Background: The ablation of advanced head and neck cancer often results in large three-dimensional defects that require free tissue transfer to optimally address functional and cosmetic issues. The subscapular system is a highly versatile donor site for flaps used for head and neck reconstruction. Traditional methods of harvesting subscapular flaps require repositioning and re-preparing, which significantly increases the operative time and prevents simultaneous harvesting of the flap. Method: This paper presents our experience of a single-stage 'sit and tilt' technique, which provides a convenient method for harvesting subscapular system free flaps without significant repositioning. Results and conclusion: This technique was used for a variety of head and neck defects, and body habitus did not seem to affect free tissue harvesting. It is hoped that utilisation of this preparation and harvesting technique will make head and neck surgeons more willing to take advantage of the subscapular system.

Approximately 60% of head and neck squamous cell carcinoma (HNSCC) patients present with locally advanced disease. Surgical candidates often receive postoperative radiation and cisplatin if they have high-risk pathological features. Despite intensive therapy, up to 50% of patients will suffer relapse. Therefore, improved treatment modalities are desperately needed. The checkpoint inhibitor, programmed death-ligand 1 (PD-L1), is upregulated in HNSCC and treatment with anti-PD-1 inhibitor (pembrolizumab) was shown to decrease tumor burden in patients with recurrent/metastatic HNSCC. Additionally, PD-L1 expression is increased in response to radiation treatment both in vitro and in vivo. Importantly, pretreatment with anti-PD-L1 antibody prior to radiation resulted in increased survival of mice with implanted HNSCC tumors compared to radiation alone. Therefore, we hypothesized that neoadjuvant pembrolizumab is active in previously untreated HNSCC and concurrent adjuvant treatment with pembrolizumab combined with standard of care would result in decreased relapse. To test this hypothesis, a multisite “Phase 2 Investigation of Adjuvant Combined Cisplatin and Radiation with Pembrolizumab in Resected HNSCC” (NCT02641093) funded by Merck was initiated. Eligible patients with high-risk (Stage III/IV) locally advanced HNSCC were consented to receive pembrolizumab 200 mg I.V. 1-3 weeks before planned surgical resection. Pretreatment biopsies and postoperative specimens were archived for H&E and immunohistochemistry. Peripheral blood was collected for ELISA. Following resection, patients were stratified based on pathological risk to receive adjuvant standard of care (SOC) combined with pembrolizumab every three weeks for a total of seven doses. Patients are followed for disease-free and overall survival. Safety was determined by delays in SOC treatment. Sixteen of 80 planned patients have been enrolled. To date, 3 patients were replaced due to pre-surgical infection, discovery of a secondary medullary thyroid cancer, and withdrawal of consent. Preliminary results show 8 of 10 patients demonstrated a pathological tumor response after a single dose of pembrolizumab. Tumor immune cell infiltration was not significantly changed, however, there was an increase in plasma proinflammatory cytokines with treatment. Interestingly, only the 2 patients without a pathological tumor response after pembrolizumab recurred (8 month [range 2-21 months] median time to follow-up). No delays in SOC treatment have occurred. Preliminary results demonstrated tumor responses after just one dose of pembrolizumab in previously untreated HNSCC patients that may predict patient outcome.

Cutaneous squamous cell carcinoma of the head and neck (cHNSCC) is a common malignancy in the United States strongly associated with exposure to ultraviolet radiation. Surgical resection is curative in the vast majority of cases, but 15% of patients with cHNSCC exhibit aggressive features with a propensity for locoregional recurrence, distant metastasis, and poor prognosis. Several large-scale whole-exome sequencing studies have provided valuable insight into the mutational landscape of mucosal HNSCC but such information is much more limited for cHNSCC. To address this deficiency, we performed exome-sequencing of cHNSCC to further elucidate potential driver mutations of cHNSCC and bolster our understanding of the molecular underpinnings of these aggressive malignancies. We obtained OCT-embedded tumor tissue and paired blood samples from 21 cases with aggressive cHNSCC from our institutional tumor bank, including tissue from 10 primary tumors, 2 nodal metastases, and 11 recurrent tumors. Genomic DNA (200 ng) was extracted from each sample using the DNeasy Blood & Tissue kit (Qiagen) according to the manufacturer’s suggested protocol for purification of total DNA from human tissue and blood, respectively, and sheared to 150-200 bp. The sequencing library was prepared using the Agilent SureSelect Human All Exon V6 Target Enrichment System. Clustered libraries were paired-end sequenced for 2′100 cycles on an Illumina HiSeq platform. Sequencing reads were demultiplexed and mapped to the GRCh37/hg19 human genome assembly using the Burrows-Wheeler aligner. Point mutations were detected via MuTect2 and insertion/deletions were identified via Indelocator using the Genome Analysis Toolkit. Intronic and silent mutations were filtered out prior to reporting. Significantly mutated genes were identified using MutSigCV v.1.41 with significance considered where P < .001. The average depth of coverage was 96.5′. The most common significantly mutated genes were CSMD3 (18/21 tumors; 85.7%), TP53 (17/21 tumors; 81.0%), NOTCH1 (14/21 tumors; 66.7%), and COL1A2 (13/21 tumors; 61.9%). Moreover, five of the significantly mutated genes previously reported by Pickering et al. (2014) were further validated by our study: TP53 (P = 7.77′10-16), NOTCH1 (P = .001), NOTCH2 (P = 0.007), FAT1 (P = .04), and CDKN2A (P = .02). The combined fraction of tumors across both studies (n = 60) that harbored a mutation in each of these genes was 90.0%, 61.7%, 48.3%, 45.0%, and 33.3%, respectively. We were able to validate several previously identified driver mutations, as well as identify novel putative driver mutations, thus advancing our understanding of the somatic mutations involved in the genesis of cHNSCC.

