External Beam Radiation Therapy With or Without 131I-MIBG Systemic Radiation Therapy in the Therapy of Patients With Malignant Pheochromocytoma and Paraganglioma

Abstract

Patients with malignant pheochromocytoma (PCC) and paraganglioma (PGL) of the thorax, abdomen and pelvis are often not considered for external beam radiation therapy (EBRT) due to concerns that these tumors are not radiosensitive. Therefore, we have reviewed our institutional experience with EBRT with particular attention to a subset of patients treated with combined 131I-MIBG systemic radionuclide therapy and EBRT to areas of bulky disease. Forty-nine consecutive patients with a diagnosis of PCC or PGL treated with EBRT at the University of Pennsylvania from 1984 to 2012 were reviewed in an IRB-approved retrospective study. Response rate was evaluated by RECIST v1.1 criteria as stable disease and partial responses. Of the 24 patients with tumors in the thorax, abdomen or pelvis, the median dose/fractionation was 50 Gy/25 fractions. 20 patients received megavoltage photons and 4 patients received protons. The in-field objective response rate in evaluable patients was 85% with 75% of patients maintaining local control at 12 months. Treatment toxicity was related to irradiation of tumor-adjacent normal tissues without clinically significant hematologic toxicity in the 16 patients receiving only EBRT. Because of non-overlapping toxicity of EBRT and 131I-MIBG and the potential for radiosensitization from combined low dose rate-high dose rate therapy, 8 patients with widespread systemic metastases were treated with external beam radiation therapy to 12 sites of bulky, symptomatic tumor in conjunction with systemic 131I-MIBG (2 mCi/kg per treatment, median 2 cycles 3 months apart and radiation typically given immediately after second cycle). In these patients, all areas irradiated with EBRT showed durable objective tumor response despite all patients eventually experiencing out-of-field systemic progression at a median time of 11.9 months. The median survival in the combined modality cohort is 29 months. Four of these patients remain alive with excellent performance status 27, 29, 35 and 36 months after EBRT. EBRT can be highly effective in local management of PCC and PGL. EBRT can be used safely in conjunction with 131I-MIBG due to non-overlapping toxicities with excellent control of locally bulky tumors. Based on these results, a clinical protocol with combined 131I-MIBG and EBRT is currently being designed.