Cost-Effectiveness Analysis of PET-CT Surveillance After Treatment of Human Papillomavirus-Positive Oropharyngeal Cancer.

OBJECTIVE: To determine the cost-effectiveness of surveillance imaging with PET/CT scan among patients with human papillomavirus-positive oropharyngeal squamous cell carcinoma. STUDY DESIGN: Cost-effectiveness analysis. SETTING: Oncologic care centers in the United States with head and neck oncologic surgeons and physicians. METHODS: We compared the cost-effectiveness of 2 posttreatment surveillance strategies: clinical surveillance with the addition of PET/CT scan versus clinical surveillance alone in human papillomavirus-positive oropharyngeal squamous cell carcinoma patients. We constructed a Markov decision model which was analyzed from a third-party payer's perspective using 1-year Markov cycles and a 30-year time horizon. Values for transition probabilities, costs, health care utilities, and their studied ranges were derived from the literature. RESULTS: The incremental cost-effectiveness ratio for PET/CT with clinical surveillance versus clinical surveillance alone was $89,850 per quality-adjusted life year gained. Flexible fiberoptic scope exams during clinical surveillance would have to be over 51% sensitive or PET/CT scan cost would have to exceed $1678 for clinical surveillance alone to be more cost-effective. The willingness-to-pay threshold at which imaging surveillance was equally cost-effective to clinical surveillance was approximately $80,000/QALY. CONCLUSION: Despite lower recurrence rates of human papillomavirus-positive oropharyngeal cancer, a single PET/CT scan within 6 months after primary treatment remains a cost-effective tool for routine surveillance when its cost does not exceed $1678. The cost-effectiveness of this strategy is also dependent on the clinical surveillance sensitivity (flexible fiberoptic pharyngoscopy), and willingness-to-pay thresholds which vary by country.

Cost-effectiveness Analysis of Submandibular Gland Preservation With Sialendoscopy for the Management of Sialolithiasis.

OBJECTIVE: To compare the cost-effectiveness of sialendoscopy with gland excision for the management of submandibular gland sialolithiasis. STUDY DESIGN: Cost-effectiveness analysis. SETTING: Outpatient surgery centers. METHODS: A Markov decision model compared the cost-effectiveness of sialendoscopy versus gland excision for managing submandibular gland sialolithiasis. Surgical outcome probabilities were found in the primary literature. The quality of life of patients was represented by health utilities, and costs were estimated from a third-party payer's perspective. The effectiveness of each intervention was measured in quality-adjusted life-years (QALYs). The incremental costs and effectiveness of each intervention were compared, and a willingness-to-pay ratio of $150,000 per QALY was considered cost-effective. One-way, multivariate, and probabilistic sensitivity analyses were performed to challenge model conclusions. RESULTS: Over 10 years, sialendoscopy yielded 9.00 QALYs at an average cost of $8306, while gland excision produced 8.94 QALYs at an average cost of $6103. The ICER for sialendoscopy was $36,717 per QALY gained, making sialendoscopy cost-effective by our best estimates. The model was sensitive to the probability of success and the cost of sialendoscopy. Sialendoscopy must meet a probability-of-success threshold of 0.61 (61%) and cost ≤$11,996 to remain cost-effective. A Monte Carlo simulation revealed sialendoscopy to be cost-effective 60% of the time. CONCLUSION: Sialendoscopy appears to be a cost-effective management strategy for sialolithiasis of the submandibular gland when certain thresholds are maintained. Further studies elucidating the clinical factors that determine successful sialendoscopy may be aided by these thresholds as well as future comparisons of novel technology.

Targeted Wellness Initiatives Are Most Effective for Reducing Otolaryngology Resident Burnout.

OBJECTIVE: Investigate the effect of a targeted wellness program on burnout in Otolaryngology residents. METHODS: Residents and faculty collaboratively developed a program aimed at improving resident wellness. Program implementation began in July of 2018 and after 1 year, residents evaluated the program's effects on burnout. We used the Maslach Burnout Inventory (MBI) and a Likert scale to evaluate the effects of the program. RESULTS: After 1 year of the resident wellness program, the MBI results showed an increase in the number of residents in the "engaged" category and a decrease in those rated as "burnout." Residents rated favorably initiatives grouped into the following themes: time away from work, faculty engaging with residents outside of the hospital environment, efforts to enhance residents' self-efficacy, fostering a positive culture among residents, and providing easy access to physical activity. The majority of initiatives were targeted to the "culture of wellness" domain, as defined by the Stanford Well MD framework. Our program targeted to a lesser extent the other 2 domains, "efficiency of practice" and "personal resilience." CONCLUSION: After 1 year, the wellness program resulted in a trend toward improving burnout. Future efforts should be focused on targeting the multidimensional drivers of burnout as defined by established wellness frameworks. Realizing new stressors brought on by the COVID-19 pandemic will also be an area of active effort and research.

Reconstruction After Salvage Total Laryngectomy: A Cost-effectiveness Analysis.

OBJECTIVE: To determine the most cost-effective reconstruction method after salvage total laryngectomy. STUDY DESIGN: Cost-effectiveness analysis. SETTING: Tertiary care hospitals with head and neck oncologic and reconstructive surgeons. SUBJECTS AND METHODS: We constructed a Markov-based decision model to compare reconstruction by primary closure to pectoralis flap and free flap after salvage total laryngectomy. The model simulated disease with transition probabilities and health utilities found in primary literature and estimated the average overall cost of each reconstructive method using Medicare billing codes. Effectiveness was compared using quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were performed to scrutinize the conclusions of our model. Reconstruction methods were compared using incremental cost-effectiveness ratios (ICERs). In the United States, less than $150,000 per QALY gained is considered cost-effective (2019 US dollars). RESULTS: Our base case analysis revealed that primary closure was less expensive ($44,370) and yielded more QALYs (0.91) than both pectoralis ($45,163, 0.81 QALYs) and free flap ($46,244, 0.85 QALYs), making it the most cost-effective option. Between flaps, free flap was cost-effective over pectoralis flap (ICER = $27,025/QALY gained). Sensitivity analyses showed primary closure as cost-effective 69% of the time over either flap. These conclusions were sensitive to the health utilities (quality of life) of each method of reconstruction. CONCLUSION: Tissue flaps to augment closure after salvage total laryngectomy are not always the most cost-effective reconstructive option. The long-term morbidity of flap surgery oftentimes outweighs the benefit of lowering fistula rates after surgery. Careful consideration must be taken when advising patients of their reconstructive options.

Enhanced Recovery After Surgery-Based Perioperative Protocol for Head and Neck Free Flap Reconstruction.

OBJECTIVES: Evaluate an enhanced recovery after surgery (ERAS)-based free flap management protocol implemented at our center. STUDY DESIGN: Prospective cohort study of patients after implementation of an ERAS-based perioperative care protocol for patients undergoing free flap reconstruction of the head and neck as compared with a historical control group. SETTING: Tertiary care academic medical center. PARTICIPANTS AND METHODS: All patients undergoing free flap reconstruction were prospectively enrolled in the ERAS protocol group. A retrospective control group was identified by randomly selecting an equivalent number of patients from a records search of those undergoing free flap surgery between 2009 and 2015. Blood transfusion, complications, 30-day readmission rates, intensive care unit (ICU) and hospital length of stay, and costs of hospitalization were compared. RESULTS: Sixty-one patients were included in each group. Patients in the ERAS group underwent less frequent flap monitoring by physicians and had lower rates of intraoperative (70.5% vs 86.8%, P = .04) and postoperative (49.2% vs 27.2%, P = .026) blood transfusion, were more likely to be off vasopressors (98.3% vs 50.8%, P < .01) and ventilator support (63.9% vs 9.8%, P < .01) at the conclusion of surgery, and had shorter ICU stays (2.11 vs 3.39 days, P = .017). Length of stay, readmissions, and complication rates did not significantly differ between groups. CONCLUSION: ERAS-based perioperative practices for head and neck free flap reconstruction can reduce time on the ventilator and in the ICU and the need for vasopressors, blood transfusions, and labor-intensive flap monitoring, without adverse effects on outcomes.

Quantifying the use of opioids in the immediate postoperative period after endoscopic sinus surgery.

