scispace - formally typeset
Search or ask a question
Author

Valeriya Semenisty

Bio: Valeriya Semenisty is an academic researcher from Technion – Israel Institute of Technology. The author has contributed to research in topics: Internal medicine & Acne. The author has an hindex of 3, co-authored 4 publications receiving 53 citations.
Topics: Internal medicine, Acne, Pazopanib, Rash, Malignancy

Papers
More filters
Journal ArticleDOI
TL;DR: This case is the first to report objective, long-lasting response to pazopanib in metastatic pulmonary epithelioid hemangioendothelioma, a rare vascular tumor of borderline or low-grade malignancy.
Abstract: Epithelioid hemangioendothelioma is a rare vascular tumor of borderline or low-grade malignancy. The lungs and liver are the two common primary organs affected. Metastatic disease was reported in more than 100 cases in the literature. However, no firm conclusions can be determined for recommended treatment options. The current case presents a patient with metastatic pulmonary epithelioid hemangioendothelioma to the cervical and mediastinal lymph nodes, lungs and liver that has been treated with pazopanib for more than two years with PET avid complete metabolic response in the mediastinum and lungs, and long-lasting stable disease. Target therapies that block VEGFR have a logical base in this rare malignancy. The current case is the first to report objective, long-lasting response to pazopanib.

51 citations

Journal ArticleDOI
TL;DR: A novel CXCR4 antagonist being developed for multiple oncology indications that increases the number of immune cells in peripheral blood and promotes CD8+ T cell infiltration into orthotropic pancreatic mouse tumors, reducing tumor load is evaluated in patients with metastatic pancreatic cancer.
Abstract: 88Background: BL-8040 is a novel CXCR4 antagonist being developed for multiple oncology indications. Preclinical studies demonstrated that BL-8040 increases the number of immune cells in peripheral blood and promotes CD8+ T cell infiltration into orthotropic pancreatic mouse tumors, reducing tumor load. BL-8040 is being evaluated in a Phase 2a, multicenter, open label trial in patients with metastatic pancreatic cancer (the COMBAT study). Patients are undergoing a 5-day period of monotherapy in which they receive daily doses of BL-8040, followed by 21-day cycles in which patients receive one dose of pembrolizumab and 3 doses/week of BL-8040 until disease progression or discontinuation. To date, 32 patients have been enrolled. Methods: On Day 1 and Day 5, blood samples were taken at pre- and post-dosing, to evaluate peripheral immune cell subset frequency by flow cytometry. In addition, core biopsies were taken from liver metastases, where possible, to assess immune cell infiltration into tumors and the tu...

6 citations

Journal ArticleDOI
TL;DR: This multicenter retrospectively evaluated real-life clinical experience with molecular profiling-guided therapy in metastatic gastric and oesophageal cancer in Israel found promising results.
Abstract: e15537Background: We evaluated real-life clinical experience with molecular profiling (MP)-guided therapy in metastatic gastric and oesophageal cancer in Israel Methods: This multicenter retrospect...

3 citations

Journal ArticleDOI
TL;DR: Whether acne vulgaris in adolescence (AinA) is predictive of a cetuximab-related rash to better understand the pathogenesis of this side effect and explore potential preventive actions is determined and the correlation between PPI treatment and severe skin toxicity related to cetUXimab is examined.
Abstract: Cetuximab, a monoclonal antibody, is a part of the treatment for metastatic colorectal cancer. The most common side effect of cetuximab is skin rash, which has a similar distribution to acne vulgaris and some overlapping pathophysiological mechanisms. The aim of the current study was to determine whether acne vulgaris in adolescence (AinA) is predictive of a cetuximab-related rash to better understand the pathogenesis of this side effect and explore potential preventive actions. From July 2013 to June 2015, patients with metastatic colorectal cancer planned for treatment with cetuximab were enrolled in the study. Before initiating treatment, patients completed a questionnaire evaluating endocrine disorders, other chronic diseases, smoking, chronic medications, allergies, and dermatologic history of AinA and its severity. Patients were followed for 6 months. Data were collected from 32 participants (16 women, 16 men). Twenty-three (69%) patients experienced a cetuximab-associated skin reaction. Nine (28%) patients had a history of AinA. Of these, seven developed a cetuximab-associated skin reaction. Three of the five (60%) patients who used proton pump inhibitors (PPIs) developed severe (grades 3-4) skin toxicity versus 4/27 (15%) patients who were not on PPIs (P=0.057). The degree of skin toxicity correlated to the median time-to-tumor-progression: 2 months for patients with grades 0-1 compared with 5.5 months for grades 2-4 skin toxicity (P=0.047, 95% confidence interval 1.06-4.95). No significant correlation was found between AinA and cetuximab-associated skin reactions. The correlation between PPI treatment and severe skin toxicity related to cetuximab should be examined further.

