Response to neoadjuvant chemotherapy combined with regional hyperthermia predicts long-term survival for adult patients with retroperitoneal and visceral high-risk soft tissue sarcomas.
OBJECTIVE
To determine the efficacy of neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for local tumor control and overall survival (OS) in adult patients with retroperitoneal or visceral (RP/V) high-risk soft tissue sarcomas (HR-STS).


METHODS
From 1991 to 1997, 58 patients with HR-STS at RP/V sites were prospectively treated with four cycles of etoposide, ifosfamide, and doxorubicin combined with RHT followed by surgery, adjuvant chemotherapy, and radiation.


RESULTS
Objective response rate assessable in 40 patients was 13% (five partial responses). Including minor responses (n = 8), the radiographic response rate was 33%. The pathologic response rate assessable in 26 patients after surgical resection was 42%. Median OS was 31 months. At a median observation time of 74 months, 5-year probability of local failure-free survival (LFFS), distant metastasis-free survival, event-free survival, and OS were 25%, 51%, 20%, and 32%, respectively. Averaged minimum temperatures (T(min)) and time-averaged temperatures achieved in 50% (T(50)) and 90% (T(90)) of all measured tumor sites differed significantly between responders and nonresponders (T(min), 39.3 degrees C v 38.0 degrees C; P =.002; T(50), 40.9 degrees C v 40.3 degrees C; P =.038; T(90), 40.1 degrees C v 39.3 degrees C; P =.017). At 5-year follow-up, probability of LFFS (59% v 0%; P <.001) and OS (60% v 10%; P <.001) was significantly in favor of patients responding to neoadjuvant thermochemotherapy.


CONCLUSIONS
Response to neoadjuvant chemotherapy combined with RHT is predictive for an improved local tumor control resulting in a long-term survival benefit for patients with HR-STS at unfavorable RP/V sites; however, the impact of RHT has to be defined in a randomized phase III trial.
Department of Internal Medicine III, Diagnostic Radiology and Institute for Biostatistics and Epidemiology, Klinikum Grosshadern Medical Center, Ludwig-Maximilians-University, Munich, Germany. Clemens.Wendtner@med3.med.uni-muenchen.de
Clemens-M
CM
Wendtner
Sultan
S
Abdel-Rahman
Matthäus
M
Krych
Jens
J
Baumert
Lars H
LH
Lindner
Andrea
A
Baur
Wolfgang
W
Hiddemann
Rolf D
RD
Issels
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011446:Prospective Studies; D011859:Radiography; D012186:Retroperitoneal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000628:therapy*; D012509:Sarcoma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D014781:Viscera / Q000000981:diagnostic imaging
D005047:Etoposide; D004317:Doxorubicin; D007069:Ifosfamide