Defining the Genomic Landscape of Diffuse Sclerosing Papillary Thyroid Carcinoma: Prognostic Implications of RET Fusions.

BACKGROUND: Diffuse sclerosing papillary thyroid carcinoma (DSPTC) is an aggressive histopathologic subtype of papillary thyroid carcinoma. Correlation between genotype and phenotype has not been comprehensively described. This study aimed to describe the genomic landscape of DSPTC comprehensively using next-generation sequencing (NGS), analyze the prognostic implications of different mutations, and identify potential molecular treatment targets. METHODS: Tumor tissue was available for 41 DSPTC patients treated at Memorial Sloan Kettering Cancer Center between 2004 and 2021. After DNA extraction, NGS was performed using the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets platform, which sequences 505 critical cancer genes. Clinicopathologic characteristics were compared using the chi-square test. The Kaplan-Meier method and log-rank statistics were used to compare outcomes. RESULTS: The most common mutation was RET fusion, occurring in 32% (13/41) of the patients. Other oncologic drivers occurred in 68% (28/41) of the patients, including 8 BRAFV600E mutations (20%) and 4 USP8 mutations (10%), which have not been described in thyroid malignancy previously. Patients experienced RET fusion-positive tumors at a younger age than other drivers, with more aggressive histopathologic features and more advanced T stage (p = 0.019). Patients who were RET fusion-positive had a significantly poorer 5-year recurrence-free survival probability than those with other drivers (46% vs 84%; p = 0.003; median follow-up period, 45 months). In multivariable analysis, RET fusion was the only independent risk factor for recurrence (hazard ratio [HR], 7.69; p = 0.017). CONCLUSION: Gene-sequencing should be strongly considered for recurrent DSPTC due to significant prognostic and treatment implications of RET fusion identification. The novel finding of USP8 mutation in DSPTC requires further investigation into its potential as a driver mutation.

Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual.

Answer questions and earn CME/CNE The recently released eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual, Head and Neck Section, introduces significant modifications from the prior seventh edition. This article details several of the most significant modifications, and the rationale for the revisions, to alert the reader to evolution of the field. The most significant update creates a separate staging algorithm for high-risk human papillomavirus-associated cancer of the oropharynx, distinguishing it from oropharyngeal cancer with other causes. Other modifications include: the reorganizing of skin cancer (other than melanoma and Merkel cell carcinoma) from a general chapter for the entire body to a head and neck-specific cutaneous malignancies chapter; division of cancer of the pharynx into 3 separate chapters; changes to the tumor (T) categories for oral cavity, skin, and nasopharynx; and the addition of extranodal cancer extension to lymph node category (N) in all but the viral-related cancers and mucosal melanoma. The Head and Neck Task Force worked with colleagues around the world to derive a staging system that reflects ongoing changes in head and neck oncology; it remains user friendly and consistent with the traditional tumor, lymph node, metastasis (TNM) staging paradigm. CA Cancer J Clin 2017;67:122-137. © 2017 American Cancer Society.

Improved Adherence to ATA Medullary Thyroid Cancer Treatment Guidelines.

BACKGROUND: The 2009 American Thyroid Association (ATA) guidelines for medullary thyroid cancer (MTC) were created to unify national practice patterns. Our aims were to (1) evaluate national adherence to ATA guidelines before and after 2009, (2) identify factors that are associated with concordance with guidelines, and (3) evaluate whether there is an association between survival and concordant treatment. PATIENTS AND METHODS: Patients with MTC were identified from the 2009 to 2015 National Cancer Database. Adherence to ATA recommendations regarding extent of surgery (R61-R66) was analyzed. Logistic regression was used to determine predictors of discordance and propensity score matching was used to compare concordant treatment rates between time periods. Kaplan-Meier survival analysis was used to determine association between survival and concordant treatment. RESULTS: There were 3421 patients with MTC, and of these 3087 had M0 disease and 334 had M1 disease. We found that 72% of M0 cases adhered to R61-66, and 68% of M0 cases without advanced local disease were adherent to R61-63. Following propensity score matching, the adherence rate was 67% before 2009 and 74% after. Patient factors associated with discordant treatment were female gender, older age, treatment at a nonacademic facility, and living within 50 miles of the treatment facility. Adherence to guidelines was associated with improved overall survival (OS) (p < 0.01). CONCLUSIONS: Treatment of MTC was discordant from guidelines in 26% of cases from 2009 to 2015 compared with 33% prior to 2009 in a propensity matched analysis, and was most often in cases with localized, noninvasive disease. Improved adherence to guidelines may improve overall survival.

Diffuse Sclerosing Papillary Thyroid Carcinoma: Clinicopathological Characteristics and Prognostic Implications Compared with Classic and Tall Cell Papillary Thyroid Cancer.

BACKGROUND: The clinical behaviour and oncologic outcome of diffuse sclerosing papillary thyroid carcinoma (DS-PTC) is poorly understood. The objectives of this study were to compare the clinicopathological characteristics and oncological outcomes of DS-PTC to classic PTC (cPTC) and tall cell PTC (TC-PTC). METHODS: After institutional review board approval, 86 DS-PTC, 2,080 cPTC, and 701 TC-PTC patients treated at MSKCC between 1986 and 2021 were identified. Clinicopathological characteristics were compared by using chi-square test. Kaplan-Meier and log rank were used to compare recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). DS-PTC patients were propensity matched to cPTC and TC-PTC patients for further comparison. RESULTS: DS-PTC patients were younger with more advanced disease than cPTC and TC-PTC (p < 0.05). Lymphovascular invasion (LVI), extranodal extension, and positive margins were more common in DS-PTC (p < 0.02). Propensity matching confirmed more aggressive histopathological features in DS-PTC. The median number of metastatic lymph nodes was significantly greater and DS-PTC metastases were RAI avid. DS-PTC 5-year RFS was 50.4% compared with 92.4% in cPTC and 88.4% in TC-PTC (p < 0.001). Multivariate analysis confirmed DS-PTC as an independent prognostic factor of recurrence. Ten-year DSS for DS-PTC was 100% compared with 97.1% in cPTC and 91.1% in TC-PTC. Differentiated high-grade, thyroid carcinoma DS had more advanced T-stage and worse 5-year RFS than DS-PTC. CONCLUSIONS: DS-PTC presents with more advanced clinicopathological features than cPTC and TC-PTC. Large-volume nodal metastases and LVI are characteristic features. Almost half of patients develop recurrence despite aggressive initial management. Despite this, with successful salvage surgery DSS is excellent.

Complications of Thyroid Cancer Surgery in Pediatric Patients at a Tertiary Cancer Center.

BACKGROUND: The incidence of complications and risk factors for hypocalcemia after pediatric thyroid cancer surgery has not been clearly defined in the literature because most reports fail to distinguish between benign and malignant disease. The trend away from total thyroidectomy (TT) to thyroid lobectomy in low-risk disease means there is a need to clearly define the complication profile of malignant disease. METHODS: After institutional review board (IRB) approval, a retrospective chart review was undertaken at Memorial Sloan Kettering Cancer Center for pediatric patients undergoing surgery for well-differentiated thyroid cancer from 1986 to 2021. Clinicopathologic characteristics and complications were evaluated. Multivariable analysis was performed to identify factors independently associated with postoperative hypocalcemia. RESULTS: The study identified 307 pediatric patients with well-differentiated thyroid carcinoma (median follow-up period, 61 months). Of these patients, 69% underwent TT and 31% received a partial thyroidectomy. Among them, 40% had N0 disease, 28% had N1a disease, and 33% had N1b disease. Postoperatively, no patients experienced a neck hematoma, 1.6% had temporary unilateral vocal cord palsy (VCP), and 0.7% had permanent VCP due to recurrent laryngeal nerve (RLN) invasion. Temporary and permanent hypocalcemia occurred in respectively 32.6 % and 5.2 % of the patients. Multivariable analysis identified central neck dissection (CND) (odds ratio [OR] 3.30; p < 0.001) and N1 disease (OR 2.51; p = 0.036) as independent risk factors for temporary hypocalcemia and N stage (OR 3.64; p = 0.018) as a risk factor for permanent hypocalcemia. CONCLUSION: Pediatric thyroid cancer surgery results in low complication rates despite nodal metastases. Vocal cord paralysis is rare unless disease is found to be invading the RLN intraoperatively. Both N stage and CND are independent risk factors for hypocalcemia, helping to identify high-risk patients.

