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Simon Ekman
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MA08 - Pawing the Way to Improve Outcomes in Stage III NSCLC (ID 127)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 12
- Now Available
- Moderators:Simon Ekman, Helena A Yu
- Coordinates: 9/08/2019, 15:15 - 16:45, Tokyo (1982)
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MA08.01 - Analysis of PD-L1 Expression on Circulating Stromal and Tumor Cells in Lung Cancer Patients Treated with Chemoradiation Therapy and Atezolizumab (Now Available) (ID 2965)
15:15 - 16:45 | Presenting Author(s): Steven H Lin | Author(s): Alexander Augustyn, Jianzhong He, Yawei Qiao, Zhongxing Liao, Ashvathi Raghavakaimal, Kirby Gardner, John Victor Heymach, Anne Tsao, Daniel Adams
- Abstract
- Presentation
Background
We have previously shown dynamic changes to PD-L1 expression during chemoradiotherapy (CRT) could be tracked by evaluating PD-L1 expression on circulating cells. How these changes relate to immunotherapy response is unknown. We prospectively monitored PD-L1 expression in 2 cell types found in circulation (Circulating tumor cells [CTCs] and Cancer Associated Macrophage-like Cells [CAMLs]) in locally advanced non-small cell lung cancer (LA-NSCLC) patients (pts) treated with atezolizumab and CRT.
Method
Samples were taken from a completed phase II DETERRED trial (NCT02525757) where atezolizumab was added for one year after completing CRT (N=10) or concurrently and after CRT (N=30). Samples from 39 pts from the study were available for analysis. Baseline blood sample (7.5 ml) were drawn prior to start of CRT (T0), and a second sample was drawn ~1 month after completing CRT (T1), and a 3rd sample was drawn ~2 months after completing CRT (T2). Blood was processed by CellSieve™ microfilters; stained for cytokeratin/PDL1/CD45 to identify CTCs and CAMLs. PD-L1 intensity was measured and grouped by 4 scores: 0-negative, 1-low, 2-medium, & 3-high. Tumor IHC for PD-L1 levels from core biopsies was done with Dako 22c3 and was compared to T0 samples. PD-L1 levels from tumor and in circulating cells were used to evaluate PFS and OS. Significance was assessed by log-rank testing.
Result
PD-L1 IHC was available for 85% of pts, and there was at least one cytokeratin positive cell (CTC or CAML) found in 100% of T0 samples. CTCs were found in 33% of T0, 24% of T1 & 43% T2. CAMLs were found in 92% of T0, 97% of T1, & 97% of T2 samples. No correlation was seen comparing tumor PD-L1 expression percentage and the T0 PD-L1 staining intensity on CTCs/CAMLs. Tumor PD-L1>1% was found in 58% and >50% in 24% of IHC samples, yet there was no correlation between tumor PD-L1 expression and PFS or OS. At T0, PD-L1 expression in CTCs/CAMLs was low (0-1) in 18 pts and high (2-3) in 15, but no relationship to PFS (HR=0.6, 95%CI 0.2-1.7, p=0.48) or OS (HR=1.7, 95%CI 0.5-6.4, p=0.66) was found. However, pts with high PD-L1 at T1 or T2, regardless of levels at T0, had a trend towards improved PFS (HR 2.5, 95%CI 0.7-8.6, p=0.13), and a significantly better OS (HR 14.2, 95%CI 2.4-81.8, p=0.003). Interestingly, of the 15 pts who had low PD-L1 at T0, 7 had induced PD-L1 expression at T1 or T2. All samples with induced PD-L1 expression had better PFS (HR 8.3, 95%CI 1.4-50.2, p=0.02) and OS (HR 8.7, 95%CI 1.2-64.0, p=0.03) compared to those who remained low.
Conclusion
While baseline tumor or circulating cellular PD-L1 expression was not correlated with clinical outcomes, sequential monitoring of high PD-L1 expression in CTCs/CAMLs after CRT appeared to be associated with better clinical outcomes in pts who received consolidation atezolizumab after CRT, particularly in pts who had induced expression at follow up during the consolidation phase. Dynamic tracking of PD-L1 may serve as a predictive biomarker for immunotherapy effectiveness in LA-NSCLC after CRT.
