Prospective Phase II Trial of Radiation Therapy in Localized Non-Gastric Marginal Zone Lymphoma With Evaluation of Autoimmunity and Helicobacter Pylori Status

• Published in: International journal of radiation oncology, biology, physics Vol. 111; no. 3; p. S105
• Main Authors: MacManus, M.P., Roos, D.E., O'Brien, P., Anne, C., Wirth, A., Bressel, M., Tsang, R.W., Lade, S., Seymour, J.F.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-11-2021
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2021.07.243

This phase 2 multicenter clinical trial evaluated the effectiveness and safety of radiotherapy in localized non-gastric marginal zone lymphoma (MZL) and assessed the prevalence of markers of autoimmunity and Helicobacter pylori (HP) infection in this population. It was designed to test the hypotheses that-long term local progression-free survival (PFS) would be > 80% and that death within 10 years would occur in < 10% of patients.
Eligibility required untreated stage I-II, or bilateral paired-organ confined (e.g., bilateral conjunctival), non-gastric MZL. CT scanning, bone marrow biopsy, autoantibody serology panel and HP evaluation by urease breath test or endoscopy were mandatory. Involved-field or involved-site, conventionally-fractionated radiotherapy was delivered to 30-30.6 Gy, except for orbital MZL which received 24-25 Gy. Patients with detected HP infections additionally received eradication therapy.
Between 2006 and 2014, six centers enrolled 70 patients, 68 of whom commenced protocol treatment. Median age was 59 (range: 23-84) years and 31 (46%) were male. Stage was I n = 55, II n = 9 and paired-organ confined n = 4. Involved extranodal sites with ≥ 3 cases were orbital n = 18, conjunctiva n = 13, lacrimal n = 8, skin n = 8, salivary n = 7, muscle n = 3. Four patients had primary nodal MZL and 14 (21%) patients were PET-staged. With a median follow-up of 5 years (range 0.7–9.4), 5-year progression-free and overall survival rates were 79% and 95% respectively. One lymphoma-related death and 2 in-field failures (after 25 and 30 Gy respectively) occurred. Distant relapse sites were skin (n = 2), lymph nodes (n = 2) duodenum, stomach, skeletal muscle and conjunctiva (1 each). No patient with bilateral paired-organ MZL relapsed. Apart from cataracts (n = 18), 6 grade 3 late adverse events occurred (3 treatment-related). Two grade 4 late events (nephrotic syndrome and thrombosis) were treatment-unrelated. Autoantibodies or auto-immune events were detected in 26 of 68 (38%) patients. HP infection was detected (and treated) in 15 of 63 patients tested (24%). Neither autoimmunity nor HP was detected in 27/68 (40%) patients.
Radiotherapy was a highly-effective, potentially-curative treatment with low toxicity in localized non-gastric MZL. Autoimmunity, HP infection or both were detected in 60% of patients.