Intestinal-Type Adenocarcinoma in Head and Neck: Dissecting Oncogenic Gene Alterations Through Whole Transcriptome and Exome Analysis.

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.

Impact of Cancer Care Regionalization on Patient Volume.

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.

NCCN Guidelines® Insights: Head and Neck Cancers, Version 1.2022.

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.

Delay to surgery after neoadjuvant chemotherapy in head and neck squamous cell carcinoma affects oncologic outcomes.

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.

Elective neck dissection versus observation in patients with head and neck cutaneous squamous cell carcinoma.

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.

Inclusion of extranodal extension in the lymph node classification of cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: The prognostic performance of the recently updated American Joint Committee on Cancer lymph node classification of cutaneous head and neck squamous cell carcinoma (HNSCC) has not been validated. The objective of this study was to assess the prognostic role of extranodal extension (ENE) in cutaneous HNSCC. METHODS: This was a retrospective analysis of 1258 patients with cutaneous HNSCC who underwent surgery with or without adjuvant therapy between 1995 and 2019 at The University of Texas MD Anderson Cancer Center. The primary outcome was disease-specific survival (DSS). Local, regional, and distant metastases-free survival were secondary outcomes. Recursive partitioning analysis (RPA) and a Cox proportional hazards regression model were used to assess the fitness of staging models. RESULTS: No significant differences in 5-year DSS were observed between patients with pathologic lymph node-negative (pN0) disease (67.4%) and those with pN-positive/ENE-negative disease (68.2%; hazard ratio, 1.02; 95% CI, 0.61-1.79) or between patients with pN-positive/ENE-negative disease and those with pN-positive/ENE-positive disease (52.7%; hazard ratio, 0.57; 95% CI, 0.31-1.01). The RPA-derived model achieved better stratification between high-risk patients (category III, ENE-positive with >2 positive lymph nodes) and low-risk patients (category I, pN0; category II, ENE-positive/pN1 and ENE-negative with >2 positive lymph nodes). The performance of the RPA-derived model was better than that of the pathologic TNM classification (Akaike information criterion score, 1167 compared with 1176; Bayesian information criterion score, 1175 compared with 1195). CONCLUSIONS: The number of metastatic lymph nodes and the presence of ENE are independent prognostic factors for DSS in cutaneous HNSCC, and incorporation of these factors in staging systems improves the performance of the American Joint Committee on Cancer lymph node classification.

Enhanced Recovery After Surgery (ERAS) in Head and Neck Oncologic Surgery: A Case-Matched Analysis of Perioperative and Pain Outcomes.

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways are well established in certain surgical specialties because findings have shown significant improvements in outcomes. Convincing literature in head and neck cancer (HNC) surgery is lacking. This study aimed to assess the effect of an ERAS pathway on National Surgical Quality Improvement Program (NSQIP)-based occurrences and pain-related outcomes in HNC surgery. METHODS: The study matched 200 patients undergoing head and neck oncologic surgery on an ERAS pathway between 1 March 2016 and 31 March 2019 with control subjects (1:1 ratio) during the same period. Demographic and perioperative data collected from the NSQIP database were extracted. Pain scores and medication usage were electronically extracted from our electronic medical record system and compared. Risk factors for high opioid usage also were assessed. RESULTS: Both groups were statistically similar in baseline characteristics. The ERAS group had fewer planned intensive care unit (ICU) admissions (4% vs. 14%; p < 0.001), a shorter mean hospital stay (7.2 ± 2.3 vs. 8.7 ± 4.2 days; p < 0.001), and fewer overall complications (18.6% vs. 27.0%; p = 0.045). Morphine milligram equivalent requirements over 72 h were significantly reduced during 72 h in the ERAS group (138.8 ± 181.5 vs. 207.9 ± 205.5; p < 0.001). In the multivariate analysis, the risk factors for high opioid analgesic usage included preoperative opioid usage, age younger than 65 years, race, patient-controlled analgesia use, and ICU admission. CONCLUSION: The study findings showed that ERAS in HNC surgery can result in improved outcomes and resource use, and that these results are sustainable. The outcomes described in this report can be further used to optimize ERAS pathways.

