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Predictive and prognostic factors associated with soft tissue sarcoma response to chemotherapy: a subgroup analysis of the European Organisation for Research and Treatment of Cancer 62012 study.

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Date
2017-07
ICR Author
Fisher, Cyril
van der Graaf, Wilhelmina
Messiou, Christina
Judson, Ian
Marsden,
Author
Young, RJ
Litière, S
Lia, M
Hogendoorn, PCW
Fisher, C
Mechtersheimer, G
Daugaard, S
Sciot, R
Collin, F
Messiou, C
Grünwald, V
Gronchi, A
van der Graaf, W
Wardelmann, E
Judson, I
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Type
Journal Article
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Abstract
Background The European Organization for Research and Treatment of Cancer (EORTC) 62012 study was a Phase III trial of doxorubicin versus doxorubicin-ifosfamide chemotherapy in 455 patients with advanced soft tissue sarcoma (STS). Analysis of the main study showed that combination chemotherapy improved tumor response and progression-free survival, but differences in overall survival (OS) were not statistically significant. We analyzed factors prognostic for tumor response and OS, and assessed histological subgroup and tumor grade as predictive factors to identify patients more likely to benefit from combination chemotherapy.Methods Central pathology review was performed by six reference pathologists. Gender, age, performance status, time from first presentation with sarcoma to starting palliative chemotherapy, tumor grade, histological subgroup, primary tumor site involvement, and sites of metastases were assessed as prognostic factors.Results Three hundred and ten patients were included in this study. Discordance between local and central pathology opinion of tumor histology and tumor grade was observed in 98 (32%) and 122 (39%) cases, respectively. In multivariate analysis, liposarcoma patients had improved tumor response compared to other histological subgroups, whilst patients with metastases other than lung, liver or bone had a poorer response [odds ratio (OR) 0.42, 95% confidence interval (CI) 0.23-0.78; p = 0.006]. Patients with bone metastases had reduced OS [hazard ratio (HR) 1.56, 95% CI 1.16-2.09; p = 0.003]. By central pathology review, patients with undifferentiated pleomorphic sarcoma (UPS) had improved tumor response and OS with doxorubicin-ifosfamide compared to single-agent doxorubicin (OR 9.90, 95% CI 1.93-50.7 and HR 0.44, 95% CI 0.26-0.79, respectively). Grade III tumors had improved response with combination chemotherapy but there was no interaction between chemotherapy and grade on OS.Conclusions Prospective central pathology review of tumor histology should be integrated into future STS clinical trials. Doxorubicin-ifosfamide may be most appropriate for young, fit patients with poorly differentiated Grade III tumors including UPS.
URI
https://repository.icr.ac.uk/handle/internal/690
DOI
https://doi.org/10.1080/0284186x.2017.1315173
Collections
  • Clinical Studies
Subject
Humans
Sarcoma
Bone Neoplasms
Liver Neoplasms
Lung Neoplasms
Lymphatic Metastasis
Ifosfamide
Doxorubicin
Antineoplastic Combined Chemotherapy Protocols
Prognosis
Survival Rate
Follow-Up Studies
Prospective Studies
Adult
Middle Aged
Female
Male
Research team
Clinical and Translational Sarcoma
Sarcoma Clinical Trials
Language
eng
License start date
2017-07
Citation
Acta oncologica (Stockholm, Sweden), 2017, 56 (7), pp. 1013 - 1020

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