New treatment opportunities for patients with advanced and/or metastatic thyroid cancer

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Improved guidance is needed to optimise diagnostics and treatment of patients with thyroid cancer in Europe

Although thyroid cancer (TC) is generally associated with a favourable prognosis, there are certain high-risk groups with a clear unmet therapeutic need. Unravelling the genomic landscape of TC has recently led to the development of novel effective targeted treatments. To date, these treatments have mostly been evaluated in non-randomised single-arm phase II clinical trials and are consequently non-reimbursed in several countries. Furthermore, most of these agents must be tailored to individual patient molecular characteristics, a context known as personalised cancer medicine, necessitating a requirement for predictive molecular biomarker testing. Existing guidelines, both in Europe and internationally, entail mostly therapeutic rather than molecular testing recommendations. This may reflect ambiguity among experts due to lack of evidence and also practical barriers in availability of the preferred molecular somatic screening and/or targeted treatments. This article reviews existing European recommendations regarding advanced/metastatic TC management with a special focus on molecular testing, and compares findings with real-world practice based on a recent survey involving TC experts from 18 European countries. Significant disparities are highlighted between theory and practice related to variable access to infrastructure, therapies and expertise, together with the insufficient availability of multidisciplinary tumour boards. In particular, practitioners’ choice of what, how and when to test is shown to be influenced by the expertise of the available laboratory, the financing source and the existence of potential facilitators, such as clinical trial access. Overall, the need of a collaborative initiative among European stakeholders to develop standardised, accessible molecular genotyping approaches in TC is underscored.</p

Improved guidance is needed to optimise diagnostics and treatment of patients with thyroid cancer in Europe

Although thyroid cancer (TC) is generally associated with a favourable prognosis, there are certain high-risk groups with a clear unmet therapeutic need. Unravelling the genomic landscape of TC has recently led to the development of novel effective targeted treatments. To date, these treatments have mostly been evaluated in non-randomised single-arm phase II clinical trials and are consequently non-reimbursed in several countries. Furthermore, most of these agents must be tailored to individual patient molecular characteristics, a context known as personalised cancer medicine, necessitating a requirement for predictive molecular biomarker testing. Existing guidelines, both in Europe and internationally, entail mostly therapeutic rather than molecular testing recommendations. This may reflect ambiguity among experts due to lack of evidence and also practical barriers in availability of the preferred molecular somatic screening and/or targeted treatments. This article reviews existing European recommendations regarding advanced/metastatic TC management with a special focus on molecular testing, and compares findings with real-world practice based on a recent survey involving TC experts from 18 European countries. Significant disparities are highlighted between theory and practice related to variable access to infrastructure, therapies and expertise, together with the insufficient availability of multidisciplinary tumour boards. In particular, practitioners’ choice of what, how and when to test is shown to be influenced by the expertise of the available laboratory, the financing source and the existence of potential facilitators, such as clinical trial access. Overall, the need of a collaborative initiative among European stakeholders to develop standardised, accessible molecular genotyping approaches in TC is underscored.</p

the curious phenomenon of dual positive circulating cells longtime overlooked tumor cells

Abstract The presence in the blood of patients with solid tumors of circulating cells expressing both epithelial and leukocyte markers (dual-positive cells, DPcells), has often been reported, though it has never been investigated in detail. A recent study suggested that DPcells are hybrid cells derived from the fusion of tumor cells with macrophages. Such fusion hybrids acquire macrophage-associated features endowing them with accelerated growth, increased motility, enhanced invasion activity and thus, a higher efficiency in metastasis formation. However, no direct evidence proving the tumor origin of circulating DPcells was provided in patients. Here we contribute a review of literature data on DPcells and on the hybrid theory with the aim of putting the current evidence both in a biological and clinical perspective and to generate new hypotheses on the mechanisms underlying tumor progression. To add further biological and clinical context to our literature review, we also report some preliminary data from our laboratory on the identification of DPcells in several solid tumors and confirmation of their malignant genotype, thus classifying them as DP-CTCs

Mining of Self-Organizing Map Gene-Expression Portraits Reveals Prognostic Stratification of HPV-Positive Head and Neck Squamous Cell Carcinoma

Patients (pts) with head and neck squamous cell carcinoma (HNSCC) have different epidemiologic, clinical, and outcome behaviors in relation to human papillomavirus (HPV) infection status, with HPV-positive patients having a 70% reduction in their risk of death. Little is known about the molecular heterogeneity in HPV-related cases. In the present study, we aim to disclose the molecular subtypes with potential biological and clinical relevance. Through a literature review, 11 studies were retrieved with a total of 346 gene-expression data points from HPV-positive HNSCC pts. Meta-analysis and self-organizing map (SOM) approaches were used to disclose relevant meta-gene portraits. Unsupervised consensus clustering provided evidence of three biological subtypes in HPV-positive HNSCC: Cl1, immune-related; Cl2, epithelial&ndash;mesenchymal transition-related; Cl3, proliferation-related. This stratification has a prognostic relevance, with Cl1 having the best outcome, Cl2 the worst, and Cl3 an intermediate survival rate. Compared to recent literature, which identified immune and keratinocyte subtypes in HPV-related HNSCC, we confirmed the former and we separated the latter into two clusters with different biological and prognostic characteristics. At present, this paper reports the largest meta-analysis of HPV-positive HNSCC studies and offers a promising molecular subtype classification. Upon further validation, this stratification could improve patient selection and pave the way for the development of a precision medicine therapeutic approach

Perspectives on window of opportunity trials in head and neck cancer: lessons from the EORTC 90111-24111-NOCI-HNCG study.

Assessing tumour response using a traditional phase I, II and III trial approach is not without limitations, particularly when targeted therapies are involved. Window of opportunity trials, performed presurgically but differing from neoadjuvant studies, were developed in an attempt to overcome the limitations of the traditional approach. A recent window of opportunity trial, the EORTC 90111-24111-NOCI-HNCG study, evaluated afatinib in treatment-naive patients with squamous cell carcinoma of the head and neck. While this study was the first to demonstrate the activity of afatinib in this setting and to define its potential predictive biomarkers, it also highlighted the challenges associated with the window of opportunity trial design, including the impact of patient selection, tumour site, and other organisational issues. This report details the key learnings from the EORTC 90111-24111-NOCI-HNCG study and provides recommendations to overcome the challenges of this particular trial design

Quality of life and financial toxicity after (chemo)radiation therapy in head and neck cancer: are there any sex- or gender-related differences?

The purpose of this article is to discuss the published evidence related to quality of life (QoL) and financial toxicity (FT) differences between female and male head and neck cancer patients treated with (chemo)radiotherapy. There is a need of promoting methods for assessing QoL difference between female and male patients in order to set up early rehabilitation, psychosocial care, and lifestyle interventions, as well as setting up specific interventions for minimizing financial stress