Comparison of different systemic therapeutic regimes in resectable high-risk soft tissue sarcoma: Results of a network meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11549-11549
Author(s):  
Jan Haussmann ◽  
Wilfried Budach ◽  
Edwin Boelke ◽  
Balint Tamaskovics ◽  
Freddy Joel Djiepmo Njanang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Soft Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Soft Tissue Sarcoma ◽  
Literature Search ◽  
Standard Treatment ◽  
Meta Analysis ◽  
Tumor Control ◽  
Regional Hyperthermia

11549 Background: The treatment of high-risk soft tissue sarcoma of the trunk or the extremities consists of surgical resection with risk-adapted radiation therapy. Further treatment options which can significantly improve local and systemic tumor control including chemotherapy are not well established. Due to the heterogeneity of disease different systemic approaches as well as their application during different time points have been attempted. Methods: We conducted a literature search for randomized clinical trials in the treatment of localized, resectable high-risk soft tissue sarcoma comparing different treatment modalities according to the PRISMA guidelines. We extracted published hazard ratios and number of events for the endpoints of 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 (ivhet) with the help of the Microsoft Excel add-in Meta-XL V5.3. Results: The literature search identified 25 studies including 3489 patients. The network analysis showed that adjuvant chemotherapy (adjCTx) results in a significant improvement in overall survival (HR = 0.86; CI-95%: 0.75-0.97; p = 0.017) compared to the standard treatment of surgery ± radiatherapy alone. Combined treatment with regional hyperthermia and neoadjuvant chemotherapy (HTx+nadjCTx) also improves OS (HR = 0.45; CI-95%: 0.20-1.00; p = 0.049). Preoperative chemotherapy alone (nadjCTx) as well as perioperative chemotherapy (periopCTx) resulted both in non-statistically significant improvements in OS (HR = 0.61; CI-95%: 0.29-1.29; p = 0.195) and (HR = 0.48; CI-95%: 0.15-1.55; p = 0.218). Histology-tailored neoadjuvant chemotherapy (tNaCTx) also showed no effect on overall survival (HR = 1.08; CI-95%: 0.45-2.61; p = 0.868). The analysis of DFS, LRFI and DRFI disclosed a similar pattern between the different treatment regimens. Conclusions: The addition of cytotoxic chemotherapy in resectable high-risk soft tissue sarcomas provides a measurable benefit in overall survival. Shifting of systemic therapy to the neoadjuvant setting and combination with regional hyperthermia might be favored. Predictive clinical and molecular markers are needed to evaluate and limit potentional risks prospectively going forward.

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

Cancers ◽  
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.

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

Sarcoma ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Veit Bücklein ◽  
Christina Limmroth ◽  
Eric Kampmann ◽  
Gesa Schuebbe ◽  
Rolf Issels ◽  
...  
Keyword(s):  
High Risk ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Disease Control ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Tumor Control ◽  
Regional Hyperthermia ◽  
Radiographic Response ◽  
Dismal Prognosis

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%.

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

JAMA Oncology ◽  
2018 ◽  
Vol 4 (4) ◽  
pp. 483 ◽  
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

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

2014 ◽  
Vol 260 (5) ◽  
pp. 749-756 ◽  
Author(s):  
Martin K. Angele ◽  
Markus Albertsmeier ◽  
Niclas J. Prix ◽  
Peter Hohenberger ◽  
Sultan Abdel-Rahman ◽  
...  
Keyword(s):  
High Risk ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Surgical Resection ◽  
Regional Hyperthermia ◽  
Complete Surgical Resection

scholarly journals Doxorubicin-Based Chemotherapy for the Palliative Treatment of Adult Patients with Locally Advanced or Metastatic Soft-Tissue Sarcoma: A Meta-Analysis and Clinical Practice Guideline

Sarcoma ◽  
2000 ◽  
Vol 4 (3) ◽  
pp. 103-112 ◽  
Author(s):  
Vivien H. C. Bramwell ◽  
Dale Anderson ◽  
Manya L. Charette
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Adverse Effects ◽  
Combination Therapy ◽  
Meta Analysis ◽  
Single Agent ◽  
Locally Advanced ◽  
Metastatic Soft Tissue Sarcoma ◽  
Single Agent Chemotherapy

Purpose.To make recommendations for the use of doxorubicin-based chemotherapy in patients with soft-tissue sarcoma.Patients.The recommendations apply to patients with symptomatic unresectable locally advanced or metastatic soft-tissue sarcoma who are candidates for palliative chemotherapy.Methods.A systematic review of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice to develop an evidence-based practice guideline.Results.Eight randomized trials comparing doxorubicin-based combination versus doxorubicin single-agent chemotherapy were reviewed. Response rates and overall survival were evaluated using pooled statistical analysis.The pooled response data in 2281 patients showed a slight trend favouring the combination therapy, although this did not reach statistical significance (odds ratio (OR), 0.79; 95% confidence interval (CI), 0.60–1.05;p=0.10). Survival data could only be abstracted from six studies involving 2097 patients, and showed no significant advantage for combination therapy (OR, 0.84; 95% CI, 0.67–1.06;p=0.13). Data on adverse effects could not be combined in a meta-analysis; however nausea, vomiting and myelosuppression were consistently more severe with combination chemotherapy than with single-agent chemotherapy.Discussion.Single-agent doxorubicin is an appropriate first-line chemotherapy option for advanced or metastatic soft-tissue sarcoma. Some doxorubicin-based combination chemotherapy regimens, given in conventional doses, produce only marginal increases in response rates, at the expense of increased adverse effects, and with no improvements in overall survival. Future randomized clinical trials should compare new regimens, whose activity has been established in single-arm studies, with single-agent doxorubicin, and include quality of life as an outcome measure.

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