Biopsy of palliative lesions following radiotherapy

Objective: Definite radiotherapy and/or chemoradiotherapy is often conducted for the treatment of non-small cell lung cancer. However, there is a potential concern regarding the mutagenic effects on tumor cells derived from the therapies, and genomic information regarding cancer cells that survived definitive radiotherapy/chemoradiotherapy is lacking. To evaluate the mutagenic effect of radiotherapy/chemoradiotherapy, we compared genomic signatures of recurrent non-small cell lung cancer tissue with those of pre-treatment. Methods: We evaluated seven specimens from three patients who developed disease recurrence after definite radiotherapy/chemoradiotherapy, and we ranked the mutations according to the Combined Annotation-Dependent Depletion score. Results: Some mutations remained in the post-therapy state, and others, including driver mutations, either newly occurred or disappeared during the course of disease. Of the four specimens obtained in the post-radiation period, 21 variants were detected. Compared with single nucleotide substitution (5, 23.8%), substantial number of deletions (16, 76.2%) was observed in specimens obtained after definite radiotherapy/chemoradiotherapy. Conclusion: Radiotherapy/chemoradiotherapy effects on tumor cells have a wide spectrum, and resequencing of a recurrent lesion is always recommended to discuss the best course of therapy for recurrent non-small cell lung cancer after definitive radiotherapy/chemoradiotherapy. Advances in knowledge: With regard to cancer cells that survived definitive radiotherapy/chemoradiotherapy, some mutations remained in the post-therapy state, and others, including driver mutations, either newly occurred or disappeared during the course of disease. Compared with single nucleotide substitution, substantial number of deletions was observed in specimens obtained after definite radiotherapy/chemoradiotherapy.