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MA08.02 - Durvalumab Impact in the Treatment Strategy of Stage III Non-Small Cell Lung Cancer (NSCLC): An EORTC Young Investigator Lung Cancer Group Survey (Now Available) (ID 608)
15:15 - 16:45 | Presenting Author(s): Matteo Giaj Levra | Author(s): Justin Benet, Baktiar Hasan, Thierry Berghmans, Alessio Bruni, Anne Marie Clasina Dingemans, Niccolo' Giaj Levra, John G Edwards, Corinne Faivre-Finn, Nicolas Girard, Elisa Gobbini, Laurent Greillier, Lizza Hendriks, Sylvie Lantuejoul, Antonin Levy, Silvia Novello, Mary O'Brien, Martin Reck, Alessia Pochesci, Jessica Menis, Benjamin Besse
- Abstract
- Presentation
Background
Stage III NSCLC represents a very heterogeneous population with extremely different treatment modalities including surgery, chemotherapy (CT) and radiotherapy (RT), mostly in combination. The results of the PACIFIC trial have now been reported in full including an overall survival (OS) benefit with durvalumab in addition to concomitant CT-RT. An electronic European survey was circulated to evaluate the impact of durvalumab in the staging and treatment strategy of stage III disease.
Method
A Young Investigator EORTC Lung Cancer Group survey containing 31 questions, was distributed between 31/01/18 and 31/03/19 to EORTC LCG and several European thoracic oncology societies’ members
Result
206 responses were analyzed (radiation oncologist: 50% [n=103], pulmonologist: 26.7% [n=55], medical oncologist: 22.3% [n=46]; 81.5% with >5 years experience in treating NSCLC). Italy (27.7%, n=57), Netherlands (22.8%, n=47), France (13.6%, n=28), and Spain (11.6%, n=24) contributed most. 83.5% (n=172) confirmed that they had access to durvalumab at the time of the survey. 97.6% (n=201) report that treatment decision is made by a multidisciplinary board. Regarding staging, 76.7% (n=158) support the need of a mediastinal pathological staging in case of suspect lymph-nodes, with a preference for EBUS/EUS (61.2%, n=126). 81.6% (n=168) treated more than half of patients with a concomitant CT-RT with the 1st cycle of chemotherapy in 39.7% (n=81). 95.1% consider durvalumab as practice changing, especially given the OS results (77.9%, n=152/195). 30% (n=119/395) will give patients concomitant CT-RT if PD-L1 >1%, and in borderline resectable cases 17.7% (n=70/395) will propose concomitant CT-RT instead of surgery. Durvalumab administration will be given regardless of PDL1 status in 13.1% (n=27) and 28.6% (n=59) would consider the possibility of a rebiopsy after CT-RT in case of negative PD-L1. 38.8% (n=80) foresee some problems with PD-L1 testing in this population due to availability of cytologic or small histologic samples. About 53.8% (n=105/195) normally will start durvalumab within 6 weeks after CT-RT and 48.5% (n=100) would also use durvalumab after sequential CT-RT
Conclusion
Durvalumab results are changing the treatment approach to stage III unresectable (and maybe resectable) NSCLC and planned strict adherence to the patient population as recruited to the PACIFIC study, was not demonstrated. This survey was released after the EMA approval of durvalumab and PD-L1 status seems to play a role in the treatment strategies, but surprisingly almost half of the clinicians will use durvalumab after sequential CT-RT without safety or efficacy data.
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MA08.03 - Adjuvant Pembrolizumab in N2 Positive NSCLC Treated with Concurrent Chemoradiotherapy Followed by Surgery: Phase II, Prospective Study (Now Available) (ID 1744)
15:15 - 16:45 | Presenting Author(s): Sehhoon Park | Author(s): Hyun Ae Jung, Jong Ho Cho, Jong-Mu Sun, Hong Kwan Kim, Se-Hoon Lee, Yong Soo Choi, Jin Seok Ahn, Jhingook Kim, Keunchil Park, Jae Ill Zo, Young Mog Shim, Myung-Ju Ahn
- Abstract
- Presentation
Background
The standard treatment option for stage IIIA-N2 subgroup is still under discussion with controversies. We hypothesize that immune checkpoint inhibitor consolidation therapy could have an additional role in prolongation of the disease-free survival (DFS) for stage IIIA-N2 NSCLC treated with tri-modalities therapy.
