Planned Dental Extractions After Radiation Therapy.

Importance: Nonrestorable teeth are recommended to be extracted prior to radiation therapy (RT). Occasionally, preradiation extractions introduce unacceptable delays in treatment initiation. Planned dental extractions immediately postradiation presents an alternative strategy, though outcomes are uncertain.

The impact of an enhanced recovery after surgery protocol for major head and neck oncologic surgery on postoperative complications and adjuvant treatment delivery.

Objective: The Commission on Cancer (CoC) recently introduced a quality metric to optimize time between major head and neck surgery and adjuvant treatment (TAT) ≤6 weeks, as TAT delay adversely impacts patient survival. This study evaluates whether enhanced recovery after surgery (ERAS) for this population reduces the rate of postoperative complications, length of stay (LOS), and TAT.

Methods: Patients undergoing larynx or oral cavity resection with free flap reconstruction, ERAS, and adjuvant treatment after 2018 were compared to a historical pre-ERAS cohort.

Weekly Versus Bolus Cisplatin Concurrent With Definitive Radiation Therapy for Squamous Carcinoma of the Head and Neck: A Systematic Review and Network Meta-Analysis.

Purpose: The schedule of cisplatin concurrent with definitive radiation for squamous carcinoma of the head and neck remains controversial. Most institutions deliver either a high-dose "bolus" schedule once every 3 weeks or a low-dose weekly schedule. We compared these 2 schedules via a simplified network meta-analysis with a common comparator.

Radiation therapy for cT1-2 carcinoma of the palatine tonsil diagnosed via a simple tonsillectomy: Dosimetry and patterns of care in the IMRT era.

Objective: Small carcinomas of the palatine tonsil are often diagnosed via simple tonsillectomy, a maneuver with non-therapeutic intent. Herein, practice patterns for this unique situation are evaluated.

Patients And Methods: A retrospective review was performed across 10 facilities to identify patients with cT1-2 squamous carcinomas of the tonsil diagnosed by simple tonsillectomy between 2010 and 2018.

Defining targets to improve care delivery for T4 larynx squamous cell carcinoma.

Objective: United States oncology trends consistently demonstrate that nearly half of T4a larynx carcinoma patients are treated with larynx preservation, despite national guidelines favoring laryngectomy. This study identifies clinical decision-making drivers and defines patient subsets that should become targets for care improvement.

Methods: Retrospective analysis of patients with cT4 squamous cell carcinoma of the larynx from US National Cancer Database 2005-2016.

Impact of a Clinical Genomics Program on Trial Accrual for Targeted Treatments: Practical Approach Overcoming Barriers to Accrual for Underserved Patients.

Purpose: Clinical trials of novel and targeted agents increasingly require biomarkers for eligibility. Precision oncology continues to evolve, but challenges hamper broad use of molecular profiling (MP) that could increase the number of patients benefiting from targeted therapy. We implemented an integrated clinical genomics program (CGP), including a virtual Molecular Tumor Board (MTB), and examined its impact on MP use and impact on clinical trial accrual in a multisite regional-based cancer system with an emphasis on effects for isolated clinicians.

Identifying an oligometastatic phenotype in HPV-associated oropharyngeal squamous cell cancer: Implications for clinical trial design.

Objectives: Patients with human papillomavirus (HPV) associated squamous cell carcinoma of the oropharynx (SCC-OP) have improved overall survival (OS) after distant metastasis (DM) compared to HPV negative patients. These patients may be appropriate candidates for enrollment on clinical trials evaluating the efficacy of metastasis-directed therapy (MDT). This study seeks to identify prognostic factors associated with OS after DM, which could serve as enrollment criteria for such trials.

Open-label, Phase I Study of Nivolumab Combined with -Paclitaxel Plus Gemcitabine in Advanced Pancreatic Cancer.

Purpose: Assess safety and efficacy of nivolumab plus -paclitaxel and gemcitabine in patients with locally advanced/metastatic pancreatic cancer in a two-part, open-label, phase I trial.

Patients And Methods: Fifty chemotherapy-naive patients received -paclitaxel 125 mg/m plus gemcitabine 1,000 mg/m (days 1, 8, and 15) and nivolumab 3 mg/kg (days 1 and 15) in 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs; part 1) and grade 3/4 treatment-emergent adverse events (TEAEs) or treatment discontinuation due to TEAEs (parts 1/2).

