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S. Jheon
Moderator of
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MA 17 - Locally Advanced NSCLC (ID 671)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 15
- Moderators:S. Jheon, Georgios Stamatis
- Coordinates: 10/17/2017, 15:45 - 17:30, F203 + F204 (Annex Hall)
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MA 17.01 - Skip N2, an Independent Prognostic Factor of Survival: Analysis of a Favourable N2 Subgroup (ID 8743)
15:45 - 17:30 | Presenting Author(s): Sara Ricciardi | Author(s): Pietro Bertoglio, C.C. Zirafa, V. Aprile, A. Mussi, M. Lucchi
- Abstract
- Presentation
Background:
To date the nodal status is considered one of the most important indicators of prognosis for resectable NSCLC. The latest edition of lung TNM does not include any changes to N descriptors, but several changing proposals are under evaluation: IASLC proposed a subclassification of pN1-N2 based on the number of nodal station involved (pN1a, pN1b; pN2a1, pN2a2, pN2b). The number of positive lymph nodes and the lymph node ratio were also proposed as prognostic indicators of resected NSCLC. The aim of this study was to compare overall survival (OS) and Disease Free Interval (DFI) of pN2a1 (“skip” metastasis) to pN1b and pN2a2-pN2b.
Method:
A retrospectively analysis of 155 patients who underwent a complete resection and a systematic lymph node dissection for T1/T2 N1-N2 NSCLC (VII TNM edition) between 2006 and 2010 was conducted. Patients who underwent induction therapies or extended resections were excluded. All patients were restaged with the new IASLC proposal. OS, DFI and risk factors of pN1b, pN2a and pN2b patients were analysed.
Result:
An overall mean number of 16 (DS 8,4) lymph nodes were resected: 7,18 (DS 4,2) from the hilum and 8,72 (DS 5,9) from the mediastinum. After restaging all cases with new IASLC proposal we observed: 48 (30,9%) pN1b, 26 (16,8%) pN2a1, 63 (40,7%) pN2a2 and 18 (11,6%) pN2b. With a median follow up of 93 months, the median overall survival of the entire cohort was 27 months. pN2a1 had a significant better overall survival when compared with the other three groups (p=0,042). 1, 3 and 5-year survival for pN1b, pN2a1, pN2a2 and pN2b were 75%, 90%, 81% and 71%; 46%, 53%, 37% and 24%; 24%, 45%, 26% and 19% respectively. A number of more than 5 positive lymph nodes and a lymph node ratio >50% were independent prognostic factors of a worse survival (p=0,004 and p=0,035).
Conclusion:
Our data supports the new IASLC proposal for the revision of N descriptors. Patients with skip lymph node metastasis (pN2a1) have a significant better prognosis compared both to other pN2 groups and to pN1b. Moreover, we confirmed the important prognostic value of the number of the involved lymph node, which should be considered as well in the next edition of the lung cancer staging system.
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- Abstract
- Presentation
Background:
Completely resected stage IIIA(N2) non-small cell lung cancer (NSCLC) patients are considered to be a heterogeneous population. The heterogeneity applies to tumor cells but to the microenvironment as well. Mounting evidence suggests that tumor infiltrating lymphocytes (TILs) are of clinical importance. Hence, we aimed to evaluate the role of the immune microenvironment as an immunoscore in a uniform cohort of patients with completely resected stage IIIA(N2) NSCLC.
Method:
All patients with pathologic stage IIIA(N2) NSCLC who underwent complete resection in our hospital from 2005 to 2012 were retrospectively reviewed. Tissue microarrays were constructed by the surgical pathology specimens from primary lung tumors. For each specimen, we selected two cores from the tumor center (CT) and two cores from invasive margin (IM) region. Densities of immune cell subpopulations (CD3+, CD45RO+, and CD8+ TILs) were evaluated using immunohistochemistry with image analysis workstation (Vectra 3.0). Immunoscore is based on the numeration of two lymphocyte populations: CD45RO+ memory lymphocytes and CD8+ cytotoxic cells, quantified within the CT and IM. The immunoscore (I) provides a score ranging from I0 when low densities of both cell types are found in both regions, to I4 when high densities are found in both regions. The results were correlated with tumor recurrence and patient survival.
Result:
Of the eligible 357 patients, 288 patients with well-established lung tumor samples were obtained and included in the analysis. The median follow-up duration was 54.9 months (range, 23.9-132 months) for the living patients. The 5-year distant metastasis-free survival (DMFS) and overall survival (OS) rates were 26% and 34%, respectively. In univariate analyses, densities of CD3+ cells were associated with neither OS nor DMFS, whereas CD45RO+ cells in IM were prognostic for DMFS (P=0.02) and OS (P=0.05). Combining CD45RO and CD8+ TILs (CT plus IM), the immunoscore(I) significantly increased the prognostic impact. Of the 288 patients, there were 68 (24%) with I0, 64 (22%) I1, 58 (20%) I2, 48 (17%) I3, and 50 (17%) I4. Five-year DMFS and OS rates were 17% and 28% for the group with low immune score (N=190, I0-2), compared with 42% and 45% for the group with high immune score (N=98, I3-4), respectively (DMFS P<0.001; OS P=0.001). Multivariate analyses showed that the immunoscore had independent effects on DMFS (P<0.001) and OS (P<0.001).
