Search

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Head and Neck (H&N) Cancers. These Insights describe the different types of particle therapy that may be used to treat H&N cancers, in contrast to traditional radiation therapy (RT) with photons (x-ray). Research is ongoing regarding the different types of particle therapy, including protons and carbonions, with the goals of reducing the long-term side effects from RT and improving the therapeutic index. For the 2015 update, the NCCN H&N Cancers Panel agreed to delete recommendations for neutron therapy for salivary gland cancers, because of its limited availability, which has decreased over the past 2 decades; the small number of patients in the United States who currently receive this treatment; and concerns that the toxicity of neutron therapy may offset potential disease control advantages.

Background: In this retrospective review, the authors examined demographic/clinical characteristics and overall survival in patients with squamous cell carcinoma of the oropharynx at a tertiary cancer center, and they report the characteristics that influenced any observed survival trends over time.Methods: The study included 3891 newly diagnosed, previously untreated patients who presented at the authors' institution between 1955 and 2004.Results: Over time, patients presented at younger ages and were more likely to have base of tongue or tonsil tumors and to be never-smokers or former smokers. Patients who were diagnosed between 1995 and 2004 were almost half as likely to die as those who were diagnosed before 1995 (hazard ratio, 0.6; 95% confidence interval, 0.6-0.8). In both multivariable and recursive partitioning survival analyses, the TNM staging system predicted the survival of patients who received treatment before 1995 but did not predict the survival patients treated during the period from 1995 to 2004.Conclusions: Survival among patients with squamous cell carcinoma of the oropharynx improved substantially over the past 50 years. The main contributing factors were changes in clinical characteristics, in particular surrogates for positive human papillomavirus status. The current TNM staging system for squamous cell carcinoma of the oropharynx is inadequate. The incorporation of human papillomavirus status and perhaps smoking status into the TNM system is encouraged. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma (ACC), a rare and progressive salivary malignancy, is characterized by histogenetic, morphologic, and clinical heterogeneity. Extensive efforts to characterize the molecular events associated with these tumors have included the identification of biomarkers for prognostication and post-therapy assessment. In a previous study of genome-wide methylation screening, the authors of the current report identified a limited number of differentially methylated gene regions in ACC, and significant hypermethylation was observed at the transcriptional start sites of genes that encode for the transcription factor engrailed homeobox 1 (EN1). Clinicopathologic correlation analyses indicated that EN1 methylation status is correlated with histologic tumor grade, tumor location, and final patient outcome. To ascertain definitively whether aberrant EN1 expression accompanies human salivary ACC, the authors used an immunohistochemical technique to directly evaluate EN1 protein expression in ACC of the salivary gland. The data revealed increased EN1 protein expression in solid type ACC, which was correlated with a significantly lower survival rate. The current results validated EN1 as a potential biomarker in a large cohort of patients with salivary ACC. Immunohistochemical analysis of EN1 in biopsy specimens obtained for diagnostic purposes and/or surgically resected material may reveal that EN1 is a biologic predictor of poor prognosis in patients with salivary ACC. [ABSTRACT FROM AUTHOR]

