Feasibility of a novel dose fractionation strategy in TMI/TMLI

Bao et al. Radiation Oncology (2018) 13:248 https://doi.org/10.1186/s13014-018-1201-0 RESEARCH Open Access Feasibility of a novel dose fractionation strategy in TMI/TMLI Zhirong Bao1,2, Hongli Zhao1,2, Dajiang Wang1,2, Jian Gong1,2, Yahua Zhong1,2, Yu Xiong1,2, Di Deng1,2, Conghua Xie1,2, An Liu3, Xiaoyong Wang1,2* and Hui Liu1,2* Abstract Background: To report our experience in planning and delivering total marrow irradiation (TMI) and total marrow and lymphatic irradiation (TMLI) in patients with hematologic malignancies. Methods: Twenty-seven patients undergoing bone marrow transplantation were treated with TMI/TMLI using Helical Tomotherapy (HT). All skeletal bones exclusion of the mandible comprised the treatment target volume and, for TMLI, lymph node chains, liver, spleen and/or brain were also included according to the clinical indication. Planned dose of 8Gy in 2 fractions was delivered over 1 day for TMI while 10Gy in 2 fractions BID was used for TMLI. Organs at risk (OAR) contoured included the brain, brainstem, lens, eyes, optic nerves, parotids, oral cavity, lungs, heart, liver, kidneys, stomach, small bowel, bladder and rectum. In particular, a simple method to avoid hot or cold doses in the overlapping region was implemented and the plan sum was adopted to evaluate dose inhomogeneity. Furthermore, setup errors from 54 treatments were summarized to gauge the effectiveness of immobilization. Results: During the TMI/TMLI treatment, no acute adverse effects occurred during the radiation treatment. Two patients suffered nausea or vomiting right after radiation course. For the 9 patients treated with TMI, the median dose reduction of major organs varied 30–65% of the prescribed dose, substantially lower than the traditional total body irradiation (TBI). Meanwhile, average biological equivalent doses to OARs with 8Gy/2F TMI approach were not different from the conventional 12Gy/6F TMI approach. In the dose junction region, the 93% of PTV was covered by the prescribed dose without obvious hotspots. For the 27 patients, the overall setup corrections were lower than 3 mm except those in the SI direction for abdomen-pelvis region, demonstrating excellent immobilization. Conclusion: The present study confirmed the technical feasibility of HT-based TMI/TMLI delivering 8-10Gy in 2 fractions over 1 day. For patients undergoing hematopoietic cell transplantation the proposed 8Gy/2F TMI (or 10Gy/2F TMLI) strategy may be a novel approach to improve delivery efficiency, increase effective radiation dose to target while maintaining low risk of severe organ toxicities. Keywords: TMI/TMLI, Helical Tomotherapy, Radiotherapy, Bone marrow transplantation Background Total body irradiation (TBI) has been an important part of conditioning regimens for patients undergoing hematopoietic cell transplantation [1]. The primary purpose of TBI is to eradicate malignant cells and provide immunosuppression to prevent rejection of the transplanted donor hematopoietic cells. Compared to the conditioning regimens based on chemotherapy alone, TBI has * Correspondence: ; 1 Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China Full list of author information is available at the end of the article several distinct advantages because it is not influenced by interpatient variability in drug absorption, metabolism, biodistribution, or clearance kinetics; and can treat the sanctuary sites not easily reached by chemotherapy drugs. TBI also contributes to the elimination of chemotherapyresistant tumor cells [2, 3]. Randomized trials showed that increased TBI doses significantly reduced the probability of post-transplant relapse rates for patients [4]. However, the dose escalation of TBI is limited by the normal tissue toxicity and treatment-related mortality rates [5, 6]. With traditional TBI delivery techniques, only lung blocks are used to © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Bao et al. Radiation Oncology (2018) 13:248 reduce lung dose to some extent and no attempt is made to spare other organs at risk (OARs) such as the eyes, heart, liver, and kidney. As a result, acute and late complications of treatment may arise. Specifically, acute effects include nausea, vomiting, diarrhea, oral mucositis, parotitis and interstitial pneumonitis; long-term effects include cataracts, growth restriction, increased likelihood of heart disease and radiation-induced second malignancies. Given the fact that the incidence of radiation-induced complications is dose related [4–6], a more targeted irradiation technique for TBI delivery is needed to reduce normal tissue toxicity and allow for dose escalation, and thus further decrease mortality and relapsed rates. Helical Tomotherapy (HT)-based total marrow (and lymphatic) irradiation (TMI-TMLI) may be one solution to optimize treatment and permit dose escalation [7–10]. Helical Tomotherapy system is a radiation therapy delivery device that equips a linear accelerator with a FAN beam mega-voltage computed tomography (MVCT) and a helical IMRT delivery, permitting the dose delivered to the target with maximum size of approximately 160 cm in length. HT allows greater sculpting of radiation doses to large complex target shapes while simultaneously reducing dose to normal organs, making it appropriate to be adopted for the delivery of TMI-TMLI. The aim of the present study was to investigate the technical feasibility of HT-based TMI-TMLI, with the total prescription dose of 8 to 10Gy delivered by 2 fractions within one day with a minimal interfraction interval of 6 h. This report detailed the retrospective review of initial experience for patients undergoing HT-based TMI-TMLI and discussed the potential advantages and challenges of this approach. The evaluation of the TMI was also done by comparing the median organ doses with the conventional TBI and TMI reported by Wong et al. [10], in which 13 patients with multiple myeloma were treated. Methods Patient selection and simulation Twenty-seven patients treated with TMI/TMLI using HT at our institution between October 2016 and September 2017 were selected for retrospective analysis. Majority of the patients included in the study were acute lymphoid leukemia (17), the rest were acute myeloid leukemia (6), multiple myeloma (2) and lymphoma (2). Of the 27 patients, 26 were adults and 1 was child. The mean an (...truncated)