Rutgers Cancer Institute of New Jersey, Department of Radiation Oncology, New Brunswick, New Jersey.
Department of Pediatric Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
Int J Radiat Oncol Biol Phys. 2022 Mar 15;112(4):890-900. doi: 10.1016/j.ijrobp.2021.10.152. Epub 2021 Nov 9.
The Children's Oncology Group protocol AHOD0831, for pediatric patients with high-risk classical Hodgkin lymphoma (cHL), used response-adapted radiation fields, rather than larger involved-field radiation therapy (IFRT) that were historically used. This retrospective analysis of patterns of relapse among patients enrolled in the study was conducted to study the potential effect of a reduction in RT exposure.
From December 2009 to January 2012, 164 eligible patients under 22 years old with stage IIIB (43%) and stage IVB (57%) enrolled on AHOD0831. All patients received 4 cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC). Those patients with a slow early response (SER) after the first 2 ABVE-PC courses were nonrandomly assigned to 2 intensification cycles with ifosfamide/vinorelbine before the final 2 ABVE-PC cycles. Response-adapted RT (21 Gy) was prescribed to initial areas of bulky disease and SER sites. Rapid early response (RER) sites without bulk were not targeted. Imaging studies at the time of progression or relapse were reviewed centrally for this retrospective analysis. Relapses were characterized with respect to site (initial, new, or both; and initial bulk or initial nonbulk), initial chemotherapy response, and radiation field (in-field, out-of-field, or both).
Of the entire cohort, 140 patients were evaluable for the patterns of failure analyses. To investigate the pattern of failure, this analysis focuses on 23 patients who followed protocol treatment and suffered relapses at a median 1.05 years with 7.97-year median follow-up time. These 23 patients (11 RER and 12 SER) experienced a relapse in 105 total sites (median, 4; range, 1-11). Of the 105 relapsed sites, 67 sites (64%) occurred within an initial site of involvement, with 12 of these 67 sites (18%) at an initial site of bulky disease and 63 of these 67 relapses (94%) occurring in sites that were not fluorodeoxyglucose (FDG)-avid after 2 cycles of ABVE-PC (PET2-negative). Of the 105 relapsed sites, 34 sites (32%) occurred in a new site of disease (that would not have been covered by RT); and, overall, only 4 of 140 patients (2.8%) (occurring in 3 RER and 1 SER) experienced isolated out-of-field relapses that would have been covered by historical IFRT.
For a cohort of high-risk patients with cHL patients, most failures occurred in nonbulky, initially involved sites, largely due to response-based consolidation RT delivered to patients with bulky disease. In this analysis, we discovered low rates of failures outside of these modern risk-adapted radiation treatment volumes. Also, FDG uptake on PET2 did not identify most relapse sites.
儿童肿瘤学组的 AHOD0831 方案用于治疗高危经典霍奇金淋巴瘤（cHL）的儿科患者，采用了适应性放疗方案，而不是过去常用的大野受累放疗（IFRT）。本研究对该研究入组患者的复发模式进行了回顾性分析，以研究放疗暴露减少的潜在影响。
2009 年 12 月至 2012 年 1 月，164 名年龄在 22 岁以下的 IIIB 期（43%）和 IVB 期（57%）患者符合 AHOD0831 方案入组标准。所有患者均接受了 4 个周期的多柔比星、博来霉素、长春新碱、依托泊苷、泼尼松和环磷酰胺（ABVE-PC）治疗。前 2 个 ABVE-PC 疗程后出现早期缓慢缓解（SER）的患者，非随机接受 2 个强化周期异环磷酰胺/长春瑞滨治疗，然后再进行最后 2 个 ABVE-PC 疗程。适应性放疗（21 Gy）用于初始大肿块疾病和 SER 部位。没有肿块的快速早期缓解（RER）部位未作为目标。为了进行这项回顾性分析，在疾病进展或复发时对中央成像研究进行了复查。根据部位（初始、新发或两者均有；初始肿块或初始非肿块）、初始化疗反应和放疗野（野内、野外或两者均有）对复发进行了描述。
在整个队列中，有 140 名患者可用于失败模式分析。为了研究失败模式，本分析重点关注了 23 名按照方案治疗并在中位 1.05 年后复发的患者，中位随访时间为 7.97 年。这 23 名患者（11 名 RER 和 12 名 SER）在 105 个部位复发（中位数为 4 个；范围为 1-11 个）。在 105 个复发部位中，有 67 个部位（64%）位于初始受累部位，其中 12 个部位（18%）为初始肿块部位，63 个部位（94%）为 2 个 ABVE-PC 周期后无氟脱氧葡萄糖（FDG）摄取（PET2 阴性）的部位。在 105 个复发部位中，有 34 个部位（32%）位于新发疾病部位（不会被放疗覆盖）；总体而言，只有 4 名患者（2.8%）（3 名 RER 和 1 名 SER）发生孤立的野外复发，而这些复发部位会被历史上的 IFRT 覆盖。
对于高危经典霍奇金淋巴瘤患者队列，大多数复发发生在非肿块、初始受累部位，主要是由于对有肿块的患者进行了基于反应的巩固性放疗。在本分析中，我们发现现代风险适应放疗治疗体积之外的失败率较低。此外，PET2 上的 FDG 摄取并不能识别大多数复发部位。