Method
This is a phase 2 study evaluating the clinical efficacy of pembrolizumab treatment after CCRT with curative resection in stage IIIA-N2 NSCLC pts (NCT03053856). Pathologically confirmed pts were treated with five cycles of CCRT, weekly paclitaxel (50mg/m2) and cisplatin (25mg/m2) combined with radiotherapy (total of 44Gy over 22 fractions) followed by curative resection. Adjuvant Pembrolizumab (200mg fixed dose) is applied every three weeks up to 2 years or until disease recurrence. The primary objective is disease-free survival of more than 20 months. The first patient was recruited in October 2017, and the data for this abstract was locked at 20th of January, 2019.
Result
Total of 40 pts were screened, and 37 pts received treatment. Median age was 64 years (range 39-74), and twenty-three pts were male (62.2%). As a curative surgery, pts received lobectomy (n=34), bi-lobectomy (n=2), or pneumonectomy (n=1). Adenocarcinoma was predominant (n=27, 73.0%). After the neoadjuvant CCRT, down-staging were observed in nine pts (24.3%). The median follow-up duration was 10.6 months (range 3.1-17.2), and pts received a median of 11 cycles (range 1-22) of adjuvant pembrolizumab. DFS is not reached. Fourteen patients discontinued treatment due to disease progression (n=9), adverse events (n=4) and withdraw consent (n=1). There was a case of grade 4 pneumonitis and a case of grade 3 autoimmune hepatitis which lead to discontinuation of the treatment. Otherwise, grade 1-2 hypothyroidism (n=6), pneumonitis (n=5), skin rash (n=3) were observed. Patients with severe immune-related adverse event showed a significantly high percentage of Ki-67 + cells among CD8 T-cells in peripheral blood.
Conclusion
This study is the first study to demonstrate the feasibility of adjuvant pembrolizumab monotherapy in stage IIIA-N2 patients. Updated clinical outcome will be presented at the conference.
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MA08.04 - Discussant - MA08.01, MA08.02, MA08.03 (Now Available) (ID 3744)
15:15 - 16:45 | Presenting Author(s): Delvys Rodriguez-Abreu
- Abstract
- Presentation
Abstract not provided
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MA08.05 - A Multi-Center Analysis of Right vs Left-Sided Pneumonectomy Following Induction Therapy (Now Available) (ID 1178)
15:15 - 16:45 | Presenting Author(s): Chi-Fu Jeffrey Jeffrey Yang | Author(s): Nicholas R Mayne, Athar Battoo, Sai Yendamuri, Todd Demmy, Robert McKenna, Thomas A D’amico, Mark Berry
- Abstract
- Presentation
Background
Previous single-center studies of pneumonectomy following induction therapy for non-small-cell lung cancer (NSCLC) have found a significant perioperative risk associated with right-sided pneumonectomy. We examined the impact of laterality on long-term survival after induction therapy followed by pneumonectomy in a multi-institutional analysis.
Method
Perioperative and long-term outcomes of patients with NSCLC who underwent pneumonectomy following induction chemotherapy with or without radiation from 2000-2016 across 3 institutions were evaluated using multivariable logistic regression, Cox proportional hazards modeling and propensity score-matched analysis. Patients who underwent a completion pneumonectomy or who had M1 disease were excluded from the analysis.
