Uncommon presentation of a rare tumour - incidental finding in an asymptomatic patient: case report and comprehensive review of the literature on intrapericardial solitary fibrous tumours

BACKGROUND: A solitary fibrous tumour is a rare, mainly benign spindle cell mesenchymal tumour most commonly originating from the pleura. An intrapericardial location of a solitary fibrous tumour is extremely unusual. We present a case of an asymptomatic patient with a slow-growing massive benign cardiac solitary fibrous tumour. CASE PRESENTATION: A 37-year-old asymptomatic female patient was referred to our hospital with an enlarged cardiac silhouette found on her screening chest X-ray. The echocardiographic examination revealed pericardial effusion and an inhomogeneous mobile mass located in the pericardial sac around the left ventricle. Cardiac magnetic resonance (MRI) examination showed an intrapericardial, semilunar-shaped mass attached to the pulmonary trunk with an intermediate signal intensity on proton density-weighted images and high signal intensity on T2-weighted spectral fat saturation inversion recovery images. First-pass perfusion and early and late gadolinium-enhanced images showed a vascularized mass with septated, patchy, inhomogeneous late enhancement. Coronary computed tomography angiography revealed no invasion of the coronaries. Based on the retrospectively analysed screening chest X-rays, the mass had started to form at least 7 years earlier. Complete resection of the tumour with partial resection of the pulmonary trunk was performed. Histological evaluation of the septated, cystic mass revealed tumour cells forming an irregular patternless pattern; immunohistochemically, the cells tested positive for vimentin, CD34, CD99 and STAT6 but negative for keratin (AE1-AE3), CD31 and S100. Thus, the diagnosis of an intrapericardial solitary fibrous tumour was established. There has been no recurrence for 3 years based on the regular MRI follow-up. CONCLUSION: Intrapericardial SFTs, showing slow growth dynamics, can present with massive extent even in completely asymptomatic patients. MRI is exceedingly useful for characterizing intrapericardial masses, allowing precise surgical planning, and is reliable for long-term follow up

Ultra-rare sarcomas: a consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities

Background Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies.Methods The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra-rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra-rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical-pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan.Results It was agreed that the best criterion for a definition of ultra-rare sarcomas would be incidence. Ultra-rare sarcomas were defined as those with an incidence of approximately <= 1 per 1,000,000, to include those entities whose rarity renders them extremely difficult to conduct well powered, prospective clinical studies. On the basis of this threshold, a list of ultra-rare sarcomas was defined, which comprised 56 soft tissue sarcoma types and 21 bone sarcoma types.conclusions Altogether, the incidence of ultra-rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas. This confirms that the challenges inherent in ultra-rare sarcomas affect large numbers of patients.Experimentele farmacotherapi

Current status of immunotherapy for gastrointestinal stromal tumor

Gastrointestinal stromal tumors (GIST) contain tumor-infiltrating immune cells and their presence provides an opportunity and rationale for developing effective forms of immunotherapy. The types of tumor-infiltrating inflammatory cells and relevant immune checkpoint inhibitors are the focus of active investigation. The most numerous tumor-infiltrating inflammatory cells are tumor-associated macrophages (TAMs) and CD3+ T cells. Studies have shown that patients with GISTs that harbor increased numbers of CD3+ T cells have better outcomes. However, the clinical behavior of GIST has not been shown to correlate with the number of TAMs. The biological significance of other less frequent tumor-infiltrating immune cells including tumor-infiltrating neurtrophils (TINs), natural killer cells (NKs), B cells, dendritic cells (DCs) remains unclear. The immune checkpoint inhibitors CTLA-4, PD1/PDL1 and TIM3/galectin-9 are molecules that can be targeted by synthesized antibodies. Clinical and pre-clinical trials using this approach against immune checkpoint inhibitors, anti-KIT antibody and the generation of chimeric antigen receptor (CAR) T-cells have shown promising results. The treatment of GIST with immunotherapy is complex and evolving; this article reviews its current status for patients with GISTs

