Risk factors and outcomes of melanoma in children and adolescents: A retrospective multicenter study.

BACKGROUND: Pediatric melanoma presents with distinct clinical features compared to adult disease. OBJECTIVE: Characterize risk factors and negative outcomes in pediatric melanoma. METHODS: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers. RESULTS: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls. LIMITATIONS: Retrospective nature, cohort size, control selection, and potential referral bias. CONCLUSION: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma.

A Comprehensive Study on the Diagnosis and Management of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features.

Background: Since the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) was introduced in 2016, most retrospective studies have included cases diagnosed as encapsulated follicular variant of papillary thyroid carcinoma. We investigate a cohort diagnosed with NIFTP at resection. Methods: Retrospective institutional cohort of NIFTP from 2016 to 2022, including clinical, cytological, and molecular data for 319 cases (6.6% of thyroid surgeries, 183 cases as NIFTP-only). Results: The patient cohort had unifocal or multifocal thyroid nodules. Female:male ratio was 2.7:1, mean age was 52 years and median NIFTP size was 2.1 cm. NIFTP was associated with multiple nodules in 23% patients (n = 73) and 12% of NIFTP were multifocal (n = 39). Fine needle aspiration (FNA) of NIFTP (n = 255) were designated as nondiagnostic = 5%, benign = 13%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) = 49%, follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) = 17%, suspicious for malignancy = 12%, or malignant = 4%. Molecular alterations were identified in 93% (n = 114), RAS or RAS-like. Thyroid Imaging Reporting and Data System (TI-RADS) score 4 was recorded in 50% of NIFTP, followed by scores 3 and 5 (26% and 20%, respectively). We also investigated the factors associated with extent of surgery. In our NIFTP-only group (n = 183), 66% were identified after hemithyroidectomy (HT) and 34% after total thyroidectomy (TT). On univariate analysis, TT patients demonstrated higher Bethesda category by FNA, more often had aberrant preoperative thyroid function, and/or underwent an FNA of additional nodule(s). With multivariable regression, Bethesda V NIFTP, in the presence of other nodules being evaluated by FNA and aberrant preoperative thyroid function, independently predicts TT. Bethesda II NIFTP correlated significantly with HT. Fifty-two patients (28%) with NIFTP-only had at least one postoperative surveillance ultrasound. In the NIFTP-only cohort, no HT patients had completion thyroidectomy or received postoperative radioactive iodine. No recurrence or metastases were recorded with median follow-up of 35 months (6-76 months; n = 120). Conclusions: Given this large cohort of NIFTP, including a large subset of isolated NIFTP-only, some with >6 years of follow-up and no tumor recurrences, consensus practical guidelines are needed for adequate postoperative management. Given the American Thyroid Association (ATA) provides guidelines for management of low-risk malignancies, guidance regarding that for borderline/biologically uncertain tumors, including NIFTP, is a reasonable next step.

A comparative analysis of RAS variants in patients with disorders of somatic mosaicism.

PURPOSE: RAS genes (HRAS, KRAS, and NRAS) are commonly found to be mutated in cancers, and activating RAS variants are also found in disorders of somatic mosaicism (DoSM). A survey of the mutational spectrum of RAS variants in DoSM has not been performed. METHODS: A total of 938 individuals with suspected DoSM underwent high-sensitivity clinical next-generation sequencing-based testing. We investigated the mutational spectrum and genotype-phenotype associations of mosaic RAS variants. RESULTS: In this article, we present a series of individuals with DoSM with RAS variants. Classic hotspots, including Gly12, Gly13, and Gln61 constituted the majority of RAS variants observed in DoSM. Furthermore, we present 12 individuals with HRAS and KRAS in-frame duplication/insertion (dup/ins) variants in the switch II domain. Among the 18.3% individuals with RAS in-frame dup/ins variants, clinical findings were mainly associated with vascular malformations. Hotspots were associated with a broad phenotypic spectrum, including vascular tumors, vascular malformations, nevoid proliferations, segmental overgrowth, digital anomalies, and combinations of these. The median age at testing was higher and the variant allelic fraction was lower in individuals with in-frame dup/ins variants than those in individuals with mosaic RAS hotspots. CONCLUSION: Our work provides insight into the allelic and clinical heterogeneity of mosaic RAS variants in nonmalignant conditions.

