Long-Term Outcomes for Patients with Limited Stage Follicular Lymphoma: An Update of a Population-based Study

Abstract

Follicular lymphoma (FL) is the most common indolent lymphoma and most frequently presents as advanced stage disease. Radiotherapy (RT) is integral in the treatment of limited stage FL and potentially curative. However, given the long natural history, mature follow-up is needed to accurately define the relapse risk. We previously reported on the long-term outcome of 237 patients with limited stage FL treated with curative intent RT with a median follow-up of 7.3 yr. Herein, we report the outcome with now a median follow-up of 13.1 yr and also re-evaluated the impact of involved node with margins ≤5cm (now known as involved site RT (ISRT)) on relapse rates. Patients diagnosed with stage 1A/IIA, grade 1–3A FL from 1986–2006 and treated with curative-intent RT alone were previously identified. Computed tomography scans but not positron emission tomography scans were used for staging. RT was categorized as IRRT vs. ISRT; IRRT encompassed the involved lymph node (LN) group plus ≥1 adjacent, uninvolved LN group(s) and ISRT covered the involved LN(s) with margins ≤5 cm. Survival rates with standard errors were calculated using the Kaplan-Meier method and comparisons made using the log-rank test. Cox regression was used for multivariable analysis (MVA). Of the 237 patients, 48% were men, 54% were >60 yr old at diagnosis, 76% had stage IA disease, 12% had grade 3A disease, 19% had LN size ≥5 cm, and 7% had elevated lactate dehydrogenase. IRRT was used in 60% and ISRT in 40%. Median follow-up was 13.1 yr (range, 0.3-28.9 yr) and 80% were followed for over 7 yr. Freedom-from-progression (FFP, unrelated deaths censored) was 65.9±3.1% at 5 yr, 49.5±3.4% at 10 yr and 43.8±3.6% at 15 yr. Five-year progression-free survival (PFS, all deaths counted) was 61.8±3.2%, 10-yr PFS was 40.1± 3.2% and 15-yr PFS was 28.0±3.1%. Overall survival was 86.5±2.2% at 5 yr, 70.9±3.0% at 10 yr and 57.2±3.2% at 15 yr. Of the 124 first relapses, 11 (9%) occurred beyond 10 yr and 3 (2%) occurred beyond 15 yr. First failures were distant alone in 107 patients (45%), in-field alone in 4 patients (1.6%) and both distant and in-field in 11 patients (4.6%). Of the 95 patients treated with ISRT, only one (1%) had a first failure that was regional-only (i.e., out-of-field but would have been covered by an IRRT approach). Ten-year FFP was 45.9±4.3% after IRRT and 55.4±5.4% after ISRT (P=0.26). On MVA, RT field size did not impact FFP; significant factors for FFP included only sex and stage, with hazard ratio [HR]=1.5 for male vs. female (P=0.028), HR=3.7 for LN size ≥5 cm vs. complete excision (P=0.007), and HR=2.7 for nodal size <5 cm vs. complete excision (P=0.032). In patients with limited stage FL, disease recurrence was uncommon after 10 yr and rare after 15 yr. At 15 yr, 44% of patients remained disease-free, confirming that a cure is possible. Reduction of RT fields to ISRT did not appear to impact relapse risk in the long-term.