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ASCO Breakthrough: Effect of ATM Mutations on Response to Radiotherapy


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Somatic mutations of DNA damage repair genes like ATM and BRCA1 or BRCA2 may result in poor disease prognosis and chemotherapy resistance. However, a study by Lee et al presented at ASCO Breakthrough: A Global Summit for Oncology Innovators (Abstract 130) investigated the possibility that these mutations may make patients more susceptible to benefits from radiotherapy.

Researchers examined whole-genome screening results of patients in a prospectively collected radiotherapy registry. Of 134 patients, they identified 33 with mutations in the ATM (n = 11) and BRCA1/2 genes (n = 22).

Results

In comparing response to radiation therapy with a group of closely matched patients with similar histology who received similar doses of radiation but did not have the mutations, researchers found that mutations in the ATM gene were associated with better rates of complete response (50% with ATM mutation vs 8% without mutation), overall response (61% vs.24%), and local control rates at targeted lesions (94% vs 58%). In addition, response duration was longer for patients with mutated ATM (median of 11 months vs 3 months, P = .001).

Radiotherapy-related toxicities were not significantly different between the two groups (17% vs 11%, P = .515). No severe toxicity occurred.

The authors concluded, “ATM mutations confer exceptional responses to radiation therapy, even with palliative dose, which has potential therapeutic implications.”

“Radiation works by damaging DNA strands. Therefore, a DNA damage-repair gene that is malfunctioning could mark a tumor as sensitive to radiation treatment. In this context, our study showed that the ATM gene may serve as a novel mutation-based marker of radiosensitivity, which could be harnessed for personalized treatment in the future,” said lead author Jason Joon Bock Lee, MD, of the Yonsei Cancer Center.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.


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