Efficacy of a commercial dry sleeve cryotherapy system for cooling the equine metacarpus.

OBJECTIVE: To determine the ability of a commercial cryotherapy system (Game Ready Equine) to cool the metacarpal subcutaneous tissue and the superficial digital flexor tendon (SDFT) in horses. STUDY DESIGN: Experimental study. ANIMALS OR SAMPLE POPULATION: Six healthy adult horses. METHODS: Thermocouples were implanted into the metacarpal subcutaneous tissues and the SDFT of six horses. Two treatments (cryotherapy or cryotherapy with 5-50 mmHg intermittent compression) were randomly assigned to forelimbs and performed for 20 minutes. Temperatures were compared to the target range of 10-19°C and between groups. RESULTS: Only one limb in the cryotherapy/compression group reached the target range after cryotherapy. Temperatures did not differ between treatment groups at time 0. Lowest temperatures achieved in the subcutaneous tissue (p = .0043) and SDFT (p = .005) were 4.9 and 7.6°C lower when intermittent compression was applied. Similarly, applying compression induced a maximum change in temperature of approximately 7.0°C in the subcutaneous tissue (p = .014) and 10.2°C in the SDFT (p = .0001). CONCLUSION: The cryotherapy system did not cool equine subcutaneous tissue or SDFT to the target temperature range, except in one limb. Combining cryotherapy with intermittent compression did result in lower temperatures and a greater change in temperature of the subcutaneous tissue and SDFT. CLINICAL SIGNIFICANCE: When using this cryotherapy system, the addition of intermittent compression should be considered to achieve lower temperatures and potentially greater reduction in inflammation. Further studies are warranted to determine the effect of longer treatment times, higher compression settings, and the optimal temperature for benefits in normal and diseased equine tissues.

Tumor predisposition: what's the skin got to do with it?

PURPOSE OF REVIEW: Recognition of skin findings associated with tumor predisposition syndromes can prompt early evaluation and surveillance and improve management. Additionally, knowing when to test and when to defer performing genetic testing can streamline management. This article reviews tumor predisposition syndromes with recently characterized skin findings and disorders for which early recognition and counseling can impact the course of disease. RECENT FINDINGS: Café au lait macules (CALMs) are important in many tumor predisposition syndromes, and 'atypical' CALMs are associated with constitutional mismatch repair deficiency and Fanconi anemia. Melanoma predisposition syndromes caused by pathogenic variants in POT1 and BAP1 are more recently described, and both are associated with Spitzoid tumors. Somatic pathogenic variants can cause segmental nevoid basal cell carcinoma syndrome and a mosaic form of Peutz-Jeghers syndrome. Patients with PTEN hamartoma syndrome have increased risk for melanoma but this might not occur until adulthood. SUMMARY: The cutaneous manifestations of tumor predisposition syndromes can aid diagnosis. Early photoprotection is key to modifying a main risk factor for skin cancer in many of these syndromes. Implementing surveillance guidelines facilitates early detection of tumors.

Impact of radiotherapy on survival in resected or unresectable anaplastic thyroid carcinomas, a Rare Cancer Network study.

