Increased Radiosensitivity of Solid Tumors Harboring ATM and BRCA1/2 Mutations

Kyung Hwan Kim, Han Sang Kim, Seung Seob Kim, Hyo Sup Shim, Andrew Jihoon Yang, Jason Joon Bock Lee, Hong In Yoon, Joong Bae Ahn, Jee Suk Chang

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose Preclinical data indicate that response to radiotherapy (RT) depends on DNA damage repair. In this study, we investigated the role of mutations in genes related to DNA damage repair in treatment outcome after RT. Materials and Methods Patients with solid tumor who participated in next generation sequencing panel screening using biopsied tumor tissue between October 2013 and February 2019 were reviewed and 97 patients that received RT were included in this study. Best response to RT and the cumulative local recurrence rate (LRR) were compared according to absence or presence of missense, nonsense, and frameshift mutations in ATM and/or BRCA1/2. Results Of the 97 patients, five patients harbored mutation only in ATM, 22 in only BRCA1/2, and six in both ATM and BRCA1/2 (ATMmtBRCAmt). Propensity score matching was performed to select the control group without mutations (ATMwtBRCAwt, n=33). In total, 90 RT-treated target lesions were evaluated in 66 patients. Highest objective response rate of 80% was observed in ATMmtBRCAmt lesions (p=0.007), which was mostly durable. Furthermore, the cumulative 1-year LRR was the lowest in ATMmtBRCAmt lesions and the highest in ATMwtBRCAwt lesions (0% vs. 47.9%, p=0.008). RT-associated toxicities were observed in 10 treatments with no significant difference among the subgroups (p=0.680). Conclusion Tumors with ATM and BRCA1/2 mutations exhibited superior tumor response and local control after RT compared to tumors without these mutations. The results are hypothesis generating and suggest the need for integrating the tumor mutation profile of DNA repair genes during treatment planning.

Original languageEnglish
Pages (from-to)54-64
Number of pages11
JournalCancer Research and Treatment
Volume54
Issue number1
DOIs
Publication statusPublished - 2022 Jan

Bibliographical note

Funding Information:
This study was supported by a Dongin Sports research grant of Yonsei University College of Medicine (6-2017-0105) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2019R1C1C1006709).

Publisher Copyright:
Copyright © 2022 by the Korean Cancer Association.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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