Survival Outcomes of Advanced Thyroid Cancer Enriched in Brain Metastases Following Treatment With Small Molecule Inhibitors.

OBJECTIVE: Small molecule inhibitors (SMIs) are targeted therapies increasingly used in advanced thyroid carcinomas. This study aimed to evaluate the survival outcomes of thyroid cancer on SMI treatment, including in patients with brain metastases. METHODS: This retrospective study included patients with thyroid carcinomas who received at least one SMI between 2008 and 2022 at a tertiary level, academic institution. SMI included lenvatinib, sorafenib, dabrafenib-trametinib, selpercatinib, and cabozantinib. Patients were grouped by the presence of brain metastasis. Kaplan-Meier and log-rank tests modeled the overall survival (OS), defined from detection of first metastasis. RESULTS: In total, 116 patients (49.1% female, median age 61.1 years [IQR, 51.1-71.0]) were included. Thyroid cancer subtypes were: 57 (49.6%) papillary, 23 (19.8%) anaplastic, 23 (19.8%) medullary, and 13 (11.2%) follicular. There were 18 (15.5%) patients with brain metastases, and 98 (84.5%) with visceral metastases. Age, sex, thyroid subtype, SMI, and time to recurrence were not different between cohorts. OS was shorter in the brain metastasis cohort (31.7 vs 42.2 months, P =.44) and was not different after excluding anaplastic thyroid cancer (29.1 vs 62.3 months, P =.21). In the case of papillary thyroid cancer, patients with brain metastases trended toward worse OS (22.0 vs 59.9 months, P =.13). Nonanaplastic histology, total thyroidectomy (OR, 40.0; P <.001), number of unique therapies (OR, 10.9; P =.047), and mutation-directed therapy (OR, 24.7; P =.003) were associated with improved OS. CONCLUSION: This single-institutional analysis reports survival outcomes of 116 patients with advanced thyroid cancer on targeted therapies, including 18 patients with brain metastases. Mutation-directed therapy for BRAFV600E mutations, RET mutations, RET fusions, and NTRK fusions had superior survival.

Preoperative Evaluation of Thyroid Cancer: A Review of Current Best Practices.

OBJECTIVE: The incidence of thyroid cancer has significantly increased in recent decades. Although most thyroid cancers are small and carry an excellent prognosis, a subset of patients present with advanced thyroid cancer, which is associated with increased rates of morbidity and mortality. The management of thyroid cancer requires a thoughtful individualized approach to optimize oncologic outcomes and minimize morbidity associated with treatment. Because endocrinologists usually play a key role in the initial diagnosis and evaluation of thyroid cancers, a thorough understanding of the critical components of the preoperative evaluation facilitates the development of a timely and comprehensive management plan. The following review outlines considerations in the preoperative evaluation of patients with thyroid cancer. METHODS: A clinical review based on current literature was generated by a multidisciplinary author panel. RESULTS: A review of considerations in the preoperative evaluation of thyroid cancer is provided. The topic areas include initial clinical evaluation, imaging modalities, cytologic evaluation, and the evolving role of mutational testing. Special considerations in the management of advanced thyroid cancer are discussed. CONCLUSION: Thorough and thoughtful preoperative evaluation is critical for formulating an appropriate treatment strategy in the management of thyroid cancer.

The follicular variant of papillary thyroid cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

PURPOSE OF REVIEW: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a new terminology proposed for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Recently, thyroid cancer incidence has increased dramatically, without affecting related mortality rate. This increase is widely attributed to the intensified surveillance leading to a substantial increase in the diagnosis of small classic papillary thyroid cancers and EFVPTCs. Recent studies emphasize the indolent behavior of the EFVPTC. Recently, there has been a reclassification of EFVPTC as NIFTP, a benign entity. The financial and emotional burden of 'cancer' diagnosis and treatment can be significant. RECENT FINDINGS: This review recapitulates the literature supporting the reclassification of EFVPTC as NIFTP, a benign entity, and reviews standardized diagnostic criteria for EFVPTC. SUMMARY: The information highlighted in this review will affect surgical decision making and may promote the offering of hemithyroidectomy over a total thyroidectomy to some patients with 'indeterminate' cytopathological category; postoperative radioiodine ablation will not be required for NIFTP patients.