PURPOSE: Anaplastic thyroid carcinomas (ATC) are a heterogenous group of tumors of overall dismal prognosis. We designed models to identify relevant prognostic factors of survival of irradiated ATC patients including radiotherapy modalities (field size, dose). MATERIAL AND METHODS: Between 2000 and 2017, 166 ATC patients' treatments were divided into surgery and postoperative radiotherapy (poRT) or definitive radiotherapy (RT). Multiple imputation approach was used for missing data. Prognostic factors were identified using Lasso-penalized Cox modelling and predicted risk scores were built. RESULTS: Patients undergoing RT (n=70) had more adverse patient and disease characteristics than those undergoing poRT (n=96). Corresponding median survival rates were 5.4 and 12.1 months, respectively. PoRT patients undergoing poRT more likely received extended-field radiotherapy with prophylactic nodal irradiation, but rather received platinum- vs. adriamycin-based chemoradiotherapy. Radiotherapy was conventionally fractionated, delivered >60Gy in 51.9% and 61.7% and used extended fields in 88.5% and 71.2% of patients with poRT or RT. Radiotherapy interruption rates for toxicity were similar in the two groups. The best poRT-group model identified age>45yo, PS≥1, pathologic tumor stage≥pT4b,>N1 and R2 resection as poor prognostic factors. The best RT-group model (C-index of 0.72) identified PS≥3,>N1 and extended-field radiotherapy with prophylactic nodal irradiation (as opposed to tumour-bed irradiation only) as poor prognostic factors. CONCLUSION: In patients undergoing poRT, radiotherapy parameters had little influence over their survival irrespective of patient, disease characteristics, and quality of resection. In patients undergoing RT, extended-field radiotherapy improved survival in addition to PS and nodal stage.

Immunosuppressant-associated eruptions in pediatric inflammatory bowel disease: A case-control study.

Paradoxically, immunosuppressive therapy for inflammatory bowel disease (IBD) can induce psoriasiform or eczematous eruptions. This case-control study identified infliximab exposure, Crohn's disease, and history of inflammatory skin conditions as significant risk factors for these eruptions in children with IBD. Our results also showed possible trends in age and race.

Survival After Adrenalectomy for Metastatic Lung Cancer.

BACKGROUND: Adrenal metastasectomy is associated with increased survival in non-small cell lung cancer (NSCLC) with isolated adrenal metastases. Although clinical use of adrenal metastasectomy has expanded, indications remain poorly defined. The aim of this study was to evaluate the clinical benefit of adrenal metastasectomy for all lung cancer subtypes. PATIENTS AND METHODS: We performed a retrospective cohort study of patients who underwent adrenal metastasectomy for metastatic lung cancer at six institutions between 2001 and 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Cox proportional hazards regressions and Kaplan-Meier survival analysis were performed. RESULTS: For 122 patients, the mean age was 60.5 years and 49.2% were female. Median time to detection of the metastasis was 11 months, and 41.8% were ipsilateral to the primary lung cancer. Median DFS was 40 months (1 year: 64.8%; 5 year: 42.9%). Factors associated with longer DFS included primary tumor resection [hazard ratio (HR): 0.001; p = 0.005], longer time to adrenal metastasis (HR: 0.94; p = 0.005), and ipsilateral metastases (HR: 0.13; p = 0.004). Shorter DFS corresponded with older age (HR: 1.11; p = 0.01), R1 resection (HR: 8.94; p = 0.01), adjuvant radiation (HR: 9.45; p = 0.02), and open adrenal metastasectomy (HR: 10.0; p = 0.03). Median OS was 47 months (1 year: 80.2%; 5 year: 35.2%). Longer OS was associated with ipsilateral metastasis (HR: 0.55; p = 0.02) and adjuvant chemotherapy (HR: 0.35; p = 0.02). Shorter OS was associated with extra-adrenal metastases at adrenalectomy (HR: 3.52; p = 0.007), small cell histology (HR: 15.0; p = 0.04), and lung radiation (HR: 3.37; p = 0.002). DISCUSSION: Durable survival was observed in patients undergoing adrenal metastasectomy and should be considered for isolated adrenal metastases of NSCLC. Small cell histology and extra-adrenal metastases are relative contraindications to adrenal metastasectomy.

Smartphone-based Assessment of Preoperative Decision Conflict and Postoperative Physical Activity Among Patients Undergoing Cancer Surgery: A Prospective Cohort Study.