Background: Adenoid cystic carcinoma (ACC), a rare and progressive salivary malignancy, is characterized by cellular, morphologic, and clinical heterogeneity. The authors of this report hypothesized that the dual cellular composition of ACC plays an important role in biomarker evaluation, tumor biologic behavior, and response to therapy.Methods: To investigate the differential localization and expression of the c-Kit protein and the epidermal growth factor receptor (EGFR) protein, immunohistochemical analyses were performed on tissue arrays that were constructed from 199 tumors, and the results were correlated with clinicopathologic factors.Results: c-Kit expression was limited to the inner ductal epithelial cells, whereas EGFR expression was limited mainly to the outer myoepithelial cells in the majority of ACCs with tubular and cribriform patterns. In solid ACCs, c-Kit uniformly was positive, whereas EGFR consistently was negative. A significant statistical correlation was observed between c-Kit expression and a poor 3-year outcome, and EGFR expression was correlated with a better 3-year outcome.Conclusions: The current findings underscored the importance of cellular subtype localization of biomarkers in the clinical and therapeutic stratification of patients with ACC. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Fluorodeoxyglucose positron emission tomography (FDG-PET) has been proposed as a sensitive method to diagnose and stage various malignancies. We assessed the efficacy of FDG-PET imaging in distinguishing tumor persistence/recurrence from posttreatment changes following radiation therapy for squamous carcinomas of the head and neckStudy Design: Retrospective analysis of FDG-PET results compared with biopsy results or outcome, or both.Methods: Twenty-eight patients who had undergone radiation therapy with or without surgery for treatment of squamous cell carcinoma were studied with FDG-PET imaging. There was clinical suspicion for recurrence in each patient, but no obvious mass or lesion to biopsy was found on physical examination or anatomic imaging. The results of FDG-PET imaging were compared with those of biopsy or clinical follow-up of at least 6 months, or both.Results: FDG-PET imaging was positive in 13 patients, and the presence of active disease was confirmed in 12. Two thirds of the 12 received further cancer treatment. There were 15 negative FDG-PET images. Thirteen of these were confirmed true-negative images, but two studies were false-negative images. The sensitivity and specificity of FDG-PET were 86% and 93%, respectively, with positive and negative predictive values of 92% and 87%, respectively. The overall accuracy was 89%.Conclusion: FDG-PET imaging is a useful modality to distinguish tumor persistence/recurrence from radiation-induced tissue changes in the neck following treatment for head and neck cancer. FDG-PET can identify patients who may benefit from further treatment, and may lead to improved outcome for individual patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate head and neck squamous cell carcinomas (SCCAs) for the expression of nerve cell adhesion molecule (N-CAM). We propose that expression of N-CAM by tumor cells may be associated with perineural invasion in SCCA of the head and neck.Methods: Seventy-six archived specimens of histologically proven SCCA were analyzed by immunohistochemistry for the expression of N-CAM. Positive and negative controls were used to assess staining. Two sections of each specimen were reviewed for the presence of perineural invasion. A retrospective chart review was performed for each patient that corresponded to the above specimens.Results: Perineural invasion was present in 28 (37%) of the 76 patients evaluated for the expression of N-CAM. N-CAM expression was demonstrated in 38 (50%) of the 76 specimens. The incidence of N-CAM expression was significantly associated with perineural invasion (P = .002). There was no significant association between the presence of staining or the presence of perineural invasion and the incidence of locoregional recurrence, distant metastasis, or survival status; however, the mean follow-up was only 13.6 months (range, 1-49 mo).Conclusion: There is a positive correlation between the presence of N-CAM expression and perineural invasion in SCCA of the head and neck. The expression of this adhesion molecule by tumor cells may facilitate both homophilic cell-to-cell and heterophilic cell-to-substrate adhesion, thereby enabling the tumor cells to use the perineural tissues or neural cells, or both as a conduit for perineural spread. [ABSTRACT FROM AUTHOR]

Electrification to reduce or eliminate greenhouse gas emissions is essential to mitigate climate change. However, a substantial portion of our manufacturing and transportation infrastructure will be difficult to electrify and/or will continue to use carbon as a key component, including areas in aviation, heavy-duty and marine transportation, and the chemical industry. In this Roadmap, we explore how multidisciplinary approaches will enable us to close the carbon cycle and create a circular economy by defossilizing these difficult-to-electrify areas and those that will continue to need carbon. We discuss two approaches for this: developing carbon alternatives and improving our ability to reuse carbon, enabled by separations. Furthermore, we posit that co-design and use-driven fundamental science are essential to reach aggressive greenhouse gas reduction targets., (© 2024. Argonne National Laboratory, Battelle Memorial Institute, UT- Battelle, LLC, Brookhaven National Laboratory, National Renewable Energy Laboratory, AMES National Laboratory, Lawrence Berkley National Laboratory, SLAC National Accelerator Laboratory, Booz Allen Hamilton, BASF Corporation and The Author(s), under exclusive licence to Springer Nature Limited. This work contains contributions, authored by US Government employees in the course of their official duties, which are not subject to copyright protection in the US. Foreign copyright protection for these contributions may still apply.)

