TY - JOUR
T1 - Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma
T2 - a systematic review and meta-analysis of randomized clinical trials
AU - Eichenauer, Dennis A
AU - Becker, Ingrid
AU - Monsef, Ina
AU - Chadwick, Nicholas
AU - de Sanctis, Vitaliana
AU - Federico, Massimo
AU - Fortpied, Catherine
AU - Gianni, Alessandro M
AU - Henry-Amar, Michel
AU - Hoskin, Peter
AU - Johnson, Peter
AU - Luminari, Stefano
AU - Bellei, Monica
AU - Pulsoni, Alessandro
AU - Sydes, Matthew R
AU - Valagussa, Pinuccia
AU - Viviani, Simonetta
AU - Engert, Andreas
AU - Franklin, Jeremy
N1 - Copyright© 2017 Ferrata Storti Foundation.
PY - 2017/10
Y1 - 2017/10
N2 - 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 meta-analysis herein, 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 rates (P=0.007) 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 treatment and chemotherapy alone, but more secondary malignant neoplasms were seen after combined-modality treatment (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 for Hodgkin lymphoma patients. However, final conclusions regarding secondary solid tumors require longer follow-up.
AB - 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 meta-analysis herein, 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 rates (P=0.007) 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 treatment and chemotherapy alone, but more secondary malignant neoplasms were seen after combined-modality treatment (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 for Hodgkin lymphoma patients. However, final conclusions regarding secondary solid tumors require longer follow-up.
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Combined Modality Therapy/adverse effects
KW - Disease-Free Survival
KW - Follow-Up Studies
KW - Hodgkin Disease/mortality
KW - Humans
KW - Neoplasms, Second Primary/etiology
KW - Odds Ratio
KW - Proportional Hazards Models
KW - Randomized Controlled Trials as Topic
U2 - 10.3324/haematol.2017.167478
DO - 10.3324/haematol.2017.167478
M3 - Review article
C2 - 28912173
SN - 0390-6078
VL - 102
SP - 1748
EP - 1757
JO - Haematologica
JF - Haematologica
IS - 10
ER -
