Boron neutron capture therapy (BNCT) is high-LET radiotherapy, where boron-10 is first targeted to tumors using a carrier compound, often L-boronophenylalanine (L-BPA), followed by low energy external neutron beam irradiation. A high target dose from BNCT is predictive for tumor response and favorable survival in patients with head and neck (H&N) squamous cell carcinoma. Constant tumor-tothe whole blood boron concentration ratios are often assumed in dose calculation, but tumor-to-normal tissue (T/N) ratios obtained from tumor imaging with PET using 18F-BPA as the tracer might also be useful in dose calculations. We investigated the association between the T/N ratios obtained from 18F-BPA PET and efficacy of BNCT in patients with H&N cancer. Materials/Methods: 117 patients with inoperable, locally recurred H&N cancer were treated with L-BPA-mediated BNCT at the FiR 1 research reactor facility, Espoo, Finland, in February, 2003 to January, 2012. To estimate tumor BPA accumulation, 33 patients underwent 18 F-BPA PET prior to BNCT. The T/N ratios were evaluated from static emission scans. Blood boron concentration was monitored with inductively coupled plasma atomic emission spectrometry during neutron irradiation. Normal tissue boron concentration was assumed to equal to that of the whole blood. Tumor response to BNCT was assessed with conventional imaging using the RECISTv.1.0 criteria. Results: Thirty-three patients (male, 55%) participated in the study. Most (25, 76%) had squamous cell carcinoma, 4 (12%) sarcoma, and 4 adenocystic carcinoma. The median minimum radiation dose to the gross tumor, calculated with the measured blood boron concentrations and the T/N ratios from PET, was 14 Gy (RBE) (range, 7 to 78 Gy [RBE]), and when a constant tumor-to-blood ratio of 3.5 was assumed, 19 Gy (RBE) (range, 10 to 29 Gy [RBE]). Two patients were unevaluable for response to BNCT (died early). Nineteen (61%) of the 31 evaluable responded (had a CR or a PR). The median overall survival (OS) time estimate was 22.8 months; 2year OS was 42%. The 18 F-BPA PET-derived T/N values ranged from 1 to 18 (median, 2.7). The median OS for the patients who had a T/N ratio >2.7 was 12.3 months as compared to 27.7 months among those with a smaller ratio (log-rank p Z 0.036). A higher than the median T/N ratio did not predict for tumor response to BNCT (p Z 0.24). Conclusion: A high tumor T/N ratio derived from 18 F-BPA-PET is associated with unfavorable survival after BNCT. Cancers with high 18 F-BPA uptake in PET may often be biologically aggressive, which hypothesis requires further study.
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