Background: An international group of experts recommended reclassifying non-invasive follicular variant of papillary thyroid cancers (FVPTC) as ‘non-invasive follicular thyroid neoplasm with papillary-like nuclear features’ (NIFTP) in April 2016. The purpose of this study was to establish preoperative clinical, laboratory, ultrasonographic, and cytological variables, which can differentiate NIFTP from FVPTC. Methods: We conducted a retrospective chart review of consecutive patients from a single institution evaluated between January 2012 and December 2017. 203 adult patients underwent lobectomy or total thyroidectomy for a FVPTC during that period. Each patient's medical chart was reviewed and information on pre-operative variables was recorded. An expert pathologist reviewed all surgical specimens and reclassified a subset of FVPTC as NIFTP according to the specific criteria. Results: Overall, 44 patients were included in the NIFTP group and 159 in the non-NIFTP group. Mean age was 50.1 years in the NIFTP group and 50.7 in the non-NIFTP group. Most patients were female (86.4% (38/44) in the NIFTP group vs 79.8% (127/159) in the non-NIFTP group). More patients underwent lobectomy in the NIFTP group (50% (22/44) vs 16.4% (26/159) in the non-NIFTP group, p = < 0.0001). Less patients received radioactive iodine in the NIFTP group (31.8% (14/44) vs 52.2% (83/159) in the non-NIFTP group, p = 0.0177). Preoperative thyroglobulin levels were lower in NIFTP patients (Median 25.55 mcg/L +/− 67.8 vs 76.06 mcg/L +/− 119.8 in Non-NIFTP, p = 0.0104). NIFTP nodules were smaller (Mean size 22.97 mm +/− 12.3 vs 25.88 mm +/− 11.2 for non-NIFTP, p = 0.0448) and more often solid than non-NIFTP (93.2% (41/44) vs 74.8% (119/159) for non-NIFTP, p = 0.0067). 2017 ACR TIRADS nodule category of 1–4 on ultrasound had a negative predictive value and a sensitivity of 100% for NIFTP. ROC Curve Analysis demonstrated that a preoperative thyroglobulin level of 31.3 mcg/L had a sensitivity of 75% and a specificity of 62.5% to differentiate NIFTP from non-NIFTP cancers. Conclusion: Lower preoperative thyroglobulin levels, smaller nodule size, solid texture and 2017 ACR TIRADS Category of 1–4 are more strongly associated with NIFTP than FVPTC and can favour less invasive surgical options such as lobectomy.

Background: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. Methods: This is a multicenter phase II study randomizing one hundred and forty patients with T1–2 N0–2 HPV+ OPC in a 1:1 ratio between de-escalated primary radiotherapy (60 Gy) ± concomitant chemotherapy and TOS ± de-escalated adjuvant radiotherapy (50–60 Gy based on risk factors). Patients will be stratified based on smoking status (< 10 vs. ≥ 10 pack-years). The primary endpoint is OS of each arm compared to historical control; we hypothesize that a 2-year OS of 85% or greater will be achieved. Secondary endpoints include progression free survival, QOL and toxicity. Discussion: This study will provide an assessment of two de-escalation approaches to the treatment of HPV+ OPC on oncologic outcomes, QOL and toxicity. Results will inform the design of future definitive phase III trials. Trial Registration: Clinicaltrials.gov identifier: NCT03210103. Date of registration: July 6, 2017, Current version: 1.3 on March 15, 2019.

Background: Molecular testing of thyroid nodules is a diagnostic tool used to better understand the nature of thyroid nodules. The aim of this study is to better comprehend the relationship between specific mutations and aggressive behavior of the tumour as demonstrated on postoperative pathological analysis. Methods: A retrospective chart review of 103 cases was performed. Included were patients who had undergone molecular testing using a panel that tests for 9 mutations (ThyGenX®) and were found to have malignant tumours. The following gene alterations were found pre-operatively in the nodules: BRAF V600E ( n = 32), BRAF K601E ( n = 4), NRAS ( n = 11), HRAS ( n = 4), KRAS ( n = 3), RET/PTC1 rearrangement ( n = 1), TERT promoter ( n = 2), PAX8-PPARγ rearrangement ( n = 1), and 45 cases where no mutation was detected. Aggressive behavior was defined by extra-thyroidal extension (ETE), lymph node metastasis (LN+), and the following variants of papillary thyroid carcinoma: tall cell, solid, diffuse sclerosing, columnar cell and hobnail. Chi-squared testing was performed to compare groups. Results: The group with BRAF V600E, RET/PTC1 rearrangement, and TERT promoter mutations was associated with ETE 37.1%, and LN+ 45.7% of the time compared to 4.3 and 13.0% in the group with other mutations, and 4.4 and 4.4% in the group with no mutations ( p-value 0.02, p-value < 0.001, p-value 0.006). In addition, the BRAF V600E, RET/PTC1 rearrangement, and TERT mutations group demonstrated tall cell variants (17.1%), columnar cell variants (5.7%), and hobnail variants (3%). The other mutations group demonstrated columnar cell variants (4.3%), and the no mutations group demonstrated solid variants (2.2%). Conclusions: In this study, BRAF V600E, RET/PTC1 rearrangement, and TERT mutations were associated with aggressive behaving thyroid malignancies as defined above. Molecular testing may be a useful method to anticipate aggressive tumour types and therefore assist in planning the extent and timing of surgery.

