Tolerability of sequential immune therapy and palliative radiotherapy to the cervical and thoracic spine

Abstract

Use of immune therapy in metastatic cancers is rapidly expanding; however, its combination with commonly prescribed palliative radiation fields and doses is not well studied. To investigate this, we evaluated the toxicity of combined immune therapy and palliative cervical or thoracic spine radiotherapy. Patients receiving cervical or thoracic spine radiation were evaluated based on administration of immune therapy within 30 days of radiation, use of 3D conformal or simpler techniques, and minimum 1 follow-up from end of treatment. Thirty patients were evaluable. Median survival following radiotherapy was 87 days. Pembrolizumab was most commonly combined with radiation (11 patients), then nivolumab (10), ipilimumab (3), and atezoliumab (2). Four patients (13.3%) had grade 3 toxicity requiring hospitalization (vomiting, esophagitis) and 12 patients (40%) had grade 2 toxicity (esophagitis, dysphagia). Ten patients (33.3%) had no toxicity. Three of the 4 patients with grade 3 toxicity received concurrent ipilimumab and nivolumab. Median dose was 30 Gy (range, 20–39) and fractions were 10 (range, 5–15). There was a trend toward increased grade 2+ toxicity with greater number of vertebral levels irradiated, 5.7 ± 3.4, vs. 4.0 ± 1.6 for none/grade 1 (P = .086). Seven of 7 patients exposed to ipilimumab developed grade 2+ toxicity vs 39% in the remaining patients (P = .007 for interaction). Radiation dose, fractionation, and timing of immune therapy were not significant contributors. Combined immune therapy and radiotherapy for palliation of spine metastases suggests increased toxicity when a greater number of vertebral bodies are irradiated, or when combined immune therapy agents are utilized.