Characteristics and outcomes of transoral robotic surgery with free-flap reconstruction for oropharyngeal cancer: a systematic review.

Transoral robotic surgery (TORS) approach for the treatment of oropharyngeal cancer allows for reduced patient morbidity, amongst other advantages over the traditional lip-splitting mandibulotomy method. Free-flap reconstruction is commonly utilized in head and neck cancer surgeries; however, safety and outcomes of this technique in TORS procedures have not been well studied. The objective of this study was to perform a systematic review to evaluate the efficacy and safety of TORS with free-flap reconstruction (TORS-FFR) for oropharyngeal cancer. A systematic search of Scopus, EMBASE, CINAHL and PubMed databases was completed. Following PRISMA guidelines, case series/reports, retrospective and prospective cohort studies were included. Primary outcomes measured were deaths and complication rates associated with TORS-FFR for oropharyngeal cancers. Secondary outcomes included functional swallowing and airway outcomes, operative time and length of hospital stay. Twenty-one studies met the inclusion criteria comprising a total of 132 patients. The mean patient age was 58.4 years. The most frequent complication was infection (8.9%) followed by flap wound dehiscence (4.2%). The average total operative time was 710 min (n = 48), while average length of hospital stay was 13.5 days (n = 48). Reconstructions were most commonly fashioned from radial forearm free flaps (RFFF), with anterolateral thigh flaps (ALT) representing the second most common free-flap subtype. TORS-FFR procedures for oropharyngeal cancer are safe, with low serious complication rates. This surgical approach may be associated with decreased length of hospital stay; however, further studies are required to better characterize post-operative outcomes.Level of evidence 1a.

Molecular Detection Methods in HPV-Related Cancers.

Human papillomavirus (HPV) is responsible for most cervical cancers and some head and neck cancers, including oropharyngeal squamous cell carcinoma and sinonasal carcinoma. Cervical cancer is commonly diagnosed by liquid-based cytology, followed by HPV testing using commercially available DNA polymerase chain reaction (PCR), p16 immunohistochemistry (IHC), or DNA/RNA in situ hybridization. HPV in head and neck cancers is commonly diagnosed by p16 IHC or by RT-qPCR of HPV-16 E6 and E7 oncoproteins. Droplet digital PCR has been reported as an ultrasensitive and highly precise method of nucleic acid quantification for biomarker analysis and has been used to detect oncogenic HPV in oropharyngeal and cervical cancers.

The Modified Alberta Reconstructive Technique: A prospective cohort study.

INTRODUCTION: Jaw defect reconstructions have been transformed by the development of free tissue transfer using vascularized bone incorporating osseointegrated dental implants. We recently developed a modification our method this procedure and termed it the Modified Alberta Reconstruction Technique (MART). The objective of this study aimed to assess the soft tissue component and outcomes of the MART as compared to the Alberta Reconstructive Technique (ART) or conventional (BDD) reconstructions. PATIENTS AND METHODS: This was a prospective cohort study of adult patients who underwent jaw reconstruction with dental implant rehabilitation between 2000 and 2019 in Edmonton, Alberta. Patients were aged-matched and placed into a cohort based on the type of reconstruction they received. Outcomes were compared between the groups. Expert and aesthetic analyses were performed. Statistical analysis was conducted to determine significance. RESULTS: A total of 46 patients (15 BDD, 15 ART and 16 MART) were included. Demographics were similar between groups. There was no difference in complications. The soft tissue component of the MART cohort was more favourable to work with as judged by the occlusal reconstructive experts. The MART was rated as more aesthetically appealing in comparison to the BDD and ART (p = 0.049). CONCLUSIONS: The MART is a safe, effective, and aesthetically appealing procedure. It yields a good functional result and a clinically better soft tissue component for occlusal reconstructions. For a select group of patients requiring jaw reconstruction, the MART is an ideal reconstructive option as the modification provides good control of the soft tissue around the implants.

Development of a patient reported outcome instrument for chronic sialadenitis.

