255 - Initial Results of the Multicenter Phase II Trial of a Novel Hypofractionated Low-Dose Radiotherapy for Indolent Non-Hodgkin Lymphoma

X. Wang¹, L. R. Gao¹, L. Wang², X. Zhang³, K. Chen⁴, X. Feng⁵, R. Zheng⁶, Y. X. Li¹, and S. Qi¹; ¹Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, ²Department of Hematology, Beijing TongRen Hospital, Capital Medical University, Beijing, China, ³Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China, ⁴Department of Radiochemotherapy, The Affiliated Peoples Hospital of Ningbo Universit, Ningbo, China, ⁵Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, ⁶Department of Nuclear Medicine, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Purpose/Objective(s): Indolent non-Hodgkin lymphoma (iNHL) has been shown to be highly radiosensitive, and the most effective radiotherapy (RT) regimen has yet to be established. Recent findings suggested that hypofractionated RT may have a more pronounced anti-tumor effect. To our knowledge, few prospective studies to date have evaluated the safety and efficacy of dose-deescalated hypofractionated radiotherapy as treatment of iNHL. We hypothesized that the 6-month complete response rate with hypofractionated low-dose radiotherapy (LDRT) of 12 Gy in four fractions is noninferior to that with conventionally fractionated 24Gy-RT. Materials/

Methods: We conducted a multicenter, single-arm, phase II trial (NCT05543070) to evaluate the efficacy and toxicity of a hypofractionated regimen and low-dose radiotherapy in patients with iNHL. Patients with indolent non-Hodgkin lymphoma aged 18 years or older, without a history of prior radiotherapy at the same site, were deemed eligible for the study. Involved-site radiotherapy (ISRT) was delivered at 12 Gy in four fractions within one week. The primary endpoint was the complete response (CR) rate per RECIL 2017 by investigators at 6 months after radiotherapy. Secondary endpoints were 6-month overall response rate (ORR), 2-year progression-free survival, 2-year local control rate (LCR), acute and late toxicity, quality of life (QOL), and immunologic biomarkers induced by hypofractionated radiotherapy. Toxicity was reported as per CTCAE v5.0. A sample size of 73 sites was determined based on the assumption that the 6-month CR rate would be at least 68%, with a one-sided significance level of 0.05 and a power of 0.8.
Results: A total of 73 sites from 71 patients were enrolled between May 8, 2022, and November 8, 2023, in 3 centers in China. The median age was 54 years (IQR, 47-64), with a male-to-female ratio of 1:1.43. 82.2% of patients were at Ann Arbor stage I or II. 75.3% of sites were marginal zone lymphoma and 23.3% were follicular lymphoma. With a median follow-up of 8.7 months (range, 3.6-21.6), the CR and ORR rates were 91.8% and 100%, respectively. Acute toxicities were minimal, with no grade 3 or greater adverse events associated with hypofractionated LDRT. The most frequent grade 1 or 2 adverse events were lymphocytopenia (30.1%), and nausea (20.5%), with 79.8% of cases occurring within 2 weeks following the completion of radiotherapy.
Conclusion: Hypofractionated low-dose radiotherapy of 12 Gy in 4 fractions in this prospective trial demonstrated promising anti-tumor activity among patients with iNHL. No severe toxicity was observed in the novel regimen. Long-term follow-up is required to assess the durability of tumor control, late toxicity, dynamic QOL, and immune biomarkers.