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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.

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).

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.

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.

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).

Most cases of thyroid carcinoma are classified as low risk. These lesions have been treated with open surgery, remote access thyroidectomy, active surveillance, and percutaneous ablation. However, there is lack of consensus and clear indications for a specific treatment selection. The objective of this study is to review the literature regarding the indications for management selection for low-risk carcinomas. Systematic review exploring inclusion and exclusion criteria used to select patients with low-risk carcinomas for treatment approaches. The search found 69 studies. The inclusion criteria most reported were nodule diameter and histopathological confirmation of the tumor type. The most common exclusions were lymph node metastasis and extra-thyroidal extension. There was significant heterogeneity among inclusion and exclusion criteria according to the analyzed therapeutic approach. Alternative therapeutic approaches in low-risk carcinomas can be cautiously considered. Open thyroidectomy remains the standard treatment against which all other approaches must be compared.

Hurthle cell carcinoma (HCC) comprises about 5% of thyroid carcinoma cases. Partly because of its rarity there is much we still need to know about HCC as compared to other histological cancer subtypes. We conducted a systematic literature review following PRISMA guidelines and meta-analysis, from 2000 to 2020, to investigate the main characteristics of HCC and clarify information concerning tumor behavior and treatment. Our review included data from 9638 patients reported in 27 articles over the past 20 years. This tumor occurred more frequently in women (67.5%). The mean age was 57.6 years, and the mean size of the neoplasm at diagnosis was 30 mm. Extrathyroidal extension was common (24%) but lymph node metastasis was not (9%). Total thyroidectomy was the most common surgical approach, with neck dissection usually performed in cases with clinically apparent positive neck nodes. Radioiodine therapy was frequently applied (54%), although there is no consensus about its benefits. The mean 5- and 10-year overall survival was 91% and 76%, respectively. This review serves to further elucidate the main characteristics of this malignancy. HCC of the thyroid is rare and most often presents with a relatively large nodule, whereas lymph node metastases are rare. Given the rarity of HCC, a consensus on their treatment is needed, as doubts remain concerning the role of specific tumor findings and their influence on management.

Importance This study reports the impact of laser surgery on quality of life in patients with oral cavity lesions. Objective To compare postoperative pain and quality of life in patients treated with flexible fiberoptic CO2 laser vs electrocautery in patients with oral cavity precancerous lesions and early stage cancers. Design Randomized controlled trial. Setting Single center. Participants Patients with premalignant oral cavity lesions and early stage oral cancer. Intervention Patients were randomized to have surgical resection using either flexible fiber carbon dioxide laser (Laser) or electrocautery (EC). The patients were then followed over a period of 28 days to assess for outcomes including pain, quality of life, performance status, return to work, and return to diet. Quality of life was measured by the University of Washington Quality of Life (UWQOL) questionnaire and the performance status score (PSS). Main outcome measure The primary endpoint for this study was the numerical pain rating on postoperative day (POD) 7. Results Sixty‐two patients were randomized (32 laser and 30 electrocautery). Lesions excised were carcinoma in 30(48%), dysplasia in 31(50%) and benign in 1(2%). There was no difference in the location of lesion, size of lesion, defect size, type of closure, resection time, and blood loss between Laser and EC arms. Patients who had Laser had less pain compared to EC (mean pain score on POD 7 L = 2.84 vs EC = 3.83, P = 0.11). better UW QOL scores and PSS scores, quicker return to normal diet (median days L = 26.0 vs EC = 28.5, P = 0.17) and faster return to work (median days L = 13.0 vs EC = 16.5, P = 0.14). However, these results were not statistically significant. Conclusion There was a trend for patients treated with laser to have less pain and better quality of life scores but these result were not statistically significant. Based on the actual observed difference, a large multicenter RCT with 90 patients in each arm is required to determine the clinical relevance of our results.

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.

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.

