Chemotherapy followed by consolidative proton therapy achieves encouraging relapse free survival rates in patients with newly diagnosed Hodgkin Lymphoma

In the Annals of Oncology on 9^th August 2017, Bradford S. Hoppe from University of Florida College of Medicine, Gainesville, FL, USA, et al. reported on current patterns-of-care and early outcomes among patients with Hodgkin Lymphoma (HL) treated with chemotherapy followed by consolidative Proton Therapy (PT) using prospective academic and community registry data.

Patients were excluded if they had relapsed/refractory HL, had received PT as a boost after photon radiation, or if they had composite HL/non-HL. Involved-Site Radiation Therapy (ISRT) or similar fields was used to deliver PT. At the physician’s discretion, a boost could be administered to high-risk sites. The median dose for adult patients was 30.6 Gy (range, 20–45).

Key Highlights:

• Median age = 20 years (range, 6–57); 93% were under 40 years old
• Female = 62%; stage I/II disease = 73%; mediastinal involvement = 96%; bulky disease = 57%; B symptoms = 37%
• Favorable early-stage = 30%; unfavorable early-stage = 28%; advanced-stage = 42%
• Median follow-up = 32 months (range, 5–92)
• The majority (90%) of adult pts were administered ABVD chemotherapy for 2–3 cycles (n = 7), four cycles (n = 33), or 5–6 cycles (n = 32)
• Response to chemotherapy by PET/CT included 115 pts with CR, 15 pts with PR, and 8 pts with unknown response
• Dose escalation for PR at physician’s discretion was performed in 10 pts, including doses up to 36–45 Gy for 6 adult pts
• The remaining pts who did not receive dose escalation included 2 adults treated to 30 Gy
• 3-year RFS:
  • In adult pts = 96%
  • In adults with - favorable early-stage = 97%; unfavorable early-stage = 93%; advanced-stage disease = 96% (P = 0.64)
  • When RFS was evaluated by PET/CT response to chemotherapy, pts who achieved PR had a significantly higher likelihood of relapsing versus pts who achieved CR or had unknown response (3-year RFS = 78% vs 94%; P = 0.0034)
• Overall, 10 recurrences developed, including 6 in-field, 1 in-field and out-of-field, and 3 out-of-field in immediately adjacent nodal regions
• There were no marginal recurrences at the edge of the proton field that could be attributed to proton range uncertainties
• No grade 3 toxicities observed during follow-up
• No clinically meaningful pneumonitis was observed

The authors concluded that PT is mainly used in HL patients most at risk of developing late toxicity, which includes young patients, female patients, patients that have mediastinal involvement. The groups findings also indicate encouraging RFS rates with PT and this strategy was tolerated well in patients. The authors concluded that their findings support the use of PT to treat HL patients in a registry setting in order for long-term follow-up to take place as well as to identify any late toxicities.

Abstract:

Background: We investigated early outcomes for patients receiving chemotherapy followed by consolidative proton therapy (PT) for the treatment of Hodgkin lymphoma (HL).

Patients and methods: From June 2008 through August 2015, 138 patients with HL enrolled on either IRB-approved outcomes tracking protocols or registry studies received consolidative PT. Patients were excluded due to relapsed or refractory disease. Involved-site radiotherapy field designs were used for all patients. Pediatric patients received a median dose of 21 Gy(RBE) [range 15–36 Gy(RBE)]; adult patients received a median dose of 30.6 Gy(RBE) [range, 20–45 Gy(RBE)]. Patients receiving PT were young (median age, 20 years; range 6–57). Overall, 42% were pediatric (≤18 years) and 93% were under the age of 40 years. Thirty-eight percent of patients were male and 62% female. Stage distribution included 73% with I/II and 27% with III/IV disease. Patients predominantly had mediastinal involvement (96%) and bulky disease (57%), whereas 37% had B symptoms. The median follow-up was 32 months (range, 5–92 months).

Results: The 3-year relapse-free survival rate was 92% for all patients; it was 96% for adults and 87% for pediatric patients (P = 0.18). When evaluated by positron emission tomography/computed tomography scan response at the end of chemotherapy, patients with a partial response had worse 3-year progression-free survival compared with other patients (78% versus 94%; P = 0.0034). No grade 3 radiation-related toxicities have occurred to date.

Conclusion: Consolidative PT following standard chemotherapy in HL is primarily used in young patients with mediastinal and bulky disease. Early relapse-free survival rates are similar to those reported with photon radiation treatment, and no early grade 3 toxicities have been observed. Continued follow-up to assess late effects is critical.