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Review
. 2021 Nov 11;13(22):5631.
doi: 10.3390/cancers13225631.

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

Jan Haussmann  1 , Christiane Matuschek  1 , Edwin Bölke  1 , Balint Tamaskovics  1 , Stefanie Corradini  2 , Rüdiger Wessalowski  3 , Kitti Maas  1 , Livia Schmidt  1 , Klaus Orth  1 , Matthias Peiper  1 , Verena Keitel  4 , Torsten Feldt  4 , Björn-Erik Ole Jensen  4 , Tom Luedde  4 , Johannes Fischer  5 , Wolfram Trudo Knoefel  6 , Hany Ashmawy  6 , Alessia Pedotoa  7 , Kai Kammers  8 , Wilfried Budach  1
Affiliations
Review

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

Jan Haussmann et al. Cancers (Basel). .

Abstract

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.

Keywords: chemotherapy; hyperthermia; network meta-analysis; overall survival; surgery.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The PRISMA flow chart of the literature search.
Figure 2
Figure 2
Overview of the network meta-analysis. Shown are the different treatment modalities with the direct comparisons (solid lines) and indirect comparisons (dashed lines) and the respective number of patients in the direct comparisons. Abbreviations: S = surgery, RT = radiotherapy, CTx = chemotherapy, HTx = hyperthermia, and htCTx = histology tailored chemotherapy.
Figure 3
Figure 3
Forest plot comparing overall survival in the network analysis of the experimental treatments against surgery ± radiation therapy. Hazard ratios with the 95% confidence intervals and the corresponding p-values are presented. The size of the diamonds are proportional to the weights in the meta-analysis. HR = hazard ratio, LCI = lower limit of 95% confidence interval, and HCI = higher limit of 95% confidence interval. Bold values signify statistically significant values.
Figure 4
Figure 4
Forest plot comparing disease-free survival in the network analysis of the experimental treatments against surgery ± radiation therapy. Hazard ratios with 95% confidence intervals and the corresponding p-values are presented. The sizes of the diamonds are proportional to the weights in the meta-analysis. HR = hazard ratio, LCI = lower limit of 95% confidence interval, and HCI = higher limit of 95% confidence interval. Bold values indicate significant p-values.
Figure 5
Figure 5
Forest plot comparing local relapse-free interval in the network analysis of the experimental treatments against surgery ± radiation therapy. Hazard ratios with lower and upper 95% confidence intervals and the corresponding p-values are presented. The sizes of the diamonds are proportional to the weights in the meta-analysis. HR = hazard ratio, LCI = low limit of 95% confidence interval, and HCI = high limit of 95% confidence interval. Bold values indicate significant p-values.
Figure 6
Figure 6
Forest plot comparing distant relapse-free interval in the network analysis of the experimental treatments against surgery ± radiation therapy. Hazard ratios with lower and higher 95% confidence interval and the corresponding p-values are presented. The sizes of the diamonds are proportional to the weights in the meta-analysis. HR = hazard ratio, LCI = lower limit of 95% confidence interval, and HCI = higher limit of 95% confidence interval. Bold values indicate significant p-values.
Figure 7
Figure 7
Forest plot showing the subgroup analysis for adjuvant chemotherapy for the endpoint of overall survival. Presented are hazard ratios with 95% confidence intervals with the corresponding p-values and the interaction tests. The size of the diamonds are proportional to the weights in the meta-analysis. HR = hazard ratio, LCI = lower limit of 95% confidence interval, and HCI = higher limit of 95% confidence interval. Bold values indicate significant p-values.
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References

    1. Davis A.M., O’Sullivan B., Turcotte R., Bell R., Catton C., Chabot P., Wunder J., Hammond A., Benk V., Kandel R., et al. Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma. Radiother. Oncol. 2005;75:48–53. doi: 10.1016/j.radonc.2004.12.020. - DOI - PubMed
    1. O’Sullivan B., Davis A.M., Turcotte R., Bell R., Catton C., Chabot P., Wunder J., Kandel R., Goddard K., Sadura A., et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: A randomised trial. Lancet. 2002;359:2235–2241. doi: 10.1016/S0140-6736(02)09292-9. - DOI - PubMed
    1. Rosenberg S.A., Tepper J., Glatstein E., Costa J., Baker A., Brennan M., DeMoss E.V., Seipp C., Sindelar W.F., Sugarbaker P., et al. The treatment of soft-tissue sarcomas of the extremities: Prospective randomized evaluations of (1) limb-sparing surgery plus radiation therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann. Surg. 1982;196:305–315. doi: 10.1097/00000658-198209000-00009. - DOI - PMC - PubMed
    1. Bonvalot S., Gronchi A., Le Péchoux C., Swallow C.J., Strauss D., Meeus P., van Coevorden F., Stoldt S., Stoeckle E., Rutkowski P., et al. Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): A multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020;21:1366–1377. doi: 10.1016/S1470-2045(20)30446-0. - DOI - PubMed
    1. Kawamoto T., Hara H., Morishita M., Fukase N., Kawakami Y., Takemori T., Fujiwara S., Kitayama K., Yahiro S., Miyamoto T., et al. Prognostic influence of the treatment approach for pulmonary metastasis in patients with soft tissue sarcoma. Clin. Exp. Metastasis. 2020;37:509–517. doi: 10.1007/s10585-020-10038-y. - DOI - PubMed

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