Radiotherapy Treatment Doses of 24 Gy in 12 Fractions Confirmed as Optimal for Patients With Indolent non-Hodgkin Lymphoma

The standard of care radiotherapy treatment of 24 Gy in 12 fractions was confirmed as the optimal dose to treat patients with indolent non-Hodgkin lymphoma, according to data published in The Lancet Oncology.

An examination of the Follicular Radiotherapy Trial (FoRT; NCT00310167) at 5 years comparing the standard of care 24 Gy in 12 fractions with 4 Gy in 2 fractions (low-dose radiation) for this patient population confirmed the former in superior when durable local control is the aim of treatment.

“These mature results from FoRT, to our knowledge the only randomised trial to have addressed the role of low-dose radiotherapy in indolent non-Hodgkin lymphoma, provide level 1 evidence for use of 24 Gy in 12 fractions in patients for whom durable local control is the aim of treatment,” wrote the investigators. “No subgroup has been identified in which this conclusion does not apply.”

At a 2-year analysis, the local progression-free rate for patients in the 24 Gy in 12 fractions group was 94.1% (95% CI, 90.6%-96.4%) versus 79.8% (95% CI, 74.8%-83.9%) for patients in the 4 Gy in 2 fractions group. At the 5-year analysis, the local progression-free survival rates were 89.9% (95% CI, 85.5%-93.1%) and 70.4% (95% CI, 64.7%-75.4%), respectively. (HR, 3.46; 95% CI, 2.25-5.33; P < .0001).

The adverse events profile of the different treatment fractions at week 12 featured alopecia (19 of 287 sites with 24 Gy [7%] vs 6 of 301 sites with 4 Gy [2%]), dry mouth (11 sites [4%] vs 5 sites [2%]), fatigue (7 sites [2%] vs 5 sites [2%]), mucositis (7 sites [2%] vs 3 sites [1%]), and pain (7 sites [2%] vs 2 sites [1%]). Of note, no treatment-related deaths were reported with this data.

The randomized, multicenter, phase 3, non-inferiority trial enrolled 548 patients aged 18 years or older with indolent non-Hodgkin lymphoma. The 614 target sites in this patient population were randomized to either 24 Gy in 12 fractions (n = 299) or 4 Gy in 2 fractions (n = 315). Median follow-up was 73.8 months (IQR 61.9–88.0), with 117 local progression events recorded.

“This finding suggests that lymphoma cells are surviving with 4 Gy radiotherapy, and these cells are either viable or able to repair damage and subsequently manifest as local recurrence, which accords with the difference in complete response rate seen between the 2 dose levels,” wrote the investigators.

While the research team was able to confirm that standard-of-care treatment is the optimal dosage for patients with indolent non-Hodgkin lymphoma, the low-dose radiation option could be considered for patients who require palliation or for patients who have definitive systemic treatment planned.

This research is not without limitations, as the investigative team acknowledged the study’s design, which allowed for multiple sequential randomizations in 1 patient, limits the data. Regardless, the team suggests the robust data collection from each site and additional analyses mitigate this limitation.

“In the palliative setting, 4 Gy of radiotherapy might provide a pragmatic treatment for local symptom control, but, for durable local control of follicular and marginal zone lymphoma, 24 Gy should be used,” wrote the investigators.

Reference:

Hoskin P, Popova B, Schofield O, et al. 4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2021;22(3):332-340. doi: 10.1016/S1470-2045(20)30686-0