BACKGROUND: Sialendoscopy assisted treatments are a minimally invasive management modality for chronic sialadenitis. Clinicians report improved patient quality of life (QoL) following sialendoscopy assisted treatments, but there exist gaps in current literature about patient reported outcomes (PROs). PROs are outcome measures developed based on patient perceptions. OBJECTIVE: The objective of this study was to create a PRO instrument for chronic sialadenitis, to assess the efficacy of sialendoscopy assisted treatments in improve patients' QoL. DESIGN: This four-phase qualitative study employed grounded theory methodology and a modified Delphi technique. In Phase I, ten patients were interviewed to identify the QoL domains impacted by chronic sialadenitis. In Phase II, these QoL domains were presented to a focus group of different chronic sialadenitis patients, who were asked to rank them by order of importance. A conceptual framework of QoL domains impacted by chronic sialadenitis was created based on patient consensus. Itemization of the PRO questionnaire was done by a focus group of four Otolaryngologists in phase III. Lastly, the questionnaire was completed in Phase IV by cognitive interviewing of five new chronic sialadenitis patients; ensuring ease of understanding and clarity. RESULTS: Patients identified 15 domains of QoL impacted by chronic sialadenitis, divided into three sub-scales: physical symptoms, psychosocial symptoms, and activity restriction. These domains provided the basis for creation of a 22-item PRO questionnaire, with a Likert-type response scale. CONCLUSION: Clinical application of the novel questionnaire produced by this study will allow for a patient-centered assessment of the patient reported effectiveness of sialendoscopy assisted therapies for management of chronic sialadenitis. Level of evidence Level V.

Clinical diagnostic utility of ultrasound-guided fine needle aspiration biopsy in parotid masses.

BACKGROUND: Fine needle aspiration (FNA) is a common diagnostic tool used in the initial evaluation of parotid masses. In the literature, variable diagnostic accuracy of FNA is reported. Therefore, when considering clinical management of these patients, the utility of FNA is unclear. The aim of this study was to determine the capability of ultrasound-guided FNA to differentiate between benign and malignant neoplasms. Further, the way in which FNA results affect clinical decision-making was assessed. METHODS: Retrospective data were collected for all patients who underwent parotidectomy at a large Canadian tertiary care center between 2011 and 2016. Patient demographics, preoperative imaging reports, preoperative FNA results, and final pathological diagnosis were analyzed. RESULTS: Of the 199 patients who underwent parotidectomy, 184 had preoperative ultrasound-guided FNA. There were a total of 13 non-diagnostic FNAs. In diagnosing malignancy, FNA had a sensitivity and specificity of 71.4% and 98.7%, respectively. The positive predictive value (PPV) was 83.3%. The negative predictive value was 97.5%. Of the non-diagnostic FNAs, 2 out of 13 (15.4%) were deemed malignant neoplasms on final pathology. CONCLUSION: FNA is a useful adjunct in the work-up of parotid masses, but it should be used with caution. Due to limited sensitivity, it should not be relied upon as the sole determinant of a surgeon's management plan.

Utility of droplet digital polymerase chain reaction for TERT and BRAF mutational profiling of thyroid nodules.

BACKGROUND: Mutations involving BRAF and TERT are important predictors of disease severity in thyroid cancer, but molecular testing is limited by cost and lack of adequate tissue sample. This study aimed to assess the utility of BRAFV600E and TERT testing using droplet digital PCR (ddPCR) as a diagnostic and prognostic tool for thyroid fine needle aspirate biopsy (FNAB). METHODS: Patients with thyroid nodules were prospectively enrolled from March 2015 to September 2018. Pre-operative FNAB was collected for standard cytology and molecular testing. BRAFV600E and TERT levels were analyzed by ddPCR. Cytology (Bethesda system) and ddPCR results were correlated to surgical pathology. RESULTS: A total of 222 patients were enrolled, of which 124 received thyroid surgery. Pre-operative cytology alone with Bethesda ≥5 was 100% specific and 70% sensitive for malignancy on final surgical pathology. BRAFV600E positivity or TERT overexpression was 100% specific and 60.0% sensitive. Combining cytology (Bethesda ≥5) with BRAFV600E and TERT testing increased the sensitivity of a malignant diagnosis to 80.0%. High TERT levels and/or BRAFV600E was associated with aggressive or advanced stage pathology. CONCLUSIONS: Combining cytology with ddPCR analysis of BRAFV600E and TERT can improve the diagnostic accuracy of thyroid FNAB, and help predict aggressive pathology.