Robotic versus laparoscopic gastrectomy for adenocarcinoma in the US: a propensity score-matching analysis of 11,173 patients on oncological adequacy.

INTRODUCTION: Surgery remains the cornerstone treatment for gastric cancer. Previous studies have reported better lymphadenectomy with minimally invasive approaches. There is a paucity of data comparing robotic and laparoscopic gastrectomy in the US. Herein, we examined whether oncological adequacy differs between laparoscopic and robotic approaches. METHODS: The National Cancer Database was utilized to identify patients who underwent gastrectomy for adenocarcinoma between 2010 and 2019. A propensity score-matching analysis between robotic gastrectomy (RG) versus laparoscopic gastrectomy (LG) was performed. The primary outcomes were lymphadenectomy ≥ 16 nodes and surgical margins. RESULTS: A total of 11,173 patients underwent minimally invasive surgery for gastric adenocarcinoma between 2010 and 2019. Of those 8320 underwent LG and 2853 RG. Comparing the unmatched cohorts, RG was associated with a higher rate of adequate lymphadenectomy (63.5% vs 57.1%, p < .0.0001), higher rate of negative margins (93.8% vs 91.9%, p < 0.001), lower rate of prolonged length of stay (26.0% vs 29.6%, p < .0.001), lower 90-day mortality (3.7% vs 5.0%, p < 0.0001), and a better 5-year overall survival (OS) (56% vs 54%, p = 0.03). A propensity score-matching cohort with a 1:1 ratio was created utilizing the variables associated with lymphadenectomy ≥ 16 nodes. The matched analysis revealed that the rate of adequate lymphadenectomy was significantly higher for RG compared to LG, 63.5% vs 60.4% (p = 0.01), respectively. There was no longer a significant difference between RG and LG regarding the rate of negative margins, prolonged length of stay, 90-day mortality, rate of receipt of postoperative chemotherapy, and OS. CONCLUSIONS: This propensity score-matching analysis with a large US cohort shows that RG was associated with a higher rate of adequate lymphadenectomy compared to LR. RG and LG had a similar rate of negative margins, prolonged length of stay, receipt of postoperative chemotherapy, 90-day mortality, and OS, suggesting that RG is a comparable surgical approach, if not superior to LG.

Environmental Chemicals and their Association with Hyperparathyroidism.

BACKGROUND: The incidence of hyperparathyroidism has increased in the USA. The previous work from our institution detected environmental chemicals (EC) within hyperplastic parathyroid tumors. The National Health and Nutrition Examination Survey (NHANES) is a program designed to assess the health status of people in the USA and includes measurements of EC in serum. Our aim was to determine which EC are associated with elevated parathyroid hormone (PTH) and calcium levels within NHANES. METHODS: NHANES was queried from 2003-2016 for our analysis with calcium. A separate subgroup was queried from 2003-2006 that included PTH levels. Subjects with elevated calcium, and elevated PTH and normal Vitamin D levels were identified. Wilcoxon rank sum tests were used to analyze levels of EC in those with elevated calcium, and those with elevated PTH in the subgroup. All EC with p < 0.05 were then included in separate multivariate models adjusting for serum vitamin D and creatinine for PTH and albumin for calcium. RESULTS: There were 51,395 subjects analyzed, and calcium was elevated in 2.1% (1080) of subjects. Our subgroup analysis analyzed 14,681 subjects, and PTH was elevated without deficient Vitamin D in 9.4% (1,377). Twenty-nine different polychlorinated biphenyls and the organochlorine pesticides hexachlorobenzene, transnonachlor, oxychlordane, and p,p'-dichlorodiphenyldichloroethylene (DDE) were found to be associated with elevated calcium and separately with elevated PTH (all p < 0.05). CONCLUSION: In NHANES, 33 ECs were found to be associated with elevated calcium as well as elevated PTH levels on our subgroup analysis. These chemicals may lead us toward a causal link between environmental factors and the development of hyperparathyroidism and should be the focus of future studies looking at chemical levels within specimens.

