Kobyzeva Daria, Shelikhova Larisa, Loginova Anna, Kanestri Francheska, Tovmasyan Diana, Maschan Michael, Khismatullina Rimma, Ilushina Mariya, Baidildina Dina, Myakova Natalya, Nechesnyuk Alexey
Department of Radiation Oncology, Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Department of Hematopoietic Cell Transplantation, Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Front Oncol. 2021 Dec 16;11:785916. doi: 10.3389/fonc.2021.785916. eCollection 2021.
Total body irradiation (TBI) in combination with chemotherapy is widely used as a conditioning regimen in pediatric and adult hematopoietic stem cell transplantation (HSCT). The combination of TBI with chemotherapy has demonstrated superior survival outcomes in patients with acute lymphoblastic and myeloid leukemia when compared with conditioning regimens based only on chemotherapy. The clinical application of intensity-modulated radiation therapy (IMRT)-based methods (volumetric modulated arc therapy (VMAT) and TomoTherapy) seems to be promising and has been actively used worldwide. The optimized conformal total body irradiation (OC-TBI) method described in this study provides selected dose reduction for organs at risk with respect to the most significant toxicity (lungs, kidneys, lenses). This study included 220 pediatric patients who received OC-TBI with subsequent chemotherapy and allogenic HSCT with TCRαβ/CD19 depletion. A group of 151 patients received OC-TBI using TomoTherapy, and 40 patients received OC-TBI using the Elekta Synergy™ linac with an Agility-MLC (Elekta, Crawley, UK) using volumetric modulated arc therapy (VMAT). Twenty-nine patients received OC-TBI with supplemental simultaneous boost to bone marrow-(SIB to BM) up to 15 Gy: 28 patients (pts)-TomoTherapy; one patient-VMAT. The follow-up duration ranged from 0.3 to 6.4 years (median follow-up, 2.8 years). Overall survival (OS) for all the patients was 63% (95% CI: 56-70), and event-free survival (EFS) was 58% (95% CI: 51-65). The cumulative incidence of transplant-related mortality (TRM) was 10.7% (95% CI: 2.2-16) for all patients. The incidence of early TRM (<100 days) was 5.0% (95% CI: 1.5-8.9), and that of late TRM (>100 days) was 5.7 (95% CI: 1.7-10.2). The main causes of death for all the patients were relapse and infection. The concept of OC-TBI using IMRT VMAT and helical treatment delivery on a TomoTherapy treatment unit provides maximum control of the dose distribution in extended targets with simultaneous dose reduction for organs at risk. This method demonstrated a low incidence of severe side effects after radiation therapy and predictable treatment effectiveness. Our initial experience demonstrates that OC-TBI appears to be a promising technique for the treatment of pediatric patients.
全身照射(TBI)联合化疗作为儿科和成人造血干细胞移植(HSCT)中的预处理方案被广泛应用。与仅基于化疗的预处理方案相比,TBI与化疗联合在急性淋巴细胞白血病和髓细胞白血病患者中已显示出更好的生存结果。基于调强放射治疗(IMRT)的方法(容积调强弧形治疗(VMAT)和螺旋断层放疗)的临床应用似乎很有前景,并已在全球范围内积极使用。本研究中描述的优化适形全身照射(OC-TBI)方法针对最显著毒性(肺、肾、晶状体)的危险器官提供了选定的剂量降低。本研究纳入了220例接受OC-TBI随后进行化疗和TCRαβ/CD19去除的同种异体HSCT的儿科患者。一组151例患者使用螺旋断层放疗接受OC-TBI,40例患者使用配备敏捷多叶准直器(Agility-MLC)的医科达Synergy™直线加速器(医科达,克劳利,英国)通过容积调强弧形治疗(VMAT)接受OC-TBI。29例患者接受OC-TBI并同时对骨髓进行补充同步推量照射(SIB至BM)至15 Gy:28例患者 - 螺旋断层放疗;1例患者 - VMAT。随访时间为0.3至6.4年(中位随访时间为2.8年)。所有患者的总生存率(OS)为63%(95%CI:56 - 70),无事件生存率(EFS)为58%(95%CI:51 - 65)。所有患者移植相关死亡率(TRM)的累积发生率为10.7%(95%CI:2.2 - 16)。早期TRM(<100天)的发生率为5.0%(95%CI:1.5 - 8.9),晚期TRM(>100天)的发生率为5.7(95%CI:1.7 - 10.2)。所有患者的主要死亡原因是复发和感染。在螺旋断层放疗治疗单元上使用IMRT VMAT和螺旋治疗方式的OC-TBI概念可在扩大靶区中最大程度地控制剂量分布,同时降低危险器官的剂量。该方法显示放疗后严重副作用的发生率较低且治疗效果可预测。我们的初步经验表明,OC-TBI似乎是治疗儿科患者的一种有前景的技术。