OBJECTIVE: To determine the prevalence of clinically significant decision conflict (CSDC) among patients undergoing cancer surgery and associations with postoperative physical activity, as measured through smartphone accelerometer data. BACKGROUND: Patients with cancer face challenging treatment decisions, which may lead to CSDC. CSDC negatively affects patient-provider relationships, psychosocial functioning, and health-related quality of life; however, physical manifestations of CSDC remain poorly characterized. METHODS: Adult smartphone-owners undergoing surgery for breast, skin-soft-tissue, head-and-neck, or abdominal cancer (July 2017-2019) were approached. Patients downloaded the Beiwe application that delivered the Decision Conflict Scale (DCS) preoperatively and collected smartphone accelerometer data continuously from enrollment through 6 months postop-eratively. Restricted-cubic-spline regression, adjusting for a priori potential confounders (age, type of surgery, support status, and postoperative complications) was used to determine trends in postoperative daily physical activity among patients with and without CSDC (DCS score >25/100). RESULTS: Among 99 patients who downloaded the application, 85 completed the DCS (86% participation rate). Twenty-three (27%) reported CSDC. These patients were younger (mean age 48.3 years [standard deviation 14.2]-vs-55.0 [13.3], P = 0.047) and more frequently lived alone (22%-vs-6%, P = 0.042). There were no differences in preoperative physical activity (115.4 minutes [95%CI 90.9, 139.9]-vs-110.8 [95%CI 95.7, 126.0], P = 0.753). Adjusted postoperative physical activity was lower among patients reporting CSDC at 30 days (difference 33.1 minutes [95%CI 5.93,60.2], P = 0.017), 60 days 35.5 [95%CI 8.50, 62.5], P = 0.010 and 90 days 31.8 [95%CI 5.44, 58.1], P = 0.018 postoperatively. CONCLUSIONS: CSDC was prevalent among patients who underwent cancer surgery and associated with lower postoperatively daily physical activity. These data highlight the importance of addressing modifiable decisional needs of patients through enhanced shared decision-making.

Impact of the COVID-19 pandemic on the practice of endocrine surgery.

BACKGROUND: This study investigates the impact of the COVID-19 pandemic on endocrine surgeons. METHODS: A survey on the professional, educational, and clinical impact was sent to active and corresponding members of the American Association of Endocrine Surgeons (AAES) in September 2020. Chi-square and paired t-test were used for analysis. RESULTS: 77 surgeons responded (14.8 %). All reported suspension of elective surgeries; 37.7 % were reassigned to other duties during this time. The median number of cases backlogged was 30 (IQR 15-50). Most surgeons reported decreased clinical volume (74.6 %). The use of virtual platforms for clinical and educational purposes increased from pre-COVID-19 levels (all p < 0.001). Use of in-office procedures (p < 0.001) and length of observation prior to discharge for thyroid surgery (p < 0.05) decreased. CONCLUSION: The COVID-19 pandemic led to suspension of operations and decreased practice volume for endocrine surgeons. Surgeons increased use of virtual platforms, decreased in-office procedures, and decreased duration of observation for thyroid surgery in response.

Four-dimensional computed tomography (4D-CT) for preoperative parathyroid localization: A good study but are we using it?

BACKGROUND: Four-dimensional computed tomography (4D-CT) scan to localize abnormal parathyroid glands is diagnostically superior to ultrasound (US) and sestamibi. The implementation of 4D-CT imaging is unknown. METHODS: The Collaborative Endocrine Surgery Quality Improvement Program (CESQIP) database from 2014 to 2018 was utilized. Patients with hyperparathyroidism undergoing an initial operation were included. The rate of US, sestamibi and 4D-CT performance was calculated for the entire study population, and for each institution. RESULTS: 7,959 patients were included. In 311(3.9%) patients, no preoperative imaging was recorded. Of patients with imaging, US was performed in 6,872(86.3%), sestamibi in 5,094(64.0%), and 4D-CT in 1,630(20.4%). The combination of US and sestamibi was most frequent (3,855, 48.4%). Institutional rates of 4D-CT performance varied from 0.1% to 88.7%. CONCLUSIONS: Of the imaging modalities, 4D-CT was utilized least frequently and with greatest variability. Given the high accuracy of 4D-CT, efforts to reduce this variation may improve overall preoperative localization in patients with hyperparathyroidism.