Result
During the study period, 172 patients (right n = 78 [45%], left n = 94 [55%]) met inclusion criteria. Right-sided pneumonectomy was associated with a similar perioperative complication rate (38% [30/78] vs 27% [25/94], p=0.10), and 30-day (13% [10/78] vs 9% [8/94], p=0.36) and 90-day mortality (23% [18/78] vs 13% [12/94], p=0.08) when compared to left-sided pneumonectomy. In multivariable analysis, right-sided pneumonectomy was not found to be a predictor of higher perioperative complications (OR 0.85 [95% CI: 0.33-2.14], p=0.73) or 30-day (OR 2.06 [95% CI: 0.44-9.69], p=0.36) and 90-day mortality (OR 2.06 [95% CI: 0.54-7.88], p=0.29). Overall survival between right and left pneumonectomy was not significantly different in unadjusted (5-year survival 30% [95% CI: 19%-41%] vs 29% [95% CI: 20%-39%], log-rank p=0.77 [Figure]) or multivariable analysis (adjusted hazard ratio, 1.05 [95% CI: 0.63-1.76], p = 0.84). A propensity score-matched analysis of 108 patients balancing baseline characteristics—including pulmonary function, tumor size and stage—was also performed, and found no significant differences in perioperative complication rates (46% [25/54] vs 48% [26/54], p=0.85), 30-day (17% [9/54] vs 7% [4/54], p=0.14) and 90-day mortality (26% [14/54] vs 13% [7/54], p=0.09) between right versus left pneumonectomy, respectively. Overall survival was not significantly different between right- and left-sided pneumonectomy (5-year survival 33% [95% CI: 20%-47%] vs 28% [95% CI: 16%-41%], log-rank p=0.98).
Conclusion
In this multi-center analysis, right-sided pneumonectomy after induction therapy was not associated with significantly higher perioperative mortality rates or worse long-term survival when compared to a left-sided pneumonectomy.
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MA08.06 - Perioperative Outcomes of Lung Cancer Patients with Interstitial Pneumonia (Now Available) (ID 1372)
15:15 - 16:45 | Presenting Author(s): Aki Katarina Kobayashi | Author(s): Yu Okubo, Masaya Yotsukura, Yukihiro Yoshida, Kazuo Nakagawa, Noriko Motoi, Shun-ichi Watanabe
- Abstract
- Presentation
Background
Interstitial lung disease is mostly found in elderly male smokers who also have relatively high risks of developing lung cancer. For these patients, modality to treat malignancy is limited to prevent acute exacerbation of interstitial pneumonia. We analyzed the perioperative outcomes of this group of patients with both interstitial pneumonitis and resectable lung cancer with curative intent.
Method
We retrieved the characteristics and medical courses of consecutive patients who had undergone pulmonary resections from medical records. In this analysis, usual interstitial pneumonia (UIP) was characterized by the presence of basal predominant, subpleural reticular abnormalities with traction bronchiectasis and honeycomb cysts detected in bilateral lung field on chest computed tomography preoperatively. Pathological findings on surgical specimen were used confirmation of diagnosis. The incidence and outcomes of acute exacerbation within 30 days from operation were analysed.
Result
From 2015 to 2017, there were 1,477 patients who underwent pulmonary resection for primary lung cancer at our institute. Among them there were 81 (5.5%) patients diagnosed as UIP by specific findings on chest computed tomography. Of 81 patients evaluated, 68 (84.0 %) were men, the median age was 73 years (range, 55-88). For Eastern Cooperative Oncology Group (ECOG) performance status, all 81 patients were categorized in status 0. Seventy-four patients (91.4%) underwent lobectomy, 1 (1.2%) bi-lobectomy, 2 (2.5%) segmentectomy and 4 (4.9%) wide wedge resections for primary lung cancer. The mean duration of surgery was 129 mins (range, 54-316), and mean value for blood loss was 36.5 ml (range, 0-396). A complete resection (R0) was achieved in 79 cases (97.5%). Postoperative complications were observed in 19 patients (23.5%) including prolonged air leakage (n=4, 4.9%), late onset of air leakage (n=3, 3.7%), surgical site infection, chylothorax and cerebral infarction. Nine patients (11.1%) manifested acute exacerbation of interstitial pneumonia within 30 days after surgery. There were 3 post-operative deaths (3.7%) within 30 days after surgery. Two deaths (2.5%) were due to acute exacerbation of interstitial pneumonia and 1 (1.2%) case of SAH on 1POD.
Conclusion
Pulmonary resection for patients with interstitial lung disease led to 9 (11.1%) cases of acute exacerbation within 30 days from surgery. Mortality related to acute exacerbation was found only 2 cases (2.5%) at our hospital, which was tolerable postoperative outcome for pulmonary resection for lung cancer with curative intent.
