Repeated resections of metastases from different localizations are a strong predictor for prolonged survival. We suggest that the progression-free interval after metastasectomy should be considered as a predictive factor for benefit from further surgery.

Background. Paratesticular liposarcomas are almost always mistakenly diagnosed as inguinal hernias subsequently followed by inadequate operation. Methods. 14 consecutive patients with paratesticular liposarcoma were retrospectively reviewed. Preoperative management was evaluated. Disease-free and overall survival were determined. Results. In 11 patients primary and in 3 patients recurrent liposarcoma of the spermatic cord were diagnosed. Regarding primary treatment in primary surgical intervention resection was radical (R0) in 7 of 14 (50%) patients, marginal (R1) in 6 (43%) patients, and incomplete with macroscopic residual tumour (R2) in 1 (7%) patient. Primary treatment secondary surgical intervention was performed in 4 patients: resection was radical (R0) in 3 (75%) patients and marginal (R1) in 1 (25%) patient. Regarding secondary treatment in recurrent disease resection was marginal (R1) in 3 patients (100%). Final histologic margins were negative in 10 patients with primary disease (71%) and positive in 4 patients with subsequent recurrent disease. After radical resection disease-free survival rates at 3 years were 100%. Overall survival at 4.5 years (54 (18–180) months) was 64%. Conclusion. An incomplete first surgical step increases the number of positive margins leading to local recurrences and adverse prognoses. Aggressive surgery should be attempted to attain 3-dimensional negative margins.

IMPORTANCE Pazopanib and gemcitabine have shown good tolerability, albeit modest single-agent activity in pretreated soft tissue sarcoma. A combined regimen to improve outcomes is required.OBJECTIVE To determine the efficacy of gemcitabine and pazopanib compared with pazopanib alone.DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized phase 2 clinical trial was conducted in Germany from September 2011 to July 2014 and included patients with an Eastern Cooperative Oncology Group performance status score of 0 to 2, adequate organ function, measurable lesion, and progression after at least 1 prior treatment with anthracyclines and/or ifosfamide. Data analysis was performed during 2019 and 2020. INTERVENTIONS Patients were randomized to pazopanib with gemcitabine (A) or without gemcitabine (B).MAIN OUTCOMES AND MEASURES The primary end point was progression-free survival rate (PFSR) at 12 weeks; secondary end points included toxicity, quality of life, overall survival, and response rates.RESULTS A total of 90 patients were randomized, and 86 eligible patients (43 women [50%]) were evaluable, with a median age of 57 (range, 22-84) years and Eastern Cooperative Oncology Group performance status score of 0/1 in 77 participants (90%). The predominant histological subtypes were leiomyosarcoma (22 [26%]) and liposarcoma (16 [19%]). After a median follow-up of 12.4 (range, 1-48) months, the primary end point was met, with a PFSR at 12 weeks of 74% (A) vs 47% (B) (hazard ratio [HR], 1.60; 90% CI, 1.15-2.23; P = .01). In the combination arm, PFSR was significantly longer, with a median of 5.6 vs 2.0 months (HR, 0.58; 95% CI, 0.36-0.92; P = .02) compared with single-agent pazopanib, whereas overall survival was similar, with 13.1 vs 11.2 months (HR, 0.98; 95% CI, 0.60-1.58; P = .83). The objective response rate was overall low, with 11% (A) vs 5% (B) (P = .10). The toxicity of the combination of pazopanib and gemcitabine was increased, but it was manageable and mainly hematological.CONCLUSIONS AND RELEVANCE This phase 2 randomized clinical trial of patients with soft tissue sarcoma found that the addition of gemcitabine to pazopanib was tolerable, and PFSR at 12 weeks was significantly higher compared with pazopanib alone. These results suggest clinical activity of the combination, but they should be confirmed in a phase 3 trial in a more homogeneous population (eg, leiomyosarcoma).

Regorafenib is a multi-target tyrosine kinase inhibitor that has been approved for the treatment of metastatic colorectal cancer, advanced hepatocellular carcinoma, and metastatic gastrointestinal stromal tumors (GIST). Severe hepatobiliary toxicity has been reported in patients with colorectal cancer treated with regorafenib, but not in those with GIST. Therefore, the aim of the present study was to investigate the incidence and clinical course of regorafenib-associated hepatic toxicity (HT) in patients with GIST in a real-world setting. Patients with metastatic GIST treated with regorafenib between September 2012 and May 2014 at three German tertiary care centers were followed up until August 2017. Patient records were retrospectively analyzed and descriptive statistics were employed. HT was defined as alterations in the serum values of aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase and bilirubin (according to the Common Terminology Criteria for Adverse Events, version 4.0), and/or corresponding clinical signs. The time to clinical progression and the overall survival were calculated by Kaplan-Meier curves. Overall, 21 patients were treated with regorafenib and 5 (23.5%) of those heavily pretreated patients suffered from severe HT during regorafenib treatment. In 4 (80%) of these cases, regorafenib treatment was continued, optimizing individual treatment benefit. Clinical monitoring and adequate therapy management are crucial for ensuring continuation of regorafenib treatment in order to achieve an optimal clinical outcome.

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