A phase 2 study of neoadjuvant chemotherapy plus durvalumab in resectable locally advanced head and neck squamous cell carcinoma.

Background: Patients with locally advanced head and neck squamous cell cancer (HNSCC) are treated with surgery followed by adjuvant (chemo) radiotherapy or definitive chemoradiation, but recurrence rates are high. Immune checkpoint blockade improves survival in patients with recurrent/metastatic HNSCC; however, the role of chemo-immunotherapy in the curative setting is not established.

Methods: This phase 2, single-arm, multicenter study evaluated neoadjuvant chemo-immunotherapy with carboplatin, nab-paclitaxel, and durvalumab in patients with resectable locally advanced HNSCC.

Comprehensive Viral Genotyping Reveals Prognostic Viral Phylogenetic Groups in HPV16-Associated Squamous Cell Carcinoma of the Oropharynx.

Unlabelled: Human papillomavirus-positive (HPV+) squamous cell carcinoma of the oropharynx (OPSCC) is the most prevalent HPV-associated malignancy in the United States and is primarily caused by HPV subtype 16 (HPV16). Favorable treatment outcomes have led to increasing interest in treatment deescalation to reduce treatment-related morbidity. Prognostic biomarkers are needed to identify appropriately low-risk patients for reduced treatment intensity.

Universal Accessible Biomarkers of Drug-Induced Tissue Injury and Systemic Inflammation in Rat: Performance Assessment of TIMP-1, A2M, AGP, NGAL, and Albumin.

The ability to monitor for general drug-induced tissue injury (DITI) or systemic inflammation in any tissue using blood-based accessible biomarkers would provide a valuable tool in early exploratory animal studies to understand potential drug liabilities. Here we describe the evaluation of 4 biomarkers of tissue remodeling and inflammation (α2-macroglobulin [A2M], α1-acid glycoprotein [AGP], neutrophil gelatinase-associated lipocalin [NGAL], and tissue inhibitor of metalloproteinases [TIMP-1]) as well as the traditional serum parameter albumin as potential blood-based biomarkers of DITI and systemic inflammatory response (SIR). Biomarker performance was assessed in 51 short-term rat in vivo studies with various end-organ toxicities or SIR and receiver operating characteristic curves were generated to compare relative performances.

Sinonasal Squamous Cell Carcinoma Survival Outcomes Following Induction Chemotherapy vs Standard of Care Therapy.

Objective: To compare oncologic outcomes in sinonasal squamous cell carcinoma (SNSCC) treated with standard of care (SOC) definitive therapy, consisting of surgery or chemoradiotherapy, vs induction therapy followed by definitive therapy.

Study Design: Retrospective review.

Setting: Academic tertiary care hospital.

A case of metastatic NUT carcinoma with prolonged response on gemcitabine and nab-paclitaxel.

Background: NUT carcinoma is an aggressive malignancy characterized by translocations in the  gene. There are currently no consensus treatment recommendations for NUT carcinomas.

Methods: Here, we describe the case of a previously healthy male diagnosed with NUT carcinoma after presenting with sinus pressure, found to have a sinonasal mass and distant metastatic disease in the lungs.

Phase 1 trial of adavosertib (AZD1775) in combination with concurrent radiation and cisplatin for intermediate-risk and high-risk head and neck squamous cell carcinoma.

Background: Adavosertib (AZD1775) is an inhibitor of the Wee1 kinase. The authors conducted a phase 1b trial to evaluate the safety of adavosertib in combination with definitive chemoradiotherapy for patients with newly diagnosed, intermediate-risk/high-risk, locally advanced head and neck squamous cell carcinoma (HNSCC).

Methods: Twelve patients with intermediate-risk/high-risk HNSCC were enrolled, including those with p16-negative tumors of the oropharynx, p16-positive tumors of the oropharynx with ≥10 tobacco pack-years, and tumors of the larynx/hypopharynx regardless of p16 status.

An overview of lurbinectedin as a new second-line treatment option for small cell lung cancer.

Small cell lung cancer (SCLC) is a highly proliferative, aggressive form of lung cancer that carries a poor prognosis. Recent approvals with new therapeutic options represent the first in more than a decade for SCLC. Lurbinectedin, a newly approved second-line option, is a synthetic alkaloid that covalently binds DNA, generating double-strand breaks, and disrupts DNA-protein interactions and RNA transcription.

The addition of chemotherapy to adjuvant radiation is associated with inferior survival outcomes in intermediate-risk HPV-negative HNSCC.