Adenocarcinomas of the nasal/paranasal sinuses are uncommon, but intestinal-type adenocarcinomas (ITACs) are important. Due to the rarity of these tumors, their molecular profile is not well known. To further investigate the molecular profile and find potential oncogenic drivers, we compared the whole transcriptome and exome of ITACs at different anatomic locations in the head and neck. Twenty-one head and neck adenocarcinomas were used in this study, divided into 10 sinonasal adenocarcinomas (SNT) and 11 extrasinonasal (T) head and neck adenocarcinomas according to anatomic location and histology. Tumor samples along with normal mucosa were microdissected from formalin-fixed, paraffin-embedded samples, and RNA and DNA were subjected to whole-transcriptome and -exome shotgun sequencing. Analysis of ITACs at sinonasal locations showed 410 subtype-specific differentially expressed (DE) genes and noncoding transcripts compared with the group of other anatomic locations, with 2909 subtype-specific DE genes. The groups shared 872 genes, with 17 highly different or opposing DE genes. Whole-exome mutation analysis revealed the gene MLL3 (KMT2C) to be exhibiting the most frequent loss-of-function mutations in all adenocarcinomas investigated. The results suggest that the head and neck ITACs investigated were mainly caused by loss-of-function mutations in MLL3 that disabled chromatin methylation and remodeling of all MLL3-targeted enhancers in the tumors. This changed the activity of multiple genes/gene clusters, supporting oncogenicity mostly via pathways of signaling, dedifferentiation, proliferation, migration, and immune and inflammatory deregulation, indicating a truly epigenetic event as the root cause for the heterogenous diversity of these enteric types of cancer. The data of this study form the basis for understanding cell fate determination and cellular homeostasis in the normal respiratory mucosa at different anatomic sites and show the contribution of different mucosal components to the etiology/molecular pathology of ITAC., (Published by Elsevier Inc.)

Purpose: The combination of cisplatin and radiation or cetuximab and radiation improves overall survival of patients with locoregionally advanced head and neck carcinoma. NRG Oncology conducted a phase 3 trial to test the hypothesis that adding cetuximab to radiation and cisplatin would improve progression-free survival (PFS)., Methods and Materials: Eligible patients with American Joint Committee on Cancer sixth edition stage T2 N2a-3 M0 or T3-4 N0-3 M0 were accrued from November 2005 to March 2009 and randomized to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Outcomes were correlated with patient and tumor features. Late reactions were scored using Common Terminology Criteria for Adverse Events (version 3)., Results: Of 891 analyzed patients, 452 with a median follow-up of 10.1 years were alive at analysis. The addition of cetuximab did not improve PFS (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.89-1.26; P = .74), with 10-year estimates of 43.6% (95% CI, 38.8- 48.4) for arm A and 40.2% (95% CI, 35.4-45.0) for arm B. Cetuximab did not reduce locoregional failure (HR, 1.21; 95% CI, 0.95-1.53; P = .94) or distant metastasis (HR, 0.79; 95% CI, 0.54-1.14; P = .10) or improve overall survival (HR, 0.97; 95% CI, 0.80-1.16; P = .36). Cetuximab did not appear to improve PFS in either p16-positive oropharynx (HR, 1.30; 95% CI, 0.87-1.93) or p16-negative oropharynx or nonoropharyngeal primary (HR, 0.94; 95% CI, 0.73-1.21). Grade 3 to 4 late toxicity rates were 57.4% in arm A and 61.3% in arm B (P = .26)., Conclusions: With a median follow-up of more than 10 years, this updated report confirms the addition of cetuximab to radiation therapy and cisplatin did not improve any measured outcome in the entire cohort or when stratifying by p16 status., (Copyright © 2022. Published by Elsevier Inc.)

Background: Cancer centers are regionalizing care to expand patient access, but the effects on patient volume are unknown. This study aimed to compare patient volumes before and after the establishment of head and neck regional care centers (HNRCCs)., Methods: This study analyzed 35,394 unique new patient visits at MD Anderson Cancer Center (MDACC) before and after the creation of HNRCCs. Univariate regression estimated the rate of increase in new patient appointments. Geospatial analysis evaluated patient origin and distribution., Results: The mean new patients per year in 2006-2011 versus 2012-2017 was 2735 ± 156 patients versus 3155 ± 207 patients, including 464 ± 78 patients at HNRCCs, reflecting a 38.4 % increase in overall patient volumes. The rate of increase in new patient appointments did not differ significantly before and after HNRCCs (121.9 vs 95.8 patients/year; P = 0.519). The patients from counties near HNRCCs, showed a 210.8 % increase in appointments overall, 33.8 % of which were at an HNRCC. At the main campus exclusively, the shift in regional patients to HNRCCs coincided with a lower rate of increase in patients from the MDACC service area (33.7 vs. 11.0 patients/year; P = 0.035), but the trend was toward a greater increase in out-of-state patients (25.7 vs. 40.3 patients/year; P = 0.299)., Conclusions: The creation of HNRCCs coincided with stable increases in new patient volume, and a sizeable minority of patients sought care at regional centers. Regional patients shifted to the HNRCCs, and out-of-state patient volume increased at the main campus, optimizing access for both local and out-of-state patients., (© 2022. Society of Surgical Oncology.)

