Background/Objectives: Since 2021, indeterminate thyroid nodules have been routinely assessed using molecular testing through Quebec's provincial ThyroSeq v3 pilot project. The primary objective of our study was to compare the molecular and clinicopathological characteristics of Bethesda III and Bethesda IV thyroid nodules evaluated through the pilot project. The secondary objective was to assess the program's economic impact. Methods: This retrospective study included 934 patients (mean age 55.7 ± 14.3 years; 79.3% female; mean nodule size 2.2 ± 0.8 cm) from two McGill University teaching hospitals in Quebec, comprising 593 Bethesda III and 341 Bethesda IV nodules that underwent molecular testing between 2021 and 2025. Eligible nodules were TI-RADS 3 or 4, measured 1-4 cm, and Bethesda III nodules required two consecutive cytology results before testing. Clinicopathological characteristics, histopathological diagnoses, molecular findings, and mutational profiles were analyzed. A projected 10-year cost analysis was also performed. Results: Of the 934 nodules tested, 280 demonstrated a genetic alteration. The risk of malignancy among surgically resected ThyroSeq v3-positive Bethesda III and IV nodules was 68% and 78%, respectively. Compared with Bethesda III nodules, Bethesda IV nodules demonstrated significantly greater vascular invasion (p = 0.029) and prevalence of oncocytic carcinomas (p = 0.010). Molecular testing was associated with an estimated reduction of 1.49 million Canadian dollars in healthcare costs over 10 years. Conclusions: Although Bethesda IV nodules exhibited more oncocytic carcinomas and invasion, molecular mutation class distribution and the prevalence of aggressive pathological features were similar between Bethesda categories. Together with the demonstrated economic savings, these findings support continued implementation of publicly funded ThyroSeq v3 testing to improve management of indeterminate thyroid nodules while reducing unnecessary surgery.

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is increasingly prevalent and accounts for 22–70

Background/Objectives: Since 2021, indeterminate thyroid nodules have been routinely assessed using molecular testing through Quebec’s provincial ThyroSeq v3 pilot project. The primary objective of our study was to compare the molecular and clinicopathological characteristics of Bethesda III and Bethesda IV thyroid nodules evaluated through the pilot project. The secondary objective was to assess the program’s economic impact. Methods: This retrospective study included 934 patients from two McGill University teaching hospitals in Quebec, comprising 593 Bethesda III and 341 Bethesda IV nodules that underwent molecular testing between 2021 and 2025. Eligible nodules were TI-RADS 3 or 4, measured 1–4 cm, and Bethesda III nodules required two consecutive cytology results before testing. Clinicopathological characteristics, histopathological diagnoses, molecular findings, and mutational profiles were analyzed. A projected 10-year cost analysis was also performed. Results: Of the 934 nodules tested, 280 demonstrated a genetic alteration. The risk of malignancy among surgically resected ThyroSeq v3-positive Bethesda III and IV nodules was 68% and 78%, respectively. Bethesda IV nodules demonstrated significantly greater vascular invasion (p = 0.029) and prevalence of oncocytic carcinomas (p = 0.010). Molecular testing was associated with an estimated CAD 1.49 million reduction in healthcare costs over 10 years. Conclusions: Although Bethesda IV nodules exhibited more oncocytic carcinomas and invasion, molecular mutation class distribution and the prevalence of aggressive pathological features were similar between Bethesda categories. Together with the demonstrated economic savings, these findings support continued implementation of publicly funded ThyroSeq v3 testing to improve management of indeterminate thyroid nodules while reducing unnecessary surgery.

