Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS).
OBJECTIVE
To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma.


METHODS
Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients).


RESULTS
After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy.


CONCLUSIONS
Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.
Kempf-Bielack
Beate
B
Cooperative Osteosarkomstudiengruppe (COSS), Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie, Albert-Schweitzer-Strasse 33, D-48149 Münster, Germany. coss@uni-muenster.de
Bielack
Stefan S
SS
Jürgens
Heribert
H
Branscheid
Detlev
D
Berdel
Wolfgang E
WE
Exner
G Ulrich
GU
Göbel
Ulrich
U
Helmke
Knut
K
Jundt
Gernot
G
Kabisch
Hartmut
H
Kevric
Mathias
M
Klingebiel
Thomas
T
Kotz
Rainer
R
Maas
Rainer
R
Schwarz
Rudolf
R
Semik
Michael
M
Treuner
Jörn
J
Zoubek
Andreas
A
Winkler
Kurt
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery*; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors