Outcomes of Conversion Surgery for Patients With Low-Risk Papillary Thyroid Carcinoma.

Importance: The outcomes of patients with low-risk thyroid cancer who undergo surgery following a period of active surveillance (AS) are not well-defined. Objective: To evaluate surgical, pathologic, and oncologic outcomes among patients undergoing conversion surgery (CS) following AS for low-risk papillary thyroid carcinoma. Design, Setting, and Participants: In this cohort study, patients who underwent CS for disease progression were compared with patients who underwent CS without disease progression and with a propensity score-matched cohort of patients who underwent initial surgery (IS). The median (IQR) postsurgical follow-up time was 40.3 (18.0-59.0) months. Patients were treated at a quaternary cancer referral center in the United States. Exposures: Surgery. Main Outcomes and Measures: Surgical complications, pathologic characteristics, overall survival (OS), and recurrence-free survival (RFS). Results: Of 550 patients who underwent AS, 55 (10.0%) had CS, of whom 39 (7.1%) had surgery due to suspected disease progression (median [IQR] age, 48 [39-56] years; 32 [82.1%] female). There were no clinically meaningful differences in rates of surgical sequalae between the progression CS group (12 of 39 [30.7%]) and the nonprogression CS group (7 of 16 [43.8%]) (Cramer V, 0.2; 95% CI, 0.01-0.5). The 5-year OS was 100% (95% CI, 100%-100%) in both the disease-progression CS cohort and the IS cohort. Although the cohort of patients undergoing CS after disease progression was by definition a subset with more aggressive tumor behavior, no clinically meaningful differences were observed in the rates of regional recurrence (2 of 39 [5.1%] vs 0 of 39 patients with IS), local recurrence (0 patients), distant metastasis (0 patients), or disease-specific mortality (0 patients) when compared with the matched IS group. Five-year RFS rates were similar: 100% in the IS group and 86% (95% CI, 70%-100%) in the CS group. Conclusions and Relevance: In this cohort study, CS for suspected disease progression was associated with surgical and oncologic outcomes similar to IS, supporting the feasibility and safety of AS for patients with low-risk papillary thyroid carcinoma.

Recurrent Laryngeal Nerve Intraoperative Neuromonitoring Indications in Non-Thyroid and Non-Parathyroid Surgery.

Introperative nerve monitoring (IONM) of the recurrent laryngeal nerve (RLN) is a well-established technique to aid in thyroid/parathyroid surgery. However, there is little evidence to support its use in non-thyroid or non-parathyroid surgery. The aim of this paper was to review the current evidence regarding the use of IONM in non-thyroid/non-parathyroid surgery in the head and neck and thorax. A literature search was performed from their inception up to January 2024, including the term "recurrent laryngeal nerve monitoring". IONM in non-thyroid/non-parathyroid surgery has mainly been previously described in oesophageal surgery and in tracheal resections. However, there is little published evidence on the role of IONM with other resections in the vicinity of the RLN. Current evidence is low-level for the use of RLN IONM in non-thyroid/non-parathyroid surgery. However, clinicians should consider its use in surgery for pathologies where the RLN is exposed and could be injured.

Current evidences in poorly differentiated thyroid carcinoma: a systematic review and subsection meta-analysis for clinical decision making.

BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) is a distinct entity with intermediate prognosis between indolent follicular thyroid cancers and anaplastic carcinoma. The management guidelines are not standardized for these cancers due its low prevalence and limited available literature. Therefore, we did this systematic review with emphasis on current evidence on diagnosis, imaging, molecular markers, and management of these carcinomas. MATERIALS AND METHODS: We searched four databases, PubMed, Medline, EMBASE, and Emcare to identify studies published till October 2023. All studies reporting diagnostic tests, imaging, molecular marker expression and management of PDTC were included in the review. The meta-analysis was conducted on expression of molecular markers in these cancers following recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Random-effects meta-analysis was used to calculate pooled estimated prevalence with 95% confidence intervals. Based on the inclusion criteria, 62 articles were selected to be incorporated for the review. Differences in pathological diagnostic criteria of PDTC was noted in literature which was addressed in WHO 2022 diagnostic terminologies with expansion of the definition. Surgical management is uniformly recommended for early stage PDTC. However, literature is divided and anecdotal for recommendations on radioactive iodine (RAI), extent of neck dissection and adjuvant treatment in PDTC. Evidence for Next Generation Sequencing (NGS), novel theragnostic approaches, immunotherapy targets are evolving. Based on the subset analysis for expression of molecular markers, we found the most common markers expressed were TERT (41%), BRAF (28%) and P 53 (25%). CONCLUSION: Poorly differentiated thyroid carcinomas have a high case fatality rate (up to 31%). Eighty-five % of the patients who succumb to the disease have distant metastasis. Even though under-represented in literature, evidence-based management of these aggressive tumors can help personalize the treatment for optimal outcomes.