Antifibrinolytics Are Not Associated With Reduced Blood Loss in Minimally-Invasive Endoscopic-Assisted Craniectomy for Repair of Single-Suture Craniosynostosis.

ABSTRACT: Minimally-invasive endoscopic-assisted craniectomy (EAC) achieves similar functional and cosmetic outcomes, whereas reducing morbidity risk that is often associated with complex cranial vault reconstruction. Antifibrinolytics (AF) usage to limit blood loss and transfusion requirements during complex cranial vault reconstruction has been studied extensively; however, studies are limited for AF therapy in EAC. The aim of this single-center retrospective observational cohort pilot study was to evaluate whether the use of AF was associated with reduced blood loss in infants undergoing EAC. The authors hypothesized that there would be no difference in blood loss between patients who received AF and those that did not receive AF during EAC. Non-syndromic patients who underwent single-suture EAC were retrospectively evaluated. Primary outcome measure was intraoperative calculated blood loss (mL/kg). Secondary outcome measures included perioperative red blood cells transfusion volumes, number of blood donor exposures, and pediatric intensive care unit and total hospital length of stay. Study cohort demographic and outcome data were analyzed; Fisher exact test was used for categorical data, Student t test was used for continuous data. A P value of <0.05 was considered statistically significant. Forty-nine EAC patients were included in the study with 34 patients in the AF cohort and 15 patients in the non-AF cohort. There were no significant differences in demographics between the 2 groups. Additionally, there was no significant difference in intraoperative calculated blood loss or any secondary outcome measure. In our single-suture EAC study cohorts, AF administration was not associated with a decrease in blood loss when compared to those that did not receive AF therapy.

Care of Congenital Melanocytic Nevi in Newborns and Infants: Review and Management Recommendations.

A pediatric dermatology expert working group performed a narrative review to describe care related to congenital melanocytic nevi (CMN) in neonates and infants. There are no published guidelines for most aspects of care, including routine skin care and visit intervals. Few guidelines exist for surgical management; newer recommendations favor conservative practice. Emerging evidence contributes to recommendations for screening MRI to evaluate for neural melanosis and related central nervous system complications, however, more research is needed. Risk for melanoma is generally low, but those with large, giant, or multiple CMN have a higher risk. Multidisciplinary care, with a focus on family and patient preferences, is of paramount importance. Without standardized screening and management guidelines, questions abound regarding appropriate physical examination intervals, potential treatment including full or partial excision, timing and frequency of imaging, melanoma risk, and assessment for neural melanosis. This review highlights the current state of knowledge concerning care of patients with CMN, reveals gaps in the literature surrounding skin care, and provides management recommendations. We additionally discuss cutaneous complications of CMN, such as pruritus, hypertrichosis, and wound healing. Resources and references for families and providers can help patients navigate this sometimes challenging diagnosis. Finally, we contribute expert care recommendations to the current body of literature as a foundation for the development of future, more comprehensive care guidelines.

Expected Versus Experienced Health-Related Quality of Life Among Patients Recovering From Cancer Surgery: A Prospective Cohort Study.

Patient expectations of the impact of surgery on postoperative health-related quality of life (HRQL) may reflect the effectiveness of patient-provider communication. We sought to compare expected versus experienced HRQL among patients undergoing cancer surgery. METHODS: Adults undergoing cancer surgery were eligible for inclusion (2017-2019). Preoperatively, patients completed a smartphone-based survey assessing expectations for HRQL 1 week and 1, 3, and 6 months postoperatively based on the 8 short-form 36 (SF36) domains (physical functioning, physical role limitations, pain, general health, vitality, social functioning, emotional role limitations, and mental health). Experienced HRQL was then assessed through smartphone-based SF36 surveys 1, 3, and 6 months postoperatively. Correlations between 1- and 6-month trends in expected versus experienced HRQL were determined. RESULTS: Among 101 consenting patients, 74 completed preoperative expectations and SF36 surveys (73%). The mean age was 54 years (SD 14), 49 (66%) were female, and the most common operations were for breast (34%) and abdominal (31%) tumors. Patients expected HRQL to worsen 1 week after surgery and improve toward minimal disability over 6 months. There was poor correlation (≤±0.4) between 1- and 6-month trends in expected versus experienced HRQL in all SF36 domains except for moderate correlation in physical functioning (0.50, 95% confidence interval [0.22-0.78], P < 0.001) and physical role limitations (0.41, 95% confidence interval [0.05-0.77], P = 0.024). Patients expected better HRQL than they experienced. CONCLUSIONS: Preoperative expectations of postoperative HRQL correlated poorly with lived experiences except in physical health domains. Surgeons should evaluate factors which inform expectations around physical and psychosocial health and use these data to enhance shared decision-making.

