TRK Fusions Are Enriched in Cancers with Uncommon Histologies and the Absence of Canonical Driver Mutations.

Purpose: TRK inhibitors achieve marked tumor-agnostic efficacy in TRK fusion-positive cancers and consequently are now an established standard of care. Little is known, however, about the demographics, outcomes, response to alternative standard therapies, or genomic characteristics of TRK fusion-positive cancers.

Experimental Design: Utilizing a center-wide screening program involving more than 26,000 prospectively sequenced patients, genomic and clinical data from all cases with TRK fusions were extracted.

Immunogenomics of Colorectal Tumors: Facts and Hypotheses on an Evolving Saga.

Immunotherapy with immune checkpoint inhibitors is an approved treatment option for a subpopulation of patients with colorectal cancers that display microsatellite instability. However, not all individuals within this subgroup respond to immunotherapy, and molecular biomarkers for effective patient stratification are still lacking. In this opinion article, we provide an overview of the different biological parameters that contribute to rendering colorectal cancers with microsatellite instability potentially sensitive to immunotherapy.

Quality of life analysis in lung cancer: A systematic review of phase III trials published between 2012 and 2018.

Objectives: We previously reported that quality of life (QoL) is not included among trial endpoints and QoL results are underreported in a significant proportion of phase III oncology trials. Here we describe QoL adoption, reporting and methodology of QoL analysis in lung cancer trials.

Materials And Methods: We selected all primary publications of lung cancer phase III trials assessing anticancer drugs published between 2012 and 2018 by 11 major journals.

Significance of TIM3 expression in cancer: From biology to the clinic.

Targeting inhibitory immune checkpoint molecules has dramatically changed treatment paradigms in medical oncology. Understanding the best strategies to unleash a pre-existing immune response or to induce an efficient immune response against tumors has emerged as a research priority. In this work, we focus on a novel target for cancer immunotherapy, the inhibitory receptor T-cell immunoglobulin and mucin domain 3 (TIM3).

Atypical haemolytic-uraemic syndrome in patient with metastatic colorectal cancer treated with fluorouracil and oxaliplatin: a case report and a review of literature.

. Thrombotic microangiopathies (TMA) are relatively rare but severe disorders characterised by non-immune haemolytic anaemia, thrombocytopaenia and organ failure. In patients with metastatic cancer, sporadic forms of TMA can be triggered by chemotherapeutic agents or can occur as complication of malignancy itself or of infections.

Molecular Assay for Ovarian Cancer Patients: A Survey through Italian Departments of Oncology and Molecular and Genomic Diagnostic Laboratories.

In Italy, 5200 new ovarian cancers were diagnosed in 2018, highlighting an increasing need to test women for . The number of labs offering this test is continuously increasing. The aim of this study was to show the results coming from the intersociety survey coordinated by four different Clinical and Laboratory Italian Scientific Societies (AIOM, SIAPEC-IAP, SIBIOC, and SIGU).

Lenalidomide-based induction and maintenance in elderly newly diagnosed multiple myeloma patients: updated results of the EMN01 randomized trial.

n the EMN01 trial, the addition of an alkylator (melphalan or cyclophosphamide) to lenalidomide-steroid induction therapy was prospectively evaluated in transplant-ineligible patients with multiple myeloma. After induction, patients were randomly assigned to maintenance treatment with lenalidomide alone or with prednisone continuously. The analysis presented here (median follow-up of 71 months) is focused on maintenance treatment and on subgroup analyses defined according to the International Myeloma Working Group Frailty Score.

Driving Cells with Light-Controlled Topographies.

Cell-substrate interactions can modulate cellular behaviors in a variety of biological contexts, including development and disease. Light-responsive materials have been recently proposed to engineer active substrates with programmable topographies directing cell adhesion, migration, and differentiation. However, current approaches are affected by either fabrication complexity, limitations in the extent of mechanical stimuli, lack of full spatio-temporal control, or ease of use.

The Stromal and Immune Landscape of Colorectal Cancer Progression during Anti-EGFR Therapy.

In this issue of Cancer Cell, Woolston et al. show that colorectal cancers that become refractory to initially effective anti-EGFR therapy contain an abundance of stromal and immune cells, irrespective of the contextual presence of resistance-conferring mutations. This reconfiguration puts forward therapeutic opportunities for patients who relapse on EGFR-targeting treatment.

CAR-Based Strategies beyond T Lymphocytes: Integrative Opportunities for Cancer Adoptive Immunotherapy.

Chimeric antigen receptor (CAR)-engineered T lymphocytes (CAR Ts) produced impressive clinical results against selected hematological malignancies, but the extension of CAR T cell therapy to the challenging field of solid tumors has not, so far, replicated similar clinical outcomes. Many efforts are currently dedicated to improve the efficacy and safety of CAR-based adoptive immunotherapies, including application against solid tumors. A promising approach is CAR engineering of immune effectors different from αβT lymphocytes.

Ovarian Cancer Immunotherapy: Turning up the Heat.

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies. Despite surgery and chemotherapy, 5-years survival rates have improved only modestly over the past few decades remaining at 45% for advanced stages. Therefore, novel therapies are urgently needed.

An unusual case of complicated rhinosinusitis of the sphenoid sinus involving the cavernous sinus and skull base: Endoscopic sinus surgery and medical therapy.