Prognostic impact of extranodal extension (ENE) in surgically managed treatment-naive HPV-positive oropharyngeal squamous cell carcinoma with nodal metastasis.

Extranodal extension (ENE) is a significant prognostic factor for human papilloma virus (HPV)-negative head and neck squamous cell carcinoma and is incorporated into AJCC 8th edition pN stage. It remains controversial whether ENE or the degree of ENE is prognostically relevant in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). A detailed clinicopathologic review was conducted in a large retrospective cohort of 232 surgically treated patients with HPV-positive OPSCC and nodal metastasis. Fifty-six patients (24%) had nodal metastasis with ENE. The median vertical extent of ENE was 2.9 mm (range 0.2-20.3 mm), and the median horizontal span of ENE was 2.5 mm (range: 0.3-14.0 mm). Comparing with patients without ENE, those with ENE were associated with a higher number of positive lymph nodes, lymphovascular invasion, perineural invasion, adjuvant chemotherapy, larger primary tumor size, and shorter follow up period. Patients with ENE had shortened overall survival (OS), disease specific survival (DSS), disease free survival (DFS), distant metastasis free survival (DMFS), and regional recurrence free survival (RRFS) on univariate survival analysis. The 5-year OS, DSS, and DFS were 95%, 97%, and 90% respectively for the group without ENE, and 64%, 71%, and 65% respectively for the group with ENE. On Multivariate survival analysis, the presence of ENE was an independent adverse prognostic factor for OS, DSS, and DFS. Additionally, major ENE defined as a vertical extent of ≥4 mm or irregular soft tissue deposit independently predicted shortened OS, DSS, and RFS. In conclusion, the presence of ENE, in particular major ENE, is an independent prognostic factor in HPV-positive OPSCC. Therefore, we propose to document the presence and extent of ENE for these tumors. Consideration may be given for AJCC 9th edition to include ENE into pN stage of HPV-positive OPSCC.

Prognostic impact of autoimmune disease in oral cavity squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Recent literature has highlighted the role of the host in the prognosis of oral squamous cell carcinoma (OSCC). In this study, we retrospectively examined the impact of autoimmune (AI) disorders as an aspect of the host status on survival outcomes in OSCC patients. METHODS: From a departmental database of OSCC patients (n = 1369), 123 patients with an AI disorder were identified. AI and no-AI groups were compared for survival outcomes. RESULTS: There were no significant differences in survival between groups for overall survival, disease-specific survival, local, regional, and distant recurrence-free probabilities. However, survival and recurrence-free probabilities were poorer in the AI group versus the no AI group. CONCLUSION: Patients with AI disease trended towards worse outcomes. This suggests immune dysregulation in these patients may impact oncologic outcomes.

[18F]PARPi Imaging Is Not Affected by HPV Status In Vitro.

