Thomas Brodowicz’s research while affiliated with Medical University of Vienna and other places

SMARCA4-deficient undifferentiated tumor (SMARCA4-UTs) is an extremely rare and aggressive entity where no consensus on systemic treatment exists to date. We report the case of a 43-year-old woman with thoracic SMARCA4-UT who presented with rapid progression of disease after surgical resection and achieved complete radiologic remission under VDC-IE chemotherapy (vincristine, doxorubicin, and cyclophosphamide [VDC], alternating with ifosfamide and etoposide [IE]). The detailed case report is followed by a brief discussion and overview of current literature.

Simple Summary Older patients ≥ 55 years represent more than 50% of all sarcoma patients and have a worse prognosis compared to younger patients. Age alone should not be a reason to deprive patients of standard treatment with chemotherapy and surgery, provided they are functionally fit enough and willing to take the risk of adverse events. The E-TRAB study evaluated the feasibility and prognostic value of a comprehensive geriatric assessment representing different domains such as activities of daily living, co-morbidities and Patient-Reported Outcomes (PROs) for quality of life (QoL) and treatment tolerability. The study included 69 patients with soft tissue sarcoma (STS) between 55 and 88 years who were unsuited for treatment with anthracyclines and ifosfamide and received trabectedin as first-line therapy. Results show evidence that specific geriatric screening instruments could help predict or limit adverse treatment effects and, thereby, optimize treatment strategies in older STS patients. Abstract E-TRAB was a non-interventional, prospective trial investigating the feasibility and predictive value of geriatric assessments (GA) in older STS patients treated with trabectedin as first-line therapy. Primary endpoints were overall survival (OS), quality of life and individual clinical benefit assessed by the patient-reported outcome measures QLQ-C30 and PRO-CTCAE. Further, several GA tools were applied and correlated with clinical outcomes and treatment-related toxicities. The final analyses included 69 patients from 12 German-speaking sites. The median age of patients was 78 years (range: 55 to 88). Baseline data on PROs and GA identified a diverse population of older patients with respect to their global health status, although a large proportion of them suffered from limitations, required geriatric help and had a high risk of morbidity. The Cancer and Age Research Group (CARG) score classified 38%, 29% and 23% of the patients with low, intermediate and high risks for therapy-related side effects, respectively. Median OS was 11.2 months [95%CI: 5.6; 19.4]. The study confirmed that trabectedin as first-line treatment in older patients with STS has an acceptable and manageable safety profile. Potential prognostic factors for clinical outcome and therapy-related toxicity were identified among the GA tools. Long Timed Up and Go (TUG) showed a significant correlation to OS and early death, whereas a high CARG score (>9) was associated with an increase in unplanned hospitalizations and the incidence of toxicities grade ≥ 3.

Background/aim: Soft tissue sarcomas are rare and heterogenous malignancies with high recurrence rates following resection and a poor prognosis in advanced stages. Eribulin is used in metastatic soft tissue sarcoma patients, who have failed first line chemotherapy and has been approved for patients with pretreated advanced liposarcoma (LPS) in the United States and Europe following the publication of data of a phase III trial. In addition, no data are available for eribulin as postoperative treatment after potentially curative surgery. We, thus, retrospectively evaluated efficacy and tolerability of adjuvant eribulin in patients with LPS not suitable for intensive chemotherapy in the routine clinical setting. Patients and methods: In this retrospective single center analysis, efficacy and safety of eribulin were retrospectively evaluated in five high risk LPS patients. Results: Eribulin as treatment was administered to five patients with LPS following surgical resection. Median progression-free survival and overall survival were 12.3 months and 44.3 months, respectively. Toxicity was generally manageable, and grade 3+4 events were rare. Conclusion: Postoperative eribulin may be feasible in selected high risk LPS patients, who are not candidates for intensive chemotherapy regimens. Further prospective trials, however, are needed.

