Comparison of Different Systemic Therapeutic Regimes in Resectable Soft-Tissue Sarcoma—Results of a Network Meta-Analysis
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 th...
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2021
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oai:doaj.org-article:35083f4e734f48ba8ef8325f137aaafd2021-11-25T17:01:51ZComparison of Different Systemic Therapeutic Regimes in Resectable Soft-Tissue Sarcoma—Results of a Network Meta-Analysis10.3390/cancers132256312072-6694https://doaj.org/article/35083f4e734f48ba8ef8325f137aaafd2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5631https://doaj.org/toc/2072-6694Background: 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; <i>p</i> = 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; <i>p</i> = 0.049). Both neoadjuvant chemotherapy alone (naCTx) and perioperative chemotherapy (periCTx) did not improve OS (HR = 0.61; CI-95%: 0.29–1.29; <i>p</i> = 0.195 and HR = 0.66; CI-95%: 0.30–1.48; <i>p</i> = 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; <i>p</i> = 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; <i>p</i> = 0.004) with no effect for female patients (HR = 1.08; CI-95%: 0.90–1.29; <i>p</i> = 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.Jan HaussmannChristiane MatuschekEdwin BölkeBalint TamaskovicsStefanie CorradiniRüdiger WessalowskiKitti MaasLivia SchmidtKlaus OrthMatthias PeiperVerena KeitelTorsten FeldtBjörn-Erik Ole JensenTom LueddeJohannes FischerWolfram Trudo KnoefelHany AshmawyAlessia PedotoaKai KammersWilfried BudachMDPI AGarticlenetwork meta-analysischemotherapyhyperthermiasurgeryoverall survivalNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5631, p 5631 (2021) |
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network meta-analysis chemotherapy hyperthermia surgery overall survival Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
network meta-analysis chemotherapy hyperthermia surgery overall survival Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jan Haussmann Christiane Matuschek Edwin Bölke Balint Tamaskovics Stefanie Corradini Rüdiger Wessalowski Kitti Maas Livia Schmidt Klaus Orth Matthias Peiper Verena Keitel Torsten Feldt Björn-Erik Ole Jensen Tom Luedde Johannes Fischer Wolfram Trudo Knoefel Hany Ashmawy Alessia Pedotoa Kai Kammers Wilfried Budach Comparison of Different Systemic Therapeutic Regimes in Resectable Soft-Tissue Sarcoma—Results of a Network Meta-Analysis |
| description |
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; <i>p</i> = 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; <i>p</i> = 0.049). Both neoadjuvant chemotherapy alone (naCTx) and perioperative chemotherapy (periCTx) did not improve OS (HR = 0.61; CI-95%: 0.29–1.29; <i>p</i> = 0.195 and HR = 0.66; CI-95%: 0.30–1.48; <i>p</i> = 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; <i>p</i> = 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; <i>p</i> = 0.004) with no effect for female patients (HR = 1.08; CI-95%: 0.90–1.29; <i>p</i> = 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. |
| format |
article |
| author |
Jan Haussmann Christiane Matuschek Edwin Bölke Balint Tamaskovics Stefanie Corradini Rüdiger Wessalowski Kitti Maas Livia Schmidt Klaus Orth Matthias Peiper Verena Keitel Torsten Feldt Björn-Erik Ole Jensen Tom Luedde Johannes Fischer Wolfram Trudo Knoefel Hany Ashmawy Alessia Pedotoa Kai Kammers Wilfried Budach |
| author_facet |
Jan Haussmann Christiane Matuschek Edwin Bölke Balint Tamaskovics Stefanie Corradini Rüdiger Wessalowski Kitti Maas Livia Schmidt Klaus Orth Matthias Peiper Verena Keitel Torsten Feldt Björn-Erik Ole Jensen Tom Luedde Johannes Fischer Wolfram Trudo Knoefel Hany Ashmawy Alessia Pedotoa Kai Kammers Wilfried Budach |
| author_sort |
Jan Haussmann |
| title |
Comparison of Different Systemic Therapeutic Regimes in Resectable Soft-Tissue Sarcoma—Results of a Network Meta-Analysis |
| title_short |
Comparison of Different Systemic Therapeutic Regimes in Resectable Soft-Tissue Sarcoma—Results of a Network Meta-Analysis |
| title_full |
Comparison of Different Systemic Therapeutic Regimes in Resectable Soft-Tissue Sarcoma—Results of a Network Meta-Analysis |
| title_fullStr |
Comparison of Different Systemic Therapeutic Regimes in Resectable Soft-Tissue Sarcoma—Results of a Network Meta-Analysis |
| title_full_unstemmed |
Comparison of Different Systemic Therapeutic Regimes in Resectable Soft-Tissue Sarcoma—Results of a Network Meta-Analysis |
| title_sort |
comparison of different systemic therapeutic regimes in resectable soft-tissue sarcoma—results of a network meta-analysis |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/35083f4e734f48ba8ef8325f137aaafd |
| work_keys_str_mv |
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