SummaryBackground Selinexor, a first-in-class, oral selective inhibitor of nuclear export (SINE) compound inhibits Exportin-1(XPO1), had demonstrated synergistic activity with many chemotherapies and conferred in vivo antitumor efficacy in hematologic as well as solid tumors. Methods This open-label, single-center, multi-arm phase 1b study used a standard 3 + 3 design and a “basket type” expansion. Selinexor with intravenous topotecan was given in one of the 13 parallel arms. Patients with advanced or metastatic relapsed/refractory solid tumors following prior systemic therapy, or in whom the addition of selinexor to standard chemotherapy deemed appropriate, were eligible. Results Fourteen patients with the median age of 61 years (range, 22–68years) were treated, and the most common cancer types were gynecological cancers; ovarian (n = 5), endometrial (n = 2), and 1 each with fallopian tube and vaginal cancers. Of the 14 patients treated, 12 (86 %) had at least one treatment-related adverse event (TRAE). The most common TRAEs were anemia (71 %), thrombocytopenia (57 %), hyponatremia (57 %), vomiting (57 %), fatigue (50 %), nausea (50 %), and neutropenia (36 %). Two patients had dose limiting toxicities. One patient dosed at selinexor 80 mg had grade 3 nausea and vomiting and one patient dosed at selinexor 60 mg experienced grade 4 neutropenia and thrombocytopenia. Of the 13 efficacy evaluable patients, one (8 %) with endometrial cancer achieved unconfirmed partial response (uPR) and the time-to-treatment failure (TTF) was 48 weeks, whereas 6 of the 13 (46 %) patients had stable disease (SD) contributing to the clinical benefit rate of 46 %. The median TTF for all patients was 9 weeks (range, 2–48weeks). Conclusions Once weekly selinexor in combination with topotecan was viable and showed some preliminary tumor efficacy. The recommend phase 2 dose of selinexor was 60 mg once weekly in combination with IV topotecan.Trial registration: NCT02419495. Registered 14 April 2015, https://clinicaltrials.gov/ct2/show/NCT02419495

Aim: Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Results: Treatment responders maintained higher FACT - Lymphoma (p = 3 adverse events and serious adverse events were not associated with clinically meaningful negative QoL impacts.

Purpose: The nuclear exporter protein exportin-1 (XPO1) is overexpressed in non-Hodgkin lymphoma (NHL) and correlates with poor prognosis. We evaluated enhancing R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) activity in NHL by targeted inhibition of XPO1 using the selective inhibitor of nuclear export (SINE) compounds. Patients and Methods: We evaluated the antitumor activity of SINE compounds in combination with CHO chemotherapy in vitro and in vivo. Newly diagnosed NHL patients in a phase I dose-escalation study received R-CHOP for 6 cycles with weekly selinexor (60, 80, and 100 mg), then selinexor maintenance therapy for one year. RT-PCR, Western blotting, and RNA sequencing were performed on patient blood samples. Results: SINE compounds synergized with CHO in vitro in NHL cell lines and in vivo in our murine xenograft model. In our phase I study, selinexor was dosed at 60 mg (n = 6) and 80 mg (n = 6). The most common adverse events (AE) among 12 patients were fatigue (67%) and nausea (100%). Grade 3–4 AEs were infrequent. Ten evaluable patients had an overall response rate of 100% and complete remission rate of 90% with sustained remissions (median follow-up: 476 days). Maximally tolerated dose was not reached; however, the recommended phase II dose was 60 mg selinexor weekly after evaluating tolerability and discontinuation rates for each dose cohort. Analysis of patient blood samples revealed downregulation of XPO1 and several prosurvival markers. Conclusions: SINE compounds enhance the activity of CHO in vitro and in vivo. Selinexor in combination with R-CHOP was generally well tolerated and showed encouraging efficacy in NHL (NCT03147885).

Characterize the population PK and exposure–response (ER) relationships of selinexor in patients with diffuse large B-cell lymphoma (DLBCL) (efficacy endpoints) or other non-Hodgkin’s lymphoma (NHL) patients (safety endpoints) to determine the optimal dose in patients with DLBCL. This work included patients from seven clinical studies, with 800 patients for PK, 175 patients for efficacy and 322 patients for safety analyses. Logistic regression models and Cox-regression models were used for binary and time-to-event endpoints, respectively. Model-based simulations were performed to justify dose based on balance between efficacy and safety outcome. Selinexor pharmacokinetics were well-described by a two-compartment model with body weight as a significant covariate on clearance and central volume of distribution and gender on clearance. Overall response rate (ORR) in patients with DLBCL increased with day 1 Cmax and decreased in patients with higher baseline tumor size (p