Conclusion:
The immunoscore in NSCLC may provide powerful prognostic information, including the prediction of DMFS and OS, and thus facilitate clinical decision making regarding systemic therapy in patients with completely resected stage IIIA(N2) NSCLC.
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- Abstract
- Presentation
Background:
Completely resected stage IIIA(N2) non-small cell lung cancer (NSCLC) patients are a heterogeneous population, with 5-year survival rates ranging from 10% to 30%. The aim of this study was to investigate the relationship between the predominant subtype according to the new IASLC/ATS/ERS pathologic classification and prognosis in completely resected stage IIIA(N2) lung adenocarcinoma.
Method:
The medical records of 179 consecutive patients with completely resected stage IIIA(N2) NSCLC were reviewed between January 2005 and July 2012. According to the new pathologic classification, each tumor was reviewed using the comprehensive histological subtyping while recording the percentage in 5% increments for each histological component. Adenocarcinoma was divided into lepidic predominant, papillary predominant, acinar predominant, micropapillary predominant and solid-predominant. The predominant pattern was defined as the pattern with the largest percentage. To compare progression-free survival (PFS) and overall survival (OS) time between difference subtypes in lung adenocarcinomas, log-rank test was used for univariate analysis, and cox regression was used for multivariate analysis.
Result:
The median follow-up time was 42.7 months (range, 4.4–96.7months). The median PFS and OS time was 19.6 and 45.5 months, respectively. The 5-year PFS and OS rates were 16.4% and 34.6%, respectively. Patients with micropapillary and solid predominant tumors had poorer PFS (p=0.027) and OS (p=0.003) as compared to those with other subtypes predominant tumors. Micropapillary and solid predominant tumors were also significantly associated with an increased risk of locoregional recurrence (P=0.025), while not significantly associated with distant metastasis (P=0.21) than other subtypes predominant tumors. Multivariate analysis revealed that the new classification, chemotherapy, clinical N stage and LN ratio were independent prognostic factors for OS. Figure 1
Conclusion:
In patients with completely resected stage IIIA(N2) NSCLC, the predominant subtype according to new IASLC/ATS/ERS classification was an independent prognostic factor. It is valuable of screening out high risk patients to receive postoperative adjuvant therapy.
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MA 17.04 - Initial Surgery in Patients with Clinical N2 Non-Small Cell Lung Cancer: A Multi-Institution Retrospective Study (ID 7349)
15:45 - 17:30 | Presenting Author(s): Tomohiro Maniwa | Author(s): Y. Shintani, J. Okami, M. Ohta, Y. Takeuchi, K. Takami, H. Yokouchi, E. Kurokawa, Ryu Kanzaki, Y. Sakamaki, H. Shiono, T. Iwasaki, K. Nishioka, K. Kodama, Meinoshin Okumura
- Abstract
- Presentation
Background:
There is no large scale study of the initial surgery for patients with cN2 disease who received positron emission tomography (PET). We investigated the outcomes of initial surgery for patients with cN2 disease who had received PET, by conducting a multi-institutional retrospective study.
Method:
Clinical data for 143 patients who had cN2 disease and underwent initial surgery at 12 Japanese institutions in Thoracic Surgery Study Group of Osaka University (TSSGO) between January 2006 and December 2013 were collected. After reviewing all the data for eligibility, completeness, and consistency, 8 cases were excluded. The remaining 135 cases were feasible for analysis. Among these patients, 98 received PET and were analyzed.
Result:
The median follow-up was 56.5 months (2-110 months). The median age was 67 (35-80) years. There were 71 males and 27 females. The histology was adenocarcinoma (n=66), non-adenocarcinoma (n=33). The tumor location was the right upper lobe and left upper segment (n=66, 67.3%), and the others (n=32, 32.6%). Of 98 patients, 85 (86.7%) had clinical single N2 disease and 80 (81.6%) had no mode of spread lesion and 90 (91.8%) underwent lobectomy. The 5-year relapse free survival (RFS) rate and the 5-year overall survival (OS) rate for patients with cN2 were 34.6% and 46.6%. There were 24 patients (24.9%) with cN2pN0,1 and 74 patients (75.5%) with pN2. Of 74 patients with cN2pN2 disease, 42 (59.5%) had pathological single N2 disease and 40 (54.0%) underwent adjuvant chemotherapy. The 5-year RFS for the patients with cN2 in the cN2pN0,1 and cN2pN2 groups were 62.2% and 26.0%, respectively (p=0.0025). The 5-year OS for the patients with cN2 in the cN2pN0,1 and cN2pN2 groups were 74.8% and 40.0%, respectively (p=0.029). Moreover, we provided the following 3 criteria: primary tumor in right upper lobe or left upper segment, N2 disease with regional mode of spread, and patients who did not undergo pneumonectomy. 60 patients who fulfilled all of these criteria were regarded as specific group. The 5-year OS for the patients with cN2 in the specific group and non-specific group was 55.8% and 32.0%, respectively (p=0.024).
