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BACKGROUND This systematic review and meta-analysis sought to assess the extent to which pretreatment depression or depressive symptoms are related to prognosis in patients with head and neck cancer (HNC). METHODS Medline, EMbase, Scopus, and The Cochrane Library databases were searched. A meta-analysis was done to generate a forest plot and pooled hazard ratio (HR) with 95% CI for overall survival (OS). RevMan 5.3 and Meta Essentials were used for statistical analysis. RESULTS Based on seven studies involving 1743 patients, the results showed that HNC patients with pretreatment depression or depressive symptoms had worse OS than patients without depression or depressive symptoms, with an HR of 1.33, 95% CI 1.16-1.52, p =

Background Recently, histologic grade was removed from salivary tumor nomenclature by the WHO to include disease of higher grade. One such entity, cribriform adenocarcinoma (CAC), is an aggressive group of polymorphous adenocarcinoma (PAC), with frequent nodal metastasis and locoregional recurrence. We aim to examine the biologic behavior of this disease as compared with the PAC general cohort inclusive of all subtypes. Methods A systematic review of the literature on polymorphous adenocarcinoma and cribriform adenocarcinoma was completed. A descriptive analysis was performed for the following predictor variables: nodal and distant metastasis, in addition to recurrence. The outcome variables, disease free recurrence, and disease specific survival, where plotted using Kaplan-Meier curves. Results PAC and CAC both show median age of diagnosis in the sixth decade of life and a female predominance. CAC occurs most frequently in the tongue and PAC in the palate. The 2 groups show a similar biologic behavior in regards to incidence of distant metastasis (4.1 vs 5.5%), recurrence (12.5 vs 17.8%), and death from disease (3 vs 2.7%). However, there was an increased incidence of nodal metastasis in CAC (53%) as compared with that in PAC of all subtypes (14%). Conclusions CAC exhibits more aggressive biologic behavior as compared with the PAC cohort. Although CAC is not an officially recognized entity, these tumors likely comprise a significant portion of the cases of PAC with poor outcomes and are deserving of attention and consideration for escalation in oncologic treatment.

Surgery is the preferred treatment of benign parotid lesions, but it carries a risk of complications. Therefore, the approach toward the surgery of these lesions should seek to avoid complications. There are no guidelines or recommendations for when not to operate. Integration of comorbidities and other factors shift the scales from surgery toward observation in a small subset of patients presenting with parotid tumors. When observation is chosen, the patient should be followed frequently and cautiously, and the surgeon should be prepared to change strategy to surgical excision if in doubt.

BACKGROUND Medical litigation is different than it was 20 years ago due to changes in health care. This study provides an updated analysis of oral cavity malpractice litigation from the past two decades (2000-2010 and 2011-2019). METHODS Verdict reviews from the Westlaw database were analyzed from January 2000 to August 2019. Data were collected and analyzed with the Statistical Package for the Social Sciences. RESULTS Sixty-five lawsuits were evaluated across 24 states. Failure to diagnose was the most common allegation in both decades. Adjusting for inflation, the average amount awarded from 2000 to 2010 was $1 721 068 and $3 925 504 from 2011 to 2019. CONCLUSIONS There has been a significant rise in allegations of failure to biopsy and failure to refer (p

Aim: 2-Hydroxyglutarate (2-HG) is a target engagement biomarker in patients after treatment with inhibitors of mutated isocitrate dehydrogenase (mIDH). Accurate measurement of 2-HG is critical for monitoring the inhibition effectiveness of the inhibitors. Materials & methods: Human plasma samples were spiked with stable isotope labelled internal standard, processed by protein precipitation, and analyzed using LC–MS/MS. This method was validated following regulatory guidance and has been successfully applied in a clinical study for mIDH inhibition. Results: An LC–MS/MS method with a surrogate analyte approach was developed and validated to measure 2-HG in human plasma with acceptable intra- and inter-assay accuracy and precision. Conclusion: A sensitive and robust LC–MS/MS method was developed and validated for measuring 2-HG in human plasma.

Objective IRX-2 is a homologous cell-derived multi-cytokine biologic with multifaceted immune modulatory effects that has been shown to induce increased lymphocyte infiltration into primary tumors in oral cavity carcinoma. Our objective was to characterize tumor immune gene expression and epigenomic changes after neoadjuvant IRX-2 immunotherapy in patients with squamous cell carcinoma of the oral cavity. Methods A randomized phase II trial was conducted of the IRX regimen 3 weeks prior to surgery for previously untreated patients with Stage II-IV oral cavity carcinoma. The treatment regimen consisted of low dose (300 mg/m2) cyclophosphamide (day 1) followed by 10 days of regional perilymphatic IRX-2 cytokine injections and daily oral indomethacin, zinc and omeprazole (Regimen 1) compared to the identical regimen without the IRX-2 cytokines (Regimen 2). The NanoString immune panel (730 genes) and Infinium MethylationEPIC BeadChip were performed to assess the gene expression and DNA methylation signatures, respectively, in pre- and post-immunotherapy tumor samples. Results A total of 51 and 79 immune-related genes were found upregulated and downregulated, respectively, in the samples from Regimen 1 patients after treatment, while 51 and 56 were found upregulated and downregulated in the samples for Regimen 2. When comparing the changes between the two regimens, we identified 9 genes significantly different, including DMBT1, a potential tumor suppressor, functioning in tumor invasion of head and neck cancer. The exploration of DNA methylation showed slight overall hypermethylation after treatment in both regimens, especially for Regimen 1 immune responders, and methylation-based cell type deconvolution demonstrated high concordance with tumor infiltrating T lymphocyte cell counts. Conclusion While a consistent patient response after treatment was observed, most changes were similar between regimens, indicating a subtle, targeted, or patient-specific effect of IRX-2 cytokines. Change in DMBT1 expression was a unique finding that will require further study to better understand its significance.

