Correlation of tumor and whole-body dosimetry with tumor response and toxicity in refractory neuroblastoma. treated with I-131-MIBG

The purpose of our study was to determine the effect of tumor-targeted radi ation in neuroblastoma by correlating administered I-131-metaiodobenzylguan idine (MIBG) activity to tumor and whole-body dosimetry, tumor volume chang e, overall response, and hematologic toxicity. Methods: Eligible patients h ad MIBG-positive lesions and tumor-free, cryopreserved hematopoietic stem c ells. Activity was administered according to body weight and protocol as pa rt of a phase I and phase II study. The whole-body radiation dose was deriv ed 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 transp lant) received a median activity of 555 MBq/kg (15 mCl/kg) (range, 93-770 M Bq/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 b etter overall disease response (P < 0.01). The median decrease in tumor vol ume was 19%; 18 tumors decreased, 4 remained stable, and 5 increased in siz e. Correlation was seen between administered activity per kilogram and whol e-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 I I patients who required hematopoietic stem cell infusion for prolo nged neutropenia versus the 31 patients who did not (323 vs. 217 cGy; P = 0 .03). Conclusion: Despite inaccuracies inherent in dosimetry methods, I-131 -MIBG activity per kilogram correlated with whole-body radiation dose and h ematologic toxicity. The TSARD by conjugate planar imaging predicted tumor volume decrease and also correlated with overall tumor response.