Early-Stage Hodgkin Lymphoma
EARLY-STAGE NLPHL
NLPHL usually presents with limited-stage disease without B symptoms and has an indolent course with a slightly better prognosis compared to cHL.72 Due to the rarity of the disease, treatment guidelines are mostly based on retrospective analyses from single or multi-institution studies or subgroup analyses, often with relatively short follow-up. These studies must be interpreted with caution because of the possibility of inaccuracies in the pathologic diagnosis, small sample sizes, and selection bias. Treatment options for limited-stage NLPHL include observation, single-agent rituximab, IFRT (or involved-site radiation therapy [ISRT]) alone, or CMT.46
Historically, patients with limited-stage NLPHL have been treated with RT alone, with 80% to 85% PFS and 85% to 95% overall survival rates.73–75 Patients who relapse or progress after RT in general can successfully undergo salvage therapy.74 In one study, rates of PFS and overall survival were similar among patients who had limited-field, regional-field, or extended-field RT,75 indicating that IFRT is preferred. Studies comparing RT alone and CMT are limited. The GHSG HD7 trial included a subset of NLPHL patients, with a trend towards improved freedom from treatment failure (96% versus 83%) favoring CMT. This, however, did not translate into improved overall survival.47 A retrospective analysis of the British Columbia Cancer Agency database compared patients with limited-stage NLPHL treated with RT alone to patients who received 2 cycles of ABVD followed by RT. A significant improvement in PFS (91% versus 65%) and overall survival (93% versus 84%) was seen, favoring CMT.76
Chemotherapy alone is not recommended for limited-stage NLPHL since studies evaluating chemotherapy alone are quite limited and indicate relatively high rates of treatment failure. Given that the malignant cells in NLPHL are CD20-positive, single-agent rituximab has also been studied in this disease, including a study as frontline therapy in limited-stage patients. In this phase 2 trial in newly diagnosed patients with stage IA disease, an overall response rate (ORR) of 100% was seen, with an 85% complete response (CR) rate.77 At 3 years, overall survival was 100% and PFS was 81%, indicating that the responses with single-agent rituximab are less durable than those with RT.
,Advani et al evaluated rituximab followed by observation versus rituximab (R) followed by maintenance rituximab (MR) for 2 years in 39 new or previously treated patients. At 4 weeks the ORR was 100% (with CR in 67%, and partial response in 33%). At a median follow up of 9.8 years for R alone, and 5 years for R+MR, median PFS was 3 and 5.6 years, respectively (P = 0.26). Estimated 5-yr PFS and overall survival in patients treated with R versus R+MR were 39.1% and 95.7% versus 58.9% and 85.7%, with Pvalues of 0.26 (PFS) and 0.38 (overall), respectively. Maintenance rituximab therefore appears to prolong remission, although the results did not quite reach statistical significance.78 Even though rituximab does not appear to be curative in NLPHL, it is a reasonable option for patients with early-stage NLPHL who are not good candidates for definitive RT. Whether combining rituximab with RT or CMT might further improve outcomes in early-stage NLPHL has not yet been determined.
In children, surgery alone may lead to long-term remission or possibly cure of limited-stage NLPHL. In a European multicenter retrospective study, 58 patients underwent surgery for limited-stage NLPHL. Among the 51 patients who achieved complete remission following surgery, 67% remained progression-free and 100% were alive at a median follow up of 43 months.79 In adults, there is no data to support surgical treatment alone for NLPHL. Finally, observation may be a reasonable option in elderly or infirm patients for whom NLPHL is unlikely to affect life expectancy. For younger patients, given the excellent outcome with modern therapy and the long-term risk of transformation of NLPHL into an aggressive non-Hodgkin lymphoma, observation is generally not recommended.
The NCCN recommends RT (ISRT or IFRT, 30–36 Gy) as the preferred treatment for stage IA and IIA non-bulky NLPHL. In patients with stage IA disease with complete excision of solitary nodule, observation may be appropriate. A course of chemotherapy with ISRT with or without rituximab is recommended for patients with stage IB or IIB disease, or patients with stage IA or IIA bulky disease.
