Multimodality immunotherapy with avelumab, short-course radiotherapy, and cyclophosphamide in head and neck cancer: the CONFRONT phase I-II trial.

Background: Inhibition of the programmed cell death protein 1-programmed death-ligand 1 (PD-1-PD-L1) axis results in a modest objective response rate (ORR) in recurrent/metastatic head and neck squamous cell carcinoma. This study aimed to evaluate whether the addition of metronomic chemotherapy and a single fraction of radiotherapy could synergistically operate with anti-PD-L1 treatment.

Patients And Methods: We conducted a phase I-II study evaluating avelumab (10 mg/kg intravenously every 2 weeks), low-dose cyclophosphamide (50 mg/day, fixed dose, without treatment breaks), and a single fraction of radiotherapy (8 Gy) to one lesion.

Diagnostic Accuracy of [Ga]Ga Labeled Fibroblast-Activation Protein Inhibitors in Detecting Head and Neck Cancer Lesions Using Positron Emission Tomography: A Systematic Review and a Meta-Analysis.

Several studies have examined the use of positron emission tomography (PET) using [Ga]Ga-radiolabeled fibroblast-activation protein inhibitors (FAPi) across multiple subtypes of head and neck cancer (HNC). The purpose of the present study was to evaluate the diagnostic accuracy of a newly developed molecular imaging approach in the context of HNC through a comprehensive review and meta-analysis. A thorough literature review was conducted to identify scholarly articles about the diagnostic effectiveness of FAP-targeted PET imaging.

Baseline Values of Circulating IL-6 and TGF-β Might Identify Patients with HNSCC Who Do Not Benefit from Nivolumab Treatment.

Background: The immunotherapy of head and neck cancer induces a limited rate of long-term survivors at the cost of treating many patients exposed to toxicity without benefit, regardless of PD-L1 expression. The identification of better biomarkers is warranted. We analyzed a panel of cytokines, chemokines and growth factors, hereinafter all referred to as 'cytokines', as potential biomarkers in patients with head and neck cancer treated with nivolumab.

Current evidence on diagnosis and treatment of parotid gland lymphomas: a systematic review.

Background And Purpose: Parotid gland lymphoma (PGL) is a rare and challenging diagnosis. Different lymphomas can develop in the parotid gland, with the most common being the mucosa-associated lymphoid tissue (MALT) lymphoma, which originates directly from the glandular parenchyma. Other histologic subtypes arise from both intraglandular and extraglandular parotid lymph nodes.

The observational clinical registry (cohort design) of the European Reference Network on Rare Adult Solid Cancers: The protocol for the rare head and neck cancers.

Introduction: Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers.

Baseline Cytokine Profile Identifies a Favorable Outcome in a Subgroup of Colorectal Cancer Patients Treated with Regorafenib.

Metastatic colorectal cancer is frequently associated with poor clinical conditions that may limit therapeutic options. Regorafenib is a small molecule approved for the treatment of metastatic colorectal cancer, but it is hampered by significative toxicities. Moreover, only a relatively limited number of patients benefit from the treatment.

Why Oncologists Should Feel Directly Involved in Persuading Patients with Head and Neck Cancer to Quit Smoking.

Introduction: Among the risk factors for squamous cell carcinoma of the head and neck, smoking is still the most important today. Several studies agree on the effect of smoking on tumor microenvironment, while the definition of former smokers and the time of smoking cessation on biologic effect differs among papers.

Methods: We conducted a narrative review on smoking effects in HNSCC.

How Risk Factors Affect Head and Neck Squamous Cell Carcinoma (HNSCC) Tumor Immune Microenvironment (TIME): Their Influence on Immune Escape Mechanisms and Immunotherapy Strategy.

Most head and neck squamous cell carcinomas (HNSCCs) are caused by lifestyle, such as cigarette smoking, or by viruses, such as human papillomavirus (HPV) and Epstein-Barr virus (EBV). HNSCC remains a clinical challenge, notwithstanding the improvements observed in the past years, involving surgery, radiotherapy, and chemotherapy. Recurrent/metastatic (R/M) disease represents an unmet clinical need.

How Chemotherapy Affects the Tumor Immune Microenvironment: A Narrative Review.

Chemotherapy is much more effective in immunocompetent mice than in immunodeficient ones, and it is now acknowledged that an efficient immune system is necessary to optimize chemotherapy activity and efficacy. Furthermore, chemotherapy itself may reinvigorate immune response in different ways: by targeting cancer cells through the induction of cell stress, the release of damage signals and the induction of immunogenic cell death, by targeting immune cells, inhibiting immune suppressive cells and/or activating immune effector cells; and by targeting the host physiology through changes in the balance of gut microbiome. All these effects acting on immune and non-immune components interfere with the tumor microenvironment, leading to the different activity and efficacy of treatments.

Circulating Cytokines in Metastatic Breast Cancer Patients Select Different Prognostic Groups and Patients Who Might Benefit from Treatment beyond Progression.

Cancer induces immune suppression to overcome its recognition and eradication by the immune system. Cytokines are messengers able to modulate immune response or suppression. There is great interest in the evaluation of their changes during treatment in order to identify their relationship with clinical outcome.

The Clinical Efficacy and Safety of Neratinib in Combination with Capecitabine for the Treatment of Adult Patients with Advanced or Metastatic HER2-Positive Breast Cancer.

Human epidermal growth factor receptor 2 (HER2) positive cancers account for 15-20% of all breast tumors. Several drugs have been approved in the metastatic setting, including monoclonal antibodies, tyrosine kinase inhibitors (TKI) and, more recently, antibody-drug conjugates. Neratinib is a pan-HER, irreversible TKI with potent preclinical activity against trastuzumab-resistant breast cancer models.

A CT-Based Radiomic Signature Can Be Prognostic for 10-Months Overall Survival in Metastatic Tumors Treated with Nivolumab: An Exploratory Study.

Baseline clinical prognostic factors for recurrent and/or metastatic (RM) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy are lacking. CT-based radiomics may provide additional prognostic information. A total of 85 patients with RM-HNSCC were enrolled for this study.

MiR-100 is a predictor of endocrine responsiveness and prognosis in patients with operable luminal breast cancer.

Purpose: Overexpression of miR-100 in stem cells derived from basal-like breast cancers causes loss of stemness, induction of luminal breast cancer markers and response to endocrine therapy. We, therefore, explored miR-100 as a novel biomarker in patients with luminal breast cancer.

Methods: miR-100 expression was studied in 90 patients with oestrogen-receptor-positive/human-epidermal growth factor receptor 2-negative breast cancer enrolled in a prospective study of endocrine therapy given either preoperatively, or for the treatment of de novo metastatic disease.

Treatment with Beta-Blockers and ACE-Inhibitors in Breast Cancer Patients Receiving Adjuvant Trastuzumab-Based Therapy and Developing Mild Cardiac Toxicity: A Prospective Study.

Background: Angiotensin Converting Enzyme inhibitors (ACEis) and beta-blockers (BB) are suggested to prevent and treat trastuzumab-related cardiac toxicity. We performed a prospective clinical trial in women experiencing mild cardiac toxicity (MCT) while on adjuvant treatment with trastuzumab.

Methods: MCT was defined as an asymptomatic absolute decrease in LVEF of ≥ 10 percentage units to >50%.

How I treat squamous ENT cancer.

The definition of 'head and neck cancer' (HNC) identifies squamous cell carcinoma arising from the pharynx, the larynx and the oral cavity. Most of them are induced by smoking and alcohol abuse, but tumours arising in the nasopharynx and in the oropharynx may be virus induced, Epstein-Barr virus and human papillomavirus, respectively. Medical oncologists are involved in HNC in locally advanced disease and in relapsed/metastatic disease not suitable for salvage radiotherapy or surgery.

Activation of immune responses in patients with relapsed-metastatic head and neck cancer (CONFRONT phase I-II trial): Multimodality immunotherapy with avelumab, short-course radiotherapy, and cyclophosphamide.

Introduction And Background: Second-line treatment of platinum-resistant relapsed/metastatic (R/M) head and neck cancer (HNC) is a currently unmet clinical need. Clinical trials showed improvement in overall survival and quality of life of R/M-HNC patients treated with anti-PD-1 regardless of the number of prior chemotherapy lines; however, the percentage of long-term survivors remains limited.This study aims to test the hypothesis that attacking the tumor microenvironment at multiple levels can increase immunogenicity of R/M-HNC without worsening the safety profile of immune checkpoint inhibitors.

Self-evaluation of duration of adjuvant chemotherapy side effects in breast cancer patients: A prospective study.

Background: We recently reported that self-evaluation of the incidence and severity of treatment-related side effects (TSEs) using a National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0-based questionnaire was feasible and more informative than doctor reports in patients undergoing standard adjuvant chemotherapy for operable breast cancer. Here, we compare self- and doctor-evaluated day of onset and duration of TSEs in the same population.

Cardiovascular safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients: a prospective evaluation.

Aim: The aim of this study is to evaluate cardiotoxicity of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer patients (pts) with cardiovascular comorbidities or coronary artery disease (CAD) risk factors.

Patients & Methods: We prospectively analyzed pts receiving AA in order to evaluate correlations between cardiotoxicity onset and CAD risk factors or cardiovascular comorbidities.

Results: Eighty-seven pts were enrolled, with median treatment duration of 9 months (1-44).

Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast cancer patient with brain metastases.

Background: Central nervous system (CNS) involvement contributes to significant morbidity and mortality in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)-derived circulating tumour DNA (ctDNA) harbours clinically relevant genomic alterations in patients with CNS metastases and could be effective in tracking tumour evolution.

Methods: In a HER2-positive mBC patient with brain metastases, we applied droplet digital PCR (ddPCR) and next-generation whole exome sequencing (WES) analysis to measure ctDNA dynamic changes in CSF and plasma collected during treatment.

PARP1 expression drives the synergistic antitumor activity of trabectedin and PARP1 inhibitors in sarcoma preclinical models.

Background: Enhancing the antitumor activity of the DNA-damaging drugs is an attractive strategy to improve current treatment options. Trabectedin is an isoquinoline alkylating agent with a peculiar mechanism of action. It binds to minor groove of DNA inducing single- and double-strand-breaks.

Impact of a risk-based follow-up in patients affected by gastrointestinal stromal tumour.

Background: Follow-up aims to precociously identify recurrences, metastases or treatment-related adverse events so as to undertake the appropriate therapy. Guidelines admit lack of knowledge on optimal surveillance schedule, but suggest follow-up based on experts' opinion and risk stratification. To identify the impact, if any, of regular follow-up, we interrogated our prospectively collected database whether early detection of recurrences affected both clinical management and, likely, the outcome.

New and developing chemical pharmacotherapy for treating hormone receptor-positive/HER2-negative breast cancer.

Endocrine therapy is the mainstay of treatment for a substantial proportion of hormone receptor positive (HR+) breast cancer (BC). Indeed, patients with metastatic disease not immediately life threatening may experience long disease control across several lines of endocrine therapy. The major limitation of this therapeutic approach is primary or acquired resistance.