Impact of neoadjuvant chemotherapy on perioperative morbidity after major surgery for head and neck cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been used in patients with advanced head and neck cancers (HNCs) with the intent of downstaging tumors and suppressing distant metastases. However, to the authors' knowledge, the perioperative impact of NAC has not been systematically explored in patients with HNC. The objective of the current study was to compare perioperative outcomes with surgery upfront compared with patients treated with NAC. METHODS: Between March 1, 2016, and March 31, 2019, patients undergoing surgery for HNC with flap reconstruction at The University of Texas MD Anderson Cancer Center in Houston were included. Data were extracted from the prospectively maintained National Surgical Quality Improvement Program database. Postoperative complications, return to operating room, and readmission rates were compared. Univariate and multivariate analyses of length of stay and overall and wound complications were performed. RESULTS: A total of 834 patients were analyzed, 687 of whom (82.4%) underwent surgery upfront and 147 of whom (17.6%) received NAC. A total of 631 cases (75.7%) involved the upper aerodigestive tract whereas 203 cases (24.3%) were cutaneous. A total of 317 patients (38.0%) had recurrent disease. The NAC group was younger (P < .001) and had less hypertension (P = .011), but had more advanced clinical stage tumors (P < .001) and surgeries with multiple flap reconstruction (P = .007). Patient groups did not differ with regard to wound complications (P = .47), return to operating room (P = .31), or readmission rates (P = .49). The NAC group received more blood transfusions (P < .001) but was found to have a lower risk of overall complications on multivariate analysis (odds ratio, 0.50; 95% CI, 0.30-0.83). The overall complication rate was unchanged with surgery performed ≤21 days after the last chemotherapy cycle. CONCLUSIONS: Patients undergoing NAC appear to have a higher disease burden but tend to be younger and healthier. Within the context of this inherent selection bias, NAC does not appear to increase perioperative morbidity among patients undergoing surgery for HNC.

Association between postoperative complications and long-term oncologic outcomes following total laryngectomy: 10-year experience at MD Anderson Cancer Center.

BACKGROUND: Postoperative complications are an independent predictor of poor survival across several tumors. However, there is limited literature on the association between postoperative morbidity and long-term survival following total laryngectomy (TL) for cancer. METHODS: We conducted a retrospective review of all TL patients at a single institution from 2008 to 2013. Demographic and clinical data were collected and analyzed, including postsurgical outcomes, which were classified using the Clavien-Dindo system. Multivariable Cox regression analyses were performed to identify factors associated with overall survival (OS) and disease-free survival (DFS). RESULTS: A total of 362 patients were identified. The mean age was 64 years, and the majority of patients were male (81%). The median follow-up interval was 21 months. Fifty-seven percent of patients had received preoperative radiation, and 40% had received preoperative chemotherapy. Fifty-seven percent of patients underwent salvage TL, and 60% underwent advanced reconstruction (45% free flap and 15% pedicled flap). A total of 136 patients (37.6%) developed postoperative complications, 92 (25.4%) of which were major. Multivariable modeling demonstrated that postoperative complications independently predicted shorter OS (hazard ratio [HR], 1.50; 95% CI, 1.16-1.96; P = .002) and DFS (HR, 1.36; 95% CI, 1.05-1.76; P = .021). Other independent negative predictors of OS and DFS included positive lymph node status, preoperative chemotherapy, comorbidity grade, and delayed adjuvant therapy. Severity of complication and reason for TL (salvage vs primary) were not shown to be predictive of OS or DFS. CONCLUSION: Postoperative complications are associated with worse long-term OS and DFS relative to uncomplicated cases. Patient optimization and timely management of postoperative complications may play a critical role in long-term survival.

Evaluating Unplanned Returns to the Operating Room in Head and Neck Free Flap Patients.

