Chemoradiotherapy plus hyperthermia (CRTH) versus chemoradiotherapy (CRT) alone in neoadjuvant treatment of soft tissue sarcoma: tumor response, treatment toxicity and disease control

Abstract

Introduction

Neoadjuvant chemotherapy and radiotherapy for the management of soft tissue sarcomas (STS) are still preferably delivered sequentially, with or without concurrent hyperthermia. Concurrent delivery of chemo-, radio- and thermotherapy may produce synergistic effects and reduce chemotherapy-free intervals. The few available studies suggest that concurrent chemoradiation (CRT) has a greater local effect. Data on the efficacy and toxicity of adding hyperthermia to CRT (CRTH) are sparse.

Materials and methods

A cohort of 101 patients with STS of the extremities and trunk who received CRT (n = 33) or CRTH (n = 68) before resection of macroscopic tumor (CRT: n = 19, CRTH: n = 49) or re-resection following a non-oncological resection, so called ‘whoops procedure’, (CRT: n = 14, CRTH: n = 19) were included in this retrospective study. CRT consisted of two cycles of doxorubicine (50 mg/m² on d2) plus ifosfamide (1500 mg/m² on d1-5, q28) plus radiation doses of up to 60 Gy. Hyperthermia was delivered in two sessions per week.

Results

All patients received the minimum dose of 50 Gy. Median doses of ifosfamide and doxorubicin were comparable between CRT (75%/95%) and CRTH (78%/97%). The median number of hyperthermia sessions was seven. There were no differences in acute toxicities. Major wound complications occurred in 15% (CRT) vs. 25% (CRTH) (p = 0.19). In patients with macroscopic disease, the addition of hyperthermia resulted in a tendency toward improved remission: regression ≥90% occurred in 21/48 (CRTH) vs. 4/18 (CRT) patients (p = 0.197). With a median postoperative follow-up of 72 months, 6-year local control and overall survival rates for CRTH vs. CRT alone were 85 vs. 78% (p = 0.938) and 79 vs. 71% (p = 0.215).

Conclusions

Both CRT and CRTH are well tolerated with an expected rate of wound complications. The results suggest that adding hyperthermia may improve tumor response.

Keywords:

• Sarcoma
• neoadjuvant
• radiotherapy
• chemoradiotherapy
• hyperthermia
• soft-tissue sarcoma
• toxicity
• chemotherapy

Acknowledgements

Alexander Willner performed research for the present work in fulfillment of the requirements for obtaining a doctoral degree in medicine (Dr. med.). We acknowledge financial support by Deutsche Forschungsgemeinschaft and Friedrich-Alexander-Universität Erlangen-Nürnberg within the funding programm “Open Access Publication Funding”.

Ethical approval

This study was carried out in accordance with all relevant guidelines and regulations. Informed consent to treatment was obtained from all patients. Patient consent for retrospective study participation was waived based on local legislation (BayKrG Art. 27 (4)) and institutional policy; formal consent was not required for retrospective study participation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used and/or analyzed in the current study are available from the corresponding author on reasonable request. Please contact the corresponding author ([email protected]).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.