Objective This study was aimed to describe our institutional experience on characteristics and treatment outcomes of sinonasal sarcomas invading the anterior skull base. Design Present study is a retrospective review. Setting The study was conducted at an academic cancer care center. Participants Thirty-one patients with skull base sarcomas treated with primary surgery from 1979 to 2015 were identified for this study from a preexisting database. Main Outcome Measures Survival and recurrence outcomes using the Kaplan–Meier method were the focus areas of the study. Results The median age was 44 years (range: 13–69 years). Twenty patients were male (64.5%). Twenty-nine patients underwent open craniofacial resection (93.5%) and two patients underwent endoscopic resection (6.5%). The majority of tumors were staged pT4 (77.4%). The most common pathologies were leiomyosarcoma (19.4%), osteosarcoma (16.1%), and chondrosarcoma (12.9%). Of those with known margin status, 10 patients had positive/close margins (32.2%) and 16 patients had negative margins (51.6%). Most tumors were high grade (74.2%). Twenty-three patients (74.2%) received adjuvant radiation and four patients (12.9%) received adjuvant chemotherapy. There were nine postoperative complications (29%) including one mortality and three cerebrospinal fluid leaks. There were 10 local, 2 regional, and 5 distant recurrences over a median follow-up of 74 months (range: 1–300 months). The 5-year disease-specific survival (DSS) was 69.8%. The 5-year locoregional recurrence-free probability (RFP) was 63.2% and the 10-year distant RFP was 71.7%. The 5-year DSS for high grade tumors was 64.2 and 85.7% for low grade tumors (p = 0.117). Conclusion This study contributes an updated analysis of anterior skull base sarcomas. Five-year DSS is approximately 70%. Analysis of survival outcomes based on grade, tumor size, and other factors is limited by small sample size and the rarity of these tumors.

OBJECTIVE. To address the lack of validated patient-reported outcome (PRO) instruments that define and quantify patient expectations in thyroid cancer surgery, we developed and initially validated ThyroidEx, a novel disease-specific PRO instrument. STUDY DESIGN. Survey study. SETTING. Single-institution tertiary care cancer center. METHODS. An expert panel drafted an initial set of thyroid cancer–specific concepts, which was used in semistructured concept elicitation interviews with patients with thyroid cancer 4 weeks before and 8 weeks after surgery. Candidate items were generated per patient responses and refined via cognitive interviewing and additional review by the expert panel. The draft ThyroidEx was then preoperatively administered to a separate cohort undergoing thyroid cancer surgery to establish a final item set and initial psychometric evidence. RESULTS. Prospective concept elicitation interviews generated 358 patient-elicited concepts (n = 15 patients). These were then placed into 70 unique subcategories from which 41 items were generated for cognitive interviews with 20 patients preoperatively and 28 postoperatively. After expert panel review, ThyroidEx included 18 items across 2 scales (Expectations and Concerns), with an additional item about beliefs. In the preoperative cohort in phase 2 (n = 67), internal consistency Cronbach’s α values ranged from 0.81 to 0.89. Descriptive analysis showed significant differences between patients’ concerns and expectations and clinicians’ perceptions. CONCLUSION. Defining expectations represents an important modifier in the measurement of PROs. Preliminary validation of ThyroidEx revealed incongruent expectations between expert opinion and patients. Future development and implementation of ThyroidEx may affect preoperative consultation and the consent process.

We assessed the safety, efficacy, maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D) of selinexor, a first in class oral selective inhibitor of nuclear export (100 mg once weekly [QW] or 60 mg twice weekly), in combination with daratumumab (16 mg/kg per label) and dexamethasone (40 mg QW) (SDd) in patients with relapsed refractory multiple myeloma (RRMM). Thirty-four patients (median prior therapies, 3 [range, 2-10]) were enrolled; MM was refractory to proteasome inhibitor (PI) in 85%, immunomodulatory agent (IMiD) in 76%, both in 74%, and daratumumab in 6% of patients. Two dose-limiting toxicities (DLTs) were reported in the selinexor 60 mg twice-weekly cohort with no DLTs in the 100 mg QW cohort, making 100 mg QW the MTD and RP2D. Common treatment-related adverse events included thrombocytopenia (70.6%), nausea (70.6%), fatigue (61.8%), anemia (61.8%), and neutropenia (50.0%). Overall response rate was 73% and median progression-free survival 12.5 months in daratumumab-naïve patients. SDd was well tolerated and its promising efficacy suggests that further study of this PI- and IMiD-free regimen in RRMM patients who had at least one prior line of therapy including a PI and an IMiD but whose disease is naïve to daratumumab is warranted.