Background: Human papillomavirus- (HPV-) associated oropharyngeal squamous cell carcinomas (OPSCCs) are clinically and pathologically distinct from HPV-negative tumors. Here, we explore whether HPV affects functional biomarkers, including γH2AX, RAD51, and PARP1. Moreover, the role of [18F]PARPi as a broadly applicable imaging tool for head and neck carcinomas is investigated. Methods: HPV-positive and HPV-negative cell lines were used to evaluate the γH2AX, RAD51, and PARP1 expression with immunoblotting and immunofluorescence. Effects of external beam ionizing radiation were investigated in vitro, and survival was investigated via colony-formation assay. [18F]PARPi uptake experiments were performed on HPV-negative and HPV-positive cell lines to quantify PARP1 expression. PARP1 IHC and γH2AX foci were quantified using patient-derived oropharyngeal tumor specimens. Results: Differences in DNA repair were detected, showing higher RAD51 and γH2AX expression in HPV-positive cell lines. Clonogenic assays confirm HPV-positive cell lines to be significantly more radiosensitive. PARP1 expression levels were similar, irrespective of HPV status. Consequently, [18F]PARPi uptake assays demonstrated that this tracer is internalized in cell lines independently from their HPV status. Conclusion: The HPV status, often used clinically to stratify patients, did not affect PARP1 levels, suggesting that PARP imaging can be performed in both HPV-positive and HPV-negative patients. This study confirms that the PET imaging agent [18F]PARPi could serve as a general clinical tool for oropharyngeal cancer patients.

The hidden curve behind COVID-19 outbreak: the impact of delay in treatment initiation in cancer patients and how to mitigate the additional risk of dying-the head and neck cancer model.

PURPOSE: The rapid spread of the SARS-CoV-2 pandemic around the world caused most healthcare services to turn substantial attention to treatment of these patients and also to alter the structure of healthcare systems to address an infectious disease. As a result, many cancer patients had their treatment deferred during the pandemic, increasing the time-to-treatment initiation, the number of untreated patients (which will alter the dynamics of healthcare delivery in the post-pandemic era) and increasing their risk of death. Hence, we analyzed the impact on global cancer mortality considering the decline in oncology care during the COVID-19 outbreak using head and neck cancer, a known time-dependent disease, as a model. METHODS: An online practical tool capable of predicting the risk of cancer patients dying due to the COVID-19 outbreak and also useful for mitigation strategies after the peak of the pandemic has been developed, based on a mathematical model. The scenarios were estimated by information of 15 oncological services worldwide, given a perspective from the five continents and also some simulations were conducted at world demographic data. RESULTS: The model demonstrates that the more that cancer care was maintained during the outbreak and also the more it is increased during the mitigation period, the shorter will be the recovery, lessening the additional risk of dying due to time-to-treatment initiation. CONCLUSIONS: This impact of COVID-19 pandemic on cancer patients is inevitable, but it is possible to minimize it with an effort measured by the proposed model.

Molecular Testing for Thyroid Nodules Including Its Interpretation and Use in Clinical Practice.

Despite advances in imaging and biopsy techniques, the management of thyroid nodules often remains a diagnostic and clinical challenge. In particular, patients with cytologically indeterminate nodules often undergo diagnostic thyroidectomy although only a minority of patients are found to have thyroid malignancy on final pathology. More recently, several molecular testing platforms have been developed to improve the stratification of cancer risk for patients with cytologically indeterminate thyroid nodules. Based on numerous studies demonstrating its accuracy, molecular testing has been incorporated as an important diagnostic adjunct in the management of indeterminate thyroid nodules in the National Comprehensive Cancer Network Guidelines as well as in the American Thyroid Association (ATA) and American Association of Endocrine Surgeons (AAES) guidelines. This overview describes the currently available molecular testing platforms and highlights the published data to date on the clinical validity and utility of molecular testing in the contemporary management of thyroid nodules.

Is a Prophylactic Central Compartment Neck Dissection Required in Papillary Thyroid Carcinoma Patients with Clinically Involved Lateral Compartment Lymph Nodes?

