Bone Marrow-Sparing IMRT in Anal Cancer Patients Undergoing Concurrent Chemo-Radiation: Results of the First Phase of a Prospective Phase II Trial

SIMPLE SUMMARY: Hematological toxicity may be a consistent issue in anal cancer patients undergoing concurrent chemo-radiation, with a potentially detrimental effect on clinical outcomes and patient compliance to treatment. Chemotherapy is the most important trigger, since it induces myelosuppression, but radiation dose delivered to the hematopoietically active bone marrow (BM) also plays an important role. Active bone marrow can be identified using functional imaging with 18-Fluoro-2-deoxy-glucose positron emission tomography ((18)FDG-PET) and selectively spared during radiation delivery via intensity-modulated radiotherapy (IMRT). We investigated, within a prospective phase II trial, the potential effectiveness of targeted avoidance of active BM comprised within pelvic bones in reducing the acute hematologic toxicity profile of anal cancer patients undergoing concomitant chemo-radiation for squamous cell carcinoma of the anus. The results of the first step of the study fulfilled the criteria to define BM-sparing IMRT as “promising” and to continue with the second step of the phase II trial. ABSTRACT: Purpose: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with (18)FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. Methods: a one-armed two-stage Simon’s design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0–G2 (vs. G3–G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the β = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0–G2 acute HT to further proceed with the trial. We employed (18)FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. Results: from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0–G2 events, way above the threshold set by the trial design. Conclusion: (18)FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial.