Absence of progression, not extent of tumour shrinkage, defines prognosis in soft-tissue sarcoma - An analysis of the EORTC 62012 study of the EORTC STBSG.
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.



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.



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.



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.
Medical School Hannover, Clinic for Hematology, Hemostasis, Oncology and Stemcelltransplantation, Hannover, Germany. Electronic address: Gruenwald.Viktor@MH-hannover.de.
Viktor
V
Grünwald
EORTC Headquarters, Brussels, Belgium.
Saskia
S
Litière
Weston Park Hospital, Sheffield, UK.
Robin
R
Young
Royal Marsden, Radiology, London, UK.
Christina
C
Messiou
EORTC Headquarters, Brussels, Belgium.
Michela
M
Lia
University Hospital Muenster, Muenster, Germany.
Eva
E
Wardelmann
The Institute of Cancer Research, Personalized Oncology & Sarcoma Research, London, UK.
Winette
W
van der Graaf
Instituto Nazionale Tumori, Surgery, Milan, Italy.
Alessandro
A
Gronchi
Royal Marsden Hospital, Sarcoma Unit, London, UK.
Ian
I
Judson
D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000556:secondary; D047368:Tumor Burden / Q000187:drug effects; D055815:Young Adult
D018943:Anthracyclines
Chemotherapy; Prognosis; Soft-tissue sarcoma; Tumour shrinkage