BACKGROUND: The 2015 American Thyroid Association guidelines state that a prophylactic central compartment neck dissection (PCND) should be considered for patients with papillary thyroid carcinoma (PTC) and clinically involved lateral neck lymph nodes (cN1b). The purpose of our study was to determine the rate of central neck recurrence in select cN1b patients, with no evidence of clinically involved central compartment lymph nodes, treated without a PCND. METHODS: After institutional review board approval, adult PTC patients with cN1b disease who were treated with a total thyroidectomy and lateral neck dissection were identified from an institutional database of 6259 patients who underwent initial surgery for well-differentiated thyroid carcinoma from 1986 to 2015. Patients with gross extrathyroidal extension, distant metastases, or no preoperative imaging were excluded. Patients with evidence of clinically involved central compartment lymph nodes, on preoperative imaging or intraoperative evaluation, also were excluded. A total of 152 cN1b patients were included and categorized into non-PCND and PCND groups. Central neck recurrence-free probability (CNRFP) was calculated using the Kaplan-Meier method and log-rank tests. RESULTS: One hundred three patients (67.8%) did not have a PCND. With a median follow-up of 65 months, the 5- and 10-year CNRFP was 98.4% in the non-PCND group and 93.6% in the PCND group (p = 0.133). CONCLUSIONS: Select PTC patients with cN1b disease but no evidence of clinically involved central compartment lymph nodes, on preoperative imaging and intraoperative evaluation, appear to have a low rate of central neck recurrence. These patients may not require or benefit from a PCND.

Depth of invasion versus tumour thickness in early oral tongue squamous cell carcinoma: which measurement is the most practical and predictive of outcome?

AIMS: The 8th edition of the American Joint Committee on Cancer (AJCC) Staging introduced depth of invasion (DOI) into the pT category of oral cavity squamous cell carcinoma. However, we noted multiple practical obstacles in accurately measuring DOI histologically in our daily practice. METHODS AND RESULTS: To compare the prognostic effects of DOI and tumour thickness (TT), a meticulous pathology review was conducted in a retrospective cohort of 293 patients with AJCC 7th edition pT1/T2 oral tongue squamous cell carcinoma. Overall survival (OS) and nodal metastasis rate at initial resection were the primary and secondary outcomes, respectively. We found that TT and DOI were highly correlated with a correlation coefficient of 0.984. The upstage rate was only 6% (18 of 293 patients) when using TT in the pT stage compared with using DOI. More importantly, DOI and TT, as well as pT stage using DOI and pT stage using TT, performed identically in predicting risk of nodal metastasis and OS. CONCLUSIONS: We therefore propose to replace DOI, a complicated measurement with many challenges, with TT in the pT staging system.

A phase I study of a PARP1-targeted topical fluorophore for the detection of oral cancer.

BACKGROUND: Visual inspection and biopsy is the current standard of care for oral cancer diagnosis, but is subject to misinterpretation and consequently to misdiagnosis. Topically applied PARPi-FL is a molecularly specific, fluorescent contrast-based approach that may fulfill the unmet need for a simple, in vivo, non-invasive, cost-effective, point-of-care method for the early diagnosis of oral cancer. Here, we present results from a phase I safety and feasibility study on fluorescent, topically applied PARPi-FL. Twelve patients with a histologically proven oral squamous cell carcinoma (OSCC) gargled a PARPi-FL solution for 60 s (15 mL, 100 nM, 250 nM, 500 nM, or 1000 nM), followed by gargling a clearing solution for 60 s. Fluorescence measurements of the lesion and surrounding oral mucosa were taken before PARPi-FL application, after PARPi-FL application, and after clearing. Blood pressure, oxygen levels, clinical chemistry, and CBC were obtained before and after tracer administration. RESULTS: PARPi-FL was well-tolerated by all patients without any safety concerns. When analyzing the fluorescence signal, all malignant lesions showed a significant differential in contrast after administration of PARPi-FL, with the highest increase occurring at the highest dose level (1000 nM), where all patients had a tumor-to-margin fluorescence signal ratio of >3. A clearing step was essential to increase signal specificity, as it clears unbound PARPi-FL trapped in normal anatomical structures. PARPi-FL tumor cell specificity was confirmed by ex vivo tabletop confocal microscopy. We have demonstrated that the fluorescence signal arose from the nuclei of tumor cells, endorsing our macroscopic findings. CONCLUSIONS: A PARPi-FL swish & spit solution is a rapid and non-invasive diagnostic tool that preferentially localizes fluorescent contrast to OSCC. This technique holds promise for the early detection of OSCC based on in vivo optical evaluation and targeted biopsy of suspicious lesions in the oral cavity. TRIAL REGISTRATION: Clinicaltrials.gov -NCT03085147, registered on March 21st, 2017.

