131I-metaiodobenzylguanidine and peptide receptor radionuclide therapy in pheochromocytoma and paraganglioma

PURPOSE OF REVIEW: Pheochromocytomas and paragangliomas are rare tumors arising, respectively, from the adrenal medulla and extra-adrenal sympathetic or parasympathetic paraganglia. The main therapeutic objectives in case of metastatic disease are the reduction of tumor burden and the control of symptoms resulting from excessive catecholamine secretion. Treatment choices constitute not only a wait and see attitude, locoregional approaches, chemotherapy regiments but also radiopharmaceutical agents, and they should be discussed in a specialized multidisciplinary board. This review will briefly discuss the radiopharmaceutical modalities in patients with pheochromocytomas and paragangliomas (I-MIBG and PRRT). RECENT FINDINGS: I-MIBG (Azedra) has received FDA approval for patients with iobenguane-scan-positive, unresectable, locally advanced or metastatic pheochromocytomas and paragangliomas who require systemic anticancer therapy, whereas peptide receptor radionuclide therapy using radiolabelled somatostatin analogues is currently performed in compassionate use, with very promising results. No prospective head-to-head comparison between the modalities has been conducted to date. SUMMARY: Promising results have been reported for both radiopharmaceutical agents, mostly in the setting of retrospective series. No prospective head-to-head comparison between the modalities is yet available.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

Anaplastic thyroid carcinoma: Advances in molecular profiling and targeted therapy

Purpose of reviewAnaplastic thyroid carcinomas (ATCs) are rare cancers with a globally very poor prognosis, because of their immensely aggressive behaviour, resulting in predominantly advanced stage of disease at diagnosis. Response to available therapies is still disappointing. Aim of the present review is to illustrate the diverse new strategies under investigation, to improve the poor outcome of these patients.Recent findingsApplying molecular analysis in ATC is unravelling potentially actionable targets of therapy. If a mutation of BRAF V600E is found, a combination of Dabrafenib and Trametinib is the recommended treatment. In the presence of another druggable mutation, a specific targeted therapy may be proposed. In the absence of druggable mutations, immunotherapy is an alternative approach, especially in case of significant PD-L1 expression.SummaryThe molecular profiling of tumour samples is elucidating the genetic alterations involved in ATC development, and new preclinical models are under study to define innovative approaches for individualized treatment of such patients. Hopefully this approach could improve ATC prognosis.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Calcitonin and Carcinoembryonic Antigen for the Diagnosis and Management of Medullary Thyroid Carcinoma

The neoplastic proliferation of parafollicular thyroid cells (C cells), generically defined as C cell disease, may occur as either medullary thyroid carcinoma (MTC) or C cell hyperplasia (CCH).The preoperative diagnosis of C cell disease is difficult. CCH, in fact, can only be recognized at surgical pathology. MTC, typically presenting as a thyroid nodule, may often be overlooked by traditional fine needle aspiration cytology (FNAC).Because neoplastic C cells maintain calcitonin (CT) expression, the hormone constitutes a very sensitive pre- and postoperative marker of C cell disease, with high prognostic value.MTC patients also present increased serum CEA levels. At variance with circulating CT, however, serum CEA displays a poor preoperative sensitivity for MTC diagnosis and a more limited efficacy as a prognostic factor.In the preoperative settings, in fact, circulating CT is the most specific and sensitive disease marker for MTC, while CEA displays a lower diagnostic accuracy, and both are of prognostic utility, allowing accurate estimation of tumor burden.During the postsurgical follow-up of MTC patients, the evolution of both CT and CEA levels allows a good estimate of MTC progression, and their increase reliably heralds persistence/relapse. Nevertheless, some patients may present discrepant results with disproportionately low circulating CT as compared to CEA levels. In such instance, the clinician should be alerted and consider the possibility of dedifferentiated, more aggressive MTC.In recent years, CT and CEA doubling times (DT) have been proposed as prognostic factors, being CT-DT a more precise indicator of MTC progression than CEA-DT.Circulating CT and CEA levels represent also accurate markers of response to local treatment in early and advanced/recurrent MTC, but their suitability for the evaluation of response to systemic therapy needs confirmation.info:eu-repo/semantics/publishe

