Outcomes for potentially Resectable patients undergoing primary chemoradiation treatment for T1-T2 HPV Negative oropharyngeal squamous cell carcinoma.

BACKGROUND: Transoral surgical resectability (TOS) is a prognostic factor for patients with HPV+ T1-2 oropharyngeal squamous cell carcinoma (OPSCC) disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV-negative (HPV-) patients. We aimed to compare outcomes of potential TOS-candidates vs. non-TOS candidates, among patients who underwent RT/CRT for early T-stage HPV- OPSCC. METHODS: For patients treated with RT/CRT for early T-stage HPV-negative OPSCC between 2014 and 2021, pretreatment imaging was reviewed by four head-and-neck surgeons, masked to clinical outcomes, to assess primary-site suitability for TOS. Extracapsular extension (ECE) was assessed by a head-and-neck neuroradiologist. We compared outcomes based on surgical resectability relating to: (1) the primary site tumor alone, and (2) the primary site plus the absence/presence of ECE (overall assessment). Kaplan-Meier curves for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were compared using the log-rank test. RESULTS: Seventy patients were included in the analysis. The primary site was TOS-favorable in 46/70 (66%). Based on the overall assessment, 41/70 (58.6%) were TOS-favorable. The 3-year OS, DSS and PFS for primary site TOS-favorable versus unfavorable were OS: 76.9% versus 37.4%; DSS: 78.1% versus 46.2%, PFS: 69.9% versus 41.3%, (log-rank test = 0.01, 0.03, 0.04; respectively). Additionally, patients with an overall assessment of TOS favorability demonstrated better survival outcomes compared with TOS-unfavorable patients (OS: 77.3% vs. 46.2%; DSS: 78.2% vs. 56.5%, PFS: 72.3% vs. 42.1%, log-rank test = 0.01, 0.04, 0.01; respectively). CONCLUSION: Patients with TOS-favorable HPV-negative early T-stage OPSCC have superior survival outcomes than TOS-unfavorable patients.

Sarcopenia as a Predictor of Feeding Tube Placement in Individuals with Oropharyngeal Cancer.

Purpose: In oropharyngeal squamous cell carcinoma (OPSCC), systemic loss of skeletal muscle mass (SMM), or sarcopenia, is a strong prognostic predictor of survival outcomes. However, the relationship between sarcopenia and nutrition-related outcomes is not well understood. This investigation evaluated the prognostic significance of sarcopenia for feeding tube (FT) placement in a cohort of OPSCC patients. Methods and Materials: A retrospective cohort study was conducted with data collected from 194 OPSCC patients treated with definitive radiation therapy (RT) or chemoradiation therapy (CRT). Sarcopenia was assessed from computed tomography imaging at the level of the third cervical (C3) and fourth thoracic (T4) vertebrae. The prognostic nature of pretreatment sarcopenia and its relationship with FT placement was explored using logistic regression. Results: The median age of patients included was 61.0 years, and the majority were male (83%). In this patient cohort, 87.6% underwent concurrent CRT, and 30.9% received a FT over the course of treatment. Sarcopenia was identified at baseline in 72.7% of patients based on C3 SMM measurements and in 41.7% based on measures at the level of T4. Based on measures at both C3 and T4, those with sarcopenia were significantly more likely to receive a FT and had significantly worse freedom from FT placement compared with patients without sarcopenia. Sarcopenia assessed at T4 was a significant predictor of FT placement. Conclusions: SMM measured at T4 may represent a novel and practical biomarker for sarcopenia detection that is associated with the need for FT placement. These findings suggest that the detection of baseline sarcopenia could guide decision-making related to the need for nutritional support in OPSCC patients undergoing RT/CRT.

Feeding outcomes in tracheostomy-dependent infants - can we predict future gastrostomy tube use?

OBJECTIVES: To identify characteristics of infants with tracheostomy that require gastrostomy tube insertion versus those likely to orally feed to predict which patients may benefit from insertion of gastrostomy at the time of tracheostomy placement. METHODS: Retrospective review of infants undergoing tracheostomy from birth to 18 months of age. The primary outcome was to identify pre-operative factors predictive of future gastrostomy tube use. Univariate and multivariate analyses evaluated association between pre-operative patient characteristics and feeding outcomes. RESULTS: Of 103 patients identified, 73 met inclusion criteria. Upper airway anomaly was the indication for tracheostomy in 70.4 %. Gastrostomy tube was required in 52 patients (75.4 %), with 7 (13.5 %) placed concurrently with tracheostomy. Infants with birth complications, a neurologic diagnosis, multiple co-morbidities, or identified with aspiration risk were more likely to require a gastrostomy tube (p < 0.05). CONCLUSIONS: Most infants who require tracheostomy placement from birth until 18 months of age will require nutritional support. Tracheostomy and gastrostomy are uncommonly placed concurrently. Coordination of placement would theoretically minimize the risk of general anesthetic exposure while potentially reducing hospital length of stay and healthcare related costs.

Sarcopenia in head and neck cancer: A scoping review.

OBJECTIVES: In those undergoing treatment for head and neck cancer (HNC), sarcopenia is a strong prognostic factor for outcomes and mortality. This review identified working definitions and methods used to objectively assess sarcopenia in HNC. METHOD: The scoping review was performed in accordance with Arksey and O'Malley's five-stage methodology and the Joanna Briggs Institute guidelines. INFORMATION SOURCES: Eligible studies were identified using MEDLINE, Embase, Scopus, Cochrane Library, and CINAHL databases. STUDY SELECTION: Inclusion criteria represented studies of adult HNC patients in which sarcopenia was listed as an outcome, full-text articles written in English, and empirical research studies with a quantitative design. DATA EXTRACTION: Eligible studies were assessed using a proprietary data extraction form. General information, article details and characteristics, and details related to the concept of the scoping review were extracted in an iterative process. RESULTS: Seventy-six studies published internationally from 2016 to 2021 on sarcopenia in HNC were included. The majority were retrospective (n = 56; 74%) and the prevalence of sarcopenia ranged from 3.8% to 78.7%. Approximately two-thirds of studies used computed tomography (CT) to assess sarcopenia. Skeletal muscle index (SMI) at the third lumbar vertebra (L3) (n = 53; 70%) was the most prevalent metric used to identify sarcopenia, followed by SMI at the third cervical vertebra (C3) (n = 4; 5%). CONCLUSIONS: Currently, the most effective strategy to assess sarcopenia in HNC depends on several factors, including access to resources, patient and treatment characteristics, and the prognostic significance of outcomes used to represent sarcopenia. Skeletal muscle mass (SMM) measured at C3 may represent a practical, precise, and cost-effective biomarker for the detection of sarcopenia. However, combining SMM measurements at C3 with other sarcopenic parameters-including muscle strength and physical performance-may provide a more accurate risk profile for sarcopenia assessment and allow for a greater understanding of this condition in HNC.

Supporting Patient Autonomy in Shared Decision Making for Individuals With Head and Neck Cancer.

PURPOSE: Management of head and neck cancer (HNC) can result in substantial long-term, multifaceted disability, leading to significant deficits in one's functioning and quality of life (QoL). Consequently, treatment selection is a challenging component of care for patients with HNC. Clinical care guided by shared decision making (SDM) can help address these decisional challenges and allow for a more individualized approach to treatment. However, due in part to the dominance of biomedically oriented philosophies in clinical care, engaging in SDM that reflects the individual patient's needs may be difficult. CONCLUSIONS: In this clinical focus article, we propose that health care decisions made in the context of biopsychosocial-framed care-one that contrasts to decision making directed solely by the biomedical model-will promote patient autonomy and permit the subjective personal values, beliefs, and preferences of individuals to be considered and incorporated into treatment-related decisions. Consequently, clinical efforts that are directed toward biopsychosocial-framed SDM hold the potential to positively affect QoL and well-being for individuals with HNC.

Assessment of Toxic Effects and Survival in Treatment Deescalation With Radiotherapy vs Transoral Surgery for HPV-Associated Oropharyngeal Squamous Cell Carcinoma: The ORATOR2 Phase 2 Randomized Clinical Trial.