RNA helicase DDX3: a novel therapeutic target in Ewing sarcoma

RNA helicase DDX3 has oncogenic activity in breast and lung cancers and is required for translation of complex mRNA transcripts, including those encoding key cell-cycle regulatory proteins. We sought to determine the expression and function of DDX3 in sarcoma cells, and to investigate the antitumor activity of a novel small molecule DDX3 inhibitor, RK-33. Utilizing various sarcoma cell lines, xenografts and human tissue microarrays, we measured DDX3 expression at the mRNA and protein levels, and evaluated cytotoxicity of RK-33 in sarcoma cell lines. To study the role of DDX3 in Ewing sarcoma, we generated stable DDX3-knockdown Ewing sarcoma cell lines using DDX3-specific small hairpin RNA (shRNA), and assessed oncogenic activity. DDX3-knockdown and RK-33-treated Ewing sarcoma cells were compared with wild-type cells using an isobaric mass-tag quantitative proteomics approach to identify target proteins impacted by DDX3 inhibition. Overall, we found high expression of DDX3 in numerous human sarcoma subtypes compared with non-malignant mesenchymal cells, and knockdown of DDX3 by RNA interference inhibited oncogenic activity in Ewing sarcoma cells. Treatment with RK-33 was preferentially cytotoxic to sarcoma cells, including chemotherapy-resistant Ewing sarcoma stem cells, while sparing non-malignant cells. Sensitivity to RK-33 correlated with DDX3 protein expression. Growth of human Ewing sarcoma xenografts expressing high DDX3 was inhibited by RK-33 treatment in mice, without overt toxicity. DDX3 inhibition altered the Ewing sarcoma cellular proteome, especially proteins involved in DNA replication, mRNA translation and proteasome function. These data support further investigation of the role of DDX3 in sarcomas, advancement of RK-33 to Ewing sarcoma clinical trials and development of RNA helicase inhibition as a novel anti-neoplastic strategy

A Dose Finding Study of Temsirolimus and Liposomal Doxorubicin for Patients with Recurrent and Refractory Bone and Soft Tissue Sarcoma

There are few effective therapies for high-risk sarcomas. Initial chemosensitivity is often followed by relapse. In vitro, mTOR inhibition potentiates the efficacy of chemotherapy on resistant sarcoma cells. Although sarcoma trials using mTOR inhibitors have been disappointing, these drugs were used as maintenance. We conducted a Phase I/II clinical trial to test the ability of temsirolimus to potentiate the cytotoxic effect of liposomal doxorubicin and present here the dose-finding portion of this study. Adult and pediatrics patients with recurrent or refractory sarcomas were treated with increasing doses of liposomal doxorubicin and temsirolimus using a continual reassessment method for escalation, targeting a dose-limiting toxicity rate of 20%. Blood samples were drawn before and after the first dose of temsirolimus in Cycles 1 and 2 for pharmacokinetic analysis. The maximally tolerated dose combination was liposomal doxorubicin 30 mg/m 2 monthly with temsirolimus 20 mg/m 2 weekly. Hematologic toxicity was common but manageable. Dose-limiting toxicities were primarily renal. Concurrent administration of liposomal doxorubicin resulted in increased exposure to sirolimus, the active metabolite of temsirolimus. Thus, the combination of liposomal doxorubicin and temsirolimus is safe for heavily pretreated sarcoma patients. Coadministration with liposomal doxorubicin did not alter temsirolimus pharmacokinetics, but increased exposure to its active metabolite

Unmet Medical Needs and Future Perspectives for Leiomyosarcoma Patients-A Position Paper from the National LeioMyoSarcoma Foundation (NLMSF) and Sarcoma Patients EuroNet (SPAEN).

As leiomyosarcoma patients are challenged by the development of metastatic disease, effective systemic therapies are the cornerstone of outcome. However, the overall activity of the currently available conventional systemic treatments and the prognosis of patients with advanced or metastatic disease are still poor, making the treatment of this patient group challenging. Therefore, in a joint effort together with patient networks and organizations, namely Sarcoma Patients EuroNet (SPAEN), the international network of sarcoma patients organizations, and the National LeioMyoSarcoma Foundation (NLMSF) in the United States, we aim to summarize state-of-the-art treatments for leiomyosarcoma patients in order to identify knowledge gaps and current unmet needs, thereby guiding the community to design innovative clinical trials and basic research and close these research gaps. This position paper arose from a leiomyosarcoma research meeting in October 2020 hosted by the NLMSF and SPAEN