Image Guided Volumetrically Modulated Total Body Irradiation (TBI): Progress on Single Institution Phase 2 Clinical Trial

Abstract

<h3>Purpose/Objective(s)</h3> TBI is a backbone of many conditioning regimens for hematopoietic stem cell transplants but can lead to both acute and late toxicity including radiation-induced interstitial pneumonitis. The incidence of idiopathic pneumonia syndrome (IPS) after TBI-based myeloablative conditioning regimens ranges from 7% to 35%. The purpose of this study is to implement image guided volumetrically modulated technique (VMAT) for TBI with the goal of lung sparing and improved target coverage. <h3>Materials/Methods</h3> Nine patients have been treated using image-guided VMAT based TBI at our institution as part of a single-arm phase 2 clinical trial for patients undergoing myeloablative conditioning regimens. The trial was approved by our internal review board (IRB) in September 2020 and aims to accrue 15 patients within one year. All patients enrolled in the trial have signed informed consent. The primary endpoints of the study are the following dosimetric constraints: V100% ≥ 90%, D98% ≥ 85% of Rx dose for the planning target volume (PTV), and a mean lung dose < 9 Gy. PTV is defined as the body contour cropped 5 mm from the surface and excluding lungs and kidneys but extended 3 mm into these organs. Additional secondary dosimetric endpoints include mean dose to each individual kidney < 11 Gy, and maximum dose to 2cc of the entire body < 130% of Rx dose. Clinical endpoints include the occurrence of IPS in the first 100 days after transplant, occurrence of acute graft versus host disease (GVHD), transplant related mortality or mortality in the first 100 days following transplant. <h3>Results</h3> Patients were treated to 12 Gy in 8 BID fractions (n = 6) or 13.2 Gy in 8 BID fractions (n = 3) over four consecutive days. All patients were able to complete treatment to the prescribed dose as planned. All patient plans met dosimetric constraints of the study. The median PTV V100% was 93.2% of Rx dose (Max: 95.6%, Min: 92.1%), the median PTV D98% was 90.2% of Rx dose (Max: 94.3%, Min: 88.3%), and the median lung dose mean was 7.63 Gy (Max: 7.94 Gy, Min: 7.29 Gy). In addition, individual kidney mean doses were < 11 Gy, and body maximum dose (D_2cc) was < 130% of Rx dose for all patients. At this time, only one patient (12 Gy treatment) has reached the 100 day post-transplant follow-up with the following findings: no relapse on bone marrow biopsy, no pneumonitis, resolved acute GVHD overall grade 1 (skin: 1, GI: 0, Liver: 0), resolved dermatitis (grade 1), resolved vomiting (grade 2), ongoing diarrhea and nausea (grade 1, previously grade 2). <h3>Conclusion</h3> Our initial results indicate that primary and secondary dosimetric endpoints were achievable for all protocol patients treated thus far. As the trial progresses, secondary clinical endpoints at 100 day follow-up will be analyzed to evaluate occurrence of IPS, survival, and treatment related toxicities.