2 citations

Journal ArticleDOI
TL;DR: In this article , the combination of intratumoral TLR9 agonist, radiosurgery and dual PD-1 and CTLA-4 blockade was found to induce a local focus of immune stimulation, evoking a systemic immune response.
Abstract: 123 Background: Microsatellite stable (MSS) or mismatch repair proficient (MMR-P) metastatic colorectal cancer is refractory to immune checkpoint inhibition. We hypothesized that a combination of intratumoral TLR9 agonist, radiosurgery and dual PD-1 and CTLA-4 blockade would induce a local focus of immune stimulation, evoking a systemic immune response. Methods: In this single institution investigator-initiated phase I study, patients with MSS / MMR-P metastatic colorectal cancer were treated with a priming dose of subcutaneous (s.c.) vidutolimod, three intratumoral injections of vidutolimod, and radiosurgery to a metastasis, combined with nivolumab 3mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. Following conclusion of intratumoral therapy, s.c. injections of vidutolimod commenced. Efficacy endpoints were based upon a non-irradiated and non-injected lesion. Cytokine levels were measured at baseline and at 7 (± 2) weeks. Patients were placed in 4 cohorts: (1) Safety run-in without radiosurgery (No RT); (2) Radiosurgery prior to intratumoral therapy (Early Liver RT Slow). An amendment was made due to early patient fall-out due to progressive disease; (3) Radiosurgery prior to intratumoral therapy with a condensed timeline (Early Liver RT Quick). An additional amendment was made due to unacceptable liver toxicity; (4) Radiosurgery to extrahepatic lesion following completion of intratumoral therapy (Late Extrahepatic RT). ClinicalTrials.gov Identifier NCT03507699. Results: A total of 19 patients were accrued (No RT, n=2; Early Liver RT Slow, n=7; Early Liver RT Quick, n=4; Late Extrahepatic RT, n=6). Median age was 59 years (range 40-71), 68% were male, median number of previous systemic treatments was 3 (range 2 – 5). None of the patients responded, aside from one patient in cohort #4 who achieved complete response, and was subsequently found to have a high tumor mutational burden (TMB) 79 mutations / Mb. Grade 3 liver toxicity, including elevated transaminases and hyperbilirubinemia, was reported in 0%, 0%, 75% and 17% in cohorts 1-4, respectively. Reactions following intratumoral injections, typically within 12 hours, included fever (68%), tachycardia (21%), chills (63%) and hypotension (47%). There was an increase in systemic CXCL10 levels at 7 (± 2) weeks compared to baseline, with a median of 407 versus 78 pg/ml, respectively, p<0.01. Conclusions: Intratumoral liver injection of vidutolimod was associated with acute systemic symptoms attributed to cytokine release. The juxtaposition of liver irradiation and intratumoral vidutolimod injection to the same lesion was associated with unacceptable hepatic toxicity. The combination of intratumoral vidutolimod, radiosurgery, nivolumab and ipilimumab was not found to be efficacious in MSS / MMR-P colon cancer. Clinical trial information: NCT03507699 .