OBJECTIVE To determine whether radiologically defined sarcopenia at the C3 or L3 level as measured by computed tomography or magnetic resonance imaging is prognostic of overall survival (OS) in head and neck cancers (HNCs). METHODS Literature searches of PubMed, Embase, and Scopus were conducted on July 12, 2019, to include articles written in the English language with no constraints on publication date. To be included in the analysis, articles had to report the prognostic impact of skeletal muscle mass measured radiologically at the C3 or L3 vertebral level in HNC patients; hazard ratios (HRs) for OS; 95% confidence intervals (CIs); be from a clinical trial, cohort, or case-control study; and have English full-text availability. Articles were reviewed in consensus by two reviewers, with disagreements reviewed by a third reviewer. Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis Of Observational Studies in Epidemiology Checklist guidelines were used for reporting. Study quality assessment was performed using Quality In Prognosis Studies tool. The random-effects DerSimonian and Laird method was used for meta-analysis. RESULTS Ten articles, nine retrospective and one prospective, were included in this meta-analysis (n = 2,181 patients). Significant differences were found in OS for HNC patients with sarcopenia (HR = 1.98; 95% CI: 1.64-2.39; P

Purpose To investigate the etiologic and prognostic role of Human Papilloma Virus (HPV) in Nasopharyngeal Carcinoma (NPC). Materials and methods Patients diagnosed with NPC were identified with the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was used to investigate the effect of clinicopathologic predictors on HPV positivity in NPC. Survival analyses were performed with Kaplan-Meier curves and Cox regression models. Results 180/517 patients (34.8%) with known HPV testing were positive for HPV-associated NPC. East Asians and individuals over 25 were less likely to have HPV-associated NPC, while controlling for AJCC-7 stage and AJCC-7 M stage. According to the survival analysis, cause-specific survival (CSS) did not differ significantly by HPV status throughout the study period, but did differ significantly by HPV ethnicity group. Conclusions The clinical implications of HPV in NPC are further elucidated but require more investigation. Level of evidence IV.

Surgery is the preferred treatment of benign parotid lesions, but it carries a risk of complications. Therefore, the approach toward the surgery of these lesions should seek to avoid complications. There are no guidelines or recommendations for when not to operate. Integration of comorbidities and other factors shift the scales from surgery toward observation in a small subset of patients presenting with parotid tumors. When observation is chosen, the patient should be followed frequently and cautiously, and the surgeon should be prepared to change strategy to surgical excision if in doubt.

Background Patients with head and neck cancer (HNC) frequently experience disease-related symptoms and treatment adverse effects that impact their overall quality of life. Cancer-specific mobile health apps for patient-related outcomes allow patients to communicate with their clinicians and proactively track their symptoms, which have been shown to improve clinical management and disease outcomes. Objective The purpose of this study was to evaluate the feasibility of LogPAL, a novel iPhone-based mobile health app designed to help HNC survivors track and manage their posttreatment symptoms. Methods Patients who completed curative treatment for HNC in the preceding 24 months were recruited from 2 clinical sites within a single institution. Upon enrollment, participants completed a brief sociodemographic survey, downloaded the app onto their iPhone devices, and were asked to complete a series of biweekly questionnaires (based on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events) via the app for an 8-week study period. The primary feasibility endpoints included retention (retaining >80% of the enrolled participants for the duration of the study period), adherence (>50% of the participants completing 100% of the questionnaires over the study period), and usability (a mean system usability scale [SUS] score >68). Additional postintervention questions were collected to assess perceived usefulness, acceptance, and overall satisfaction. Results Between January and October 2019, 38 participants were enrolled in the study. Three participants dropped out, and 3 were classified as nonusers. The remaining 32 (87%) were eligible for analysis. Their mean age was 57.8 (SD 12.3) years (range 24-77 years, 81% [26/32] male). Overall, 375 of 512 (73.2%) questionnaires were completed, with 17 (53%) of the 32 participants adherent. Participant-reported usability was acceptable; the mean SUS score was 71.9 (95% CI 64.3-79.5) with high satisfaction of LogPAL usefulness and likelihood to recommend to other cancer survivors. Conclusions This single-arm prospective pilot study showed that LogPAL is a feasible, regularly used, accepted app for HNC survivors, justifying a full-scale pilot. Based on the findings from this study, future iterations will aim to improve usability and test intervention efficacy.

This article provides best practice guidelines regarding nasopharyngolaryngoscopy and OHNS clinic reopening during the COVID‐19 pandemic. The aim is to provide evidence‐based recommendations defining the risks of COVID‐19 in clinic, the importance of pre‐visit screening in addition to testing, along with ways to adhere to CDC guidelines for environmental, source, and engineering controls.

