Early, precise, and safe clinical evaluation of the pharmacodynamic effects of novel agents in the intact human tumor microenvironment.

Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs.

Clarification of the margin status by the multidisciplinary tumor board following transoral robotic surgery for p16 positive oropharyngeal squamous cell carcinoma.

Objectives: Margin status interpretation following transoral robotic surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC) is challenging. This study aims to assess the discrepancy between status of margins as reported by the pathologist versus as determined by multi-disciplinary team review (MDTB).

Methods: A retrospective study of 57 patients with OPSCC who underwent TORS from January 2010 to December 2016 was conducted.

Radiation therapy for low- and high-risk perineural invasion in head and neck cutaneous squamous cell carcinoma: Clinical outcomes and patterns of failure.

Background: Perineural invasion (PNI) in head and neck squamous cell carcinoma (HNSCC) portends poor prognosis. Extent of treatment of nerve pathways with varying degrees of PNI and patterns of failure following elective neural radiotherapy (RT) remain unclear.

Methods: Retrospective review of HNSCC patients with high-risk (clinical/gross, large-nerve, extensive) or low-risk (microscopic/focal) PNI who underwent curative-intent treatment from 2010 to 2021.

Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment.

Purpose: Cancer drug development is currently limited by a paradigm of preclinical evaluation that does not adequately recapitulate the complexity of the intact human tumor microenvironment (TME). To overcome this, we combined trackable intratumor microdosing (CIVO) with spatial biology readouts to directly assess drug effects in patient tumors in situ.

Experimental Design: In a first-of-its-kind phase 0 clinical trial, we explored the effects of an investigational stage SUMOylation-activating enzyme (SAE) inhibitor, subasumstat (TAK-981) in 12 patients with head and neck carcinoma (HNC).

Peripheral lymphocytes and lactate dehydrogenase correlate with response and survival in head and neck cancers treated with immune checkpoint inhibitors.

Background: Little is known regarding associations between peripheral blood biomarkers (PBBMs) and survival, response, and toxicity in recurrent/metastatic head and neck squamous cell carcinomas (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs).

Methods: In this single-institution retrospective cohort study, a dataset of patients with R/M HNSCC treated with ICIs between 08/2012-03/2021 was established, including demographic and clinicopathologic characteristics. Pretreatment PBBMs were collected and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv5, objective response (ORR) by RECIST 1.

Neutrophil to lymphocyte ratio and peripheral blood biomarkers correlate with survival outcomes but not response among head and neck and salivary cancer treated with pembrolizumab and vorinostat.

Background: Associations between peripheral blood biomarkers and oncologic outcomes were explored in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HN) and salivary gland cancer (SGC) treated with pembrolizumab and vorinostat on a phase II trial (NCT02538510).

Experimental Design: Twenty-five HN and 25 SGCs were treated with pembrolizumab and vorinostat. Baseline peripheral blood was available in 21 HN and 20 SGCs and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv4, objective response rate (ORR), overall survival (OS), and progression-free survival (PFS).

Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer.

The tumour-associated microbiota is an intrinsic component of the tumour microenvironment across human cancer types. Intratumoral host-microbiota studies have so far largely relied on bulk tissue analysis, which obscures the spatial distribution and localized effect of the microbiota within tumours. Here, by applying in situ spatial-profiling technologies and single-cell RNA sequencing to oral squamous cell carcinoma and colorectal cancer, we reveal spatial, cellular and molecular host-microbe interactions.

Oncologic outcomes of salvage surgery and immune checkpoint inhibitor therapy in recurrent head and neck squamous cell carcinoma: A single-institution retrospective study.

Background: Survival outcomes in recurrent head and neck squamous cell carcinoma (HNSCC) are poor. This study aimed to compare survival outcomes between salvage surgery and immunotherapy in patients with recurrent advanced HNSCC.

Methods: Patients with advanced stage (stage III or IV) recurrent HNSCC following treatment with platinum-based chemotherapy were included.

A Biofabrication Strategy for a Custom-Shaped, Non-Synthetic Bone Graft Precursor with a Prevascularized Tissue Shell.

Critical-sized defects of irregular bones requiring bone grafting, such as in craniofacial reconstruction, are particularly challenging to repair. With bone-grafting procedures growing in number annually, there is a reciprocal growing interest in bone graft substitutes to meet the demand. Autogenous osteo(myo)cutaneous grafts harvested from a secondary surgical site are the gold standard for reconstruction but are associated with donor-site morbidity and are in limited supply.

Performance status (PS) as a predictor of poor response to immune checkpoint inhibitors (ICI) in recurrent/metastatic head and neck cancer (RMHNSCC) patients.

Background: Anti-PD1 checkpoint inhibitors (ICI) represent an established standard-of-care for patients with recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥2; the benefit of ICI in this population is therefore unknown.

Methods: We retrospectively reviewed RMHNSCC patients who received 1+ dose of ICI at our institution between 2013 and 2019.

Management of Malignant Salivary Gland Conditions.

Salivary cancers are rare tumors that arise in major and minor salivary glands. Workup almost always includes fine-needle aspiration or core needle biopsy in select cases. Imaging with ultrasound, computed tomography, or MRI is also helpful, particularly with MRI to assess facial nerve involvement or skull base involvement.

High End-of-Life Health Care Utilization in a Contemporary Cohort of Head and Neck Cancer Patients Treated with Immune Checkpoint Inhibitors.

