Response-adapted ultra-low-dose 4 Gy radiation as definitive therapy of gastric MALT lymphoma: a single-centre, pilot trial.

in The Lancet. Haematology by Jillian R Gunther, Jie Xu, Manoop S Bhutani, Paolo Strati, Penny Q Fang, Susan Y Wu, Bouthaina S Dabaja, Wenli Dong, Priya R Bhosale, Christopher R Flowers, Ranjit Nair, Luis Malpica Castillo, Luis Fayad, Swaminathan P Iyer, Simrit Parmer, Michael Wang, Hun Ju Lee, Felipe Samaniego, Jason Westin, Sairah Ahmed, Chijioke C Nze, Preetesh Jain, Sattva S Neelapu, Maria A Rodriguez, Dai Chihara, Loretta J Nastoupil, Chelsea C Pinnix

TLDR

  • This study looked at how well a type of radiation therapy called 4 Gy radiotherapy worked for people with a type of cancer called gastric MALT lymphoma. The study found that most people who got this radiation therapy had a complete response to it, meaning that their cancer went away completely. The study also found that the radiation therapy was safe and had a low risk of causing side effects. The study suggests that this type of radiation therapy could be used to help people with gastric MALT lymphoma who need more treatment after their initial treatment. However, more research is needed to see if this type of radiation therapy is effective for other types of cancer or when used with other treatments.

Abstract

Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach. We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total dose of 4 Gy in two fractions. Patients with a complete response to 4 Gy via endoscopy and imaging at 3-4 months were observed; patients with a partial response were re-evaluated in 6-9 months. Residual disease at 9-13 months or stable or progressive disease at any time required additional treatment with 20 Gy. The primary endpoint was gastric complete response at 1 year (second evaluation timepoint) after 4 Gy treatment. All analyses were performed as intention to treat. This trial is registered at ClinicalTrials.gov (NCT03680586) and is complete and closed to enrolment. Between March 27, 2019, and Oct 12, 2021, we enrolled 24 eligible patients. The median age of participants was 67 years (IQR 58-74; range 40-85); 15 (63%) were female and nine (37%) male; 18 (75%) were White, four (17%) Asian, and two (8%) Hispanic; 20 (83%) had stage I disease, one (4%) stage II, and three (13%) stage IV. Median follow-up time was 36 months (IQR 26-42). 20 patients (83%) had a complete response to 4 Gy (16 at 3-4 months, four at 9-13 months); two patients received 20 Gy for symptomatic stable disease at 3-4 months and two for residual disease at 9-13 months; all had a complete response. The 3-year local control rate was 96% (95% CI 88-100), with one local relapse at 14 months after 4 Gy radiotherapy salvaged successfully with 20 Gy. One patient with stage IV disease had a distant relapse. The most common adverse events were grade 1 nausea (nine [38%] of 24 patients who received 4 Gy and two [50%] of four patients who received 20 Gy) and grade 1 abdominal pain (five [21%] of 24 and zero of four, respectively). No grade 3 or worse adverse events were noted, including no treatment-related deaths. Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months. This response-adapted strategy could be used to select patients who would benefit from additional radiotherapy and spare others potential associated toxicity. National Cancer Institute.

Overview

  • The study aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach for patients with gastric MALT lymphoma. The study was conducted at MD Anderson Cancer Center and included 24 eligible patients with newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. The primary endpoint was gastric complete response at 1 year after 4 Gy treatment. Performance status was not an exclusion criterion, and patients received external beam photon-based radiotherapy for a total dose of 4 Gy in two fractions. Residual disease at 9-13 months or stable or progressive disease at any time required additional treatment with 20 Gy. All analyses were performed as intention to treat.

Comparative Analysis & Findings

  • The study found that 20 patients (83%) had a complete response to 4 Gy radiotherapy, with 16 achieving a complete response at 3-4 months and four at 9-13 months. Two patients received 20 Gy for symptomatic stable disease at 3-4 months and two for residual disease at 9-13 months, all of whom had a complete response. The 3-year local control rate was 96% (95% CI 88-100), with one local relapse at 14 months after 4 Gy radiotherapy salvaged successfully with 20 Gy. One patient with stage IV disease had a distant relapse. The most common adverse events were grade 1 nausea (nine [38%] of 24 patients who received 4 Gy and two [50%] of four patients who received 20 Gy) and grade 1 abdominal pain (five [21%] of 24 and zero of four, respectively). No grade 3 or worse adverse events were noted, including no treatment-related deaths. Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months.

Implications and Future Directions

  • The study's findings suggest that a response-adapted strategy could be used to select patients who would benefit from additional radiotherapy and spare others potential associated toxicity. The study's low toxicity profile and high local control rate make it a promising approach for patients with gastric MALT lymphoma. Future research could explore the use of this strategy in other types of lymphoma or in combination with other treatments. Additionally, further studies could investigate the optimal timing and duration of additional radiotherapy for patients who require it.
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