Feasibility of Total Neoadjuvant Treatment With HYPErthermia in Patients With High-risk Extremity and Trunk Soft Tissue Sarcoma (TNT-HYPE)

Trial treatment consists of 3 neoadjuvant cycles of doxorubicin with either ifosfamide or dacarbazine (the latter only in case of leiomyosarcoma). Doxorubicin will be given at a dose of 75 mg/m2 Body surface area (BSA) on day 1 of each cycle as a intravenous infusion over 15 minutes.

Trial treatment consists of 3 neoadjuvant cycles of doxorubicin with either ifosfamide or dacarbazine (the latter only in case of leiomyosarcoma). Ifosfamide will be given at a dose of 3 g/m2 BSA on days 1 to 3 of each cycle, for a total dose per cycle of 9 g/m2 BSA, as an intravenous infusion of 3 g/m2 daily over 4 hours.

Trial treatment consists of 3 neoadjuvant cycles of doxorubicin with either ifosfamide or dacarbazine (the latter only in case of leiomyosarcoma). Dacarbazine will be given at a daily dose of 300 mg/m2 BSA on days 1 to 3 of each cycle, for a total dose per cycle of 900 mg/m2 BSA, as an intravenous infusion over 30 minutes.

Hyperthermia (HT) sessions are scheduled on days 1 and 3 of each chemotherapy cycle. The duration of the preheating phase is always 30 minutes. Together with the treatment phase of 60 minutes, the duration of a HT session is uniformly 90 minutes (Total treatment time). On days 2, chemotherapy will be applied without HT.

"Radiotherapy (RT) treatment should start ideally 19 days after last chemotherapy dose received (range -4 / +7), preferably on a Monday to omit that the last RT fractions will be applied directly after the weekend. Start of RT can be postponed up to 14 days due to medical reasons without violating treatment protocol.~Patients will preferably receive normofractionated RT to a total dose of 50 Gy in 25 fractions of 2 Gy over 5 weeks23.~Alternatively, patients can receive a moderate hypofractionated RT to either a total dose of 42.75 Gy in 15 fractions of 2.85 Gy over 3 weeks or a total dose of 42 Gy in 14 fractions of 3 Gy over 2 weeks and four days41. The respective total treatment time changes respectively.~The RT treatment should be delivered once daily except on weekends."

"Standard of care surgical resection must be done by an experienced sarcoma surgeon. All lesions of the trunk and extremities will be resected after total neoadjuvant treatment with chemotherapy, HT and RT.~Surgery will take place preferentially 6 weeks (+/- 2 weeks) after end of radiation."