ImportanceChatGPT has emerged as a medical resource through advanced language processing. Patients with thyroid nodules classified under The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) may use it to complement discussions with physicians.ObjectiveWe aimed to determine whether ChatGPT's recommendations on managing thyroid nodules classified by TBSRTC align with those of experienced thyroid specialists.Setting/ParticipantsA multidisciplinary panel of 5 thyroid cancer specialists, including otolaryngologists and endocrinologists, from 3 university-affiliated teaching hospitals in Montreal, Canada, evaluated the responses.Intervention/ExposureChatGPT-3.5 was prompted with 4 questions for each of the 6 Bethesda categories regarding the meaning and management of thyroid nodules, generating 24 responses for evaluation.Main Outcome/MeasuresWe assessed ChatGPT's accuracy against the latest American Thyroid Association (ATA) guidelines using a 4-point Likert scale (<50%, 50-74%, 75-89%, >90%). Additionally, specialists rated their comfort or reluctance in recommending ChatGPT as a complementary tool for patient discussions.ResultsOf the 24 ChatGPT-generated responses, 19 (79.2%) demonstrated moderate to good consistency with the ATA guidelines. The mean consistency score was 3.38/4 and median was 3.5. Consensus (IQR ≤ 1) was achieved in 23 out of 24 responses (95.8%), reflecting strong inter-rater reliability. Consistency scores were highest in Bethesda I-III and declined progressively in higher-risk categories, with the lowest mean score observed in Bethesda VI. Similarly, an upward trend in clinician reluctance was observed from Bethesda I through VI, indicating greater caution in recommending ChatGPT responses for patients suspicious for or diagnosed with malignancy (Bethesda V-VI).Conclusion and RelevanceWhile ChatGPT's responses generally align with specialist recommendations, they are not fully reliable. ChatGPT lacks the ability to serve as an independent or accurate source of medical advice for thyroid nodule management. It remains a useful complement for patient discussions, especially in low-risk scenarios, but further improvements are necessary to make it a safe, reliable component of patient care in complex cases.

ImportanceRecently, the Québec public health care system established a pilot project to cover costs of molecular testing for select patients with cytologically-indeterminate thyroid nodules.ObjectiveThis study aimed to evaluate the clinical utility of the ThyroSeqv3 molecular test pilot project at McGill University in surgical management of thyroid nodules within Canada's single-payer health care system.DesignMulticenter cohort study, in liaison with the Québec Health Ministry.SettingJewish General Hospital and Royal Victoria Hospital in Montreal, Canada.ParticipantsPatients with a Bethesda III or IV and TIRADS 3 or 4 thyroid nodule measuring between 1 and 4 cm in size on ultrasound were analyzed across pre- and post-pilot project phases.InterventionThe pre-pilot project surgical control group included patients who underwent surgical intervention, excluding those who opted for out-of-pocket molecular testing. The post-pilot project surgical exposure group encompassed participants in the pilot project, undergoing publicly-funded ThyroSeqv3 molecular testing and subsequent surgical intervention.Main Outcome MeasuresSurgical malignancy/noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) rate.ResultsA total of 314 patients qualified for the pilot project, with 207 (65.9%) having Bethesda III nodules and 107 (34.1%) having Bethesda IV nodules. Molecular testing yielded a result of negative in 238 (75.8%) cases and positive in 76 (24.2%) cases. Histopathology reports of positive patients who opted for surgery revealed a surgical malignancy/NIFTP rate of 73.1%. The surgical malignancy/NIFTP rate at our institution prior to the implementation of the pilot project for patients adhering to the inclusion criteria was statistically significantly lower at 47.9% (P = .0025).ConclusionsThe ThyroSeqv3 molecular test pilot project has improved upon physicians' traditional clinical practice by enabling a wider patient population to access this otherwise costly technology. It not only curtailed futile diagnostic hemithyroidectomies but also led to a more discerning allocation of surgeries, as corroborated by an increased surgical malignancy/NIFTP rate post-implementation.RelevanceThe results of our study suggest that publicly-funded molecular testing could contribute positively to the Canadian single-payer health care system by optimizing patient outcomes as well as fiscal policy.

