Complete Radiotherapy Response of Chemoresistant Para-Aortic Lymph Node Metastases in an Endometrial Cancer Patient Meeting the Amsterdam II Criteria for Lynch Syndrome

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.