Conclusion:
Among patients with cN2 disease, those with pN2 disease were more in number in our study than in previous reports. Our patients with cN2pN2 had better survival compared with those in previous reports. In particularly, patients with clinical N2 disease in specific group have a favorable prognosis. An initial surgery may be considered as a treatment option for these patients.
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MA 17.05 - Discussant - MA 17.01, MA 17.02, MA 17.03, MA 17.04 (ID 10793)
15:45 - 17:30 | Presenting Author(s): Jin Seok Ahn
- Abstract
- Presentation
Abstract not provided
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MA 17.06 - Safety Data from Randomized Phase II Study of CDDP+S-1 vs CDDP+PEM Combined with TRT for Locally Advanced Non-Squamous NSCLC (ID 8296)
15:45 - 17:30 | Presenting Author(s): Akira Ono | Author(s): T. Takahashi, Seiji Niho, T. Yoshida, T. Akimoto, K. Sakamaki, Takashi Seto, Makoto Nishio, N. Yamamoto, T. Hida, Hiroaki Okamoto, T. Kurata, Miyako Satouchi, Koichi Goto, T. Yamanaka, Yuichiro Ohe
- Abstract
- Presentation
Background:
Both cisplatin (CDDP)+S-1 and CDDP+pemetrexed (PEM) can be given at full systemic doses with thoracic radiotherapy (TRT) in locally advanced non-small cell lung cancer (NSCLC), and CDDP+PEM is one of the standard chemotherapy regimens in patients with advanced non-squamous (non-sq) NSCLC. This multicenter, randomized, open-label, phase II study (SPECTRA) compared the efficacy and safety of the two above-mentioned promising regimens combined with TRT in patients with unresectable locally advanced non-sq NSCLC.
Method:
Patients were randomly assigned to receive CDDP+S-1 (CDDP 60mg/m2, d1, and S-1 80mg/m2, d1-14, q4w, up to 4 cycles) or CDDP+PEM (CDDP 75mg/m2, d1, and PEM 500mg/m2, d1, q3w, up to 4 cycles) combined with TRT 60Gy in 30 fractions. The primary endpoint was 2-year progression-free survival (PFS) rate. If the 2-year PFS rate is assumed to be 25% in the inferior therapy group and 15% higher in the superior therapy group of this study, the sample size needed for selection of the optimum treatment group at a probability of approximately 95% will be 51 cases/group with the Simon’s selection design. The sample size was set at 100 patients.
Result:
Between Jan 2013 and Oct 2016, 102 patients were enrolled in this study from 9 institutions in Japan. All 102 patients were eligible and assessable, of whom 52 were assigned to CDDP+S-1 and 50 to CDDP+PEM. Baseline characteristics were similar (CDDP+S-1/CDDP+PEM): median age (range) 64.5 (39-73)/63.5 (32-74) years; women, n=17 (33%)/n=17 (34%); stage IIIB, n=21 (40%)/n=20 (40%); ECOG PS of 1, n=14 (27%)/n=14 (28%); never smoker, n=12 (23%)/n=12 (24%); and adenocarcinoma, n=47(90%)/n=45(90%). Completion rate of TRT (60Gy) and chemotherapy (4 cycles) was 92%/98% and 73%/86%, respectively. Response rate was 60%/64%. Grade 3 or higher toxicities included febrile neutropenia (12%/2%), anorexia (8%/16%), diarrhea (8%/0%), esophagitis (6%/8%), pneumonia (4%/4%), neutropenia (38%/52%), anemia (8%/12%), thrombocytopenia (4%/6%), and hyponatremia (12%/12%). Grade 1 radiation pneumonitis was observed in 8 (15%)/2 (4%) patients on the basis of the data collected 30 days or less after the discontinuation of protocol treatment. No treatment-related death was observed. The data on PFS and overall survival are immature.
Conclusion:
Response rate was similar between the two arms. Toxicities were tolerable and manageable in both arms; however febrile neutropenia was more frequently observed in the CDDP+S-1 arm. We will present the updated safety data of this study at the conference. Survival data will be analyzed in late 2018.