The Functional & Quality of Life Outcomes of Total Glossectomy with Laryngeal Preservation.

BACKGROUND: The tongue is an essential organ for human interaction, communication and survival. To date, there is a paucity of objective functional, patient reported, or quality of life outcomes of patients undergoing a total glossectomy with preservation of the larynx (TGLP). OBJECTIVE: To examine prospectively collected objective, self-reported functional and quality of life (QOL) data in patients undergoing TGLP and free flap reconstruction. METHODS: Sixteen TGLP patients were identified in the prospective head and neck cancer and functional outcomes database between January of 2009 and December 2017. Data collection included patient age, sex, performance status, TNM staging, diagnosis and adjuvant treatment. Swallowing and speech functions were measured and prospectively recorded pre- and postoperatively. Patient reported outcomes were measured with the Speech Handicap Index (SHI) and the M.D. Anderson Dysphagia Inventory (MDADI). RESULTS: All patients had a significant reduction in their objective swallowing (P = 0.035), sentence (P = 0.001) and word intelligibility (P < .001) scores. There was no significant reduction in SHI or total MDADI scores. All patients maintained their QOL in the post-treatment time frame. There was no relationship between free-flap type and outcome. CONCLUSION: Total glossectomy with laryngeal sparing and free flap reconstruction results in significant reduction in objective functional measurements, but patients report stable functional and quality of life outcomes after treatment.

Epidemiological trends of head and neck Cancer survivors in Alberta: towards improved understanding of the burden of disease.

BACKGROUND: With an increase in the incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and more favourable survival outcomes, there is now a population of head and neck cancer survivors that are different from preceding decades. In addition, their long-term survivorship issues have become increasing research interests. This study was undertaken to determine the changing epidemiological trends of head and neck cancer survivors in Alberta to better anticipate future demands on healthcare services. METHODS: The Alberta Cancer Registry was queried for adult (aged > 18 years), head and neck cancer (HNC) patients who were at least 1-year post-treatment completion between 1997 to 2016. Cutaneous head and neck and thyroid cancer patients were excluded. Extracted data was then used to calculate the incidence and prevalence of early (< 5 years from treatment), intermediate (5 to < 10 years from treatment), and late (> 10 years from treatment) survivors of head and neck cancer. Point prevalence of HNC survivors in 2005, 2010, and 2015 were then further stratified by gender, sub-site and age. RESULTS: Over this time period, head and neck cancer survivors tended to be younger (64.0 vs. 62.1, p = 0.046) and male (M:F 2.45:1 vs 2.54:1). In 1997, the predominant subsites were the oral cavity and larynx at 45.8% and 30.9%, respectively. In 2015 the predominant subsites were the oral cavity and oropharynx at 33.0% and 29.4%, respectively. Within the cohort, the prevalence of late HNC survivors increased to 13.3 per 100,000 people in 2015. CONCLUSIONS: There is a significant population of head and neck survivors who are younger, male, and more than 10 years post-treatment. While oral cavity cancers have shown stable disease prevalence in recent decades, the number of OPSCC survivors have increased. With an improved understanding of the distribution and characteristics of HNC survivors, a more guided healthcare support network can be fostered for these patients.

Functional outcomes of the modified submandibular gland transfer procedure.