PROGNOSTIC VARIABLES AFFECTING PRIMARY TREATMENT OUTCOME FOR MEDULLARY THYROID CANCER.

OBJECTIVE: Identifying prognostic risk factors and determining the efficacy of common surgical treatments is critical to determine optimal treatment strategies for patients with medullary thyroid carcinoma (MTC). The objective of this study was to review a contemporary institutional experience with MTC primary treatment with 2 goals: to identify prognostic factors that impact survival and to study the effect of neck dissection on those outcomes. METHODS: This study was a retrospective case series of patients with MTC who underwent at least a total thyroidectomy with curative intent. Clinical parameters including tumor and nodal staging with corresponding pathology findings were identified. Survival endpoints included overall survival, disease-free survival, and biochemical cure. RESULTS: Sixty-seven patients were included. The majority presented with early T-stage disease. Fifty (76%) patients were N0 at presentation. Seventeen (24%) had some evidence of neck disease on clinical examination or imaging. Forty (71%) achieved biochemical cure, and the 5-year biochemical recurrence-free survival for those cases was 86.5%. Among patients who had successful resection of all gross disease, 92% had no evidence of structural disease at 5 years. Overall survival was 91% at 5 years. Increased pre-operative calcitonin (Ct) level, primary tumor size, extrathyroidal extension, and neck metastases decrease the rate of biochemical cure. Larger tumor size increases the risk of structural disease recurrence and biochemical relapse after initial cure. The presence and number of neck metastases correlate with biochemical relapse. The presence of lateral neck nodes (pN1b) does not have different survival implications than centrally confined disease (pN1a). CONCLUSION: This study shows increasing tumor size, increased Ct level, and cervical metastases are poor prognostic factors. Patients with large tumors, high Ct level, or unfavorable pathologic findings may warrant more aggressive initial treatment, although limitations of the study prevent any conclusion regarding the effect of neck dissection. ABBREVIATIONS: ATA = American Thyroid Association BRFS = biochemical recurrence-free survival CND = central neck dissection Ct = calcitonin DFS = disease-free survival MTC = medullary thyroid carcinoma OR = odds ratio OS = overall survival pCND = prophylactic CND.

The contemporary utility of intraoperative frozen sections in thyroid surgery.

PURPOSE: To determine the accuracy of intraoperative frozen section analysis on thyroidectomy specimens stratified by the Bethesda classification scheme and its utility for intraoperative decision-making. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective review was performed on all patients who underwent thyroidectomy or thyroid lobectomy with intraoperative frozen sections at a tertiary care academic center from 2009 to 2015. RESULTS: There were 74 total patients who underwent partial or total thyroidectomy with intraoperative frozen section analysis of a thyroid nodule whom had previously undergone a thyroid fine needle aspiration of the nodule. The sensitivity, specificity, positive predictive value, and negative predictive value for a thyroid frozen section with respect to its prediction for malignancy was 81%, 95%, 98%, and 66%, respectively, with a diagnostic accuracy of 85%. For 37 patients with an indeterminate cytologic diagnosis on fine needle aspiration (Bethesda categories III-V), the sensitivity, specificity, positive predictive value, and negative predictive value for a thyroid frozen section was 81%, 91%, 95%, and 67%, respectively, with a diagnostic accuracy of 84%. False positives and false negatives resulted in 1 completion thyroidectomy for benign pathology and 3 reoperations for malignancy not discovered on frozen section. CONCLUSION: While intraoperative frozen sections on thyroid specimens may be helpful if positive, the false negative rate remains high. There appears to be limited value in routine frozen sections to guide clinical management and decision-making in the era of the Bethesda system.

Inferior outcomes in immunosuppressed patients with high-risk cutaneous squamous cell carcinoma of the head and neck treated with surgery and radiation therapy.

