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ABSTRACT Purpose This study describes oncological outcomes and investigates prognostic factors for patients with gliosarcomas (GSM). Methods Histopathologically confirmed GSM patients who underwent treatment at five European institutions were retrospectively analyzed. Results We analyzed 170 patients with a median clinical follow‐up time of 9.2 months. The majority received surgery (94.1%), postoperative radiotherapy (pRT, 81.8%), and temozolomide (TMZ)‐based postoperative chemotherapy (66.5%). The median overall survival (OS) and progression‐free survival (PFS) were 12.3 and 6.6 months, respectively. In the multivariable Cox regression analysis (MVA), the following factors were significantly associated with OS: age per year (hazard ratio (HR): 1.03, p

Abstract Background Soft tissue sarcomas (STS) represent a diverse group of rare malignant tumors. Currently, five to six weeks of preoperative radiotherapy (RT) combined with surgery constitute the mainstay of therapy for localized high-grade sarcomas (G2–G3). Growing evidence suggests that shortening preoperative RT courses by hypofractionation neither increases toxicity rates nor impairs oncological outcomes. Instead, shortening RT courses may improve therapy adherence, raise cost-effectiveness, and provide more treatment opportunities for a wider range of patients. Presumed higher rates of adverse effects and worse outcomes are concerns about hypofractionated RT (HFRT) for STS. This systematic review summarizes the current evidence on preoperative HFRT for the treatment of STS and discusses toxicity and oncological outcomes compared to normofractionated RT. Methods We conducted a systematic review of clinical trials describing outcomes for preoperative HFRT in the management of STS using PubMed, the Cochrane library, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Embase, and Ovid Medline. We followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Trials on retroperitoneal sarcomas, postoperative RT, and hyperthermia were excluded. Articles published until November 30th, 2021, were included. Results Initial search yielded 94 articles. After removal of duplicate and ineligible articles, 13 articles qualified for analysis. Eight phase II trials and five retrospective analyses were reviewed. Most trials applied 5 × 5 Gy preoperatively in patients with high-grade STS. HFRT courses did not show increased rates of adverse events compared to historical trials of normofractionated RT. Toxicity rates were mostly comparable or lower than in trials of normofractionated RT. Moreover, HFRT achieved comparable local control rates with shorter duration of therapy. Currently, more than 15 prospective studies on HFRT + / − chemotherapy are ongoing. Conclusions Retrospective data and phase II trials suggest preoperative HFRT to be a reasonable treatment modality for STS. Oncological outcomes and toxicity profiles were favorable. To date, our knowledge is mostly derived from phase II data. No randomized phase III trial comparing normofractionated and HFRT in STS has been published yet. Multiple ongoing phase II trials applying HFRT to investigate acute and late toxicity will hopefully bring forth valuable findings.

Abstract Background Ewing family of tumors (EFT) is rarely diagnosed in patients (pts) over the age of 18 years (years), and data on the clinical course and the outcome of adult EFT pts is sparse. Methods In this retrospective analysis, we summarize our experience with adult EFT pts. From 2002 to 2020, we identified 71 pts of whom 58 were evaluable for the final analysis. Results Median age was 31 years (18–90 years). Pts presented with skeletal (n = 26), and extra‐skeletal primary disease (n =32). Tumor size was ≥8 cm in 20 pts and 19 pts were metastasized at first diagnosis. Between the age groups (≤25 vs. 26–40 vs. ≥41 years) we observed differences of Charlson comorbidity index (CCI), tumor origin, as well as type and number of therapy cycles. Overall, median overall survival (OS) was 79 months (95% confidence interval, CI; 28.5–131.4 months), and median progression‐free survival (PFS) 34 months (95% CI; 21.4–45.8 months). We observed a poorer outcome (OS, PFS) in older pts. This could be in part due to differences in treatment intensity and the CCI (

