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Cancer Research and Treatment > Epub ahead of print
doi: https://doi.org/10.4143/crt.2020.1247    [Epub ahead of print]
Increased Radiosensitivity of Solid Tumors Harboring ATM and BRCA1/2 Mutations
Kyung Hwan Kim1, Han Sang Kim2, Seung-seob Kim3, Hyo Sup Shim4, Andrew Jihoon Yang1, Jason Joon Bock Lee1, Hong In Yoon1, Joong Bae Ahn2, Jee Suk Chang1
1Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
2Division of Medical Oncology, Department of Internal Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea
3Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
4Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
Correspondence  Joong Bae Ahn ,Tel: 82-2-2228-8134, Fax: 82-2-2227-7823, Email: vvswm513@yuhs.ac
Jee Suk Chang ,Tel: 82-2-2228-8095 , Fax: 82-2-2227-7823 , Email: changjeesuk@yuhs.ac
Received: November 25, 2020;  Accepted: June 3, 2021.  Published online: June 4, 2021.
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.
Key words: Radiotherapy, ATM, BRCA, DNA repair, Radiosensitivity
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