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.

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.

Well-Differentiated Thyroid Cancer: Who Should Get Postoperative Radiation?

BACKGROUND: The mainstay of treatment of well-differentiated thyroid cancer (WDTC) is surgery followed by adjuvant radioactive iodine therapy. Postoperative radiation therapy (PORT) is rarely used. OBJECTIVE: The aim of our study was to report our experience of patients with WDTC who were selected to receive PORT. MATERIALS AND METHODS: After Institutional Review Board approval, patients who received PORT were identified from a departmental database of 6259 patients with WDTC treated with primary surgery from 1986 to 2015. We carried out propensity matching to compare outcomes with a cohort of patients who did not receive PORT. The main outcome of interest was central neck recurrence-free probability (CNRFP), while secondary outcomes were lateral neck recurrence-free probability (LNRFP), disease-specific survival (DSS), and overall survival (OS). RESULTS: From 6259 patients, 32 (0.5%) patients with a median age of 65.2 years received PORT. Tall-cell variant papillary thyroid carcinoma was the most common pathology (45%). Patients who received PORT had no difference in CNRFP compared with patients treated without PORT (10-year CNRFP 88% vs. 73%; p = 0.18). Furthermore, patients who received PORT had superior LNRFP (10-year LNRFP 100% vs. 62%; p = 0.001) compared with the no-PORT cohort. Despite this, patients who received PORT had similar DSS (71% PORT vs. 75% no-PORT) and OS (65% PORT vs. 58% no-PORT group) as the no-PORT cohort. CONCLUSIONS: Our data show that select patients who received PORT had improved locoregional recurrence-free probability; however, this did not translate into improved DSS and OS. At our institution, we recommend the use of PORT only in highly selected patients with locally advanced primary tumors who are deemed to have a high risk of central neck recurrence for which salvage surgery would result in unacceptable risk to the airway.

Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).

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.

Head and neck surgical oncology.

During the past five decades, major technological advances, including availability of imaging techniques such as computed tomography, magnetic resonance imaging, and positron emission tomography scans, have improved accurate assessment of tumors. Major advances in reconstructive surgery with development of microvascular free-flap reconstruction have made one-stage resection and reconstruction a reality, leading to a better quality of life. Multimodality treatments combining chemotherapy with radiation have led to development of organ preservation strategies and improved locoregional control of head and neck cancer.

Surgical management of vascular tumors and malformations of the head and neck in adults.

Vascular tumors and malformations present a diagnostic and therapeutic challenge to many physicians. Because these lesions are rare, few surgeons have enough experience with them other than those practicing in tertiary vascular anomaly treatment centers. Some patients may have been misdiagnosed or mistreated during childhood and present in adult age with either recurrence or with an untreated lesion. Ideally, a multidisciplinary treatment team should be involved to discuss management with the patient including specialists in surgery, interventional radiology, pathology, hematology, genetics, and dermatology. As our understanding of the pathogenesis of these lesions grows, novel therapies are being employed which may decrease the need for surgery. Nevertheless, some lesions need definitive treatment with surgery. Improving understanding of the surgical management of vascular anomalies will improve cosmetic and functional outcomes for patients.

John Wayne Clinical Research Lecture: New Avenues for Uplifting the Global Quality of Care in Surgical Oncology.

Health care equality is an idealistic goal that is difficult to achieve. However, uplifting the quality of care in surgery for cancer is achievable through several means, the most important of which is training of surgeons through properly structured training programs. However, such programs vary greatly, and no uniformity of curriculum exists throughout the world. On the other hand, several avenues are available for uplifting the quality of care through education and dissemination of knowledge at an individual level, an institutional level, a national level, and an international level. Efforts to uplift the quality of surgical care at an individual level can be by direct delivery of care or by dissemination of knowledge and experiences through personal interactions, lectures, and published works. Conferences, webinars, and travel grants are effective means offered by several institutions and national professional organizations. At an international level, however, much more can be done. For example, in the specialty of head and neck surgery, the International Federation of Head and Neck Oncologic Societies (IFHNOS) has done extraordinary work through world congresses, world tour programs, master courses on operative techniques, and its most impactful program, the Global On Line Fellowship in head and neck surgery and oncology. The programs offered by IFHNOS have had a huge impact on the quality of surgical care for head and neck cancer worldwide. This prototype can be used in many other specialties of surgical oncology to uplift the quality of care globally.

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.

Staging of human papilloma virus related cancers of the oropharynx.

For the past two decades an increasing number of oropharyngeal cancers have been found to be associated with the human papilloma virus (HPV). These tumors are a biologically distinct entity with better prognosis and excellent response to therapy. Therefore, a separate staging system has been introduced for HPV-related oropharyngeal tumors in the latest edition of the American Joint Committee on Cancer (AJCC eighth Ed).

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.

Comparison of different guidelines for oral cancer.