OBJECTIVES/HYPOTHESIS: The opioid crisis is a public health emergency. There is limited evidence regarding how much opioid medication is necessary and which patients will require additional pain medication following endoscopic sinus surgery (ESS). The objective of this study was to quantify the use of opioids in the first 24 hours following ESS and determine the risk factors associated with increased need for opioid analgesia. STUDY DESIGN: Retrospective chart review. METHODS: A review of opioid-naïve patients routinely admitted to the hospital following ESS between June 2016 and August 2018 was performed. Opioid consumption was quantified for each patient and converted to a morphine milligram equivalents (MME) dose. Pain intensity scores were also recorded throughout the postoperative period. Sociodemographic characteristics as well as surgical procedures performed were evaluated for impact on MME. RESULTS: A total of 130 patients (45.4% female) were included for analysis. The mean opioid dose consumed per patient in the first 24 hours following ESS was 24.1 MME, and the mean pain intensity was 2.4/10. Increasing pain scores were strongly associated with increasing MME (R = 0.78, P < .001). Multiple linear regression identified that patients taking antidepressants required an additional 17.2 MME (95% confidence interval [CI]: 5.5-28.9, P = .004) in the first 24 hours following ESS, whereas patients undergoing papilloma resection required an additional 16.9 MME (95% CI: 2.5-31.4, P = .022). CONCLUSIONS: Patients undergoing ESS require different amounts of opioids for pain control in the immediate postoperative period. A history of antidepressant use and inverted papilloma resection during ESS were associated with increased opioid consumption postoperatively. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1122-1127, 2020.

Visualization of macrophage recruitment in head and neck carcinoma model using fluorine-19 magnetic resonance imaging.

PURPOSE: To evaluate the role of infiltrating macrophages in murine models of single and double mutation head and neck tumors using a novel fluorine-19 (19 F) MRI technology. METHODS: Tumor cell lines single-hit/SCC4 or double-hit/Cal27, with mutations of TP53 and TP53 & FHIT, respectively, were injected bilaterally into the flanks of (n = 10) female mice. With tumors established, perfluorocarbon nanoemulsion was injected intravenously, which labels in situ predominantly monocytes and macrophages. Longitudinal spin density-weighted 19 F MRI data enabled quantification of the macrophage burden in tumor and surrounding tissue. RESULTS: The average number of 19 F atoms within the tumors was twice as high in the Cal27 group compared with SCC4 (3.9 × 1019 and 2.0 × 101919 F/tumor, respectively; P = 0.0034) two days after contrast injection, signifying increased tumor-associated macrophages in double-hit tumors. The difference was still significant 10 days after injection. Histology stains correlated with in vivo results, exhibiting numerous perfluorocarbon-labeled macrophages in double-hit tumors and to a lesser extent in single-hit tumors. CONCLUSIONS: This study helps to establish 19 F MRI as a method for quantifying immune cells in the tumor microenvironment, allowing distinction between double and single-hit head and neck tumors. This technique would be extremely valuable in the clinic for pretreatment planning, prognostics, and post-treatment surveillance. Magn Reson Med 79:1972-1980, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Early detection of squamous cell carcinoma in carcinogen induced oral cancer rodent model by ratiometric activatable cell penetrating peptides.

OBJECTIVES: Ratiometric cell-penetrating-peptides (RACPP) are hairpin-shaped molecules that undergo cleavage by tumor-associated proteases resulting in measurable Cy5:Cy7 fluorescence ratiometric change to label cancer in vivo. We evaluated an MMP cleavable RACPP for use in the early detection of malignant lesions in a carcinogen-induced rodent tumor model. METHODS: Wild-type immune-competent mice were given 4-nitroquinoline-oxide (4NQO) for 16weeks. Oral cavities from live mice that had been intravenously administered MMP cleavable PLGC(Me)AG-RACPP were serially imaged from week 11 through week 21 using white-light reflectance and Cy5:Cy7 ratiometric fluorescence. RESULTS: In an initial study we found that at week 21 nearly all mice (13/14) had oral cavity lesions, of which 90% were high-grade dysplasia or invasive carcinoma. These high-grade lesions were identifiable with white light reflectance and RACPP Cy5:Cy7 ratiometric fluorescence with similar detectability, Area Under Curve (AUC) for RACPP detection was 0.97 (95% Confidence interval (CI)=0.92-1.02, p<0.001), sensitivity=89%, specificity=100%. In a follow up study, oral cavity lesions generated by 4NQO were imaged and histologically analyzed at weeks 16, 18 and 21. In this study we showed that RACPP-fluorescence detection positively identified 15 squamous cell carcinomas (in 6 separate mice) that were poorly visible or undetectable by white light reflectance. CONCLUSIONS: RACPP ratiometric fluorescence can be used to accurately detect carcinogen-induced carcinoma in immunocompetent mice that are poorly visible or undetectable by white light reflectance.

