Comprehensive peripheral blood immunoprofiling reveals five immunotypes with immunotherapy response characteristics in patients with cancer.

The lack of comprehensive diagnostics and consensus analytical models for evaluating the status of a patient's immune system has hindered a wider adoption of immunoprofiling for treatment monitoring and response prediction in cancer patients. To address this unmet need, we developed an immunoprofiling platform that uses multiparameter flow cytometry to characterize immune cell heterogeneity in the peripheral blood of healthy donors and patients with advanced cancers. Using unsupervised clustering, we identified five immunotypes with unique distributions of different cell types and gene expression profiles. An independent analysis of 17,800 open-source transcriptomes with the same approach corroborated these findings. Continuous immunotype-based signature scores were developed to correlate systemic immunity with patient responses to different cancer treatments, including immunotherapy, prognostically and predictively. Our approach and findings illustrate the potential utility of a simple blood test as a flexible tool for stratifying cancer patients into therapy response groups based on systemic immunoprofiling.

Modified Frailty Index Associates With Transoral Robotic Surgery Complications and Survival: A National Database Study.

OBJECTIVE: The modified frailty index (mFI-5) is a National Surgical Quality Improvement Program-derived 5-factor index that has been proven to reflect frailty and predict morbidity and mortality. We hypothesize that mFI-5 is a valid predictive measure in the transoral robotic surgery (TORS) population. METHODS: Retrospective study utilizing the TriNetX US-collaborative health records network querying for TORS patients. Cohorts were stratified by mFI-5 score which uses five ICD-10 codes: nonindependent functional status, hypertension, obstructive respiratory disease, heart failure, and diabetes mellitus. Cohorts were matched by age using propensity score matching. Outcome measures included survival, infection, pneumonia, tracheostomy dependence, and percutaneous endoscopic gastrostomy dependence. Reported odds ratios were normalized to mFI-5 = 0. RESULTS: A total of 9,081 patients were included in the final analysis. Greater mFI-5 scores predicted decreased survival and increased incidence of postoperative infection and pneumonia. Odds of 5-year mortality were 1.93 (p = 0.0003) for mFI-5 = 2 and 1.90 (p = 0.0002) for mFI-5 = 3. Odds of 2-year mortality were 1.25 (p = 0.0125) for mFI-5 = 1, 1.58 (p = 0.0002) for mFI-5 = 2, and 1.87 (p = 0.003) for mFI-5 = 3. Odds of postoperative infection were 1.51 (p = 0.02) for mFI-5 = 2 and 1.78 (p = 0.05) for mFI-5 = 3. Two-year odds of developing pneumonia were 1.69 (p = 0.0001) for mFI-5 = 2 and 2.84 (p < 0.0001) for mFI-5 = 3. Two-month odds of pneumonia were 1.50 (p = 0.0259) for mFI-5 = 2 and 2.55 (p = 0.0037) for mFI-5 = 3. mFI-5 = 4 or 5 had too few patients to analyze. Using polynomial regression to model age versus incident 5-year post-TORS death (R2 = 0.99), mFI-5 scores better predicted survival than age alone. CONCLUSION: This study demonstrates that mFI-5 predicts mortality, pneumonia, and postoperative infection independently of age. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

MiR-200c reprograms fibroblasts to recapitulate the phenotype of CAFs in breast cancer progression.

Mesenchymal-epithelial plasticity driving cancer progression in cancer-associated fibroblasts (CAFs) is undetermined. This work identifies a subgroup of CAFs in human breast cancer exhibiting mesenchymal-to-epithelial transition (MET) or epithelial-like profile with high miR-200c expression. MiR-200c overexpression in fibroblasts is sufficient to drive breast cancer aggressiveness. Oxidative stress in the tumor microenvironment induces miR-200c by DNA demethylation. Proteomics, RNA-seq and functional analyses reveal that miR-200c is a novel positive regulator of NFκB-HIF signaling via COMMD1 downregulation and stimulates pro-tumorigenic inflammation and glycolysis. Reprogramming fibroblasts toward MET via miR-200c reduces stemness and induces a senescent phenotype. This pro-tumorigenic profile in CAFs fosters carcinoma cell resistance to apoptosis, proliferation and immunosuppression, leading to primary tumor growth, metastases, and resistance to immuno-chemotherapy. Conversely, miR-200c inhibition in fibroblasts restrains tumor growth with abated oxidative stress and an anti-tumorigenic immune environment. This work determines the mechanisms by which MET in CAFs via miR-200c transcriptional enrichment with DNA demethylation triggered by oxidative stress promotes cancer progression. CAFs undergoing MET trans-differentiation and senescence coordinate heterotypic signaling that may be targeted as an anti-cancer strategy.