OBJECTIVES: Treatment for advanced head and neck cancers typically includes surgery followed by radiation therapy (RT). Radiation-induced xerostomia is a common sequela of these treatments. The modified submandibular gland transfer (M-SGT) procedure was developed to decrease xerostomia in the treatment of oral cavity cancer by sparing one submandibular gland (SMG) from radiation. This study's objectives were to: 1) elucidate the radiation-sparing capacity of the M-SGT, and 2) study the xerostomia-reducing potential of the M-SGT based on the University of Washington Quality-of-Life Questionnaire (UW-QOL). METHODS: Radiation therapy treatment plans were reviewed for all patients treated with surgery and RT who had a M-SGT at the University of Alberta Hospital during the study period. Outcomes included: 1) radiation dose received by the transferred SMG within the periparotid area compared to the submandibular triangle (ST), and 2) patient-reported saliva scores on the UW-QOL compared to historical controls without a gland transfer. RESULTS: Twenty-two patients were included. The mean radiation dose received by the transferred SMG was 29.00 grays (Gy) (standard deviation 14.59 Gy), thus reducing the mean radiation dose to the SMG by a statistically significant 18.34 Gy (confidence interval 95% (13.37, 23.32), P < 0.01) compared to the ST and below the D50 of the SMG (34 Gy). Sixty-five percent of patients rated their saliva as normal or mildly reduced on the UW-QOL as compared to 16% of controls (P = 0.01). CONCLUSION: The M-SGT technique is successful at reducing the radiation dose sustained by the SMG during adjuvant treatment and provides a significant improvement in xerostomia-related functional outcomes as compared to historical controls not receiving a gland transfer. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:925-929, 2020.

Association of human papillomavirus related squamous cell carcinomas of the oropharynx and cervix.

BACKGROUND: Human Papillomavirus (HPV) infection is well established in oropharyngeal squamous cell carcinoma (OPSCC) and cervical cancer (CC). However, the association between both HPV related cancers remains unclear. The purpose of this study was to investigate the association between HPV related cancers of the oropharynx and cervix. METHODS: A provincial cancer registry was used to retrospectively identify all patients diagnosed with OPSCC from 1997-2015. The standardized incidence ratio (SIR) of CC history in women with p16+/-OPSCC was measured. RESULTS: From 372 women with OPSCC included, the SIR of CC was significantly higher across all ages compared to the general population in Alberta, Canada (p < 0.0001). CONCLUSIONS: Women with HPV/p16+ OPSCC have a significantly higher risk of CC compared to the general population.

Antitumour effects of metformin and curcumin in human papillomavirus positive and negative head and neck cancer cells.

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has significantly increased in recent decades due to human papillomavirus (HPV)-mediated oncogenesis. Unfortunately, a growing number of HPV-positive (+) OPSCC survivors are living with the irreversible side effects of treatment. The novel, well-tolerated chemotherapeutics with improved side effect profiles are, therefore, in high demand. Metformin is one such drug, widely used as a first-line oral agent in the treatment of type 2 diabetes mellitus. Curcumin is another well-tolerated agent quickly gaining attention for its medicinal properties. Both metformin and curcumin have been shown to display anticancer properties. This study aimed to determine the antitumor effects of these agents, individually and combined, in HPV+​​​​ ​​​and HPV-negative (-) head and neck squamous cell carcinoma (HNSCC) cell lines. This was achieved by assessing the efficacy of varying drug concentrations on the overall cell viability, proliferation, and expression of common HNSCC biomarkers. The results from protein and RNA expression data are highly variable, as expected, with multiple pathways being affected in cancer. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and immunofluorescence microscopy suggest that both agents are capable of slowing proliferation and inducing apoptosis. We conclude that curcumin and metformin display effective antitumor effects in both HPV+ and HPV- HNSCC cell lines. The curcumin effects appear more pronounced in the HPV- cell lines. Metformin appears to be more effective at reducing the overall cell numbers in HPV+ cell lines. Metformin and curcumin combined did not appear to have synergistic effects on the proliferation or apoptosis of the treated cell lines.

Development of the Alberta facial clinical evaluation scale: A patient-centred outcomes instrument for facial nerve paralysis.