The tall cell variant of papillary thyroid carcinoma has traditionally been treated more aggressively than classic papillary thyroid carcinoma. However, this may not be justified in patients with T1/T2 tall cell variant node-negative tumors.We evaluated well-differentiated thyroid cancers treated surgically between 1985 and 2015 at our institution. We compared patients undergoing lobectomy for node-negative T1/T2 tall cell variant tumors with the same cohort with classic papillary thyroid carcinoma. Patients who underwent early planned completion thyroidectomy were excluded. Tall cell variant tumors were defined as those with ≥30% tall cells. Survival and recurrence outcomes were determined by the Kaplan-Meier method and groups compared using the log-rank test.Thyroid lobectomy was performed for T1/T2 N0X disease in 70 (15%) tall cell cases and 429 (23%) classic papillary thyroid carcinoma cases. There was no significant difference in 10-year overall survival (P = .56) or locoregional recurrence-free probability (P = .52). Disease-specific survival and local or central nodal recurrence-free probability were 100% in both groups. In 9 papillary thyroid carcinoma cases, subsequent contralateral lobe tumors developed, and in 5, lateral neck metastases developed. No recurrences were seen in the tall cell group.T1 node-negative tumors with tall cell histology can be satisfactorily managed with thyroid lobectomy, with equivalent oncological outcomes to classic papillary thyroid carcinoma.

BACKGROUND: Sinonasal malignancies are a complex and diverse group of tumors. Over the past five decades, treatment advances have changed the management paradigms for these tumors. Our aim was to analyze the outcomes of patients from a comprehensive cancer center. MATERIALS AND METHODS: We retrospectively assessed 400 patients with sinonasal malignancies treated with surgery at our center between 1973 and 2015. Multiple variables were reviewed to assess the influence on 5-year outcomes. RESULTS: The median age was 56 years (IQR 46.8–68). Two hundred and fifty-nine (65%) were males and 141 (35%) were females. Overall survival (OS) and disease-specific survival (DSS) improved in the last analyzed decade. Orbital invasion, advanced pT-classification and pN-classification, and melanoma histology were associated with poorer outcomes. CONCLUSION: Treatment outcomes for patients with sinonasal malignancy have improved over time. This is likely multifactorial with advances in surgical technique, adjuvant treatment, and patient selection. pT-classification, pN-classification, orbital invasion, and histology are predictive of survival.

Endoscopic endonasal surgery has been demonstrated to be effective in the treatment of selected cases of sinonasal cancers. However, in cases of locally advanced neoplasms, as well as recurrences, the most appropriate approach is still debated. The present review aims to summarize the current state of knowledge on the utility of open approaches to resect sinonasal malignant tumours. Published comparative studies and meta-analyses suggest comparable oncological results with lower morbidity for the endoscopic approaches, but selection biases cannot be excluded. After a critical analysis of the available literature, it can be concluded that endoscopic surgery for selected lesions allows for oncologically safe resections with decreased morbidity. However, when endoscopic endonasal surgery is contraindicated and definitive chemoradiotherapy is not appropriate, craniofacial and transfacial approaches remain the best therapeutic option.

The phase 2b, open-label, multicenter SADAL study evaluated single agent oral selinexor, a selective inhibitor of nuclear export (SINE) compound, in patients with diffuse large B cell lymphoma (DLBCL) after >= 2 lines of systemic therapy. Similar activity was observed in GCB- and non-GCB DLBCL with a trend to higher response rates in DLBCL transformed from follicular lymphoma. Lower response rates were observed in double expressor DLBCL; higher response rates were observed in patients with baseline hemoglobin >= 10 g/dL and normal levels of C-MYC or BCL-2 expression (51%). Overall, strong single agent activity with selinexor were observed in patients with relapsed/refractory DLBCL.Background: The SADAL study evaluated oral selinexor in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. In this post-hoc analysis, we analyzed the outcomes of the SADAL study by DLBCL subtype to determine the effects of DLBCL subtypes on efficacy and tolerability of selinexor. Patients and Methods: Data from 134 patients in SADAL were analyzed by DLBCL subtypes for overall response rate (ORR), overall survival (OS), duration of treatment response, progression-free survival, and adverse events rate. Results: ORR in the entire cohort was 29.1%, and similar in patients with germinal center (GCB) versus non-GCB DLBCL (31.7% vs. 24.2%, P = 0.45); transformed DLBCL showed a trend towards higher ORR than de novo DLBCL: 38.7% vs. 26.2% (P = 0.23). Despite similar prior treatment regimens and baseline characteristics, patients with DLBCL and normal C-MYC/BCL-2 protein expression levels had a significantly higher ORR (46.2% vs.14.8%, P = 0.012) and significantly longer OS (medians 13.7 vs. 5.1 months, hazard ratio 0.43 [95% CI, 0.23-0.77], P = 0.004) as compared with those whose DLBCL had C-MYC and BCL-2 overexpression. Among patients who had normal expression levels of either C-MYC or BCL-2 and baseline hemoglobin levels >= 10g/dL, ORR was 51.5% (n = 47), with median OS of 15.5 months and median PFS of 4.6 months. Similar rates of adverse events were noted in all subgroups. Conclusions: Overall, single agent oral selinexor showed strong responses in patients with limited treatment alternatives regardless of germinal center B-cell type or disease origin. (C) 2021 Elsevier Inc. All rights reserved.

Introduction: Anaplastic thyroid cancer (ATC) is one of the most lethal diseases known to humans with a median survival of 5 months. The American Thyroid Association (ATA) recently published guidelines for the treatment of this dreadful thyroid malignancy. Areas covered: This review presents the current therapeutic landscape of this challenging disease. We also present the results from trials published over the last five years and summarize currently active clinical trials. Expert opinion: Recent attempts to improve the prognosis of these tumors are moving toward personalized medicine, basing the treatment decision on the specific genetic profile of the individual tumor. The positive results of dabrafenib and trametinib for ATC harboring the BRAF V600E mutation have provided a useful treatment option. For the other genetic profiles, different drugs are available and can be used to individualize the treatment, likely using drug combinations. Combinations of drugs act on different molecular pathways and achieve inhibition at separate areas. With new targeted therapies, average survival has improved considerably and death from local disease progression or airway compromise is less likely with improvement in quality of life. Unfortunately, the results remain poor in terms of survival.

BACKGROUND: Sinonasal mucosal melanoma (SNMM) is an aggressive cancer with high mortality. Identifying patients at risk of distant metastasis assists with management and prognostication. We aimed to define the relationship between volume, survival, and risk of distant metastases. METHODS: A retrospective review of all patients with SNMM treated at a single institution over a 21-year period was conducted. Tumor volume was calculated using cross-sectional imaging and survival analysis was performed. RESULTS: Sixty-one patients were included. Tumor volume was predictive of local progression free survival (LPFS) (p=0.032), distant metastases free survival (DMFS) (p=0.002), and overall survival (OS) (p=0.022). It was a better predictor than AJCC stage and T-classification. Tumor volume equal to or greater than 5cm(3) was associated with a significantly worse DMFS and OS (p=0.022 and 0.009, respectively). CONCLUSION: Calculation of tumor volume assists in quantifying the risk of distant metastases and death in SNMM.

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 aim 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 6,259 patients who underwent initial surgery for well-differentiated thyroid carcinoma from 1986 to 2015. Patients with gross extrathyroidal extension, distant metastases, and no pre-operative imaging were excluded. Patients with evidence of clinically involved central compartment lymph nodes, on pre-operative imaging or intra-operative evaluation, were also excluded. One hundred fifty-two 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 pre-operative imaging and intra-operative evaluation, appear to have a low rate of central neck recurrence. These patients may not require or benefit from a PCND.

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., Cancer care is undeniably affected by the coronavirus disease 2019 (COVID‐19) public health emergency, but quality cancer care must persist. A high‐volume cancer center from the domestic epicenter of the COVID‐19 crisis shares its multidisciplinary approach to integrating current public health restrictions and adopting telemedicine to optimize the care of patients with head and neck cancer; it is hoped that this center's experience will provide helpful insights to oncology colleagues.