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MA08.07 - The Concordance Between Patient Reported Outcomes and Clinician Reported Outcomes During Radiotherapy in Lung Cancer Patients (Now Available) (ID 2507)
15:15 - 16:45 | Presenting Author(s): Evalien Veldhuijzen | Author(s): Iris Walraven, Margriet Kwint, Laura Roose, José Belderbos, Tomas Janssen
- Abstract
- Presentation
Background
Capturing information on toxicity in (non-)small cell lung cancer patients receiving radiotherapy or chemoradiotherapy, is crucial for optimal symptom management. Patient Reported Outcomes (PROs) have the potential to improve toxicity detection by adding direct information from the patient perspective. The aim of this study is therefore to determine the predictive and additional value of PROs on prospectively scored clinician reported toxicity.
Method
An observational study was performed in lung cancer patients (n=111) treated with (chemo)radiation with curative intent. The EORTC QLQ-C30 and the EORTC LC-13 questionnaires were used to score PROs on a scale of 0-100 for a selection of commonly occurring toxicities (i.e. dysphagia, dyspnea, anorexia, fatigue, cough and nausea). Clinicians prospectively scored the maximum toxicity during, and at the end of treatment using the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0. Receiver operating characteristic (ROC) curves were constructed to evaluate the performance (i.e. discrimination) of PROs on predicting clinician scored CTCAE toxicity (grade ≥2). Furthermore, cut-off points were determined from the ROC-curve on the basis of the best trade‐off values between sensitivity and specificity (0,5). Validity of the model was assessed with the ability to predict the number of grade ≥2 toxicities (calibration).
Result
Assessment of predictive performance in our cohort demonstrated a good fit for anorexia (AUC: 0,810 95% CI 0,699 to 0,921) and dysphagia (AUC: 0,828 95% CI 0,743 to 0,914) with sensitivity scores of 85,7%, 67,4% and specificity scores of 74,0% and 92,6% respectively. Both dyspnoea (AUC: 0,765 95% CI 0,60 to 0,910) and nausea (AUC: 0,745, 95% CI 0,548 to 0,942) showed a fair fit with sensitivity score of 74,1% for both toxicities and specificity of 69,1% and 68,3% respectively. A poor fit was found for cough (AUC: 0,667 95% CI 0,495-0,839) with a sensitivity of 55,6% and specificity of 30,4%. The model failed to discriminate for fatigue (AUC: 0,507 95% CI 0,368-0,645). Calibration showed that clinician based CTCAE toxicities substantially underestimated all PRO-based toxicities.
Conclusion
This study has identified that patient reported toxicities and clinician reported toxicities do not always concord. Only anorexia and dysphagia showed good agreement, while for the other toxicities, the agreement was only fair to poor. Furthermore, we showed that clinicians substancially underreport the existence of toxicities. This study adds to the growing body of evidence indicating the potential beneficial role of using PRO-based toxicity reporting in clinical cancer care for lung cancer.
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MA08.08 - Discussant - MA08.05, MA08.06, MA08.07 (Now Available) (ID 3745)
15:15 - 16:45 | Presenting Author(s): Norihiko Ikeda
- Abstract
- Presentation
Abstract not provided
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MA08.09 - Results of Trimodality Therapy for Patients with cN2 Lung Cancer Diagnosed by Video-Assisted Mediastinoscopic Lymphadenectomy (VAMLA) (Now Available) (ID 1295)
15:15 - 16:45 | Presenting Author(s): Sergi Call | Author(s): Carme Obiols, Ramon Rami-Porta, Silvia Catot, Miriam Nuñez, Marc Campayo, Francisco Perez Ochoa, Mireia Serra-Mitjans, Jose Belda-Sanchis
- Abstract
- Presentation
Background
After a properly performed transcervical lymphadenectomy, invasive restaging of the mediastinum is unnecessary because there is no material left for a new biopsy. Therefore, when video-assisted mediastinoscopic lymphadenectomy (VAMLA) is used at primary staging, the only parameters to select patients for lung resection after induction therapy are: the stability of the primary tumor and the absence of extrathoracic disease assessed by PET-CT. The aim of this study is to analyze the results of those patients with cN2 NSCLC diagnosed by VAMLA who underwent trimodality treatment in terms of feasibility and survival.
