Newer Staging Method Helps Confirm Potential of Radiotherapy Alone for Stage I/II Follicular Lymphoma

Results of a multi-institutional, retrospective analysis showed that radiotherapy (RT) in localized follicular lymphoma resulted in 68.9% of patients having no disease progression at 5 years with fewer than 2% of patients experiencing an in-field relapse, according to a study published inBlood.

“Our study suggests that [RT] 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,” investigators on the study reported.

Brady et al suggested that the curative value of RT in this setting had previously been underestimated in historical series with prior standard methods of staging patients with follicular lymphoma. They hypothesized that more accurate disease staging ultimately results in better treatment selection subsequently leading to improved treatment results.

The study included 512 patients treated between 2000 and 2017 who had stage I to II disease were eligible for analysis. Staging was completed using¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET-CT, which is now considered the best imaging technique for staging follicular lymphoma.

RT was delivered by a variety of different modalities including 2-dimensional (n = 5), 3-dimensional conformal (n = 315), intensity modulated (n = 100), and electron beam (n = 15); treatment volumes included involved-field, involved-site, and involved-node RT.

The primary endpoint of the study was freedom from progression (FFP)—defined as the date of RT completion to first progression based on clinical, radiographic, or pathologic evidence—with secondary endpoints of local control, overall survival (OS), and metabolic response rates on PET-CT.

Recurrences were defined as either distant—occurring outside the RT target volume, local—within the RT target volume, and marginal—within the same anatomical region but outside the RT target volume.

Among the patients with stage I disease (n = 410; 80.1%), 297 (72.4%) had nodal disease only with cervical (n = 201) and axillary/pectoral (n = 26) nodes being those most commonly affected. For all 102 patients with stage II disease, there was nodal site involvement with cervical (n = 40) and axillary/pectoral (n = 20) nodes being the most commonly affected. Only 8 patients with stage II disease had noncontiguous nodal sites. Extranodal disease was present in 113 patients (26.3%) and 14 patients (13.7%) of the stage I and stage II patient subgroups, respectively.

For the entire cohort of patients with stage I and II disease, the OS was 96.0% (95% CI, 93.2%-97.6%). The majority of relapses (91.9%) occurred outside of the irradiated sites. The local-control rate was 97.6% with only 8 patients (1.6%) relapsing in-field and 4 patients (0.8%) having marginal recurrence. Median follow-up was 52.3 months.

Disease stage was a significant predictor of FFP with 74.1% of those in the stage I group and 49.1% of those with stage II disease being free from disease progression at 5 years (P< .0001).

Besides stage, BCL2 expression was the only other factor significantly associated with risk of relapse. Patients with BCL2-positive expression had a significantly worse 5-year FFP rate compared with those without expression (62.5% vs 77.2%;P= .02).

On multivariable analysis, both patients with BCL2-positive status and stage II disease had a higher risk of disease progression than those patients with BCL2-negative and stage I disease after accounting for patient baseline characteristics such as sex, age, and extranodal status.

No significant difference was observed between patients treated according to nodal and extranodal presentation; there were no recurrences for the 28 patients with duodenal involvement—an FL presentation increasingly recognized as having a favorable prognosis.

About half of patients were assessed 6 months after the completion of RT, with 273 (53.3%) having either a PET-CT or a CT. With PET-CT, 143 patients (86.1%) achieved a complete metabolic response (CMR), defined as those with a Deauville score of 1 to 3, which was strongly associated with a decreased risk of relapse.

&ldquo;These results suggest that PET-CT response after RT is worth exploring further to elucidate whether a high-risk subset of patients who might benefit from additional systemic treatment can be identified,&rdquo; the investigators said.

Failure to achieve CMR was associated with a higher risk of progression. Of the 23 patients who did not reach CMR, 10 (43.4%) developed recurrent disease with all occurring distantly to the radiation field. Of the 13 patients who did not develop recurrent disease, 4 had subsequent normalization, 7 had stable disease or complete response on subsequent CT, and 2 had no recurrence based on follow-up.

No significant difference was observed when comparing time to relapse for those with or without post-RT PET (P= .25), and there was no significant difference between age, sex, stage, extranodal status, or size.

There were 372 patients available for acute and late toxicity data analysis. Patients experiencing grade 1/2 toxicities accounted for 22.8% of the total cohort (n = 85) and included those with radiation dermatitis (n = 25), mucositis (n = 18), fatigue (n = 11), dysphagia (n = 9), xerostomia (n = 8), and nausea (n = 8). Only 3 cases of grade 3 adverse events were observed.

Second malignancies occurred in 11 patients (2.1%) and included 2 each of de novo metastatic melanoma, endometrial cancer, colorectal adenocarcinoma and 1 each of cutaneous melanoma, ductal carcinoma in situ of the breast, neuroendocrine carcinoma, acute myeloid leukemia, and clear cell renal carcinoma.

&ldquo;Bearing in mind the low toxicity of modern RT, it should be considered as an initial treatment option for limited-stage follicular lymphoma in suitable patients,&rdquo; the investigators concluded.

Reference:

Brady JL, Binkley MS, Hajj M, et al. Definite radiotherapy for localized follicular lymphoma stage by¹⁸F-FDG PET-CT: a collaborative study by ILROG.Blood. 2019;133(3):237-245. doi: 10.1182/blood-2018-04-843540.