Genomic analyses for predictors of response to chemoradiation in stage III non-small cell lung cancer Journal Article
| Authors: | Luo, L. Y.; Samstein, R. M.; Dick-Godfrey, R.; Sidiqi, B.; Wang, C.; Oro, F.; Sonnick, M.; Paik, P. K.; Chaft, J. E.; Shaverdian, N.; Gomez, D. R.; Rimner, A.; Wu, A. J. |
| Article Title: | Genomic analyses for predictors of response to chemoradiation in stage III non-small cell lung cancer |
| Abstract: | 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) |
| Journal Title: | Advances in Radiation Oncology |
| Volume: | 6 |
| Issue: | 1 |
| ISSN: | 2452-1094 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2021-01-01 |
| Start Page: | 100615 |
| Language: | English |
| DOI: | 10.1016/j.adro.2020.10.027 |
| PROVIDER: | scopus |
| PMCID: | PMC7897765 |
| PUBMED: | 33665490 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2021 -- Source: Scopus |
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