Aim: Current guidelines recommend p16 immunohistochemistry (IHC) for testing human papillomavirus (HPV) in oropharyngeal carcinoma (OPSCC). We evaluated the value of adding DNA in situ hybridization (ISH) to p16 IHC. Methods: Fifty patients with OPSCC were analyzed. Concordance between HPV–DNA ISH and p16 IHC was measured by Gwet's agreement coefficient. Results: p16 IHC was positive in 35/48 (72.9%), negative in 8/48 (16.7%) patients. Wide spectrum DNA–ISH was positive in 9/23 (39%) and negative in 14/23 (60.9%) patients. High-risk 16/18 (HR) HPV DNA–ISH was positive in 11/23 (47.8%) and negative in 12 (52.2%) patients. The agreement between HPV DNA–ISH and p16 IHC is fair (Gwet's AC1 = 0.318). Conclusion: The agreement between p16 IHC and HPV–DNA ISH was fair. However, ISH sensitivity was low. Our findings add to the current data that p16 IHC testing is reliable and may be enough as a stand-alone test for HPV detection in OPSCC., Lay abstract Current testing guidelines recommend p16 immunochemistry (IHC) for detecting human papillomavirus (HPV) in oropharyngeal cancer (OPSCC). We evaluated the value of adding HPV DNA in situ hybridization (ISH) to p16 IHC. Fifty patients with OPSCC were analyzed. p16 IHC was positive in 72.9% of patients and DNA–ISH was positive in 39% of patients when wide spectrum probe was used and positive in 47.8% of patients when high-risk probe was used. The agreement between the two tests was fair. However, DNA–ISH sensitivity was low. p16 IHC may be enough as a stand-alone test for detection of HPV in OPSCC.

BACKGROUND Patients with head and neck cancer (HNC) frequently experience disease-related symptoms and treatment adverse effects that impact their overall quality of life. Cancer-specific mobile health apps for patient-related outcomes allow patients to communicate with their clinicians and proactively track their symptoms, which have been shown to improve clinical management and disease outcomes. OBJECTIVE The purpose of this study was to evaluate the feasibility of LogPAL, a novel iPhone-based mobile health app designed to help HNC survivors track and manage their posttreatment symptoms. METHODS Patients who completed curative treatment for HNC in the preceding 24 months were recruited from 2 clinical sites within a single institution. Upon enrollment, participants completed a brief sociodemographic survey, downloaded the app onto their iPhone devices, and were asked to complete a series of biweekly questionnaires (based on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events) via the app for an 8-week study period. The primary feasibility endpoints included retention (retaining >80% of the enrolled participants for the duration of the study period), adherence (>50% of the participants completing 100% of the questionnaires over the study period), and usability (a mean system usability scale [SUS] score >68). Additional postintervention questions were collected to assess perceived usefulness, acceptance, and overall satisfaction. RESULTS Between January and October 2019, 38 participants were enrolled in the study. Three participants dropped out, and 3 were classified as nonusers. The remaining 32 (87%) were eligible for analysis. Their mean age was 57.8 (SD 12.3) years (range 24-77 years, 81% [26/32] male). Overall, 375 of 512 (73.2%) questionnaires were completed, with 17 (53%) of the 32 participants adherent. Participant-reported usability was acceptable; the mean SUS score was 71.9 (95% CI 64.3-79.5) with high satisfaction of LogPAL usefulness and likelihood to recommend to other cancer survivors. CONCLUSIONS This single-arm prospective pilot study showed that LogPAL is a feasible, regularly used, accepted app for HNC survivors, justifying a full-scale pilot. Based on the findings from this study, future iterations will aim to improve usability and test intervention efficacy.

During last 22 years the different reports have shown successful using of vascularized single fibular transplant for a simultaneous bilateral segmental mandibular reconstruction. The surgeries were performed in cases of bilateral mandibular defects of different origin: 1) bilateral infected pseudoarthrosis, 2) bilateral squamous cell carcinoma of the mandible, 3) bilateral ossifying fibroma, 4) osteoradionecrosis that caused mandibular defects, and 5) traumatic mandibular defects. We present a case of a 60-year-old patient who was referred to our clinic with osteoradionecrosis of bilateral mandible, which was reconstructed using a single fibula flap. A 6-month follow-up images are presented.

To investigate the association between race and ethnicity and prognosis in head and neck cancers (HNC), while controlling for socioeconomic status (SES).Medline, Scopus, EMBASE, and the Cochrane Library were used to identify studies for inclusion, from database inception till March 5th 2019. Studies that analyzed the role of race and ethnicity in overall survival (OS) for malignancies of the head and neck were included in this study. For inclusion, the study needed to report a multivariate analysis controlling for some proxy of SES (for example household income or employment status). Pooled estimates were generated using a random effects model. Subgroup analysis by tumor sub-site, meta-regression, and sensitivity analyses were also performed. RevMan 5.3, Meta Essentials, and OpenMeta[Analyst] were used for statistical analysis.Ten studies from 2004 to 2019 with a total of 108,990 patients were included for analysis in this study. After controlling for SES, tumor stage, and treatment variables, blacks were found to have a poorer survival compared to whites (HR = 1.27, 95%CI: 1.18-1.36, p 0.00001). Subgroup analysis by sub-site and sensitivity analysis agreed with the primary result. No differences in survival across sub-sites were observed. Meta-regression did not identify any factors associated with the pooled estimate.In HNC, blacks have poorer OS compared to whites even after controlling for socioeconomic factors.