Introduction Soft tissue sarcomas are rare and heterogenous malignancies with high recurrence rates following resection and a poor prognosis in advanced stages. Eribulin is used in metastatic soft tissue sarcoma patients, who have failed first line chemotherapy and has been approved in patients with pretreated advanced liposarcoma (LPS) in the United States and Europe due to data from a phase III trial. In addition, no data are available for eribulin as postoperative treatment after potentially curative surgery. We have thus retrospectively evaluated efficacy and tolerability of adjuvant eribulin in LPS patients not suitable for intensive chemotherapy in the routine clinical setting. Methods In this retrospective single center analysis, efficacy and safety of eribulin were retrospectively evaluated in 5 high risk LPS patients. Results Eribulin as postoperative treatment following surgical resection was administered to 5 patients with LPS. Median progression free survival (PFS) and overall survival (OS) were 12.3 months (95% CI 5.6–18.9 months) and 44.3 months (3.8–84.8 95% CI), respectively. Toxicity was generally manageable, and grade 3 + 4 events were rare. Conclusions Postoperative eribulin may be feasible in selected high risk LPS patients, who are not candidates for intensive chemotherapy regimens. Further prospective trials, however, are needed.

Background Owing to the rarity and heterogeneity in biology and presentation, there are multiple areas in the diagnosis, treatment and follow-up of soft tissue sarcoma (STS), with no, low-level or conflicting evidence. Methods During the first Consensus Conference on the State of Science in Sarcoma (CSSS), we used a modified Delphi process to identify areas of controversy in the field of sarcoma, to name topics with limited evidence-based data in which a scientific and knowledge gap may remain and a consensus statement will help to guide patient management. We determined scientific questions which need to be addressed in the future in order to generate evidence and to inform physicians and caregivers in daily clinical practice in order to improve outcomes of patients with sarcoma. We conducted a vote on STS key questions and controversies prior to the CSSS meeting, which took place in May 2022. Results Sixty-two European sarcoma experts participated in the survey. Sixteen strong consensus (≥95%) items were identified by the experts, as well as 30 items with a ≥75% consensus on diagnostic, and therapeutic questions. Ultimately, many controversy topics remained without consensus. Conclusions In this manuscript, we summarize the voting results and the discussion during the CSSS meeting. Future scientific questions, priorities for clinical trials, registries, quality assurance, and action by stakeholders are proposed. Platforms and partnerships can support innovative approaches to improve management and clinical research in STS.

Introduction: Soft tissue sarcomas (STS) are rare and heterogenous malignancies with a poor prognosis in advanced disease stages. Eribulin is used in metastatic Liposarcoma (LPS) patients, who have failed first line chemotherapy and has been approved for the use in patients with LPS in the United States and Europe due to its efficacy in this histological subtype in a phase III trial. We have evaluated efficacy and tolerability of eribulin in LPS and Leiomyosarcoma (LMS) patients in the routine clinical setting at our department. Methods: In this retrospective single center analysis, efficacy and safety of eribulin were retrospectively evaluated in advanced LPS and LMS patients at the Division of Oncology, Medical University of Vienna. Results: A total of 32 adult patients treated with eribulin were identified and included in this analysis. Overall response rate (ORR) was 9.4% for all patients, with one patient with LPS and two patients with leiomyosarcoma (LMS) showing a partial response (PR). Disease control rate (PR plus stable disease -SD) for all patients was 50% (LPS: 47.1%; LMS 53.3%). No statistically significant difference in median progression free survival (PFS) and overall survival (OS) was detected between patients with LPS and LMS (p=0.807 and p=0.519), respectively. Patients with LMS (n=2) had received fewer previous therapy lines than patients with LPS (n=14) (≤ previous treatment lines, p < 0.001). Toxicity was generally manageable, and grade 3+4 events were rare. Conclusion: The activity and tolerability of eribulin in LPS as well in LMS patients in the routine clinical setting is comparable to outcomes reported in published phase III trials.