A case of invasive, keratinizing squamous cell carcinoma of the larynx in an 8-year-old female treated with laryngectomy is presented. Perinatal exposure to human papilloma virus and constitutional heterozygosity for a FANCC mutation were identified, though FANCC heterozygosity is not known to be cancer predisposing. An additional tumor-associated mutation in NOTCH1 was also identified potentially contributing to oncogenesis. This case illustrates an exceedingly rare type of cancer in the pediatric population and discusses diagnostic workup, evaluation of risk factors for head and neck cancer, and treatment options.

Head and neck cancer remains the sixth most common cancer worldwide. Although infection with human papillomavirus (HPV) has emerged as a favorable prognostic factor, no plasma biomarkers currently exist to predict tumor response and/or relapse. One candidate plasma biomarker is encoded by the human DEK gene. DEK is an apoptosis and differentiation inhibitor and overexpression results in oncogenesis. DEK knockdown results in decreased growth and apoptosis of cancer cells. DEK mRNA and protein are highly up-regulated in tissue specimens from several tumor types, including head and neck squamous cell carcinoma (HNSCC), breast cancer, and melanoma, and antibodies to DEK are detected in patients with autoimmune disease. High levels of tumor DEK mRNA are correlated with advancing stage and poor survival. However, our previous work has demonstrated that DEK protein is present in HNSCC tissue specimens regardless of stage or HPV infection. Additionally, in vitro data have suggested that tumor-associated macrophages secrete DEK protein. Therefore, we sought to determine whether plasma DEK protein may have a different value than tissue levels leading to the hypothesis that DEK may be present in the plasma of cancer patients and may be correlated with patient outcome. Peripheral blood was collected from patients with newly diagnosed or untreated HNSCC and age-matched normal healthy controls. Plasma was separated from the samples and subjected to DEK-specific ELISA (Cusabio, Wuhan, China). Plasma DEK levels were compared to normal controls, tumor stage, age, and smoking status. Plasma DEK levels were also compared to inflammatory markers in the plasma and tissue. DEK was indeed found to be present in the plasma of both healthy control subjects and those with head and neck cancer. DEK was decreased in head and neck cancer patients compared to healthy patients and inversely correlated with IL-6 in the plasma. Immune infiltration (defined by presence of CD8+ T cells) of the tumor also appeared to be correlated with high DEK plasma levels. Interestingly, although DEK expression is increased in head and neck cancer tissue, plasma DEK levels are decreased in patients with cancer compared to controls and are further decreased with advancing stage. DEK plasma levels are inversely correlated with IL-6 levels, suggesting that high plasma DEK levels may be correlated with a better prognosis. Furthermore, high DEK levels in the plasma may predict superior immune infiltration of tumors. Further analyses are ongoing to determine whether DEK levels predict response to various treatment modalities, correlate with the body’s immune response, and whether DEK presence in the plasma will predict residual disease and/or early relapse. These data will be important to verify DEK plasma measurements as a clinically useful test and may give insight to future personalized and targeted treatment strategies for HNSCC.

Each year, more than 12,000 people in the United States are diagnosed with cancer of the larynx, and nearly 3700 die from the disease. The 2 primary treatment options for patients with advanced disease are chemoradiation (CRT) or surgery. The results of the Veterans Affairs Laryngeal Study Group demonstrated equivalent 2-year overall survival between these 2 approaches. Due to this, definitive therapy for locally advanced laryngeal cancer has shifted to an organ-preservation approach with surgery increasingly being reserved for salvage; however, approximately 25% of the patients initially undergoing CRT will eventually require salvage total laryngectomy due to recurrent disease or an incompetent larynx. Patients that require salvage surgery have the possibility of long-term survival, but there is a subset of patients that do poorly, either from postoperative complications or early secondary recurrence. The aim of the study was to identify clinical factors that might predict early failure and/or worse outcome after salvage laryngectomy in patients initially treated with definitive CRT for advanced laryngeal cancer. This was a retrospective chart review of salvage laryngectomies performed for advanced laryngeal squamous cell carcinoma at a single academic institution. An existing prospectively collected database of head and neck cancer patients was queried to identify patients who had undergone salvage laryngectomies. Additional pertinent information on the identified patients was gathered from manual chart review for analysis after institutional review board approval was obtained. Patients were separated into groups based upon how quickly they recurred after primary therapy with CRT: group 1 was defined as patients that relapsed in less than 1 year, and group 2 consisted of patients that recurred after the 1-year mark. Survival in each group was estimated using the Kaplan-Meier method, and differences between curves were assessed by the log-rank test. A multivariable Cox proportional hazards model was used to estimate the hazard ratio, adjusted for age and initial stage at diagnosis. The 2 groups were homogeneous with respect to age, sex, race, and disease location/severity. The Kaplan-Meier analysis indicated that laryngeal cancer patients with a recurrence less than 1 year after definitive chemoradiation (group 1) fared poorer than those with later recurrences (P=.06). After adjusting for patient age and stage at diagnosis, patients in group 1 still experienced poorer outcomes, although the results were not significant (hazard ratio=2.30, 95% confidence interval: 0.79-6.73). Patients with larynx cancer who initially undergo CRT who relapse in less than a year have lower overall survival and are less likely to benefit from a salvage total laryngectomy.