Assessing the quality of life of head and neck healthcare workers during the COVID-19 pandemic-A self-reported global cross-sectional questionnaire study by the International Federation of Head and Neck Oncologic Societies.

BACKGROUND: Considering the pandemic's mode of transmission, the impact on quality of life (QOL) is likely to be exaggerated among healthcare workers (HCWs) who treat head and neck diseases (hHCWs). METHODS: A cross-sectional self-reported QOL assessment was undertaken between July and September 2020 using the World Health Organization Quality of Life instrument sent out to hHCWs. Factors that predicted a poorer QOL were identified using regression models and mediation analysis. RESULTS: Responses from 979 individuals across 53 countries were analyzed with 62.4% participation from low- and middle-income countries. The physical domain had the highest mean scores of 15 ± 2.51, while the environmental domain was the lowest (14.17 ± 2.42). Participants from low- and middle-income countries had a significantly worse physical (p < 0.001) and environmental (p < 0.001) domains, while a low coronavirus disease 2019-related mortality significantly impacted the environmental domain (p-0.034). CONCLUSION: QOL-related issues among hHCWs are a vexing problem and need intervention at an individual and systems level in all parts of the world.

Nodal characteristics associated with adverse prognosis in oral cavity cancer are linked to host immune status.

BACKGROUND AND OBJECTIVE: Nodal metastasis is one of the strongest predictors of outcomes in oral cavity squamous cell carcinomas (OSCC). The aim was to analyze the interplay of nodal characteristics in OSCC prognosis. METHODS: In this retrospective cohort study we included OSCC patients treated with primary surgery including neck dissection between 2005 and 2015 (n = 619). Disease-specific survival (DSS) was the primary endpoint. Optimal cutoffs were identified using recursive-partitioning analysis (RPA). A novel characteristic-metastatic focus-to-lymph node size ratio (MLR)-was introduced. We compared the American Joint Committee on Cancer, Eighth Edition (AJCC8) pN categories to a new categorization. RESULTS: Patients with higher neutrophil-to-lymphocyte ratio had more adverse nodal characteristics. All nodal characteristics were significant predictors of DSS in univariable analysis. In multivariable analysis, only number of positive nodes and MLR remained significant. An RPA including all nodal covariates confirmed the results. Compared with AJCC8, our RPA categorization had better hazard discrimination (0.681 vs. 0.598), but poorer balance value (0.783 vs. 0.708). CONCLUSION: Patients with higher neutrophil-to-lymphocyte ratio had more adverse nodal characteristics. Total number of metastatic lymph nodes is the strongest predictor of outcomes in OSCC. MLR is a more powerful predictor than metastatic lymph node size or metastatic focus size alone.

Diagnostic and Prognostic Utility of 18F-FDG PET/CT in Recurrent Salivary Gland Cancers.

OBJECTIVE. The role of 18F-FDG PET/CT in the evaluation of recurrent salivary gland tumors remains poorly defined. We investigated the diagnostic and prognostic utility of PET in this setting. MATERIALS AND METHODS. A total of 146 patients with recurrent salivary gland cancer were treated at our institution between January 2002 and December 2015. Patients who underwent FDG PET/CT and conventional imaging (CT or MRI) within 3 months of recurrence (n = 78) were included in this retrospective analysis. On FDG PET/CT, we measured the SUVmax, total body metabolic tumor volume of all lesions, and total lesion glycolysis of all lesions to determine the intensity and extent of FDG-avid disease. We assessed the correlation of FDG PET/CT findings with clinicopathologic features, progression-free survival, and overall survival. RESULTS. FDG PET/CT was positive for recurrence in 74 of 78 patients (94.9%) and falsely negative in four patients (5.1%). In comparison with conventional imaging, FDG PET/CT performed for restaging detected additional recurrent lesions in 14 patients (17.9%). The median SUVmax was 7.4, the median total body metabolic tumor volume was 30.1 cm3, and median total lesion glycolysis was 97.3 g/mL × cm3. Sixty-six patients had progressive disease, and 54 died. Univariate and multivariate Cox hazards analysis identified pathologic risk group (p = .04), total body metabolic tumor volume (p < .001), and total lesion glycolysis (p < .001) as independent prognostic factors for progression-free survival and identified age (p = .05), total body metabolic tumor volume (p < .001), and total lesion glycolysis (p < .001) as independent prognostic factors for overall survival. CONCLUSION. In patients with recurrent salivary gland cancer, FDG PET/CT is useful as a single test for defining the extent of disease and providing prognostic information, which may help in selecting appropriate treatment strategies.

