Viktor Grünwald1, Saskia Litière2, Robin Young3, Christina Messiou4, Michela Lia2, Eva Wardelmann5, Winette van der Graaf6, Alessandro Gronchi7, Ian Judson8. 1. Medical School Hannover, Clinic for Hematology, Hemostasis, Oncology and Stemcelltransplantation, Hannover, Germany. Electronic address: Gruenwald.Viktor@MH-hannover.de. 2. EORTC Headquarters, Brussels, Belgium. 3. Weston Park Hospital, Sheffield, UK. 4. Royal Marsden, Radiology, London, UK. 5. University Hospital Muenster, Muenster, Germany. 6. The Institute of Cancer Research, Personalized Oncology & Sarcoma Research, London, UK. 7. Instituto Nazionale Tumori, Surgery, Milan, Italy. 8. Royal Marsden Hospital, Sarcoma Unit, London, UK.
Abstract
BACKGROUND: Anthracycline-based chemotherapy remains the mainstay of first-line treatment in metastatic or advanced soft-tissue sarcoma (STS). Age, performance status, tumour histology and tumour grade are recognised prognostic factors; however, the prognostic value of tumour response and tumour shrinkage is ill-defined. METHODS: Patients recruited to the European Organisation for Research and Treatment of Cancer 62012 trial with advanced intermediate or high-grade STS, who received at least one cycle of chemotherapy and one tumour assessment of response, were eligible for this study. Kaplan-Meier estimates of overall survival (OS) by tumour response were computed using a landmark approach after two, four, and six cycles of chemotherapy. The prognostic role of the kinetics of tumour response was analysed by Cox proportional hazards. RESULTS: Three hundred eighty-nine patients were included in this study. Compared to stable or responding patients, patients with progressive disease (PD) after two, four and six cycles of chemotherapy achieved a worse OS: hazard ratio [HR] 2.62 (95% confidence interval [CI] 1.72-4.00), p < 0.001; HR 2.23 (95% CI 1.4-3.56), p = 0.0001; and HR 3.16 (95% CI 1.96-5.08), p = 0.0001, respectively. However, patients with stable or responding disease achieved similar OS outcomes. Correspondingly, patients with an increase in tumour size by 10% or more correlated with a worse OS in Cox proportional hazard analysis. CONCLUSIONS: No association between prognosis and amount of tumour shrinkage was detected. Interestingly, an increase in tumour size by at least 10% correlated with a worse OS, but re-defining PD as a ≥10% increase in tumour size did not translate into a better discrimination of survival outcomes for responders versus stable disease. Disease control rather than tumour response is a valuable end-point in advanced or metastatic STS receiving palliative anthracycline-based chemotherapy, supporting the use of time-to-event end-points in future STS trials.
BACKGROUND:Anthracycline-based chemotherapy remains the mainstay of first-line treatment in metastatic or advanced soft-tissue sarcoma (STS). Age, performance status, tumour histology and tumour grade are recognised prognostic factors; however, the prognostic value of tumour response and tumour shrinkage is ill-defined. METHODS:Patients recruited to the European Organisation for Research and Treatment of Cancer 62012 trial with advanced intermediate or high-grade STS, who received at least one cycle of chemotherapy and one tumour assessment of response, were eligible for this study. Kaplan-Meier estimates of overall survival (OS) by tumour response were computed using a landmark approach after two, four, and six cycles of chemotherapy. The prognostic role of the kinetics of tumour response was analysed by Cox proportional hazards. RESULTS: Three hundred eighty-nine patients were included in this study. Compared to stable or responding patients, patients with progressive disease (PD) after two, four and six cycles of chemotherapy achieved a worse OS: hazard ratio [HR] 2.62 (95% confidence interval [CI] 1.72-4.00), p < 0.001; HR 2.23 (95% CI 1.4-3.56), p = 0.0001; and HR 3.16 (95% CI 1.96-5.08), p = 0.0001, respectively. However, patients with stable or responding disease achieved similar OS outcomes. Correspondingly, patients with an increase in tumour size by 10% or more correlated with a worse OS in Cox proportional hazard analysis. CONCLUSIONS: No association between prognosis and amount of tumour shrinkage was detected. Interestingly, an increase in tumour size by at least 10% correlated with a worse OS, but re-defining PD as a ≥10% increase in tumour size did not translate into a better discrimination of survival outcomes for responders versus stable disease. Disease control rather than tumour response is a valuable end-point in advanced or metastatic STS receiving palliative anthracycline-based chemotherapy, supporting the use of time-to-event end-points in future STS trials.
Authors: Brian A Menegaz; Branko Cuglievan; Jalen Benson; Pamela Camacho; Salah-Eddine Lamhamedi-Cherradi; Cheuk Hong Leung; Carla L Warneke; Winston Huh; Vivek Subbiah; Robert S Benjamin; Shreyaskumar Patel; Najat Daw; Andrea Hayes-Jordan; Joseph A Ludwig Journal: Oncologist Date: 2017-12-06
Authors: Veit Bücklein; Christina Limmroth; Eric Kampmann; Gesa Schuebbe; Rolf Issels; Falk Roeder; Martin Angele; Hans Roland Dürr; Thomas Knösel; Sultan Abdel-Rahman; Dorit Di Gioia; Lars H Lindner Journal: Sarcoma Date: 2020-02-27