Treatment for HPV-negative head and neck squamous cell carcinoma (HNSCC) has seen little innovation, particularly in advanced-stage disease, where outcomes remain suboptimal. The public healthcare system's delays in access to care can exacerbate this issue, allowing tumors to progress prior to treatment initiation. This study explores the use of capecitabine, an oral chemotherapy agent, in both preoperative and recurrent settings for HPV-negative HNSCC. We conducted a prospective cohort study of patients with stage III/IV HPV-negative HNSCC at two academic centers in Montreal, Canada. The study evaluated clinical and pathological responses in patients receiving capecitabine in a preoperative setting, with radiological and clinical outcomes assessed for those with unresectable recurrent disease. Among the 34 patients included in the study (23 oral cavity, 1 oropharynx, 5 skin, 5 larynx), 31 received capecitabine preoperatively, while 3 had recurrent, unresectable disease. Of the 31 patients undergoing surgery, 16 exhibited clinical tumor reduction, 13 remained stable, and 2 experienced tumor growth. Pathological responses were observed in 15 patients, including 1 complete response (skin) and 6 major responses based on the modified Ryan criteria. Two non-responders developed recurrences within one year. The mean follow-up for surgical patients was 6 months. In the non-surgical cohort, all three patients showed reduced pain and radiological improvements, with a mean follow-up of 8 months. No significant toxicity related to capecitabine was reported. Capecitabine, used either in a preoperative window of opportunity or in the recurrent setting, demonstrated measurable clinical and pathological responses in patients with HPV-negative HNSCC. Given its efficacy and low toxicity, further investigation of this oral agent is warranted, particularly in resource-constrained settings where timely access to treatment may be a challenge. Marco Antonio Mascarella, Nisha Suarez, Keith Richardson, Alex Mlynarek, Michael Hier, Nader Sadeghi, Khalil Sultanem, Derin Caglar, Marc Pusztaszeri, Livia Florianova, Nathaniel Bouganim, Khashayar Esfahani. Old dog, new tricks: The role of capecitabine in HPV-negative head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4522.

ABSTRACTBackgroundAirway obstruction secondary to chyle leak is an exceptionally rare phenomenon. Here, we describe this complication in a patient with anaplastic thyroid carcinoma (ATC) undergoing consolidative surgery after BRAF‐targeted therapy.MethodsA 55‐year‐old man presented with a rapidly enlarging neck mass. Work‐up was consistent with metastatic unresectable BRAFV600E‐mutant ATC. After a remarkable response to neoadjuvant dabrafenib and trametinib, he underwent curative‐intent surgery with a right hemithyroidectomy and bilateral neck dissection. Within 48 h, he developed an expanding left neck mass with laryngeal obstruction due to a chyle leak.ResultsDespite surgical repair and maximal medical therapy, the leak persisted necessitating thoracoscopic ligation of the thoracic duct. Final pathology showed a completely excised residual tumor. The patient remains disease‐free on long‐term dabrafenib and trametinib.ConclusionsBRAF‐directed therapy has transformed the care of patients with mutated ATC. As more patients undergo consolidative surgery, increased vigilance is paramount in minimizing complications and their associated morbidity.

Patients with head and neck squamous cell cancer (HNSCC) are at a greater risk of developing pulmonary metastases and/or second primary lung cancer. However, it remains uncertain whether lung screening in these patients, when the initial staging studies are negative, confers any survival benefit. To evaluate long-term cancer survival outcomes in patients with HNSCC undergoing chest radiography vs low-dose computed tomography screening for pulmonary metastasis and/or second primary lung cancer. This randomized parallel trial was conducted at a large academic hospital in Canada enrolling treatment-naive patients with de novo HNSCC from September 2015 to December 2022. Eligible patients did not meet the criteria for lung screening established by the US National Comprehensive Cancer Network guidelines. Participants were randomized to chest radiography or low-dose computed tomography screening groups. Data were analyzed from March to August 2024. Comparison of chest radiography vs low-dose computed tomography screening methods. Primary outcomes were the lung cancer detection rate measured by comparing the sensitivity and specificity of low-dose computed tomography with chest radiography. Secondary outcomes were overall survival and disease-free survival. A total of 137 patients (mean [SD] age, 65.1 [14.1] years; 34 [24.8%] females and 103 [75.2%] males) were included and randomized, 68 (49.6%) to chest radiography and 69 (50.4%) to low-dose computed tomography. Nine of 137 patients (6.5%) developed a second primary lung cancer (6 patients) or lung metastases (3 patients). There were no clinically meaningful differences in survival outcomes between the 2 groups (hazard ratio, 1.2; 95% CI, 0.4-3.9). Chest radiography exhibited a relatively low sensitivity of 66.7% but a specificity of 100%. Low-dose computed tomography demonstrated both high sensitivity (100%) and specificity (100%), for an overall accuracy of 100%. The findings of this randomized parallel trial indicate that low-dose computed tomography exhibits statistically significant superior sensitivity compared with chest radiography for diagnosing lung metastases and second primary lung cancer. However, there were no important differences in survival rates. These results hold practical significance, offering valuable insights to clinicians who are guiding decisions regarding lung screening protocols. ISRCTN10954990.

