Patients with Lynch syndrome often have a strong family history of colorectal and endometrial cancers and exhibit mismatch repair (MMR) deficiency, which may be associated with chemoresistance. Radiotherapy can enhance tumor-specific immune responses and may be effective in such patients. A 49-year-old perimenopausal woman with a family history of colon cancer in three relatives was diagnosed with endometrial carcinoma with para-aortic lymph node metastases. She underwent surgical staging, including pelvic and para-aortic lymphadenectomy. Pathological examination revealed a mixed endometrioid (grade 2) and serous carcinoma. Lymph node metastases were identified in 15 of the 25 nodes removed (including 7 of 10 para-aortic nodes). Although she received adjuvant taxane/platinum-based chemotherapy, para-aortic nodal recurrence developed three months after completion of treatment. Radiotherapy was administered, resulting in complete regression of the para-aortic nodes. She remains well with no evidence of disease 150 months after surgery. The patient meets the Amsterdam II criteria for Lynch syndrome but without molecular confirmation. MMR-deficient tumor cells contain numerous frameshift peptides resulting from DNA mismatch, and tumors exhibit significant infiltration of tumor-infiltrating lymphocytes. Ionizing radiation induces tumor cell death and neoantigen release, resulting in the trafficking of T cells to the tumor, which, hypothetically, may convert the irradiated tumor into an efficient, individualized in situ vaccine. Radiotherapy may be a promising option for chemoresistant lesions in selected, similar cases. Further studies are warranted to identify the specific subgroup of patients who are likely to benefit from radiotherapy.
Otsuka et al. (Wed,) studied this question.