Background: The ThyroSeq v2 next-generation sequencing assay (ThyroSeq) estimates the probability of malignancy in indeterminate thyroid nodules (ITN). Its diagnostic accuracy in different practice settings and patient populations is not well understood. Methods: We analyzed 273 Bethesda III/IV ITN evaluated with ThyroSeq at 4 institutions: 2 comprehensive cancer centers (n=98 and 102), a multicenter healthcare system (n=60), and an academic medical center (n=13). The positive (PPV) and negative predictive values (NPV) of ThyroSeq, and distribution of final pathology were analyzed and compared to values predicted by Bayes Theorem. Results: Across 4 institutions, the PPV was 35% (22-43%), and NPV was 93% (88-100%). Predictive values correlated closely with Bayes Theorem estimates (r2=.84), although PPVs were lower than expected. RAS mutations were the most frequent molecular alteration. Among 84 RAS- mutated nodules, malignancy risk was variable (25%, range 10-37%), and distribution of benign diagnoses differed across institutions (adenoma/hyperplasia 12-85%, NIFTP 5-46%). Conclusions: In a multi-institutional analysis, ThyroSeq PPVs were variable and lower than expected. This is attributable to differences in the prevalence of malignancy, and variability in pathologist interpretations of non-invasive tumors. It is important that clinicians understand ThyroSeq performance in their practice setting when evaluating these results.

Purpose To investigate the presence of plasma circulating tumor DNA (ctDNA) in patients with uveal melanoma during and after primary tumor treatment. Methods Detectability and variant allele frequency of ctDNA were assessed using a 129-oncogene panel using next-generation deep sequencing and hybridization capture in 69 patients with uveal melanoma undergoing primary treatment with enucleation ( n = 8, during surgery) or plaque brachytherapy ( n = 61; postoperative day 0, 1, 2, or 3). Follow-up assessments were performed in 39 patients over a median of 21 months (range, 3.2–31.9 months) of follow-up. Correlations between genomic data and disease parameters were performed. Results Overall, ctDNA was detectable in 20 of 69 patients with uveal melanoma (28.9%) during the perioperative period. On the day of enucleation, ctDNA was detected in two of eight patients (25%). In patients undergoing brachytherapy, ctDNA was significantly more detectable on postoperative days 2 or 3 compared with postoperative day 0 or 1 (32.4% vs 0.0%; P = 0.0015). Patients with follow-up ctDNA that became detectable or had an increased variant allele frequency were significantly more likely to develop metastasis compared with patients with follow-up ctDNA that became undetectable or decreased variant allele frequency ( P = 0.04). In patients with detectable vs. undetectable ctDNA, there was no significant difference in tumor size, stage or location. Conclusions ctDNA is significantly more detectable at 48 to 72 hours after plaque brachytherapy compared with less than 48 hours. ctDNA can be detected during enucleation. Relative increases in ctDNA levels may herald the development of clinically apparent metastases.

Purpose: Circulating tumor DNA (ctDNA) is released by many tumors into the plasma. Its analysis has minimal procedural risk and, in many cancers, has the potential for clinical applications. In retinoblastoma, the clinical correlations of ctDNA in eyes treated without enucleation have not been studied. This purpose of this study was to determine how the ctDNA RB1 variant allele frequency (VAF) changes in patients with unilateral retinoblastoma after intra-arterial chemotherapy (IAC) treatment. Variant allele frequency is a proxy for tumor fraction.Design: Case series from a single tertiary cancer referral center.Participants: Five patients with retinoblastoma with at least 1 measurable ctDNA plasma specimen both at the time of active intraocular retinoblastoma before IAC and after at least 1 IAC cycle.Methods: Circulating tumor DNA RB1 was detected and VAF was measured before and after IAC treatment. Clinical correlations were made using clinical examination, fundus photography, ultrasound, and OCT.Main Outcome Measures: Comparison of ctDNA RB1 VAF before and after IAC treatment for retinoblastoma and concordance of ctDNA RB1 detectability with activity of intraocular disease.Results: Twenty-three ctDNA specimens were included from 5 patients. The 5 baseline RB1 VAFs ranged from 0.27% to 4.23%. In all patients, the subsequent posteintra-arterial RB1 VAF was lower than baseline (0.0%e0.17%). At 4 months (2 months after IAC completion), the ctDNA consistently was negative in the patients who demonstrated clinically inactive intraocular disease.Conclusions: In this small cohort, a decremental decrease in ctDNA RB1 VAF was found after IAC, suggesting that relative VAF changes could be a biomarker of treatment response. Ophthalmology

Objective To propose a distinct anatomical classification for the superior thyroid pole that may serve as a surgical landmark and could help reduce complications in thyroid surgery. Materials and Methods A comprehensive anatomical study based on existing literature and surgical observations. Results The proposed superior pole classification is based on two parameters that closely interact: one is the shape of the superior pole and the other is the structure of the vascular pedicle of the superior pole. We have come up with three distinct types of superior thyroid pole anatomical structure that may be predictive of the risk for both hemorrhage and nerve injury. Conclusions Superior pole classification may serve as a guiding tool during thyroid surgery in order to reduce complications such as bleeding and injury to the external branch of the superior laryngeal nerve.

Identifying biomarkers that predict survival outcomes and response to treatment is an unmet need in oncology. Few biomarkers predictive of response to immune checkpoint inhibitor (ICI) drugs have been described for patients with head and neck squamous cell cancer (HNSCC). Maximum standardized uptake value (SUVmax) on positron emission tomographycomputed tomography (PET-CT) has been previously reported as a potential clinical predictor for survival outcome among patients with HNSCC. 1 Our objective was to analyze the association between SUVmax on PET-CT and survival in patients with head and neck cancer receiving ICI therapies.Methods | After approval by the Memorial Sloan Kettering Cancer Center Institutional Review Board and patient written informed consent, we analyzed clinical and genomic data from patients treated with ICI for HNSCC between 2013 and 2018. Patients who received PET-CT imaging within 180 days prior to ICI start date were included, and SUVmax was categorized as above or below the median. Other clinical and genomic covariates with prior evidence of prognostic value were analyzed, including pretreatment peripheral blood neutrophilto-lymphocyte ratio (NLR) and tumor mutation burden (TMB), as assessed using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), a targeted genomic sequencing panel of 341-468 genes. 2 The outcomes analyzed were overall and progression-free survival, and response to treatment was assessed using RECIST version 1.1 criteria. Analyses were performed using Stata version 16.