Lattice radiotherapy-induced dramatic regression of bulky metastases challenges radioresistance compared with homogeneous hypofractionation in anorectal mucosal melanoma: a case report

Abstract Backgrounds Anorectal mucosal melanoma (AMM) is a rare and aggressive malignancy with poor prognosis and limited response to systemic therapies, including immune checkpoint inhibitors. Radiotherapy has traditionally been considered ineffective due to melanoma’s radioresistance, but advanced techniques like Lattice radiotherapy (LRT) may improve local control and modulate tumor immunity. This report presents a comparison between LRT and a homogeneous hypofractionated schedule in AMM, highlighting the potential of spatially fractionated irradiation to overcome melanoma radioresistance. Case presentation A 61-year-old male with metastatic AMM underwent multiple courses of radiotherapy in the setting of oligoprogression during immunotherapy. He received stereotactic body radiotherapy (SBRT) to a lymph node metastasis, moderately hypofractionated radiotherapy to a lesion in the midline upper dorsal region, and positron emission tomography (PET)-guided LRT to bulky, symptomatic lesions in the right thigh and right axilla. LRT induced rapid volumetric regression and durable control, with no in-field recurrence observed for over one year. In contrast, the moderately hypofractionated regimen with a homogeneous dose distribution to the upper dorsal target led to a slower and less pronounced response. All treatments were well tolerated and contributed to prolonged symptom relief despite systemic progression. Conclusions This case highlights the differential responses of AMM to various radiation techniques and supports the use of advanced modalities such as LRT in managing radioresistant tumors. Radiotherapy, particularly in its spatially fractionated form, may provide meaningful local control and palliation in patients with limited systemic options, warranting further investigation in AMM.