Near-Perfect Control of Slow-Growing Lymphoma With Low-Dose Radiotherapy

Low-dose radiotherapy for a slow-growing stomach lymphoma achieved near-perfect disease control with no severe toxicity, a small prospective study showed.

After a 4 Gy dose of radiotherapy in two fractions, 20 of 24 patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma had complete responses. The four patients with residual disease achieved complete responses after an additional 25 Gy. One relapse after 4 Gy was successfully treated with 20 Gy salvage therapy, and one patient with stage IV disease had a distant relapse.

The most common adverse events were grade 1 nausea and abdominal pain, reported Jillian Gunther, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and coauthors in Lancet Haematology.

“To our knowledge, this is the first report of a prospective trial using response-adapted radiation therapy to dramatically decrease the dose of radiotherapy given to patients with gastric mucosa-associated lymphoid tissue lymphoma, while still providing a mechanism to ensure that patients requiring a higher dose are adequately treated,” the authors stated.

“Our study adds to the body of existing evidence for the efficacy of 4 Gy in the treatment of marginal zone lymphoma, with a greater proportion of patients experiencing complete response in this study than in some of the older studies due to the planned ability to give an additional dose if necessary,” they added. “For patients with a higher risk of toxicity from radiotherapy or when observation alone is considered for any reason, this approach provides a nontoxic and effective alternative.”

Despite the “excellent outcomes,” longer follow-up is needed to determine whether more late relapses occur, according to the authors of an accompanying commentary.

“The question remains of whether we are ready to implement this strategy more widely, based on the current findings,” wrote Peter Meidahl Petersen, MD, and Dorte Schou Nørøxe, MD, of Copenhagen University Hospital in Denmark. “The study did not include patients with more severe symptoms, such as bleeding, weight loss, and vomiting, or patients with bulky disease.”

“The radiotherapy planning and delivery as outlined in this study could be easily implemented in radiotherapy centers,” they continued. “However, to achieve precise staging and to assess status of disease at follow-up, which are vital in a study, a large number of procedures are needed such as gastroscopies with numerous biopsies and scans. It would be interesting to see an analysis of which of these procedures are necessary to keep the treatment strategy safe. This information would be relevant if this strategy were to be implemented more widely.”

If careful follow-up is not possible, a standard radiotherapy dose of about 24 Gy will probably be needed, Petersen and Nørøxe added.

Historically, treatment for gastric MALT lymphoma has evolved from aggressive interventions — radical surgery, combination chemotherapy, extended-field high-dose radiotherapy — to a moderate radiotherapy approach, particularly for early-stage disease, the authors noted in their introduction. Some attempts have been made to omit radiotherapy by starting treatment with an antibiotic, even for patients without identified driver infections.

With respect to radiotherapy, a focus on de-escalation has led to smaller involved-site radiation fields and use of treatment techniques to help reduce doses to normal tissue, the authors continued. A response-adapted approach starting with 4 Gy initially was validated in patients with orbital indolent B-cell lymphoma. Given encouraging results with the strategy, Gunther and colleagues explored a novel response-adapted approach for Helicobacter pylori-negative stage I-IV gastric MALT lymphoma.

Investigators prospectively enrolled adults with newly diagnosed or previously treated gastric MALT lymphoma. Initial treatment consisted of a 4 Gy dose of radiotherapy in two fractions, using three-dimensional conformal technique. Patients with a complete response to 4 Gy after 3-4 months were observed while those with a partial response were re-evaluated after 6-9 months. Patients received an additional 20 Gy dose of intensity-modulated radiotherapy if they had residual disease at 9-13 months or stable or progressive disease at any time.

The primary endpoint was complete response at 1 year, and data analysis included 24 patients. One patient had stage II disease and three had stage IV; the remaining 20 had stage I disease. Median follow-up was 36 months.

Low-dose RT resulted in a complete response rate of 83% (20 of 24), which occurred at 3-4 months in 16 cases and the remaining four at 9-13 months. Two patients received 20 Gy for symptomatic stable disease at 3-4 months and two others for residual disease at 9-13 months. All four had a complete response. The local control rate was 96% at 3 years (one relapse at 14 months).

Nine patients who received 4 Gy had grade 1 nausea, as did two patients who received 20 Gy. Five patients who received 4 Gy had grade 1 abdominal pain. No patients had grade ≥3 adverse events.

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