Effect of preoperative programmed death-1 or programmed death ligand-1 immune check point inhibition on complications after surgery for primary head and neck cancer.

BACKGROUND: There is sparse literature on the effect of preoperative immunotherapy on complications after surgery for primary head and neck squamous cell carcinoma (HNSCC). The objectives are to compare complication rates in patients receiving surgery with and without neoadjuvant immune checkpoint inhibitors (nICI) for primary HNSCC and to evaluate factors associated with increased odds of surgical complications. METHODS: A retrospective review of patients who underwent ablation and free flap reconstruction or transoral robotic surgery (TORS) for primary HNSCC between 2017-2021 was conducted. Complications were compared between patients who underwent surgery with or without nICI before and after propensity score matching. Regression analysis to estimate odds ratios was performed. RESULTS: A total of 463 patients met inclusion criteria. Free flap reconstruction constituted 28.9% of patients and TORS constituted 71.1% of patients. nICI was administered in 83 of 463 (17.9%) patients. There was no statistically significant difference in surgical, medical, or overall complications between patients receiving surgery with or without nICI. In the unmatched cohort, multivariable model identified non-White race, former/current smoking history, free flap surgery, and perineural invasion as factors significantly associated with increased complications. In the matched cohort, multivariable model identified advanced age and free flap surgery as factors significantly associated with increased complications. PLAIN LANGUAGE SUMMARY: It is safe to give immunotherapy before major surgery in patients who have head and neck cancer. Advanced age, non-White race, current/former smoking, free flap surgery, and perineural invasion may be associated with increased the odds of surgical complications.

Outcomes of Head and Neck Free Tissue Transfer in Renal Failure Patients.

OBJECTIVE: To assess if there is increased risk of free flap failure in renal failure patients undergoing head and neck reconstruction. We seek to primarily assess free flap outcomes based on stages of chronic kidney disease (CKD) and secondarily determine increased risk for postoperative complications. METHODS: Retrospective chart review was performed at five tertiary care centers. Patients were identified that had undergone microvascular free flap reconstruction of the head and neck with diagnosis of renal failure, classified as Stage 3 CKD or higher. Demographic data was collected. Outcomes in the postoperative period were examined. RESULTS: Seventy-three patients met inclusion criteria. The average patient age was 69 years with a male predominance (n = 48). The majority of patients had CKD Stage 3 (n = 52). Overall flap failure rate was 12.33% (n = 9, CKD stage 3 = 7.69%, CKD stage 4 = 30%, CKD stage 5 = 18%). There was an increased risk of flap failure on multivariate analysis for CKD stage 4/5 patients when compared to CKD 3 patients (p = 0.0095). When compared to matched controls, there was an increased risk of flap failure in CKD patients (p = 0.01) as well as an increased risk of overall complications (p < 0.0001). CONCLUSIONS: Patients with CKD undergoing head and neck reconstruction are at a higher risk of flap failure and overall complications. When comparing CKD stages there may be increased risk of flap failure in later stages of CKD compared to CKD 3. Appropriate patient counseling is recommended pre-operatively in this patient population with consideration for regional flaps in the appropriate patient. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:688-694, 2024.

IL-8 correlates with nonresponse to neoadjuvant nivolumab in HPV positive HNSCC via a potential extracellular vesicle miR-146a mediated mechanism.

Therapy using anti-PD-1 immune checkpoint inhibitors (ICI) has revolutionized the treatment of many cancers including head and neck squamous cell carcinomas (HNSCC), but only a fraction of patients respond. To better understand the molecular mechanisms driving resistance, we performed extensive analysis of plasma and tumor tissues before and after a 4-week neoadjuvant trial in which HNSCC patients were treated with the anti-PD-1 inhibitor, nivolumab. Luminex cytokine analysis of patient plasma demonstrated that HPVpos nonresponders displayed high levels of the proinflammatory chemokine, interleukin-8 (IL-8), which decreased after ICI treatment, but remained higher than responders. miRNAseq analysis of tetraspanin-enriched small extracellular vesicles (sEV) purified from plasma of HPVpos nonresponders demonstrated significantly lower levels of seven miRNAs that target IL-8 including miR-146a. Levels of the pro-survival oncoprotein Dsg2, which has been to down-regulate miR-146a, are elevated with HPVpos tumors displaying higher levels than HPVneg tumors. Dsg2 levels decrease significantly following ICI in responders but not in nonresponders. In cultured HPVpos cells, restoration of miR-146a by forced expression or treatment with miR-146a-loaded sEV, reduced IL-8 level, blocked cell cycle progression, and promoted cell death. These findings identify Dsg2, miR-146a, and IL-8 as potential biomarkers for ICI response and suggest that the Dsg2/miR-146a/IL-8 signaling axis negatively impacts ICI treatment outcomes and could be targeted to improve ICI responsiveness in HPVpos HNSCC patients.