Method
Prospective observational single-center study of 250 patients (206 men; median age, 65.7; range, 42-86) with NSCLC cN0-1 (by PET-CT) who underwent VAMLA from 01-2010 to 12-2017. Patients with cN2 diagnosed by VAMLA who underwent trimodality treatment (cisplatin-based chemotherapy concomitant with radical radiotherapy [mean 54Gy, range 40-70Gy] plus lung resection) were analyzed. Follow-up was completed in March 2019. Median follow-up for surviving patients was 39.5 months (range, 8-108). Survival analysis was performed by the Kaplan-Meier method; the log-rank test was used for comparisons. Patients who died within 90 days after resection were excluded from survival analyses. A p-value of less than 0.05 was considered significant. The IBM SPSS Statistics for Mac, version 20.0 was used.
Result
The rate of unsuspected N2-3 disease in the whole series was 14.5% (35 patients). 28 patients out of 35 were considered for trimodality treatment. The results of restaging based on the PET-CT were: disease progression in 8 (28.5%) (mostly distant metastases), and stability of the primary tumor or partial response in 20 patients (71.5%). Of 20 patients without progression, 13 (46.5%) underwent lung resection; the remaining 7 were considered unfit for surgery. Three- and 5-year survival rates for those candidates for chemoradiotherapy (n=28) were: 91.7% and 80.2%, respectively, for patients in whom complete lung resection was achieved; 34.3% and 0%, respectively, for those considered unfit for surgery; and 19% and 0%, respectively, for those with progression after chemoradiotherapy (p < 0.0001)(Figure 1).
Conclusion
The use of VAMLA to select patients for trimodality treatment is feasible. Based on the results obtained (high rate of unsuspected cN2 diagnosed by VAMLA and prolonged survival of those patients in whom the trimodality treatment was accomplished), VAMLA should be included in the current staging algorithms, especially for those tumors with intermediate risk of N2 and normal mediastinum by PET-CT.
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MA08.10 - Early and Late Outcomes After Surgery for pT4 NSCLC Reclassified by AJCC 8<sup>th</sup> Edition Criteria (Now Available) (ID 2941)
15:15 - 16:45 | Presenting Author(s): Jack G Mouhanna | Author(s): Amit Katz, Pierre O Fiset, Roni F Rayes, Aya Siblini, Emma Lee, Andrew Seely, Christian Sirois, David Mulder, Jonathan Cools-Lartigue, Lorenzo E. Ferri, Jonathan D. Spicer
- Abstract
- Presentation
Background
Classically, T4 non-small cell lung cancers (NSCLC) are tumors of any size that have features of local extension often precluding surgical resection or necessitating complex extended pulmonary surgery. However, the new AJCC 8thedition includes tumors greater than 7cm regardless of adjacent organ extension. The early perioperative outcomes from T4 resections must be contextualized to the increasingly heterogeneous classification offered by the new staging system. Our goal was to examine perioperative and long-term outcomes from pT4 resections based on the AJCC 7thedition versus those of the expanded criteria of the 8thedition.
Method
This is a retrospective study of pT4 surgical resections at the Montreal General Hospital from 2011-2018. Data was analyzed using GraphPad Prism and SPSS.
Result
We identified 158 patients with pT4 tumors based on AJCC-8: 40 by AJCC-7 criteria (Group1) and 118 with tumors >7cm considered pT4 in AJCC-8 (Group2). Demographics and clinical characteristics are detailed in Table 1. The incidence of major complications (grade 3 or 4) was similar in both cohorts (17.5% in Group1 and 13.6% in Group2; p=0.37), with 3.8% in-hospital mortality (7.5% in Group1 and 2.5% in Group2; p=0.16). Overall survival was 76% at 1 year, 44% at 3 years and 34% at 5 years. Median overall survival was 27 months and was similar between Group1 and Group2 (25.8 and 27.4 months, respectively p=0.7). Nevertheless, Group2 had better peri-operative survival than Group1: 99% vs 92% 90-day mortality (p=0.02) and 95% vs 83% 6-month mortality (p<0.01). Finally, Kaplan-Meier curves adjusted for predictors of survival with Cox regression analysis show early mortality in Group 1 with equalization of the curves at 1 year (Figure 1).