Short-term morbidity after the endoscopic modified Lothrop (Draf-III) procedure compared with Draf-IIa.

BACKGROUND: The endoscopic modified Lothrop (Draf-III) surgery has improved treatment of recalcitrant frontal sinus disease, with favorable safety and long-term results. However, the short-term clinical and quality-of-life morbidity after Draf-III relative to less-extensive procedures has yet to be investigated. OBJECTIVE: To evaluate the surgical and quality-of-life outcomes, including the burden of follow-up care, in patients who underwent endoscopic modified Lothrop (Draf-III), and compared these results with a less-extensive intervention, the endoscopic frontal sinusotomy (Draf-IIa). METHODS: A retrospective review of early (<8 weeks) postoperative recovery of patients who underwent Draf-III (2014 to 2016) for chronic rhinosinusitis was conducted and compared with age and radiographically matched Draf-IIa controls. Primary outcomes included perioperative complications, the number of postoperative clinic visits, debridements, and steroid and antibiotic therapy days. Secondary outcomes included the change in the 22-item Sino-Nasal Outcome Test (SNOT-22) scores and/or subscores (domains). RESULTS: Thirty-eight patients (19 Draf-III, 19 Draf-IIa) were included. Patients who underwent Draf-III versus Draf-IIa required more postoperative clinic visits (4.9 ± 1.7 versus 3.3 ± 0.8; p < 0.05), debridements (4.2 ± 2.0 versus 2.3 ± 0.8; p < 0.05), and antibiotic therapy days (24.4 ± 11.8 versus 15.6 ± 6.3; p < 0.05). The mean (SD) SNOT-22 scores improved for both groups (-12.7 ± 34.5 versus -9.5 ± 20.4; p = 0.74) over the follow-up period, and subscore (domain) analysis demonstrated worsening extranasal symptoms (2.5 ± 3.0 versus -1.5 ± 4.7; p < 0.05) at the first postoperative visit, and less improvement in ear/facial symptoms at the second (-0.5 ± 2.6 versus -3.9 ± 4.7; p = 0.03) and third postoperative visits (-1.1 ± 1.6 versus 3.5 ± 3.3; p = 0.01). CONCLUSION: Draf-III is associated with more postoperative clinic visits, debridements, and antibiotic therapy days. The patients who underwent Draf-III demonstrated worsening of extranasal symptoms at the first postoperative visit and less improvement in the ear/facial score at the second and third visits. Informed consent and counseling patients who may require Draf-III should include a detailed discussion of the burden of postoperative care and recovery.

Cost-Effectiveness Analysis of Elective Neck Dissection in Patients With Clinically Node-Negative Oral Cavity Cancer.

Purpose Recently, a large randomized trial found a survival advantage among patients who received elective neck dissection in conjunction with primary surgery for clinically node-negative oral cavity cancer compared with those receiving primary surgery alone. However, elective neck dissection comes with greater upfront cost and patient morbidity. We present a cost-effectiveness analysis of elective neck dissection for the initial surgical management of early-stage oral cavity cancer. Methods We constructed a Markov model to simulate primary, adjuvant, and salvage therapy; disease recurrence; and survival in patients with T1/T2 clinically node-negative oral cavity squamous cell carcinoma. Transition probabilities were derived from clinical trial data; costs (in 2015 US dollars) and health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollar per quality-adjusted life-year (QALY), were calculated with incremental cost-effectiveness ratios less than $100,000/QALY considered cost effective. We conducted one-way and probabilistic sensitivity analyses to examine model uncertainty. Results Our base-case model found that over a lifetime the addition of elective neck dissection to primary surgery reduced overall costs by $6,000 and improved effectiveness by 0.42 QALYs compared with primary surgery alone. The decrease in overall cost despite the added neck dissection was a result of less use of salvage therapy. On one-way sensitivity analysis, the model was most sensitive to assumptions about disease recurrence, survival, and the health utility reduction from a neck dissection. Probabilistic sensitivity analysis found that treatment with elective neck dissection was cost effective 76% of the time at a willingness-to-pay threshold of $100,000/QALY. Conclusion Our study found that the addition of elective neck dissection reduces costs and improves health outcomes, making this a cost-effective treatment strategy for patients with early-stage oral cavity cancer.