A novel simulation module for segmental mandibulectomy and mandible reconstruction using 3D models.

INTRODUCTION: Mandibular resection and reconstruction are common but complex procedures in head and neck surgery. Resection with adequate margins is critical to the success of the procedure but technical training is restricted to real case experience. Here we describe our experience in the development and evaluation of a mandibular resection and reconstruction simulation module. METHODS: 3D printed (3DP) models of a mandible with a pathologic lesion were developed from imaging data from a patient with an ameloblastoma. During an educational conference, otolaryngology trainees participated in a simulation in which they reviewed a CT scan of the pathologic mandible and then planned their osteotomies before and after handling a 3DP model demonstrating the lesion. The adequacy of the osteotomy margins was assessed and components of the simulation were rated by participants with pre- and post-training surveys. RESULTS: 52 participants met criteria. After reviewing the CT scan, 34 participants (65.3 %) proposed osteotomies clear of the lesion. This proportion improved to 48 (92.3 %, p = 0.001) after handling the 3D model. Among those with initially adequate margins (n = 33), 45.5 % decreased their margins closer to the ideal, 27.2 % made no revision, 21.2 % widened their margins. 92 % of participants found the simulation beneficial for surgical planning and technical training. After the exercise, the majority of participants had increased confidence in conceptualizing the boundaries of the lesion (69.2 %) and their abilities to ablate (76.5 %). CONCLUSIONS: The structured mandibulectomy simulation using 3DP models was useful in the development of trainee experience in segmental mandible resection. LAY SUMMARY: This study presents the first mandibulectomy simulation module for trainees with the use of 3DP models. The use of a 3DP model was also shown to improve the quality of surgical training.

Differences in Functional and Survival Outcomes Between Patients Receiving Primary Surgery vs Chemoradiation Therapy for Treatment of T1-T2 Oropharyngeal Squamous Cell Carcinoma.

Importance: Due to lack of data from high-powered randomized clinical trials, the differences in functional and survival outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) undergoing primary transoral robotic surgery (TORS) vs primary radiation therapy and/or chemoradiation therapy (RT/CRT) are unclear. Objectives: To compare 5-year functional (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) and survivorship outcomes in patients with T1-T2 OPSCC receiving primary TORS vs RT/CRT. Design, Setting, and Population: This national multicenter cohort study used data from a global health network (TriNetX) to identify differences in functional and survival outcomes among patients with OPSCC who underwent primary TORS or RT/CRT in 2002 to 2022. After propensity matching, 726 patients with OPSCC met inclusion criteria. In the TORS group, 363 (50%) patients had undergone primary surgery, and in the RT/CRT group, 363 (50%) patients had received primary RT/CRT. Data analyses were performed from December 2022 to January 2023 using the TriNetX platform. Exposure: Primary surgery with TORS or primary treatment with radiation therapy and/or chemoradiation therapy. Main Outcomes and Measures: Propensity score matching was used to balance the 2 groups. Functional outcomes were measured at 6 months, 1 year, 3 years, 5 years, and more than 5 years posttreatment and included dysphagia, gastrostomy tube dependence, and tracheostomy dependence according to standard medical codes. Five-year overall survivorship was compared between patients undergoing primary TORS vs RT/CRT. Results: Propensity score matching allowed a study sample with 2 cohorts comprising statistically similar parameters with 363 (50%) patients in each. Patients in the TORS cohort had a mean (SD) age of 68.5 (9.9) vs 68.8 (9.7) years in RT/CRT cohort; 86% and 88% were White individuals, respectively; 79% of patients were men in both cohorts. Primary TORS was associated with clinically meaningful increased risk of dysphagia at 6 months (OR, 1.37; 95% CI, 1.01-1.84) and 1 year posttreatment (OR, 1.71; 95% CI, 1.22-2.39) compared with primary RT/CRT. Patients receiving surgery were less likely to be gastrostomy tube dependent at 6 months (OR, 0.46; 95% CI, 0.21-1.00) and 5 years posttreatment (risk difference, -0.05; 95% CI, -0.07 to -0.02). Differences in overall rates of tracheostomy dependence (OR, 0.97; 95% CI, 0.51-1.82) between groups were not clinically meaningful. Patients with OPSCC, unmatched for cancer stage or human papillomavirus status, who received RT/CRT had worse 5-year overall survival than those who underwent primary surgery (70.2% vs 58.4%; hazard ratio, 0.56; 95% CI, 0.40-0.79). Conclusions and Relevance: This national multicenter cohort study of patients undergoing primary TORS vs primary RT/CRT for T1-T2 OPSCC found that primary TORS was associated with a clinically meaningful increased risk of short-term dysphagia. Patients treated with primary RT/CRT had an increased risk of short- and long-term gastrostomy tube dependence and worse 5-year overall survival than those who underwent surgery.

