Radiation Underutilized in Low-Grade Follicular Lymphoma

The use of radiation therapy has declined despite evidence demonstrating it is often more beneficial than single-agent chemotherapy or observation-alone in patients with low-grade follicular lymphoma.

J. Austin Vargo, MD

The use of radiation therapy has declined despite evidence demonstrating it is often more beneficial than single-agent chemotherapy or observation-alone in patients with low-grade follicular lymphoma, according to a study presented at the 2015 American Society for Radiation Oncology (ASTRO) Annual Meeting.

“Our study highlights the increasing omission of radiation therapy in non-Hodgkin lymphoma and its associated negative effect on overall survival at a national level. This increasing bias towards the omission of radiation therapy is despite proven efficacy and increasing adoption of lower radiation therapy doses and more modern radiation therapy techniques, which decrease risk of side effects. More patients should be offered this effective yet underused treatment,” lead study author J. Austin Vargo, MD, a radiation oncologist at UPMC CancerCenter, partner with the University of Pittsburgh Cancer Institute, said in a statement.

Using population-based data from the National Cancer Data Base (NCDB), researchers at the University of Pittsburgh School of Medicine (UPMC) conducted a retrospective study of 35,961 patients with nodal and extra-nodal stage I-II, grade I-II follicular lymphoma diagnosed from 1998 to 2012. Sixty-three percent of patients had stage I disease, 79% were without extra-nodal disease, and 61% were older than 60 years. The median follow-up was 58 months (interquartile range, 28-93).

The study found that patients receiving radiation therapy had 5- and 10-year overall survival (OS) rates of 86% and 68%, respectively, versus 74% and 54% for those not receiving radiation therapy (P <.0001).

Utilization of chemotherapy had no significant impact on survival (P = .43). Observation without any initial treatment resulted in 5-year and 10-year OS of 74% and 52%, respectively, versus 80% and 62% for patients receiving any initial therapy (P <.0001). On propensity-adjusted Cox multivariate analysis, radiation therapy remained independently associated with improved OS (hazard ratio, 0.54; 95% CI, 0.47-0.63; P <.0001).

“Survival with radiation therapy in these cases are higher and we think that an evidence-based approach should be used by more oncologists when discussing treatments for their patients,” Dwight E. Heron, MD, director of Radiation Services, UPMC CancerCenter, and professor of UPMC’s Department of Radiation Oncology, Otolaryngology and Head & Neck Surgery, said in a statement.

NCCN and ESMO guidelines both list radiation therapy as the preferred treatment for low-grade follicular lymphoma. However, the UPMC study found that radiation therapy use decreased from 37% in 1999 to 24% in 2012 (P <.0001). In contrast, there were significant increases in both observation, with 34% of low-grade follicular lymphoma patients being managed through observation in 1998 and 44% in 2012 (P <.0001), and single-agent chemotherapy, with 5.4% of patients receiving chemotherapy in 1999 and 11.7% in 2006 (P = .01).

In the study, univariate and multivariate analyses were performed to identify sociodemographic, treatment, and tumor characteristics predictive of OS and treatment utilization.

Decreases in radiation therapy utilization was associated with increasing age, female gender, African American race, increasing comorbidity score, treatment at an academic/research program, stage II disease, presence of B-symptoms, absence of extranodal disease, receipt of chemotherapy, and increasing year of diagnosis.

Based on these findings and a lack of randomized evidence suggesting otherwise, study authors recommend that, physicians should strongly reconsider excluding radiation therapy outside of clinical trials. Decreasing radiation therapy utilization in favor of alternative management strategies may lead to a survival decrement.

Low-grade follicular lymphoma is a common type of non-Hodgkin lymphoma that grows slowly. It is most likely to occur in people age 60 and older.

Vargo JA, Gill BS, Balasubramani G, Beriwal S. Early-stage, low-grade follicular lymphoma: how much evidence do we need to adopt radiation therapy as the primary treatment?” Presented at: 2015 ASTRO Annual Meeting; October 18-21, 2015; San Antonio, TX. Abstract 183.


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