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MA 17.07 - Veliparib in Combination with Paclitaxel/Carboplatin (P/C)-Based Chemoradiotherapy (CRT) in Patients with Stage III NSCLC (ID 10210)
15:45 - 17:30 | Presenting Author(s): Thomas E. Stinchcombe | Author(s): D. Kozono, J.K. Salama, J. Bogart, W. Petty, M.J. Guarino, Lyudmila A Bazhenova, J.M. Larner, Jared Weiss, T.A. Dipetrillo, S.J. Feigenberg, T. Xu, B. Hu, S. Nuthalapati, L. Rosenwinkel, L. Bensman, E.F. Johnson, M.D. McKee, Everett E Vokes
- Abstract
- Presentation
Background:
CRT is a standard for patients with Stage III non-small cell lung cancer (NSCLC). Veliparib (V) is a potent, orally bioavailable PARP1/2 inhibitor that can delay DNA repair following chemotherapy or radiation induced damage. A phase 2 study indicated favorable efficacy of V vs placebo when added to P/C in advanced NSCLC (Ramalingam et al. Clin Cancer Res. 2016). Based on these results, a phase 1/2 trial was initiated to study the safety and efficacy of V/P/C-based CRT in the treatment of Stage III NSCLC.
Method:
Patients without prior NSCLC therapy suitable for definitive CRT received V plus C AUC 2 + P 45 mg/m[2] weekly + 60 Gy over 6-9 weeks. V was escalated from 60 mg BID to a maximum planned dose based on prior studies of 240 mg BID via 3+3 design with over-enrollment allowed followed by consolidation therapy of V 120 mg BID + C AUC 6 + P 200 mg/m[2] for up to two 21-day cycles.
Result:
Thirty-nine patients (median age 66; 14 male) have been enrolled to date into dosing cohorts at 60 mg (7), 80 mg (9), 120 mg (7), 200 mg (8), and a maximum planned dose of 240 mg (8). Median tumor volume at screening was 81 cc (16-555 cc). PK of V was dose proportional. CRT or V required dose reduction for 0 or 1 patient, respectively. Four (10%) patients discontinued study during CRT. No DLTs were observed and an MTD has not been identified. The most common any-grade AEs were esophagitis (23), nausea (22), fatigue (20), neutropenia (19), and thrombocytopenia (19). 27 SAEs occurred including 12 SAEs with reasonable attribution to V but outside the DLT window including G3/4 febrile neutropenia (2), G3 dehydration (1), G3 vomiting (1), G3 esophagitis (1), G3 radiation esophagitis (1), G3 esophageal stricture (1), G3 intractable N/V (1), G3 aspiration pneumonia (1), G3 radiation pneumonitis (1), G4 sepsis (1), and G5 sepsis during consolidation (1). Of 29 patients evaluable for tumor assessment, best response was CR (2), PR (22), SD (3), and PD (2).
Conclusion:
V/P/C-based CRT followed by V/P/C consolidation therapy is a tolerable regimen for the treatment of Stage III NSCLC. The RPTD for V during CRT is 240mg BID. A randomized placebo-controlled phase 2 extension of this study is planned. Clinical trial information: NCT02412371
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MA 17.08 - The Validity of TNM Classification After Induction Treatment in Patients with NSCLC: Pulmonary Resection with or Without Induction Treatment (ID 9613)
15:45 - 17:30 | Presenting Author(s): Cengiz Gebitekin | Author(s): Huseyin Melek, Gamze Cetinkaya, E. Özer, E. Yentürk, T. Sevinç, T. Evrensel, A.S. Bayram
- Abstract
- Presentation
Background:
Pathological staging (pTNM) after lung resection provides the most reliable data for staging non-small cell lung cancer (NSCLC) and predicting long-term survival. However, the survival rate of patients who undergo direct surgical treatment (pTNM) may differ from those who undergo lung resection after induction treatment due to locally advanced lung cancer (ypTNM). In this study we aim to compare the survival rate of pTNM versus ypTNM.
Method:
In this study, we retrospectively reviewed the prospectively recorded data of the patients undergoing surgery (segmentectomy or more) for NSCLC between 2006 and 2016. The patients were staged according to the 8th edition of TNM staging and divided into two groups. Group 1: patients who underwent direct surgical resection (n:450), Group 2: patients who received induction treatment before surgical resection for locally advanced NSCLC (n:345). We compared the survival rates and additional factors that affected the survival rates.