Objectives:To characterize practice patterns and outcomes in the management of low- and intermediate-grade salivary gland carcinoma prior to the existence of treatment guidelines. Methods:Analysis of a registry of patients who underwent parotid and submandibular gland resections for low-and intermediate-grade carcinomas between 2010 and 2019. Results:Of all 786 patients included in the study, 726 (92%) had preoperative imaging and 653 (83%) had preoperative biopsy. Of the 729 patients with parotid gland cancer, the majority underwent superficial (n = 384, 53%) or total (n = 254, 35%) parotidectomy. In patients with facial nerve preservation, total parotidectomy was associated with a significant increase in transient facial weakness (72/177 (41%) vs. 82/311 (26%), RR 0.65, 95% CI 0.50-0.84, p < 0.05) and permanent facial nerve weakness (23/176 (13%) vs. 16/301 (5%), RR 0.41, 95% CI 0.22-0.75, p < 0.05) compared to superficial parotidectomy. Adjuvant radiation therapy (RT) was delivered to 285 (36%) patients. The proportion of patients receiving adjuvant RT declined significantly over the time period from 2015 to 2019 compared to 2010 to 2014 at 162/504 (32%) and 123/282 (44%), respectively (RR 0.74, 95% CI 0.61-0.89, p < 0.05). When comparing the time periods from 2015 to 2019 and 2010 to 2014, there was no significant difference in local control rates (RR 0.52, 95% CI 0.26-1.04, p = 0.06) or regional control rates (RR 0.75, 95% CI 0.26-2.13, p = 0.58). Conclusions:Management of low- and intermediate-grade salivary cancer from 2010 to 2019 was variable, which is expected given the rarity and heterogeneity of the disease and the lack of treatment guidelines prior to 2021. Most patients with parotid malignancies underwent superficial or total parotidectomy. The extent of parotidectomy had an impact on facial nerve function outcomes. Delivery of adjuvant radiation trended down with time. The data presented here will support dissemination of the guidelines and provide data that could inform future trials. Level of Evidence:2b.