Isolated sphenoid sinus diseases are generally asymptomatic and relatively uncommon with the potential for serious complications. Patients with this condition should be monitored closely and treated aggressively and either diagnostic or therapeutic intent is often indicated. In the management of a complex, life-threatening condition that involves many different fields of expertise, the otolaryngologist plays a key role in orchestrating different specialists and gaining direct access to the affected area, thus taking the first and essential step towards diagnosis and therapy.

Recommendations for the implementation of BRCA testing in ovarian cancer patients and their relatives.

The current availability of new Poly(ADP-ribose) Polymerase (PARP)-inhibitors for the treatment of ovarian cancer patients independently of the presence of a BRCA pathogenic variant, together with the validation of somatic test for the analysis of BRCA1/2 genes, involves the need to optimise the guidelines for BRCA testing. The AIOM-SIGU-SIBIOC-SIAPEC-IAP Italian Scientific Societies, in this position paper, recommend the implementation of BRCA testing with 2 main objectives: the first is the identification of ovarian cancer patients with higher probability of benefit from specific anticancer treatments (test for response to therapy); the second goal, through BRCA testing in the family members of ovarian cancer patients, is the identification of carriers of pathogenic variant, who have inheredited predisposition to cancer development (test for cancer risk). These individuals with increased risk of cancer, should be encouraged to participate in dedicated high-risk surveillance clinics and specific risk-reducing measures (primary and/or secondary prevention programs).

Combined blockade of MEK and PI3KCA as an effective antitumor strategy in HER2 gene amplified human colorectal cancer models.

Background: Targeting the epidermal growth factor receptor (EGFR) either alone or in combination with chemotherapy is an effective treatment for patients with RAS wild-type metastatic colorectal cancer (mCRC). However, only a small percentage of mCRC patients receive clinical benefits from anti-EGFR therapies, due to the development of resistance mechanisms. In this regard, HER2 has emerged as an actionable target in the treatment of mCRC patients with resistance to anti-EGFR therapy.

The Penetration-Aspiration Scale: Adaptation to Open Partial Laryngectomy and Reliability Analysis.

A standard for assessing swallowing function after open partial horizontal laryngectomy (OPHL) is still not established. The variability in the measures used to investigate swallowing functional outcomes after OPHL limits the communication among clinicians and the possibility to compare and combine results from different studies. The study aims to adapt the PAS to the altered anatomy after OPHLs using fiberoptic endoscopic evaluation of swallowing (FEES) and to test its reliability.

Death for life: a path from apoptotic signaling to tissue-scale effects of apoptotic epithelial extrusion.

Apoptosis plays a crucial role in clearing old or critically compromised cells, and actively maintains epithelial homeostasis and epithelial morphogenesis during embryo development. But how is the apoptotic signaling pathway able to orchestrate such complex and dynamic multi-cellular morphological events at the tissue scale? In this review we collected the most updated knowledge regarding how apoptosis controls different cytoskeletal components. We describe how apoptosis can control epithelial homeostasis though epithelial extrusion, a highly orchestrated process based on high- order actomyosin structures and on the coordination between the apoptotic and the neighboring cells.

Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5.

Malignant pleural mesothelioma (MPM) is a tumor with high chemoresistance and poor prognosis. MPM-initiating cells (ICs) are known to be drug resistant, but it is unknown if and how stemness-related pathways determine chemoresistance. Moreover, there are no predictive markers of IC-associated chemoresistance.

Development and characterization of a canine-specific anti-CD94 (KLRD-1) monoclonal antibody.

Natural killer (NK) cells are non-T, non-B lymphocytes are part of the innate immune system and function without prior activation. The human NK cell surface determinant, CD94, plays a critical role in regulation of NK cell activity as a heterodimer with NKG2 subclasses. Canine NK cells are not as well defined as the human and murine equivalents, due in part to the paucity of reagents specific to cell surface markers.

Role of Cyclin-Dependent Kinase Inhibitors in Endometrial Cancer.

Endometrial Cancer (EC) is an important cause of death in women worldwide. Despite early diagnosis and optimal treatment of localized disease, relapsed patients have few therapeutic options because after first line therapy, currently no standard of care exists. On the basis of endocrine positivity of most endometrioid ECs, Endocrine Therapy (ET) is a reasonable and widely accepted option.

Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma.

Introduction: A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified.

Methods: We enrolled 275 patients with an initial clinical diagnosis of pleural effusion.

Veliparib: a new therapeutic option in ovarian cancer?

The role of poly ADP ribose polymerase inhibitors in ovarian cancer is rapidly evolving. Three different poly ADP ribose polymerase inhibitors (olaparib, niraparib and rucaparib) have been already approved as maintenance after response to platinum-based chemotherapy; two of them (olaparib and rucaparib) also as single agents. Veliparib, a novel PARPI, showed promising results in preclinical and early clinical settings.

Salvage open partial horizontal laryngectomy after failed radiotherapy: A multicentric study.

Objectives: The primary aim of the present study was to report our multi-institutional experience in surgical salvage with open partial horizontal laryngectomies (OPHL) after failed radiotherapy (RT) for laryngeal squamous cell carcinoma (LSCC). Secondary aims were to analyze the prognostic meaning of the main clinical and pathological parameters in relation to the oncologic outcome and to compare our results with the available literature.

Study Design: A retrospective multicenter analysis of surgical oncological outcomes.

Swallowing Safety and Efficiency after Open Partial Horizontal Laryngectomy: A Videofluoroscopic Study.

Dysphagia is common after an open partial horizontal laryngectomy (OPHL). The mechanisms causing lower airways' invasion and pharyngeal residue are unclear. The study aims to examine physio-pathological mechanisms affecting swallowing safety and efficiency after OPHL.