Result:
Postoperative histopathological investigation revealed ypT0N0 in 66 patients (complete response, group 2), stage 1 in 310 patients (group 1 n=211, group 2 n= 99) stage 2 in 223 patients (group 1 n=133, group 2 n= 90), stage 3 in 177 patients (group 1 n=100, group 2 n= 77), stage 4 in 19 patients (group 1 n=6, group 2 n= 13). Five year survival rate in all patients was 59,4% (group 1= 64,6%, group 2= 52,7%, p=0,001). Five year survival rate was 69,7% for complete response group. For patients with stage 1 disease survival rates were 81,9% for group 1 and 63,5% for group 2 (p=0,001). Patients with stage 2 had 5 year survival rates of 55,9% for group 1 and 45,9% for group 2 (p=0,11). Patients staged 3 and 4 had 5 year survival rates of 44,8% for group 1 and 34,4% for group 2 (p=0,10).
Conclusion:
This study revealed that survival rates varied between the patients who underwent direct surgery (pTNM) and the patients who underwent induction treatment before lung resection for locally advanced NSCLC. We recommend that the IASLC should examine the ypTNM stage in more detail in order to achieve more accurate results.
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MA 17.09 - Discussant - MA 17.06, MA 17.07, MA 17.08 (ID 10794)
15:45 - 17:30 | Presenting Author(s): Clarissa Mathias
- Abstract
- Presentation
Abstract not provided
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MA 17.10 - Toxicity Results from the Randomized Phase III NVALT-11 Study of Prophylactic Cranial Irradiation vs. Observation in Stage III NSCLC (ID 9262)
15:45 - 17:30 | Presenting Author(s): Dirk K De Ruysscher | Author(s): Anne-Marie C. Dingemans, J. Praag, J. Belderbos, C. Tissing-Tan, J. Herder, T. Haitjema, F. Ubbels, F.J. Lagerwaard, J. Stigt, Egbert F Smit, H. Van Tinteren, V. Van Der Noort, H.J. Groen
- Abstract
- Presentation
Background:
NVALT-11 randomized trial showed that PCI reduced the proportion of stage III NSCLC patients with symptomatic BM from 28 % to 5 % (Groen ASCO 2017). Here, we report on the toxicity.
Method:
We randomized between PCI or observation in radically treated stage III NSCLC. Primary endpoint: incidence of symptomatic brain metastases; secondary endpoints: OS, toxicity and quality of life.
Result:
Between 2009 and 2015 a total of 195 pts were registered, 175 were randomized, 87 received PCI and 88 pts were in the observation arm. Median follow up: 48.5 months (95% CI, 39-54). Neurological adverse events (AE) of all grades that occurred more frequently in the PCI vs. the observation arm: cognitive disturbance (18 vs. 2 pt; p< 10[-4]) and memory impairment (25 vs. 7 pt; p<10[-3]). No significant difference in G3-4 cognitive disturbance and memory impairment. Non-neurological AE of all grades that were more frequent in the PCI arm: alopecia (36 vs. 5 pt; p<10[-6]), fatigue (55 vs. 29 patients; p<10[-4]), nausea (30 vs. 15 patients; p=0.01), anorexia (6 vs. 0 patients; p=0.01) and dysphagia (11 vs. 2 pt; p=0.01). Of the G3-4 AE, only fatigue was significantly more present in the PCI arm (13 vs. 2 pt, p < 0.01). Scored as treatment-related, neurological toxicities of all grades that occurred more frequently in the PCI vs. the observation arm: cognitive disturbance (7 vs. 0 pt; p=0.01), dizziness (7 vs. 0 pt; p=0.01) and memory impairment (14 vs. 0 pt; p<10[-4]). No significant differences in G3-4 toxicities, with only one patient reporting severe cognitive disturbance in the PCI group. Scored as treatment-related, non-neurological toxicities of all grades that were more frequent in the PCI arm: alopecia (26 vs. 1 pt; p<10[-6]), fatigue (19 vs. 2 patients; p<10[-4]), nausea (16 vs. 0 patients; p<10[-5]), headache (19 vs. 1 pt; p<10[-5]), rash (8 vs. 0 pt; p<0.01) and vomiting (9 vs. 0 pt; p<0.01). No significant differences in G3-4 toxicities, with 3 patients reporting severe fatigue, 2 nausea and 1 vomiting, all in the PCI group. Overall Qol was worse in the PCI arm 3 months post-treatment, but was similar to observation thereafter.
Conclusion:
PCI related symptoms were mainly grade 1-2 memory and cognitive disturbances and fatigue. G3-4 toxicities were very rare. QoL was only temporarily affected by PCI. The side effects of PCI should be balanced against deteriorating BM symptoms and the lack of OS benefit (Groen ASCO 2017).
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MA 17.11 - Prediction of Response to Trimodality Therapy Using CT-Derived Radiomic Features in Stage III Non-Small Cell Lung Cancer (NSCLC) (ID 10336)
15:45 - 17:30 | Presenting Author(s): Vamsidhar Velcheti | Author(s): P. Jain, U. Ahmad, Sudish Murthy, K. Stephans, M. Khorrami, A. Madabhushi
- Abstract
- Presentation
Background:
There are no clinically validated biomarkers to identify patients with locally advanced NSCLC who benefit from trimodality therapy (TMT) (i.e. neoadjuvant chemoradiation (NAT) followed by surgery). In this study, we evaluate radiomic (i.e. computer extracted imaging) features of tumor phenotype as potential predictors of pathological response.
