Soft tissue sarcomas are a heterogeneous group of malignant tumours, accounting for the fifth most common paediatric cancer. Next-generation sequencing-based (NGS) comprehensive genomic profiling (CGP) of paediatric soft tissue sarcomas tumours associated with a poor prognosis can identify actionable biomarkers and determine prognostic and therapeutic stratification of patient management. Diagnostic samples of 20 patients diagnosed with various paediatric sarcomas were investigated using a CGP assay (Illumina TruSight Oncology 500). The identified single nucleotide variants, small insertions or deletions, copy number alterations, gene fusions, microsatellite stability status, and the tumour mutation burden were analysed. Using Clinical insight (Qiagen) and PierianDx (Pierian) software, actionable variants were determined. Our study revealed potentially actionable alterations for therapeutic intervention in 75% of cases (15/20). Novel variants were detected in several tumour entities which have not previously been published. All cases were characterised by low tumour mutation burden, with none of the cases characterised by microsatellite instability. The targetable gene fusions included three NTRK fusions, TFG-ROS1, ROS1-GIT2 and EML4-ALK fusions. The most frequent copy number alterations affected the CDK4, ALK and FGFR1 genes, identified in 28.6% (4/20), 14.3% (2/14) and 14.3% (2/14) of the cases, respectively. Single nucleotide variants were detected in 7 genes, including ALK, CHEK2, ESR1, FANCL, MET, NBN and NRAS, across six cases. Based on the NGS results, targeted therapy was prescribed in 5 cases (tazemetostat in epithelioid sarcoma, entrectinib in inflammatory myofibroblastic tumour and infantile fibrosarcoma, larotrectinib in angiosarcoma and infantile fibrosarcoma). At least partial remission was achieved in all patients receiving targeted therapies. In our study, routine application of the TSO500 CPG assay led to administration of targeted therapies in 25% of the patients with at least partial clinical response in this patient cohort.

Hafnium oxide nanoparticles (NBTXR3) activated by radiotherapy (RT) increase radiation dose deposit within cancer cells compared to RT alone. Currently 7 clinical trials are underway to evaluate NBTXR3+RT. To date, no dose limiting toxicities (DLTs) have been observed. Given that RT can prime an anti-tumor immune response we hypothesized that this response could be enhanced by NBTXR3+RT in both animals and humans. Immunocompetent mice were injected in both flanks with CT26 cells. An intratumoral injection of NBTXR3 (or vehicle) was performed in right flank tumors, followed by RT (3x4Gy). Tumor growth was followed, and animals sacrificed when tumors reached 800mm3. Alternatively, tumors were collected 3 days after last RT fraction and immune cell infiltrates analyzed by immunohistochemistry (IHC). Pts with locally advanced soft tissue sarcoma (STS) [NCT02379845] received either NBTXR3+RT or RT alone. Pre- and post-treatment tumor tissues (biopsy and tumor resection respectively) from pts were analyzed by IHC and Digital Pathology for immune biomarkers (>16 pts per arm). Animal studies demonstrated that NBTXR3+RT can induce an immune response which was not observed with RT alone. IHC analyses showed that significantly more CD8+ cells were present in NBTXR3+RT treated and untreated tumors, compared to tumors from mice treated with RT alone. Similarly, increased CD8+ T cell infiltration pre- vs post-treatment was observed in tumor tissues from STS pts treated with NBTXR3+RT. An increase in biomarkers, including CD8 and PD1, following NBTXR3 +RT was also observed by IHC in tumor samples from STS pts compared to RT alone. These results demonstrate that NBTXR3+RT induces a specific adaptive immune profile in both mice and STS pts. As such, it may convert immunologically "cold" tumors into "hot" tumors, opening the potential for combination with immunotherapeutic agents. We have therefore sought to investigate the safety and systemic effect of NBTXR3 activated by stereotactic ablative radiotherapy (SABR) in combination with anti-PD-1 antibody in pts with locoregionally recurrent or metastatic (to lung or liver) head and neck squamous cell carcinoma (HNSCC), as well as in metastatic non-small cell lung cancer (NSCLC) and liver metastasis patients [NCT03589339].

