Neoadjuvant chemotherapy and radiotherapy for large extremity soft-tissue sarcomas.
OBJECTIVE
Treatment of extremity soft-tissue sarcomas yields excellent local control, but distant failure is common with large, high-grade tumors. A regimen of preoperative chemotherapy consisting of mesna, adriamycin, ifosfamide, and dacarbazine (MAID) interdigitated with radiotherapy followed by resection and postoperative chemotherapy with or without radiotherapy was designed to improve treatment outcome. We report the mature outcome data on 48 treated patients and compare them with the data of an historical matched control patient population.


METHODS
Adult patients with high-grade extremity soft-tissue sarcomas >or=8 cm were treated with three cycles of preoperative chemotherapy combined with 44 Gy of radiotherapy followed by surgery. Three cycles of postoperative MAID were planned. For patients with positive surgical margins, 16 Gy was delivered postoperatively.


RESULTS
All 48 patients (M0) received the MAID protocol treatment, and their outcome was superior to that of the historical control patients. The 5-year actuarial local control, freedom from distant metastasis, disease-free survival, and overall survival rate was 92% and 86% (p = 0.1155), 75% and 44% (p = 0.0016), 70% and 42% (p = 0.0002), and 87% and 58% (p = 0.0003) for the MAID and control patient groups, respectively. Acute hematologic toxicity in the MAID group included febrile neutropenia in 12 patients (25%). Wound healing complications occurred in 14 (29%) of 48 MAID patients. One MAID patient developed late fatal myelodysplasia.


CONCLUSIONS
After aggressive chemoradiation and surgery, these patients showed a significant reduction in distant metastases, with a highly significant gain in disease-free and overall survival compared with a historical control group. On the basis of this experience, the Radiation Therapy Oncology Group conducted a multi-institutional trial.
DeLaney
Thomas F
TF
Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA. tdelaney@partners.org
Spiro
Ira J
IJ
Suit
Herman D
HD
Gebhardt
Mark C
MC
Hornicek
Francis J
FJ
Mankin
Henry J
HJ
Rosenberg
Andrew L
AL
Rosenthal
Daniel I
DI
Miryousefi
Fariba
F
Ancukiewicz
Marcus
M
Harmon
David C
DC
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005121:Extremities; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D015080:Mesna / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D011878:Radiotherapy / Q000009:adverse effects; D012509:Sarcoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D016896:Treatment Outcome
D003606:Dacarbazine; D004317:Doxorubicin; D015080:Mesna; D007069:Ifosfamide