Objectives: We sought to determine overall survival (OS), prognostic factors, cost, and functional outcomes after surgery for locally recurrent oral cavity squamous cell carcinoma (OCSCC)., Materials and Methods: We retrospectively reviewed 399 cases of locally recurrent OCSCC from 1997 to 2011, of which 259 patients were treated with salvage surgery. Survival and prognostic factors were evaluated using univariable and multivariable Cox regression, the Kaplan-Meier method, and the log-rank test., Results: The 5-year OS for patients undergoing surgical salvage, nonsurgical therapy, or supportive care was 44.2%, 1.5%, and 0%, respectively. For patients who underwent surgical salvage, 133 (51%) patients experienced a second recurrence at a median of 17 months. Factors associated with OS included disease-free interval ≤ 6 months (P =.0001), recurrent stage III-IV disease (P <.0001), and prior radiation (P =.0001). Patients with both advanced stage and prior radiation had a 23% 5-year OS, compared with 70% for those with neither risk (P <.001). Functionally, 85% of patients had > 80% speech intelligibility and 81% were able to eat by mouth following salvage surgery. Of the patients who required tracheostomy, 78% were decannulated. The adjusted median hospital and professional charges for patients were $129,696 (range $9,238-$956,818)., Conclusions: Patients with recurrent OCSCC who underwent salvage surgery have favorable functional outcomes with half of alive at 5 years but poorer OS for advanced disease, disease-free interval ≤ 6 months, and prior radiation. Additionally, treatment is associated with high cost, and about half of patients ultimately develop another recurrence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: Map regional lymph node metastases for lateralized oral cavity squamous cell carcinoma (OCSCC) and evaluate factors associated with regional metastases and recurrence., Materials and Methods: Retrospective cohort study of 715 patients with lateralized OCSCC surgically treated in 1997-2011. Analysis was performed using log-rank, Kaplan-Meier, and multivariable logistic and Cox regression., Results: Regional metastases were identified in ipsilateral levels IIA (24%), IB (18%), III (13%), V (9%), IV (7%), IA (2%) and IIB (1%) and the contralateral neck (3%). Lymphovascular invasion (LVI) (Hazard Ratio [HR] 2.2, 95% Confidence Interval [CI] 1.2-3.9) and T category (T3 vs. T1: HR 4.1, 95% CI 1.9-9.3; T4 vs. T1: HR 2.3, 95% CI 1.2-4.3) were associated with regional metastases. Most (71%) isolated regional metastatic recurrences were in undissected levels of the neck, including 58% in levels IV and V. Tumors of the hard palate (HR 4.3, 95% CI 1.2-16.1), upper alveolus (HR 3.2, 95% CI 1.0-4.7) or with LVI (HR 2.0, 95% CI 1.0-3.9) were associated with isolated regional recurrence. For upper alveolar/hard palate tumors, depth of invasion (DOI) ≥4 mm (P = .003) and LVI (P = .04) were associated with regional metastases., Conclusions: For lateralized OCSCC, elective neck dissection of level IIB or the contralateral neck may rarely be needed, but additional surgical or radiation treatment of levels IV and V may be considered based on patient risk factors, including T category 3-4 or LVI. For upper alveolar/hard palate tumors, DOI ≥4 mm is an appropriate threshold for elective neck dissection., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mark E. Zafereo reports research funding (PI clinical trials) from Merck and Eli Lilly not relevant to this research. Otherwise, the authors have no financial disclosures, nor conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Enhanced Recovery After Surgery (ERAS) pathways in head and neck cancer (HNC) have shown to improve perioperative outcomes and reduce complications. The longer term implications on adjuvant treatment and survival have not been studied. We hereby report the first study on the impact of an ERAS pathway on return to intended oncologic treatment (RIOT) and overall survival (OS) in HNC., Methods: 200 patients undergoing head and neck oncologic surgery on an ERAS pathway between March 1, 2016 and March 31, 2019 were matched to controls over the same interval. Demographic, tumor and adjuvant therapy-related data were collected, including time to adjuvant therapy(TAT) and treatment package time(TPT). Risk factors for TAT > 42 days and TPT ≥ 85 days were assessed. OS was compared and risk factors for inferior OS determined., Results: Baseline characteristics including co-morbidities and tumor stage were similar. Of 179 patients planned for adjuvant treatment, there was no difference in RIOT rate (89.0% vs 87.5%, p = 0.753), proportion of TAT > 42 days of surgery (55.6% vs 59.7%, p = 0.642), or TPT ≥ 85 days (48.1% vs 57.1, p = 0.258), for the ERAS and control groups, respectively. On multivariate analysis, alcohol use (OR 3.58; 95 %CI 1.11-11.52) and recurrent disease status (OR 2.88; 95 %CI 1.40-5.93) were independently associated with prolonged TAT. Three-year OS was similar between the ERAS and control groups (73% vs 76%, p = 0.521)., Conclusion: ERAS has not shown to improve RIOT or OS in the current study. However, its benefit for perioperative outcomes is undeniable and further studies are required on longer term quality and survival outcomes., (Published by Elsevier Ltd.)