Importance: The optimal approach for treatment deescalation in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) is unknown. Objective: To assess a primary radiotherapy (RT) approach vs a primary transoral surgical (TOS) approach in treatment deescalation for HPV-related OPSCC. Design, Setting, and Participants: This international, multicenter, open-label parallel-group phase 2 randomized clinical trial was conducted at 9 tertiary academic cancer centers in Canada and Australia and enrolled patients with T1-T2N0-2 p16-positive OPSCC between February 13, 2018, and November 17, 2020. Patients had up to 3 years of follow-up. Interventions: Primary RT (consisting of 60 Gy of RT with concurrent weekly cisplatin in node-positive patients) vs TOS and neck dissection (ND) (with adjuvant reduced-dose RT depending on pathologic findings). Main Outcomes and Measures: The primary end point was overall survival (OS) compared with a historical control. Secondary end points included progression-free survival (PFS), quality of life, and toxic effects. Results: Overall, 61 patients were randomized (30 [49.2%] in the RT arm and 31 [50.8%] in the TOS and ND arm; median [IQR] age, 61.9 [57.2-67.9] years; 8 women [13.6%] and 51 men [86.4%]; 31 [50.8%] never smoked). The trial began in February 2018, and accrual was halted in November 2020 because of excessive toxic effects in the TOS and ND arm. Median follow-up was 17 months (IQR, 15-20 months). For the OS end point, there were 3 death events, all in the TOS and ND arm, including the 2 treatment-related deaths (0.7 and 4.3 months after randomization, respectively) and 1 of myocardial infarction at 8.5 months. There were 4 events for the PFS end point, also all in the TOS and ND arm, which included the 3 mortality events and 1 local recurrence. Thus, the OS and PFS data remained immature. Grade 2 to 5 toxic effects occurred in 20 patients (67%) in the RT arm and 22 (71%) in the TOS and ND arm. Mean (SD) MD Anderson Dysphagia Inventory scores at 1 year were similar between arms (85.7 [15.6] and 84.7 [14.5], respectively). Conclusions and Relevance: In this randomized clinical trial, TOS was associated with an unacceptable risk of grade 5 toxic effects, but patients in both trial arms achieved good swallowing outcomes at 1 year. Long-term follow-up is required to assess OS and PFS outcomes. Trial Registration: Clinicaltrials.gov Identifier: NCT03210103.

Routine follow-up care for head and neck cancer after curative treatment: A 3-year experience of measuring patients' self-reported needs, preferences, quality of life and attitudes towards follow-up.

OBJECTIVE: To evaluate and describe attitudes, quality of life (Qol), needs and preferences of patients with head and neck cancer after 3 years of follow-up care. METHODS: This is an exploratory prospective study of recurrence-free patients. Survey results were compared between 1-, 2- and 3-year post-treatment and by disease characteristics. RESULTS: A total of 116 patients were included with 46% oropharyngeal cancer, 66% early stage disease and 41% having had surgery. After 3 years, most patients reported good to excellent health (88%), however expressed uncertainty regarding recurrence (66%), multiple needs (information on prognosis 91%, long-term sequalae 72%) and wanted to continue with follow-up (96%). Few changes were observed over time, with exceptions. Patients with more advanced disease, oral cancer or who had surgery experienced declining Qol (p < 0.050). Women experienced improvements in Qol domains (pain p = 0.028, speech p = 0.009) over time. Attitudes towards communication with oncologists demonstrated improved patient comfort (p = 0.044) over the 3 years; however, patients' beliefs about their prognosis did not (71% vs. 73% vs. 77% did not believe they were cured, p = 0.581). CONCLUSION: Although patients' needs, preferences and attitudes towards follow-up did not change drastically, important needs persist. This work supports identifying individual patient needs and the challenges in addressing prognostic expectations.

Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Long-Term Results of the ORATOR Trial.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking. METHODS: We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial. RESULTS: Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time (P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years (P = .015). Dry mouth scores were higher in RT patients over time (P = .041). CONCLUSION: On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355).

Detection of Circulating Tumor DNA in Patients with Thyroid Nodules.