Abstract Background Standard treatment of soft tissue sarcoma (STS) of the extremities includes limb-sparing surgery combined with pre- or postoperative radiotherapy (RT). The role of perioperative chemotherapy (CTX) remains uncertain. STS patients with high-risk features for local recurrence, distant metastases, and increased mortality may require additional systemic therapy. The objective of this study was to evaluate predictors of outcome regarding local control (LC), overall survival (OS), and freedom from distant metastases (FFDM) in a large single-center cohort of patients suffering from localized high-grade STS (grade 2/3, G2/G3). Special emphasis was put on a subgroup of patients who received combined neoadjuvant radiochemotherapy (RCT). Methods Overall, 115 adult STS patients were included in this retrospective study. The median follow-up was 34 months. Twenty-three patients (20.0%) were treated with neoadjuvant RCT, 92 (80.0%) received other therapies (adjuvant RT alone (n = 58); neoadjuvant CTX + adjuvant RT (n = 17); adjuvant RCT (n = 10), neoadjuvant RT alone (n = 7)). To assess potential prognostic factors on LC, OS, and FFDM, univariate (UVA) and multivariable (MVA) Cox proportional hazards models were applied. Results UVA showed significantly better LC rates in the neoadjuvant RCT group (p = 0.025), with trends in MVA (p = 0.057). The 3-year LC rate was 89.7% in the neoadjuvant RCT group vs. 75.6% in the "other therapies" group. UVA also showed significantly better OS rates in the neoadjuvant RCT group (p = 0.049), however, this was not confirmed in MVA (p = 0.205), the 3-year OS rate was 85.8% for patients treated with neoadjuvant RCT compared to 73.5% in the "other therapies" group. UVA showed significantly better FFDM rates in (p = 0.018) and a trend towards better FFDM rates in MVA (p = 0.059). The 3-year FFDM rate was 89.7% for patients treated with neoadjuvant RCT compared to 65.9% in the "other therapies" group. In the subgroup of patients with G3 STS, neoadjuvant RCT was a significant positive predictor of LC and FFDM in MVA (p = 0.047, p = 0.027) but not for OS. Overall grade 3 and 4 toxicities were significantly higher (p = 0.019) in the neoadjuvant RCT group and occurred in 73.9% vs. 38.0% in patients receiving other therapies. Conclusions The results suggest that neoadjuvant RCT might improve LC and FFDM in patients with localized G3 STS while also being associated with increased acute complication rates. Further prospective research is warranted to confirm these findings.

Abstract Background The antibody targeting platelet-derived growth factor receptor alpha (PDGFRA), olaratumab, was approved in 2016 for metastatic soft tissue sarcoma (STS) in combination with doxorubicin based on promising results of a phase Ib/II trial by the Food and Drug Administration (FDA). However, recently the phase III ANNOUNCE trial could not confirm the additional value of olaratumab in this context. Methods Here, in a retrospective analysis we share our single-centre experience with olaratumab/doxorubicin in STS by including n = 32 patients treated with olaratumab/doxorubicin between 2016 and 2019. Results Median progression-free survival (PFS) in the overall cohort was 3.1 months (range 0.6–16.2). A response [complete remission (CR), partial remission (PR) or stable disease (SD)] was seen in n = 11 (34%) cases, whereas n = 21 (66%) patients showed progressive disease (PD). In n = 9 patients surgery was performed subsequently in an individual therapeutic approach. Out of n = 5 patients receiving additional regional hyperthermia, n = 3 achieved PR or SD. Conclusions This single-centre experience does also not support the promising phase Ib/II results for olaratumab/doxorubicin in STS. However, our findings do not preclude that olaratumab combination therapy could be valuable in a neoadjuvant setting. This warrants further exploration also taking into account the heterogeneous nature of STS.

BackgroundThe Mucin-family protein, MUC1, impacts on carcinogenesis and tumor invasion. We evaluated the impact of MUC1 expression on outcome in a cohort of 158 patients with resected pancreatic ductal adenocarcinomas (PDAC) in the CONKO-001 study (adjuvant gemcitabine [gem] vs. observation [obs]).MethodsThe percentage of MUC1-positive tumor cells by immunohistochemistry (IHC) and the staining intensity were evaluated by two observers blinded to outcome. The numeric values of both parameters were multiplied, resulting in an immunoreactivity score (IRS) ranging from 0 to 12. The level of MUC1 expression was defined as follows: IRS 0–4 (low) vs IRS >4 (high). Outcomes in terms of disease-free (DFS) and overall survival (OS) were evaluated by Kaplan–Meier method, log-rank tests and Cox regressions.ResultsIn total, tumors of 158 study patients were eligible for immunohistochemistry of MUC1. High cytoplasmic MUC1 expression was associated with impaired DFS and OS in the overall study population (hazard ratio (HR) for DFS: 0.49, 95% CI 0.31 to 0.78, p = .003; HR for OS: 0.46, 95% CI 0.29 to 0.73, p = .001). In the study arms, prognostic effects of MUC1 were also evident in the observation group (HR for DFS: 0.55; 95% CI 0.29 to 1.04, p = .062; HR for OS: 0.34, 95% CI 0.17 to 0.67, p = .001) and trending in the gem group (HR for DFS: 0.48, 95% CI 0.24 to 0.95, p = .041; HR for OS: 0.56, 95% CI 0.28 to1.11, p = .093).ConclusionOur data suggest that MUC1 expression is a powerful prognostic marker in patients with PDAC after curatively intended resection.