Objectives: To analyze charges, complications, survival, and functional outcomes for definitive surgery of mandibular osteoradionecrosis (ORN)., Materials and Methods: Retrospective analysis of 76 patients who underwent segmental mandibulectomy with reconstruction from 2000 to 2009., Results: Complications occurred in 49 (65%) patients and were associated with preoperative drainage (odds ratio [OR] 4.40, 95% confidence interval [CI] 1.01-19.27). The adjusted median charge was $343 000, and higher charges were associated with double flap reconstruction (OR 8.15, 95% CI 2.19-30.29) and smoking (OR 5.91, 95% CI 1.69-20.72). Improved swallow was associated with age <67 years (OR 3.76, 95% CI 1.16-12.17) and preoperative swallow (OR 3.42, 95% CI 1.23-9.51). Five-year ORN-recurrence-free survival was 93% while overall survival was 63% and associated with pulmonary disease (HR [hazard ratio] 3.57, 95% CI 1.43-8.94)., Conclusions: Although recurrence of ORN is rare, surgical complications are common and charges are high. Poorer outcomes and higher charges are associated with preoperative factors., (© 2022 Wiley Periodicals LLC.)

In the second half of the twentieth century, twin and family studies established beyond a reasonable doubt that all forms of psychopathology are substantially heritable and highly polygenic. These conclusions were simultaneously an important theoretical advance and a difficult methodological obstacle, as it became clear that heritability is universal and undifferentiated across forms of psychopathology, and the radical polygenicity of genetic effects limits the biological insight provided by genetically informed studies at the phenotypic level. The paradigm-shifting revolution brought on by the Human Genome Project has recapitulated the great methodological promise and the profound theoretical difficulties of the twin study era. We review these issues using the rubric of genetic architecture, which we define as a search for specific genetic insight that adds to the general conclusion that psychopathology is heritable and polygenic. Although significant problems remain, we see many promising avenues for progress.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

Background: While the majority of pediatric tracheostomies are performed in the setting of chronic and complex medical comorbidities, perioperative tracheostomies following head and neck tumor ablation are generally short-term. Deliberate planning is required for decannulation in this setting and no published protocols currently exist. Our study outlines a management strategy for short-term tracheostomy in pediatric patients following head and neck surgery., Methods: A retrospective study of pediatric head and neck tumor patients undergoing tracheostomy was performed at a quaternary children's hospital from February 1, 2016 to December 31, 2018. Charts were reviewed for demographics, surgical operation, relevant tracheostomy-related complications, and time to decannulation., Results: Eleven patients with a mean age of 10.4 years (st.dev. 6.7, range: 0.5-23) underwent tracheostomy during their primary ablative/reconstructive surgery. Trans-tracheal pressure monitoring helped direct the need for tracheostomy downsizing and readiness for capping trials. All patients were decannulated before hospital discharge after a mean of 12.8 days (st.dev. 2.5, range: 9-18) and were discharged after a mean of 14.8 days (st.dev. 2.5, range: 11-20)., Conclusion: Pediatric head and neck surgery patients can be quickly and safely decannulated with an instructive protocol and multidisciplinary care., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The survival benefit of elective neck dissection (END) for patients with cutaneous squamous cell carcinoma (cSCC) of the head and neck and no evidence of regional metastasis (cN0) has never been reported. The aim of this study was to determine the effect of END on patient survival., Methods: The authors included patients with head and neck cSCC who had undergone primary surgery from 1995 to 2017. The primary end point was survival, and the secondary end points were the incidence of occult regional disease and regional disease control. To assess the impact of END on survival, the authors used multivariable Cox proportional hazards models with propensity score and matching techniques for internal validation., Results: A total of 1111 patients presented with no evidence of nodal disease; 173 had END, and 938 were observed. Adjuvant radiotherapy to the neck was administered to 101 patients (9%). END resulted in a 5-year overall survival rate of 52%, whereas the rate was 63% in the observation group (P = .003 [log-rank]). The 5-year disease-free survival rate for patients undergoing END was similar to that for the observation group (73% vs 75%; P = .429). A multivariate regression model showed that the performance of END was not associated with improved rates of overall, disease-specific, or disease-free survival; similarly, among patients with advanced disease (T3-4), those who underwent END did not have improved survival rates., Conclusions: Among patients with cSCC of the head and neck, observation of the neck nodes resulted in noninferior survival rates in comparison with END at the time of primary surgery. Further studies are required to elucidate the role of END in patients with advanced disease., (© 2021 American Cancer Society.)