Background: Only high-risk tumors with extranodal extension (ENE) and/or positive surgical margins (PSM) benefit from adjuvant therapy (AT) with concurrent chemoradiation (CRT) compared to radiation therapy (RT) in locally advanced head and neck squamous cell carcinoma (HNSCC). Optimal treatment for intermediate-risk tumors remains controversial. We categorized patients based on their surgical pathologic risk factors and described AT treatment patterns and associated survival outcomes.

Consolidation With Pembrolizumab and Nab-Paclitaxel After Induction Platinum-Based Chemotherapy for Advanced Non-Small Cell Lung Cancer.

Background: Induction with four cycles of platinum-based chemotherapy was the standard of care for metastatic non-small cell lung cancer (NSCLC) until the approval of immune checkpoint blockade (ICB) in the first-line setting. Switch maintenance therapy has shown promise in improving survival by exposing patients to novel, non-cross-resistant agents earlier in their treatment course.

Methods: We performed this open-label, three-arm, randomized phase II study (NCT02684461) to evaluate three sequences of consolidation with pembrolizumab and nab-paclitaxel in patients without progressive disease post induction chemotherapy.

PARP Inhibitors in Small-Cell Lung Cancer: Rational Combinations to Improve Responses.

Despite recent advances in first-line treatment for small-cell lung cancer (SCLC), durable responses remain rare. The DNA repair enzyme poly-(ADP)-ribose polymerase (PARP) was identified as a therapeutic target in SCLC using unbiased preclinical screens and confirmed in human and mouse models. Early trials of PARP inhibitors, either alone or in combination with chemotherapy, showed promising but limited responses, suggesting that selecting patient subsets and treatment combinations will prove critical to further clinical development.

Advances in the Treatment of Non-Small Cell Lung Cancer: Immunotherapy.

Clinical development of immune checkpoint blockade has dramatically changed the treatment paradigm and prognosis for patients with non-small cell lung cancer. Immune checkpoint blockade with PD-1 and PD-L1 antibodies generates clinically significant, durable responses in patients with advanced non-small cell lung cancer. These agents are approved for first- and second-line treatment, either as single agents or in combination with chemotherapy and angiogenesis inhibitors.

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication.

Purpose: Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune stimulation, which may potentiate anti-PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC.

A randomized placebo-controlled trial of desipramine, cognitive behavioral therapy, and active placebo therapy for low back pain.

This clinical trial evaluated the independent and combined effects of a tricyclic antidepressant (desipramine) and cognitive behavioral therapy (CBT) for chronic back pain relative to an active placebo treatment. Participants (n = 142) were patients experiencing daily chronic back pain at an intensity of ≥4/10 who were randomized to a single-center, double-blind, 12-week, 4-arm, parallel groups controlled clinical trial of (1) low concentration desipramine titrated to reach a serum concentration level of 15 to 65 ng/mL; (2) CBT and active placebo medication (benztropine mesylate, 0.125 mg); (3) low concentration desipramine and CBT; and (4) active benztropine placebo medication.

Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer.

Purpose: Plasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence.

Methods And Materials: A prospective biomarker clinical trial was conducted among patients with nonmetastatic HPV-associated (p16-positive) OPSCC.

PIK3CA Mutation in HPV-Associated OPSCC Patients Receiving Deintensified Chemoradiation.

PIK3CA is the most frequently mutated gene in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC patients treated with definitive chemoradiation (CRT).

Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

Purpose: To report the results of a phase II clinical trial of de-intensified chemoradiotherapy for patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma.

Materials And Methods: Major inclusion criteria were (1) having American Joint Committee on Cancer (AJCC) 7th edition T0-T3, N0-N2c, M0 (AJCC 8th edition T0-T3, N0-N2, M0), (2) being p16 positive, and (3) reporting minimal or remote smoking history. Treatment was limited to 60 Gy intensity-modulated radiotherapy with concurrent intravenous cisplatin 30 mg/m once per week.

Telehealth Therapy Effects of Nurses and Mental Health Professionals From 2 Randomized Controlled Trials for Chronic Back Pain.

Objective: To compare the efficacy of mental health professional versus primary care nurse-delivered telehealth cognitive-behavioral therapy (CBT) and supportive care (SC) treatments for chronic low back pain, using data from 2 separate randomized controlled trials. Both trials were completed in the same hospital and used the same study design, research team, and outcome measures.

