Response-Adapted Ultralow-Dose Radiation Therapy for Orbital Indolent B-Cell Lymphoma: A Phase 2 Nonrandomized Controlled Trial.

IF 28.4 1区医学 Q1 Biochemistry, Genetics and Molecular Biology

Jama Oncology Pub Date : 2024-09-01 DOI:10.1001/jamaoncol.2024.2112

Chelsea C Pinnix, Bouthaina S Dabaja, Jillian R Gunther, Penny Q Fang, Susan Y Wu, Loretta J Nastoupil, Paolo Strati, Ranjit Nair, Sairah Ahmed, Raphael Steiner, Jason Westin, Sattva Neelapu, Maria A Rodriguez, Hun Ju Lee, Michael Wang, Christopher Flowers, Lei Feng, Bita Esmaeli

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引用次数: 0

Abstract

Importance: Radiation therapy to doses of 24 to 36 Gy is currently used to treat indolent B-cell lymphoma of the ocular adnexa; however, ocular adverse effects are common.

Objective: To determine if a response-adapted radiation therapy strategy will result in excellent disease outcomes while reducing orbital morbidity.

Design, setting, and participants: This single-institution, phase 2 prospective nonrandomized controlled trial of a response-adapted strategy involved 50 evaluable patients with stage I to IV indolent B-cell lymphoma of the ocular adnexa enrolled between July 2015 and January 2021. This treatment approach was also retrospectively evaluated with a separate 55-patient cohort treated between March 2013 and October 2021. All data were analyzed between November 2021 and December 2023.

Interventions: Patients were treated with ultralow-dose radiation therapy to 4 Gy in 2 fractions and assessed for response at 3-month intervals. Patients with persistent orbital lymphoma were offered an additional 20 Gy in 10 fractions to complete the response-adapted treatment.

Main outcome and measures: The primary end point was 2-year local orbital control within the irradiated field after response-adapted therapy. Secondary end points included overall survival and complete response rate.

Results: The 50 prospective patients were a median (range) of 63 (29-88) years old, and 31 (62%) were female. Among the 50 patients, 32 (64%) had mucosa-associated lymphoid tissue lymphoma, 12 (24%) had follicular lymphoma, and 6 (12%) had unclassifiable low-grade B-cell lymphoma. Thirty-one patients (62%) had stage I disease, and 36 (72%) were newly diagnosed. At a median follow-up of 37.4 (95% CI, 33.7-52.5) months, the 2-year local control rate was 89.4% (95% CI, 81.0%-98.7%), and the 2-year overall survival rate was 98.0% (95% CI, 94.1%-100%); 45 patients (90.0%; 95% CI, 78.2%-96.7%) experienced a complete response to response-adapted radiation, including 44 patients with a complete response to ultralow-dose radiation and 1 patient with a complete response after an additional 20 Gy. No local recurrences were observed among patients with a complete response to response-adapted therapy. No grade 3 or higher toxic effects were observed. In a planned subset analysis of 22 patients with newly diagnosed, untreated stage I mucosa-associated lymphoid tissue lymphoma, the 2-year local control rate was 90.7% (95% CI, 79.2%-100%), and the 2-year freedom from distant relapse rate was 95.2% (95% CI, 86.6%-100%).

Conclusion and relevance: In this nonrandomized controlled trial, response-adapted ultralow-dose therapy for indolent orbital B-cell lymphoma resulted in reduced radiation exposure, negligible toxic effects, and excellent disease outcomes.

Trial registration: ClinicalTrials.gov Identifier: NCT02494700.

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眼眶惰性 B 细胞淋巴瘤的反应适应性超低剂量放射治疗：2期非随机对照试验》。

重要性：目前，24 至 36 Gy 剂量的放射治疗用于治疗眼附件的轻度 B 细胞淋巴瘤；然而，眼部不良反应很常见：目的：确定适应反应的放射治疗策略是否能在减少眼眶发病率的同时获得良好的疾病治疗效果：这项针对反应适应策略的单一机构2期前瞻性非随机对照试验涉及50例可评估的I期至IV期眼附件惰性B细胞淋巴瘤患者，入组时间为2015年7月至2021年1月。此外，还对2013年3月至2021年10月期间接受治疗的55名患者进行了回顾性评估。所有数据分析时间为 2021 年 11 月至 2023 年 12 月：患者接受超低剂量放射治疗，每次4Gy，分2次进行，每隔3个月进行一次反应评估。眼眶淋巴瘤持续存在的患者可再接受一次20 Gy、10次分割的治疗，以完成反应适应性治疗：主要结果：主要终点是接受反应适应治疗后在照射区域内的2年局部眼眶控制率。次要终点包括总生存期和完全反应率：50名前瞻性患者的年龄中位数（范围）为63（29-88）岁，其中31人（62%）为女性。50名患者中，32人（64%）患有粘膜相关淋巴组织淋巴瘤，12人（24%）患有滤泡性淋巴瘤，6人（12%）患有无法分类的低级别B细胞淋巴瘤。31名患者（62%）处于疾病的I期，36名患者（72%）是新确诊的。中位随访时间为37.4个月（95% CI，33.7-52.5个月），2年局部控制率为89.4%（95% CI，81.0%-98.7%），2年总生存率为98.0%（95% CI，94.1%-100%）；45名患者（90.0%；95% CI，78.2%-96.7%）对适应反应的放射治疗有完全反应，其中44名患者对超低剂量放射治疗有完全反应，1名患者在追加20 Gy后有完全反应。在对反应适应疗法完全反应的患者中，没有观察到局部复发。没有观察到 3 级或更高的毒性反应。在对22名新诊断、未经治疗的I期粘膜相关淋巴组织淋巴瘤患者进行的计划子集分析中，2年局部控制率为90.7%（95% CI，79.2%-100%），2年无远处复发率为95.2%（95% CI，86.6%-100%）：在这项非随机对照试验中，反应适应性超低剂量疗法治疗惰性眼眶B细胞淋巴瘤减少了放射线暴露，毒性反应可忽略不计，疾病疗效极佳：试验注册：ClinicalTrials.gov Identifier：试验注册：ClinicalTrials.gov Identifier：NCT02494700。

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来源期刊

Jama Oncology Medicine-Oncology

CiteScore

37.50

自引率

1.80%

发文量

423

期刊介绍： At JAMA Oncology, our primary goal is to contribute to the advancement of oncology research and enhance patient care. As a leading journal in the field, we strive to publish influential original research, opinions, and reviews that push the boundaries of oncology science. Our mission is to serve as the definitive resource for scientists, clinicians, and trainees in oncology globally. Through our innovative and timely scientific and educational content, we aim to provide a comprehensive understanding of cancer pathogenesis and the latest treatment advancements to our readers. We are dedicated to effectively disseminating the findings of significant clinical research, major scientific breakthroughs, actionable discoveries, and state-of-the-art treatment pathways to the oncology community. Our ultimate objective is to facilitate the translation of new knowledge into tangible clinical benefits for individuals living with and surviving cancer.