BACKGROUND: Immunosuppressed patients have higher rates of cutaneous squamous cell carcinoma of the head and neck. OBJECTIVE: This study reviews the effect of immune status on disease characteristics and treatment outcomes. METHODS: Patients with cutaneous squamous cell carcinoma of the head and neck treated with surgery and postoperative radiotherapy between 2000 and 2011 were included. Immunosuppressed patients underwent prior organ transplantation or chemotherapy. Baseline variables were compared using χ(2) and unpaired t tests. Overall survival and disease-free survival were calculated using the Kaplan-Meier method. RESULTS: In this study of 59 patients, 38 (64%) were immunocompetent and 21 (36%) were immunosuppressed. Most patients had recurrent tumors (63%) and node-positive disease (61%), which were well balanced between the groups. Poorly differentiated tumors (62% vs 21%; P = .009), lymphovascular invasion (29% vs 11%; P = .08), and extracapsular extension (57% vs 41%; P = .09) were more frequent in the immunosuppressed group. Two-year disease-free survival (45% vs 62%) and 2-year overall survival (36% vs 67%) were inferior for immunosuppressed patients. LIMITATIONS: Limitations include single institution, retrospective study with small sample size, and potential referral bias. CONCLUSIONS: Immunosuppressed patients with cutaneous squamous cell carcinoma of the head and neck more frequently present with high-risk pathologic features and inferior outcomes. Early multidisciplinary assessment and alternate management strategies merit prospective investigation.

Ansa to recurrent laryngeal neurorrhaphy in the setting of laryngeal nerve sacrifice: a cadaveric study to evaluate a reconstructive option.

OBJECTIVE: In certain cases, the recurrent laryngeal nerve (RLN) has to be sacrificed. This often results in an inadequate length of residual RLN to be used in a reinnervation procedure. We investigated the length of the distal stump of the RLN from the inferior border of the inferior pharyngeal constrictor muscle (IPCM), where it is frequently compromised, to its entrance into the larynx. Our objective was to determine whether this residual nerve stock was sufficient for margin clearance and neurorrhaphy. STUDY DESIGN: Cadaveric study METHODS: Recurrent laryngeal nerves were identified in fresh frozen cadavers. The IPCM was divided, revealing the distal stump of the RLN, which was measured. RESULTS: Dissection was performed in 20 cadavers (40 nerves). The average length of the right RLN and the left RLN from the IPCM until it entered the larynx was 15mm and 14mm, respectively. All residual RLN remnants were of sufficient length for neurorrhaphy. CONCLUSION: Concomitant RLN reinnervation procedures in the setting of nerve sacrifice are not well described. A barrier to reinnervation in this setting may be insufficient residual nerve length for a neurorrhaphy. Often, when the RLN is sacrificed intraoperatively either iatrogenically or due to tumor invasion, it is close to the cricoarytenoid joint, at the inferior border of the IPCM. This study demonstrates that by splitting the IPCM, sufficient length can be obtained for neurorrhaphy.

Failed organ preservation strategy for adult laryngeal embryonal rhabdomyosarcoma.

PURPOSE: To present a case of embryonal rhabdomyosarcoma of the intrinsic laryngeal musculature and discuss the treatment of this rare tumor. METHODS AND MATERIALS: A 45year-old male presented with an eleven month history of hoarseness. A mass of the posterior glottis was noted on fiberoptic laryngoscopy. Computed tomography indicated a 1.5×2.5cm laryngeal mass without cartilage involvement. Direct laryngoscopy and biopsy were consistent with embryonal rhabdomyosarcoma involving the interarytenoid muscle. A multidisciplinary tumor board recommended multimodality therapy including total laryngectomy. His case was reviewed along with the available English language literature. RESULTS: The patient refused surgery, and he qualified for a pediatric rhabdomyosarcoma treatment protocol with induction chemotherapy followed by combined chemoradiation. There was no noted response and the patient was taken off protocol to increase the radiation dose without chemotherapy. Fifteen weeks following radiation, a repeat biopsy revealed viable tumor. The patient elected further experimental chemotherapy at an outside hospital. The patient currently is alive at 34months post-treatment with suspected persistent disease and continues to refuse surgery. CONCLUSIONS: Embryonal rhabdomyosarcoma involving the larynx is an extremely rare tumor usually seen in children. There have been few previous adult cases reported and treatment options are not well described. We present a case of chemoradiation failure in an adult with embryonal rhabdomyosarcoma refusing surgical intervention. Although pediatric tumors can be effectively treated with organ preservation strategies, adult tumors may have a poorer response. Based upon our experience and existing literature regarding adult embryonal rhabdomyosarcoma of the larynx, multimodality therapy including surgical resection should be the treatment of choice.

