Effectiveness of regional hyperthermia with chemotherapy for high-risk retroperitoneal and abdominal soft-tissue sarcoma after complete surgical resection: a subgroup analysis of a randomized phase-III multicenter study.
OBJECTIVE
To determine whether regional hyperthermia (RHT) in addition to chemotherapy improves local tumor control after macroscopically complete resection of abdominal or retroperitoneal high-risk sarcomas.


BACKGROUND
Within the prospectively randomized EORTC 62961 phase-III trial, RHT and systemic chemotherapy significantly improved local progression-free survival (LPFS) and disease-free survival (DFS) in patients with abdominal and extremity sarcomas. That trial included macroscopically complete and R2 resections.


METHODS
A subgroup analysis of the EORTC trial was performed and long-term survival determined. From 341 patients, 149 (median age 52 years, 18-69) were identified with macroscopic complete resection (R0, R1) of abdominal and retroperitoneal soft-tissue sarcomas (median diameter 10 cm, G2 48.3%, G3 51.7%). Seventy-six patients were treated with EIA (etoposide, ifosfamide, doxorubicin)+RHT (≥5 cycles: 69.7%) versus 73 patients receiving EIA alone (≥5 cycles: 52.1%, P=0.027). LPFS and DFS as well as overall survival were determined.


RESULTS
RHT and systemic chemotherapy significantly improved LPFS (56% vs 45% after 5 years, P=0.044) and DFS (34% vs 27% after 5 years, P=0.040). Overall survival was not significantly improved in the RHT group (57% vs 55% after 5 years, P=0.82). Perioperative morbidity and mortality were not significantly different between groups.


CONCLUSIONS
In patients with macroscopically complete tumor resection, RHT in addition to chemotherapy resulted in significantly improved local tumor control and DFS without increasing surgical complications. Within a multimodal therapeutic concept for abdominal and retroperitoneal high-risk sarcomas, RHT is a treatment option beside radical surgery and should be further evaluated in future trials.
*Department of General, Visceral, Transplantation, Vascular, and Thoracic Surgery and †Department of Internal Medicine III, University of Munich-Campus Grosshadern, Munich, Germany ‡Sarcoma Unit ITM-Interdisciplinary Tumor Center Mannheim, Mannheim University Medical Center, University of Heidelberg, Mannheim, Germany §Institute of Medical Informatics, Biometry, and Epidemiology, University of Munich-Campus Großhadern, Munich, Germany ¶Department of General, Visceral, and Vascular Surgery, University Hospital Magdeburg, University of Magdeburg, Magdeburg, Germany.
Martin K
MK
Angele
Markus
M
Albertsmeier
Niclas J
NJ
Prix
Peter
P
Hohenberger
Sultan
S
Abdel-Rahman
Nelli
N
Dieterle
Michael
M
Schmidt
Ulrich
U
Mansmann
Christiane J
CJ
Bruns
Rolf D
RD
Issels
Karl-Walter
KW
Jauch
Lars H
LH
Lindner
D000005:Abdomen; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012186:Retroperitoneal Neoplasms / Q000628:therapy*; D012307:Risk Factors; D012509:Sarcoma / Q000628:therapy*; D016896:Treatment Outcome