OBJECTIVE: Detection of circulating tumor DNA (ctDNA) in cancer patients can potentially serve as a noninvasive, sensitive test of disease status. The purpose of this study was to determine the ability to detect BRAF (V600E) mutations in the plasma of patients with thyroid nodules, with the goal of distinguishing between benign and malignant nodules. METHODS: Consecutive patients with thyroid nodules who consented for surgery were recruited. Plasma samples were obtained preoperatively and one month postoperatively. Quantitative PCR was used to determine the levels of the BRAF (V600E) mutation preoperatively and postoperatively. RESULTS: A total of 109 patients were recruited. On final pathology, 38 (32.8%) patients had benign thyroid nodules, 45 (38.8%) had classical papillary thyroid cancer (PTC), 23 (19.8%) had nonclassical PTC, and 3 (2.6%) had follicular thyroid cancer. 15/109 patients had detectable BRAF (V600E) ctDNA in their preoperative samples-all of them having classical PTC. Higher T-stage and extrathyroidal extension in PTC were associated with positive BRAF (V600E) ctDNA (p < 0.05). Eighty-eight pairs of preoperative and postoperative plasma samples were collected and analyzed. Of these eighty-eight paired samples, a total of 13/88 (14.8%) patients had detectable BRAF (V600E) ctDNA in their preoperative samples-all of them having classical PTC. 12 of these 13 patients had no detectable BRAF (V600E) postoperatively, while one remaining patient had a significant decline in his levels (p < 0.05). CONCLUSION: BRAF (V600E) circulating thyroid tumor DNA can be detected in plasma and is correlated with a final diagnosis of the classical variant of PTC. Given that a postoperative drop in BRAF (V600E) ctDNA levels was observed in all cases suggests its utility as a tumor marker.

"Cured" but not "healed": The application of principles of palliative care to cancer survivorship.

Application of principles of palliative care to the concept of survivorship may serve to establish an interdisciplinary approach to guide those treated for cancer through the experience of being "cured" but not "healed". Valuable lessons may be garnered from palliative care if its principles are considered within the context of survivorship. This work aims to define key terms including cured, healed, survivorship, and quality of life (QoL) and delineate the central tenets of palliative care and disease-modifying care. Since pursuit of a cure tends to dominate provision of oncological care, Western society's prevailing death denying attitudes often equate to the prioritization of advanced medial treatment to postpone death. Accordingly, the "modern paradox" of medicine (Cassell, 2004) is examined in consideration of the suffering that often results from advanced medical treatment that is intended to alleviate the cause of suffering and ultimately, "deny" death. However, owing to the profound consequences of advanced medical treatment and the associated losses of function concomitant with cancer, there is an apparent need for a framework of care that attends to these survivorship issues. When the experience of being cured but not healed is articulated through a theoretical discussion of liminality and the "remission society" (Frank, 1995), the applicability of palliative care to survivorship care becomes apparent. By embracing principles of palliative care, survivorship care may be guided by a theoretical foundation that provides cancer survivors with care that supports increased QoL, biopsychosocial symptom management, and a holistic perspective of the illness experience. Accordingly, application of palliative care to survivorship may establish congruence between notions of cured and healed.

Resilience: an essential element in head and neck cancer survivorship and quality of life.

PURPOSE: Individuals with head and neck cancer (HNCa) face myriad biopsychosocial challenges. Even after treatment completion, these challenges may cause continued disablement and diminished quality of life (QoL). Resilience may serve to minimize the disabling impact of HNCa and, in turn, maximize QoL. The purpose of this study was to formally assess resilience in HNCa survivors and explore its relationship with QoL. METHODS: A cross-sectional descriptive study was conducted. Forty HNCa survivors completed three validated, self-report questionnaires pertaining to the collection of resilience and QoL data. Descriptive and correlational analyses were performed. RESULTS: Resilience was identified in HNCa survivors and a positive correlation was found between resilience and QoL. CONCLUSIONS: Data suggest that resilience may buffer the influence of HNCa on QoL. Thus, screening for reduced levels of resilience may proactively facilitate identification of those who are most vulnerable to the psychosocial impact of HNCa. Interventions that foster resilience may ameliorate the challenges of HNCa and maximize QoL.

The natural history of weight and swallowing outcomes in oropharyngeal cancer patients following radiation or concurrent chemoradiation therapy.

PURPOSE: Patients treated for oropharyngeal cancer (OPC) are at increased risk for functional decline due to cancer-related impairments and treatment toxicities, often leading to recommendations for enteral nutritional support. This study investigated the natural history of weight and swallowing outcomes in patients with and without feeding tube (FT) placement. METHODS: Data were collected from electronic medical records of OPC patients treated with (chemo)radiotherapy at a single regional cancer center between January 2013 and December 2015. Weight measurements, Functional Oral Intake Scale (FOIS) scores, Performance Status Scale for Head and Neck Cancer (PSS-HN) normalcy of diet scores, and M.D. Anderson Dysphagia Inventory (MDADI) composite scores were gathered at baseline and at 3-, 6-, and 12-months post-treatment. Patients were grouped based on FT placement and change over time was assessed using linear mixed effects analysis. RESULTS: Of 122 eligible patients, 38 (31.1%) received a FT (FT group). Compared with baseline, weight decreased significantly at 3 and 6 months in both groups and at 12 months for patients without a FT (NFT group). Swallowing-related quality of life (QoL) decreased significantly at 3 and 6 months only in the NFT group. CONCLUSION: OPC patients experience clinically relevant decreases in weight and swallowing-related QoL in the first-year post-treatment irrespective of FT placement. These findings will contribute to improved patient monitoring and communication within the clinical setting which may ultimately lead to better outcomes for those with OPC.

