Ultra Low-Dose Radiation for Extranodal Marginal Zone Lymphoma of the Lung

Abstract

Definitive radiation treatment (RT) for extranodal marginal zone lymphoma (ENMZL) of mucosal associated lymphoid tissue historically involves treatment to 24-30 Gy. There is increasing data supporting the use of ultra-low dose RT as part of a response-adapted approach in the treatment of orbital and gastric ENMZL. With this approach, patients receive initial treatment with 4 Gy, and additional RT is considered for those with persistent or locally progressive disease. However limited data to date assesses the efficacy of 4 Gy in the management of ENMZL of the lung. We performed an IRB-approved retrospective review of 17 patients with ENMZL of the lung treated with 4 Gy between 7/2015 and 12/2022 with response assessed after RT. Clinical/treatment characteristics, response, and toxicity were extracted from medical records. Statistics were performed using Mann-Whitney U and Fisher's Exact Test. Eight patients (47%) were female, 15 (88%) white, and 1 (6%) Hispanic. Median age at RT was 66 (interquartile range (IQR) 59-77). All had disease limited to the lung at diagnosis and 15 had stage IE disease. Four patients (24%) were diagnosed incidentally on screening/surveillance imaging in the absence of symptoms. Sixteen patients received 4 Gy in 2 fractions, while one patient received a single fraction of 4 Gy. Median SUVmax prior to RT was 4.5 (IQR 3.2-7.2). Median planning target volume (PTV) was 74 cc (IQR 47-130cc). Six patients (35%) had respiratory symptoms prior to RT, which improved or resolved in 3 (50%). A larger PTV was associated with improvement in symptoms following RT with a median PTV of 266 cc (IQR 171-402) in those who experienced improvement vs. 64 cc (IQR 42-100) in those who did not (p = 0.032). One patient experienced toxicity following RT with pleuritic chest pain, which resolved with corticosteroids. At a median follow-up of 15 months following RT (IQR 7-43 months), the overall response rate (ORR) was 100% (CR, n = 15; PR, n = 2). Fourteen patients had follow-up PET/CT, of whom 13 had a complete metabolic response (CMR) at a median of 3 months following RT (IQR 3-5 months). Two additional patients had a complete response (CR) on CT while one had a partial response on CT. Achieving a CR was not associated with SUV prior to RT (p = 0.50) or PTV size (p = 0.62). In patients with stage IE disease, the ORR rate was 100% and there have been no distant failures to date. Fifteen of 17 patients were alive at last follow-up; two passed away of unrelated causes (one from Alzheimer's disease and one from recurrent squamous cell carcinoma). Ultra-low dose radiation of 4 Gy is associated with excellent local control in the management of ENMZL of the lung and is very well tolerated. Four Gy was effective for local control and symptom palliation even for larger tumors and is an effective initial therapy as part of a response-adapted approach even in limited stage patients.