Microbiomic subprofiles and MDR1 promoter methylation in head and neck squamous cell carcinoma.

Clinical observations and epidemiologic studies suggest that the incidence of head and neck squamous cell carcinoma (HNSCC) correlates with dental hygiene, implying a role for bacteria-induced inflammation in its pathogenesis. Here we begin to explore the pilot hypothesis that specific microbial populations may contribute to HNSCC pathogenesis via epigenetic modifications in inflammatory- and HNSCC-associated genes. Microbiomic profiling by 16S rRNA sequencing of matched tumor and adjacent normal tissue specimens in 42 individuals with HNSCC demonstrate a significant association of specific bacterial subpopulations with HNSCC over normal tissue (P < 0.01). Furthermore, microbial populations can separate tumors by tobacco status (P < 0.008), but not by alcohol status (P = 0.41). If our subhypothesis regarding a mechanistic link from microorganism to carcinogenesis via inflammation and consequent aberrant DNA methylation is correct, then we should see hypermethylation of relevant genes associate with specific microbiomic profiles. Methylation analysis in four genes (MDR1, IL8, RARB, TGFBR2) previously linked to HNSCC or inflammation shows significantly increased methylation in tumor samples compared with normal oral mucosa. Of these, MDR1 promoter methylation associates with specific microbiomic profiles in tumor over normal mucosa. Additionally, we report that MDR1 methylation correlates with regional nodal metastases in the context of two specific bacterial subpopulations, Enterobacteriaceae and Tenericutes (P < 0.001 for each). These associations may lead to a different, and potentially more comprehensive, perspective on the pathogenesis of HNSCC, and support further exploration of mechanistic linkage and, if so, novel therapeutic strategies such as demethylating agents and probiotic adjuncts, particularly for patients with advanced or refractory disease.

Outcomes in Minor Salivary Gland Tumors-A 20+ Year Tertiary-Care Center Experience.

Objective: Minor salivary gland carcinomas are challenging to study due to their rarity and heterogeneity. We aim to further characterize clinical characteristics, treatment, and outcomes over 20 years within a single institution. Study Design: Retrospective chart review was conducted on 210 patients who received primary treatment for minor salivary gland malignancy from 2000 to 2022. Setting: Single tertiary-care center. Methods: Multivariable Cox proportional hazards method was used to examine the relationship between pre-determined clinically important variables and outcomes. Results: Five-year overall survival was 77.8% (72.0-84.1). Advanced clinical T stage portended over a 2 times higher risk of death and recurrence. High pathologic grade was associated with a near 3 times higher risk of death and recurrence. There was a predominance of occult nodal metastases in level II for oral cavity and oropharynx site tumors. Conclusion: Clinical T stage and grade were important for overall survival, local, regional, and distant recurrence-free survival. Occult nodal metastases occurred most often in level II.

Primary fit tracheoesophageal puncture in primary versus salvage laryngectomy: Short-term and long-term complications and functional outcomes.

BACKGROUND: Primary fit tracheoesophageal puncture (TEP) is widely preferred for individuals who have not undergone prior radiation. However, there is no consensus on the relative utility of primary-fit TEP in the setting of salvage laryngectomy. METHODS: A retrospective, single-center review was conducted of individuals undergoing laryngectomy with primary fit TEP between 2012 and 2018. Multivariable analysis was conducted to compare short-term and long-term complications, as well as speech and swallowing outcomes, of those who underwent primary versus salvage laryngectomy. RESULTS: In this study, 134 patients underwent total laryngectomy with primary fit TEP. Aside from a higher rate of peristomal dehiscence (13.1% vs. 1.4%) found in the salvage group, there was no difference in incidence of all other complications, including pharyngocutaneous fistula formation. The groups had comparable speech and swallow outcomes. CONCLUSION: Primary fit TEP is a safe and effective surgical choice for individuals undergoing salvage laryngectomy who desire a voice prosthesis.