The International Federation of Head and Neck Oncologic Societies and Memorial Sloan Kettering Cancer Center in New York have partnered to create the Global On Line Fellowship program, a postgraduate fellowship training opportunity for candidates all around the world who are not able to get on-site fellowship training at centers of excellence. This article delineates the successes, challenges, and future goals for the program.

BACKGROUND: Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer with a median overall survival of less than 6 months. We aimed to assess the response to single-agent selinexor, an oral selective inhibitor of nuclear export, in patients with relapsed or refractory DLBCL who had no therapeutic options of potential clinical benefit. METHODS: SADAL was a multicentre, multinational, open-label, phase 2b study done in 59 sites in 19 countries. Patients aged 18 years or older with pathologically confirmed diffuse large B-cell lymphoma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received two to five lines of previous therapies, and progressed after or were not candidates for autologous stem-cell transplantation were enrolled. Germinal centre B-cell or non-germinal centre B-cell tumour subtype and double or triple expressor status were determined by immunohistochemistry and double or triple hit status was determined by cytogenetics. Patients received 60 mg selinexor orally on days 1 and 3 weekly until disease progression or unacceptable toxicity. The study was initially designed to evaluate both 60 mg and 100 mg twice-weekly doses of selinexor; however, the 100 mg dose was discontinued in the protocol (version 7.0) on March 29, 2017, when an improved therapeutic window was observed at 60 mg. Primary outcome was overall response rate. The primary outcome and safety were assessed in all patients who received 60 mg selinexor under protocol version 6.0, or enrolled under protocol versions 7.0 or higher and received at least one dose of selinexor. This trial is registered at ClinicalTrials.gov, NCT02227251 (active but not enrolling). FINDINGS: Between Oct 21, 2015, and Nov 2, 2019, 267 patients were randomly assigned, with 175 allocated to the 60 mg group and 92 to the discontinued 100 mg group. 48 patients assigned to the 60 mg group were excluded due to enrolment before version 6.0 of the protocol; the remaining 127 patients received selinexor 60 mg and were included in analyses of primary outcome and safety. The overall response rate was 28% (36/127; 95% CI 20·7-37·0); 15 (12%) achieved a complete response and 21 (17%) a partial response. The most common grade 3-4 adverse events were thrombocytopenia (n=58), neutropenia (n=31), anaemia (n=28), fatigue (n=14), hyponatraemia (n=10), and nausea (n=8). The most common serious adverse events were pyrexia (n=9), pneumonia (n=6), and sepsis (n=6). There were no deaths judged as related to treatment with selinexor. INTERPRETATION: Single-drug oral selinexor induced durable responses and had a manageable adverse events profile in patients with relapsed or refractory DLBCL who received at least two lines of previous chemoimmunotherapy. Selinexor could be considered a new oral, non-cytotoxic treatment option in this setting. FUNDING: Karyopharm Therapeutics Inc.

INTRODUCTION: Aggressive variants of papillary thyroid cancer (PTC) have been described with increasing frequency. These variants include diffuse sclerosing variant, tall cell variant, columnar cell variant, solid variant, and hobnail variant. METHODS: We have performed a review of the more aggressive variants of PTC with respect to main characteristics, histological and molecular features, and the consequences that the knowledge of these variants should have in the treatment of the patients. RESULTS: At the present time, we do not know the prognostic value of these aggressive PTC variants. The extent of the surgical treatment and adjuvant therapy necessary should be decided on the basis of the extent of the tumor at presentation and the opinion of experienced clinicians. CONCLUSION: These aggressive variants should be known by clinicians, to avoid underdiagnosis, and treated according to the latest recommendations in the literature. ispartof: ADVANCES IN THERAPY vol:37 issue:7 pages:3112-3128 ispartof: location:United States status: published

Background We aimed to review our experience and the changing trends in the management of head and neck paragangliomas (HNPG) over the last three decades. Methods We retrospectively reviewed 103 patients with HNPG treated at our center (1986-2017). We included patients treated with surgery, radiotherapy, and patients maintained under active surveillance. Results Of the surgically treated patients (n = 79), 20% (12/59) of the carotid body tumors (CBT) had a cranial nerve deficit as sequela compared to 95% (19/20) of the non-CBT. Radiotherapy controlled growth in all tumors treated with this modality (n = 10). Of the initially observed patients, 70% (14/20) remained stable and did not require additional treatment. Stratifying by decades, there was a progressive increase in patients initially attempted to be observed and a decrease in upfront surgery. No deaths attributable to the HNPG were encountered. Conclusions Surgery is an effective treatment for CBT. Nonsurgical treatment should be considered for non-CBT.