Purpose: In locoregionally advanced, resectable cutaneous squamous cell carcinoma of the head and neck (CSCC-HN), surgery followed by radiotherapy is standard but can be cosmetically and functionally devastating, and many patients will have recurrence., Patients and Methods: Newly diagnosed or recurrent stage III-IVA CSCC-HN patients amenable to curative-intent surgery received two cycles of neoadjuvant PD-1 inhibition. The primary endpoint was ORR per RECIST 1.1. Secondary endpoints included pathologic response [pathologic complete response (pCR) or major pathologic response (MPR; ≤10% viable tumor)], safety, DSS, DFS, and OS. Exploratory endpoints included immune biomarkers of response., Results: Of 20 patients enrolled, 7 had recurrent disease. While only 6 patients [30%; 95% confidence interval (CI), 11.9-54.3] had partial responses by RECIST, 14 patients (70%; 95% CI, 45.7-88.1) had a pCR ( n = 11) or MPR ( n = 3). No SAEs ocurred during or after the neoadjuvant treatment. At a median follow-up of 22.6 months (95% CI, 21.7-26.1), one patient progressed and died, one died without disease, and two developed recurrence. The 12-month DSS, DFS, and OS rates were 95% (95% CI, 85.9-100), 89.5% (95% CI, 76.7-100), and 95% (95% CI, 85.9-100), respectively. Gene expression studies revealed an inflamed tumor microenvironment in patients with pCR or MPR, and CyTOF analyses demonstrated a memory CD8 + T-cell cluster enriched in patients with pCR., Conclusions: Neoadjuvant immunotherapy in locoregionally advanced, resectable CSCC-HN is safe and induces a high pathologic response rate. Pathologic responses were associated with an inflamed tumor microenvironment., (©2021 American Association for Cancer Research.)

Purpose: Patients have been increasingly using physician-rating websites (PRWs); however, few studies have analyzed the validity of star ratings on PRWs. We aimed to compare PRW patient satisfaction scores with internally generated patient satisfaction scores (internal scores) of physicians at a large quaternary cancer center., Methods: We collected internal scores and PRW scores for physicians at MD Anderson Cancer Center. Internal scores were based on patient responses to the Clinician and Group Consumer Assessment of Healthcare Providers and Systems patient experience (CG-CAHPS) survey. Only physicians with an internal score on the basis of ≥ 30 patient reviews were included. The median numbers of reviews and median scores were compared between internal data and four PRWs (Google, HealthGrades, Vitals, and WebMD). Both internally and on PRWs, possible scores ranged from 1 (least satisfied) to 5 (most satisfied)., Results: Of 640 physicians with an internal score, 510 (79.7%) met the inclusion criteria. For these 510 physicians, the median (IQR) number of internal reviews was 49.5 (30-93) and the median (IQR) internal score was 4.89 (4.81-4.93); the median number of reviews on PRWs ranged from 2 to 7, and the median score on PRWs ranged from 4.40 to 5.00. No physician had an internal score < 4, but the proportions with score < 4 on PRWs ranged from 16% to 30%., Conclusion: Internal patient satisfaction scores were higher and calculated from more reviews than PRW patient satisfaction scores and correlated weakly with PRW scores. Given that patients rely on PRWs when evaluating potential physicians, we recommend publishing internal scores online to give patients more complete information regarding physician performance., Competing Interests: Michael FrumovitzConsulting or Advisory Role: Stryker, Biom'upSpeakers' Bureau: StrykerResearch Funding: Tesaro/GSK, AstraZeneca/MedImmuneNo other potential conflicts of interest were reported.

