[Current therapeutic standards in advanced soft tissue sarcomas]. / Neues zu Weichteilsarkomen.

Soft tissue sarcomas account for less than 1% of tumors in adults. With more than 80 different subtypes and often dismal prognosis, treatment of patients with soft tissue sarcomas is diagnostically and therapeutically complex. In patients with localized disease, surgery remains the mainstay of therapy. A multimodal approach consisting of neoadjuvant chemotherapy +/- regional hyperthermia may be suitable in patients with high-risk disease to maximize tumor shrinkage before surgery and to treat micrometastases. In patients with oligometastatic disease, local treatment options should be discussed within a specialized tumor board. In patients with disseminated metastatic disease, chemotherapy with anthracyclines remains the backbone of therapy. Immune checkpoint inhibitors have proven to be effective for patients with alveolar soft part sarcoma and targeted therapies with NTRK-inhibitors should be evaluated in patients with NTRK-fusions. This article focuses on current standards and developments in the treatment of soft tissue sarcomas.

Differentiation of benign and metastatic lymph nodes in soft tissue sarcoma.

Lymph node metastasis (LNM) occurs in less than 5% of soft tissue sarcoma (STS) patients and indicates an aggressive course of disease. Suspicious lymph nodes (LN) in staging imaging are a frequent topic of discussion in multidisciplinary tumor boards. Predictive markers are needed to facilitate stratification and improve treatment of STS patients. In this study, 56 STS patients with radiologically suspicious and subsequently histologically examined LN were reviewed. Patients with benign (n = 26) and metastatic (n = 30) LN were analyzed with regard to clinical, laboratory and imaging parameters. Patients with LNM exhibited significantly larger short axis diameter (SAD) and long axis diameter (LAD) vs. patients with benign LN (median 22.5 vs. 14 mm, p < 0.001 and median 29.5 vs. 21 mm, p = 0.003, respectively). Furthermore, the presence of central necrosis and high maximal standardized uptake value (SUVmax) in FDG-PET-CT scans were significantly associated with LNM (60 vs. 11.5% of patients, p < 0.001 and median 8.59 vs. 3.96, p = 0.013, respectively). With systemic therapy, a slight median size regression over time was observed in both metastatic and benign LN. Serum LDH and CRP levels were significantly higher in patients with LNM (median 247 vs. 187.5U/L, p = 0.005 and 1.5 vs. 0.55 mg/dL, p = 0.039, respectively). This study shows significant associations between LNM and imaging features as well as laboratory parameters of STS patients. The largest SAD, SUVmax in FDG-PET-CT scan, the presence of central necrosis, and high serum LDH level are the most important parameters to distinguish benign from metastatic LNs.

Implementing precision oncology for sarcoma patients: the CCCLMUmolecular tumor board experience.

PURPOSE: Due to poor outcomes and limited treatment options, patients with advanced bone and soft tissue sarcomas (BS/STS) may undergo comprehensive molecular profiling of tumor samples to identify possible therapeutic targets. The aim of this study was to determine the impact of routine molecular profiling in the setting of a dedicated precision oncology program in patients with BS/STS in a German large-volume sarcoma center. METHODS: 92 BS/STS patients who received comprehensive genomic profiling (CGP) and were subsequently discussed in our molecular tumor board (MTB) between 2016 and 2022 were included. Patient records were retrospectively reviewed, and the clinical impact of NGS-related findings was analyzed. RESULTS: 89.1% of patients had received at least one treatment line before NGS testing. At least one molecular alteration was found in 71 patients (82.6%). The most common alterations were mutations in TP53 (23.3% of patients), followed by PIK3CA and MDM2 mutations (9.3% each). Druggable alterations were identified, and treatment recommended in 32 patients (37.2%). Of those patients with actionable alterations, ten patients (31.2%) received personalized treatment and six patients did benefit from molecular-based therapy in terms of a progression-free survival ratio (PFSr) > 1.3. CONCLUSION: Our single-center experience shows an increasing uptake of next-generation sequencing (NGS) and highlights current challenges of implementing precision oncology in the management of patients with BS/STS. A relevant number of patients were diagnosed with clinically actionable alterations. Our results highlight the potential benefit of NGS in patients with rare cancers and currently limited therapeutic options.

