Ifosfamide, Carboplatin, and Etoposide (ICE) in Combination with Regional Hyperthermia as Salvage Therapy in Patients with Locally Advanced Nonmetastatic and Metastatic Soft-Tissue Sarcoma

Abstract

Patients with localized relapse of soft-tissue sarcoma (STS) after anthracycline-based chemotherapy have a dismal prognosis, particularly when surgery is not possible. To facilitate resection and improve long-term tumor control, we applied an intensified perioperative treatment consisting of ICE (ifosfamide 6 g/m2, carboplatin 400 mg/m2, and etoposide 600 mg/m2) in combination with regional hyperthermia (RHT) to maximize local control. Here, we retrospectively evaluate the safety and efficacy of this strategy. Patients aged ≥18 years with locally advanced high-risk STS, either with or without metastasis, treated with ICE + RHT after the failure of first-line anthracycline-based chemotherapy were included in this analysis. Radiographic response, toxicity, progression-free survival (PFS), and overall survival (OS) were assessed. Between 1996 and 2018, 213 sarcoma patients received ICE at our centre. Of these, 110 patients met the selection criteria (progressive disease, suitable high-grade STS histology, anthracycline pretreatment, RHT treatment) for this analysis. Fifty-four patients had locally advanced disease without metastases (LA-STS), and 56 patients had additional metastatic disease (M-STS). Disease control was achieved in 59% of LA-STS patients and in 47% of M-STS patients. For LA-STS, 21% of the patients achieved radiographic response, facilitating resection in 4 patients (7%), compared with 11% of the M-STS patients, facilitating resection in 5 patients (9%). PFS was significantly longer in LA-STS than in M-STS (10 vs. 4 months, p<0.0001). Median OS was 26 months in LA-STS and 12 months in M-STS. Disease control was the only independent prognostic factor for improved OS in multivariate analysis. Toxicity was high with neutropenic fever occurring in 25% of the patients and three therapy-related deaths (3%). ICE + RHT demonstrated activity in high-risk STS and facilitated resection in selected patients after anthracycline failure. Disease control was associated with improved OS. Based on the observed toxicities, the dose should be reduced to 75%.

Hyperthermia in Cancer Care: A Literature Review

“…The other study included 110 participants with locally advanced high-risk STS receiving combined chemotherapy and LRHT. 58 Disease control occurred in 59% of non-metastatic cases and 47% in those with metastases, with a median OS of 26 and 12 months, respectively.…”

“…One RCT (yielding three publications), [13][14][15] five observational studies [56][57][58][59][60] , and seven single-arm trials [61][62][63][64][65][66][67] were identified. Additionally, one single-arm trial 68 included deep seated sarcomas, and one observational study mixed soft tissue tumours.…”

Geriatric Assessment of Older Patients Receiving Trabectedin in First-Line Treatment for Advanced Soft Tissue Sarcomas: The E-TRAB Study from The German Interdisciplinary Sarcoma Group (GISG-13)

“…However, in up to 50% of patients, distant metastases occur. In previous years, the median overall survival (OS) in the metastatic setting was reported to be 12 to 15 months [5,6]. More recently, median OS appears to have improved and ranged from 20 to 24 months in randomized trials [7].…”

Susceptibility artifact correction in MR thermometry for monitoring of mild radiofrequency hyperthermia using total field inversion

“…Regional heating of tissue can be induced with radiofrequency (RF) antennas that create a focus in the target area. This treatment modality has become part of clinical practice for the treatment of various cancer types, including the treatment of sarcoma patients and patients with cervical cancer 2‐4 . To prevent tissue damage by overheating, many procedures rely on temperature probes that are placed intraluminally or superficially onto the skin.…”