American Association of Clinical Endocrinology And Associazione Medici Endocrinologi Thyroid Nodule Algorithmic Tool.

OBJECTIVE: The first edition of the American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi Guidelines for the Diagnosis and Management of Thyroid Nodules was published in 2006 and updated in 2010 and 2016. The American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi multidisciplinary thyroid nodules task force was charged with developing a novel interactive electronic algorithmic tool to evaluate thyroid nodules. METHODS: The Thyroid Nodule App (termed TNAPP) was based on the updated 2016 clinical practice guideline recommendations while incorporating recent scientific evidence and avoiding unnecessary diagnostic procedures and surgical overtreatment. This manuscript describes the algorithmic tool development, its data requirements, and its basis for decision making. It provides links to the web-based algorithmic tool and a tutorial. RESULTS: TNAPP and TI-RADS were cross-checked on 95 thyroid nodules with histology-proven diagnoses. CONCLUSION: TNAPP is a novel interactive web-based tool that uses clinical, imaging, cytologic, and molecular marker data to guide clinical decision making to evaluate and manage thyroid nodules. It may be used as a heuristic tool for evaluating and managing patients with thyroid nodules. It can be adapted to create registries for solo practices, large multispecialty delivery systems, regional and national databases, and research consortiums. Prospective studies are underway to validate TNAPP to determine how it compares with other ultrasound-based classification systems and whether it can improve the care of patients with clinically significant thyroid nodules while reducing the substantial burden incurred by those who do not benefit from further evaluation and treatment.

Somatic PIK3R1 variation as a cause of vascular malformations and overgrowth.

PURPOSE: Somatic activating variants in the PI3K-AKT pathway cause vascular malformations with and without overgrowth. We previously reported an individual with capillary and lymphatic malformation harboring a pathogenic somatic variant in PIK3R1, which encodes three PI3K complex regulatory subunits. Here, we investigate PIK3R1 in a large cohort with vascular anomalies and identify an additional 16 individuals with somatic mosaic variants in PIK3R1. METHODS: Affected tissue from individuals with vascular lesions and overgrowth recruited from a multisite collaborative network was studied. Next-generation sequencing targeting coding regions of cell-signaling and cancer-associated genes was performed followed by assessment of variant pathogenicity. RESULTS: The phenotypic and variant spectrum associated with somatic variation in PIK3R1 is reported herein. Variants occurred in the inter-SH2 or N-terminal SH2 domains of all three PIK3R1 protein products. Phenotypic features overlapped those of the PIK3CA-related overgrowth spectrum (PROS). These overlapping features included mixed vascular malformations, sandal toe gap deformity with macrodactyly, lymphatic malformations, venous ectasias, and overgrowth of soft tissue or bone. CONCLUSION: Somatic PIK3R1 variants sharing attributes with cancer-associated variants cause complex vascular malformations and overgrowth. The PIK3R1-associated phenotypic spectrum overlaps with PROS. These data extend understanding of the diverse phenotypic spectrum attributable to genetic variation in the PI3K-AKT pathway.

Patient Perspectives on the Extent of Surgery and Radioactive Iodine Treatment for Low-Risk Differentiated Thyroid Cancer.