Method:
123 patients with stage III NSCLC who received TMT were selected for this study. Of these, 33 patients including those with distant metastasis at presentation and those without baseline pre-NAT CT scans were excluded. Lung tumors were retrospectively contoured on 3D SLICER software by an expert reader. A total of 1542 radiomic features (textural and shape) were extracted from intra and peritumoral region using the MATLAB® 2016a platform (Mathworks, Natick, MA). A random forest (RF) machine classifier was trained with the most predictive features identified on the training set (n=45) and then validated on an independent test set (n=45). The primary endpoint of our study was pathological response defined as the percentage of the residual viable tumor.
Result:
90 patients with NSCLC were included for analysis with a median age of 64 years (38−88), and 54.4 % men. Tumor histology was predominantly adenocarcinoma (71.1%), stage IIIA (94.4%), with positive N2 nodes (91.1%). Pathological response was achieved in 36 (40%) patients; labeled responders (R) and the rest 54 (60%) were labeled non-responders (NR). No statistically significant difference was found in clinical characteristics. We identified five radiomic features (intratumoral and peritumoral textural patterns) predictive of pathological response (Area under Receiver Operating Characteristic (ROC) Curve = 0.7806, RF classifier). Figure 1
Conclusion:
Texture features extracted from within and around the lung tumor on CT images were predictive of pathological response to NAT. Additional validation of these quantitative image-based biomarkers is warranted for accurate early identification of responders who could be potentially spared surgery.
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MA 17.12 - Comparison of EORTC, PERCIST, PeterMac & Deauville PET Response Criteria after Radical ChemoRT in Non-Small-Cell Lung Cancer (ID 8169)
15:45 - 17:30 | Presenting Author(s): Guy-Anne Turgeon | Author(s): A. Iravani, T. Akhurst, J. Callahan, A.J. Cole, M. Bressel, S.J. Everitt, S. Siva, David L Ball, M.P. Mac Manus
- Abstract
- Presentation
Background:
Response criteria for 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for thoracic malignancies include European Organization for Research and Treatment of Cancer (EORTC) criteria, Positron Emission tomography Response Criteria In Solid Tumors 1.0 (PERCIST), PeterMac Metabolic Visual Criteria and Deauville Criteria. It is unknown which criteria have the highest prognostic value in NSCLC.
Method:
Between 2004 and 2016, three NSCLC prospective trials included patients treated with radical radiotherapy (RT) or chemoRT with baseline and post-treatment FDG-PET imaging. For each patient, the four FDG-PET response criteria were reported retrospectively and blinded to outcome. Responses to therapy were categorized as complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD) or progressive metabolic disease (PMD) and correlated with subsequent survival using Cox proportional hazard models, c-statistic, r[2] and Akaike information criterion (AIC).
Result:
Eighty-seven NSCLC patients underwent FDG-PET before and after radical RT (n=7) or chemoRT (n=80). Follow-up FDG-PET scans were performed at a median of 89 days (range 47-123 days) after RT. After a median follow-up of 49 months, median survival after PET response imaging was 28 months. Both qualitative response criteria (PeterMac and Deauville) showed perfect agreement (kappa = 1.0). Both semiquantitative criteria (EORTC and PERCIST) showed almost perfect agreement (kappa = 0.96). All four response criteria showed statistically significant associations with overall survival. The PeterMac and the Deauville criteria showed stronger survival associations (AIC=357.9) compared to EORTC (AIC=362.3) and PERCIST (AIC=362.6). The two qualitative criteria also performed better in the distinction between CMR and non-CMR (HR = 1.9, CI 1.0-3.4, p=0.047) versus EORTC (HR=1.2, CI 0.6-2.3, p=0.566) and PERCIST (HR 1.2, CI 0.6-2.3, p=0.548). Only 1, 4 and 6 patients had SMD in respectively PeterMac/Deauville, EORTC and PERCIST. Figure 1
Conclusion:
The visual PeterMac and Deauville criteria showed stronger predictive capacity than EORTC and PERCIST criteria, especially for distinguishing CMR from non-CMR.