OBJECTIVES: Facial nerve paralysis has functional, psychological and social consequences for patients. Traditionally, outcome measurements for facial nerve injuries have been clinician derived. Recent literature has shown that patient perspective is valuable and necessary in outcomes research. This study aimed to identify patient domains of concern and subsequently, develop a point-of-care questionnaire for clinical use. DESIGN: This mixed-methods prospective study was completed in three phases. In Phase I, 15 facial nerve injury patients were interviewed individually. Interviews were digitally recorded, transcribed and coded with NVivo software. Analysis led to a conceptual framework detailing the most important quality of life outcomes. During Phase II, a focus group was held with five new patients in order to prioritise the outcome themes to a top six list. A second focus group was held with Otolaryngology-Head and Neck staff surgeons to create a 25-item questionnaire based on these six themes. In Phase III, the questionnaire was administered to 10 new patients to test for comprehension. SETTING: University of Alberta Hospital, Edmonton, Alberta, Canada. PARTICIPANTS: A total of 30 patients with facial nerve injury were included in the various phases in the study. In addition, 5 staff Otolaryngology-Head and Neck surgeons participated as focus group contributors. MAIN OUTCOME MEASURES: Domains of concern and quality of life outcomes as reported by facial nerve injury patients. RESULTS: Patients identified a total of 16 themes encompassing both functional and psychological deficits related to their facial nerve injury. From these findings, a 25-item Likert-type scale, the A-FaCE scale, was developed for clinical use. CONCLUSIONS: Patients with facial nerve paralysis experience functional and psychological deficits. This study led to the creation of the first patient-reported instrument for this population that addresses functional impairment, social function, psychological well-being and self-perception of appearance.

The Alberta Reconstructive Technique: An Occlusion-Driven and Digitally Based Jaw Reconstruction.

OBJECTIVES/HYPOTHESIS: The free flap reconstructive protocols of the jaws have been refined over the years and presently are based on bone-driven approaches that generally use the lower border of the mandible or the anterior surface of the maxilla as the templates for reconstruction because these contours are deemed important to the eventual cosmetic outcomes of patients. The ultimate goal of functional jaw reconstruction, however, is the reconstruction of the dental occlusion and oral rehabilitation. The purpose of the present study was to evaluate the Alberta reconstructive technique (ART), which is a new approach of occlusion-driven jaw reconstruction with digitally planned immediate osseointegrated implant installation. STUDY DESIGN: Prospective cohort study. METHODS: This research study considers the ART's safety, effectiveness, accuracy, timeliness of reconstruction, aesthetic appeal, and cost-effectiveness in comparison with the standard bone-driven and delayed osseointegrated implant installation (BDD) protocol. RESULTS: The ART procedures were as safe and more effective at achieving full occlusal reconstruction and oral rehabilitation. The ART cohort of patients achieved oral rehabilitation in 21.4 month as compared to 73.1 months for the BDD cohort. There were no differences in the aesthetic appeal the two groups. The ART cost an average of $22,004 less than BDD and we calculated the quality adjusted life years gain to be between 2.14 and 4.04 in favour of ART. CONCLUSIONS: The ART is a good option for patients with jaw defects. It provides a safe, effective, accurate, aesthetic, and cost-effective reconstruction that restores form and function in a timely manner. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:S1-S14, 2019.

Donor site morbidity following radial forearm free flap reconstruction with split thickness skin grafts using negative pressure wound therapy.

BACKGROUND: Donor site complications secondary to radial forearm free flap (RFFF) reconstruction can limit recovery. Optimizing hand and wrist function in the post-operative period may allow more efficient self-care and return to activities of daily living. Negative pressure wound dressings (NPD) may increase blood flow and perfusion as compared to static pressure dressings (SPD) designed to minimize shear forces during the healing period. This study aims to compare subjective and objective hand and wrist functional outcomes following RFFF reconstruction with split thickness skin grafts (STSG) in patients treated with NPD and SPD. METHODS: Adult patients undergoing RFFF with STSG were identified preoperatively and randomized to receive NPD or SPD following their RFFF reconstruction. NPD involved a single-use, portable device capable of applying 80 mmHg of negative pressure to the forearm donor site. SPD involved a volar splint. Dressings were left in place for seven days with subjective and objective function assessed at seven days, one month and three months postoperatively. The primary outcome was self-reported hand function as measured with the function subscale of the Michigan Hand Questionnaire (MHQ). Secondary outcomes included hand and wrist strength, range of motion, sensation, scar aesthetics, and skin graft complications. RESULTS: Twenty-four patients undergoing RFFF were randomized to NPD or SPD. Patients treated with NPD had improved MHQ self-reported functional scores as compared to those treated with SPD at seven days postoperatively (P = 0.016). Flexion at seven days was improved in NPD group (P = 0.031); however, all other strength and range of motion outcomes were similar between groups. There were no differences in rates of graft complications, scar aesthetics, or sensation. CONCLUSIONS: In the immediate post-operative period, NPD was associated with improved patient-reported hand and wrist function. Wound care to optimize hand and wrist function could allow for improved patient outcomes in the immediate postoperative period.