Papillary thyroid carcinoma tall cell subtype (PTC-TC) and high-grade differentiated thyroid carcinoma tall cell phenotype (HGDTC-TC) have different clinical behaviour: a retrospective study of 1456 patients.

AIMS: Papillary thyroid carcinoma, tall cell subtype (PTC-TC) is a potentially aggressive histotype. The latest World Health Organisation (WHO) classification introduced a novel class of tumours; namely, high-grade differentiated thyroid carcinoma (HGDTC), characterised by elevated mitotic count and/or necrosis, which can exhibit a tall cell phenotype (HGDTC-TC). METHODS AND RESULTS: We analysed the clinical outcomes in a large retrospective cohort of 1456 consecutive thyroid carcinomas with a tall cell phenotype, including PTC-TC and HGDTC-TC. HGDTC-TC is uncommon, accounting for 5.3% (77 of 1379) of carcinomas with tall cell morphology. HGDTC-TC was associated with significantly older age, larger tumour size, angioinvasion, gross extrathyroidal extension, higher AJCC pT stage, positive resection margin and nodal metastasis (P < 0.05). Compared with PTC-TC, HGDTC was associated with a significantly decreased DSS, LRDFS and distant metastasis-free survival (DMFS; P < 0.001). The 10-year DSS was 72 and 99%, the 10-year LRDFS was 61 and 92% and the 10-year DMFS was 53 and 97%, respectively, for HGDTC-TC and PTC-TC. On multivariate analysis, the classification (HGDTC-TC versus PTC-TC) was an independent adverse prognostic factor for DSS, LRDF, and DMFS when adjusted for sex, age, angioinvasion, margin status, AJCC pT and pN stage. CONCLUSIONS: Compared with PTC-TC, HGDTC-TC is associated with adverse clinicopathological features, a higher frequency of TERT promoter mutations (59% in HGDTC-TC versus 34% in PTC-TC) and incurs a significantly worse prognosis. HGDTC-TC is an independent prognostic factor for carcinoma with tall cell morphology. This validates the concept of HGDTC and the importance of tumour necrosis and high mitotic count for accurate diagnosis and prognosis of differentiated thyroid carcinomas.

Active surveillance for micropapillary thyroid carcinoma: a clinical review.

With the rapid rise in the incidence of micropapillary carcinoma, there is increasing concern about its overdiagnosis and overtreatment. There is considerable interest in managing patients with micropapillary carcinoma with active surveillance or deferred intervention. Various institutions around the world are practicing active surveillance. The major question remains as to who the ideal candidates are and how best to monitor these patients. This clinical review will discuss the ideal, appropriate, and inappropriate patients for active surveillance. It will also discuss the follow-up strategy for these patients and some of the adverse clinical features that will be used to decide against active surveillance. There are uncertainties as to who should be offered active surveillance. Various studies have shown approximately 10% of the patients switching to surgery primarily related to fear factor rather than increase in the tumor size or lymph node metastasis. The results of immediate surgery do raise issues related to complications of thyroid surgery and quality of life. The most ideal candidate would be patients with a tumor below 1 cm, intrathyroidal. For the patient who is a minimalist, the follow up strategy includes, ultrasound every 6 months for the first 1 or 2 years, and then every year after that. If there is a substantial change in the tumor volume or nodal metastasis, surgery should be considered, which happens in less than 10 percent of patients according to many studies. Based on existing literature and clinical experience, it appears that active surveillance is an appropriate strategy for monitoring micropapillary carcinoma.

NCCN Guidelines® Insights: Merkel Cell Carcinoma, Version 1.2024.

The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC." This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term "nonsurgical" by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.

Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise. Exposure to radiation, from either sunlight or previous medical therapy, is a key player in BCC development. BCC is not as aggressive as other skin cancers because it is less likely to metastasize. However, surgery and radiation are prevalent treatment options, therefore disfigurement and limitation of function are significant considerations. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline an updated risk stratification and treatment options available for BCC.

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

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

Artificial Intelligence in Head and Neck Cancer: A Systematic Review of Systematic Reviews.

INTRODUCTION: Several studies have emphasized the potential of artificial intelligence (AI) and its subfields, such as machine learning (ML), as emerging and feasible approaches to optimize patient care in oncology. As a result, clinicians and decision-makers are faced with a plethora of reviews regarding the state of the art of applications of AI for head and neck cancer (HNC) management. This article provides an analysis of systematic reviews on the current status, and of the limitations of the application of AI/ML as adjunctive decision-making tools in HNC management. METHODS: Electronic databases (PubMed, Medline via Ovid, Scopus, and Web of Science) were searched from inception until November 30, 2022. The study selection, searching and screening processes, inclusion, and exclusion criteria followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A risk of bias assessment was conducted using a tailored and modified version of the Assessment of Systematic Review (AMSTAR-2) tool and quality assessment using the Risk of Bias in Systematic Reviews (ROBIS) guidelines. RESULTS: Of the 137 search hits retrieved, 17 fulfilled the inclusion criteria. This analysis of systematic reviews revealed that the application of AI/ML as a decision aid in HNC management can be thematized as follows: (1) detection of precancerous and cancerous lesions within histopathologic slides; (2) prediction of the histopathologic nature of a given lesion from various sources of medical imaging; (3) prognostication; (4) extraction of pathological findings from imaging; and (5) different applications in radiation oncology. In addition, the challenges in implementation of AI/ML models for clinical evaluations include the lack of standardized methodological guidelines for the collection of clinical images, development of these models, reporting of their performance, external validation procedures, and regulatory frameworks. CONCLUSION: At present, there is a paucity of evidence to suggest the adoption of these models in clinical practice due to the aforementioned limitations. Therefore, this manuscript highlights the need for development of standardized guidelines to facilitate the adoption and implementation of these models in the daily clinical practice. In addition, adequately powered, prospective, randomized controlled trials are urgently needed to further assess the potential of AI/ML models in real-world clinical settings for the management of HNC.

Is Multifocality a Predictor of Poor Outcome in Childhood and Adolescent Papillary Thyroid Carcinoma?

CONTEXT: Total thyroidectomy in pediatric papillary thyroid carcinoma (PTC) is recommended in national guidelines because of the high incidence of multifocal disease (MFD). OBJECTIVE: To determine the incidence of MFD in childhood and adolescent vs adult PTC and whether MFD is a predictor for poorer outcomes in childhood and adolescent PTC. METHODS: We conducted an institutional review board-approved review of patients with PTC undergoing surgery (1986-2021) at Memorial Sloan Kettering Cancer Center. Clinical and pathological characteristics in patients with unifocal disease (UFD) and MFD were compared using Pearson's χ2 test. Survival outcomes were analyzed using the Kaplan-Meier method and log-rank test. Multivariate analysis assessed the impact of MFD on outcome. RESULTS: MFD was less common in childhood and adolescent patients with PTC (45%; 127/283) than in adults (54%; 3023/5564; P = .002). Childhood and adolescent patients with UFD and MFD had similar tumor stage and PTC subtype at presentation, with no significant difference in histopathologic features. Median follow-up was 68 months. There was no significant difference in 5-year recurrence-free probability and overall survival was 100% in both groups. There was no significant difference in 5-year contralateral lobe PTC-free probability between patients with UFD and MFD treated with lobectomy. Multivariate analysis showed MFD was not a predictor for recurrence. CONCLUSION: MFD was less common in childhood and adolescent patients with PTC than adults and was not a predictor of poor outcome on multivariate analysis, with excellent long-term outcomes in all patients with PTC. MFD does not appear to warrant completion thyroidectomy in childhood and adolescent patients selected for lobectomy.

Locoregional strategies to decrease postoperative pain and neck discomfort after open thyroidectomy: A scoping review.