Background: Medullary thyroid cancer (MTC) cells are capable of secreting various tumor markers including calcitonin and carcinoembyronic antigen (CEA). The purpose of this study is to determine whether abnormal CEA levels may be used as a tumor marker to predict the severity of disease in MTC. Methods: A retrospective analysis was completed for 33 patients with MTC who had preoperative serum CEA levels. Univariate and multivariate analyses were used to quantify the relationship between serum CEA levels and tumor stage and prognosis. Results: On multivariate analysis, elevated preoperative CEA levels were significantly associated with the size and stage of tumor, distant metastasis, decreased biochemical cure, and mortality. There was a significant association between tumor size greater than 37 mm and elevated CEA levels (> 271 ng/ml). There was also a positive correlation with increased cancer stage (> 377 ng/ml), distant metastasis (> 405 ng/ml), and contralateral compartment location of lymph node metastasis (> 162 ng/ml). When pre-operative CEA levels are > 500 ng/ml, patient mortality was 67%. Conclusion: In this study, both pre-operative calcitonin and CEA levels were significantly correlated with the extent of disease in MTC. While calcitonin has a linear relationship with disease progression, abnormal CEA levels were a better indicator of advanced disease. CEA levels > 271 ng/ml are significant for advanced tumor size and staging, metastasis to the central compartment, and decreased chance of biochemical cure. CEA levels greater than 500 ng/ml are associated with significant patient mortality.

Background: Tumor thickness has been shown in oral tongue squamous cell carcinoma (OTSCC) to be a predictor of cervical metastasis. The postoperative histological measurement is certainly the most accurate, but it would be of clinical interest to gain this information prior to treatment planning. This retrospective study aimed to compare the tumor thickness measurement between preoperative, CT scan, and surgical specimens. Methods: We retrospectively included 116 OTSCC patients between 2001 and 2013. Thickness was measured on computer tomography imaging and again surgical specimens. Results: The median age was 66 years. 62.8 % of patients were smokers with a mean of 31.4 pack-years. Positive nodal disease was reported in 41.2 %. Mean follow-up time was 33.1 months. The correlation between CT scan-based tumor thickness and surgical specimens based thickness was significant (Spearman rho = 0.755, P < 0.001). Conclusion: Tumor thickness assessed by CT scan may provide an accurate estimation of true thickness and can be used in treatment planning.

Background: The 2016 American Thyroid Association guidelines indicate that patients with Graves’ disease who undergo a thyroidectomy should be rendered euthyroid through the use of antithyroid drugs (ATD) prior to surgery to avoid complications such as a thyroid storm. At times, the use of ATDs can have limited efficacy and therefore some patients will inevitably remain biochemically hyperthyroid at the time of surgery. The aim of this study is to assess if hyperthyroid patients undergoing a thyroidectomy are at an increased risk of developing a thyroid storm in comparison to euthyroid patients. Furthermore, this study seeks to establish a correlation between thyroid storm identified by the levels of thyroid hormones (T3 and T4) and the level of thyroid stimulating hormone (TSH). Methods: A retrospective cohort study was conducted at two Canadian centers, one in Montreal and the other in Nova Scotia. Sixty-seven patients undergoing thyroidectomy for Graves’ disease from January 2006 to December 2016 were evaluated. Results: The study comprised 67 participants with a mean age of 46 years (range16–78 years). A total of 78% of patients were on methimazole, 34% on beta-blockers, 27% on potassium iodine solution, 10% on propylthiouracil and 7% on steroids. At the time of surgery 21% were in an overt hyperthyroid state and 33% were in a subclinical hyperthyroid state. The average TSH level of 0.03 mIUL/L (range 0.01–0.23 mIUL/L). Sixteen percent of patients had a TSH level less than 0.01 mIUL/L. The average free T4 level was 29.58 pmol/L (range 11.5–95.2 pmol/L). The average total T3 level was 11.52 nmol/L (range 4.5–29.1 nmol/L) and free T3 level was 6.35 pmol/L (range 6.1–6.6 pmol/L). No patient developed thyroid storm. Conclusions: In our study, biochemically hyperthyroid patients undergoing thyroidectomy did not develop thyroid storm. Additional studies with larger sample sizes are needed to better understand the risk of thyroid storm in hyperthyroid patients.