Association of Patient and Tumor Characteristics With Outcomes in Young Head and Neck Squamous Cell Carcinoma Patients.

Introduction: We retrospectively studied young patients with head and neck squamous cell carcinoma (HNSCC) to identify factors associated with disease-specific survival (DSS).

Methods: Patient and tumor characteristics of patients aged ≤45 who received treatments for non-metastatic HNSCC were collected to identify factors associated with DSS. Proportional hazards regression was applied separately for surgical and non-surgical patients.

Expression of lymphoid structure-associated cytokine/chemokine gene transcripts in tumor and protein in serum are prognostic of melanoma patient outcomes.

Background: Proinflammatory chemokines/cytokines support development and maturation of tertiary lymphoid structures (TLS) within the tumor microenvironment (TME). In the current study, we sought to investigate the prognostic value of TLS-associated chemokines/cytokines (TLS-kines) expression levels in melanoma patients by performing serum protein and tissue transcriptomic analyses, and to then correlate these data with patients clinicopathological and TME characteristics.

Methods: Levels of TLS-kines in patients' sera were quantitated using a custom Luminex Multiplex Assay.

Evaluation of electromagnetic navigational bronchoscopic biopsy of lung lesions performed by a thoracic surgical service.

Background: With the increasing use of computed tomography scans for lung cancer screening and surveillance of other cancers, thoracic surgeons are being referred patients with lung lesions for biopsies. Electromagnetic navigational bronchoscopy-guided lung biopsy is a relatively new technique for bronchoscopic biopsy. Our objective was to evaluate the diagnostic yields and safety of electromagnetic navigational bronchoscopy-guided lung biopsy.

Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma.

We sought to develop a sentinel lymph node gene expression signature score predictive of disease recurrence in patients with cutaneous melanoma. Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips.

Phase I Trial of Cetuximab, Radiotherapy, and Ipilimumab in Locally Advanced Head and Neck Cancer.

Purpose: Concurrent radiotherapy with cetuximab, an anti-EGFR mAb, is a standard treatment for locally advanced head and neck squamous carcinoma (HNSCC). Cytotoxic T lymphocyte antigen-4-positive (CTLA-4+) regulatory T cells (Treg) dampen cellular immunity and correlate negatively with clinical outcomes. This phase I study added ipilimumab, an anti-CTLA-4 mAb, to cetuximab-radiotherapy.

Phase I Trial Combining Chemokine-Targeting with Loco-Regional Chemoimmunotherapy for Recurrent, Platinum-Sensitive Ovarian Cancer Shows Induction of CXCR3 Ligands and Markers of Type 1 Immunity.

Purpose: Increased prevalence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts positive outcomes in patients with epithelial ovarian cancer (EOC), whereas the regulatory T cells (Treg) predict poor outcomes. Guided by the synergistic activity of TLR3 ligands, IFNα, and COX-2 blockers in selectively enhancing CTL-attractants but suppressing Treg-attractants, we tested a novel intraperitoneal chemoimmunotherapy combination (CITC), to assess its tolerability and TME-modulatory impact in patients with recurrent EOC.

Patients And Methods: Twelve patients were enrolled in phase I portion of the trial NCT02432378, and treated with intraperitoneal cisplatin, intraperitoneal rintatolimod (dsRNA, TLR3 ligand), and oral celecoxib (COX-2 blocker).

Do Ultrasound Patterns and Clinical Parameters Inform the Probability of Thyroid Cancer Predicted by Molecular Testing in Nodules with Indeterminate Cytology?

Molecular testing (MT) is commonly used to refine cancer probability in thyroid nodules with indeterminate cytology. Whether or not ultrasound (US) patterns and clinical parameters can further inform the risk of thyroid cancer in nodules predicted to be positive or negative by MT remains unknown. The aim of this study was to test if clinical parameters, including patient age, sex, nodule size (by US), Bethesda category (III, IV, V), US pattern (American Thyroid Association [ATA] vs.

Transoral endoscopic repair of Zenker diverticulum by a thoracic surgical service.

Objective: Zenker diverticulum (ZD), a pulsion diverticulum of the esophagus, has been traditionally managed with an open surgical approach, but endoscopic transoral stapling has been reported with increasing frequency. The objective of this study was to evaluate the results of endoscopic repair of ZD by a thoracic surgery service.

Methods: We conducted a retrospective review of patients who underwent transoral stapling repair of ZD at our institution by the thoracic surgery service.

PET/CT Poorly Predicts AJCC 8th Edition Pathologic Staging in HPV-Related Oropharyngeal Cancer.

Objective: The American Joint Committee on Cancer (AJCC) 8th edition introduced distinct clinical and pathological staging paradigms for human papilloma virus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). Treatment planning for OPSCC often utilizes positron emission tomography/computed tomography (PET/CT) to assess clinical stage. We hypothesize that PET/CT will accurately predict final pathologic AJCC 8th edition staging in patients with HPV+ OPSCC.

Phase II Trial of Adjuvant Dendritic Cell Vaccine in Combination with Celecoxib, Interferon-α, and Rintatolimod in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases.

Background: Peritoneal metastases portend poor prognosis in the setting of standard chemotherapy. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves outcomes, but relapse is common. We report a phase II trial evaluating the safety and efficacy of adjuvant αDC1 vaccination with chemokine modulation (CKM) after CRS/HIPEC.

Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer.

Cetuximab, an anti-EGFR monoclonal antibody (mAb), is approved for advanced head and neck squamous cell carcinoma (HNSCC) but benefits a minority. An established tumor-intrinsic resistance mechanism is cross-talk between the EGFR and hepatocyte growth factor (HGF)/cMet pathways. Dual pathway inhibition may overcome cetuximab resistance.

Protein Signatures and Tissue Diagnosis of Pancreatic Cancer.

Background: Endoscopic ultrasound-guided fine-needle aspiration fails to diagnose up to 25% of patients with pancreatic ductal adenocarcinoma (PDAC). Proteomics can help to overcome this clinical dilemma. We hypothesized that soluble protein signatures can differentiate PDAC from benign tissues.

Biliary palliation for unresectable pancreatic adenocarcinoma: surgical bypass or self-expanding metal stent?

Background: Standard of care guidelines endorse self-expanding metal stents (SEMS) rather than open surgical biliary bypass (OSBB) for biliary palliation in the setting of unresectable pancreatic ductal adenocarcinoma (PDAC). This study used competing risk analysis to compare short- and long-term morbidity and overall survival among patients undergoing SEMS or OSBB after unresectable or metastatic disease is identified at the time of exploration.

Methods: Single institution retrospective cohort study (n = 127) evaluating outcomes after OSBB and SEMS for biliary palliation in patients found to have unresectable PDAC at exploration.

Early squamous cell carcinoma of the oral tongue with histologically benign lymph nodes: A model predicting local control and vetting of the eighth edition of the American Joint Committee on Cancer pathologic T stage.

Background: The eighth edition of the American Joint Committee on Cancer staging manual (AJCC8) added depth of invasion to the definition of pathologic T stage (pT). In the current study, the authors assess pT stage migration and the prognostic performance of the updated pT stage and compare it with other clinicopathologic variables in patients with early squamous cell carcinoma of the oral tongue (OTSCC; tumors measuring ≤4 cm) with histologically benign lymph nodes (pN0).

Methods: A multi-institutional cohort of patients with early OTSCC was restaged as per AJCC8.

Circulating exosomes measure responses to therapy in head and neck cancer patients treated with cetuximab, ipilimumab, and IMRT.

: Exosomes, small extracellular vesicles (EVs) derived from the endocytic compartment of their parent cells, are present in plasma of cancer patients and may serve as non-invasive biomarkers of disease outcome. Here, we asked whether tumor-derived (TEX) and/or T-cell derived exosomes can predict outcome in head and neck squamous cell carcinoma (HNSCC) patients treated with oncological therapy. : 18 HNSCC patients enrolled in phase I clinical trial and receiving a combination of cetuximab, ipilimumab and radiation therapy were serially monitored for TEX and T cell-derived exosomes.

Hypopharyngeal cancer treatment: Does initial surgery confer survival benefit?

Background: Organ preservation protocols have increasingly been applied for the treatment of head and neck cancers, including hypopharyngeal squamous cell carcinoma (HSCC). We sought to evaluate whether patients treated with primary surgery followed by adjuvant therapy had survival benefit over patients treated with initial nonsurgical modalities.

Methods: We retrospectively reviewed patients with new diagnosis of HSCC at the University of Pittsburgh (1994-2014) treated with either primary total laryngectomy with pharyngectomy or organ preservation.

Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for -altered head and neck cancer.

is the most commonly altered oncogene in head and neck squamous cell carcinoma (HNSCC). We evaluated the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on survival in a -characterized cohort of 266 HNSCC patients and explored the mechanism in relevant preclinical models including patient-derived xenografts. Among subjects with mutations or amplification, regular NSAID use (≥6 mo) conferred markedly prolonged disease-specific survival (DSS; hazard ratio 0.

Phase 1 study of EGFR-antisense DNA, cetuximab, and radiotherapy in head and neck cancer with preclinical correlatives.

Background: Cetuximab combined with radiation therapy (RT) is an evidence-based treatment for locally advanced head and neck squamous cell carcinoma (HNSCC); however, locoregional failure remains the primary cause of cancer-related death in this disease. Intratumoral injection of epidermal growth factor receptor (EGFR)-antisense plasmid DNA (EGFR-AS) is safe and has been associated with promising lesional responses in patients who have recurrent/metastatic HNSCC. For the current study, the authors investigated the antitumor effects of cetuximab and EGFR-AS in preclinical HNSCC models and reported their phase 1 experience adding intratumoral EGFR-AS to cetuximab RT.

STING activation enhances cetuximab-mediated NK cell activation and DC maturation and correlates with HPV status in head and neck cancer.

Objectives: The intracellular DNA sensor stimulator of interferon genes (STING) has recently been shown to play a vital role in anti-viral and anti-tumor immune responses stimulating cytokine production. While human papillomavirus (HPV) is a causative agent for a subset of head and neck squamous cell carcinoma (HNSCC) with unique etiology and clinical outcome, how the STING pathway is regulated in a virus-induced tumor microenvironment is not well understood. Since STING inactivation likely reflects immunoescape via innate immunity, we hypothesized that its restoration would improve efficacy of the immune modulatory monoclonal antibody (mAb), cetuximab.