Rethinking the 10-pack-year rule for favorable human papillomavirus-associated oropharynx carcinoma: A multi-institution analysis.

Background: De-intensified treatment strategies for early human papillomavirus-positive (HPV+) oropharynx cancer (OPC) rely on selecting patients with an excellent prognosis. The criterion for enrollment in current de-intensification trials is ≤10 pack-years. More nuance to the pack-year criteria may expand enrollment, improve patient outcomes, and prevent overtreatment.

Gene Therapy in Head and Neck Cancer.

Although overall cancer death rates are decreasing, comparative improvements in head and neck squamous cell cancer are modest. Although new advances targeting immune checkpoints may soon improve these numbers, additional research for new therapeutic options is vital. One potential treatment avenue is the use of gene therapy.

Tamoxifen Dose Escalation in Patients With Diminished CYP2D6 Activity Normalizes Endoxifen Concentrations Without Increasing Toxicity.

Background: Polymorphic CYP2D6 is primarily responsible for metabolic activation of tamoxifen to endoxifen. We previously reported that by increasing the daily tamoxifen dose to 40 mg/day in CYP2D6 intermediate metabolizer (IM), but not poor metabolizer (PM), patients achieve endoxifen concentrations similar to those of extensive metabolizer patients on 20 mg/day. We expanded enrollment to assess the safety of CYP2D6 genotype-guided dose escalation and investigate concentration differences between races.

New strategies in immunotherapy for non-small cell lung cancer.

Treatment for the most common form of cancer (lung cancer) has historically involved use of cytotoxic chemotherapy. With the advent of mutation analysis, more therapies beyond traditional cytotoxics have been discovered. Most recently, the use of immunotherapy has entered the treatment arsenal of non-small cell lung cancer (NSCLC).

In vivo assessment of the metabolic activity of CYP2D6 diplotypes and alleles.

Aims: A prospectively enrolled patient cohort was used to assess whether the prediction of CYP2D6 phenotype activity from genotype data could be improved by reclassification of diplotypes or alleles.

Methods: Three hundred and fifty-five patients receiving tamoxifen 20 mg were genotyped for CYP2D6 and tamoxifen metabolite concentrations were measured. The endoxifen : N-desmethly-tamoxifen metabolic ratio, as a surrogate of CYP2D6 activity, was compared across four diplotypes (EM/IM, EM/PM, IM/IM, IM/PM) that are typically collapsed into an intermediate metabolizer (IM) phenotype.

New targets and new mechanisms in lung cancer.

With the advent of the importance of histology in non-small-cell lung cancer (NSCLC) and the development of targeted agents that work on newly found mutations, the field of lung cancer therapy has greatly changed. In addition to new uses of chemotherapeutics and targeted agents, the possibilities of immunotherapy are also being explored. This review will describe the well-known use of vascular endothelial growth factor (VEGF) antibodies; the current uses of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors; newer agents being used against MET, fibroblast growth factor receptor (FGFR), and other intracellular targets; insights regarding the field of immunotherapy in lung cancer; and finally, newer developments in chemotherapy.

The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation.

BACKGROUND: Cranberry products have been implicated in several case reports to enhance the anticoagulant effect of warfarin. The mechanism could involve inhibition of the hepatic CYP2C9-mediated metabolic clearance of warfarin by components in cranberry. Because dietary/natural substances vary substantially in bioactive ingredient composition, multiple cranberry products were evaluated in vitro before testing this hypothesis in vivo.

Identification of a cranberry juice product that inhibits enteric CYP3A-mediated first-pass metabolism in humans.

An in vivo study in rats showed a cranberry juice product to inhibit the intestinal first-pass metabolism of the CYP3A substrate nifedipine. However, a clinical study involving the CYP3A probe substrate midazolam and a different cranberry juice product showed no interaction. Because the composition of bioactive components in natural products can vary substantially, a systematic in vitro-in vivo approach was taken to identify a cranberry juice capable of inhibiting enteric CYP3A in humans.

Adjuvant systemic therapy in young women.

About a third of all newly diagnosed breast cancers occur in women under the age of 50 [1,2]. Young women face many of the same adjuvant treatment issues that their postmenopausal counterparts encounter. Unfortunately, they also experience issues that are unique to their age, their hormonal status, and their longer life expectancy.