Radiotherapy-induced anti-tumor immune response and immune-related adverse events in a case of recurrent nasopharyngeal carcinoma undergoing anti-PD-1 immunotherapy

BACKGROUND: Treatment of recurrent nasopharyngeal carcinoma is a challenging clinical problem. We report the case of a 46 year old male showing excellent response and signs of immunostimulation following re-re-irradiation for recurrent nasopharyngeal carcinoma under systemic treatment with pembrolizumab. CASE PRESENTATION: Patient was first diagnosed with locoregionally advanced, non-keratinizing nasopharyngeal carcinoma in 2010. After achieving complete remission following induction chemotherapy and concurrent curative chemoradiation, the patient subsequently developed distant and locoregionally recurrent disease. He received various treatments (neck dissection, radiotherapy to a bony metastasis, palliative chemotherapy, stereotactic re-irradiation of local recurrence) before initiation of anti- PD-1 immunotherapy with pembrolizumab in January of 2016. Following marked local progression 6 months thereafter, we performed re-re-irradiation of the recurrent tumor after careful evaluation and treatment planning. While treatment was well tolerated, the patient subsequently developed marked clinical and radiological signs of immunostimulation with mucosal irritation and swelling of lacrimal and salivary glands as described in the report. Immunotherapy with pembrolizumab was reinitiated, with re- staging showing excellent response with regression of all tumorous lesions. At the time of this report, following near complete recovery of inflammatory symptoms, the patient remains in excellent condition and free from recurrence under treatment with pembrolizumab. CONCLUSIONS: To our knowledge, we report the first observation of a combined effect of immunotherapy and radiotherapy in a patient with recurrent nasopharyngeal carcinoma. Demonstrating distinct signs of immunostimulation as well as excellent tumor response in a heavily pretreated patient progressing under anti-PD-1 immunotherapy, the case adds to the rising paradigm of an immunostimulatory effect of radiotherapy in patients undergoing treatment with immune checkpoint inhibitors.