Untapped Radiotherapy Potential in Localized FL?

Patients with follicular lymphoma staged with PET-CT and treated with radiotherapy appeared to have better outcomes than earlier research with CT staging alone, according to a recent study.

These results suggest “the curative potential of radiotherapy for truly localized FL has been underestimated,” Jessica L. Brady, MBBCh, FRCR, of Guy’s Cancer Centre, Guy’s and St Thomas’ Hospital, London, and colleagues, wrote in Blood.

According to the study, historical data show a 10-year disease-free survival between 40%–50% in patients with localized follicular lymphoma. However, staging with PET-CT upstages as many as 60% of patients compared with CT staging.

Patients included in this retrospective study had undergone radiotherapy alone for untreated stage I/II follicular lymphoma with dose equivalent of 24 Gy or more, were staged by PET-CT, and followed for 3 or more months. The researchers were evaluating whether these patients staged with PET had better outcomes.

The study included 512 patients treated from 2000 to 2017 from 16 centers in the United Kingdom. The majority of patients had stage I disease (80.1%), and the median dose of radiotherapy was 30 Gy.

After a follow-up longer than 4 years, the 5-year freedom from progression was 68.9% with an overall survival of 95.7%. According to the researchers, local control was excellent, and “consistent with other reports.” Only 8 patients relapsed in field (1.6%) and 4 patients had marginal recurrences (0.8%). This translated to a local control rate of 97.6%.

The researchers found a significant difference in treatment outcomes by stage of disease. Patients with stage I disease had a 5-year freedom from progression of 74.1% compared with 49.1% for patients with stage II disease (P < .0001).

Molecular marking testing revealed that patients with BCL2 over-expression (BCL2+) had significantly worse 5-year freedom from progression compared with those without expression (62.5% vs 77.2%; P = .02).

“BCL2 over-expression is present in approximately 80–90% of cases of FL and while it confers a poor prognosis in DLBCL, a relationship between BCL2+ and outcome in FL has not been established,” the researchers noted.

Multivariable analysis showed that stage II disease was associated with double the risk for progression (hazard ratio [HR], 2.26; 95% CI, 1.60–3.19; P < .0001) and BCL2+ was also associated with an increased risk for progression (HR, 1.63; 95% CI, 1.07–2.47; P = .02).

“Bearing in mind the low toxicity of modern radiotherapy, it should be considered as an initial treatment option for patients with limited-stage FL in suitable patients,” the researchers wrote. “Our study suggests that it is a highly effective treatment, with nearly three quarters of patients with stage I and approximately half of patients with selected localized stage II disease remaining disease free at 5 years.”

Commenting on this trial, Sushil Beriwal, MD, of UPMC Hillman Cancer Center, told Cancer Network these results show the importance of PET-CT in the modern era for select patients with early-stage follicular lymphoma who are suitable for definitive radiation therapy.

"Earlier data in [the] CT only era has shown 40%–50% disease-free survival with 10 years or longer follow-up," Beriwal said. "This study suggests better outcome at 5 years in comparison to historical control, but needs longer follow-up to see if a similar trend continues."

"The recent trend in decline in use of radiotherapy in this subset as seen in NCDB and SEER studies is concerning and this study again emphasizes that these patients should be offered involved field radiotherapy even in the PET-CT era," Beriwal added. "It is a potential curative modality with two out of three being in remission at 5 years and, hopefully, longer follow-up continues to show a similar trend."

Rachel Rabinovitch, MD, FASTRO, a professor in the department of radiology at University of Colorado Denver, added “Down-staging of patients in the last decade due to better imaging and assessment of bone marrow with flow cytometry has enhanced identification of patients with true early-stage disease who will benefit most from localized therapy. As radiotherapy results in outstanding local disease control, future consideration of low-dose radiation with rituximab or other targeted therapy is warranted."