Die Nachfrage von Patienten nach informativen Videos wächst. Das können sich Therapeuten zunutze machen, indem sie per Video ihr Fachwissen jederzeit und überall verfügbar machen. Damit steigern sie ihren Expertenstatus und gewinnen an Wertschätzung. Physiotherapeut und physiopraxis-Themenscout Dennis Kraus zeigt, wie man in neun Schritten zur perfekten Aufnahme kommt.

OBJECTIVE To determine if delayed or prolonged treatment-related time intervals (TRTIs) was associated with survival in patients with nasopharyngeal carcinoma (NPC) undergoing curative-intent concurrent chemoradiation (CCRT). The TRTIs investigated were duration of radiation treatment (RTd), time to radiation start (TTR), and time to chemotherapy start (TTC). METHODS Observational cohort study using the National Cancer Database (NCDB). In this observational cohort study, 3,893 eligible patients with NPC were identified from the NCDB. Patients received CCRT of at least 66 grays and radiation treatment time of at least 40 days. Separate univariable Cox regression model was used to analyze overall survival (OS) as a function of TRTIs, as well as for Charlson/Deyo Score, tumor classification, node classification, histological type, ethnicity, age, sex, and facility type. Upon finding significance at P < 0.05, the multivariable Cox regression analysis with backward elimination was performed to yield the final prediction model. Results were considered statistically significant when P < 0.05. RESULTS Radiation treatment was significantly associated with OS in the univariable analysis (hazard ratio: 1.006, 95% confidence interval = 1.004-1.008, P < 0.001). However, RTd was not related to OS in the multivariable analysis (P = 0.19). The TTR and TTC variables were not associated with OS in the univariable analysis (P = 0.88 and P = 0.88, respectively). CONCLUSION TRTIs were not independently associated with OS in this cohort of NPC patients in the NCDB. Future research into the association of TRTI with other disease outcomes, such as disease-free survival and locoregional control, is needed. LEVEL OF EVIDENCE NA. Laryngoscope, 129:2514-2520, 2019.

Im Schnitt suchen Inhaber von physiotherapeutischen Praxen mehr als 150 Tage nach neuen Mitarbeitern. Bei Ergotherapeuten ist die Lage nicht anders – man kann also sagen, dass die aktuelle Mitarbeitersituation mehr als bescheiden aussieht. Es braucht Ideen, auch ungewöhnliche. physiopraxis-Themenscout Dennis Kraus gibt ein paar wertvolle Tipps, wie die Suche erfolgreich werden kann.

Im Schnitt suchen Inhaber von physiotherapeutischen Praxen mehr als 150 Tage nach neuen Mitarbeitern. Bei Ergotherapeuten ist die Lage nicht anders – man kann also sagen, dass die aktuelle Mitarbeitersituation mehr als bescheiden aussieht. Es braucht Ideen, auch ungewöhnliche. physiopraxis-Themenscout Dennis Kraus gibt ein paar wertvolle Tipps, wie die Suche erfolgreich werden kann.

Aktiv zuhören, screenen, erste Hypothese, Probebehandlung, Wiederbefund. Gehen Sie so vor? Oder erschlägt Sie die Komplexität Ihres Wissens und des vielerorts formulierten Anspruchs nach evidenzbasierter Therapie? Im Durchschnitt kommen die Patienten mit einem Sechser-Rezept in die Praxis. Beispielsweise mit Problemen im Bereich des SIG. Ich kenne etwa 15 Tests – nicht alle erfüllen die Gütekriterien. Wo fange ich an, wo höre ich auf? Kommt Ihnen das bekannt vor?

The positive predictive value (PPV) of 12-week post-therapy FDG-PET/CT is low in patients with Human Papillomavirus (HPV)-associated Oropharyngeal Squamous Cell Carcinoma (OPSCC) after treatment with definitive chemoradiation (CRT). Moreover, the diagnostic performance of post-CRT fine needle aspiration (FNA) in detecting persistent disease is unknown in this population. Given these important shortcomings in post-CRT treatment assessment, head and neck oncologists are limited in appropriately selecting patients for consolidative neck dissection, which results in over-treatment of a favorable risk population. Using the PubMed database, we performed a literature review of published series in HPV-associated OPSCC to investigate potential strategies for improvement of post-CRT neck assessment. Several different approaches were found, including continued surveillance with PET/CT, delayed timing of restaging PET/CT, initial response evaluation with multimodality or alternative imaging, and detection of circulating HPV DNA. At present, the optimal approach to post-CRT treatment assessment is unclear; further investigation and incorporation of new technologies and surveillance protocols will be highly beneficial for patients with HPV-associated OPSCC.

