Outcomes after initial refusal of curative treatment in patients with Hodgkin’s lymphoma in British Columbia.
Authors: Chahal Manik , Jiang Aixiang , Hayden Anna , Savage Kerry J. , Villa Diego , Scott David W. , Gerrie Alina S. , Lo Andrea , Chan Matthew , Pickles Tom , Connors Joseph M. , Sehn Laurie Helen , Freeman Ciara L 
Published: June 2021

e19518

Background: Classical Hodgkin lymphoma (cHL) is considered a highly curable cancer. With standard combination chemotherapy regimens, long-term survival exceeds 95% for limited-stage and 85% for advanced-stage patients. Despite these excellent outcomes some patients delay or decline conventional treatment for cHL. We retrospectively assessed the impact of initial treatment refusal on outcomes of patients with cHL in British Columbia (BC). Methods: Using the BC Cancer Lymphoid Cancer Database, we identified all patients aged 18-70 diagnosed between 1st Jan 1999- 31st Dec 2020 that had documented treatment refusal at initial presentation (‘refusers’ defined as not receiving or delaying treatment > 16 weeks). We identified a control cohort (min. 3 controls/refuser) treated within 8 weeks of diagnosis, matched for age, stage, diagnosis date within 3 years, and blinded for outcome. All patients had centrally reviewed biopsies and were treated with ABVD or ABVD-like regimens +/- radiotherapy if appropriate. Patient and disease characteristics at baseline and at time of treatment were analyzed with Chi-squared test and one-way ANOVA test. The Kaplan-Meier method was used to assess progression-free survival (PFS) and overall survival (OS), and statistical significance between groups was determined using the log-rank test. Results: We identified a cohort of 15 patients who initially refused treatment and 47 matched controls. The control cohort was well-matched, with no statistically significant differences in baseline characteristics (age, sex, Ann Arbor stage, B symptoms, International Prognostic Score (IPS) score, ECOG PS, and disease bulk) between groups. The most common reason for initial treatment refusal was to pursue alternative therapy (73%). 13 of 15 refusers eventually accepted treatment (mean time to treatment 76 weeks [range 26-214] vs. 5 weeks [range 1-8] for controls, p < 0.001). At time of treatment, the proportion of refusers with advanced-stage disease increased from 20% to 62% (p = 0.03) and had an associated alteration of treatment plan, and 62% of patients developed higher risk disease with increased IPS score (p = 0.02). At median follow-up of 5 years (0.4-21 years) for all living patients, estimated 5-year PFS was 65% vs 84%, and 5-year OS was 93% vs 98% for refusers and controls respectively. With extended follow up, 13% of refusers (1 late death at 8 years) compared to only 4% of controls died of cHL specifically. Conclusions: This study highlights the impact of treatment refusal in this highly curable malignancy. Initial refusal of treatment is associated with progression of stage, worsening prognostic score, escalation to more prolonged treatment than required at diagnosis, and increased risk of death from cHL. This analysis may help to provide guidance to counselling physicians, as well as inform patients who may be considering alternatives to standard of care for cHL.