OBJECTIVE: To understand patient perspective regarding recommended changes in the 2015 American Thyroid Association (ATA) guidelines. Specifically, in regard to active surveillance (AS) of some small differentiated thyroid cancer (DTC), performance of less extensive surgery for low-risk DTC, and more selective administration of radioactive iodine (RAI). METHODS: An online survey was disseminated to thyroid cancer patient advocacy organizations and members of the ATA to distribute to the patients. Data were collected on demographic and treatment information, and patient experience with DTC. Patients were asked "what if" scenarios on core topics, including AS, extent of surgery, and indications for RAI. RESULTS: Survey responses were analyzed from 1546 patients with DTC: 1478 (96%) had a total thyroidectomy, and 1167 (76%) underwent RAI. If there was no change in the overall cancer outcome, 606 (39%) of respondents would have considered lobectomy over total thyroidectomy, 536 (35%) would have opted for AS, and 638 (41%) would have chosen to forego RAI. Moreover, (774/1217) 64% of respondents wanted more time with their clinicians when making decisions about the extent of surgery. A total of 621/1167 of patients experienced significant side effects with RAI, and 351/1167 of patients felt that the risks of treatment were not well explained. 1237/1546 (80%) of patients felt that AS would not be overly burdensome, and quality of life was the main reason cited for choosing AS. CONCLUSION: Patient perspective regarding choice in the management of low-risk DTC varies widely, and a large proportion of DTC patients would change aspects of their care if oncologic outcomes were equivalent.

Progress in Treating Advanced Thyroid Cancers in the Era of Targeted Therapy.

Background: Thyroid cancer is a common malignancy whose detection has increased significantly in past decades. Most of the increased incidence is due to detection of early well-differentiated thyroid cancer, but the incidence of more advanced thyroid cancers has increased as well. Recent methodological advancements have allowed for a deep understanding of the molecular underpinnings of the various types of thyroid cancer. Summary: Thyroid cancers harbor a high frequency of potential druggable molecular alterations, including the highest frequency of oncogenic driver kinase fusions seen across all solid tumors. Analyses of poorly differentiated and anaplastic thyroid carcinoma confirmed that these tumors develop from more well-differentiated follicular-derived thyroid cancers through acquired additional mutations. The recognition of driver genomic alterations in thyroid cancers not only predicts tumor phenotype but also now can inform treatment approaches. Conclusions: Major progress in understanding the oncogenic molecular underpinnings across the array of thyroid cancers has led to considerable gains in gene-specific systemic therapies for many cancers. This article focuses on the molecular characteristics of aggressive follicular-derived thyroid cancers and medullary thyroid cancer and highlights advancements in treating thyroid cancer in the era of targeted therapy.

Time to Surgery and Thyroid Cancer Survival in the United States.

BACKGROUND: Longer time to surgery worsens survival in multiple malignancies, including lung, colorectal, and breast cancers, but limited data exist for well-differentiated thyroid cancer. We sought to investigate the impact of time to surgery on overall survival in patients with papillary thyroid cancer. METHODS: In a retrospective cohort study of the National Cancer Database, we used Cox proportional hazard models to investigate overall survival as a function of time between diagnosis and surgery for adults with papillary thyroid cancer, adjusting for demographic, patient, and cancer-related variables. Time to surgery was investigated both as a continuous variable and as intervals of 0-90 days, 90-180 days, and > 180 days. Subgroup analyses were conducted by T stage. RESULTS: Overall, 103,812 adults with papillary thyroid cancer were included from 2004 to 2016. Median follow-up was 55.2 months (interquartile range 28.4-89.5). Increasing time to surgery was associated with increased mortality: delaying by 91-180 days increased the risk by 30% (adjusted hazard ratio [aHR] 1.30, 95% CI 1.19-1.43) and delaying by over 180 days increased the risk by 94% (aHR 1.94, 95% CI 1.68-2.24). Five-year overall survival was 95.7% for 0-90 days, 93.0% for 91-180 days, and 87.9% for over 180 days. On subgroup analysis, increasing delay was associated with worse overall survival for T1, T2, and T3 tumors, but not T4 tumors. CONCLUSIONS: Increasing time to surgery in papillary thyroid cancer is associated with reduced overall survival. Further research is necessary to assess the impact of surgical delay on disease-specific survival.