Preservation of swallowing in resected oral cavity squamous cell carcinoma: examining radiation volume effects (PRESERVE): study protocol for a randomized phase II trial.

BACKGROUND: Patients with resected oral cavity squamous cell carcinoma (OCSCC) are often treated with adjuvant radiation (RT) ± concomitant chemotherapy based on pathological findings. Standard RT volumes include all surgically dissected areas, including the tumour bed and dissected neck. RT has significant acute and long-term toxicities including odynophagia, dysphagia, dermatitis and fibrosis. The goal of this study is to assess the rate of regional failure with omission of radiation to the surgically dissected pathologically node negative (pN0) hemi-neck(s) compared to historical control, and to compare oncologic outcomes, toxicity, and quality of life (QoL) profiles between standard RT volumes and omission of RT to the pN0 neck. METHODS: This is a multicentre phase II study randomizing 90 patients with T1-4 N0-2 OCSCC with at least one pN0 hemi-neck in a 1:2 ratio between standard RT volumes and omission of RT to the pN0 hemi-neck(s). Patients will be stratified based on overall nodal status (nodal involvement vs. no nodal involvement) and use of concurrent chemotherapy. The primary endpoint is regional failure in the pN0 hemi-neck(s); we hypothesize that a 2-year regional recurrence of 20% or less will be achieved. Secondary endpoints include overall and progression-free survival, local recurrence, rate of salvage therapy, toxicity and QoL. DISCUSSION: This study will provide an assessment of omission of RT to the dissected pN0 hemi-neck(s) on oncologic outcomes, QoL and toxicity. Results will inform the design of future definitive phase III trials. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03997643 . Date of registration: June 25, 2019, Current version: 2.0 on July 11 2020.

Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial.

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.

Lessons learned in practice-based research: Studying language interventions for young children in the real world.

Background and aims: Practice-based research holds potential as a promising solution to closing the research-practice gap, because it addresses research questions based on problems that arise in clinical practice and tests whether systems and interventions are effective and sustainable in a clinical setting. One type of practice-based research involves capturing practice by collecting evidence within clinical settings to evaluate the effectiveness of current practices. Here, we describe our collaboration between researchers and clinicians that sought to answer clinician-driven questions about community-based language interventions for young children (Are our interventions effective? What predicts response to our interventions?) and to address questions about the characteristics, strengths, and challenges of engaging in practice-based research. Methods: We performed a retrospective chart review of 59 young children who had participated in three group language interventions at one publicly funded community clinic between 2012 and 2017. Change on the Focus on the Outcomes of Communication Under Six (FOCUS), a government mandated communicative participation measure, was extracted as the main outcome measure. Potential predictors of growth during intervention were also extracted from the charts, including type of intervention received, attendance, age at the start of intervention, functional communication ability pre-intervention, and time between pre- and post-intervention FOCUS scores. Results: Overall, 49% of children demonstrated meaningful clinical change on the FOCUS after their participation in the language groups. Only 3% of participants showed possibly meaningful clinical change, while the remaining 46% of participants demonstrated not likely meaningful clinical change. There were no significant predictors of communicative participation growth during intervention. Conclusions: Using a practice-based research approach aimed at capturing current practice, we were able to answer questions about the effectiveness of interventions delivered in real-world settings and learn about factors that do not appear to influence growth during these interventions. We also learned about benefits associated with engaging in practice-based research, including high clinical motivation, high external validity, and minimal time/cost investment. Challenges identified were helpful in informing our future efforts to examine other possible predictors through development of a new, clinically feasible checklist, and to pursue methods for improving collection of outcome data in the clinical setting.Implications: Clinicians and researchers can successfully collaborate to answer clinically informed research questions while considering realistic clinical practice and using research-informed methods and principles. Practice-based research partnerships between researchers and clinicians are both valuable and feasible.

Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial.

BACKGROUND: Transoral robotic surgery (TORS) with concurrent neck dissection has supplanted radiotherapy in the USA as the most common treatment for oropharyngeal squamous cell carcinoma (OPSCC), yet no randomised trials have compared these modalities. We aimed to evaluate differences in quality of life (QOL) 1 year after treatment. METHODS: The ORATOR trial was an investigator-initiated, multicentre, international, open-label, parallel-group, phase 2, randomised study. Patients were enrolled at six hospitals in Canada and Australia. We randomly assigned (1:1) patients aged 18 years or older, with Eastern Cooperative Oncology Group scores of 0-2, and with T1-T2, N0-2 (≤4 cm) OPSCC tumour types to radiotherapy (70 Gy, with chemotherapy if N1-2) or TORS plus neck dissection (with or without adjuvant chemoradiotherapy, based on pathology). Following stratification by p16 status, patients were randomly assigned using a computer-generated randomisation list with permuted blocks of four. The primary endpoint was swallowing-related QOL at 1 year as established using the MD Anderson Dysphagia Inventory (MDADI) score, powered to detect a 10-point improvement (a clinically meaningful change) in the TORS plus neck dissection group. All analyses were done by intention to treat. This study is registered with ClinicalTrials.gov (NCT01590355) and is active, but not currently recruiting. FINDINGS: 68 patients were randomly assigned (34 per group) between Aug 10, 2012, and June 9, 2017. Median follow-up was 25 months (IQR 20-33) for the radiotherapy group and 29 months (23-43) for the TORS plus neck dissection group. MDADI total scores at 1 year were mean 86·9 (SD 11·4) in the radiotherapy group versus 80·1 (13·0) in the TORS plus neck dissection group (p=0·042). There were more cases of neutropenia (six [18%] of 34 patients vs none of 34), hearing loss (13 [38%] vs five [15%]), and tinnitus (12 [35%] vs two [6%]) reported in the radiotherapy group than in the TORS plus neck dissection group, and more cases of trismus in the TORS plus neck dissection group (nine [26%] vs one [3%]). The most common adverse events in the radiotherapy group were dysphagia (n=6), hearing loss (n=6), and mucositis (n=4), all grade 3, and in the TORS plus neck dissection group, dysphagia (n=9, all grade 3) and there was one death caused by bleeding after TORS. INTERPRETATION: Patients treated with radiotherapy showed superior swallowing-related QOL scores 1 year after treatment, although the difference did not represent a clinically meaningful change. Toxicity patterns differed between the groups. Patients with OPSCC should be informed about both treatment options. FUNDING: Canadian Cancer Society Research Institute Grant (#701842), Ontario Institute for Cancer Research Clinician-Scientist research grant, and the Wolfe Surgical Research Professorship in the Biology of Head and Neck Cancers grant.

Routine follow-up care after curative treatment of head and neck cancer: A survey of patients' needs and preferences for healthcare services.

OBJECTIVE: The experience of a cancer diagnosis and receiving treatment can have profound impacts on health and subsequently patients may require significant support. Often, these needs are not identified or addressed. Given that less is known about the follow-up requirements for head and neck cancer patients, this study aimed to describe their follow-up needs and preferences. METHODS: In Ontario, Canada from 2012-2014, 175 patients completed a questionnaire at an appointment one year after treatment. To identify associations between characteristics and follow-up needs, bivariate analyses and ordinal logistic regression models were employed. RESULTS: A diversity of follow-up requirements was found. The most commonly reported follow-up needs were having imaging tests performed (66%), receiving information on treatment side effects (84%) and prognosis details (95%). Many patients experienced an improvement in their health (79%) but notably, not all. Characteristics such as psychosocial and well-being measures (functional status, anxiety, fear of recurrence, quality of life), attitudes towards follow-up (reassurance, communication), demographics (age, sex, marital status), and stage of disease predicted needs and preferences for follow-up care (p < 0.05). CONCLUSION: While awaiting top-level evidence, this work demonstrates the variation in needs and supports the identification of patients with higher follow-up requirements by screening for well-being and enquiring about expectations in follow-up care.

Predictors of plate extrusion in oromandibular free flap reconstruction.