Autoimmune disease and oral squamous cell carcinoma: A systematic review.

BACKGROUND: Oral cancer is typically related to environmental carcinogen exposure including tobacco and alcohol. Other less investigated risk factors may be related to a suppressed or dysregulated immune state, and in oral cancer, various levels of immune dysregulation have been found to affect survival and recurrence rates. The rationale for this systematic review was to investigate the possible role that a growing chronic host condition like an autoimmune disease may play in this disease. METHODS: A systematic search of the literature was carried out using four electronic databases in order to identify original research of any analytic study design type that investigated the relationship between autoimmune disease and oral cancer. Out of 1,947 identified records, 24 observational studies were included for qualitative synthesis. RESULTS: The studies varied in end points ranging from overall survival (OS), standardized incidence ratio (SIR), and hazard ratio (HR). Due to the heterogenous sampling of studies even within the same study design group, a meta-analysis was not employed. The current state of the literature is varied and heterogenous in both study design and endpoints. CONCLUSION: Major limitations existed introducing significant bias especially in determining cancer risk such as lack of information surrounding known etiologic risk factors such as alcohol and tobacco consumption. Despite these limitations, a signal was seen between autoimmune disease and oral cancer outcomes and risk. Future studies investigating the relationship between autoimmune disease and oral cancer in a more focused and quantitative manner are therefore needed.

Pretreatment peripheral blood leukocytes are independent predictors of survival in oral cavity cancer.

BACKGROUND: Inflammation and immune surveillance evasion are cancer hallmarks. Peripheral blood leukocytes (PBLs) represent both. The aim of the current study was to examine PBLs as predictors of outcomes in oral cavity squamous cell carcinoma (OSCC), and to find specific cutoffs with the goal of including PBLs as host factor in patients' preoperative risk assessment. METHODS: Previously established head and neck squamous cell carcinoma (HNSCC) cutoffs were examined in an independent cohort of 1369 OSCC patients. Then optimal OSCC cutoffs were found and validated in the subset of patients with OSCC (n = 119) from the external HNSCC cohort. The PBLs analyzed were neutrophils, monocytes, and lymphocytes individually, the neutrophil-to-lymphocyte ratio (NLR), and a combined index using all PBLs called Systemic Inflammation Response Index (SIRI). RESULTS: All parameters were significant predictors of survival using the previous cutoffs. However, OSCC cutoffs stratified survival outcomes better. Considering neutrophils ≤4.8 × 109 /L as reference, patients with 4.8-9.1 × 109 /L neutrophils had 1.536 times higher risk of death (95% CI, 1.295-1.822), and patients with ≥9.1 × 109 /L had 3.076 times higher risk (95% CI: 2.170-4.360). All PBLs maintained independent prognostic capacity in multivariable analysis. Neutrophils, NLR, and SIRI were significant predictors of survival when validating OSCC cutoffs in the external validation cohort. CONCLUSIONS: Pretreatment peripheral blood neutrophils, NLR, and SIRI are the most robust independent predictors of overall survival among all PBLs in OSCC. The authors report externally validated cutoffs that demonstrate the feasibility of including PBLs as host features in the preoperative prognostication of OSCC.