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.

Tumor molecular differences associated with outcome disparities of Black patients with head and neck cancer.

BACKGROUND: Numerous studies of head and neck squamous cell carcinoma (HNSCC) have demonstrated disparate outcomes by race and ethnicity. Beyond known associations with socioeconomic variables, whether these are also associated with differences in tumor molecular composition has thus far been poorly explored. METHODS: We downloaded clinical and multiplatform molecular data from The Cancer Genome Atlas and other published studies. These were compared between non-Hispanic Black (n = 43) and White (n = 354) patients with non-HPV-related tumors, using multivariable models. Publicly available validation cohorts were used. RESULTS: Black patients had poorer progression-free survival than White patients. Tumors of Black patients had greater copy number aberrations, and increased SFRP1 methylation and miRNA-mediated PRG4 silencing associated with poor survival. PI3K/AkT/mTOR pathway proteins were differentially expressed. CONCLUSIONS: There are molecular differences between tumors of Black and White patients that may partially account for differences in survival. These may inform targeted treatment decisions to achieve equitable outcomes.

Assessment of shoulder function following scapular free flap.

BACKGROUND: The scapular system free flap has been increasing in popularity to reconstruct short segment mandibular bony defects. It is important to assess donor site morbidities systematically. METHODS: Prospective cohort study using objective measures of range of motion (ROM) and shoulder strength were measured. Subjective disability was evaluated with validated questionnaires-Neck Disability Impairment Index and Shoulder Pain and Disability Index. RESULTS: Twenty-six patients were recruited-19 with scapular tip and 7 with lateral border scapular free flap. Decreased ROM on the operated side was noted for shoulder abduction, shoulder flexion, and external rotation. No significant difference was noted for shoulder extension. Strength was reduced for shoulder flexion, shoulder abduction, and external rotation. Subjective measurements did not indicate significant shoulder function disruption. CONCLUSION: Patients with scapular free flap reconstruction did not experience significant shoulder morbidity. Measures of shoulder ROM and power were objectively affected; however, subjective measures of shoulder disability were not significantly affected.

Medialization thyroplasty versus injection laryngoplasty: a cost minimization analysis.

BACKGROUND: Medialization thyroplasty and injection laryngoplasty are widely accepted treatment options for unilateral vocal fold paralysis. Although both procedures result in similar clinical outcomes, little is known about the corresponding medical care costs. Medialization thyroplasty requires expensive operating room resources while injection laryngoplasty utilizes outpatient resources but may require repeated procedures. The purpose of this study, therefore, is to quantify the cost differences in adult patients with unilateral vocal fold paralysis undergoing medialization thyroplasty versus injection laryngoplasty. STUDY DESIGN: Cost minimization analysis conducted using a decision tree model. METHODS: A decision tree model was constructed to capture clinical scenarios for medialization thyroplasty and injection laryngoplasty. Probabilities for various events were obtained from a retrospective cohort from the London Health Sciences Centre, Canada. Costs were derived from the published literature and the London Health Science Centre. All costs were reported in 2014 Canadian dollars. Time horizon was 5 years. The study was conducted from an academic hospital perspective in Canada. Various sensitivity analyses were conducted to assess differences in procedure-specific costs and probabilities of key events. RESULTS: Sixty-three patients underwent medialization thyroplasty and 41 underwent injection laryngoplasty. Cost of medialization thyroplasty was C$2499.10 per patient whereas those treated with injection laryngoplasty cost C$943.19. Results showed that cost savings with IL were C$1555.91. Deterministic and probabilistic sensitivity analyses suggested cost savings ranged from C$596 to C$3626. CONCLUSIONS: Treatment with injection laryngoplasty results in cost savings of C$1555.91 per patient. Our extensive sensitivity analyses suggest that switching from medialization thyroplasty to injection laryngoplasty will lead to a minimum cost savings of C$596 per patient. Considering the significant cost savings and similar effectiveness, injection laryngoplasty should be strongly considered as a preferred treatment option for patients diagnosed with unilateral vocal fold paralysis.

Development of a transoral robotic surgery program in Canada.