Cited by
More filters
Journal ArticleDOI
TL;DR: There is evidence to support the use of chemotherapeutics and targeted therapies specifically focusing on anti-angiogenesis, and the current landscape of oncology with the emergence and excitement of immunotherapy could also translate in a role for immunotherapy in this disease.
Abstract: Epithelioid hemangioendothelioma (EHE) is an extremely rare sarcoma, as such it can pose a clinical dilemma based solely on its rarity. Also, the spectrum of disease varies greatly between an indolent disease and aggressive disease with widespread metastases. In our clinical practice, the primary focus has been to get a handle on the aggressive nature of the disease, which will then dictate how urgently one needs to treat the patient. Pathological review with immunohistochemistry and molecular characterization is paramount. Our treatment strategy is watch-and-wait versus active therapy on clinical trial or based on results of prior clinical trials. There is evidence to support the use of chemotherapeutics and targeted therapies specifically focusing on anti-angiogenesis. The current landscape of oncology with the emergence and excitement of immunotherapy could also translate in a role for immunotherapy in this disease. While rare, there is certainly no reason that research and trials for patients with EHE should not remain on utmost importance for those of us who specialize in the treatment of sarcomas.

91 citations

Journal ArticleDOI
TL;DR: A clinical benefit was achieved in 56 % of patients receiving sirolimus, which lasted >24 months in four patients, and most patients with pleural effusion did not benefit from siro Limus and had a poor outcome.
Abstract: The aim of this study was to report on sirolimus activity in a series of patients with hemangioendothelioma (HE) treated at the National Cancer Institute, Milan (Istituto Nazionale Tumori; INT) and within the Italian Rare Cancer Network (“Rete Tumori Rari”; RTR). We retrospectively reviewed patients with advanced and progressing epithelioid hemangioendothelioma (EHE) treated with sirolimus at the INT and/or within the RTR. Pathologic review and molecular analysis for WWTR1 rearrangement were performed. Sirolimus was administered until unacceptable toxicity or progression, with the dose being adjusted to reach target plasma levels of 15–20 ng/dL. Responses were assessed using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Since 2005, 18 patients (17 EHE, 1 retiform HE; 1 locally advanced, 17 metastatic; WWTR1 rearrangement: 16) have been identified, with 17/18 patients being evaluable for response. Mean sirolimus daily dose was 4.5 mg. According to RECIST, best responses in EHE were 1 partial response (PR), 12 stable disease (SD), and 3 progressive disease (PD); the patient with retiform HE also achieved a PR, lasting >2 years. Four patients with a reversed interval progression on interruption were observed. Median overall survival was 16 months, and median progression-free survival was 12 months (range 1–45), with four patients progression-free at 24 months. The clinical benefit (complete response [CR] + PR + SD >6 months) was 56 %. Seven patients receiving sirolimus experienced an increase in pleural/peritoneal effusion plus worsening of tumor-related symptoms; six of these patients died within 1–8 months from evidence of effusion progression, while a RECIST PD was assessed in two of seven patients. A clinical benefit was achieved in 56 % of patients receiving sirolimus, which lasted >24 months in four patients. Most patients with pleural effusion did not benefit from sirolimus and had a poor outcome.

