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Sheng Zhang
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EP1.12 - Small Cell Lung Cancer/NET (ID 202)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.12-10 - Molecular Characterization of NSCLC-Like and SCLC-Like Subsets in Chinese Pulmonary Large-Cell Neuroendocrine Carcinoma (LCNEC) (Now Available) (ID 1341)
08:00 - 18:00 | Author(s): Sheng Zhang
- Abstract
Background
LCNEC is an aggressive, biologically heterogenous carcinoma which can be molecularly characterized as SCLC-like and NSCLC-like. Accurate distinction of molecular subset is of major clinical relevance since it may guide treatment choices in LCNEC. Here we determined the genomic characteristics of the two LCNEC subsets in a Chinese cohort to clarify their correlations with traditional lung cancer histologies.
Method
FFPE samples from 31 LCNECs were sequenced using a 520-cancer-related gene panel, with an average sequencing depth of 1385X. Comparative mutational analysis was conducted between NSCLC-like LCNECs from our cohort and adenocarcinomas from TCGA dataset
Result
Despite similar clinical features in terms of stage and age at diagnosis, NSCLC-like (42%, 13/31) and SCLC-like (32%, 10/31) subsets from LCNEC displayed distinct molecular characteristics. NSCLC-like subset harbored significant higher mutation frequencies of STK11, KEAP1 and FAT3 (53.8%, 38.5% and 38.5%, p=.007, .046 and .046), while SCLC-like subset was characterized by highly mutated RB1 (100%, p<.001) and PTEN (50%, p=.007). Compared with TCGA adenocarcinomas, NSCLC-like LCNEC displayed more frequent mutations in TP53, STK11, APC, KMT2D and SMARCA4 (76.9%, 53.8%, 30.8%, 30.8% and 23.1%; p=.043, .004, .045, .005 and .049). In addition, potential targetable alterations were present in 46.2% (6/13) pts of NSCLC-like subset. For those advanced stage pts, 2/5 NSCLC-like and 5/5 SCLC-like pts received relevant chemotherapy according to their molecular characteristics. The clinical outcomes of these pts are still under follow-up.
Conclusion
This study demonstrates the distinct molecular features between NSCLC-like and SCLC-like subsets, and highlights the predominant genomic similarity and separate entities between NSCLC-like LCNEC with adenocarcinoma. Given the evidence that genomic profiling may aid in informing treatment decisions for pts with LCNEC, our study indicates that, based on accurate molecular typing, 46.2% NSCLC-like pts may benefit from potential targeted therapy and the rest of them may be more suitable to receive NSCLC-chemotherapy
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MA01 - Oligometastatic Disease (ID 114)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Now Available
- Moderators:Anne Marie Clasina Dingemans, Matthias Guckenberger
- Coordinates: 9/08/2019, 10:30 - 12:00, Copenhagen (1980)
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MA01.09 - Concomitant SBRT and EGFR-TKI Versus EGFR-TKI Alone for Oligometastatic NSCLC: A Multicenter, Randomized Phase II Study (Now Available) (ID 2214)
10:30 - 12:00 | Author(s): Sheng Zhang
- Abstract
- Presentation
Background
NSCLC patients harboring EGFR mutation generally develop resistance to EGFR TKI less than one year. Prior studies indicated that local consolidative therapy is associated with improved outcomes in patient with limited metastatic NSCLC. Radiotherapy is one of the ideal control methods for locally progressed patients, however, the optimal intervention time in order to slow the occurrence of EGFR-TKI resistance for advanced NSCLC patients with EGFR-sensitive mutations is still unclear. Our preliminary clinical and animal studies suggest that early combined radiotherapy prior to EGFR-TKI resistance can significantly improve the prognosis of patients. Our hypothesis is that the optimal intervention time of radiotherapy for EGFR mutation patients is 3 months after the beginning of EGFR-TKI.
Method
This is a prospective, multicenter, randomized controlled study to evaluate stereotactic body radiation therapy (SBRT) as a potential treatment for limited stage IV NSCLC (primary plus up to 3 metastatic sites) with sensitive EGFR mutation. The patients did achieve partial response or stable disease after three months treatment of the first-generation EGFR-TKI would be randomized to TKI combined SBRT (TS) or TKI alone. The primary endpoint was PFS (the time from the beginning of EGFR-TKI treatment to disease progression or death). The secondary endpoint was overall survival (OS) and safety. TKI wasn’t interrupted during the irradiation.