EGFR as a biomarker of smoking status and survival in oropharyngeal squamous cell carcinoma.

BACKGROUND: This study aims to investigate EGFR as a prognostic biomarker in oropharyngeal squamous cell carcinoma (OPSCC). METHODS: OPSCC patients from retrospective (1998-2009) and prospective cohorts (2014-2017) were included. Retrospectively collected tumors were used to construct tissue microarrays (TMAs), which were stained with EGFR, p16, DAPI and Pan-cytokeratin, and digitally quantified. EGFR, CDKN2A and HPV E6/7 levels from prospectively collected OPSCC was measured by droplet digital PCR (ddPCR). Biomarkers were compared to patient covariates, factors and survival outcomes. RESULTS: A total of 249 patients were included retrospectively and 64 patients were enrolled prospectively. p16 status (p < 0.001), smoking above 10 pack years (p = 0.04), smoking above 20 pack years (p < 0.001), total EGFR tumor levels (p = 0.016), and high EGFR within high or low Ki67 tumor nuclear staining (p = 0.03) were found to be significant predictors of 5-year disease specific survival (DSS). A Cox proportional hazard model of DSS showed smoking status and eGFR expression to be dependent of each other on predicting 5-year DSS. ddPCR analysis showed a significant association between smoking status and EGFR levels. CONCLUSIONS: Total EGFR tumor levels are predictive of 5-year DSS. EGFR levels correlate with. smoking and could be an objective marker for this disease etiology.

The association of Bcl-xL and p53 expression with survival outcomes in oropharyngeal cancer.

BACKGROUND: The role of molecular biomarkers in oropharyngeal squamous cell carcinoma (OPSCC) has recently been increasingly recognized. There is conflicting evidence in the literature with regards to the prognostic value of p53 and Bcl-xL. OBJECTIVE: The purpose of this study was to investigate the association between p53 and Bcl-xL expression profiles and survival outcomes in OPSCC. METHODS: Patients diagnosed with OPSCC and treated with curative intent between 1998 and 2009 were included in the study. Patient demographics, disease, treatment, and oncologic outcomes were collected prospectively. A tissue microarray (TMA) from patients' biopsies or surgical specimens was retrospectively constructed. The expression levels of p53, Bcl-xL, and p16 were digitally quantified and correlated to patient survival outcomes. RESULTS: One hundred and sixty-six patients were included (mean age 56.7 years; standard deviation (SD) ± 10.0; 78% male). High expression of Bcl-xL (p= 0.04) was significantly associated with nodal disease at presentation, and decreased overall survival (OS) (p= 0.04). Combined expression of low Bcl-xL and low p53 conferred a survival advantage in non-smokers (p= 0.04). Multivariate analysis supported smoking and p16 status as independent prognosticators for OS. CONCLUSIONS: This study suggests that biomarker profiling using Bcl-xL and p53 levels may be of prognostic value in select patients with OPSCC.

Long-term survival and swallowing outcomes in advanced stage oropharyngeal squamous cell carcinomas.

