The potential of a-particle emitters to treat cancer has been recognized since the early 1900s. Advances in the targeted delivery of radionuclides and radionuclide conjugation chemistry, and the increased availability of a-emitters appropriate for clinical use, have recently led to patient trials of radiopharmaceuticals labeled with a-particle emitters. Although a-emitters have been studied for many decades, their current use in humans for targeted therapy is an important milestone. The objective of this work is to review those aspects of the field that are pertinent to targeted a-particle emitter therapy and to provide guidance and recommendations for human a-particle emitter dosimetry.

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Preliminary outcomes suggest that concurrent chemotherapy and IMRT for anal canal cancers is effective and tolerated favorably compared with historical standards.

PURPOSE To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy (CRT), and to develop a normal tissue complication probability (NTCP) model for HT. METHODS AND MATERIALS We tested associations between hematologic nadirs during CRT and the volume of BM receiving ≥ 10 and 20 Gy (V10 and V20) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with 37 identically treated patients from a prior study, forming a cohort of 81 patients for NTCP analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. RESULTS In the validation cohort, significant negative correlations were observed between white blood cell count (WBC) nadir and V10 (regression coefficient (β)=−0.060, p=0.009) and V20 (β=−0.044, p=0.010). In the combined cohort, the (adjusted) β estimates for log(WBC) vs. V10 and V20 were: −0.022 (p=0.025) and −0.021 (p=0.002), respectively. Patients with V10 ≥ 95% were more likely to experience grade ≥ 3 leukopenia (68.8% vs. 24.6%, p<0.001) as were patients with V20 > 76% (57.7% vs. 21.8%, p=0.001). CONCLUSIONS These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V10 < 95% and V20 < 76% may reduce HT.