Adequate pain control enhances patients' quality of life and allows a quick return to normal activities. Current pain management practices may contribute to the crisis of opioid addiction. We summarize the evidence that evaluates locoregional interventions to decrease pain and neck discomfort after thyroidectomy. We designed a scoping review. The search strategy was made in the Pubmed/MEDLINE and EMBASE database. We included only systematic reviews and RCTs that compared two or more strategies. Forty-nine publications including 5045 patients fulfilled criteria. Sore throat frequency is higher for endotracheal intubation and topical administration of anesthetic before intubation decreases this. Pre-incisional infiltration of the surgical wound decreases postoperative pain. Bilateral superficial plexus nerve block decreases analgesic requirements during and after thyroidectomy. Wound massage and neck exercises decrease postoperative discomfort. Locoregional interventions significantly impact postoperative pain and may reduce opioid use and improve patient outcomes.

Proton Beam Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma.

Purpose: To discuss the role of proton beam therapy (PBT) in the treatment of patients with oropharyngeal squamous cell carcinoma (OPSCC). Materials and Methods: A review of the pertinent literature. Results: Proton beam therapy likely results in reduced acute and late toxicity as compared with intensity-modulated radiation therapy (IMRT). The extent of the reduced toxicity, which may be modest, depends on the endpoint and technical factors such as pencil beam versus passive scattered PBT and adaptive replanning. The disease control rates after PBT are likely similar to those after IMRT. Conclusion: Proton beam therapy is an attractive option to treat patients with OPSCC. Whether it becomes widely available depends on access.

IgG4-related sclerosing thyroiditis (Riedel-Struma): a review of clinicopathological features and management.

We present a thorough review of the literature on Riedel thyroiditis (RT) with emphasis on aetiology, diagnosis and management, using the PubMed, Sinomed, and China National Knowledge Infrastructure databases. Although the exact aetiology of RT remains obscure, the histopathological features are consistent with a localized form of IgG4-related systemic disease (IgG4-RSD). Nevertheless, IgG4-RSD as a systemic fibroinflammatory disorder per se rarely affects the thyroid in the context of multiorgan manifestations. The initial diagnosis of RT is based on clinical history and imaging, but confirmation by histopathological examination is mandatory. In contrast to the historical surgical approach, glucocorticosteroid therapy is currently considered first line therapy, in line with the RT currently being viewed as a manifestation of, or analogous to, IgG4-RSD. For disease relapse, immunomodulatory agents (azathioprine, methotrexate, rituximab) can be used.

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

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

Molecular Profiling of 50 734 Bethesda III-VI Thyroid Nodules by ThyroSeq v3: Implications for Personalized Management.

CONTEXT: Comprehensive genomic analysis of thyroid nodules for multiple classes of molecular alterations detected in a large series of fine needle aspiration (FNA) samples has not been reported. OBJECTIVE: To determine the prevalence of clinically relevant molecular alterations in Bethesda categories III-VI (BCIII-VI) thyroid nodules. METHODS: This retrospective analysis of FNA samples, tested by ThyroSeq v3 using Genomic Classifier and Cancer Risk Classifier at UPMC Molecular and Genomic Pathology laboratory, analyzed the prevalence of diagnostic, prognostic, and targetable genetic alterations in a total of 50 734 BCIII-VI nodules from 48 225 patients. RESULTS: Among 50 734 informative FNA samples, 65.3% were test-negative, 33.9% positive, 0.2% positive for medullary carcinoma, and 0.6% positive for parathyroid. The benign call rate in BCIII-IV nodules was 68%. Among test-positive samples, 73.3% had mutations, 11.3% gene fusions, and 10.8% isolated copy number alterations. Comparing BCIII-IV nodules with BCV-VI nodules revealed a shift from predominantly RAS-like alterations to BRAF V600E-like alterations and fusions involving receptor tyrosine kinases (RTK). Using ThyroSeq Cancer Risk Classifier, a high-risk profile, which typically included TERT or TP53 mutations, was found in 6% of samples, more frequently BCV-VI. RNA-Seq confirmed ThyroSeq detection of novel RTK fusions in 98.9% of cases. CONCLUSION: In this series, 68% of BCIII-IV nodules were classified as negative by ThyroSeq, potentially preventing diagnostic surgery in this subset of patients. Specific genetic alterations were detected in most BCV-VI nodules, with a higher prevalence of BRAF and TERT mutations and targetable gene fusions compared to BCIII-IV nodules, offering prognostic and therapeutic information for patient management.