Patterns of failure after salvage head and neck surgery.

BACKGROUND: Advancements in immunotherapy for recurrent head and neck cancer have necessitated a better understanding of salvage surgical outcomes. This study aimed to determine patterns of failure following salvage head and neck surgery. METHODS: A retrospective cohort study was conducted of 280 patients who underwent salvage surgery for recurrent mucosal squamous cell carcinoma from 1997 to 2018. Cumulative incidence was calculated using the nonparametric Aalen-Johansen estimator. Time to recurrence (TTR) and overall survival (OS) were estimated using the Kaplan-Meier method and multivariable Cox proportional hazard models were used to evaluate associated factors. RESULTS: The 2 and 5-year cumulative incidence rates of second recurrence were 48.3 % (95 % CI 42.4-54.3) and 54.9 % (95 % CI 48.9-60.8), respectively. At 5 years, second locoregional recurrence was twice as common as distant recurrence (41.5 % [95 % CI 35.6-47.4] vs. 21.7 % [95 % CI 16.8-26.6]). The median TTR was 21.1 months (95 % CI 4.4-34.8), which varied by site (38.2 larynx/hypopharynx, 13.9 oral cavity, 8.3 sinonasal, and 7.8 oropharynx, P=.0001). The median OS was 32.1 months (95 % CI 24.1-47.6) and was worse for patients who were Black (hazard ratio [HR] 2.15, 95 % CI 1.19-3.9), current smokers (HR 2.73, 95 % CI 1.53-4.88), former smokers (HR 2.00, 95 % CI 1.19-3.35), ≥ 60 years of age (HR 1.41, 95 % CI 1.01-1.97), or received multimodal primary therapy (HR 1.98, 95 % CI 1.26-3.13). CONCLUSION: Rates of recurrence and mortality after salvage surgery were poor but worse for patients who were Black, older, smoked, had initial multimodal therapy, or had sinonasal or oropharyngeal cancers.

Evaluating the impact of the degree of extranodal extension on outcomes in locally advanced oral cavity cancer.

BACKGROUND: Evaluate whether extranodal extension (ENE) extent impacts outcomes in patients with oral cavity squamous cell carcinoma (OCSCC). METHODS: From an institutional database, patients with OCSCC and pathologic ENE who received adjuvant treatment were included. Surgical slides were reviewed to confirm ENE extent. Multivariable Cox regression was used to relate patient/treatment characteristics with disease-free survival (DFS) and overall survival (OS). ENE was analyzed as both a dichotomous and continuous variable. RESULTS: A total of 113 patients were identified. Between major (>2 mm) versus minor ENE (≤2 mm), there was no significant difference in DFS (HR 1.18, 95%CI 0.72-1.92, p = 0.51) or OS (HR 1.17, 95%CI 0.70-1.96, p = 0.55). There was no significant association between ENE as a continuous variable and DFS (HR 0.97 per mm, 95%CI 0.87-1.4, p = 0.96) or OS (HR 0.96 per mm, 95%CI 0.83-1.11, p = 0.58). CONCLUSION: No significant relationship was seen between ENE extent and DFS or OS in individuals with OCSCC.

Primary Ewing's sarcoma of the ethmoid sinus with intracranial and orbital extension: case report and literature review.

The Ewing's sarcoma family of tumors is a group of cancers that commonly arises in young adults during their second decade of life. It frequently involves the trunk and long bones of the body with primary Ewing's sarcoma of the paranasal sinuses being exceedingly rare. We describe the case of a 39 year-old female with primary Ewing's Sarcoma originating from the ethmoid sinus with intracranial extension into the anterior cranial fossa and the orbit. The radiologic and histopathologic profiles are presented with a review of the literature. To our knowledge, this is the second reported case with the tumor involving the anterior cranial fossa, but the only case where immunochemical staining and molecular genetic analysis are available for definitive diagnosis.