Conclusion
While long-term oncological outcomes are similar for pT4 >7cm to those of AJCC-7 pT4 patients, differences in perioperative outcomes point to the heterogeneity of the new AJCC-8 classification with regards to surgical management.
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MA08.11 - SLCG SCAT Trial: Surgical Audit to Lymph Node Assessment Based on IASLC Recommendations (Now Available) (ID 2252)
15:15 - 16:45 | Presenting Author(s): Jose Ramon Jarabo Sarceda | Author(s): SERGIO Bolufer, Roberto Mongil, Pedro Lopez De Castro, RAMON Moreno, JUAN CARLOS PeÑalver, Raúl Embún, Joaquín Pac, Francisco Javier Algar, Pablo Gámez, Marcelo Jiménez, Gabriel Sales, Eva Pereira, Bartomeu Massuti, Mariano Provencio, Florentino Hernando-Trancho
- Abstract
- Presentation
Background
The Spanish Lung Cancer Group (SLCG) developed a multicenter trial in which completely resected pathological N positive NSCLC patients received different schemes of adjuvance based on level of tumoral BRCA expression (SCAT trial). We assess here surgical topics, with an in-depth analysis of quality of lymphadenectomy based on IASLC recommendations, evaluating their effect on survival.
Method
Phase-III SLCG-SCAT trial included patients with completely resected (R0) NSCLC with pathological hilar and/or ipsilateral mediastinal lymph node (LN) involvement. Patients from SLCG-SCAT trial in which complete pathologic report with information about mediastinal lymph node dissection was available (including number of lymph nodes assessed and involved by tumor in each hilar and mediastinal region), were included for our study. We also analyzed data about estimated overall survival (OS) and disease-free survival (DFS). All patients underwent surgical resection in high-volume departments of thoracic surgery.
Result
Lymph node assessment
From the whole series (451 patients), in 33.7%, 17.7% and 49.9% of cases, regions 7, 10 and 11 respectively were not assessed. No lymph nodes were biopsied from region 8, 9 and 12 in 80%, 61.9% and 91.1% of cases, respectively. Region 10 was that with the higher number of lymph nodes resected (medium 4.64). From them, 27.9% were involved by tumor. Median assessed mediastinal regions was 4. In 21.1% of patients, lymph nodes from only one or two regions were obtained. In most of the patients (91.8%), one or two N1 regions were assessed. From 272 patients with N1 (no N2) involvement, 15.4% had no N2 regions biopsied, 20.2% had one N2 region evaluated and only 39.7% had three or more N2 regions assessed. On the other hand, from 179 patients with positive N2, 8.9% had no N1 regions biopsied and 54.7% had one. From 409 patients with at least one N2 lymph node resected, 120 (29.3%) shown the highest region involved. Number of mediastinal regions assessed and affected, and number of lymph nodes resected and affected were significantly higher in patients with N1 plus N2 disease than those with isolated N1 or N2 involvement.
Survival
Median follow-up was 52.3 months. Five-year OS was 55.7% (CI95% 50.8%-60.3%). Differences were found on OS regarding type of lymph node involvement (N1, N2 or both) (p=0.002). Five-year OS was 61.7% (CI95%:55.4%-67.4%), 51.5% (CI95%:39.2%-62.4%) and 42.3% (CI95%:32.1-52.2%) for patients with N1, N2 and N1+N2 disease, respectively. No differences were found in survival regarding total number of N1 or N2 regions evaluated. Both number of regions involved and number of lymph nodes with tumor were significantly related to worse prognosis.
Conclusion
International recommendations for surgical lymph node assessment in NSCLC were not deemed for the design of the trial and were not followed in a high proportion of cases. Patterns of N1 and N2 involvement shown to impact prognosis. The design of trials assessing surgical series of patients undergoing complete resection requires the control of surgical procedures in order to avoid recruitment biases.