Capsule endoscopy is a relatively safe and sensitive examination in detecting small intestinal bleeding and mass-like lesions. We aimed to evaluate small intestinal mass-like cases among patients who underwent capsule endoscopy with MiroCam system in the 2nd Department of Internal Medicine during 2014. The age range of total 54 cases, who underwent capsule endoscopy in 2014, was 17 – 84 years (mean: 56.2), 35 were female, 19 were male. All cases were referred to our clinic to assess the cause of obscure gastrointestinal bleeding, and all underwent careful workup on gastrointestinal bleeding by esophagogastroduodenoscopy and colonoscopy. Five (9.3%) out of 54 had small intestinal mass-like lesion. All had histopathological confirmation following surgical resection. 1st case, 65 year old female had direct progression of colonic adenocarcinoma to small intestine at multiple sites. 2nd case, 69 year old female had grade I small intestinal adenocarcinoma causing severe stenosis. 3 rd case, 65 year old male previously diagnosed and treated for metastatic GIST tumor had his primary tumor been found. 4th case, 43 year old male had clear cell sarcoma of the ileum. 5th case, 64 year old female had a Masson's hemangioma. Masson's hemangioma, also known as intravascular papillary endothelial hyperplasia (IPEH), is a sporadic disease with either benign dermal/mucosal presentation or rarely as major GI bleeding. In the literature 10 gastrointestinal IPEH has been reported, out of which 4 were found in the small intestine presenting with melena. Here we report a 64 year old woman who was referred to our clinic to perform microcytic anemia workup caused by obscure gastrointestinal bleeding. On capsule endoscopy we observed an intraluminal polyp-like mass in the mid small intestine with superficial ulceration and fresh coagulum. Small intestinal bowel resection resolved the obscure bleeding symptoms. Pathologic examination of the surgical specimen showed IPEH after careful exclusion of other vascular malformations, i.e. angiosarcoma. To our knowledge, the pathognomonic feature of IPEH during capsule endoscopy has not yet been described in medical literature, here we present its feature. Capsule endoscopy can be a useful guide in further endoscopic or surgical treatment of intestinal mass like lesions.

Introduction: Kaposi sarcoma (KS) is a low-grade vascular tumor associated with human herpesvirus-8 infection (HHV-8). Gastrointestinal (GI) involvement can precede, with or without the appearance of skin lesions. 4 forms of this disease have been described. HHV-8 has been detected in all type of Kaposi sarcoma. The third type is the transplant- or immunsuppression-associated variant of Kaposi sarcoma with corresponding lesions. The primary diagnosis of Kaposi sarcoma in the GI tract should be considered in elderly men from specific geographic regions, and in immunosuppressed and AIDS patients. Although, GI KS is usually asymptomatic, but may present with gastric complains, small bowel intussusceptions or bleeding.

Angiosarcoma is a rare entity, comprising less than 1% of all sarcomas. Epithelioid angiosarcoma with the epithelioid appearance of their cells is a unique morphologic subtype, where the cells carry both the epithelial and the mesenchymal differentiation markers. Considering the location they arise predominantly in the deep soft tissue, but skin and visceral organs are also mentioned as primary sites. Epithelioid angiosarcoma spreads in an early phase to the lymphnodes and to the solid organs. Treatment modalities include surgical resection, radiotherapy and paclitaxel-based chemotherapy. Despite all therapeutic approaches more than 50% of the patients are dead within 2 to 3 years from diagnosis.

Cancer diseases are one of the most lethal, incurable diseases today, thus fighting cancer is an actual and urgent problem in clinical practice. Beside classical therapies, a new approach is represented by model-based therapies, where human body works as a complex system. These therapies are called targeted molecular therapies (TMTs). TMTs are fighting specifically against different cancer mechanisms and usually don't eliminate the whole tumor, but control the tumor into a given state and keep it there. The aim of antiangiogenic cancer therapy is to prevent tumors from forming new blood vessels, because without angiogenesis tumor growth is inhibited. In this paper we analyze a nonlinear tumor growth model and design linear controllers based on a linear model acquired from working point linearization. Realized controllers are state feedback with pole placement, LQ control method and both controllers with state observer. Simulations are carried out and the controllers are analyzed in many aspects, including the working points used at linearization.