Noncanonical HPV carcinogenesis drives radiosensitization of head and neck tumors.

We analyzed transcriptional data from 104 HPV+ (Human papillomavirus) HNSCC (head and neck squamous cell carcinoma) tumors together with two publicly available sources to identify highly robust transcriptional programs (modules) which could be detected consistently despite heterogeneous sequencing and quantification methodologies. Among 22 modules identified, we found a single module that naturally subclassifies HPV+ HNSCC tumors based on a bimodal pattern of gene expression, clusters all atypical features of HPV+ HNSCC biology into a single subclass, and predicts patient outcome in four independent cohorts. The subclass-defining gene set was strongly correlated with Nuclear factor kappa B (NF-κB) target expression.

FDA analyses of survival in older adults with metastatic non-small cell lung cancer in controlled trials of PD-1/PD-L1 blocking antibodies.

Background: Among patients with newly diagnosed non-small cell lung cancer (NSCLC), approximately 70% occur in those above 65 years of age and more than half are metastatic or locally advanced NSCLC.

Methods: Retrospective analyses pooling data across 4 randomized clinical trials comparing programmed death 1 receptor (PD-1) or programmed death ligand 1 (PD-L1) to docetaxel for the treatment of patients with advanced or metastatic NSCLC with disease progression on or after a platinum-containing therapy were conducted. Demographics, efficacy, and safety data from these trials were pooled and aggregated based on age.

Randomized phase II trial of cixutumumab alone or with cetuximab for refractory recurrent/metastatic head and neck squamous cell carcinoma.

Objectives: Cixutumumab (CIX) and cetuximab (CET) monoclonal antibodies block ligand-binding to insulin-like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) respectively. The objective of this study was to assess the efficacy of CIX alone or combined with CET in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients.

Methods: In this open-label phase II trial, 91 R/M HNSCC patients who progressed within 90 days of platinum-based chemotherapy, were randomized to CIX 10 mg/kg alone or with CET 500 mg/m every 2 weeks.

E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx- ECOG-ACRIN Cancer Research Group.

Purpose Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is treatment-responsive. Definitive chemoradiation results in high cure rates but causes long-term toxicity and may represent overtreatment of some patients. This phase II trial evaluated whether complete clinical response (cCR) to induction chemotherapy (IC) could select patients with HPV-associated OPSCC for reduced radiation dose as a means of sparing late sequelae.

Head and Neck Squamous Cell Carcinoma: Update on Epidemiology, Diagnosis, and Treatment.

Squamous cell carcinoma arises from multiple anatomic subsites in the head and neck region. The risk factors for development of cancers of the oral cavity, oropharynx, hypopharynx, and larynx include tobacco exposure and alcohol dependence, and infection with oncogenic viruses is associated with cancers developing in the nasopharynx, palatine, and lingual tonsils of the oropharynx. The incidence of human papillomavirus-associated oropharyngeal cancer is increasing in developed countries, and by 2020, the annual incidence could surpass that of cervical cancer.

A phase I study afatinib/carboplatin/paclitaxel induction chemotherapy followed by standard chemoradiation in HPV-negative or high-risk HPV-positive locally advanced stage III/IVa/IVb head and neck squamous cell carcinoma.

Introduction: Afatinib is an ErbB family receptor inhibitor with efficacy in head and neck squamous cell carcinoma (HNSCC). A phase I trial was conducted to determine the maximally tolerated dose (MTD) of afatinib in combination with carboplatin and paclitaxel as induction chemotherapy (IC).

Material And Methods: Patients with newly diagnosed, locally advanced HPV-negative or HPV-positive HNSCC with a significant smoking history were enrolled.

Cetuximab activity in dysplastic lesions of the upper aerodigestive tract.

Background: High risk head and neck mucosal premalignancy has a malignant conversion rate of up to 40%, despite adequate surgical therapy. Epidermal Growth Factor Receptor (EGFR) blocking agents, including cetuximab, have shown activity in head and neck squamous cell carcinoma (HNSCC) and have potential for therapy in high risk premalignancy.

Methods: We conducted a randomized, prospective, phase II clinical trial to determine the effects of cetuximab on patients with high risk premalignancy.

Unusual Paraneoplastic Presentation of Cholangiocarcinoma.

Introduction. Cutaneous paraneoplastic syndromes are a heterogeneous group of skin manifestations that occur in relation to many known malignancies. Paraneoplastic occurrence of SCLE has been noted but is not commonly reported.

Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma.

Purpose: To determine if phosphodiesterase 5 (PDE5) inhibitors can augment immune function in patients with head and neck cancer through inhibition of myeloid-derived suppressor cells (MDSC).

Experimental Design: We performed a randomized, prospective, double blinded, placebo controlled, phase II clinical trial to determine the in vivo effects of systemic PDE5 inhibition on immune function in patients with head and neck squamous cell carcinoma (HNSCC).

Results: Tadalafil augmented immune response, increasing ex vivo T-cell expansion to a mean 2.

Oropharyngeal squamous cell carcinoma treatment: current standards and future directions.

Purpose Of Review: To discuss the changing landscape and significant developments in the diagnosis and management of oropharyngeal squamous cell carcinoma.