Anaplastic thyroid cancer in young patients: a contemporary review.

PURPOSE: Little is known about prognostic factors and treatment outcomes in young patients with anaplastic thyroid cancer (ATC). The goal of this study is to define the clinical features of this subgroup. MATERIAL AND METHODS: Patients age 55 or younger with either ATC or well-differentiated thyroid cancer (WDTC) with anaplastic changes were identified using electronic medical record at the Cleveland Clinic. The same number of patients older than 55 was randomly selected to serve as control. Progression-free survival (PFS), overall survival time (OST) and cause-specific mortality (CSM) were measured against age, tumor histology, extent of disease, and treatment modalities. RESULTS: Twelve patients age 55 or younger were identified. The median age was 51 years. Four patients had WDTC with anaplastic components--mixed tumor group (MTG). Their median PFS, OST, and CSM at 24 months were 21.5 months, 51 months, and 25%, respectively. For the other 8 patients who had pure ATC, their median PFS, OST, and CSM were 3.5 months, 6 months, and 100%, respectively. Patients in the MTG had better survival compared to the pure ATC and control group in terms of PFS (p = 0.0047 and p = 0.0053), OST (p = 0.0028 and p = 0.0029) and the CSM at 24 months (p = 0.0339 and p = 0.0096). In the pure ATC group, patients with positive cervical lymph node and distant metastases had similar overall survival outcomes (6 vs. 8 months, p = 0.4995). CONCLUSION: Prognostic factors favoring survival in young patients with ATC include ATC arising within WDTC. Once full anaplastic transformation occurs, age was not a significant factor in survival.

Margin Assessment Methods in Oral Cavity Squamous Cell Carcinoma and Recurrence: Tumor Bed vs Resection Specimen Sampling.

Importance: Positive margins and margin clearance are risk factors for recurrence in oral cavity squamous cell carcinoma (OCSCC), and these features are used to guide decisions regarding adjuvant radiation treatment. However, the prognostic value of intraoperative tumor bed vs resection specimen sampling is not well defined. Objective: To determine the prognostic implications of intraoperative margin assessment methods (tumor bed vs resection specimen sampling) with recurrence among patients who undergo surgical resection for OCSCC. Design, Setting, and Participants: This was a retrospective study of patients who had undergone surgical resection of OCSCC between January 1, 2000, and December 31, 2021, at a tertiary-level academic institution. Patients were grouped by margin assessment method (tumor bed [defect] or resection specimen sampling). Of 223 patients with OCSCC, 109 patients had localized tumors (pT1-T2, cN0), 154 had advanced tumors, and 40 were included in both cohorts. Disease recurrence after surgery was estimated by the cumulative incidence method and compared between cohorts using hazard ratios (HRs). Data analyses were performed from January 5, 2023, to April 30, 2023. Main Outcome and Measures: Recurrence-free survival (RFS). Results: The study population comprised 223 patients (mean [SD] age, 62.7 [12.0] years; 88 (39.5%) female and 200 [90.0%] White individuals) of whom 158 (70.9%) had defect-driven and 65 (29.1%) had specimen-driven margin sampling. Among the 109 patients with localized cancer, intraoperative positive margins were found in 5 of 67 (7.5%) vs 8 of 42 (19.0%) for defect- vs specimen-driven sampling, respectively. Final positive margins were 3.0% for defect- (2 of 67) and 2.4% for specimen-driven (1 of 42) margin assessment. Among the 154 patients with advanced cancer, intraoperative positive margins were found in 29 of 114 (25.4%) vs 13 of 40 (32.5%) for defect- and specimen-driven margins, respectively. Final positive margins were higher in the defect-driven group (9 of 114 [7.9%] vs 1 of 40 [2.5%]). When stratified by margin assessment method, the 3-year rates of local recurrence (9.7% vs 5.1%; HR, 1.37; 95% CI, 0.51-3.66), regional recurrence (11.0% vs 10.4%; HR, 0.85; 95% CI, 0.37-1.94), and distant recurrence (6.4% vs 5.0%; HR, 1.10; 95% CI, 0.36-3.35) were not different for defect- vs specimen-driven sampling cohorts, respectively. The 3-year rate of any recurrence was 18.9% in the defect- and 15.2% in the specimen-driven cohort (HR, 0.93; 95% CI, 0.48-1.81). There were no differences in cumulative incidence of disease recurrence when comparing defect- vs specimen-driven cases. Conclusions and Relevance: The findings of this retrospective cohort study indicate that margin assessment methods using either defect- or specimen-driven sampling did not demonstrate a clear association with the risk of recurrence after OCSCC resection. Specimen-driven sampling may be associated with reduced surgical margin positivity rates, which often necessitate concurrent chemotherapy with adjuvant radiation therapy.