Head and neck cancer (HNC) treatment is highly complex, with substantial toxicity risks from curative therapies, often including surgery, radiation, and chemotherapy. Poor treatment tolerance can hinder optimal recovery, impacting patient outcomes. Current predictive tools lack precision in forecasting treatment intolerance for HNC patients undergoing curative surgery. Frailty and sarcopenia, especially muscle quantity biomarkers, are increasingly recognized as crucial predictive factors. This study aims to develop a comprehensive risk index incorporating sarcopenia, frailty, and patient-specific factors to better predict intolerance. An ambispective observational study was conducted with 542 patients undergoing curative-intent HNC surgery from 2015 to 2024. Patient data on demographics, frailty, sarcopenia (via cervical paraspinal muscle index or CPSMI), tumor staging, and planned adjuvant therapy were collected. Using logistic regression, we evaluated predictive factors for treatment intolerance, defined as major adverse events (MAEs) or incomplete treatment. Risk model performance was validated internally and externally and compared against ASA, mFI, and RAI. In 542 patients, lower CPSMI (first tertile) correlated significantly with intolerance (OR 1.85, 95% CI 1.10-3.13). High-density muscle was protective, while low-density muscle predicted intolerance (OR 1.88, 95% CI 1.18-2.99). Sarcopenia and frailty were independently predictive, with the mFI also strongly correlating with intolerance (OR 4.92, 95% CI 1.88-12.9). The new risk index demonstrated superior predictive accuracy, showing a 0.04 increase in the C-statistic compared to existing indices (p=0.02). The multimodal risk index effectively predicts treatment intolerance in HNC surgery patients. By integrating sarcopenia, frailty, and patient-specific factors, the tool enables better preoperative counseling and intervention planning, with particular utility for high-risk individuals. Further research on prehabilitation strategies may enhance treatment tolerance in vulnerable patients, supporting a proactive approach to HNC care. Marco Antonio Mascarella, Keith Richardson, Nader Sadeghi, Alex Mlynarek, Michael Hier, Khalil Sultanem, Christina Tsien, Khashayar Esfahani, Marie-Jeanne Kergoat. Personalized risk prediction for treatment intolerance in operable HPV-negative head and neck cancer: Beyond the eyeball test [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4523.

ImportanceOral cavity squamous cell carcinoma (OCSCC) is rare in patients ≤40 years, and their risk factors, presentation, and outcomes may differ from older patients.ObjectiveTo assess the epidemiology, risk factors, and oncologic outcomes of young patients (≤40 years) with OCSCC compared to those >40 years.DesignA multi-institutional retrospective cohort study.SettingNine Canadian institutions from 2005 to 2019.ParticipantsIn total, 4506 adults with OCSCC, of whom 205 (4.55%) were young and 4301 were older than 40.Interventions or ExposuresThe primary outcomes were overall survival (OS) and disease-free survival (DFS), comparing young and older patients. The identification of risk factors for OCSCC development in young patients was a secondary outcome.Main Outcome MeasuresOS, DFS, and risk factor identification.ResultsOral tongue cancer was the most common subsite (48.9%), with a significantly higher proportion of cases in young patients (73.4% vs 47.7%, P < .01). Young patients were more likely to present at an earlier clinical stage (T1: 44% young vs 31% old, P < .01) and were less likely to smoke (57% young vs 31% old, P < .01) or consume alcohol (72% young vs 58% old, P < .01). Multivariable analysis showed that smoking status, previous head and neck cancer, and advanced stage were significantly associated with decreased OS and DFS (P < .05). No significant differences were found in local (P = .61), regional (P = .67), or distant (P = .50) disease failure between age groups.Conclusions and RelevanceYoung patients with OCSCC were less likely to smoke or drink and presented at earlier stages, but they did not experience improved OS or DFS compared to older patients. These findings emphasize the need for further research into biological differences in OCSCC between young and older patients.

BACKGROUND:Malnutrition is associated with worse outcomes in head and neck cancer (HNC). The geriatric nutritional risk index (GNRI) may predict postoperative morbidity and survival, but its role remains underexplored. METHODS:An ambispective study of patients undergoing HNC surgery at two academic centers (2015-2024) was performed. Preoperative GNRI was categorized into moderate-to-high risk (< 92), low risk (92-98), and no risk (> 98). Outcomes included 90-day mortality, treatment intolerance, overall survival, and disease-free survival. Analyses were performed using multivariable logistic and Cox regression adjusted for age, Charlson Comorbidity Index (CCI), tumor stage, primary tumor site, and percutaneous endoscopic gastrostomy (PEG) status. Patients with prior head and neck cancer or prior radiation were excluded. RESULTS:Among 312 treatment-naïve surgical patients, 13% were moderate-to-high GNRI risk and 8% low risk. Moderate-to-high GNRI risk had higher major adverse events (57% vs. 36% in no-risk), greater treatment intolerance (61% vs. 41%), and a trend toward higher 90-day mortality (11% vs. 4%). On multivariable models adjusted for tumor site and pathologic stage, moderate-to-high GNRI risk was associated with higher odds of 90-day mortality (OR 2.99, 95% CI 1.01-9.31; p = 0.048) and treatment intolerance (OR 2.35, 95% CI 1.21-4.56; p = 0.012). Cox regression showed shorter overall (HR 2.28, 95% CI 1.44-3.62; p < 0.001) and disease-free survival (HR 1.87, 95% CI 1.20-2.91; p = 0.005). CONCLUSIONS:The GNRI predicted treatment intolerance and poorer survival in patients with operable HNC.