Purpose: To examine the role age plays in the treatment and prognosis of locally advanced head and neck cancer (LAHNC) treated definitively with radiation alone or combined modality therapy., Methods: A retrospective analysis was performed of three NRG/RTOG trials examining either radiation alone or combined radiation and systemic therapy for LAHNC. The effect of age (≥70 yrs.) on cause-specific survival (CSS), overall survival (OS), and toxicity was evaluated., Results: A total of 2688 patients were analyzed, of whom 309 patients (11.5%) were ≥ 70. For all studies combined, the hazard ratio (HR) for CSS for patients age ≥ 70 vs. those <70 was 1.33 (95%CI: 1.14-1.55, p < 0.001). For OS, the HR for patients age ≥ 70 vs. those <70 for all studies combined was 1.55 (95% CI 1.35-1.77, p < 0.001). After adjustment for all covariates, age ≥ 70 was associated with worse OS regardless of adjustment for smoking and p16 status. The survival difference was more pronounced in those receiving combined radiation and systemic therapy. Hematologic and renal toxicities were increased in combined modality trials in patients ≥70 years old., Conclusions: Patients age ≥ 70 with LAHNC were underrepresented in these clinical trials. Their CSS and OS proved inferior to patients <70 years old., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Neoadjuvant chemotherapy (NAC) is used in head and neck squamous cell carcinoma (HNSCC) for downstaging advanced disease and decreasing distant metastasis (DM). To the authors' knowledge, no study has specifically examined the impact of a delayed time to surgery (TTS) after NAC on oncologic outcomes. They thus aimed to identify a cutoff for TTS after NAC and its effect on survival indices., Methods: This was a retrospective review of all patients with HNSCC receiving NAC followed by surgery with curative intent between March 2016 and March 2019 at the MD Anderson Cancer Center. Receiver operating characteristic analysis was used to identify a cutoff for TTS, and this cutoff was used to analyze the overall survival (OS), locoregional recurrence rate, DM-free rate, and disease-free survival (DFS). A multivariate Cox regression analysis was performed., Results: One hundred one patients were analyzed with a median follow-up of 24.7 months. The 3-year OS and locoregional recurrence rates did not differ with a TTS ≥ 34 days. However, the 3-year DM-free rate was significantly worse (56% vs 90%; P = .001) in the group with a TTS ≥ 34 days, and the 3-year DFS was significantly lower (26% vs 64%; P = .006). In a multivariate analysis, a TTS ≥ 34 days (hazard ratio [HR], 4.92; 95% confidence interval [CI], 1.84-13.13) and extracapsular extension (HR, 3.01; 95% CI, 1.13-8.00) were significant independent predictors of a poorer DM-free rate. Weight loss > 10% (HR, 5.53; 95% CI, 1.02-30.24) was the only independent predictor for a TTS ≥ 34 days., Conclusions: Emphasis should be placed on early definitive locoregional treatment after NAC, particularly in patients who do not respond to NAC. There is a need to validate these findings and establish new benchmarks for the interval between NAC and surgery., (© 2021 American Cancer Society.)

Background: The outcomes of patients treated with cytotoxic or targeted systemic therapy is not well defined for cutaneous squamous cell carcinoma of the head and neck (cSCCHN)., Methods: Patients with cSCCHN treated with cytotoxic or targeted systemic therapy were included. Patients were divided into two groups based on the presence of distant metastasis (M1 vs. M0) at presentation. A proportional hazards model was used to assess for independent predictors of overall survival., Results: Of 129 patients with cSCCHN, 20 (16%) were M1 and 109 (84%) were M0. Independent predictors of improved survival were M0 status, treatment of locally advanced disease with radiotherapy, and lower Eastern Cooperative Oncology Group (ECOG) score., Conclusions: Survival was worse in M1 patients treated with cytotoxic or targeted systemic therapy and poor baseline performance status but improved in those receiving radiotherapy. These data can serve as historical controls for future systemic therapy trials, including immunotherapy., (© 2021 Wiley Periodicals LLC.)