Risk Factors Associated With Recurrence and Death in Patients With Tall Cell Papillary Thyroid Cancer: A Single-Institution Cohort Study With Predictive Nomogram.

Importance: Tall cell morphology (TCM) is a rare and aggressive variant of papillary thyroid carcinoma (PTC) that has been associated with poor outcomes; however, the risk factors for worse survival are not well characterized. Objective: To identify prognostic factors associated with cancer recurrence and death in patients with PTC-TCM. Design, Setting, and Participants: All patients treated for PTC-TCM at a single tertiary-level academic health care institution from January 1, 1997, through July 31, 2018, were included. Tall cell variant (TCV) was defined as PTC with TCM of 30% or more; and tall cell features (TCF) was defined as PTC with TCM of less than 30%. Patients with other coexisting histologic findings and/or nonsurgical management were excluded. Clinicopathologic features associated with worse outcomes were identified using Kaplan-Meier and Cox proportional-hazards model. Data were analyzed from March 1, 2018, to August 15, 2018. Main Outcomes and Measures: Locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and overall survival (OS) after surgery. Results: A total of 365 patients (median [range] age, 51.8 [15.9-91.6] years; 242 [66.3%] female) with PTC-TCM (TCV, 32%; TCF, 68%) were evaluable. Total thyroidectomy was performed in 336 (92%) patients; 19 (5.2%) received radiotherapy; and 15 (4.1%) received radioactive iodine. Clinical features were pT3 or T4, 65%; node-positive, 53%; and positive surgical margins, 24%. LRRFS at 1-, 3-, 5-, and 10-year was 95%, 87%, 82%, and 73%, respectively. On multivariable analysis, male sex and age were not independent predictors of inferior 5-year LRRFS, whereas positive surgical margins (HR, 3.5; 95% CI, 2.0-6.3), positive lymph nodes (HR, 2.8; 95% CI, 1.4-5.8), and primary tumor size of 3 cm or more (HR, 3.3; 95% CI, 1.4-7.8) were strongly associated with worse LRRFS. Age 55 years or older (HR, 3.2; 95% CI, 1.5-7.0), male sex (HR 4.5; 95% CI, 2.1-10.0), positive surgical margins (HR, 2.7; 95% CI, 1.2-6.0), nodal positivity (HR, 3.1; 95% CI, 1.3-7.7), tumor diameter of 1.5 cm or more (HR, 20.6; 95% CI, 2.8-152.1), and TCV vs TCF (HR, 3.1; 95% CI, 1.5-6.7) were associated with worse DRFS. Male sex (HR, 3.1; 95% 1.4-6.8) and tumor diameter of 1.5 cm or more (HR, 2.8; 95% CI, 1.0-7.4) were associated with worse OS. A findings-based nomogram was constructed to predict 10-year LRRFS (C index, 0.8). Conclusions and Relevance: This retrospective cohort study found that in patients with PTC-TCM, positive surgical margins, node positive disease, and tumor size of 3 cm or more were risk factors for worse LRRFS. Intensified locoregional therapy, including adjuvant radiation, may be considered for treating these patients.

Immunotherapy response in patients with cutaneous squamous cell carcinoma of head and neck with cranial nerve involvement.