ABSTRACT Background Neck hematoma following thyroid surgery is a potentially life‐threatening complication. Methods This retrospective case–control study reviewed neck hematoma reoperations following thyroid surgery (2009–2024), using 3:1 matching. Univariable analysis identified hematoma and delayed onset (≥ 6 h) risk factors, with odds ratios (ORs) and 95% confidence intervals (CIs). Results Among 5502 surgeries, the hematoma incidence was 0.55% ( n = 30). The mean age was 54 and the female‐to‐male ratio was 7:3. Key risk factors included pre‐induction blood pressure > 160 mmHg (OR = 3.04 [95% CI = 1.25–7.39], p = 0.014) and limited blood pressure change postmedication (OR = 6.25 [95% CI = 1.03–38.08], p = 0.047). The hematoma group had higher rates of smoking, hypertension, diabetes, Graves' disease, and prior thyroid surgery, and, in delayed hematoma cases, larger nodules, total thyroidectomy, and central neck dissection, though not statistically significant. Conclusion Patients with poorly controlled blood pressure may not be candidates for outpatient thyroidectomy.

BACKGROUND:Pretreatment neutrophil to lymphocyte ratio (NLR) is a negative prognostic marker for survival in head and neck cancer (HNC). Its association with treatment toxicity and intolerance in patients undergoing curative-intent surgery is unknown. METHODS:Ambispective study of patients with operable stage II-IV, HPV-negative HNC treated at two academic hospitals. Multiple logistic regression was performed to evaluate the association between pretreatment NLR and short-term treatment outcomes including treatment toxicity and intolerance. RESULTS:Among 456 patients, 194 experienced treatment-related toxicity, defined as grade ≥ 3 adverse events, and 200 exhibited treatment intolerance, defined as treatment discontinuation or delay due to poor tolerance. High pretreatment NLR was significantly associated with an increased risk of toxicity (OR 1.04; 95% CI: 1.00-1.09) and intolerance (OR 1.06; 95% CI: 1.01-1.12). Patients with an NLR < 2.5 had significantly lower odds of experiencing toxicity (OR 0.50; 95% CI: 0.26-0.96) and intolerance (OR 0.57; 95% CI: 0.33-0.99) after adjusting for multiple confounders. CONCLUSIONS:Low pretreatment NLR was associated with reduced treatment toxicity and lower rates of intolerance in patients undergoing curative-intent surgery for HNC.