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MA 17.13 - Impact of Histologic Subtype of Locally Advanced Lung Adenocarcinoma on Outcomes After Definitive Chemoradiation (ID 10382)
15:45 - 17:30 | Presenting Author(s): Abraham J. Wu | Author(s): S.H. Patel, Andreas Rimner, J. Montecalvo, William D Travis
- Abstract
- Presentation
Background:
Micropapillary and solid subtypes of lung adenocarcinoma have significantly worse outcomes and survival after surgical resection for early-stage disease. These subtypes have recently been shown to have higher locoregional and metastatic progression after definitive stereotactic radiation therapy (SBRT) as well. However, the potential impact of histologic subtype on locally advanced disease treated with definitive concurrent or sequential chemoradiation (CRT) has not been previously explored. We sought to identify high-risk subtype patients treated with CRT, and compare their outcomes with those not known to have high-risk histologic subtypes.
Method:
We identified 249 consecutive patients with stage IIIA-B lung adenocarcinoma who had undergone CRT at our institution from 2008 to 2015. All patients had pathology reviewed by pathologists at our institution with subspecialty expertise in thoracic pathology. Twenty-five patients had elements of micropapillary and/or solid subtype on core biopsy, according to the 2015 World Health Organization classification. The remaining 224 patients were considered non-high-risk (8 patients had core biopsy with no high-risk subtypes identified; 216 patients either did not undergo core biopsy or did not have subtyping performed). Local, nodal, regional, and distant failure were estimated using cumulative incidence (CI) curves and compared using the log-rank test. Time to each event was measured from the date of diagnosis until the event of interest or the last follow-up visit.
Result:
With median followup of 19.7 months, there was a trend towards greater 2-year CI of local failure in the high-risk vs. non-high-risk group (40.7% vs. 26.7% p=0.060). The 2-year CI of nodal, regional, and distant failure in high-risk versus non-high-risk groups was 30.9% vs. 32.6% (p=0.576), 24.7% vs. 20.1% (p=0.468), and 63.9% vs. 59.8% (p=0.272), respectively, though statistical power was limited due to the small number of known high-risk patients.
Conclusion:
Though only a limited proportion of patients had demonstrated high-risk subtypes in this cohort, there was a trend towards earlier local failure in locally advanced adenocarcinoma patients treated with definitive concurrent or sequential chemoradiation, similar to what has been observed for early-stage tumors treated with SBRT. Hence, high-risk histologic subtype may be a prognostic factor for early treatment failure in locally advanced adenocarcinoma patients treated with CRT. We suggest that core biopsies, which are required for histologic subtyping, should be obtained more often in these patients, to allow for further study of the hypothesis that histologic subtype predicts outcomes after definitive chemoradiation.
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MA 17.14 - Phase I Trial Evaluating MEK Inhibitor Selumetinib with Concomitant Thoracic Radiotherapy in Non-Small-Cell Lung Cancer (ID 8982)
15:45 - 17:30 | Presenting Author(s): Kate Haslett | Author(s): Fiona Blackhall, P.K. Koh, L. Ashcroft, M. Asselin, C. Harris, A. Jackson, P. Manoharan, D. Mullan, D.J. Ryder, M.B. Taylor, Corinne Faivre-Finn
- Abstract
- Presentation
Background:
The RAS/RAF/MEK/ERK signalling pathway has a pivotal role in cancer proliferation and modulating response to treatment. Selumetinib, an inhibitor of MEK, has been shown to enhance the effect of radiotherapy (RT) in preclinical studies.
Method:
Single-arm, single-centre, open-label phase I trial. Patients with stage III non-small cell lung cancer (NSCLC) not suitable for concurrent chemo-radiotherapy or stage IV with dominant thoracic symptoms. Patients were recruited to a dose-finding stage (based on the Fibonacci 3+3 design; maximum number =18) followed by the recruitment of an expanded cohort (n=15). Oral Selumetinib (AZD6244, ARRY-142886) was administered at a starting dose of 50mg twice daily commencing 7 days prior to RT, then in combination with thoracic RT for 6-6.5 weeks (60-66Gy in 30-33 fractions). The primary objective was to determine the recommended Phase II dose.
Result:
From 06/10-02/15, 21patients enrolled. Median age 63 years (range 50-73). M:F ratio 12(57%):9(43%). ECOG PS 0:1, 7(33%):14(67%). Stage III 16(76%):IV 5(24%). Mean GTV 64cm[3] (range 0.8–223.7). In the dose-finding stage, 2 out of 6 patients experienced dose-limiting toxicities (DLT) but only one DLT (G3 diarrhoea) was attributable to treatment. Despite meeting criteria for escalation, trial management group elected to treat patients on the expanded cohort (n=15) at the starting dose. All 21 patients completed RT as planned and received induction chemotherapy. Compliance rate of Selumetinib was >80%. Common adverse events are listed-see table. There were 2 survivors (24 & 26months) at analysis. The median survival was 9.7 months and 2-year survival was 24%. The main cause of disease progression was distant metastases in 16/21 (76%).
