Volumetric modulated arc therapy total body irradiation in pediatric and adolescent/young adult patients undergoing stem cell transplantation: Early outcomes and toxicities

Abstract

Introduction: Total body irradiation (TBI) is an important component of many conditioning regimens for hematopoietic stem cell transplantation (HSCT), most commonly used in pediatric and adolescent/young adult (AYA) patients. We aimed to evaluate outcomes and toxicities among pediatric and AYA patients treated with TBI utilizing volumetric modulated arc therapy total body irradiation (VMAT-TBI). Methods:We reviewed pediatric and AYA patients treated with VMAT-TBI at our institution from 2019 to 2021. Data on patient and disease characteristics, treatment details, outcomes and toxicities were collected. Overall survival (OS) and relapse-free survival (RFS) were analyzed using the Kaplan-Meier method.Results: Among 38 patients, 16 (42.1%) were treated with myeloablative regimens and 22 (57.9%) with nonmyeloablative regimens. Median age was 7.2 years (range: 1-27) and median follow-up was 8.7 months (range: 1-21). Lungs D mean was 7.3 ± 0.3 Gy for myeloablative regimens (range: 6.8-7.8). Kidneys were spared to average mean dose of 71.4 ± 4.8% of prescription dose. Gonadal sparing was achieved for patients treated for nonmalignant diseases to D mean of 0.7 ± 0.1 Gy. No patient experienced primary graft failure; one (2.6%) experienced secondary graft failure. The most common grade 1-2 acute toxicities were nausea (68.4%) and fatigue (55.3%). Mucositis was the most common grade 3-4 acute toxicity, affecting 39.5% of patients. There were no cases of pneumonitis or nephrotoxicity attributable to TBI. Conclusion:VMAT-TBI offers increased ability to spare organs at risk in pediatric and AYA patients undergoing HSCT, with a favorable acute/subacute toxicity profile and excellent disease control.

Long-term follow up of patients with hematological malignancies treated with total body irradiation using intensity modulated radiation therapy

“…Similarly, almost all patients achieved a mean kidney dose of less than <12 Gy, with no nephrotoxicity events, though this was not unexpected, with low rates at baseline and no nephrotoxicity in the standard cohort either. Overall, our dosimetry is similar to results reported by Marquez et al, who achieved mean lung dose of 7.3 Gy and mean kidney dose of 71.4% of prescription dose, and also experienced no pneumonitis or nephritis (13). In fact, our mean doses of 6.2 Gy and 5.7 Gy respectively reflect potential to further limit exposure of critical organs, which may improve transplantrelated morbidity and mortality (16).…”

“…Advances in radiation technology have led to implementation of more advanced radiation techniques such as IMRT into the transplant conditioning regimen. Several studied have reported on the procedure for performing IMRT TBI, including initial clinical outcomes (11)(12)(13). However, among these studies, the highest median follow-up was 2.8 years, with a maximum follow up of 6.4 years (11).…”

“…Most recently, researchers at Stanford reported on a group of 38 pediatric and adolescent/young adult (AYA) patients who received VMAT-TBI at both myeloablative and nonmyeloablative doses. At a median follow-up of 8.7 months, they reported an OS of 89.5% and relapse-free survival (RFS) of 94.7% for all patients (13). While these studies emphasize the safety and efficacy of IMRT TBI, their median follow-up periods do not exceed three years, limiting our understanding of the long-term effects of IMRT TBI.…”

Improved organ sparing using auto‐planned Stanford volumetric modulated arc therapy for total body irradiation technique

“…Although the study shows significant decrease in dose to the kidneys, lenses, brain, and thyroid, it is unclear that this benefit will be clinically meaningful, although the early outcomes and toxicity report is promising 19 . Despite this possibility, our institution generally abides by the ALARA (as low as reasonably achievable) principle, which would argue that lower organ doses are desirable in and of itself for patients without active disease; however, further studies will be necessary to elucidate the exact dose response of this lung toxicity at these lower observed doses.…”

Full Body Surface Coverage with Water-Equivalent Bolus as Novel Technique for Total Body Irradiation before Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoid Leukemia

“…Organ shift and intra-fraction motion could be detected with cone-beam CT scans performed before treatment, between isocenter shifts, and after radiation. Therefore, favorable acute and subacute toxicity profiles and excellent disease controls can be achieved [ 19 ].…”