Systematic Review and Individual Patient Data Meta-Analysis Of Treatment-Related Risk Of Secondary Malignant Neoplasms After Hodgkin Lymphoma

Abstract

IntroductionSecondary malignant neoplasms (SMN) are a major late effect of treatment for Hodgkin lymphoma (HL). Single trials have inadequate power to detect differences in SMN rates, while the many large-scale cohort-based studies of SMN after HL suffer from non-randomised, potentially biased comparisons of treatment strategies. The consequences of choice of first-line treatment for SMN risk remain unclear. We performed a Cochrane systematic review addressing this question based on our previous such review in 2000-2004. Material and methodsIndividual patient data (IPD) were collected from randomised controlled trials testing 5 currently relevant experimental strategies: avoidance of additional radiotherapy (RT) after chemotherapy (CT); reduction of RT field; reduction of RT dose; use of fewer CT cycles; intensification of CT regimen. All trials employed modern ABVD-like regimens and limited radiation fields, and recruited at least 50 patients per treatment group. Incidence of SMN, overall survival (OS) and progression-free survival (PFS) were analysed. Due to small numbers of events, SMN was analysed using Peto's method. Results and DiscussionData from 16 of the 21 eligible trials were obtained, including 9498 patients. These trials recruited between 1984 and 2007 and randomised between 100 and 1351 patients each. Standard chemotherapy was predominantly ABVD, followed by COPP/ABVD and MOPP/ABV. Most frequent intensified chemotherapies were escalated BEACOPP and Stanford V. For each study question, key information and resulting odds ratios are shown in the table. Avoidance of additional RT significantly reduced the SMN risk (Peto odds ratio 0.433, 95% confidence interval (0.28; 0.82), p=0.010). Intensified chemotherapy regimens were associated with a consistent slightly higher risk but the effect was not significant. Other study questions showed no marked effects on SMN risk. Regarding solid tumors, follow-up is still too short: an update after 5 to 10 years is necessary.Study questionNo. of trialsNo. of patients (total)Median follow-up (yr.)No. of SMNPeto odds ratio95% confidence intervalP-valueavoidance of RT (after CT)310117.8400.433(0.28; 0.82)0.010smaller RT field (after CT)4239710.81880.862(0.64; 1.16)0.32lower RT dose (after CT)329627.41101.032(0.71; 1.50)0.87fewer CT cycles324037.81011.096(0.74; 1.62)0.65intensified CT regimen729966.7911.37(0.89; 2.10)0.15 Disclosures:No relevant conflicts of interest to declare.