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Correlation of Tumor and Whole-Body Dosimetry with Tumor Response and Toxicity in Refractory Neuroblastoma Treated with ¹³¹I-MIBG

Departments of Pediatrics, Radiology, Epidemiology, and Biostatistics, University of California, San Francisco, San Francisco, California

The purpose of our study was to determine the effect of tumor-targeted radiation in neuroblastoma by correlating administered ¹³¹I-metaiodobenzylguanidine (MIBG) activity to tumor and whole-body dosimetry, tumor volume change, overall response, and hematologic toxicity. Methods: Eligible patients had MIBG-positive lesions and tumor-free, cryopreserved hematopoietic stem cells. Activity was administered according to body weight and protocol as part of a phase I and phase II study. The whole-body radiation dose was derived from daily 1-m exposure measurements, the tumor self-absorbed radiation dose (TSARD) was determined from scintillation-camera conjugate views, and the tumor volume was measured using CT or MRI. Results: Forty-two patients with refractory neuroblastoma (16 with prior hematopoietic stem cell transplant) received a median activity of 555 MBq/kg (15 mCi/kg) (range, 93–770 MBq/kg) and a median total activity of 11,470 MBq (310 mCi) (range, 3,330–30,969 MBq). The median whole-body radiation dose was 228 cGy (range, 57–650 cGy) and the median TSARD was 3,300 cGy (range, 312–30,500 cGy). Responses among evaluable patients included 16 partial response, 3 mixed response, 14 stable disease, and 9 progressive disease. Higher TSARD values predicted better overall disease response (P < 0.01). The median decrease in tumor volume was 19%; 18 tumors decreased, 4 remained stable, and 5 increased in size. Correlation was seen between administered activity per kilogram and whole-body dose as well as hematologic toxicity (assessed by blood platelet and neutrophil count nadir) (P < 0.05). The median whole-body dose was higher in the 11 patients who required hematopoietic stem cell infusion for prolonged neutropenia versus the 31 patients who did not (323 vs. 217 cGy; P = 0.03). Conclusion: Despite inaccuracies inherent in dosimetry methods, ¹³¹I-MIBG activity per kilogram correlated with whole-body radiation dose and hematologic toxicity. The TSARD by conjugate planar imaging predicted tumor volume decrease and also correlated with overall tumor response.

Key Words: neuroblastoma • MIBG • dosimetry • ¹³¹I

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