title: Concurrent chemoradiotherapy vs. radiotherapy alone in locally advanced cervix cancer: A systematic review and meta-analysis.
abstract: The efficacy of concurrent chemoradiotherapy (CTRT) in locally advanced cervix cancer (LACC, stages IIB-IVA) is contentious. This is due to the variable extent of therapeutic benefit reported in different randomized clinical trials and meta-analyses that usually include all stages of cervix cancer. A systematic review and meta-analysis was therefore conducted to evaluate the efficacy of concurrent CTRT over radiotherapy (RT) alone, predominantly in LACC for the key endpoints; complete response (CR), long-term loco-regional control (LRC), overall survival (OS), grade III/IV acute and late toxicities. Six databases namely - PubMed, EMBASE, SCOPUS, Web of Science, Google Scholar and Cochrane library were explored and supplemented by hand-searching. Only prospective randomized trials conducted in LACC between concurrent CTRT and RT alone with no surgical interventions were included. Fourteen English language articles from 1788 citations were shortlisted for the final analysis. Of the 2445 patients evaluated (CTRT: n=1217; RT: n=1228), 95.7% had LACC and 96% had a squamous cell histology. Eight studies used cisplatin alone, 4 had cisplatin-based combination chemotherapy (CT) while 2 used mitomycin-C, either alone or in combination. CTRT improved the CR (+10.2%, p=0.027), LRC (+8.4%, p<0.001) and OS (+7.5%, p<0.001) over RT alone. However a 10.4% higher incidence of grade III/IV acute toxicities (p<0.001) was also evident with CTRT. Late toxicities in both groups were equivalent. Subgroup analysis and meta-regression did not reveal any significant advantage in outcomes between the 3 CTRT regimens. Thus, although concurrent CTRT provides conclusive therapeutic benefit over RT alone in LACC, the choice of CT agents should be based on their cost-effectiveness and the anticipated expenses for the management of any associated acute toxicities. This assumes importance particularly in resource-constrained low-middle-income countries with the highest burden of LACC, where majority of the patients meet the treatment costs as out-of-pocket expenses.
authors.affiliation: Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, Aarau, Switzerland. Electronic address: niloyranjan.datta@ksa.ch.
authors.forename: Niloy Ranjan
authors.initials: NR
authors.lastname: Datta
authors.affiliation: Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Stutz
authors.affiliation: Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Liu
authors.affiliation: Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Rogers
authors.affiliation: Swiss Group for Clinical Cancer Research (SAKK), Coordinating Centre, Bern, Switzerland.
authors.forename: Dirk
authors.initials: D
authors.lastname: Klingbiel
authors.affiliation: Department of Oncology, University Hospital Zurich, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Siebenhüner
authors.affiliation: Department of Radiotherapy, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Shalini
authors.initials: S
authors.lastname: Singh
authors.affiliation: Centre for Radiation Oncology KSA-KSB, Kantonsspital Aarau, Aarau, Switzerland; Department of Radiation Oncology, University Hospital Zurich, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Bodis
mesh_terms: D059248:Chemoradiotherapy; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D016032:Randomized Controlled Trials as Topic; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
keywords: Cervix cancer; Chemoradiotherapy; Meta-analysis; Radiotherapy; Systematic review