BACKGROUND: Head and neck oncologic surgery with reconstruction represents one of the most complex operations in otolaryngology. Unplanned return to the operating room represents an objective measure of postoperative complications. The purpose of this study was to identify reasons and risk factors for unplanned return to the operating room in patients undergoing head and neck surgery with reconstruction. METHODS: This retrospective cohort study of 467 patients undergoing head and neck surgery with free flap reconstruction used a previously-developed Head and Neck-Reconstructive Surgery-specific National Surgical Quality Improvement Program. Disease and site-specific preoperative, intraoperative, and postoperative data were gathered. Comparisons between those with and without an unexpected return to the operating room were completed with univariate and multiple logistic regression models. RESULTS: The rate of unexpected return to the operating room was 18.8% (88 patients). Most common reasons for URTOR were flap compromise (24 patients, 5.1%), postoperative infection (21 patients, 4.5%), and hematoma (20 patients, 4.3%). Two risk factors were identified by multivariate analysis: coagulopathy (ORadjusted = 2.83, 95% CI = 1.24-6.19, P = 0.010), and use of alcohol (ORadjusted = 1.9, 95% CI = 1.14-3.33, P = 0.025). CONCLUSIONS: Preexisting coagulopathy and increased alcohol consumption were associated with increased risk of unexpected return to the operating room. These findings can aid physicians in preoperative patient counseling and medical optimization and can inform more precise risk stratification of patients undergoing head and neck surgery with reconstruction. Strategies to prevent and mitigate unexpected returns to the operating room will improve patient outcomes, decrease resource utilization, and facilitate successful integration into alternative payment models.

Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.

Feasibility of an Enhanced Recovery After Surgery (ERAS) pathway for major head and neck oncologic surgery.

OBJECTIVES: Enhanced Recovery After Surgery (ERAS) protocols are gaining traction in the field of head and neck surgery following success in other specialties. Various institutions have reported on the feasibility of implementation and early outcomes in their centers. We report our experience of setting up an ERAS program in a high-volume tertiary cancer care center, including the challenges faced and overcome. METHODS: With multidisciplinary input, an ERAS protocol was developed consisting of pre-, intra-, and post-operative interventions based on current evidence. We then assessed an initial series of 104 patients on the ERAS protocol and tracked the compliance rates for various interventions. RESULTS: Compliance rates to interventions including pre-operative medication (84.6%), multimodal analgesia (84.6%95.1%), early removal of urinary catheters (76.0%) and early mobilization (56.7%) show a wide variation. However, response rates in the assessment of patient-reported outcomes are low. We discuss factors surrounding the feasibility of implementing an ERAS protocol and tracking outcomes in a diverse, high volume center. DISCUSSION: While there are challenges in implementation, results indicate that a successful ERAS pathway in major head and neck oncologic surgery is feasible. Engaging shareholders and making full use of technology in the form of electronic medical systems are essential to this success. IMPLICATIONS FOR PRACTICE: ERAS pathways should be encouraged in head and neck surgery, given their proven feasibility in a range of institutions. Further study is needed to confirm this program's impact on outcomes.

von Ebner's glands intercalated duct adenocarcinoma with PALB2 gene mutation.

Secretory carcinoma of the salivary glands is a distinct entity with distinct morphologic features, immunohistochemical profile and molecular alterations. It mainly affects middle aged individuals with slight male predominance and parotid gland is the most common site of involvement. Although ETV6-NTRK3 gene fusion is considered pathognomonic for secretory carcinoma, advances in molecular profiling of this tumor have led to the discovery of novel ETV6 fusion partners and gene mutations. Herein, we describe a case of an adenocarcinoma of intercalated duct origin favor secretory carcinoma, in a unique location of von Ebner's glands of mobile tongue in a 40-year-old Caucasian female. Aside from being in a unique location, the tumor showed somatic mutation for PALB2 gene which has not been described so far in secretory carcinoma. Discovery of novel fusions and mutations have therapeutic implications with respect to targeted therapy.

Validation of NRG oncology/RTOG-0129 risk groups for HPV-positive and HPV-negative oropharyngeal squamous cell cancer: Implications for risk-based therapeutic intensity trials.

