Background: The 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]).Methods: The 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.Results: In 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).Conclusion: Our data suggest that MUC1 expression is a powerful prognostic marker in patients with PDAC after curatively intended resection.

Soft tissue sarcomas (STSs) are a diverse group of rare malignant soft tissue tumors with a high disease burden. Treatment protocols are complex and, to this day, a precise recommendation for the surgical margin width is lacking. The present study aims to analyze the width of the surgical margins in STS resection specimens and analyze them for local and systemic disease-free survival as well as for most frequent histologic STS subtypes. A total of 169 consecutive patients diagnosed and treated in curative intent in our institution following a primary and localized STS of the extremities or trunk from January 2010 to December 2020 were included in this study regardless of age. Our data reveal that low-grade STSs are best controlled locally by a surgical margin ≥2 mm and in this way also preventing distant metastases effectively. Local recurrence-free survival and metastasis-free survival in high-grade STS were improved by intact muscle fascia or periosteum at the margin when compared only to soft tissue. However, the outcome was independent of the surgical margin width, suggesting a close but negative margin may be safe in high-grade STS subtypes with less invasive growth patterns when combined with adjunct radiochemotherapy.

Background: Primary objective of this present trial was to define the maximum tolerable dose of lapatinib in combination with oxaliplatin, 5-fluorouracil, and folinic acid (OFF) in refractory pancreatic cancer. The secondary objective was to assess the safety and efficacy of lapatinib plus OFF. Methods: We conducted a phase I trial using an accelerated dose escalation design in patients with refractory pancreatic cancer. Lapatinib was given on days 1 to 42 in combination with folinic acid 200 mg/m² day + 5-fluorouracil 2000 mg/m² (24 h) on days 1, 8, 15, and 22, and oxaliplatin 85 mg/m² days 8 and 22 of a 43-day cycle (OFF). Toxicity and efficacy were evaluated. Results: In total, eighteen patients were enrolled: dose level 1 (1000 mg) was assigned to seven patients, dose level 2 (1250 mg), five patients; and dose level 3 (1500 mg), six patients. Dose-limiting toxicities were diarrhea and/or neutropenic enterocolitis observed in two of six patients: one diarrhea III°, one diarrhea IV°, as well as neutropenic enterocolitis. The maximum tolerable dose of lapatinib was 1250 mg OD. Conclusions: The combination of lapatinib 1250 mg OD with platinum-containing chemotherapy is safe and feasible in patients with refractory pancreatic cancer and warrants further investigation.

Sarcopenia is a known negative prognostic factor in oncology, yet its role in osteosarcoma remains unclear. This study evaluated CT-based body composition changes and their association with survival and functional outcomes in adult osteosarcoma patients undergoing chemotherapy and surgery. We retrospectively analyzed 36 patients (mean age 44.2 ± 19.0 years) with histologically confirmed, non-metastatic osteosarcoma (TNM N0M0) and at least two CT scans. Skeletal Muscle Index (SMI), Paraspinal Muscle Index (PSMI), Psoas Muscle Index (PMI), Skeletal Muscle Density (SMD), and Visceral Adipose Tissue (VAT) were measured at the L3 level. Patients were stratified by baseline sarcopenia (using established SMI cut-offs) and by ≥ 25 % vs. <25 % SMI loss. Survival was assessed using Kaplan-Meier curves and Cox regression adjusted for age, sex, ECOG, tumor necrosis, margin, and tumor size. All CT-morphometric parameters declined significantly over time (p < 0.01). Baseline sarcopenia predicted poorer survival (HR 1.30, p = 0.014). A ≥25 % SMI reduction was associated with significantly worse survival (HR 1.70, p = 0.014) and poorer functional status (higher ECOG, p < 0.01). Patients with high tumor activity (elevated LDH, CRP, AP) experienced greater muscle and fat loss (p < 0.01). Baseline sarcopenia and progressive SMI loss are independent predictors of poor survival in osteosarcoma patients. Severe muscle loss is also linked to functional decline. Routine CT-based body composition assessment may enhance risk stratification and guide supportive care strategies.

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 includingn = 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 inn = 11 (34%) cases, whereasn = 21 (66%) patients showed progressive disease (PD). Inn = 9 patients surgery was performed subsequently in an individual therapeutic approach. Out ofn = 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.

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 (<3 vs. ≥3; hazard ratio, HR 0.334, 95% CI 0.15–0.72, p = 0.006). In addition, tumor stage had a significant impact on PFS (localized vs. metastasized stage: HR 0.403, 95% CI 0.18–0.87, p = 0.021).Conclusions: Our data confirms the feasibility of intensive treatment regimens in adult EFT pts. While in our cohort outcome was influenced by age, due to differences in treatment intensity, CCI, and tumor stage, larger studies are warranted to further explore optimized treatment protocols in adult EFT pts.