Advanced Stage Classical Hodgkin Lymphoma Patients with a Negative PET-Scan Following Treatment with ABVD Have Excellent Outcomes without the Need for Consolidative Radiotherapy Regardless of Disease Bulk at Presentation
Authors: Savage Kerry J. , Connors Joseph M. , Villa Diego R , Hapgood Greg , Gerrie Alina S , Shenkier Tamara N , Scott David W , Gascoyne Randy D. , Benard Francois , Morris James , Pickles Tom , Parsons Christina , Wilson Don , Sehn Laurie H. 
Published: October 2019

Abstract
Background: Consolidative radiotherapy (RT) is frequently administered to patients (pts) with classical Hodgkin lymphoma (CHL) that have bulky disease at diagnosis and/or residual abnormalities on post-chemotherapy CT imaging. However, this may contribute to the development of secondary malignancies and cardiac disease. The HD15 trial demonstrated that RT can be omitted in cases with residual disease on CT imaging following BEACOPP-based chemotherapy that are PET-negative (PET-neg). It is unknown whether this can be extended to patients treated with ABVD chemotherapy including patients presenting with a bulky disease at diagnosis. Further, it is unclear whether consolidative RT can be used to salvage cases that are PET positive (PET-pos) following ABVD.
Methods: The British Columbia (BC) Cancer Agency Centre for Lymphoid Cancer Database and case records were screened to identify all adult (> 16 y) pts with advanced stage CHL (stage 1 bulky (> 10cm), stage 2 with B symptoms and/or bulky disease and all stage III/IV) treated with curative intent using ABVD chemotherapy who underwent a restaging PET scan at the end of treatment. Clinical factors including mass size at diagnosis, mediastinal involvement, residual mass size post therapy and relapse site were collected. Patients that were HIV positive, had refractory disease (progression during chemotherapy or at the time of post-treatment imaging) or toxicity that precluded response evaluation, were excluded for this analysis. Since July 2005, all pts in BC with advanced stage HL, including those with bulky disease, were recommended to be treated with 6 cycles of ABVD followed by a PET scan if residual abnormalities > 2 cm were observed on CT imaging.
Results: In total, 316 pts with CHL who met the above criteria were identified. Pt characteristics were: 48% females; median age 33 y (16-82 y); stage 1 1.3%; stage 2 47.2%; stage III/IV 51.5%; extranodal disease 40.5%; B symptoms 66%; 13% international prognostic score > 4 13%; bulky disease 62%. At the end of treatment, 264 (83.5%) were PET-neg (indeterminate n=4), none of whom received RT, and 52 (16.5%) were PET-pos, of which 79% (n=41) received consolidative RT (30-35 Gy). With a median follow-up for living pts of 4.6 y (range 0.6 - 13.5 y), the 5-y freedom from treatment failure (FFTF) for the whole cohort was 83% and 5-y overall survival (OS) was 94.5%. Overall, pts with a PET-neg scan post treatment had a superior 5-y FFTF compared to those with a PET-pos scan (89% vs 56%, P < 0.00001) (Figure 1a). In the PET-neg group, there was no difference in outcome comparing the bulky (n=112) and non-bulky (n=152) subgroups (5-y FFTF 89% vs 88.5%, p=0.50, respectively, Figure 1b; 5-y OS 96% vs 94%, P=0.51). Similar survival estimates were observed when the analysis is restricted to PET-neg cases with a bulky mediastinal mass at diagnosis (n=102) (5 y FFTF 89%; 5 y OS 96%). Of the PET-pos pts who were able to receive consolidative RT (PET-pos RT) (n=41), the 5-y FFTF was 60% and the 5 y OS was 94%. For those with mediastinal PET-pos disease who received RT (n=29, 72% bulky at diagnosis), the 5-y FFTF was 69.5%. For all PET-pos RT pts, 13 subsequently relapsed: 1 within the RT field only; 5 outside of the RT field only; and 7 relapsed both within and outside of the RT field.
Conclusions: Advanced stageCHL pts, including those with bulky disease, that have a negative PET scan following ABVD chemotherapy have an excellent outcome without additional consolidative RT, thus potentially avoiding long-term effects. Radiotherapy may be useful in select responding patients with PET-pos residual uptake. With a PET-guided approach, we have significantly reduced the need for RT.

Disclosures
Savage: Seattle Genetics: Honoraria, Speakers Bureau; BMS: Honoraria; Infinity: Honoraria; Roche: Other: Institutional research funding. Connors:Seattle Genetics: Research Funding; Roche: Research Funding. Villa:Lundbeck: Honoraria. Gerrie:Janssen: Other: Advisory board; Roche: Honoraria, Other: Advisory board, Research Funding; Lundbeck: Honoraria, Other: Advisory board, Research Funding. Shenkier:Roche: Honoraria, Other: Travel funds. Scott:Celgene: Consultancy, Honoraria. Pickles:Janssen: Honoraria; Oncura: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria; Amgen: Honoraria, Other: Advisory board; Astellas: Honoraria, Other: Advisory board.