Conclusion:
The combination of thoracic RT and Selumetinib is feasible and associated with an acceptable toxicity profile. However our efficacy results, based on 21 patients, suggest that this combination should not be pursued in a subsequent phase II trial.Acute Toxicity (CTCAE v4.0) (during treatment and including up to 3 months post treatment) Toxicity Grade N = 21 (%) Acneiform rash 0 1 2 3 4 (19.04%) 7 (33.33%) 9 (42.86%) 1 (4.76%) AST[1] increased 0 1 3 17 (80.95%) 3 (14.29%) 1 (4.76%)** Diarrhoea 0 1 2 3 5 (23.81%) 13 (61.90%) 2 (9.52%) 1 (4.76%)* GGT[2] increased 0 1 2 3 16 (76.19%) 2 (9.52%) 2 (9.52%) 1 (4.76%) Haemoptysis 0 1 19 (90.48%) 2 (9.52%) Maculo-papular rash 0 1 3 16 (76.19%) 4 (19.05%) 1 (4.76%) Mucositis 0 1 2 18 (85.71%) 2 (9.52%) 1 (4.76%) Nausea 0 1 2 11 (52.38%) 9 (42.86%) 1 (4.76%) Radiation dermatitis 0 1 2 3 8 (38.10%) 7 (33.33%) 5 (23.81%) 1 (4.76%) Radiation oesophagitis 0 1 2 3 3 (14.29%) 2 (9.52%) 15 (71.43%) 1 (4.76%) Radiation pneumonitis 0 1 2 15 (71.43%) 0 6 (28.57%) Late Toxicity (follow up from 3+ months onwards) Toxicity Grade N = 21 (%) Pneumonitis 0 1 2 16 2 (9.52%) 3 (14.29%) Pulmonary fibrosis 0 1 19 2 (9.52%) Radiation oesophagitis 0 2 19 (90.48%) 2 (9.52%) * patient stopped drug on day 49 **patient stopped drug on day 29 abbreviations: 1) AST, Aspartate aminotransferase 2) GGT; Gamma-glutamyltransferase
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MA 17.15 - Discussant - MA 17.10, MA 17.11, MA 17.12, MA 17.13, MA 17.14 (ID 10792)
15:45 - 17:30 | Presenting Author(s): Olfred Hansen
- Abstract
- Presentation
Abstract not provided
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Author of
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MA 13 - New Insights of Diagnosis and Update of Treatment (ID 674)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:S. Ishikura, H. Nakayama
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 311 + 312
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MA 13.12 - Wedge Resection and Segmentectomy Are Associated with Comparable Outcomes for Patients with Less Than 2cm Non-Small Cell Lung Cancer (ID 10162)
15:45 - 17:30 | Author(s): S. Jheon
- Abstract
- Presentation
Background:
Sublobar resection is widespread for selected patients with small sized non-small cell lung cancer (NSCLC). Segmentectomy has been considered superior to wedge resection, however well-balanced comparative studies are lacking. We compared oncologic outcomes between wedge resection and segmentectomy for patients with less than 2cm of NSCLC according to parenchymal safety margin
Method:
A retrospective review of a prospective database was performed (2003-2015), excluding patients with poor lung function (FEV~1~ or DLCO <50%), neoadjuvant therapy, previous lobar resection for primary lung cancer, and multiple primary other cancer. Demographic, clinical, and pathological data were reviewed. Overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method and differences compared using log-rank test. Lymph nodes (LN) were evaluated preoperatively by PET/CT and EBUS-FNA if chest CT showed more than 1cm of LN short diameter
Result:
Two hundred nighty-six patients met our selection criteria, including wedge resection (W) in 188 and segmentectomy (S) in 108. There was no difference in smoking history, comorbidity, pulmonary reserve, cell type, and postoperative complication rate. All enrolled patients had clinically negative LN and 3 patients (1 in W, 2 in S) had pathologically node positive LN. The segmentectomy had more likely to have larger tumor (1.26 vs 1.36, p=0.045), more total nodes resected (1 vs 6, p<0.001), more distance of safety margin (median 0.5 vs 1.5, p<0.001). There was no statistical difference in OS (p=0.897), CSS (p=0.844), and RFS (p=0.763) between two groups. Patients were stratified by safety margin into ≤ 5mm in 118 (w101 vs s17), 5~10mm in 65 (w48 vs s17), 11~15mm in 45 (w23 vs s22), 16~20mm in 23 (w9 vs s14), and >20mm in 45 (w7 vs s38). Recurrence was developed in 8 (7%, w5 vs s3), 2 (3%, w2 vs s0), 1 (2%, s1), 0 (0%), 1 (2%, s1) of each safety margin. There was no significant difference of RFS between wedge resection and segmentectomy in each safety margin
Conclusion:
Wedge resection and segmentectomy showed comparable oncologic outcomes for carefully staged less than 2cm NSCLC patients. After thorough preoperative LN evaluation, wedge resection of sufficient safety margin is good surgical option
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