BACKGROUND: Radiation Therapy Oncology Group (RTOG)-0129 recursive partitioning analysis was the basis for risk-based therapeutic intensification trials for oropharyngeal cancer (OPC). To the authors' knowledge, the question of whether RTOG-0129 overall survival (OS) estimates for low-risk, intermediate-risk, and high-risk groups are similar in other data sets or applicable to progression-free survival (PFS) is unknown. Therefore, the authors evaluated whether survival differences between RTOG-0129 risk groups persist at 5 years, are reproducible in an independent clinical trial, and are applicable to PFS, and whether toxicities differ across risk groups. METHODS: Prospective randomized clinical trials were analyzed retrospectively. RTOG-0129 evaluated standard versus accelerated fractionation radiotherapy concurrent with cisplatin. RTOG-0522 compared the combination of cisplatin and accelerated fractionation with or without cetuximab. Patients with OPC with available p16 status and tobacco history were eligible. RESULTS: There was a total of 260 patients and 287 patients, respectively, from RTOG-0129 and RTOG-0522, with median follow-ups for surviving patients of 7.9 years (range, 1.7-9.9 years) and 4.7 years (range, 0.1-7.0 years), respectively. Previous OS differences in RTOG-0129 persisted at 5 years. In RTOG-0522, the 5-year OS rates for the low-risk, intermediate-risk, and high-risk groups were 88.1%, 69.9%, and 45.1%, respectively (P for trend, <.001). The 5-year PFS rates for the same 3 groups were 72.9%, 56.1%, and 42.2%, respectively. In RTOG-0522 among a subgroup of patients considered to be at very good risk (p16-positive disease, smoking history of ≤10 pack-years, and classified with T1-T2 disease with ipsilateral lymph nodes measuring ≤6 cm or T3 disease without contralateral or >6 cm lymph nodes), the 5-year OS and PFS rates were 93.8% and 82.2%, respectively. Overall rates of acute and late toxicities were similar by risk group. CONCLUSIONS: RTOG-0129 risk groups persisted at 5 years and were reproducible in RTOG-0522. However, there was variability in the estimates. These data underscore the importance of long-term follow-up and appropriate patient selection in therapeutic deintensification trials.

Usefulness of surveillance imaging in patients with head and neck cancer who are treated with definitive radiotherapy.

BACKGROUND: The current study was performed to assess the efficacy of surveillance imaging in patients with head and neck cancer (HNC) who are treated definitively with radiotherapy. METHODS: Eligible patients included those with a demonstrable disease-free interval (≥1 follow-up imaging procedure without evidence of disease and a subsequent visit/imaging procedure) who underwent treatment of HNC from 2000 through 2010. RESULTS: A total of 1508 patients were included. The median overall survival was 99 months, with a median imaging follow-up period of 59 months. Of the 1508 patients, 190 patients (12.6%) experienced disease recurrence (107 patients had locoregional and 83 had distant disease recurrence). A total of 119 patients (62.6%) in the group with disease recurrence were symptomatic and/or had an adverse clinical finding associated with the recurrence. Approximately 80% of patients with locoregional disease recurrences presented with a clinical finding, whereas 60% of distant disease recurrences were detected by imaging in asymptomatic patients. Despite the earlier detection of disease recurrence via imaging, those patients in the group of patients with clinically detected disease recurrence were significantly more likely to undergo salvage therapy compared with those whose recurrence was detected on imaging (odds ratio, 0.35). There was no difference in overall survival noted between those patients with disease recurrences that were detected clinically or with imaging alone. Approximately 70% of disease recurrences occurred within the first 2 years. In those patients who developed disease recurrence after 2 years, the median time to recurrence was 51 months. After 2 years, the average number of imaging procedures per patient for the detection of a salvageable recurrence for the imaging-detected group was 1539. CONCLUSIONS: Surveillance imaging in asymptomatic patients with HNC who are treated definitively with radiotherapy without clinically suspicious findings beyond 2 years has a low yield and a high cost. Physicians ordering these studies must use judicious consideration and discretion.

PD-L1 expression by immunohistochemistry in salivary duct carcinoma.

BACKGROUND: Immune checkpoint inhibitors play an increasing role in oncologic care. PD-L1 expression is associated with survival and predicts response to PD-1 or PD-L1 inhibitors in a variety of tumors. Our aim is to evaluate the frequency and prognostic significance of PD-L1 expression in salivary duct carcinoma. DESIGN: We retrospectively evaluated the expression of PD-L1 by two different antibodies (PD-L1 28-8 and PD-L1 22C3) in salivary duct carcinomas. PD-L1 expression in at least 1% of tumor cells was considered immunoreactive. Kaplan-Meier analysis was performed to determine the impact of PD-L1 expression on survival; differences between survival curves were assessed by the chi-square test, and pairwise comparisons of factors were assessed with the log-rank test. RESULTS: A total of 113 patients' specimens were evaluated. Seventy-six (76%) of the patients were male. Mean age at time of presentation was 61.2 (SD = 12.4) years. PD-L1 expression was found in 26% of the samples. Median follow-up time was 36.6 months (range = 1.4-249 months). Overall survival at 3, 5 and 10 years were 52.6%, 37.9% and 25.6%, respectively. There was no statistical difference in survival between patients with PD-L1-immunoreactive tumors and those without, regardless of which antibody was used (chi2 result for all plots: p = 0.53; log rank test for pairwise comparison: p > 0.256). CONCLUSION: In our analysis, PD-L1 expression occurred in a small proportion of salivary duct carcinomas, usually at low levels, and did not correlate with survival. Its predictive value and utility in selecting patients with salivary duct carcinoma who might benefit from PD-1/PD-L1 inhibitors warrants further investigation.

Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy.

BACKGROUND: Patients with advanced primary and recurrent salivary duct carcinoma (SDC), a rare and lethal malignancy, have limited therapeutic options. Novel small-molecule agents aimed at targeting critical signaling associated with SDC tumorigenesis may lead to new therapeutic options for patients with these tumors. The human epidermal growth factor receptor 2 (HER2)/phosphoinositide 3-kinase (PI3K) axis, an important oncogenic pathway, has been targeted for therapy in several solid tumors. Currently, little is known about the role and clinical implications of alterations of the HER2/PI3K pathway in patients with SDC. METHODS: The authors investigated the clinicopathologic features, genetic alterations, and expression of key members of the HER2/PI3K pathway in 43 primary tumors and conducted in vitro functional and targeted drug-response analyses on cell lines derived from salivary epithelial carcinomas. RESULTS: In primary tumors, loss of phosphatase and tensin homolog (PTEN) expression was identified in 22 of 43 tumors (51%), overexpression of HER2 was observed in 12 of 43 tumors (28%), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations were identified in 12 of 43 tumors (28%). Phosphorylated protein kinase B (p-AKT) was highly expressed in most tumors. Most tumors (70%) displayed mutually exclusive alterations of PI3K members, whereas 8 tumors (19%) had 2 or more concurrent abnormalities. In vitro studies demonstrated a direct association between PTEN loss and PI3K pathway activation and evidence of response to combined PI3Kα and PI3Kß and/or pan-PI3K inhibitors. CONCLUSIONS: The current analyses reveal frequent PTEN loss and mutually exclusive alterations of key PI3K pathway members in SDC and demonstrate in vitro evidence of a response to pan-PI3K inhibitors. These results provide a framework for a biomarker-based substratification of patients with SDC in future targeted therapy. Cancer 2018;124:3523-32. © 2018 American Cancer Society.

NCCN Guidelines Insights: Head and Neck Cancers, Version 1.2018.

The NCCN Guidelines for Head and Neck (H&N) Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the H&N, and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding evaluation and treatment of nasopharyngeal carcinoma.

Performance Improvement in Head and Neck Cancer.

Performance improvement requires establishing a platform to set benchmarks and monitor the quality of care provided through quality indicators and metrics. This has long been recognized as critical to overall quality improvement and more recently, has become federally mandated. Here, we review recent studies evaluating performance in head and neck cancer care, from those spanning all phases of head and neck cancer care to others focused on head and neck surgical performance, including both national and departmental/institutional efforts.