BACKGROUND Oropharyngeal squamous cell carcinomas (OPSCC) can occur in either tonsillar related areas (TRA) or nontonsillar areas (nTRA). The prognostic differences between these sites are unclear. This study investigated this question using the National Cancer Database (NCDB), controlling for other confounders including human papillomavirus (HPV) status. METHODS This NCDB study was conducted by stratifying the HPV-positive oropharyngeal cancer cohort into two primary groups, TRA and nTRA. Kaplan Meier survival analysis was stratified according to HPV status, and further analysis was conducted using multivariable Cox regression. RESULTS A total of 23 297 patients were included in this study. In the multivariable cox regression analysis, OPSCC subsite was found to be an independent prognostic factor for survival (TRA vs nTRA HR: 0.76, 95% CI: 0.67-0.86, P

The objective of this study was to investigate the prognostic role of three inflammatory markers: the neutrophil to lymphocyte ratio (NLR), the lymphocyte to monocyte ratio (LMR), and the platelet to lymphocyte ratio (PLR) as prognostic indicators in squamous cell carcinoma of the head and neck (HNSCC). Patients with HNSCC treated with primary surgery, with or without adjuvant radiochemotherapy were enrolled. The preoperative NLR, LMR, and PLR were recorded. Confounding variables were also recorded: age, sex, BMI, comorbidities, performance status, AJCC T and N stage and HPV status. Endpoints were overall survival (OS) and event-free survival (EFS). Survival analysis was performed using Kaplan–Meier analysis, and multivariable analysis was performed using Cox proportional hazards regression. Survival models were evaluated using Harrell’s concordance index (c-index). NLR (p = 0.2413), PLR (p = 0.1593), and LMR (p = 0.0552) were not significantly associated with OS in the multivariable analysis. With regard to EFS, low LMR (HR = 2.95, 95% CI 1.54–5.65, p = 0.001), high PLR (HR = 2.68, 95% CI 1.42–5.09, p = 0.003), and high NLR (HR = 3.37, 95% CI 1.7–6.69, p

Purpose To investigate the multidisciplinary management of patients with Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and an incomplete nodal response on restaging PET/CT after definitive chemoradiation (CRT). Materials and methods A retrospective chart review was performed of patients diagnosed with node-positive HPV-associated OPSCC from 2012 to 2017, who underwent definitive upfront CRT, and had an incomplete response on post-therapy PET/CT according to NCCN criteria. Post-CRT PET/CT results, management decisions, and clinical outcomes were recorded. Results Seventy-four patients with node-positive HPV-associated OPSCC were identified; 20 patients with incomplete neck response on PET/CT according to NCCN criteria were included in the final case series. Median follow-up time was 33 months. Patients were managed as follows: 8 underwent observation and surveillance imaging, 6 underwent ultrasound-guided fine needle aspiration (FNA), and 6 had immediate neck dissection. All the observed patients were disease-free at most recent follow-up. None of the patients who underwent immediate neck dissection had residual neck disease on pathological examination; two patients in this group ultimately developed metastatic disease. Among the 6 who underwent FNA, 1 individual had positive pathology, along with residual primary disease, for which the patient underwent salvage surgery. The 5 remaining individuals had negative FNA results, were subsequently observed, and remained free of disease. Conclusions This institutional experience supports the notion of a high threshold for neck dissection in this low-risk population; only 1 of 20 patients with suspicious PET/CT findings had residual disease in the neck. Moreover, these patients should be managed by a multidisciplinary tumor board (MTB) since current algorithms do not universally include HPV status. Finally, the use of restaging PET/CT to guide management of the neck can be improved with changes in terminology and consideration of FDG-avidity at the primary site and on pre-therapy scans.

Background The American Joint Committee on Cancer (AJCC) Precision Medicine Core (PMC) has recognized the need for more personalized probabilistic predictions above the "TNM" staging system and has recently released a checklist of inclusion and exclusion criteria for evaluating prognostic models. Methods A systematic review of articles in which nomograms were created for head and neck cancer (HNC) was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The AJCC PMC criteria were used to score the individual studies. Results Forty-four studies were included in the final qualitative analysis. The mean number of inclusion criteria met was 9.3 out of 13, and the mean number of exclusion criteria met was 2.1 out of 3. Studies were generally of high quality, but no single study fulfilled all of the AJCC PMC criteria. Conclusion This is the first study to utilize the AJCC checklist to comprehensively evaluate the published prognostic nomograms in HNC. Future studies should attempt to adhere to the AJCC PMC criteria. Recommendations for future research are given. Summary The AJCC recently released a set of criteria to grade the quality of prognostic cancer models. In this study, we grade all published nomograms for head and neck cancer according to the new guidelines.

Since most HPV-associated disease occurs in the tonsillar-related areas (TRA) - palatine and lingual tonsils, the effect of HPV on survival in non-tonsillar oropharyngeal subsites (nTRA) is not well established. The objective of this study was to use a large population-based cohort to investigate the survival impact of HPV in nTRA subsites versus TRA subsites.This SEER database study was conducted by stratifying the HPV-positive oropharyngeal cancer cohort into two primary groups, TRA and nTRA.HPV-positive squamous cell cancer was significantly more common in TRAs (73%) compared to nTRAs (31.2%, p 0.001). After controlling for age, treatment, stage, race, and income, patients with HPV-positive disease in nTRAs had a worse cause-specific survival (CSS) than individuals with HPV-positive disease in TRAs (HR = 2.16, 95% CI 1.20-3.86, p = 0.01).Patients with HPV-positive OPSCC in nTRAs had poorer survival outcomes compared to patients with HPV-positive OPSCC in TRAs.

