The impact of chemotherapy on survival of patients with extremity and trunk wall soft tissue sarcoma: revisiting the results of the EORTC-STBSG 62931 randomised trial.


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:
03 2019
Historique:
received: 04 10 2018
revised: 29 11 2018
accepted: 11 12 2018
pubmed: 29 1 2019
medline: 22 5 2020
entrez: 29 1 2019
Statut: ppublish

Résumé

This study was aimed at determining whether patients with high-risk soft tissue sarcoma (STS), as identified using the nomogram Sarculator, benefitted from adjuvant chemotherapy in the EORTC-STBSG 62931 randomised controlled trial (RCT), which failed to detect an impact for adjuvant doxorubicin plus ifosfamide (Adj) over observation (Obs). Patients with extremity and trunk wall STS in the EORTC-STBSG 62931 RCT were analysed (N = 290/351). Ten-year predicted probability of overall survival (pr-OS) was calculated using the prognostic nomogram Sarculator. Patients were grouped into three categories of predicted pr-OS: high (pr-OS>66%), intermediate (51<pr-OS≤66) and low (pr-OS≤51%). OS and disease-free survival (DFS) were calculated. Nomogram pr-OS was dispersed (median 72%, interquartile range 57-83%) and had prognostic value for OS and DFS (log-rank test: P < 0.001). One hundred seventy, 68 and 52 patients had high (58.6%, 90 Obs/80 Adj), intermediate (23.5%, 34 Obs/34 Adj) and low pr-OS (17.9%, 24 Obs/28 Adj), respectively. Adjuvant chemotherapy halved the risk of recurrence (hazard ratio [HR] = 0.46, 95% confidence interval [CI] 0.24-0.89) and death (HR = 0.46, 95% CI 0.23-0.94) in the low pr-OS category, while no effect was detected in intermediate and high pr-OS categories. To strengthen these findings, study participants with pr-OS<60% were combined (N = 80, 27.6%, 39 Obs/41 Adj), and a significant DFS (HR = 0.49, 95% CI 0.28-0.85) and OS (HR = 0.50, 95% CI 0.30-0.90) benefit was detected. Patients of the EORTC-STBSG 62931 RCT with extremity and trunk wall STS and a low predicted pr-OS (high-risk patients) had better outcomes when treated with adjuvant chemotherapy. This may help reconcile the disparate results of clinical studies on adjuvant/neoadjuvant chemotherapy in STS.

Sections du résumé

BACKGROUND
This study was aimed at determining whether patients with high-risk soft tissue sarcoma (STS), as identified using the nomogram Sarculator, benefitted from adjuvant chemotherapy in the EORTC-STBSG 62931 randomised controlled trial (RCT), which failed to detect an impact for adjuvant doxorubicin plus ifosfamide (Adj) over observation (Obs).
METHODS
Patients with extremity and trunk wall STS in the EORTC-STBSG 62931 RCT were analysed (N = 290/351). Ten-year predicted probability of overall survival (pr-OS) was calculated using the prognostic nomogram Sarculator. Patients were grouped into three categories of predicted pr-OS: high (pr-OS>66%), intermediate (51<pr-OS≤66) and low (pr-OS≤51%). OS and disease-free survival (DFS) were calculated.
RESULTS
Nomogram pr-OS was dispersed (median 72%, interquartile range 57-83%) and had prognostic value for OS and DFS (log-rank test: P < 0.001). One hundred seventy, 68 and 52 patients had high (58.6%, 90 Obs/80 Adj), intermediate (23.5%, 34 Obs/34 Adj) and low pr-OS (17.9%, 24 Obs/28 Adj), respectively. Adjuvant chemotherapy halved the risk of recurrence (hazard ratio [HR] = 0.46, 95% confidence interval [CI] 0.24-0.89) and death (HR = 0.46, 95% CI 0.23-0.94) in the low pr-OS category, while no effect was detected in intermediate and high pr-OS categories. To strengthen these findings, study participants with pr-OS<60% were combined (N = 80, 27.6%, 39 Obs/41 Adj), and a significant DFS (HR = 0.49, 95% CI 0.28-0.85) and OS (HR = 0.50, 95% CI 0.30-0.90) benefit was detected.
CONCLUSION
Patients of the EORTC-STBSG 62931 RCT with extremity and trunk wall STS and a low predicted pr-OS (high-risk patients) had better outcomes when treated with adjuvant chemotherapy. This may help reconcile the disparate results of clinical studies on adjuvant/neoadjuvant chemotherapy in STS.

Identifiants

pubmed: 30690293
pii: S0959-8049(18)31555-7
doi: 10.1016/j.ejca.2018.12.009
pii:
doi:

Substances chimiques

Doxorubicin 80168379AG
Ifosfamide UM20QQM95Y

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

51-60

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Auteurs

Sandro Pasquali (S)

Sarcoma Service, Department of Surgery, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. Electronic address: sandro.pasquali@istitutotumori.mi.it.

Sara Pizzamiglio (S)

Unit of Bioinformatics and Biostatistics, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.

Nathan Touati (N)

European Organisation for Research and Treatment of Cancer (EORTC), Belgium.

Saskia Litiere (S)

European Organisation for Research and Treatment of Cancer (EORTC), Belgium.

Sandrine Marreaud (S)

European Organisation for Research and Treatment of Cancer (EORTC), Belgium.

Bernd Kasper (B)

University of Heidelberg, Mannheim University Medical Center, Interdisciplinary Tumor Center, Sarcoma Unit, Mannheim, Germany.

Hans Gelderblom (H)

Department of Clinical Oncology, Leiden University Medical Centre, Leiden, the Netherlands.

Silvia Stacchiotti (S)

Medical Oncology Unit 2, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.

Ian Judson (I)

The Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, United Kingdom.

Angelo P Dei Tos (AP)

Treviso General Hospital, Treviso, Italy; Department of Medicine, University of Padova, Padova, Italy.

Paolo Verderio (P)

Unit of Bioinformatics and Biostatistics, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.

Paolo G Casali (PG)

Medical Oncology Unit 2, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy; The Institute of Cancer Research, Royal Marsden NHS Foundation Trust, London, United Kingdom; Treviso General Hospital, Treviso, Italy; Department of Medicine, University of Padova, Padova, Italy; Oncology and Haemato-Oncology Department, University of Milan, Italy.

Penella J Woll (PJ)

Academic Unit of Clinical Oncology, University of Sheffield, Sheffield, UK.

Alessandro Gronchi (A)

Sarcoma Service, Department of Surgery, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. Electronic address: alesssandro.gronchi@istitutotumori.mi.it.

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