3 years ago

Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma: A systematic review and meta-analysis of randomized clinical trials.

Treatment intensification to maximize disease control and reduced-intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the present meta-analysis based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 1984 and 2007. Secondary malignant neoplasms were meta-analyzed using Peto's method as time-to-event outcomes. For progression-free and overall survival, hazard ratios derived from each trial using Cox regression were combined by inverse-variance weighting. Five study questions (combined-modality treatment vs chemotherapy alone; more extended vs involved-field radiotherapy; radiation at higher doses vs radiation at 20 Gy; more vs fewer cycles of the same chemotherapy protocol; standard-dose chemotherapy vs intensified chemotherapy) were investigated. After a median follow-up of 7.4 years, dose-intensified chemotherapy resulted in better progression-free survival (p=0.007) rates as compared with standard-dose chemotherapy, but was associated with an increased risk of therapy-related acute myeloid leukemia/myelodysplastic syndromes (p=0.0028). No progression-free or overall survival differences were observed between combined-modality and chemotherapy alone, but more secondary malignancies were seen after combined-modality (p=0.010). For the remaining three study questions, outcomes and secondary malignancy rates did not differ significantly between treatment strategies. The results of this meta-analysis help to weigh up efficacy and secondary malignancy risk for the choice of first-line treatment of Hodgkin lymphoma patients. However, final conclusions regarding secondary solid tumors require longer follow-up.

Publisher URL: http://doi.org/10.3324/haematol.2017.167478

DOI: 10.3324/haematol.2017.167478

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