Background/Objectives: Papillary thyroid microcarcinoma (MPTC), a subset of papillary thyroid carcinoma (PTC), is increasingly detected with advanced imaging. While most MPTCs are indolent, some exhibit aggressive behavior, complicating clinical management. The BRAF V600E mutation, common in PTC, is linked to aggressive features, and its allele frequency (AF) may serve as a biomarker for tumor aggressiveness. This study explored the association between BRAF V600E AF and aggressive histopathological features in MPTC. Methods: Data from 1 January 2016 to 23 December 2023 were retrieved from two McGill University teaching hospitals. Inclusion criteria comprised patients aged ≥ 18 years with thyroid nodules ≤ 1 cm, documented BRAF V600E mutation and AF results, and available surgical pathology reports. Tumor aggressiveness was defined as the presence of lymph node metastasis, aggressive histological subtype (tall cell, hobnail, columnar, solid/trabecular or diffuse sclerosing), extra thyroidal extension, or extensive lymphovascular extension. Associations were explored using t-tests. Results: Among 1564 records, 34 met the inclusion criteria and were included in analyses. The mean BRAF V600E AF was significantly higher in aggressive tumors (23.58) compared to non-aggressive tumors (13.73) (95% CI: −18.53 to −1.16, p = 0.03). Although not statistically significant, trends were observed for higher BRAF V600E AF in tumors with lymph node metastasis (mean AF: 25.4) compared to those without (mean AF: 16.67, p = 0.08). No significant difference was noted in BRAF V600E AF by histological subtype (mean AF for aggressive: 19.57; non-aggressive: 19.15, p = 0.94). Conclusions: Elevated BRAF V600E AF is associated with aggressive behavior in MPTC, highlighting its potential as a biomarker to inform treatment strategies. Larger studies are warranted to validate these findings and enhance clinical management of MPTC patients.

OBJECTIVE:To evaluate the diagnostic accuracy of 18F-FDG-PET/CT compared to conventional imaging modalities (CIM) to detect recurrence of primary salivary gland cancers (SGCs). DATA SOURCES:Review performed on December 26, 2024, using Embase, CINHAL, MEDLINE, and PubMed. REVIEW METHODS:Two blinded reviewers selected studies reporting diagnostic accuracy of PET/CT in identifying locoregional recurrence and/or metastasis in patients with SGCs. The analysis was performed adhering to PRISMA guidelines using R 4.3.3. Pooled analysis with 95% confidence intervals (CI) were analyzed. RESULTS:A total of 12 studies were retained from the systematic review, including 264 patients evaluated in the meta-analysis. For local recurrence, there was a pooled sensitivity of 0.86 (95% CI 0.73-0.93) and a pooled specificity of 0.95 (95% CI 0.92-0.97) for PET/CT, and a pooled sensitivity of 0.89 (95% CI 0.80-0.94) and a pooled specificity of 0.91 (95% CI 0.79-0.97) for CIM (p = 0.90). For regional metastasis, there was a pooled sensitivity of 0.90 (95% CI 0.73-0.97) and a pooled specificity of 0.96 (95% CI 0.92-0.98) for PET/CT, and a pooled sensitivity of 0.80 (95% CI 0.62-0.91) and a pooled specificity of 0.95 (0.90-0.98) for CIM (p = 0.26). For distant metastasis, there was a pooled sensitivity of 0.96 (95% CI 0.90-0.99) and a pooled specificity of 0.95 (95% CI 0.85-0.98) for PET/CT, and a pooled sensitivity of 0.80 (95% CI 0.71-0.86) and a pooled specificity of 0.97 (95% CI 0.87-0.99) for CIM (p = 0.018). CONCLUSIONS:18F-FDG-PET/CT imaging is accurate for the detection of SGC recurrence, particularly for the detection of regional and distant metastases. LEVEL OF EVIDENCE:NA Laryngoscope, 135:1884-1898, 2025.

Background: Thyroid cancer is the most common endocrine malignancy, and accurate diagnosis is crucial for effective management. Fine needle aspiration cytology, guided by the Bethesda System for Reporting Thyroid Cytopathology, categorizes thyroid nodules into six categories, with Bethesda III and IV representing indeterminate diagnoses that pose significant challenges for clinical decision-making. Understanding the molecular profiles of these categories may enhance diagnostic accuracy and guide treatment strategies. Methods: This study retrospectively analyzed data from 217 patients with Bethesda III and IV thyroid nodules who underwent ThyroSeq v3 molecular testing followed by thyroid surgery at McGill University teaching hospitals. The analysis focused on the presence of specific molecular mutations, copy number alterations (CNAs), and gene expression profiles (GEPs) within these nodules. The relationship between these molecular findings and the clinico-pathological features of the patients was also examined. Results: This study identified notable differences in the molecular landscape of Bethesda III and IV thyroid nodules. Bethesda IV nodules exhibited a higher prevalence of CNAs and distinct GEPs compared to Bethesda III nodules. Interestingly, the BRAFV600E mutation was found exclusively in Bethesda III nodules, which correlated with more aggressive malignant behavior. These findings underscore the potential of molecular profiling to differentiate between the clinical behaviors of these indeterminate nodule categories. Conclusions: Molecular profiling, including the assessment of CNAs, GEPs, and specific mutations like BRAFV600E, provides valuable insights into the nature of Bethesda III and IV thyroid nodules. The distinct molecular characteristics observed between these categories suggest that such profiling could be instrumental in improving diagnostic accuracy and tailoring treatment approaches, ultimately enhancing patient outcomes in thyroid cancer management.