Materials And Methods: Participants from Study 1 (Mental Health Professional Study) (N=66; 2007 to 2011) and Study 2 (Nursing Study) (N=61; 2012 to 2016) were patients with chronic low back pain (≥4/10 intensity) randomized to either an 8-week CBT or an SC telehealth condition matched for contact frequency, format, and time.

Randomized Controlled Trial of Nurse-Delivered Cognitive-Behavioral Therapy Versus Supportive Psychotherapy Telehealth Interventions for Chronic Back Pain.

Unlabelled: This study evaluated a nurse-delivered, telehealth intervention of cognitive-behavioral therapy (CBT) versus supportive psychotherapy for chronic back pain. Participants (N = 61) had chronic back pain (pain "daily" ≥6 months at an intensity of ≥4 of 10 scale) and were randomized to an 8-week, 12-session, CBT or to supportive care (SC) matched for frequency, format, and time, with each treatment delivered by a primary care nurse. The primary outcome was the Roland Morris Disability Questionnaire (RMDQ).

Parturient With Barnes Syndrome (Thoracolaryngopelvic Dysplasia) Undergoing Cesarean Delivery of a Neonate With Barnes Syndrome: A Case Report.

This case describes a parturient with Barnes syndrome, a rare disorder characterized by subglottic stenosis, thoracic dystrophy, and small pelvic inlet, who underwent cesarean delivery of a neonate diagnosed with Barnes syndrome. Live simulation training was performed by multidisciplinary team to prepare for the spinal anesthetic, personnel flow between 2 operating rooms, and management of various airway scenarios for the newborn. After delivery, the neonate underwent laryngoscopy-bronchoscopy with successful intubation in the operating room because of labored breathing.

Combination Cancer Therapy with Immune Checkpoint Blockade: Mechanisms and Strategies.

The success of immune checkpoint blockade in patients with a wide variety of malignancies has changed the treatment paradigm in oncology. However, combination therapies with immune checkpoint blockade will be needed to overcome resistance and broaden the clinical utility of immunotherapy. Here we discuss a framework for rationally designing combination therapy strategies based on enhancing major discriminatory functions of the immune system that are corrupted by cancer-namely, antigenicity, adjuvanticity, and homeostatic feedback inhibition.

Randomized Controlled Trial of Telephone-delivered Cognitive Behavioral Therapy Versus Supportive Care for Chronic Back Pain.

Objective: The objective of this study was to evaluate the efficacy of a telephone-delivered, home-based cognitive-behavioral intervention for chronic low back pain in comparison to a matched supportive care (SC) treatment.

Methods: Participants (N=66) were patients with chronic back pain that were randomized to either an 8-week Cognitive-Behavioral Therapy (CBT) or a SC condition matched for contact frequency, format, and time. Participants completed validated measures of improvement in back pain disability, pain severity, and overall improvement.

Vascular Imaging of Matrix Metalloproteinase Activity as an Informative Preclinical Biomarker of Drug-induced Vascular Injury.

Lack of biomarkers specific to and either predictive or diagnostic of drug-induced vascular injury (DIVI) continues to be a major obstacle during drug development. Biomarkers derived from physiologic responses to vessel injury, such as inflammation and vascular remodeling, could make good candidates; however, they characteristically lack specificity for vasculature. We evaluated whether vascular remodeling-associated protease activity, as well as changes to vessel permeability resulting from DIVI, could be visualized ex vivo in affected vessels, thereby allowing for visual monitoring of the pathology to address specificity.

Adding Adjuvant Systemic Treatment after Neoadjuvant Therapy in Breast Cancer: Review of the Data.

Purpose Of Review: Residual disease after neoadjuvant chemotherapy is a poor prognostic factor; however, proven strategies to reduce recurrence risk and improve overall survival in this patient population are limited. Previous studies of residual disease have illustrated the importance of tumor intrinsic subtypes in treatment response and mechanisms of resistance. This review summarizes the rationale for various therapeutic approaches as well as completed and ongoing clinical trials for this high-risk group of patients.

Impact of Interfacility Transport Method and Specialty Teams on Outcomes of Pediatric Trauma Patients.

Objective: The aim of the study was to evaluate the impact of ground versus air transport and use of pediatric specialty versus generalist transport teams on outcomes of pediatric trauma victims requiring interfacility transport.

Methods: A retrospective review of our hospital's trauma registry database was performed. Children with traumatic injuries who were transported from a referring hospital by either our pediatric specialty transport team or an outside generalist transport team were included in the analysis.