BACKGROUND: Metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC) can be treated with immunotherapy (IO). Cranial nerve involvement (CNI) is uncommon in cSCC and is a poor prognostic factor. Our aim is to describe how patients with CNI respond to IO monotherapy and/or as an adjunct to RT. METHODS: Under an IRB approved protocol, patients with histologically proven cSCC of the head and neck with CNI treated with IO were retrospectively reviewed. RESULTS: Twelve patients were included and received cemiplimab or pembrolizumab. Eight patients had CNI at diagnosis, and 4 at time of recurrence after non-IO therapy. Best responses were complete response (1), partial response (7), stable disease (1), progressive disease (2), and pending response (1). Nine patients are alive, 6 of which remain on IO. CONCLUSIONS: In this cohort, IO showed clinical response in 83% of patients, indicating IO can be an effective monotherapy, reserving RT for instances of local failure after IO.

Utilizing Dynamic Risk Stratification in Patients With Tall Cell Variant Papillary Thyroid Cancer.

OBJECTIVES: Tall cell variant (TCV) papillary thyroid cancer (PTC) is a subtype of PTC associated with aggressive tumor behavior, advanced stage, and higher rates of recurrence and mortality. The present study aimed to test an established dynamic risk stratification tool in the TCV population, with the goal of better predicting the postoperative course of these patients. STUDY DESIGN: Retrospective chart review. METHODS: A total of 94 patients with TCV who underwent total thyroidectomy with radioactive iodine ablation were retrospectively reviewed from 1998 through 2020. Biochemical, structural, and overall response to treatment was determined for each patient, based on postoperative thyroglobulin levels and imaging findings. Primary outcomes were locoregional and distant recurrence, presence of disease at final follow-up, need for additional intervention, and disease-specific mortality. RESULTS: Patients with TCV who were stratified as having an excellent overall response to treatment had lower rates of locoregional recurrence than indeterminate, biochemical incomplete, and structural incomplete responses (2.0%, 33.3%, 55.0%, and 85.7% at 5 years respectively, p < 0.001). The same was true for distant recurrence as well (2.0%, 9.0%, 35.1%, and 42.9%, p < 0.001). An excellent response was also associated with lower rates of presence of disease at final follow-up, need for additional intervention, and disease-specific mortality. CONCLUSIONS: Although TCV is an aggressive subtype associated with worse clinical outcomes than classical PTC, patients with an excellent overall response to treatment have significantly improved outcomes when compared to indeterminate, biochemical incomplete, and structural incomplete responses. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2430-2438, 2023.

Primary Total Laryngectomy versus Organ Preservation for Locally Advanced T3/T4a Laryngeal Cancer.

OBJECTIVE: Organ preservation (OP) treatment for advanced laryngeal cancer has increased compared to primary total laryngectomy. Our study compares oncologic and functional outcomes between these approaches. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary care institution. METHODS: Retrospective review of patients receiving primary total laryngectomy or OP for laryngeal cancer between 1/1/2000 and 12/31/2018. RESULTS: A total of 118 patients received primary total laryngectomy and 119 received OP. Overall survival was similar between total laryngectomy and OP. When stratified by T stage, disease-free survival was worse among T3 patients receiving OP versus total laryngectomy. In T3 patients, 28 OP patients experienced local recurrence (28.9%) compared to 3 total laryngectomy patients (7.1%; p < 0.01). In total, 20 OP patients with local recurrence received salvage surgery. These patients had similar overall survival to patients who underwent initial total laryngectomy (TL). About 14 OP patients with local recurrence did not receive salvage surgery. About 89 (75.4%) TL patients achieved normal diet as compared to 64 (53.8%) OP patients (p < 0.001). In TL patients, 106 (89.8%) received primary or secondary tracheoesophageal-prosthesis, 82 (77.4%) of whom achieved completely understandable speech. CONCLUSIONS: There was no difference in survival by treatment in T4 patients, possibly because of strict patient selection. However, disease-free survival was worse in T3 patients receiving OP, likely due to a high local recurrence rate. Approximately 40% of patients with local recurrence were not eligible for salvage laryngectomy. TL patients had comparable swallowing and speech outcomes with OP patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1122-1131, 2023.