Genomic Analyses for Predictors of Response to Chemoradiation in Stage III Non-Small Cell Lung Cancer.

Autor:	Luo LY; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York., Samstein RM; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York., Dick-Godfrey R; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York., Sidiqi B; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York., Wang C; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York., Oro F; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York., Sonnick M; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York., Paik PK; Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York., Chaft JE; Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York City, New York., Shaverdian N; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York., Gomez DR; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York., Rimner A; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York., Wu AJ; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York.
Jazyk:	angličtina
Zdroj:	Advances in radiation oncology [Adv Radiat Oncol] 2020 Nov 14; Vol. 6 (1), pp. 100615. Date of Electronic Publication: 2020 Nov 14 (Print Publication: 2021).
DOI:	10.1016/j.adro.2020.10.027
Abstrakt:	Background: Radiation with platinum-based chemotherapy is the standard of care for 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 mutations are associated with response to chemoradiation therapy. Methods: We retrospectively reviewed clinical outcomes of patients with stage III NSCLC treated with definitive radiation who had undergone tumor molecular profiling through a next-generation DNA sequencing platform. Cox proportional hazards model was used to investigate associations between clinical outcomes and genetic mutations detected by next-generation sequencing. Results: 110 patients were identified with stage III NSCLC and underwent definitive radiation between 2013 and 2017 and tumor molecular profiling. Concurrent or sequential chemotherapy was given in 104 patients (95%). Unbiased genomic analyses revealed a significant association between AKT2 mutations and decreased local-regional tumor control and overall survival (hazard ratios [HR] 12.5 and 13.7, P = .003 and P = .003, respectively). Analyses restricted to loss-of-function mutations identified KMT2C and KMT2D deleterious mutations as negative prognostic factors for overall survival (HR 13.4 and 7.0, P < .001 and P < .001, respectively). Deleterious mutations in a panel of 38 DNA damage response and repair pathway genes were associated with improved local-regional control (HR 0.32, P = .049). Conclusions: This study coupled multiplexed targeted sequencing with clinical outcome and identified mutations in AKT2, KMT2C, and KMT2D as negative predictors of local-regional control and survival, and deleterious mutations in damage response and repair pathway genes were associated with improved local-regional disease control after chemoradiation therapy. These findings will require validation in a larger cohort of patients with prospectively collected and detailed clinical information. (© 2020 The Author(s).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu