Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas: an exploratory, retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG).
BACKGROUND
Adult patients with advanced soft tissue sarcomas (STS) are generally treated similarly, regardless of great differences between STS subtypes, disease presentation and patients' characteristics. As ifosfamide is frequently applied in first line systemic therapy, we aimed to establish prognostic and predictive factors for outcome to ifosfamide-based therapy.


METHODS
A retrospective, exploratory analysis was performed on data from 1337 advanced STS patients who received first-line ifosfamide-containing chemotherapy. For predictive factor analysis, 660 patients treated with doxorubicin monotherapy served as comparators.


RESULTS
Independent favourable prognostic factors for overall survival (OS) were good performance status, female gender, low histological grade, extremity primary tumour site and locally advanced disease; for progression-free survival (PFS), the combination of doxorubicin and ifosfamide, locally advanced disease, and tumour entity with a lower risk to progress for synovial sarcoma patients compared to leiomyosarcoma. For response, independent favourable prognostic factors were doxorubicin combined with ifosfamide, higher histological grade, and histology with synovial sarcoma patients having the highest chance to respond. Predictive factor analysis showed that compared to doxorubicin monotherapy, patients who benefited less from ifosfamide-based therapies were leiomyosarcoma patients in terms of OS, and patients with liposarcoma for response. No predictive factors were found for PFS.


CONCLUSIONS
In this study, we established an independent set of prognostic and predictive factors for outcome to ifosfamide-based chemotherapy in advanced STS patients. This study provides important information for the interpretation and design of clinical trials for specific STS entities and may contribute to further treatment individualisation of advanced STS patients.
Sleijfer
Stefan
S
Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands. s.sleijfer@erasmusmc.nl
Ouali
Monia
M
van Glabbeke
Martine
M
Krarup-Hansen
Anders
A
Rodenhuis
Sjoerd
S
Le Cesne
Axel
A
Hogendoorn
Pancras C W
PC
Verweij
Jaap
J
Blay
Jean-Yves
JY
D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D004317:Doxorubicin; D007069:Ifosfamide