Pooled Analysis of external-beam RADiotherapy parameters in phase II and phase III trials in radiochemotherapy in Anal Cancer (PARADAC).
Anus Neoplasms
/ epidemiology
Chemoradiotherapy
/ adverse effects
Clinical Trials, Phase II as Topic
/ methods
Clinical Trials, Phase III as Topic
/ methods
Combined Modality Therapy
Fluorouracil
/ administration & dosage
Humans
Mitomycin
/ administration & dosage
Neoplasm Recurrence, Local
/ ethnology
Radiotherapy Dosage
Treatment Outcome
Anal cancer
Chemoradiation
Overall treatment time
Radiation
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
20
05
2019
revised:
16
08
2019
accepted:
24
08
2019
pubmed:
2
10
2019
medline:
9
6
2020
entrez:
2
10
2019
Statut:
ppublish
Résumé
Concomitant external-beam radiochemotherapy (5-fluorouracil-mitomycin C) has become the standard of care in anal cancer since the '90s. A pooled analysis of individual patient data from 7 major trials was performed quantifying the effect of radiation therapy (RT)-related parameters on the outcome of patients with anal cancer. Pooling databases from combined modality trials, the impact of RT parameters (total dose, gap duration, OTT: overall treatment time) on outcome including locoregional failure (LRF), 5-year progression free survival (PFS) and toxicities were investigated. Individual patient data were received for 10/13 identified published studies conducted from 1987 to 2008 (n = 3031). A Cox regression model was used (landmark = 3 months after RT for first follow-up). After data inspection indicating severe heterogeneity between trials, only 1343 patients from 7/10 studies received were analysed (the most recent ones, since 1994; median follow-up = 4.1 years). A higher overall 5-year LRF rate [22.8% (95% confidence interval [CI] 22.3-27.3%)] significantly correlated with longer OTT (p = 0.03), larger tumour size (p < 0.001) and male gender (p = 0.045). Although significant differences were not observed, subset analyses for LRF (dose range: 50.4-59 Gy) seemed to favour lower doses (p = 0.412), and when comparing a 2-week gap versus 3 (dose: 59.4 Gy), results suggested 3 weeks might be detrimental (p = 0.245). For a 2-week gap versus none (dose range: 55-59.4 Gy), no difference was observed (p = 0.89). Five-year PFS was 65.7% (95% CI: 62.8-68.5%). Higher PFS rates were observed in women (p < 0.001), smaller tumour sizes (p < 0.001) and shorter OTT (p = 0.025). Five-year overall survival [76.7% (95% CI: 73.9%-79.3%)] correlated positively with female gender (p < 0.001), small tumour size (p = 0.027) and short OTT (p = 0.026). Descriptive toxicity data are presented. For patients receiving concurrent external-beam doublet chemoradiation, a longer OTT seems detrimental to outcome. Further trials involving modern techniques may better define optimal OTT and total dose.
Identifiants
pubmed: 31574418
pii: S0959-8049(19)30482-4
doi: 10.1016/j.ejca.2019.08.022
pmc: PMC6924923
mid: NIHMS1542153
pii:
doi:
Substances chimiques
Mitomycin
50SG953SK6
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
130-143Subventions
Organisme : NCI NIH HHS
ID : U10 CA180822
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180868
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.
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