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Excellent response to very-low-dose radiation (4 Gy) for indolent B-cell lymphomas: is 4 Gy suitable for curable patients?

ABSTRACT: Radiotherapy plays an important role in managing highly radiosensitive, indolent non-Hodgkin lymphomas, such as follicular lymphoma and marginal zone lymphoma. Although the standard of care for localized indolent non-Hodgkin lymphomas remains 24 Gy, de-escalation to very-low-dose radiotherapy (VLDRT) of 4 Gy further reduces toxicities and duration of treatment. Use of VLDRT outside palliative indications remains controversial; however, we hypothesize that it may be sufficient for most lesions. We present the largest single-institution VLDRT experience of adult patients with follicular lymphoma or marginal zone lymphoma treated between 2005 and 2018 (299 lesions; 250 patients) using modern principles including positron emission tomography staging and involved site radiotherapy. Outcomes include best clinical or radiographic response between 1.5 and 6 months after VLDRT and cumulative incidence of local progression (LP) with death as the only competing risk. After VLDRT, the overall response rate was 90% for all treated sites, with 68% achieving complete response (CR). With a median follow-up of 2.4 years, the 2-year cumulative incidence of LP was 25% for the entire cohort and 9% after first-line treatment with VLDRT for potentially curable, localized disease. Lesion size >6 cm was associated with lower odds of attaining a CR and greater risk of LP. There was no suggestion of inferior outcomes for potentially curable lesions. Given the clinical versatility of VLDRT, we propose to implement a novel, incremental, adaptive involved site radiotherapy strategy in which patients will be treated initially with VLDRT, reserving full-dose treatment for those who are unable to attain a CR.

SUBMITTER: Imber BS

PROVIDER: S-EPMC8945632 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Excellent response to very-low-dose radiation (4 Gy) for indolent B-cell lymphomas: is 4 Gy suitable for curable patients?

Imber Brandon S BS Chau Karen W KW Lee Jasme J Lee Jisun J Casey Dana L DL Yang Joanna C JC Wijentunga N Ari NA Shepherd Annemarie A Hajj Carla C Qi Shunan S Chelius Monica R MR Hamlin Paul A PA Palomba M Lia ML Joffe Erel E Zhang Zhigang Z Zelenetz Andrew D AD Salles Gilles A GA Yahalom Joachim J

Blood advances 20211001 20

Radiotherapy plays an important role in managing highly radiosensitive, indolent non-Hodgkin lymphomas, such as follicular lymphoma and marginal zone lymphoma. Although the standard of care for localized indolent non-Hodgkin lymphomas remains 24 Gy, de-escalation to very-low-dose radiotherapy (VLDRT) of 4 Gy further reduces toxicities and duration of treatment. Use of VLDRT outside palliative indications remains controversial; however, we hypothesize that it may be sufficient for most lesions. W ...[more]

PMID: 34529789

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Project description:National Comprehensive Cancer Network guidelines recommend radiation therapy (RT) for localized indolent non-Hodgkin lymphomas (iNHL). Many referring physicians avoid RT to the head and neck (HN) due to fears of toxicity. Very low-dose radiation (4 Gy) for select patients produces sustained local control and recently gained popularity. We compared early and late toxicities of standard 24-30 Gy to 4 Gy in patients with HN iNHL. We retrospectively analyzed 266 consecutive patients with HN iNHL receiving RT from 1994 to 2017. Patient characteristics, outcomes, and toxicities were collected from medical records. Early (≤2 months post-RT) and late (>2 months post-RT) toxicities were graded per Common Terminology Criteria for Adverse Events version 4. Grades 1-2 were defined as "low-grade" and 3-4 "high-grade." Toxicity incidence was compared between 4 and >4 Gy, grouped by treated site (orbit, nonorbital head, neck, skin) and early versus late. Median follow-up was 23 months (2-145) and 68 months (2-256) for 4Gy and >4 Gy cohorts, respectively. Median dose for the >4 Gy cohort was 30 Gy (10.5-54 Gy). Early and late toxicity incidences were lower in the 4 Gy cohort compared to >4 Gy across all RT-sites: early toxicity, orbit, 42% versus 96%; nonorbital head, 24% versus 96%; neck, 22% versus 94%; skin, 31% versus 87%; late toxicity, orbit, 20% versus 71%; nonorbital head, 6% versus 66%; neck, 6% versus 57%; skin, 0% versus 46% (4 Gy vs. >4 Gy, respectively). Toxicities among both cohorts were largely low-grade. High-grade early and late toxicities did not occur in the 4 Gy cohort. There was 1 high-grade early toxicity (Grade 3 dry mouth) and 17 high-grade late toxicities (Grade 3 cataracts) in the >4 Gy cohort. RT to HN for iNHL is associated with minimal short- and long-term toxicity and excellent local control among 4 Gy and >4 Gy treatments. In this setting, "toxicity" concerns should not deter oncologists from potentially curative RT. In select patients where toxicity remains a concern, very low dose 4 Gy could be considered.

Project description:PurposeRadiation therapy (RT) with doses ranging from 24 Gray (Gy) to 40 Gy is a proven treatment modality for indolent orbital adnexal lymphoma (IOAL), but recently the use of low dose RT (LDRT, defined as 2 Gy x 2 fractions) has become a notable alternative. However, limited data exists comparing outcomes following LDRT to moderate-dose RT (MDRT, RT dose 4 - 36 Gy). We present a single institution retrospective analysis comparing outcomes of patients with IOALs following LDRT or MDRT.MethodsA total of 36 patients treated with 38 consecutive courses of RT were identified; LDRT was delivered for 14 courses and MDRT for 24 courses. Overall response rates (ORR) were recorded according to Deauville or RECIST criteria with a response characterized as a complete response (CR) or partial response. Local control (LC), orbital control (OC), and overall survival (OS) rates were estimated with the Kaplan-Meier method. RT toxicity was graded per CTCAEv5 and compared with the Fisher's exact test.ResultsMedian follow-up time was 29 months (m) (range, 4-129m), and median MDRT dose used was 24 Gy (range 21-36 Gy). Overall response rates (ORR) were 100% (CR 50%) and 87.5% (CR 58.3%) following LDRT and MDRT, respectively. OS at 2 years was 100% and 95% for the LDRT and MDRT groups, respectively (p=0.36). LC rates at 2 years was 100% for both LDRT and MDRT groups and at 4 years was 100% and 89% for the LDRT and MDRT groups, respectively (p=0.56). The 4-year OC rate (including both ipsilateral and contralateral relapses) was 80% and 85% for the LDRT and MDRT groups, respectively (p=0.79). No patient required treatment with RT to a previously irradiated orbit. Acute toxicities were reported following 6 LDRT courses compared to 20 MDRT courses (p=.014). No Grade 3 or higher acute toxicities occurred in either group. Late toxicities were reported following 2 LDRT courses compared to 10 MDRT courses (p=0.147).ConclusionsLDRT produced similar ORR, LC, OC, and OS rates compared to MDRT with fewer acute and minimal late toxicities reported. Future multi-center studies with larger patient numbers are warranted to show significant associations.

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Excellent response to very-low-dose radiation (4 Gy) for indolent B-cell lymphomas: is 4 Gy suitable for curable patients?

Publications

Excellent response to very-low-dose radiation (4 Gy) for indolent B-cell lymphomas: is 4 Gy suitable for curable patients?

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