Effectiveness of Regional Hyperthermia With Chemotherapy for High-Risk Retroperitoneal and Abdominal Soft-Tissue Sarcoma After Complete Surgical Resection

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%.

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1LBA Impact of regional hyperthermia (RHT) on response to neo-adjuvant chemotherapy and survival of patients with high-risk soft-tissue sarcoma (HR-STS): Results of the randomized EORTC-ESHO intergroup trial (NCI-00003052)

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(09)72027-0 ◽

2009 ◽

Vol 7 (3) ◽

pp. 2 ◽

Cited By ~ 4

Author(s):

R. Issels ◽

L.H. Lindner ◽

C.M. Wendtner ◽

P. Hohenberger ◽

P. Reichardt ◽

...

Keyword(s):

High Risk ◽

Adjuvant Chemotherapy ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Regional Hyperthermia ◽

Intergroup Trial ◽

Neo Adjuvant Chemotherapy

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Regional hyperthermia for high-risk soft tissue sarcoma treatment

Current Opinion in Oncology ◽

10.1097/cco.0000000000000316 ◽

2016 ◽

Vol 28 (5) ◽

pp. 447-452 ◽

Cited By ~ 5

Author(s):

Rolf Issels ◽

Lars H. Lindner

Keyword(s):

High Risk ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Regional Hyperthermia ◽

Sarcoma Treatment

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Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term Outcomes Among Patients With Localized High-Risk Soft Tissue Sarcoma

JAMA Oncology ◽

10.1001/jamaoncol.2017.4996 ◽

2018 ◽

Vol 4 (4) ◽

pp. 483 ◽

Cited By ~ 88

Author(s):

Rolf D. Issels ◽

Lars H. Lindner ◽

Jaap Verweij ◽

Rüdiger Wessalowski ◽

Peter Reichardt ◽

...

Keyword(s):

High Risk ◽

Soft Tissue ◽

Neoadjuvant Chemotherapy ◽

Soft Tissue Sarcoma ◽

Long Term Outcomes ◽

Regional Hyperthermia

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Comparison of Different Systemic Therapeutic Regimes in Resectable Soft-Tissue Sarcoma—Results of a Network Meta-Analysis

Cancers ◽

10.3390/cancers13225631 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5631

Author(s):

Jan Haussmann ◽

Christiane Matuschek ◽

Edwin Bölke ◽

Balint Tamaskovics ◽

Stefanie Corradini ◽

...

Keyword(s):

High Risk ◽

Adjuvant Chemotherapy ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Literature Search ◽

Standard Treatment ◽

Meta Analysis ◽

Treatment Modalities ◽

Regional Hyperthermia ◽

Male Patients

Background: The standard treatment of high-risk soft-tissue sarcoma consists of surgical resection followed by risk-adapted radiation therapy. Further treatment options that may improve local and systemic tumor control, including chemotherapy, are not well established. Due to the heterogeneity of the disease, different systemic approaches as well as their application at different time points have been attempted. Methods: We conducted a systematic literature search for randomized clinical trials in the treatment of localized, resectable high-risk adult soft-tissue sarcoma comparing different treatment modalities according to the PRISMA guidelines. We extracted published hazard ratios and number of events for the endpoints overall and disease-free survival (OS; DFS) as well as local and distant recurrence-free interval (LRFI; DRFI). The different modalities were compared in a network meta-analysis against the defined standard treatment surgery ± radiotherapy using the inverse-variance heterogeneity model. Results: The literature search identified 25 trials including 3453 patients. Five different treatment modalities were compared in the network meta-analysis. The addition of adjuvant chemotherapy significantly improved OS compared to surgery ± radiotherapy alone (HR = 0.86; CI-95%: 0.75–0.97; p = 0.017). Likewise, neoadjuvant chemotherapy combined with regional hyperthermia (naCTx + HTx) also led to superior OS (HR = 0.45; CI-95%: 0.20–1.00; p = 0.049). Both neoadjuvant chemotherapy alone (naCTx) and perioperative chemotherapy (periCTx) did not improve OS (HR = 0.61; CI-95%: 0.29–1.29; p = 0.195 and HR = 0.66; CI-95%: 0.30–1.48; p = 0.317, respectively). Histology-tailored chemotherapy (htCTx) also did not improve survival compared to surgery ± radiotherapy (HR = 1.08; CI-95%: 0.45–2.61; p = 0.868). The network analysis of DFS, LRFI, and DRFI revealed a similar pattern between the different treatment regimens. Adjuvant chemotherapy significantly improved DFS, LRFI, and DRFI compared to surgery ± radiotherapy. In direct comparison, this advantage of adjuvant chemotherapy was restricted to male patients (HR = 0.78; CI-95%: 0.65–0.92; p = 0.004) with no effect for female patients (HR = 1.08; CI-95%: 0.90–1.29; p = 0.410). Conclusions: Standardized chemotherapy in high-risk soft-tissue sarcoma appears to be of added value irrespective of timing. The benefit of adjuvant chemotherapy seems to be restricted to male patients. The addition of regional hyperthermia to neodjuvant chemotherapy achieved the best effect sizes and might warrant further investigation.

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