Faculty Bibliography

BACKGROUND:Guidelines recommend treatment package time < 85 days and time from surgery to radiation initiation < 6 weeks in head and neck cancer patients. However, HPV positive primaries treated with TORS and adjuvant radiotherapy traditionally demonstrate favorable outcomes. METHODS:Single center retrospective chart review of patients diagnosed with HPV positive treatment naïve primary squamous cell carcinoma treated with TORS and postoperative radiation therapy with or without Chemotherapy from 2012 to 2022 with data collection from December 2022-April 2023. Kaplan-Meier survival analysis with log-rank testing assessed the impact of time intervalsbetween diagnosis, TORS, radiation initiation and radiation completion on recurrence free and disease specific survival. Univariate Cox proportional hazards regression analysis was performed to identify factors associated with recurrence free and disease specific survival. Subgroup analysis was done with high risk (positive lymph nodes > 5, >1mm extracapsular extension, positive margins) patients who underwent concurrent Chemotherapy. RESULTS:Of 255 patients (225 males [89 %], average age 58 years, 163 [64 %] high-risk, median follow-up 4.3 years), 22 (8.6 %) had recurrence and 14 died due after disease recurrence.Only radiation length of 5-7 weeks prolonged survival in the entire population. In the high-risk cohort, time from TORS to radiation initiation < 6 weeks improvedrecurrence free survival, while total package time < 14 weeks wasassociated with greater recurrence free and disease specific survival.

Head and neck squamous cell carcinoma (HNSCC) constitutes one of the most common types of human cancers and often metastasizes to lymph nodes. Platinum-based chemotherapeutic drugs are commonly used for treatment of a wide range of cancers, including HNSCC. Its mode of action relies on its ability to impede DNA repair mechanisms, inducing apoptosis in cancer cells. However, due to acquired resistance and toxic side-effects, researchers have been focusing on developing novel combinational therapeutic strategies to overcome cisplatin resistance. In the current study, we identified p90RSK, an ERK1/2 downstream target, as a key mediator and a targetable signaling node against cisplatin resistance. Our results strongly support the role of p90RSK in cisplatin resistance and identify the combination of p90RSK inhibitor, BI-D1870, with cisplatin as a novel therapeutic strategy to overcome cisplatin resistance. In addition, we have identified TMEM16A expression as a potential upstream regulator of p90RSK through the ERK pathway and a biomarker of response to p90RSK targeted therapy in the context of cisplatin resistance.

PURPOSE:Neoadjuvant targeted therapy provides a brief, preoperative window of opportunity that can be exploited to individualize cancer care based on treatment response. We investigated whether response to neoadjuvant therapy during the preoperative window confers survival benefit in patients with operable head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS:A pooled analysis of treatment-naïve patients with operable HNSCC enrolled in one of three clinical trials from 2009 to 2020 (NCT00779389, NCT01218048, NCT02473731). Neoadjuvant regimens consisted of EGFR inhibitors (n = 83) or anti-ErbB3 antibody therapy (n = 9) within 28 days of surgery. Clinical to pathologic stage migration was compared with disease-free survival (DFS) and overall survival (OS) while adjusting for confounding factors using multivariable Cox regression. Circulating tumor markers validated in other solid tumor models were analyzed. RESULTS:92 of 118 patients were analyzed; all patients underwent surgery following neoadjuvant therapy. Clinical to pathologic downstaging was more frequent in patients undergoing neoadjuvant targeted therapy compared with control cohort (P = 0.048). Patients with pathologic downstage migration had the highest OS [89.5%; 95% confidence interval (CI), 75.7-100] compared with those with no stage change (58%; 95% CI, 46.2-69.8) or upstage (40%; 95% CI, 9.6-70.4; P = 0.003). Downstage migration remained a positive prognostic factor for OS (HR, 0.22; 95% CI, 0.05-0.90) while adjusting for measured confounders. Downstage migration correlated with decreased circulating tumor markers, SOX17 and TAC1 (P = 0.0078). CONCLUSIONS:Brief neoadjuvant therapy achieved pathologic downstaging in a subset of patients and was associated with significantly better DFS and OS as well as decreased circulating methylated SOX17 and TAC1.

OBJECTIVE:To assess the validity of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) for evaluating thyroid nodules in children. METHODS:Patients aged <19 years with thyroid nodule(s) evaluated by ultrasound (US) from 2007-2018 at a tertiary children's hospital were included. Two radiologists scored de-identified thyroid US images using ACR TI-RADS (from 1, "benign" to 5, "highly suspicious"). The radiologists recorded size and rated vascularity for each nodule. Ultrasound findings were compared to pathology results (operative cases, n = 91) and clinical follow-up without disease progression (non-operative cases, n = 15). RESULTS:Thyroid images from 115 patients were reviewed. Nine patients were excluded due to the absence of an evaluable nodule. Forty-seven benign and 59 malignant nodules were included. Median age at ultrasound was 15 years (range 0.9-18 years). Twenty (18.9%) patients were male. There was moderate agreement between TI-RADS levels assigned by the two raters (kappa = 0.57, p < 0.001). When the raters' levels were averaged, >3 as the threshold for malignancy correctly categorized the greatest percentage of nodules (68.9%). Eleven (18.6%) malignant nodules received a TI-RADS level of 2 (n = 3) or 3 (n = 8). Sensitivity, specificity, and positive and negative predictive values were 81.4%, 53.2%, 68.6%, and 69.4%, respectively. Although not part of TI-RADS, vascularity was similar between benign and malignant nodules (p = 0.56). CONCLUSION/CONCLUSIONS:In a pediatric population, TI-RADS can help distinguish between benign and malignant nodules with comparable sensitivity and specificity to adults. However, the positive and negative predictive values suggest TI-RADS alone cannot eliminate the need for FNA. LEVEL OF EVIDENCE/METHODS:3 Laryngoscope, 2022.

OBJECTIVES/OBJECTIVE:Head and neck cancer patients that require major reconstruction often have advanced-stage disease. Discharge disposition of patients can vary and impact time to adjuvant treatment. We sought to examine outcomes in patients discharged to skilled nursing facilities (SNF) compared to those discharged home, including the impact on adjuvant therapy initiation and treatment package time (TPT). METHODS:Patients with head and neck squamous cell carcinoma treated with surgical resection and microvascular free flap reconstruction from 2019 to 2022 were included. Retrospective review was conducted to evaluate the impact of disposition on time to radiation (RT) and TPT. RESULTS:230 patients were included, with 165 (71.7%) discharged to home and 65 (28.3%) discharged to SNF. 79.1% of patients were recommended adjuvant therapy. Average time to RT was 59 days for patients discharged to home compared to 70.1 days for patients discharged to SNF. Disposition was an independent risk factor for delays to starting RT (p = 0.03). TPT was 101.7 days for patients discharged to home versus 112.3 days for those who discharged to SNF. Patients discharged to SNF had higher rates of readmission (p < 0.005) compared to patients discharged home in an adjusted multivariate logistic regression. CONCLUSIONS:Patients discharged to an SNF had significantly delayed time to initiation of adjuvant treatment and higher rates of readmission. Timeliness to adjuvant treatment has recently been established as a quality measure, thus identifying delays to adjuvant treatment initiation should be a priority. LEVEL OF EVIDENCE/METHODS:3 Laryngoscope, 2023.