC in BC despite the availability of multiple local community oncology services. SES did not appear to impact the proportion of patients treated, congruent with a government funded health care system. An in depth assessment of distances to local cancer services and treatment delivery is warranted to investigate these differences and their effect on mortality.

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      MA14.08 - Discussant - MA 14.05, MA 14.06, MA 14.07 (ID 14637)

      11:15 - 11:30  |  Presenting Author(s): Christos Chouaid

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      MA14.09 - Mortality of Lung Cancer as a Second Primary Malignancy among Cancer Survivors: A Study of Surveillance, Epidemiology, and End Results Database (ID 11862)

      11:30 - 11:35  |  Presenting Author(s): Lei Deng  |  Author(s): Huan Song, Zhengrui Xiao, Changchuan Jiang, Qian Wang, Haiying Cheng, Donghao Lu

      • Abstract
      • Presentation
      • Slides

      Background

      Cancer survivors are at increased risk of developing a second primary malignancy, including lung cancer. However, the prognosis of lung cancer as a second primary malignancy (lung-2) remains largely unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Primary lung cancer patients diagnosed from 1988 to 2014 in the SEER program were included. Lung-2 was ascertained by a previous diagnosis of primary malignancy in SEER. Hazard ratios (HRs) of overall and lung cancer specific mortality were estimated among patients with lung-2 compared to lung-1.

      4c3880bb027f159e801041b1021e88e8 Result

      679,541(88.8%) and 85,758 (11.2%) patients were identified as lung-1 and lung-2, respectively. The median time from first primary malignancy to lung-2 diagnosis was 4.8 years. Compared to lung-1, patients with lung-2 were more likely to be diagnosed at localized stage, with smaller primary tumor, and treated with surgery. Lung-2 patients were at lower risk of lung cancer specific mortality in the first five years (HR 0.77, 95% CI 0.76 - 0.78 at < 1 year; HR 0.87, 95% CI 0.86 - 0.89 from 1 to < 5 years) but at higher risk thereafter. Patients with lung-2 were associated with reduced risk of overall mortality during the first year after diagnosis (HR 0.91, 95% CI 0.91 - 0.92), but with significantly increased risks thereafter.

      Table Hazard ratios (HRs) of overall and lung cancer specific mortality among patients with lung-2

      N (%) of patients

      From 0 to <1 year after diagnosis

      From 1 year to < 5 years after diagnosis

      From 5 years to 10 years of follow-up after diagnosis

      N (IR)

      HR (95% CI) *

      N (IR)

      HR (95% CI)*

      N (IR)

      HR (95% CI)*

      Overall mortality

      First primary lung cancer

      679,541

      383,208 (99.9)

      1.00

      135,513 (29.3)

      1.00

      16,821 (9.8)

      1.00

      Second primary lung cancer

      85,758

      44,288 (84.1)

      0.91 (0.91-0.92)

      20,073 (29.4)

      1.10 (1.08-1.12)

      3,133 (14.6)

      1.32 (1.27-1.37)

      Lung cancer specific mortality

      First primary lung cancer

      679,541

      325,633 (84.9)

      1.00

      111,348 (24.1)

      1.00

      8,147 (4.7)

      1.00

      Second primary lung cancer

      85,758

      31,247 (59.3)

      0.77 (0.76-0.78)

      12,485 (18.3)

      0.87 (0.86-0.89)

      1,158 (5.4)

      1.10 (1.03-1.17)

      N, number of deaths; IR, incidence rate per 100 person-years

      * HR was adjusted for age and calendar period at diagnosis, sex, race, cohabitation status, percentile of cost of living and high-school education in county of residence, tumor stage, histology, tumor grade, surgery, radiation therapy, and chemotherapy.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Lung-2 is associated with favorable lung cancer specific and overall survival within early period of diagnosis. Inferior overall survival afterwards cannot be attributed to aggressiveness of lung-2, highlighting the importance of managing first malignancy and comorbidities.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA14.10 - QTc Interval-Prolonging Medications in Lung Cancer: Implications for Clinical Trial Eligibility and Routine Clinical Care (ID 12305)

      11:35 - 11:40  |  Presenting Author(s): David E Gerber

      • Abstract
      • Presentation
      • Slides

      Background

      Concomitant medication use, including agents that prolong the QTc interval, may exclude cancer patients from clinical trials. To estimate potential impact on accrual, we determined the prevalence of QTc-prolonging medication prescriptions in a national patient cohort.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We identified adult patients in the United States Veterans’ Affairs system diagnosed with lung cancer 2003-2016. QTc-interval prolonging medications and risk category were obtained from CredibleMeds®. We calculated prevalence of prescriptions for QTc-prolonging medications with known or possible risk of torsades de pointes (the most common criteria employed as trial exclusion criteria) in the 3 months up to and including date of cancer diagnosis. Rates across patient groups and time periods were compared using Chi-square test.

      4c3880bb027f159e801041b1021e88e8 Result

      280,068 patients were included in the study. Mean age was 70 years, 98% were male, and 72% were white. Overall, 29.7% were prescribed a QTc-prolonging medication. Patients receiving QTc-prolonging medications were marginally younger (mean age 68.9 years versus 70.9 years; P<0.001) and more likely to be black (14.1% versus 11%; P<0.001). The most commonly prescribed QTc-prolonging medications were antimicrobials (14.0%), psychiatric agents (10.2%), antiemetics (2.6%), and cardiovascular medications (1.7%). Seven percent of patients were prescribed two or more QTc-prolonging medications. Over the period of study, the rate of QTc-prolonging medication use increased 20% (25% in 2004 versus 31% in 2016; P<0.001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      A substantial and growing proportion of individuals with lung cancer are prescribed QTc-prolonging medications. These prescriptions may limit eligibility for clinical trials and complicate the administration of standard cancer therapies. Given the prevalence of chronic and/or multiple QTc-prolonging medication prescriptions, it may be challenging to address this obstacle to trial enrollment simply through prescription substitution or discontinuation. Further research into the actual clinical risks and optimal management of QTc-prolonging medications in cancer populations is warranted.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA14.11 - Factors Associated with Early Mortality in Non-Small Cell Lung Cancer Patients Following Systemic Anti-Cancer Treatment (ID 12970)

      11:40 - 11:45  |  Presenting Author(s): Amanda Jane Williams Gibson  |  Author(s): Haocheng Li, Adrijana D'Silva, Roxana A. Tudor, Anifat A. Elegbede, Shannon Mary Otsuka, Winson Y Cheung, Gwyn Bebb

      • Abstract
      • Presentation
      • Slides

      Background

      To determine a 30-day mortality rate benchmark and assess factors associated with early mortality of non-small cell lung cancer (NSCLC) patients following receipt of systemic anti-cancer therapies (SACT).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In a 10-year population-based analysis, NSCLC patients receiving SACT in 2005-2014, with or without other treatments, and captured in the Glans-Look Lung Cancer Database, which contains demographic, clinical, pathological, treatment and outcome data were reviewed. 30-day mortality after most recent SACT cycle was calculated, and end-of life (EOL) regimen changes in the last 14 days of life were identified. Univariate analysis and multivariable logistic regression were used to identify demographic, tumor or treatment-related factors that correlated with mortality risk.

      4c3880bb027f159e801041b1021e88e8 Result

      1044 eligible NSCLC patients receiving at least one cycle of SACT in 2005-2014 were identified. 51% were female, 62% adenocarcinoma, 79% current/former smokers, 83% advanced stage at diagnosis, and 77% receiving palliative-intent treatment. 233 (22.3%) deaths occurred ≤ 30 days following SACT receipt, and 32 (13.7%) EOL regimen changes identified. Risk of early mortality decreased for never-smokers and those receiving SACT between 2010-2014, and increased in association with male gender, advanced disease at diagnosis, palliative-intent treatment, and use of EGFR-targeting agents. No factors were associated with a decreased risk of EOL regimen change. (Table 1). The predominant SACT-modality among those experiencing 30-day mortality was EGFR-targeting agents (54%).
      abstract #12790 table.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our findings from a real-world population identify several factors which affect the risk of early mortality in NSCLC patients following SACT, and establish a 30-day mortality benchmark for Canadian NSCLC populations. Evolving SACT modalities may facilitate an increased use of SACT at EOL and associated early mortality; however, in this cohort, decreased early mortality risk in the 2010-2014 timeframe suggests concomitant evolution of decisions regarding EOL SACT and/or palliative and EOL care may be underway at our centre, but represents an area for ongoing investigation.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      MA14.12 - Discussant - MA 14.09, MA 14.10, MA 14.11 (ID 14638)

      11:45 - 12:00  |  Presenting Author(s): Amanda Tufman

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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    MS13 - Novel Mediators of Lung Cancer Metastasis (ID 792)

    • Type: Mini Symposium
    • Track: Biology
    • Presentations: 6
    • Moderators:
    • Coordinates: 9/25/2018, 10:30 - 12:00, Room 201 F