51 citations

Journal ArticleDOI
Silvia Stacchiotti, Aisha Miah1, A.M. Frezza, Christina Messiou1, Carlo Morosi2, Augusto Caraceni, Cristina R. Antonescu3, Jyoti Bajpai4, Elizabeth H. Baldini5, Sebastian Bauer6, R. Biagini, Stefan S. Bielack, Jean-Yves Blay7, Sylvie Bonvalot8, Ioannis Boukovinas, Judith V.M.G. Bovée9, Kjetil Boye10, Thomas Brodowicz, Dario Callegaro, E. de Álava11, M. Deoras-Sutliff, Armelle Dufresne7, Mikael Eriksson12, C. Errani, A. Fedenko, Virginia Ferraresi, Andrea C. Ferrari, Christopher D.M. Fletcher5, X. Garcia del Muro13, Hans Gelderblom9, Rebecca A. Gladdy14, François Gouin, Giovanni Grignani, J. Gutkovich, Rick L. Haas9, Rick L. Haas15, Nadia Hindi11, Peter Hohenberger16, Paul H. Huang1, Heikki Joensuu17, Robin L. Jones1, C. Jungels18, Bernd Kasper16, Akira Kawai, A. Le Cesne19, F. le Grange20, Andreas Leithner21, H. Leonard, A. Lopez Pousa, J. Martin Broto, O. Merimsky22, P. Merriam23, Rosalba Miceli, Olivier Mir19, M. Molinari24, Michael Montemurro25, G. Oldani, Emanuela Palmerini, Maria Abbondanza Pantaleo, Shreyaskumar Patel26, Sophie Piperno-Neumann27, Chandrajit P. Raut23, Chandrajit P. Raut5, V. Ravi26, Albiruni Ryan Abdul Razak28, Peter Reichardt, Brian P. Rubin29, Piotr Rutkowski, Akmal Safwat30, Claudia Sangalli, G. Sapisochin31, Marta Sbaraglia, Susanne Scheipl32, Patrick Schöffski33, Dirk C. Strauss1, Sandra J. Strauss34, K. Sundby Hall10, William D. Tap3, Annalisa Trama, A. Tweddle1, W.T.A. van der Graaf15, M. A. J. van de Sande9, W.J. van Houdt15, G. van Oortmerssen35, Andrew J. Wagner23, M. Wartenberg, J. Wood36, Nadia Zaffaroni, C. Zimmermann28, Paolo G. Casali, A. P. Dei Tos, Alessandro Gronchi 
01 Jun 2021
TL;DR: A global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN), the meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE.
Abstract: Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.

38 citations

Journal ArticleDOI
10 Jul 2018-Cancers
TL;DR: Understanding TAZ biology and the molecular mechanisms by which it promotes unregulated cell proliferation will yield insights and possibly improved treatments for both EHE as well as much more common cancers.
Abstract: Epithelioid hemangioendothelioma (EHE) is a rare soft-tissue sarcoma involving cells with histologic markers that suggest an endothelial origin Around 90% of EHEs are caused by the fusion of Transcriptional Co-activator with a PDZ-motif (TAZ) with Calmodulin Binding Transcription Activator 1 (CAMTA1), a central nervous system-specific transcription activator The 10% of EHEs that lack the TAZ⁻CAMTA1 fusion instead have a fusion of Yes-associated Protein (YAP) and Transcription Factor E3 (TFE3) genes (YAP-TFE3) YAP and TAZ are well-defined downstream effectors in the Hippo pathway that promote cell growth when translocated to the nucleus The TAZ⁻CAMTA1 fusion transcript is insensitive to the Hippo inhibitory signals that normally prevent this process and thus constitutively activates the TAZ transcriptome In EHE, this causes tumors to form in a variety of organs and tissue types, most commonly the liver, lung, and bone Its clinical course is unpredictable and highly variable TAZ activation is known to contribute to key aspects of the cancer phenotype, including metastasis and fibrosis, and increased expression of TAZ is thought to be causally related to the progression of many cancers, including breast, lung, and liver Therefore, understanding TAZ biology and the molecular mechanisms by which it promotes unregulated cell proliferation will yield insights and possibly improved treatments for both EHE as well as much more common cancers

29 citations

Journal ArticleDOI
TL;DR: Whether pazopanib induces eryptosis and, if so, whether it is effective by Ca2+ entry, oxidative stress and/or ceramide, and how much it increases DCF fluorescence and ceramide abundance was explored.
Abstract: Background/Aims: The multi-targeted kinase inhibitor pazopanib, a drug employed for the treatment of a wide variety of malignancies, has previously been shown to

29 citations