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MA08.12 - Discussant - MA08.09, MA08.010, MA08.11 (Now Available) (ID 3746)
15:15 - 16:45 | Presenting Author(s): Leah Backhus
- Abstract
- Presentation
Abstract not provided
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Author of
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-38 - Gene Expression Profiling of CNS Metastases in Non-Small Cell Lung Cancer - Matched Analyses with Primary Tumors (Now Available) (ID 2636)
10:15 - 18:15 | Author(s): Simon Ekman
- Abstract
Background
Dissemination of non-small cell lung cancer (NSCLC) in the central nervous system (CNS) is a frequent and challenging clinical problem. Systemic or local therapies rarely prolong survival and have modest activity regarding local control. Alterations in gene expression in brain metastasis (BM) versus primary tumour may increase aggressiveness and could explain the worse prognosis of brain metastatic NSCLC.
Method
We identified patients with surgically removed BM from NSCLC in two cohorts. The first cohort consisted of 725 patients with surgically removed NSCLC and the second of 280 patients who had received whole brain radiotherapy during the course of their disease. Gene expression analysis with nanoString PanCancer IO 360 panel was performed in BM and primary tumour samples. A minimum of 50 ng of total RNA was used as input for each sample. Identification of differentially expressed genes was conducted on normalized data using the nSolver analysis software.
Result
30 patients with surgically removed BM were identified from both cohorts. For 13 of these patients primary tumour samples were available. We compared gene expressions in BM with primary tumour samples and found a statistically significant downregulation of certain genes, especially genes related to immune response and immune cell activation. Gene expression profiles from BM samples displayed a distinct clustering pattern compared to primary tumour samples. Results from KEGG-term analysis on differentially expressed genes revealed a concomitant enrichment of multiple KEGG-terms associated with the immune system.
Conclusion
We identified a unique gene downregulation pattern in BM samples compared to primary tumour. This finding may explain the lower clinical efficacy of systemic therapy, especially immunotherapy, in BM of NSCLC patients.
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-33 - An Open-Label PET-MRI Study to Determine Brain Exposure of Osimertinib in Patients with EGFR Mutant NSCLC and CNS Metastases (ID 142)
10:15 - 18:15 | Presenting Author(s): Simon Ekman
- Abstract
Background
CNS metastases are associated with poor prognosis in patients with advanced NSCLC. Osimertinib is a third-generation, irreversible, oral EGFR-TKI that potently and selectively inhibits both EGFR-TKI sensitising (EGFRm) and EGFR T790M mutations, and has demonstrated efficacy in NSCLC CNS metastases. Osimertinib has also shown superior brain exposure (preclinical/clinical), compared to other EGFR-TKIs. We report preliminary data on brain distribution of 11C-labelled osimertinib ([11C]osimertinib) in patients with NSCLC with brain metastases (BM) using positron emission tomography (PET). Early effects on BM measured by magnetic resonance imaging (MRI) is also presented.
Method
This open-label, single-centre Phase I study (NCT03463525) enrolled adult patients with EGFR-mutated advanced NSCLC and BM, as confirmed by MRI. Patients could be EGFR-TKI-naïve or have progressed on a prior EGFR-TKI with confirmed EGFR T790M. Intravenous microdoses of [11C]osimertinib and PET examinations were performed pre-dose on Day1, ~6hrs post-dose on Day2, and following ≥21 days of once-daily dosing with osimertinib 80mg. Following the 3rd PET scan, patients completed another MRI scan to investigate early effects on tumour size according to RECIST 1.1 criteria. The primary objective was determination of brain exposure of [11C]osimertinib at baseline and following treatment, in the whole brain. During PET examinations, arterial blood samples were collected to measure radioactivity/radiometabolites of [11C]osimertinib.
Result
Currently, six patients have been screened. Three enrolled, of whom two completed all imaging visits. PET examinations demonstrated rapid uptake of [11C]osimertinib into the brain and distribution into metastases; MRI scans showed significant decrease in size of brain lesions after 21 treatment days, consistent with partial response according to RECIST 1.1 criteria (Figure).
Conclusion
These early outcomes support the CNS efficacy reported in previous osimertinib studies: high brain-uptake and efficacy after a short dosing period. Further data on distribution, efficacy and PET/MRI imaging will be presented.
