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

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% (alpha = 0.05 and the beta = 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.