OBJECTIVES: Plate extrusions after free tissue transfer for mandibular reconstruction can be problematic and generally require revision surgery. Our objective was to assess the predictors of plate extrusion and compare outcomes between fibular free flaps (FFF), lateral border scapular flaps (LBSF), and scapular tip free flaps (STFF). METHODS: Retrospective review of consecutive patients who underwent osseous free tissue reconstruction of the mandible (2008-2014) at Victoria Hospital, London, Ontario. Patient demographics and treatment-related information were collected. RESULTS: We identified 134 procedures and 27 (20.2%) plate extrusions (21/61 FFF, 3/49 STFF, and 3/24 LBSF). Freedom from extrusion after 2 years was significantly associated with the use of FFF (P = .003, HR 6.09 1.82-20.44), performing 1 osteotomy (P = .03, HR 2.61 1.08-6.31), and anterior mandibular defects (P = .01, HR 2.66 1.25-5.66) in the univariate model. FFF's were employed more frequently in younger patients, with 2.4 mm plates, more anterior defects, and with a greater number of osteotomies (P < .001). However, after controlling for these variables in multivariate analyses the use of a FFF was the only significant predictor of extrusion at 2 years (P = .006, HR 3.68 1.46-9.28). CONCLUSIONS: At our institution, use of the STFF predicts mandibular defects that are less prone to developing plate extrusion and FFF tended to be used more frequently in anterior defects with osteotomies. However, after controlling for these factors use of the FFF appeared to have higher rates of extrusion than scapular flaps. Further prospective studies controlling for defect variables are needed to elucidate the risk factors for plate extrusion.

Swallowing Preparation and Execution: Insights from a Delayed-Response Functional Magnetic Resonance Imaging (fMRI) Study.

The present study sought to elucidate the functional contributions of sub-regions of the swallowing neural network in swallowing preparation and swallowing motor execution. Seven healthy volunteers participated in a delayed-response, go, no-go functional magnetic resonance imaging study involving four semi-randomly ordered activation tasks: (i) "prepare to swallow," (ii) "voluntary saliva swallow," (iii) "do not prepare to swallow," and (iv) "do not swallow." Results indicated that brain activation was significantly greater during swallowing preparation, than during swallowing execution, within the rostral and intermediate anterior cingulate cortex bilaterally, premotor cortex (left > right hemisphere), pericentral cortex (left > right hemisphere), and within several subcortical nuclei including the bilateral thalamus, caudate, and putamen. In contrast, activation within the bilateral insula and the left dorsolateral pericentral cortex was significantly greater in relation to swallowing execution, compared with swallowing preparation. Still other regions, including a more inferior ventrolateral pericentral area, and adjoining Brodmann area 43 bilaterally, and the supplementary motor area, were activated in relation to both swallowing preparation and execution. These findings support the view that the preparation, and subsequent execution, of swallowing are mediated by a cascading pattern of activity within the sub-regions of the bilateral swallowing neural network.

Feasibility of Targeting PIK3CA Mutations in Head and Neck Squamous Cell Carcinoma.

PIK3CA is the only frequently-mutated, directly druggable oncogene in head and neck squamous cell carcinoma (HNSCC). However, it is unclear if a molecularly-driven intervention trial can be launched successfully, particularly within a single-institution setting secondary to the infrastructure necessary for mutation detection, mutation prevalence, and patient willingness to participate. This study aimed to evaluate 1) local frequency of PIK3CA activating mutations in HNSCC, 2) timeliness of our mutation-profiling clinical pathway, and 3) patients' willingness to enroll in a novel neoadjuvant drug trial. Tissue biopsies of 25 consecutive cases of HNSCC were tested for activating PIK3CA mutations at three mutational hotspots by real-time polymerase chain reaction. Mutations prevalence and number of working days accrued in determining PIK3CA mutational status were calculated. In addition, 30 HNSCC patients were surveyed prospectively regarding their willingness to participate in a hypothetical drug trial. Survey data were summarized descriptively. 4 of 25 (16 %) tumors harbored a PIK3CA activating mutation, including one at codon E542K, two at codon E545K/D, and one at codon H1047R. On average, this result was obtained in approximately 15 working days (range, 9-24 working days). The majority of patients surveyed (70 %) indicated their willingness to participate in a targeted PIK3CA trial. This study provides evidence that within a single institution, PIK3CA activating mutations can be detected with expected frequency, with sufficient timeliness and sufficient patient interest to mount a targeted intervention trial that may lead to improved tumor response in selected HNSCC patients.