Key Clinical Message Adenoid cystic carcinoma (ACC) is a rare malignant tumor of the salivary glands, with higher frequency in the submandibular gland, a prolonged clinical course, and poor long‐term survival. It tends to metastasize to lungs, bone, liver, brain, and rarely to skin. Comprehensive skin examination and appropriate follow‐up is recommended, since cutaneous metastasis represents disease progression, requiring management and prognosis adjustment.

Objectives IRX-2 is a primary-cell-derived immune-restorative consisting of multiple human cytokines that act to overcome tumor-mediated immunosuppression and provide an in vivo tumor vaccination to increase tumor infiltrating lymphocytes (TILs). A randomized phase II trial was conducted of the IRX regimen 3 weeks prior to surgery consisting of an initial dose of cyclophosphamide followed by 10 days of regional perilymphatic IRX-2 cytokine injections and daily oral indomethacin, zinc and omeprazole (Regimen 1) compared to the identical regimen without IRX-2 cytokines (Regimen 2). Methods A total of 96 patients with previously untreated, stage II-IV oral cavity SCC were randomized 2:1 to experimental (1) or control (2) regimens (64:32). Paired biopsy and resection specimens from 62 patients were available for creation of tissue microarray (n = 39), and multiplex immunohistology (n = 54). Increases in CD8+ TIL infiltrate scores of at least 10 cells/mm2 were used to characterize immune responders (IR). Results Regimen 1 was associated with significant increases in CD8+ infiltrates (p = 0.01) compared to Regimen 2. In p16 negative cancers (n = 26), significant increases in CD8+ and overall TILs were evident in Regimen 1 (p = 0.004, and 0.04 respectively). IRs were more frequent in Regimen 1 (74% vs 31%, p = 0.01). Multiplex immunohistology for PD-L1 expression confirmed an increase in PD-L1 H score for Regimen 1 compared to Regimen 2 (p = 0.11). Conclusions The findings demonstrate significant increases in TILs after perilymphatic IRX-2 injections. Three quarters of patients showed significant immune responses to IRX-2. (NCT 02609386).

Regional flaps remain a cornerstone of head and neck reconstruction. Among their many functions, they serve a vital role in salvage surgery and for those in whom medical comorbidities preclude the use of microvascular free flaps. Recent research has also examined their potential benefit in value-based healthcare metrics such as operative time, cost, intensive care unit care, and length of stay as compared to free-flap reconstruction. The submental island flap is one such entity that is well described and validated to provide predictable, oncologically sound coverage for defects of the lower third of the face and oral cavity. Its application has also been documented for repair of defects of the midface, temporal region, oropharynx, and hypopharynx, albeit less frequently. Since its original description, there have been several modifications of this axial-based flap, though none of a vertically oriented long axis. We describe a case of a vertically based submental island flap for maxillary reconstruction that allowed for debulking and recontouring of prior pectoralis flap and correction of submental ptosis.

We are reporting a validated LC–MS/MS assay for the quantitation of 2-Hydroxyglutarate (2-HG), an endogenous oncometabolite, in human brain tumors. To address the challenges of endogenous levels of 2-HG in biological matrix and the limited availability of human brain tumors, a surrogate analyte in conjunction with a surrogate matrix approach was used (stable isotope labeled 2-HG in monkey brain homogenate). Human brain tumor homogenate samples were spiked with stable isotope labeled internal standard, processed by protein precipitation, and analyzed using LC–MS/MS. The mass spectrometer was optimized to ensure equal molar response between 2-HG – the authentic analyte and 13C5 2-HG – the surrogate analyte. Parallelism was successfully demonstrated between human brain tumor homogenate (the authentic matrix) and monkey brain homogenate (the surrogate matrix). The linear analytical range of the assay was set at 0.15–150 μM. This validated LC–MS/MS method demonstrated excellent accuracy and precision. For 13C5 2-HG in monkey brain homogenate and human brain tumor homogenate, the overall accuracy was between 98.4 % and 102 %, and the intra- and inter-assay precision (%CV) were less than 5.7 %. 2-HG was found to be stable in human brain tumor homogenate for at least 26 h at room temperature, 454 days when stored at 70 °C and after five freeze/thaw cycles. The assay has been successfully applied to human brain tumor samples to support clinical studies. Novel Aspect: A surrogate matrix and surrogate analyte approach to quantify endogenous 2-HG concentrations in human brain tumors.

