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

Robin J. Young, Saskia Litière, Michela Lia, Pancras C.W. Hogendoorn, Cyril Fisher, Gunhild Mechtersheimer, Søren Daugaard, Raf Sciot, Françoise Collin, Christina Messiou, Viktor Grünwald, Alessandro Gronchi, Winette van der Graaf, Eva Wardelmann, Ian Judson

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1013-1020
Number of pages8
JournalActa Oncologica
Volume56
Issue number7
DOIs
Publication statusPublished - Jul 3 2017

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Sarcoma
Drug Therapy
Neoplasms
Combination Drug Therapy
Survival
Confidence Intervals
Pathology
Neoplasm Metastasis
Doxorubicin
Histology
Odds Ratio
Bone and Bones
Liposarcoma
Disease-Free Survival
Multivariate Analysis
Clinical Trials
Lung

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

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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. / Young, Robin J.; Litière, Saskia; Lia, Michela; Hogendoorn, Pancras C.W.; Fisher, Cyril; Mechtersheimer, Gunhild; Daugaard, Søren; Sciot, Raf; Collin, Françoise; Messiou, Christina; Grünwald, Viktor; Gronchi, Alessandro; van der Graaf, Winette; Wardelmann, Eva; Judson, Ian.

In: Acta Oncologica, Vol. 56, No. 7, 03.07.2017, p. 1013-1020.

Research output: Contribution to journalArticle

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 2017, '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', Acta Oncologica, vol. 56, no. 7, pp. 1013-1020. https://doi.org/10.1080/0284186X.2017.1315173
Young, Robin J. ; Litière, Saskia ; Lia, Michela ; Hogendoorn, Pancras C.W. ; Fisher, Cyril ; Mechtersheimer, Gunhild ; Daugaard, Søren ; Sciot, Raf ; Collin, Françoise ; Messiou, Christina ; Grünwald, Viktor ; Gronchi, Alessandro ; van der Graaf, Winette ; Wardelmann, Eva ; Judson, Ian. / 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. In: Acta Oncologica. 2017 ; Vol. 56, No. 7. pp. 1013-1020.
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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.",
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T1 - Predictive and prognostic factors associated with soft tissue sarcoma response to chemotherapy

T2 - a subgroup analysis of the European Organisation for Research and Treatment of Cancer 62012 study

AU - Young, Robin J.

AU - Litière, Saskia

AU - Lia, Michela

AU - Hogendoorn, Pancras C.W.

AU - Fisher, Cyril

AU - Mechtersheimer, Gunhild

AU - Daugaard, Søren

AU - Sciot, Raf

AU - Collin, Françoise

AU - Messiou, Christina

AU - Grünwald, Viktor

AU - Gronchi, Alessandro

AU - van der Graaf, Winette

AU - Wardelmann, Eva

AU - Judson, Ian

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N2 - 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.

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