Lung Cancer

PD 16 - Lung 4 - Poster Discussion

1143 - Genetic Predictors of Response to Chemoradiation in Stage III Non-Small-Cell Lung Cancer

Wednesday, October 24
11:48 AM - 11:54 AM
Location: Room 217 C/D

Genetic Predictors of Response to Chemoradiation in Stage III Non-Small-Cell Lung Cancer
L. Luo, R. Samstein, R. Dick-Godfrey, F. Oro, M. Sonnick, P. Paik, J. Chaft, A. Rimner, and A. J. Wu; Memorial Sloan Kettering Cancer Center, New York, NY

Purpose/Objective(s): Radiation with platinum-based doublet chemotherapy is the standard of care for patients with unresectable stage III non-small-cell lung cancer (NSCLC). Despite aggressive treatment, progression-free survival and overall survival remain poor. It is unclear whether any tumor genetic alterations are associated with response to therapy.

Materials/Methods: We retrospectively reviewed clinical outcomes of patients with stage III NSCLC treated with definitive radiation, who had undergone tumor molecular profiling through an institutional next-generation sequencing platform. This platform is an FDA-approved, targeted-DNA-sequencing panel that contains 341 (now expanded to 468) somatic mutations and other genetic alterations. Basic patient and tumor characteristics, clinical outcomes including loco-regional recurrence, distant recurrence, and overall survival, were collected. Overall and recurrence-free survivals were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to investigate association between clinical outcome and genetic alterations.

Results: We identified 61 patients with stage III NSCLC who were treated with definitive radiation between 2013 and 2017 and underwent tumor molecular profiling. Twenty-four patients (39%) had stage IIIA disease and 37 patients (61%) had stage IIIB disease. Median radiation dose delivered was 60Gy in 30 fractions (range 48.6Gy to 74Gy). All but two patients received concurrent or sequential chemotherapy. One patient received induction crizotinib and one patient died before start of chemotherapy. With a median follow-up time of 14 months, the median overall survival was 30.7 months. Several genetic mutations were significantly associated with worse overall survival after therapy, including KMT2D (p=0.005), HIST1H1C (p=0.007), ERRFL1 (p=0.01), NF1 (p=0.01), and FLT1 (p=0.03). Among these genes, KMT2D (p=0.01) and FLT1 (p=0.002) were also associated with increased loco-regional recurrence. Mutations in the CDKN2A gene, encoding p16 protein, were significantly associated with improved loco-regional tumor control (p=0.02). Association of other common genetic alterations such as EGFR or KRAS mutations with response to therapy was not observed.

Conclusion: This study coupled multiplex targeted sequencing with clinical outcome information to identify several potential genetic predictors of response to chemotherapy and radiation in locally advanced NSCLC. Further analysis in a larger cohort is necessary and under way to validate the findings.

Author Disclosure: L. Luo: None. R. Samstein: None. R. Dick-Godfrey: None. M. Sonnick: None. P. Paik: None. J. Chaft: None. A. Rimner: Research Grant; Varian Medical Systems, Boehringer Ingelheim, Pfizer, Astra Zeneca. Advisory Board; Astra Zeneca, Merck.

Leo Luo, MD

Disclosure:
No relationships to disclose.

Presentation(s):

Send Email for Leo Luo


Assets

1143 - Genetic Predictors of Response to Chemoradiation in Stage III Non-Small-Cell Lung Cancer



Attendees who have favorited this

Please enter your access key

The asset you are trying to access is locked. Please enter your access key to unlock.

Send Email for Genetic Predictors of Response to Chemoradiation in Stage III Non-Small-Cell Lung Cancer