BACKGROUND: There is a paucity of studies reporting long-term survival outcomes for HPV/p16 positive oropharyngeal squamous cell carcinoma (OPSCC). This study aims to compare long-term outcomes of advanced stage p16 positive and negative OPSCCs, treated by surgical and non-surgical modalities. METHODS: OPSCC patients from 1998 to 2012 were identified through a prospectively collected cancer registry. P16 immunohistochemistry was used as a surrogate marker for HPV-OPSCC. Overall survival (OS) and aspiration free survival (AFS) comparisons were made between patients treated with chemoradiation (CRT) versus primary surgery and radiation/chemoradiation (S+RT/CRT) at 5, 10 and 15 years post-treatment. RESULTS: A total of 319 patients were included. P16 positive patients and non-smokers had significantly higher long-term (5, 10 and 15-year) OS. Smokers and p16 negative patients treated with S+RT/CRT had improved long-term OS compared to patients who received CRT. Smokers and p16 negative patients had lower long-term AFS. Multivariate analysis showed improved OS was associated with p16 positivity (HR 0.42, 0.28-0.61) and surgery (HR 0.47, 0.32-0.69), whereas lower OS was associated with ECOG ≥ 2 (HR 2.46, 1.61-3.77), smoking (HR 2.37, 1.41-3.99) and higher stage (HR 1.68, 1.05-2.68). CONCLUSIONS: In smokers and p16-negative OPSCC patients, primary surgery may be associated with improved long-term survival and dysphagia-related outcomes.

Validation of a novel method for localization of parathyroid adenomas using SPECT/CT.

BACKGROUND: Accurate localization of parathyroid adenomas is of critical importance in surgical planning for minimally invasive parathyroidectomy. SPECT/CT is considered the investigation of choice but has limitations regarding localization of superior versus inferior adenomas. We proposed a novel method for localization using SPECT/CT by determining the anterior-posterior relationship of the adenoma to a horizontal line in the coronal plane through the tracheoesophageal groove. Our objective was to determine the accuracy, validity, and inter-rater reliability of this method. METHOD: This was a retrospective review of patients who underwent parathyroidectomy for a single adenoma between 2010-2017. SPECT/CT images were reviewed by two staff Otolaryngologists, a Radiologist, an Otolaryngology fellow and Otolaryngology resident. Results were compared using intra-operative report as the gold standard. Overall accuracy in determining superior/inferior and right/left adenomas was calculated, as well as Cohen's Kappa to determine agreement with operative report and inter-rater reliability. The performance was compared to that of the original radiology report. RESULTS: One hundred thirty patients met criteria and were included. Our method correctly identified the location of the adenoma in terms of both side and superior/inferior position in 80.4% [76 - 84%] of patients, which considerably outperformed the original radiology report at 48.5% [4-78%] accuracy. The agreement level between our method and operative report was high (Kappa=0.717 [0.691-0.743]), as was the inter-rater reliability (Kappa=0.706 [0.674-0.738]). CONCLUSION: We report a novel method for localization of parathyroid adenomas using SPECT/CT which outperforms standard radiology reporting. This tool can be used by surgeons and radiologists to better inform and plan for minimally invasive parathyroidectomy.

Analytic and clinical validity of thyroid nodule mutational profiling using droplet digital polymerase chain reaction.

BACKGROUND: Recent guidelines for the management of thyroid nodules incorporate mutation testing as an adjunct for surgical decision-making, however current tests are costly with limited accuracy. Droplet digital PCR (ddPCR) is an ultrasensitive method of nucleic acid detection that is particularly useful for identifying gene mutations. This study aimed to assess the analytic and clinical validity of RAS and BRAF ddPCR mutational testing as a diagnostic tool for thyroid fine needle aspirate biopsy (FNAB). METHODS: Patients with thyroid nodules meeting indication for FNAB were prospectively enrolled from March 2015 to September 2017. In addition to clinical protocol, an additional FNAB was obtained for ddPCR. Optimized ddPCR probes were used to detect mutations including HRASG12 V, HRASQ61K, HRASQ61R, NRASQ61R, NRASQ61K and BRAFV600E. The diagnostic performance of BRAF and RAS mutations was assessed individually or in combination with Bethesda classification against final surgical pathology. RESULTS: A total of 208 patients underwent FNAB and mutational testing with the following Bethesda cytologic classification: 26.9% non-diagnostic, 55.2% benign, 5.3% FLUS/AUS, 2.9% FN/SPN, 2.4% SFM and 7.2% malignant. Adequate RNA was obtained from 91.3% (190) FNABs from which mutations were identified in 21.1% of HRAS, 11.5% of NRAS and 7.4% of BRAF. Malignant cytology or BRAFV600E was 100% specific for malignancy. Combining cytology with ddPCR BRAF600E mutations testing increased the sensitivity of Bethesda classification from 41.7 to 75%. Combined BRAFV600E and Bethesda results had a positive predictive value (PPV) of 100% and negative predictive value (NPV) of 89.7% for thyroid malignancy in our cohort. CONCLUSIONS: DdPCR offers a novel and ultrasensitive method of detecting RAS and BRAF mutations from thyroid FNABs. BRAFV600E mutation testing by ddPCR may serve as a useful adjunct to increase sensitivity and specificity of thyroid FNAB.