Due to significant differences in healthcare structure between the United States and Canada, there are unique barriers to adopting new medical technology in Canada. In this article, we describe our experience developing a transoral robotic surgery (TORS) program at Western University. Specifically, we outline the steps that were necessary to obtain institutional and multidisciplinary team approval, financial support, as well as surgeon and allied healthcare personnel training. This experience can potentially be used as a roadmap for other Canadian institutions pursuing a TORS program.

Type I thyroplasty: risk stratification approach to inpatient versus outpatient postoperative management.

BACKGROUND: type I thyroplasty is an effective and safe procedure for unilateral vocal fold paralysis and is shifting toward outpatient postoperative care. However, serious airway complications have been reported. OBJECTIVES: the aims of this study were to investigate whether risk stratification into inpatient/outpatient postoperative care reduces outpatient airway complications and to compare the cost-effectiveness and surgical outcomes of risk stratification to a historical inpatient control group (non-risk stratified). SETTING: tertiary, university-based medical centre. DESIGN AND RESULTS: Three retrospective groups were examined: historical inpatient control (n = 15), risk-stratified (RS)- inpatient (n = 16), and RS outpatient (n = 17). Laryngeal edema was encountered in two historical controls (13.3%), two RS inpatients (12.5%), and one RS outpatient (5.9%). One case of implant extrusion occurred in the RS outpatient group. There was no difference in maximum phonation time or voice-related quality of life between RS versus historical controls (p > .5). The cost savings of risk stratification versus entirely inpatient care was $CAD 633.12/patient. The average duration in hospital for RS inpatient versus RS outpatient was 29.8 and 8.3 hours, respectively. CONCLUSIONS: postoperative RS may reduce potentially serious outpatient airway complications and cost while improving patient satisfaction.

Development of a new visual analogue scale for the assessment of area scars.

OBJECTIVE: Clinical scar assessment lacks standardized methodology and consensus on the most appropriate evaluation instrument. This study empirically evaluated whether area scars could be validly assessed by naive observers with the objective to develop and validate a novel multidimensional visual analogue scale (VAS) for the assessment of area scars. METHODS: Standardized digital photographs of radial forearm free flap (RFFF) donor sites were obtained. Naive observers evaluated the images in three sequential psychophysical experiments, which led to the development of the new scar scale. These experiments involved initial evaluation of four dimensions (pigmentation, vascularity, observer comfort, acceptability) using a paired comparison (PC) paradigm and correlation with ratings of overall severity using a VAS, and initial VAS test phase followed by formal debriefing, and, subsequently, evaluation of a VAS for the four dimensions in addition to contour. Validation involved determination of intra- and interrater reliability and correlational analysis. RESULTS: Across all three experiments, 56 observers evaluated 101 images, generating 12 720 observations for analysis. PC data demonstrated that observers could assess scars with high reliability and internal consistency for all dimensions (> 95%). Overall (VAS) severity correlated highly with all dimensions, including contour. The new VAS yielded high levels of correlation (r = .72-.98, p < .01). CONCLUSION: Comprehensive VAS analysis demonstrates high reliability in mirroring PC results for multiple dimensions of area scars. These data support our novel multidimensional VAS method as a valid, reliable, simple, and time-efficient instrument for clinical and research use. We introduce the Western Scar Index as a new measurement tool with many potential applications.

A prospective randomized evaluation of scar assessment measures.

OBJECTIVES/HYPOTHESIS: To determine the efficacy of interventions to improve and monitor skin scarring, a valid assessment instrument must be used. Current tools used for the evaluation of skin scarring employ equal appearing interval (EAI) scales that assume scar dimensions conform to linear models. Some scar features meet these assumptions, whereas others may not be accurately described. This study determined if current methods of scar evaluation validly characterize inherent features of scars, and in doing so, empirically validate if specific scar dimensions were best represented by linear or nonlinear mathematical models. STUDY DESIGN: Prospective, randomized, cross-over trial. METHODS: Twenty-seven observers evaluated 30 scar photos utilizing both EAI and direct magnitude estimation (DME) scaling methods. The method of scaling and the assessed dimensions of vascularity, pigmentation, thickness, pliability, and surface area were randomized. EAI and DME data were evaluated to identify whether each scar dimension conformed to linear or curvilinear mathematical models. RESULTS: Best-fit analysis revealed the dimensions of vascularity and pigmentation to be more accurately described using curvilinear functions, whereas pliability, thickness and surface area were best defined using linear models. CONCLUSIONS: The scar dimension under assessment must be considered when attempting to validly apply an assessment instrument. Several commonly evaluated dimensions of skin scarring are not appropriately characterized using linear EAI scales. Thus, present assessment instruments must be revised to account for this aberration to allow for a valid means of objectively evaluating skin scarring.