Recent Findings: High-risk human papilloma viruses (HPVs) have been recognized as important causative factors for oropharyngeal cancer. The diagnosis is established with type-specific and broad-spectrum in-situ hybridization probes and/or p16 immunohistochemistry assays on fresh frozen paraffin-embedded tissue blocks.

Association between severe treatment-related lymphopenia and progression-free survival in patients with newly diagnosed squamous cell head and neck cancer.

Background: Severe treatment-related lymphopenia occurs commonly in many cancers and is associated with early tumor progression. Data are lacking as to whether this occurs in squamous cell head and neck cancer.

Methods: Serial total lymphocyte counts were retrospectively reviewed in patients with newly diagnosed squamous head and neck cancer undergoing chemoradiation and associated with treatment outcomes.

Addition of 18F-FDG PET/CT to clinical assessment predicts overall survival in HNSCC: a retrospective analysis with follow-up for 12 years.

Unlabelled: (18)F-FDG PET/CT is used in the follow-up of patients with head and neck squamous cell cancer (HNSCC). However, its impact on clinical decision making and patient outcome is not fully established. The objective of this study was to determine the prognostic value of (18)F-FDG PET/CT for overall survival (OS) of HNSCC patients when performed in addition to clinical assessment between 4 and 24 mo after treatment.

Phase II study of TAS-106 in patients with platinum-failure recurrent or metastatic head and neck cancer and nasopharyngeal cancer.

TAS-106, a RNA polymerase inhibitor, was studied in solid tumors with potential clinical benefit and reasonable tolerability. We conducted a multicenter, international phase II trial of TAS-106 in salvage metastatic or recurrent head and neck squamous cell cancer (HNSCC) and nasopharyngeal cancer (NPC) patients. TAS-106 monotherapy was given at 6.

Randomized safety and efficacy study of fosbretabulin with paclitaxel/carboplatin against anaplastic thyroid carcinoma.

Background: Anaplastic thyroid cancer (ATC), a rare highly vascularized tumor, has a dismal outcome. We conducted an open-label study of doublet carboplatin/paclitaxel chemotherapy with or without fosbretabulin in patients with ATC.

Methods: Patients were randomly assigned in a 2:1 ratio to 6 cycles of paclitaxel 200 mg/m(2) followed by carboplatin AUC 6 on day 1 every 3 weeks (CP), or these drugs were given on day 2 after fosbretabulin 60 mg/m(2) (CP/fosbretabulin) on days 1, 8 and 15.

Comment on "epidermal growth factor receptor is essential for toll-like receptor 3 signaling".

Epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) play important roles in tumor growth, which has stimulated efforts toward the design of targeted cancer therapeutics that inhibit their function. A growing body of literature indicates that EGFR and mTOR are also essential to support a functional innate immune response. Hence, although combination therapies that block both EGFR and mTOR may have improved activity against tumors, they may also place patients at risk of fulminant infections.

Retrospective review of positron emission tomography with contrast-enhanced computed tomography in the posttreatment setting in human papillomavirus-associated oropharyngeal carcinoma.

Objective: To determine the value of positron emission tomography (PET) with contrast-enhanced computed tomography (CT) in assessing the need for neck dissection by retrospectively reviewing the pathology reports of patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC).

Design: Retrospective cohort study.

Setting: Tertiary medical center.

Thyroidectomy followed by fosbretabulin (CA4P) combination regimen appears to suggest improvement in patient survival in anaplastic thyroid cancer.

Background: Anaplastic thyroid cancer (ATC) is an aggressive neoplasm for which a paucity of data exist about the relative role of operative procedures in disease management.

Methods: The FACT trial was a randomized, controlled phase 2/3 trial assessing the safety and efficacy of carboplatin/paclitaxel with CA4P (experimental arm) or without CA4P (control arm) in ATC, 2007-11. Patients were permitted to have had an operation before enrollment, which was stratified on the basis of exposure to operation.

Volumetric change of human papillomavirus-related neck lymph nodes before, during, and shortly after intensity-modulated radiation therapy.

Background: To assess volumetric changes of human papillomavirus (HPV)-related lymph nodes (LN) before, during, and after a course of intensity-modulated radiation therapy (IMRT) ± chemotherapy.

Methods: Each "pathologic" LN (≥1 cm) was contoured on the available diagnostic/planning CTs before, during each week, and after treatment.

Results: Seventy-nine LNs in 50 patients were identified.

Effect of radiotherapy and chemotherapy on the risk of mucositis during intensity-modulated radiation therapy for oropharyngeal cancer.

Purpose: To define the roles of radiotherapy and chemotherapy on the risk of Grade 3+ mucositis during intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer.

Methods And Materials: 164 consecutive patients treated with IMRT at two institutions in nonoverlapping treatment eras were selected. All patients were treated with a dose painting approach, three dose levels, and comprehensive bilateral neck treatment under the supervision of the same radiation oncologist.

Multidisciplinary head and neck cancer clinic and adherence with speech pathology.

Objectives: To determine the effect of referral patterns on compliance with speech-language pathology (SLP) treatment of voice and swallowing difficulties in patients with head and neck cancer (HNCA).

Study Design: Retrospective cohort study.

Methods: Patients with newly diagnosed oropharyngeal HNCA referred for pretreatment SLP evaluation comprised the study population.