Association of Fludeoxyglucose F 18-Labeled Positron Emission Tomography and Computed Tomography With the Detection of Oropharyngeal Cancer Recurrence.

Importance: No guidelines at present describe when fludeoxyglucose F 18-labeled positron emission tomography and computed tomography (FDG PET-CT) should be used in the initial posttreatment period for evaluation of oropharyngeal squamous cell carcinoma treatment outcome and recurrence. Objective: To compare accuracies of the initial posttreatment PET-CT between primary treatment groups and to define indicators of false-positive findings. Design, Setting, and Participants: This retrospective cohort study identified adults with a new diagnosis of oropharyngeal squamous cell carcinoma who received treatment with curative intent from October 1, 2006, through November 30, 2016, using the Alberta Cancer Registry (n = 380). Patients who underwent PET-CT within 1 year of treatment completion were included (n = 190). Of these, 103 patients (54.2%) had PET-CT findings positive for residual or recurrent disease, and 61 (32.1%) had false-positive findings. Among the 61 patients, 42 (68.9%) had received chemoradiotherapy (CRT) and 19 (31.1%) had primary surgery. Forty-two patients had true-positive findings, indicating a prevalence rate of disease of 22.1%. Data were analyzed from July through October 2017. Exposures: One of 2 primary treatment modalities (surgery with or without adjuvant therapy vs CRT). All patients had posttreatment FDG PET-CT. Main Outcomes and Measures: Primary outcome measures included the diagnostic odds ratio, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET-CT for detecting residual and/or recurrent disease. A multivariate analysis determined indicators of false-positive findings. Discriminative ability was assessed using receiver operating characteristic curve analysis of maximum standardized uptake value (SUVmax) metabolic data. Results: Of the 190 participants, 77.9% were men, with a mean (SD) age at diagnosis of 58.5 (8.5) years. The diagnostic odds ratio was 19.3 (95% CI, 5.7-65.1); pooled sensitivity, 93.3% (95% CI, 80.7%-98.3%); and pooled specificity, 57.9% (95% CI, 49.4%-66.0%). The PPV of detecting disease was 54.7% (95% CI, 38.8%-69.8%) for primary surgery and 31.1% (95% CI, 20.2%-44.4%) for CRT. The NPV was 100% (95% CI, 94.7%-100%) for primary surgery and 96.6% (95% CI, 89.5%-99.1%) for CRT. Multivariate analysis identified treatment type, p16 disease, and smoking status as indicative of false-positive findings. In the receiver operating characteristic curve analysis for primary tumors, the optimal cutoff SUVmax for indicating true- vs false-positive results was 5.1 for surgically treated patients (area under the curve, 0.729; 95% CI, 0.570-0.888) and 5.3 for patients treated with CRT (area under the curve, 0.844; 95% CI, 0.700-0.989). Conclusions and Relevance: The results indicate a higher specificity for FDG PET-CT for initial posttreatment surveillance imaging among patients treated with primary surgery compared with nonsurgical management. Both sets of patients with posttreatment FDG PET-CT findings with an SUVmax greater than 5.0 should undergo close evaluation for possible residual or recurrent disease.