Needs assessment of undergraduate education in otolaryngology among family medicine residents.

OBJECTIVES: To investigate the adequacy of otolaryngology teaching in undergraduate medical education (UME) and to determine the general level of comfort of family medicine residents in managing and assessing diseases affecting the ears, nose, and throat. DESIGN: Cross-sectional survey. METHODS: A sample of family medicine residents at the University of Western Ontario (N = 68) completed a questionnaire inquiring into their exposure to topics in otolaryngology during their UME. They were also asked to comment on their present comfort with knowledge and skills specific to otolaryngology. RESULTS: Family medicine residents suggest that there is generally little otolaryngology training in UME; 66.7% of respondents who received UME in Canada suggested that they received very little classroom instruction and 75.6% received very little clinical otolaryngology instruction. Residents identified specific otolaryngologic conditions with which they felt particularly uncomfortable. CONCLUSIONS: This study demonstrated that students receive very little exposure to otolaryngology in UME and highlighted specific conditions and procedures that family medicine residents lack confidence in managing and performing.

Agitated colloid is superior to saline and equivalent to levovist in enhancing tricuspid regurgitation Doppler envelope and in the opacification of right heart chambers: a quantitative, qualitative, and cost-effectiveness study.

BACKGROUND: Doppler spectrum of tricuspid regurgitation (TR) is used to noninvasively assess right ventricular (RV) pressure. With mild TR, the native (Nat) TR envelope may not allow accurate pressure evaluation. Proprietary contrast agents, such as Levovist (Lev) can be used to augment TR Doppler and opacify right-sided heart chambers, but they are expensive, and their efficacy has not been objectively evaluated in patients with difficult baseline studies or compared with less expensive saline (Sal) or colloid solutions, such as Gelofusine (Gel). METHODS: Twenty-five consecutive patients with poor quality Nat TR envelopes on transthoracic echocardiogram were reexamined after serial intravenous injection of 3 contrast agents (Sal, Gel, and Lev). Doppler signals for each agent recorded on video and digitally on optical disk were assessed for signal quality, estimated RV pressure, interobserver and intraobserver variation, and longevity of signal. Quality of right ventricular-right atrial (RV-RA) opacification was also determined for Sal and Gel. Of the 25 patients, 9 underwent percutaneous right-sided heart catheterization. We used the pressures obtained from the catheterization to independently evaluate the pressure estimates from echocardiography. RESULTS: All 3 contrast agents significantly improved the mean quality grade (grades 0-5) of TR envelopes (Nat 1.12, Sal 1.97, Gel 2.56, Lev 2.41, P <.001), decreased the number of uninterpretable envelopes (grade 0) (Nat 49%, Sal 12%, Gel 4%, Lev 12%, P <.0001 for comparison of each agent relative to Nat), and improved the correlation between echocardiographic and catheter-derived RV-RA pressure measurements (Nat r = 0.65, Sal r = 0.75, Gel r = 0.90, Lev r = 0.88). The persistence of enhanced Doppler signals of interpretable quality (> grade 1) was greater for Lev (15.8 seconds) and Gel (15 seconds) than Sal (7.6 seconds) (P =.002). Opacification of RV and RA, measured as mean luminosity score during 2-dimensional harmonic imaging, was significantly higher for Gel than Sal (92.84 +/- 31.2 vs 56.06 +/- 25.6, respectively; P =.0003). Sal, Gel and Lev, respectively, cost $0.10, $2.50, and $75.00 per study. CONCLUSION: Agitated colloid is a novel, effective, and inexpensive alternative to proprietary agents and saline for the assessment of pulmonary systolic pressure and right-sided heart opacification.