Radiotherapy Compared to Other Strategies in the Treatment of Stage I/II Follicular Lymphoma: A Study of 404 Patients with a Median Follow-Up of 15 Years

<div><p>Purpose</p><p>To investigate outcome for patients with follicular lymphoma (FL) stage I-II treated at a population-based referral institution with a median follow-up of 15 years. Overall and cause-specific survival was compared to that of a sex, age and residency matched individuals from normal population.</p><p>Material and Methods</p><p>404 patients with early stage FL treated between 1980 and 2005 were retrospectively analyzed. Two of three patients had stage I disease. Based on clinical characteristics, first line treatments were radiotherapy (RT) (48% of patients), chemotherapy (CT) (16%), combined chemo-and radiotherapy (CRT) (16%) or observation (OBS) (15%). Survival was modeled with Kaplan-Meier methodology. Multivariate analyses were performed with the Cox model.</p><p>Results</p><p>Fifteen years overall survival (OS), progression free survival (PFS) and time to next treatment (TNT) were 50% (95% confidence interval [CI]: 45–55), 42% (95% CI: 36–47) and 48% (95% CI, 42–54), respectively. For patients treated with RT 97% achieved a complete remission, and 15 year OS, PFS and TNT were 57% (95% CI, 50–64), 46% (95% CI, 39–54) and 49% (95% CI, 42–57), respectively. Relapse rate after RT and CRT was 49% and 36%, respectively. Only 2% of patients who received RT or CRT relapsed inside the radiation field and 5% had isolated near-field relapse. No statistical differences were found between treatment groups regarding death from cardiovascular disease or incidence of second cancer. Compared to a matched normal population, non-lymphoma cancer mortality was higher among patients given RT, hazard ratio 1.66 (95% CI: 1.14–2.42; P<0.01). Compared to other treatment modalities, patients selected for observation without treatment did not have inferior outcome.</p><p>Conclusions</p><p>A differentiated treatment strategy in early stage FL results in long term survival for the majority of patients. OBS is a valid initial choice for selected patients without lymphoma-related symptoms.</p></div

Overall survival for patients compared to controls.

<p>Overall survival for patients compared to controls.</p

Kaplan-Meier survival curves showing overall survival (OS), progression free survival (PFS) and time to next treatment (TNT).

<p>Survival curves are illustrated as follows: (A) OS for all follicular lymphoma (FL) patients; (B) PFS for all FL patients; (C) TNT for all FL patients; (D) OS by stage; (E) PFS by stage; (F)TNT by stage; (G) OS by involvement site; (H) PFS by involvement site; (I) TNT by involvement site; (J) OS by treatment type; (K) PFS by treatment type; and (L) TNT by treatment type. Note: Pointwise confidence bands are not shown when survival curves overlap or run close to each other. P-values in (D) to (I) are from log-rank tests comparing the two groups, in (J) to (L) from generalized log-rank tests comparing all groups.</p

A simplified frailty score predicts survival and can aid treatment-intensity decisions in older patients with DLBCL

Diffuse large B-cell lymphoma (DLBCL) patients have a median age of 70 years. Yet, empirical knowledge on treatment for older patients is limited as they are frequently excluded from clinical trials. We aimed to construct a simplified frailty score and examine survival and treatment-related mortality (TRM) according to frailty status and treatment intensity in an older, real-world DLBCL population. All patients ≥70 years diagnosed with DLBCL 2006-2016 in south-eastern Norway (n=784) were included retrospectively, and divided into a training (n=522) and validation cohort (n=262). We constructed and validated a frailty score based on geriatric assessment variables, and examined survival and TRM according to frailty status and treatment. The frailty score identified three frailty groups with distinct survival and TRM, independent of established prognostic factors (2-year overall survival (OS) fit 82%, unfit 47%, frail 14%, P80%) was associated with better survival than attenuated R-CHOP (2-year OS 86% vs 70%, P=0.012), also in adjusted analysis. For unfit and frail patients, full-dose R-CHOP was not superior to attenuated R-CHOP, while an anthracycline-free regimen was associated with poorer survival in adjusted analyses. A simplified frailty score identified unfit and frail patients with higher risk of death and TRM, which can aid treatment intensity decisions in older DLBCL patients. In this study, fit patients benefit from full-dose R-CHOP, while unfit and frail patients have no benefit of full-dose R-CHOP over R-miniCHOP. An online calculator for assessment of the frailty score is available at https://wide.shinyapps.io/app-frailty