Result
A total of 61 patients were enrolled from Feb, 2017 to Jan, 2019. Median follow up was 22.3 months. Patients who TS (n: 30) had a significantly longer median PFS compared to those with TKI alone (n: 31) (PFS: 17.4 vs. 8.9 months P =0.042). T790M mutation was observed in 57.9% acquired resistance patients for TS group, and 39.3% for TKI alone group. Median PFS of T790M mutated patients was 17.4 months compared to 10.3 months of TKI alone group (P = 0.007). Multivariable analysis revealed that radiation fields were positively associated with PFS, 21.8 months for just primary tumor; 10.6 months for metastatic lesions and 18.3 months for primary and metastatic lesions (P= 0.006). OS data was not yet mature. None experienced >= grade 3 SBRT related toxicities.
Conclusion
A trend of improved long term PFS was noted in patients receiving SBRT for primary tumor combined EGFR TKI at the third month after the beginning of TKI. Moreover, this data suggested that benefit from radiation might be associated with delay the occurrence of T790M mutation. Further studies are required to investigate the molecular mechanisms underlying this association.
Clinical Trial information: NCT03595644
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OA03 - Systemic Therapies for SCLC: Novel Targets and Patients' Selection (ID 121)
- Event: WCLC 2019
- Type: Oral Session
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
- Moderators:Christine Lee Hann, Makoto Nishio
- Coordinates: 9/08/2019, 13:30 - 15:00, Hilton Head (1978)
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OA03.05 - Characterization of Genomic Alterations in Chinese LCNEC and SCLC via Comprehensive Genomic Profiling (Now Available) (ID 1486)
13:30 - 15:00 | Author(s): Sheng Zhang
- Abstract
- Presentation
Background
LCNEC and SCLC are aggressive neuroendocrine carcinomas with overlap in clinical, histopathologic, morphologic and genomic features. Differential molecular features between the two subtypes have not been well elucidated, contributing the uncertainty for optimal clinical strategy for each subtype. Here we interrogated the genomic characteristics in LCNEC as compared to SCLC along with their histologically related subtypes: carcinoids and atypical carcinoids via comprehensive genomic profiling.
Method
FFPE samples from 31 LCNECs, 35 SCLCs, 14 carcinoids and 22 atypical carcinoids were sequenced in a CLIA-certified sequencing laboratory using 520-cancer-related gene panel, with an average sequencing depth of 1385X.
Result
Comparative mutational analysis revealed that both LCNEC and SCLC sub-cohorts displayed higher rate of TP53 alterations than that of carcinoid (p<0.001, p<0.001). SCLC patients harbored more RB1 and PIK3CA mutations than LCNECs (p<0.001, p=0.014) and carcinoids (p<0.001, p=0.018). In addition, mutation frequencies of LRP1B, FAT1, PRKDC, PIK3CA, NOTCH1, SPTA1 and EPHA3 in SCLC were significantly higher than that in carcinoid. Mutations in TP53 and RB1 occurred concurrently in 83% (29/35) SCLC patients, whereas in only 32.3% (10/31) LCNECs.（Fig.1） We further investigated the distribution of mutations across KEGG pathways and found that mutation frequencies in both HIF-1 and Notch signaling pathways were lower in LCNEC than SCLC (p=0.032, p=0.025). Copy number variation (CNV) analysis revealed that LCNEC and SCLC had comparable CNVs which were significantly higher than carcinoid (p<0.001, p<0.001) and atypical carcinoid (p=0.010, p=0.028). TMB analysis also revealed a comparable TMB status of LCNEC (12.7/Mb) and SCLC (11.9/Mb), and relatively lower TMB in both carcinoid (2.4/Mb, p<0.001, p<0.001) and atypical carcinoid (5.6/Mb, p=0.003, p=0.009) than LCNEC and SCLC.
Conclusion
We demonstrated the differential genomic characteristics in the four subtypes of neuroendocrine carcinomas. Compared with SCLC, LCNEC has lower mutation frequencies in RB1, PIK3CA, as well as HIF-1 and Notch signaling pathways. In addition, LCNEC and SCLC had comparable CNV and TMB status, which significantly higher than that of carcinoids and atypical carcinoid.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