BACKGROUND: Guidelines should provide accessible and reliable information for decision-making. Also, they should be translatable to multiple settings, allowing their use in diverse situations. METHODS: We searched in GOOGLE, PUBMED, SCIELO, and SCOPUS for guidelines on oral squamous cell carcinoma. They were evaluated using the AGREE II protocol. RESULTS: We identified 16 guidelines that fulfilled inclusion criteria. The mean score and range for each AGREE II domain were: "scope and purpose" 74.1% (6-100.0%); "stakeholder" 78.6% (0-100.0%); "rigor of development" 71.4% (0-100.0%); "clarity of presentation" 71.4% (6-100.0%); "applicability" 50.0% (0-85.7%); "editorial independence" 57.1% (14.3-85.7%) and "overall assessment" 57.1% (14.3-100.0%). CONCLUSION: Guidelines for oral cancer present variable quality. Among those available, only four surpassed the 70% AGREE II score threshold.

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.

Distant metastasis of salivary gland cancer: Incidence, management, and outcomes.

BACKGROUND: Distant metastases (DMs) are the primary cause of treatment failure in patients with salivary gland carcinoma. There is no consensus on the standard treatment. METHODS: Patients with DMs were identified from an institutional database of 884 patients with salivary gland cancer who underwent resection of the primary tumor between 1985 and 2015. Survival outcomes for patients with DMs were determined with the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify factors associated with DM. RESULTS: Of the 884 patients identified, 137 (15%) developed DMs during follow-up. Most of the primary tumors (n = 77 [56%]) were located in a major salivary gland. At clinical presentation, 53% of the tumors were classified as T3 or T4, and 32% had clinical node metastases. The median time to DM was 20.3 months. The factors associated with shorter distant recurrence-free survival were male sex, high-risk tumor histology, and advanced pathological T and N classifications. Patients with bone metastases had a lower survival rate than patients with lung metastases. The total number of DMs in a patient was inversely associated with survival. Patients who underwent surgical resection of DMs had a significantly higher 5-year rate of metastatic disease-specific survival than patients who underwent observation or nonsurgical treatment (44%, 29%, and 19%, respectively; P = .003). CONCLUSIONS: In patients with DMs of salivary gland carcinoma, survival is negatively associated with high-grade histology, bone DMs, and the total number of DMs. Metastasectomy can help to lengthen disease-free survival.

The 3 Bs of cancer care amid the COVID-19 pandemic crisis: "Be safe, be smart, be kind"-A multidisciplinary approach increasing the use of radiation and embracing telemedicine for head and neck cancer.

Because of the national emergency triggered by the coronavirus disease 2019 (COVID-19) pandemic, government-mandated public health directives have drastically changed not only social norms but also the practice of oncologic medicine. Timely head and neck cancer (HNC) treatment must be prioritized, even during emergencies. Because severe acute respiratory syndrome coronavirus 2 predominantly resides in the sinonasal/oral/oropharyngeal tracts, nonessential mucosal procedures are restricted, and HNCs are being triaged toward nonsurgical treatments when cures are comparable. Consequently, radiation utilization will likely increase during this pandemic. Even in radiation oncology, standard in-person and endoscopic evaluations are being restrained to limit exposure risks and preserve personal protective equipment for other frontline workers. The authors have implemented telemedicine and multidisciplinary conferences to continue to offer standard-of-care HNC treatments during this uniquely challenging time. Because of the lack of feasibility data on telemedicine for HNC, they report their early experience at a high-volume cancer center at the domestic epicenter of the COVID-19 crisis.

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.

Does age influence disease-specific survival in patients with squamous cell carcinomas of the head and neck?

BACKGROUND AND OBJECTIVES: The number of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) at an advanced age has increased. The aim of this study is to evaluate the age at which disease-specific survival (DSS) significantly decreases in HNSCC. METHODS: We performed a retrospective study of 5469 patients with HNSCC treated at our center (1985-2016). External validation with 2082 oral squamous cell carcinomas from a collaborative institution from another continent was performed. RESULTS: We observed an orderly decrease in overall survival as age at diagnosis increased. There were no differences in DSS based on age for patients <80 years old (P = .623), while older patients had a significant decrease in DSS. These results were validated in the independent dataset. In a multivariable analysis performed in the test set, compared to patients <80 years old, patients between 80 to 85 had a 1.50 times higher risk of disease-specific death (95% confidence interval [CI]: 1.19-1.89; P = .001), and patients >85 had a 2.19 times higher risk (95% CI: 1.68-2.87; P < .001). CONCLUSIONS: DSS started to significantly decrease in HNSCC at 80 years old. These findings, validated in an independent cohort, indicate that chronological age on its own should not withhold curative treatment in the majority of patients with HNSCC.

Management of the Neck in Well-Differentiated Thyroid Cancer.

PURPOSE OF REVIEW: In this narrative review, we discuss the indications for elective and therapeutic neck dissections and the postoperative surveillance and treatment options for recurrent nodal disease in patients with well-differentiated thyroid cancer. RECENT FINDINGS: Increased availability of advanced imaging modalities has led to an increased detection rate of previously occult nodal disease in thyroid cancer. Nodal metastases are more common in young patients, large primary tumors, specific genotypes, and certain histological types. While clinically evident nodal disease in the lateral neck compartments has a significant oncological impact, particularly in the older age group, microscopic metastases to the central or the lateral neck in well-differentiated thyroid cancer do not significantly affect outcome. As patients with clinically evident nodal disease are associated with worse outcomes, they should be treated surgically in order to reduce rates of regional recurrence and improve survival. The benefit of elective neck dissection remains unverified as the impact of microscopic disease on outcomes is not significant.