Background While ultrasound-guided fine-needle aspiration cell block (FNACB) is a cost-effective, expeditious, and reliable procedure used routinely in the initial evaluation of head and neck masses, it has limited efficacy in diagnosing lymphoproliferative disorders such as non-Hodgkin lymphoma (NHL). Flow cytometry performed on an fine-needle aspiration (FNA) sample [ultrasound-guided fine-needle aspirate flow cytometry or flow cytometry performed on an FNA sample (FNAFC)], has been shown to be a valuable adjunct to FNACB in the diagnosis of lymphoproliferative disorders of the spleen, kidney, and thyroid. The objective of this study was to appraise FNAFC's utility as an ancillary tool to detect NHL arising in the head and neck region in adult patients.Methods This is a retrospective study involving 52 adult patients with head and neck lymphadenopathies and masses suspicious for lymphoproliferative disorders, who underwent ultrasound-guided FNACB and ultrasound-guided FNAFC between January 2017 and November 2022. Patient demographics, FNACB histopathological and immunophenotypic results, postoperative histopathology results (when available), and follow-up information until May 2023 were reviewed.Results Of the 52 FNACB samples, 23 samples (44.2%) yielded a diagnosis negative for carcinoma, 20 samples (38.5%) were nondiagnostic on account of scant cellularity, 8 samples (15.4%) were suspicious for malignancy, and a single sample (1.9%) was compatible with malignancy. Regarding FNAFC samples, 37 samples (71.2%) were diagnosed as showing no evidence for a lymphoproliferative disorder, 4 samples (7.7%) as nondiagnostic because of insufficient cell count, 4 samples (7.7%) as suspicious for a lymphoproliferative neoplasm, and 7 samples (13.5%) as compatible with a lymphoproliferative neoplasm, most frequently a B-cell lymphoma. 7 of the 11 patients (63.6%) with a suspicious/positive FNAFC result underwent excisional biopsy for additional work up. Postoperative histopathology reports corroborated FNAFC's findings in 6 patients (85.7%), while the remaining patient's (14.3%) suspicious FNAFC result was discordant with postoperative histopathology results. The other 4 patients (36.4%) did not require excisional biopsy as the hemato-oncologist deemed the information provided by the FNAFC as sufficient for the diagnosis and treatment of an NHL in the specific clinical contexts of those patients. All patients with nondiagnostic (due to insufficient cell count), inconclusive, or negative FNAFC (ie, nondiagnostic of a lymphoproliferative disorder) were followed up for a mean follow-up period of 11.9 months (range: 61.2 months; SD: 10.2 months), during which no new lymphadenopathies/masses nor progression was observed.Conclusions FNAFC is a useful and practical supplementary tool in the diagnosis of lymphoproliferative disorders in the head and neck region, principally B-cell lymphoma. While conventional FNACB offers a valuable insight into the initial work up of head and neck masses, FNAFC can routinely detect small abnormal cell populations. Furthermore, in specific clinical contexts, it can reliably diagnose NHL, thereby averting the need for an excisional biopsy in a subset of patients.

PURPOSE:The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking.METHODS:We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial.RESULTS:Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time (P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years (P = .015). Dry mouth scores were higher in RT patients over time (P = .041).CONCLUSION:On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355).