BACKGROUND This study sought to develop prognostic tools that will accurately predict overall and cancer-related mortality and risk of recurrence in individual patients with oral cancer based on host and tumor characteristics. These tools would take into account numerous prognosticators beyond those covered by the traditional TNM (tumor–node–metastasis) staging system. METHODS Demographic, host, and tumor characteristics of 1617 patients with cancer of the oral cavity, who were treated primarily with surgery at a single-institution tertiary care cancer center between 1985 and 2009, were reviewed from a preexisting database. Recurrent disease was recorded in 509 patients (456 locoregional and 116 distant); 328 patients died of cancer-related causes, and 542 died of other causes. The median follow-up was 42 months (range, 1-300 months). The following variables were analyzed as predictors of prognosis: age, sex, race, alcohol and tobacco use, oral cavity subsite, invasion of other structures, comorbidity, tumor size, and clinical nodal status. The stepdown method was used to select the statistically most influential predictors for inclusion in the final nomogram for each outcome of interest. RESULTS The most influential predictors of both recurrence and cancer-specific mortality probability (CSMP) were tumor size, nodal status, subsite, and bone invasion. Nomograms were generated for prediction of overall survival (OS), CSMP, and locoregional recurrence-free probability (LRRFP). The nomograms were internally validated with an overfit-corrected predictive discrimination metric (concordance index) for OS of 67%, CSMP of 66%, and LRRFP of 60%. CONCLUSIONS Nomograms have been developed that can reasonably estimate OS, CSMP, and LRRFP based on specific tumor and host characteristics in patients with oral cancer. Cancer 2014;120:214–221. © 2013 American Cancer Society.

Management of recurrent head and neck squamous cell carcinoma is a common and challenging clinical problem in head and neck oncology.Here we present the first reported case of super-selective intra-arterial (SSIA) microcatheter based local delivery of cetuximab for head and neck cancer. This technical report describes the techniques used to deliver the SSIA dose of cetuximab, as well as the patient outcome.This technical report is part of an ongoing Phase I Clinical Trial.The New York Head and Neck Institute (NYHNI) is a full-service otolaryngology and neurosurgery department at Lenox Hill Hospital, part of the Northwell Health System. The NYHNI serves a diverse patient population with a wide range of head and neck diseases in a tertiary hospital setting.SSIA Cetuximab.A patient presents to our clinic with recurrent unresectable squamous cell carcinoma of the nasopharynx. He is recruited into the first cohort of a phase I clinical trial to assess the safety of SSIA cetuximab, dose starting at 100mg/mSafety, as measured by toxicity of SSIA cetuximab.SSIA Cetuximab has been demonstrated to be a safe and feasible procedure in this technical report.This case illustrates technical feasibility and a very preliminary assessment of the safety of a novel delivery of a biologic agent for squamous cell carcinoma of the head and neck, which is part of an ongoing phase I clinical trial.NCT02438995.

BACKGROUND Sentinel lymph node mapping and biopsy (SLNB) has become a standard staging procedure for patients with cutaneous neoplasms of known metastatic potential. In the current study, the authors explored the use of SLNB in patients with primary sweat gland carcinomas (SGCs). METHODS Six patients with SGC underwent SLNB. The tumors and lymph nodes were examined using routine hematoxylin and eosin (H&E) stained sections and by immunohistochemistry using antibodies against epithelial membrane antigen and cytokeratins. RESULTS Metastases were detected in the SLNs of four of the six patients with SGC. One patient with a primary tumor of the neck was found to have bilateral positive SLNs. Tumor deposits were detected by H&E stained sections alone in all but two SLNs, in which the metastatic cells were recognized only with the aid of immunohistochemical stains. Positive non-SLNs were found in two patients after complete regional lymph node dissection was performed. CONCLUSIONS The high frequency of positive SLNs in this small series suggests that SLNB is a useful staging tool for patients with SGC. As in SLNBs of other tumors, immunohistochemistry appears to facilitate the recognition of small microscopic metastases. Cancer 2003;97:2279–84. © 2003 American Cancer Society. DOI 10.1002/cncr.11327