End-of-life health care utilization (EOLHCU) is largely uncharacterized among patients with recurrent/metastatic head and neck squamous cell carcinomas (RMHNSCC), particularly now that immune checkpoint inhibitors (ICI) have been introduced to the treatment landscape. We examined this in a single-institution, retrospective study. We utilized a database of deceased, ICI-treated RMHNSCC patients to obtain demographic and EOLHCU data, the latter of which included advanced care plan documentation (ACPD) and systemic therapy or emergency room (ER)/hospital/intensive care unit (ICU) admission within 30 days of death (DOD).

Timing of postoperative radiation therapy and survival in resected salivary gland cancers: Long-term results from a single institution.

Objectives: Timely administration of postoperative radiation therapy (PORT) impacts oncologic outcomes in resected squamous cell carcinomas of the head and neck. Salivary gland cancers (SGCs) are uncommon, and timing of PORT has not been extensively explored. We aimed to determine if the interval between surgery and PORT impacts outcomes in SGCs.

High rates of postoperative radiotherapy delay in head and neck cancer before and after Medicaid expansion.

Background: The objective is to study the effect of Medicaid expansion on postoperative radiation therapy (PORT) delay in patients with head and neck squamous cell carcinoma (HNSCC).

Methods: Patients from the National Cancer Database with HNSCC undergoing curative-intent surgery in the 2 years before and after Medicaid expansion were analyzed (n = 11 717) using the difference-in-differences technique to study the effect on PORT delay.

Results: The rate of PORT delay before and after expansion was 66.

Oncologic outcomes of human papillomavirus-associated oropharynx carcinoma treated with surgery alone: A 12-institution study of 344 patients.

Background: The oncologic outcomes of surgery alone for patients with American Joint Committee on Cancer 7th edition (AJCC 7th) pN2a and pN2b human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+OPSCC) are not clear.

Methods: The authors performed a 12-institution retrospective study of 344 consecutive patients with HPV+OPSCC (AJCC 7th pT0-3 N3 M0) treated with surgery alone with 6 months or more of follow-up using univariate and multivariate analyses.

Results: The 2-year outcomes for the entire cohort were 91% (182 of 200) disease-free survival (DFS), 100% (200 of 200) disease-specific survival (DSS), and 98% (200 of 204) overall survival (OS).

Neutron Therapy for High-Grade Salivary Carcinomas in the Adjuvant and Primary Treatment Setting.

Objectives/hypothesis: Our primary objective was to compare differences in survival of patients with high-grade salivary gland carcinomas (SGCs) receiving adjuvant neutron versus photon radiotherapy using a hospital-based national cohort and restricted mean survival time (RMST) analysis. Our secondary objective was to compare survival of similar patients treated with primary neutron versus photon radiation.

Study Design: Multicenter, retrospective population-based study of patients within the National Cancer Database from 2004 to 2014.

The role of elective neck dissection in high-grade parotid malignancy: A hospital-based cohort study.

Objectives/hypothesis: The role of elective neck dissection (END) in patients with clinically N0 (cN0), high-grade parotid carcinoma is unclear. The objective of this study was to assess the association between END and survival in patients with cN0, high-grade parotid carcinoma.

Study Design: Retrospective, multicenter cohort study.

Optimizing value in head and neck cancer free flap surgery.

Purpose Of Review: Value has become an increasingly important topic in healthcare delivery as our systems attempt to deliver increased value to patients at lower costs. This review highlights research performed regarding value for head and neck cancer reconstruction in three evolving areas: care pathway development, virtual surgical planning (VSP), and free flap versus locoregional flap reconstruction.

Recent Findings: Improvements in quality-driven patient care in head and neck free tissue transfer are possible in a number of areas.

Surgical Options for Locally Advanced Oropharyngeal Cancer.

Oropharyngeal squamous cell carcinoma (OPSCC) incidence rates have been steadily increasing over the past several decades, and this has been largely attributed to human papillomavirus (HPV)-related OPSCC. The rise of HPV-related OPSCC and the observed distinct survival advantage it offers compared to HPV-unrelated OPSCC have resulted in the development of a new staging system specifically for OPSCC in the eighth edition of the AJCC Staging Manual for head and neck cancer. The observations on HPV-related OPSCC and its prognostic implications have coincided with increasing utilization of transoral surgical approaches to oropharyngeal tumors, such as transoral laser microsurgery (TLM) and transoral robotic surgery (TORS).

Adjuvant radiation for positive margins in adult head and neck sarcomas is associated with improved survival: Analysis of the National Cancer Database.

Background: Adult head and neck (H&N) sarcomas are a rare malignancy with limited data delineating the role of postoperative radiotherapy (PORT), particularly for a positive surgical margin. There are no randomized trials supporting the use of PORT, therefore treatment trends vary between institutions. A positive margin predicts recurrence and poor survival outcomes.

Patterns of cervical node positivity, regional failure rates, and fistula rates for HPV+ oropharyngeal squamous cell carcinoma treated with transoral robotic surgery (TORS).

Objectives: (1) Report the patterns of cervical node positivity for HPV + oropharyngeal squamous cell carcinoma (OPSCC) treated with transoral robotic surgery (TORS) and a unilateral level II-IV node dissection. (2) Investigate the regional failure rate following this operation. (3) Report the rate of pharyngocutaneous fistula (PCF) formation intraoperatively and postoperatively following TORS/neck dissection.

Treatment of Tonsillar Carcinoma following Nononcologic Tonsillectomy: Efficacy of Transoral Robotic Revision Tonsillectomy.

Objective: To evaluate whether transoral robotic surgery (TORS) is a suitable treatment approach for patients diagnosed with tonsillar carcinoma after a standard palatine tonsillectomy.

Study Design: Retrospective cohort study.

Setting: Tertiary care medical center.