TIM-3 Qualifies as a Potential Immunotherapeutic Target in Specific Subsets of Patients with High-Risk Soft Tissue Sarcomas (HR-STS).

(1) Background: The expression of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), an immune checkpoint receptor on T cells, has been associated with dismal outcomes and advanced tumor stages in various solid tumors. The blockade of TIM-3 is currently under examination in several clinical trials. This study examines TIM-3 expression in high-risk soft tissue sarcomas (HR-STS). (2) Methods: Tumor cell expression of TIM-3 on protein level was analyzed in pre-treatment biopsies of patients with HR-STS. TIM-3 expression was correlated with clinicopathological parameters including tumor-infiltrating lymphocyte (TIL) counts, programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PDL-1) expression in patients with HR-STS. Survival dependent on the expression of TIM-3 was analyzed. (3) Results: TIM-3 expression was observed in 101 (56%) out of 179 pre-treatment biopsies of patients with HR-STS. TIM-3 expression was significantly more often observed in undifferentiated pleomorphic sarcomas (UPS) compared to other histological subtypes (p < 0.001), high TIL counts (p < 0.001), and high PD-1 (p < 0.001) and PD-L1 expression (p < 0.001). TIM-3 expression did not have a prognostic impact on survival in patients with HR-STS. (4) Conclusions: This is the first study to demonstrate a significant tumor cell expression of TIM-3 in specific subsets of patients with HR-STS. TIM-3 qualifies as a potential immunotherapeutic target in HR-STS.

Expression Patterns of TOP2A and SIRT1 Are Predictive of Survival in Patients with High-Risk Soft Tissue Sarcomas Treated with a Neoadjuvant Anthracycline-Based Chemotherapy.

Molecular predictors of response to chemotherapy and survival have not been put into clinical practice in high-risk soft tissue sarcomas (HR-STS) by now. The expression of TOP2A and SIRT1 has implications for the mechanism of action of doxorubicin, which is the backbone of chemotherapy in HR-STS. Pre-treatment samples of 167 patients with HR-STS were collected. Protein expression levels of TOP2A and SIRT1 were evaluated with tissue microarrays and immunohistochemistry and correlated with clinicopathological parameters, including overall survival (OS). The expression of TOP2A and SIRT1 was seen in 47% and 60% of patients with HR-STS, respectively. TOP2A expression was associated with higher tumor grading and shorter 5-year OS. The expression of SIRT1 was correlated with a better 5- and 10-year OS. The combination of high SIRT1 and low TOP2A ("Top survivors") significantly predicted a better OS compared to other biomarker combinations. A multivariate analysis confirmed the expression of SIRT1 and the "Top survivor" biomarker combination as independent predictive factors of OS. This is the first study to associate SIRT1 overexpression with a statistically significant prolongation of OS in HR-STS. Both individual markers and their combination can be used as predictive indicators for HR-STS patients scheduled for neoadjuvant anthracycline-based chemotherapy.

The Impact of a Nanocellulose-Based Wound Dressing in the Management of Thermal Injuries in Children: Results of a Retrospective Evaluation.

The aim of this retrospective study is to evaluate for the first time the impact of a nanocellulose-based wound dressing in the treatment of pediatric patients with both partial- and deep-thickness burns. Usability and effectiveness were defined based on parameters such as frequency of dressing changes under narcosis, duration of hospital stay, onset of complications, need for additional treatments, and follow up scar formation assessment. Fifty-six children who sustained burns in the year 2018 and were treated with a nanocellulose-based wound dressing were included in the trial. The mean stay in hospital was 6.7 days. Patients underwent dressing changes under narcosis 2.4 times on average, and none had wound-associated infection. In all, 82% of the patients were treated only with nanocellulose-based wound dressings, and reepithelialization occurred after ten days. The majority of patients had scars with normal pigmentation (98%), vascularization (91%), height (92%), and pliability (92%). In conclusion, using a nanocellulose-based wound dressing for the treatment of both superficial, partial-thickness and deep, full-thickness burns has several advantages. Compared with the results published in literature on other wound dressings, it requires a moderate number of dressing changes under narcosis and results in short hospital stays. Additionally, it has a low associated infection rate and promotes wound healing.