Proton Therapy for Lymphoma: A Multi-institutional Patterns of Care Study

Abstract

Patients with Hodgkin (HL) or Non-Hodgkin's Lymphoma (NHL) are at risk of developing radiation-induced toxicities. Multiple dosimetric reports demonstrate normal tissue sparing with the use of proton therapy (PT), especially when targeting mediastinal volumes. To test the hypothesis if this has resulted in increased use of PT in lymphoma patients, we investigated the characteristics of patients with HL or NHL treated with PT within the prospective Proton Collaborative Group (PCG) registry. We reviewed 139 consecutive patients with HL or NHL treated with PT within seven PCG institutions between the years 2010 and 2016. Patients receiving PT alone (without any component of photon therapy) were analyzed. In addition to descriptive analyses, analyses of variance/ANOVA (to compare means) and regression analyses (to compare categorical variables) were used. Disease diagnosis was HL: 83 (60%) and NHL: 56 (40%). Median age was 33.5 years (range, 6.5-90) stratified into age groups of children <19 years: 15%, adolescent and young adults (AYA) 19-39 years: 44% and adults ≥ 40 years: 40% patients, respectively. Majority of the patients were female (53%) and white (66%). Stage grouping was I/II: 60%, III/IV: 14% and relapsed/refractory (R/R): 17%. Bulky disease was reported in 32% of patients. Chemotherapy prior to PT was received in 83% of patients. The median PT dose was 30.6 Gy(RBE) (range, 19-54). The median PT dose in the three age-cohorts (<19, 19-39 and ≥ 40 years) was 21, 30.6 and 36 Gy(RBE), p < 0.001; the three stage groups (I/II, III/IV and R/R) was 30.6, 30 and 36.3 Gy(RBE), p < 0.001 and diagnosis (HL, NHL) was 30.6 and 36 Gy(RBE), p<0.001, respectively. On multivariate regression analysis, older age (p<0.001), NHL diagnosis (p =0.004) and R/R stage (p=0.014) predicted for higher PT dose with no impact of gender and enrollment date. Mediastinum/hilum, either alone (27%) or with nodal head-neck region (28%) were the most common anatomical sites treated followed by nodal head-neck alone (10%). Miscellaneous treated sites included paranasal sinuses/orbit/salivary glands (7%), axilla with or without other sites (7%), Waldeyer’s ring (3%), spine (3%) or others (15%). In parallel to the overall cancer patient numbers treated with PT within the registry, the absolute numbers of lymphoma patients has increased from 2010 to 2016, though the proportion of lymphoma patients stayed relatively constant (range, 1-2.3%). Through review of the prospectively maintained registry data, we demonstrate stable proportional use of PT in lymphoma with predominant use seen in HL, AYA age-group, early-stage disease and PT targeting mediastinum/hilar regions. This analysis provides a benchmark to assess impact of NCCN recommendations which in the year 2015 has emphasized consideration of advanced radiation modalities including PT for patients with lymphomas.