Combination therapy with Olaratumab/doxorubicin in advanced or metastatic soft tissue sarcoma -a single-Centre experience.

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.

Effective symptom relief through continuous integration of palliative care in advanced renal cell carcinoma patients: comprehensive measurement using the palliative care base assessment.

Background: Due to modern therapies, survival in metastatic renal cell carcinoma (mRCC) has been significantly prolonged. Nevertheless, patients suffering from advanced disease often present with severe symptoms. Early integration of palliative care into anti-cancer treatment has been shown to improve quality of life and may even prolong survival. Therefore, it is recommended to offer palliative care to patients with complex symptoms at the beginning of an advanced disease stage. To our knowledge, so far, no study has been conducted to examine the role of palliative care in patients with mRCC. Objectives: This study aimed to assess the symptom burden and quality of life before and after an inpatient palliative care treatment. Design: The study design is a retrospective observational study. Methods: We included patients with mRCC, who were admitted to our palliative care unit between 2011 and 2017 due to severe symptoms. The symptom burden was assessed at admission, throughout treatment, and at discharge. The evaluation consisted of the palliative care base assessment and daily documentation of relevant symptoms. Results: We evaluated 110 hospitalizations of 58 RCC patients. On average, patients were admitted to the palliative care unit 7 years after initial diagnosis (range 1-305 months). The median age was 70.5 years, 69% of the patients were male, 3% female. The main causes for admission were pain (52%) and dyspnea (26%), and the most frequent patient-reported symptoms were fatigue/exhaustion (87%), weakness (83%), and need for assistance with activities of daily living (83%). Multidisciplinary palliative care treatment led to a significant reduction in the median minimal documentation system (MIDOS) symptom score (15.6-9.9, p < 0.001), the median numeric pain rating scale (3-0, p < 0.001), and a significant reduction in mean ratings of the distress thermometer (5.5-3.1, p = 0.016). Conclusion: Our analysis shows that the integration of palliative care treatment is effective throughout the disease in mRCC and could measurably reduce the symptom burden in our patient population. Palliative care should not be equated with end-of-life care but should rather be integrated throughout advanced disease, particularly as soon as a cure is impossible.

Comorbidities rather than older age define outcome in adult patients with tumors of the Ewing sarcoma family.

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.

Vascular dysfunction following polymicrobial sepsis: role of pattern recognition receptors.

AIMS: Aim was to elucidate the specific role of pattern recognition receptors in vascular dysfunction during polymicrobial sepsis (colon ascendens stent peritonitis, CASP). METHODS AND RESULTS: Vascular contractility of C57BL/6 (wildtype) mice and mice deficient for Toll-like receptor 2/4/9 (TLR2-D, TLR4-D, TLR9-D) or CD14 (CD14-D) was measured 18 h following CASP. mRNA expression of pro- (Tumor Necrosis Factor-α (TNFα), Interleukin (IL)-1ß, IL-6) and anti-inflammatory cytokines (IL-10) and of vascular inducible NO-Synthase (iNOS) was determined using RT-qPCR. Wildtype mice exhibited a significant loss of vascular contractility after CASP. This was aggravated in TLR2-D mice, blunted in TLR4-D animals and abolished in TLR9-D and CD14-D animals. TNF-α expression was significantly up-regulated after CASP in wildtype and TLR2-D animals, but not in mice deficient for TLR4, -9 or CD14. iNOS was significantly up-regulated in TLR2-D animals only. TLR2-D animals showed significantly higher levels of TLR4, -9 and CD14. Application of H154-ODN, a TLR9 antagonist, attenuated CASP-induced cytokine release and vascular dysfunction in wildtype mice. CONCLUSIONS: Within our model, CD14 and TLR9 play a decisive role for the development of vascular dysfunction and thus can be effectively antagonized using H154-ODN. TLR2-D animals are more prone to polymicrobial sepsis, presumably due to up-regulation of TLR4, 9 and CD14.