Introduction: IRX-2 is a primary-cell-derived immune-restorative biologic consisting of a well-defined set of human cytokines that act on multiple immune system cell types to overcome tumor-mediated immunosuppression. The IRX-2 biologic stimulates T cells and natural killer cells and turns immature or defective dendritic cells into mature antigen-presenting cells. The IRX-2 biologic is provided as part of the IRX-2 regimen, which contains cyclophosphamide, indomethacin, and zinc to support an anticancer immune response. In a phase 2a clinical trial in 27 patients with therapy-naïve head and neck squamous cell carcinoma (HNSCC), treatment with the IRX-2 regimen was well tolerated and associated with immunologically mediated antitumor effects. The new multicenter randomized IRX-2 Neoadjuvant Therapy in Head and Neck SCC to Provide Immune Response Enhancement (INSPIRE) trial (NCT02609386) is designed to evaluate the safety and effectiveness of combined neoadjuvant and adjuvant therapy with the IRX-2 regimen in patients with oral cavity HNSCC, a disease known to have a disordered immune function. Study Design: Patients enrolled in INSPIRE must be at least 18 years of age; have previously untreated Stage II, III, or IVa SCC of the oral cavity that is surgically resectable with curative intent; and have a Karnofsky Performance status ≥70%. Up to 200 patients will be randomized 2:1 to either the IRX-2 biologic regimen arm or the IRX-2 regimen control arm (the IRX regimen minus the IRX-2 biologic). The neoadjuvant stage of INSPIRE begins 21 days before resection, when patients in both treatment arms will receive the IRX-2 regimen each day until resection. This regimen consists of the immunomodulatory chemotherapeutic agent cyclophosphamide, provided as a low-dose intravenous infusion, as well as two oral drugs, a zinc-containing multivitamin and indomethacin, a nonselective COX-1/COX-2 inhibitor. During this period, patients in the IRX-2 biologic regimen arm will also receive 10 days of the IRX-2 biologic subcutaneously injected into their bilateral sternocleidomastoid insertion regions. After resection, patients receive standard adjuvant radiation or chemoradiation therapy followed by adjuvant IRX-2 booster regimens at 3, 6, 9, and 12 months. During each 10-day booster period, patients in the IRX-2 biologic regimen arm also receive, for 5 consecutive days, the IRX-2 biologic subcutaneously injected into their bilateral deltoid regions. Study Endpoints: INSPIRE is now enrolling patients at 12 selected institutions in the United States. The primary endpoint of INSPIRE is event-free survival (EFS). Secondary endpoints include overall survival (OS) and safety as assessed by the incidence and severity of adverse events. Exploratory endpoints include changes in tumor size and histologic differences between pre- and post-treatment specimens in lymphocytic infiltration, assessed by both cell-surface marker expression (Perkin Elmer multiplex IHC) and immune cell gene signatures (NanoString). Conclusion: With enrollment of up to 200 patients, the randomized INSPIRE trial provides the opportunity to assess the ability of the IRX-2 regimen to improve EFS and OS by inhibiting tumor-mediated immunosuppression. Analysis of the exploratory endpoints will generate data to better describe the mechanism of action of the IRX-2 regimen and provide insight into the differences between inflammatory and non-inflammatory responses to SCCs of the oral cavity. Citation Format: Gregory T. Wolf, Mihir Patel, Audrey Erman, Jason G. Newman, Greg Krempl, Jorge Nieva, R. Bryan Bell, Michael Kaplan, Dennis Kraus, Jeffrey Moyer, Aru Panwar, Joseph Valentino. The INSPIRE trial: A randomized trial of neoadjuvant and adjuvant therapy with the IRX-2 regimen in patients with newly diagnosed stage II, III, or IVa squamous cell carcinoma of the oral cavity [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 31.

Objective: Although the majority of pharyngocutaneous fistulas close spontaneously with conservative measures, 20% to 30% of patients do not respond to this approach, thereby necessitating major reconstruction with adjacent or free tissue transfers. These procedures carry considerable risk, particularly in patients with medical comorbidities or a history of prior surgery/radiation. Less invasive treatment approaches designed to reverse tissue damage or promote spontaneous healing would represent an important medical advance. Autologous fat grafts have been previously shown to promote healing of persistent wounds and improve the quality of radiation-damaged tissue. In this report, successful closure of a persistent pharyngocutaneous fistula with use of autologous fat grafting is described. Method: The history and details of pharyngocutaneous fistula closure in a patient with recurrent head and neck cancer are reported. Result: A 67-year-old patient with recurrent head and neck cancer and prior radiotherapy underwent reresection including partial pharyngectomy with pectoralis major myocutaneous flap closure. Postoperatively, he developed an enterocutaneous fistula, which failed to close with conservative measures including 8 months of nothing per os. Two rounds of autologous fat grafting were performed with successful fistula healing. Conclusion: Autologous fat grafting is a useful treatment for closure of persistent pharyngocutaneous fistulas. Autologous fat grafting should be considered in poor surgical candidates, particularly in the setting of extensive radiation-induced tissue damage.

Sarcomas of the head, neck, and skull base represent a heterogeneous group of tumors with distinct prognostic features. There have been significant improvements in characterizing these sarcomas using traditional morphologic assessments and more recent immunohistochemical analysis. Surgery is the mainstay of treatment followed by radiation therapy. Treatment modalities have changed in select pediatric sarcomas, for which new chemotherapeutic combinations have improved survival statistics. The high rate of distant failure emphasizes the need for novel systemic and directed molecular therapies. Tumor grade, size, and margin status are key factors in survival.

Combined anterior cranial base resection is the mainstay of therapy for skull base malignancies. Improvements in surgical techniques and reconstruction have led to a reduction in morbidity and overall better survival rates. Meticulous attention to dural and skull base reconstruction is essential for reducing the major complications, including cerebrospinal fluid leak and pneumocephalus. Complications can be devastating, but timely effective management can limit the severity.

Metastasis to the regional lymph node is the most important prognostic indicator for the outcomes of patients with sold cancer. In general, it is well recognized that cancer development is genetically determined with progression from the microenvironment of the primary tumor site, oftentimes via the SLN gateway, to the distant sites. In about 20 % of the time, the cancer cells may spread directly through the blood vascular system to the distant sites. Thus, in general, cancer progression is consistent with Hellman’s spectrum theory in that development of nodal and systemic metastasis from a localized cancer growth is a progressive process. Cancer proliferation within the tumor microenvironment may give rise to increased tumor heterogeneity, which is further complicated by its continuous change through its evolution within the host in a Darwinian sense. It is crucial to understand the molecular process of lymphangiogenesis and hemangiogenesis in the tumor microenvironment with respect to the initial steps of cancer cells entering into the lymphatic and vascular systems so that rational therapy can be developed to curb the process of specific routes of metastasis. This chapter elucidates the role of lymphatics, nodal metastasis and antitumor immunity. We present novel immune targets in nodal metastases, the importance of the lymph node as a pre-metastatic niche, and immune-related proteins as biomarkers of metastasis.