Purpose The aim of this study was to evaluate whether (preoperative) plasma levels of fibrinogen, an essential clotting and acute phase protein, are associated with the prognosis of patients with a liposarcoma, a subtype of sarcoma derived from adipose tissue. Methods We performed a retrospective cohort study of 158 patients with liposarcoma treated at the Department of Orthopaedics of the Medical University of Vienna in Austria from May 1994 to October 2021. Kaplan-Meier curves as well as uni- and multivariable Cox proportional hazard models were performed to evaluate the association between fibrinogen levels and overall survival. Results Elevated fibrinogen was associated with adverse overall survival in cause specific hazards analysis of mortality (hazard ratio [HR] per 10g/L increase: 1,04; 95% CI 1,02–1,06; p < 0,001). This association prevailed in multivariable analysis after adjustment for AJCC tumor stage (HR 1,03; 95% CI 1.01–1.05; p = 0.013). Conclusions Increasing levels of fibrinogen, a routinely available and inexpensive parameter, predicts the risk of mortality in patients with liposarcoma.

11555 Background: Results of the double-blind randomized phase 2 trial (NCT01900743), showed that regorafenib (REG) is an active treatment in patients (pts) previously treated with chemotherapy for an NASTS (cohorts B-leiomyosarcoma, C-synovial sarcoma, D-other sarcoma, Mir 2016), and in pts previously treated with pazopanib (PAZ) (cohort E, Penel 2019). We now present an updated analysis of progression-free survival (PFS) in all NASTS pts to assess the heterogeneity of treatment effect according to histological subtype and prior exposure to PAZ. Methods: Pts received REG 160 mg/d, 21/28 d, or placebo (PB). Pts receiving PB were offered optional cross over in case of centrally confirmed disease progression. The primary endpoint was PFS, according to RECIST-1.1, based on full blinded central review of imaging (including a re-review for cohorts B, C and D, because first analysis was based on a partial central review in these cohorts). Overall survival (OS) was a secondary endpoint. We performed a pooled analysis of cohorts B, C, D and E, on the intent-to-treat dataset, including a multivariate analysis with interaction terms to assess the heterogeneity of treatment effect according to covariates. Results: From 06/2013 to 10/2017, 175 pts were randomized (87 REG vs 88 PB; 56, 27, 55, 37 pts in cohorts B, C, D and E, respectively). The median age was 59 yrs (range, 20-81). There were 101 women (58%). Histological subtype was leiomyosarcoma in 80 pts (LMS; 41 REG vs 39 PB; 56 in cohort B and 24 in cohort E), synovial sarcoma in 28 (SS; 13 REG vs 15 PB; 27 in cohort C and 1 in cohort E), and other sarcoma in 67 (33 REG vs 34 PB; 55 in cohort D and 12 in cohort E). The median number of prior lines of systemic treatment was 2 (range, 1-6). Overall, 43 pts had received prior PAZ (21 REG vs 22 PB). Out of 88 pts assigned to PB, 69 switched to REG after progression (79%). We confirmed a significant PFS-benefit associated with REG in multivariate analysis of the pooled study population, with a HR = 0.48 (95%CI, 0.35–0.66, p < 0.001); median PFS = 2.1 vs 1.0 months, respectively. This benefit appears significant in each histological subtype. However, we observed a borderline interaction between histological subtype and treatment effect (p = 0.09): PFS benefit appears larger in pts with SS (HR = 0.21, 0.10-0.48, p < 0.001) and other sarcoma (HR = 0.49, 0.30-0.81, p = 0.006) than in LMS (HR = 0.59, 0.37-0.93, p = 0.022). PFS benefit appears rather homogeneous across strata of pts with vs without prior exposure to PAZ (interaction test, p = 0.26). Overall, in this study, regorafenib does not show any statistically significant OS-benefit (HR = 0.77, 0.57–1.05, p = 0.10), likely due to the fact that 79% of PB pts crossed over to REG at progression. Conclusions: The present study confirms the clinical PFS benefit associated with regorafenib in all NASTS pts, regardless of prior treatment with pazopanib. Clinical trial information: NCT01900743.

Osteosarcomas are rare malignant bone tumors, most frequently occurring in children as well as adolescents and young adults. Therapy of initially localized disease consists of neoadjuvant chemotherapy followed by surgical resection and adjuvant chemotherapy. Osteosarcomas often present relapses, most commonly lung metastases. Treatment of isolated lung metastasis most commonly includes surgical resection. The correct adjuvant treatment option is still under investigation. In this manuscript we describe the clinical course of an osteosarcoma patient and give a review of the literature regarding current standard treatment for localized as well as pulmonary metastatic disease.