Background: Retropharyngeal lymph node metastases (RPMs) from differentiated thyroid carcinoma (DTC) are rare. Treatment includes surgical resection, radioactive iodine (RAI) therapy, or external beam radiation therapy (EBRT). The objective of this study was to describe our experience in the management of DTC-associated RPMs. Methods: Patients diagnosed with a DTC-associated RPM from 1999 to 2018 were identified at our institution, using key search terms in imaging and histology reports. Patient and tumor characteristics were recorded, and patients were grouped according to RPM management: observation, nonsurgical treatment, or surgical resection. The estimated rates of local RPM control, disease-specific survival (DSS), and distant metastasis-free probability (DMFP) were calculated by using the Kaplan-Meier method. Results: Of the 65 patients identified, 53 (82%) had an RPM as a manifestation of recurrent disease. Twenty-five patients (38%) underwent observation, 13 (20%) received nonsurgical treatment (RAI, EBRT, and/or systemic therapy), and 27 (42%) underwent surgical resection. In the observation cohort, all patients had a stable RPM, which in the majority (80%) of cases remained

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 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.

Selinexor is an oral, small molecule inhibitor of the nuclear export protein exportin 1 with demonstrated activity in hematologic and solid malignancies. Side effects associated with selinexor include nausea, vomiting, fatigue, diarrhea, decreased appetite, weight loss, thrombocytopenia, neutropenia, and hyponatremia. We reviewed 437 patients with multiple myeloma treated with selinexor and assessed the kinetics of adverse events and impact of supportive care measures. Selinexor reduced both platelets and neutrophils over the first cycle of treatment and reached a nadir between 28 and 42 days. Platelet transfusions and thrombopoietin receptor agonists were effective at treating thrombocytopenia, and granulocyte colony stimulating factors were effective at resolving neutropenia. The onset of gastrointestinal side effects (nausea, vomiting, and diarrhea) was most common during the first 1–2 weeks of treatment. Nausea could be mitigated with 5-HT3 antagonists and either neurokinin 1 receptor antagonists, olanzapine, or cannbainoids. Loperamide and bismuth subsalicylate ameliorated diarrhea. The primary constitutional side effects of fatigue and decreased appetite could be managed with methylphenidate, megestrol, cannabinoids or olanzapine, respectively. Hyponatremia was highly responsive to sodium replacement. Selinexor has well-established adverse effects that mainly occur within the first 8 weeks of treatment, are reversible, and respond to supportive care.

Introduction: Despite unprecedented advances in the treatment of multiple myeloma (MM), almost all patients develop a disease that is resistant to the five most commonly used and active anti-MM agents. The prognosis for this patient population is particularly poor resulting in an unmet need for additional therapeutic options. Exportin-1 (XPO-1) is a major nuclear export protein of macromolecular cargo frequently overexpressed in MM. Selinexor is a first-in-class, oral Selective-Inhibitor-of-Nuclear-Export (SINE) compound that impedes XPO-1. Based on results of the STORM-trial, selinexor in combination with dexamethasone was granted accelerated FDA approval for patients with penta-refractory MM in July 2019.Areas covered: This article summarizes our up-to-date knowledge on the pathophysiologic role of XPO-1 in MM. Furthermore, it reviews the most recent clinical data on selinexor in combination with dexamethasone and other anti-MM agents; and discusses its safety profile, management strategies; and potential future developments.Expert opinion: Selinexor represents a next-generation-novel agent with an innovative mechanism of action that marks a significant advance in the treatment of heavily pretreated MM patients. Ongoing studies investigate its therapeutic potential also in earlier lines of therapy. Additional data is needed to confirm that selinexor and other SINE compounds are a valuable addition to our current therapeutic armamentarium.