Immunotherapy and targeted therapies efficacy in thymic epithelial tumors : a systematic review

Abstract: Background: Thymic epithelial tumors (TET) are rare neoplasms of the anterior mediastinum. Surgery is the mainstay treatment for resectable TET, whereas systemic treatments are reserved for unresectable and metastatic tumors. The development of new treatments, such as immune checkpoint inhibitors (ICI) and targeted therapies, with promising results in other types of solid tumors, has led to the investigation of their potential efficacy in TET. The study of tumor microenvironments (TME) is another field of investigation that has gained the interest of researchers. Taking into account the complex structure of the thymus and its function in the development of immunity, researchers have focused on TME elements that could predict ICI efficacy. Materials and Methods: The primary objective of this systematic review was to investigate the efficacy of ICI in TET. Secondary objectives included the toxicity of ICI, the efficacy of targeted therapies in TET, and the evaluation of the elements of TME that may be predictive factors of ICI efficacy. A literature search was conducted in February 2023 using the Ovid Medline and SciVerse Scopus databases. Results: 2944 abstracts were retrieved, of which 31 were retained for the systematic review. Five phase II and one retrospective study assessed ICI efficacy. The overall response rate (ORR) varied from 0% to 34%. Median progression-free survival (PFS) ranged from 3.8 to 8.6 months, being lower in thymic carcinoma (TC) (3.8-4.2 months). Median overall survival (OS) ranged from 14.1 to 35.4 months. Treatment-related adverse events occurred in 6.6% to 27.3% of patients. Sixteen studies assessed targeted therapies. The most active molecule was lenvatinib, with 38% ORR in patients with TC while no activity was detected for imatinib, erlotinib plus bevacizumab, and saracatinib. Ten studies assessed TME elements that could predict ICI efficacy. Four studies focused on the tumor-infiltrating immune cells suggesting improved outcomes in patients with TC and high tumor-infiltrating lymphocyte densities. Another study showed that CD8+, CD20+, and CD204+ tumor-infiltrating immune cells in cancer stroma might be prognostic biomarkers in TC. Another study identified the immune-related long non-coding RNAs as a predictor of response to ICI. Tumor mutational burden was identified as a predictive factor of ICI efficacy in one study. Conclusions: Despite study heterogeneity, this review shows that ICI could be a therapeutic option for selected patients with TET that are not amenable to curative radical treatment after first-line chemotherapy

Immunotherapy and Targeted Therapies Efficacy in Thymic Epithelial Tumors: A Systematic Review

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Trabectedin-Related Heart Failure: Case Report and a Systematic Review of the Literature

New drugs come not only with benefits but also with unexpected toxicities which need to be promptly recognized and managed. Starting from a scholar case of acute heart failure with preserved ejection fraction following the administration of trabectedin (ET-743, Yondelis®) in a patient with a metastatic solitary fibrous tumor, we performed a systematic review of the literature encompassing the results of previous cardiac safety analysis published ten years ago, a review of clinical trials published during the last 10 years as well as single-case descriptions related to trabectedin cardiotoxicity. The estimated incidence of cardiac toxicity was 3,4% among patients receiving trabectedin, with recent data suggesting a higher rate of heart failure than previously recognized. Previous or concomitant anthracyclines exposure may represent a risk factor. Assaying for NT-pro-BNP may be useful for the early detection of individuals with trabectedin-induced heart failure.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Extra-osseous Ewing sarcoma of the thyroid gland mimicking a hemorrhagic cyst of Hashimoto thyroiditis

