Survival differences between patients with Hodgkin lymphoma treated inside and outside clinical trials. A study based on the EORTC‐Netherlands Cancer Registry linked data with 20 years of follow‐up

Abstract

SummaryThe survival of patients diagnosed with Hodgkin lymphoma (HL) has improved from 70% to 90% in clinical trials. However, population-based data has shown lower survival. In this study, clinical trial data were linked with cancer registry to identify trial and non-trial participants and differences in overall survival and associated factors were assessed. In 1986-2004, 27% of HL patients aged 15-70 years participated in clinical trials. Compared to non-trial participants, trial participants were younger (median age, 31 vs. 34 years), had staging registered more accurately and had an 8% higher 20-year survival rate (73% vs. 65%). After adjusting for baseline differences, no differences in survival (hazard ratio = 0Á96, 95% confidence interval 0Á82-1Á12), or in subgroup analysis according to stage, remained. Over time, increased administration of chemotherapy in combination with radiotherapy, together with the decreased use of radiotherapy alone was observed among the trial population. This trend was later followed in nontrial participants, coinciding with a similar 'take-up' in survival. The observed superior survival among patients with HL treated in clinical trials can be largely explained by the differences in baseline characteristics, particularly younger age. High trial participation rate and centralized expertise facilitates the implementation of trial findings to real-world practice.Keywords: overall survival, hodgkin lymphoma, clinical trials, populationbased cancer registry, deterministic data linkage. Between 1964 and, the Lymphoma Group of the European Organisation for Research and Treatment of Cancer (EORTC) has conducted a series of phase III randomized clinical trials (RCTs) aiming to improve the efficacy of treatment in Hodgkin Lymphoma (HL), while minimizing longterm treatment-related toxicities. These subsequent trials have successfully improved the 10-year relative survival (RS) of HL patients, diagnosed between 1964 and 2004, with early stage disease from 72% to 93% and with advanced staged disease from 63% to 78% (Favier et al, 2009). However, compared to the high survival rate observed in the most recent clinical trials, that of the general patient population seems to be lower. In the Netherlands, for instance, for patients diagnosed with HL between 1989 and 2000, the 5-year RS was 78% in the general patient population (including trial participants), which is much lower than the 5-year RS seen in patients entered in clinical trials (87%). With longer follow-up, the survival gap between these two patient research paper ª

Advanced Hodgkin lymphoma in the East of England: a 10-year comparative analysis of outcomes for real-world patients treated with ABVD or escalated-BEACOPP, aged less than 60 years, compared with 5-year extended follow-up from the RATHL trial

“…The PFS curves of the real-world ABVD patients and RATHL trial patients, aged younger than 60 years, are remarkably similar in both the absolute 5-year estimates of progression-free survival and in the kinetics of relapse. This is observed in both the whole ABVD cohort and IPS 3+ subgroup, and is consistent with data published from the Netherlands that suggest similar outcomes are achieved for HL patients who are treated within or outside of clinical trials [7].…”

Cancer survivorship: an integral part of Europe's research agenda

“…An alternative approach to collecting long‐term follow‐up data from clinical trial participants is to initiate prospective observational studies based on population‐based cohorts that represent real‐world survivors. Collaborating with population scientists and their databases where patients are actively followed can greatly improve the efficiency of outcomes research (Liu et al ., , ; van de Poll‐Franse et al ., ; Thong et al ., ).…”

Contemporary Outcomes for Advanced-Stage Classical Hodgkin Lymphoma in the U.S.: Analysis of Surveillance, Epidemiology, and End Results Database

“…Although recent clinical trials using risk‐adapted treatments and novel salvage strategies have demonstrated a significant improvement in the outcomes of patients with advanced‐stage HL, it is important to note that such results are only applicable to carefully selected patients who would meet the inclusion criteria for such trials . This was even demonstrated in a recent study that highlighted the differences in baseline characteristics of the patients enrolled versus not enrolled in clinical trials to be an important determinant of outcomes in patients with HL . Hence, it is crucial to understand the limitations of applicability of these advances at the population level and how they influence “real‐world” outcomes.…”