Ewing’s family of tumors, including Ewing sarcoma, Askin tumor, and peripheral primitive neuroectodermal tumors, were first identified by James Ewing in 1921. Ewing sarcoma is more common in bones. However, extra-osseous Ewing sarcoma (EoES) is a very rare separate entity and was first described by Tefft and al. in 1969. It is a highly malignant round-cell tumor and contains a reciprocal translocation between chromosomes 11 and 22, t(11;22).In this report, we present the case of a 34 years old female patient who was unfortunately diagnosed with Ewing sarcoma of the thyroid after being operated for a hemorrhagic cyst in a context of Hashimoto thyroiditis.The patient was followed at the endocrinology department for an auto-immune thyroiditis for two years. She complained of neck pain and a suspicious hemorrhagic cyst was discovered on thyroid ultrasound. She underwent total thyroidectomy; three weeks later, she suffered from right sided firm swelling in her neck. The pathology was in favor of EoES of the thyroid.To date and to the best of our knowledge, this is the first case of Ewing sarcoma of the thyroid in auto-immune thyroiditis. EoES of the thyroid is a very rare entity and should be considered in the differential diagnosis of a solid tumor in the thyroid. Diagnosis is based on ultrastructural examination, immunostaining and evidence of abnormal translocation t(11;22). It is usually an aggressive disease.Early diagnosis with adequate surgical management and chemotherapy are the mainstay of the treatment and may change the outcomeinfo:eu-repo/semantics/publishe

Adenoid cystic carcinoma of the breast – an aggressive presentation with pulmonary, kidney, and brain metastases: a case report

Abstract Background Adenoid cystic carcinoma of the breast is a rare malignant neoplasm associated with an excellent prognosis and a very rare occurrence of metastases. Case presentation We report the case of an aggressive presentation in a 65-year-old woman, of Belgian origin, who was diagnosed as having adenoid cystic carcinoma of the breast and developed metastases to her lung, kidney, and brain. Conclusions We describe similar cases reported in the literature and discuss the molecular characteristics and treatment paradigm of this controversially aggressive disease entity

Successful treatment of synchronous chemoresistant pulmonary metastasis from pleomorphic rhabdomyosarcoma with stereotaxic body radiation therapy: A case report and a review of the literature.

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First-in-human, dose-escalation, phase 1 study of anti-angiopoietin-2 LY3127804 as monotherapy and in combination with ramucirumab in patients with advanced solid tumours

Desenvolupament de fàrmacsDesarrollo de fármacosDrug developmentBackground This is the first-in-human study of novel anti-angiopoietin-2 (Ang-2) monoclonal antibody LY3127804 as monotherapy and in combination with ramucirumab in advanced solid tumours. Methods Patients received intravenous LY3127804 monotherapy (4, 8, 12, 16, 20 and 27 mg/kg) in part A; LY3127804 (8, 12, 16, 20 and 27 mg/kg) with 8 mg/kg ramucirumab in part B; and LY3127804 (20 mg/kg) with 12 mg/kg ramucirumab in part C. Treatments were administered every 2 weeks (Q2W) during 28-day cycles. Dose-escalation was based on cycle 1 dose-limiting toxicities (DLTs). Results Sixty-two patients were treated in part A (n = 20), part B (n = 35) and part C (n = 7). Constipation, diarrhoea and fatigue were the most common treatment-emergent adverse events (TEAEs) in part A; hypertension and peripheral oedema were the most frequent TEAE in parts B and C. No DLT was observed and maximum tolerated dose for LY3127804 was not reached. Four patients achieved partial response with combination therapy (clear cell endometrial carcinoma, cervix squamous cell carcinoma, carcinoma of unknown primary and gastroesophageal junction carcinoma), 29 achieved stable disease, and 24 had progressive disease. Conclusions LY3127804 monotherapy and its combination with ramucirumab are well tolerated. LY3127804 20 mg/kg was the recommended Phase 2 dose.The trial was sponsored by Eli Lilly and Company