Evaluating the impact of hemodynamic support measures on head and neck free tissue transfer outcomes: A population-based analysis.

OBJECTIVES: This study sought to analyze the effects of perioperative blood transfusions and vasopressors on 30-day surgical complications and 1-year mortality after reconstructive surgery in head and neck free tissue transfer (FTT) and to identify predictors of administration of perioperative blood transfusions or vasopressors. MATERIALS AND METHODS: TriNetX (TriNetX LLC, Cambridge, USA), an international population-level electronic health record database, was queried to identify subjects that underwent FTT requiring perioperative (intraoperative to postoperative day 7) vasopressors or blood transfusions. Primary dependent variables were 30-day surgical complications and 1-year mortality. Propensity score matching was used to control for population differences, and covariate analysis was used to identify preoperative comorbidities associated with perioperative vasopressor or transfusion requirements. RESULTS: 7,631 patients met inclusion criteria. Preoperative malnutrition was associated with increased odds of perioperative transfusion (p = 0.002) and vasopressor requirement (p < 0.001). Perioperative blood transfusion (n = 941) was associated with increased odds of any surgical complication (p = 0.041) within 30 days postoperatively and specifically increased odds of wound dehiscence (p = 0.008) and FTT failure (p = 0.002), respectively. Perioperative vasopressor was (n = 197) was not associated with 30-day surgical complications. Vasopressor requirement was associated with increased hazards-ratio of mortality at 1-year (p = 0.0031). CONCLUSION: Perioperative blood transfusion in FTT is associated with increased odds for surgical complications. Judicious use as a hemodynamic support measure should be considered. Perioperative vasopressor use was associated with an increased risk of one-year mortality. Malnutrition is a modifiable risk factor for perioperative transfusion and vasopressor requirement. These data warrant further investigation to assess causation and potential opportunity for practice improvement.

Improved Tumor Control Following Radiosensitization with Ultrasound-Sensitive Oxygen Microbubbles and Tumor Mitochondrial Respiration Inhibitors in a Preclinical Model of Head and Neck Cancer.

Tumor hypoxia (oxygen deficiency) is a major contributor to radiotherapy resistance. Ultrasound-sensitive microbubbles containing oxygen have been explored as a mechanism for overcoming tumor hypoxia locally prior to radiotherapy. Previously, our group demonstrated the ability to encapsulate and deliver a pharmacological inhibitor of tumor mitochondrial respiration (lonidamine (LND)), which resulted in ultrasound-sensitive microbubbles loaded with O2 and LND providing prolonged oxygenation relative to oxygenated microbubbles alone. This follow-up study aimed to evaluate the therapeutic response to radiation following the administration of oxygen microbubbles combined with tumor mitochondrial respiration inhibitors in a head and neck squamous cell carcinoma (HNSCC) tumor model. The influences of different radiation dose rates and treatment combinations were also explored. The results demonstrated that the co-delivery of O2 and LND successfully sensitized HNSCC tumors to radiation, and this was also enhanced with oral metformin, significantly slowing tumor growth relative to unsensitized controls (p < 0.01). Microbubble sensitization was also shown to improve overall animal survival. Importantly, effects were found to be radiation dose-rate-dependent, reflecting the transient nature of tumor oxygenation.

Variance in 3D anatomic localization of surgical margins based on conventional margin labeling in head and neck squamous cell carcinoma.

OBJECTIVE: In head and neck cancer (HNC), positive margins are strongly predictive of treatment failure. We sought to measure the accuracy of localization of margin sampling sites based on conventional anatomic labels using a digital 3D-model. METHODS: Preoperative CT scans for 9 patients with HNC treated operatively at our institution were imported into a multiplanar radiology software, which was used to render a digital 3D model of each tumor intended to represent the resection specimen. Surgical margin labels recorded during the operative case were collected from pathology records. Margin labels (N = 64) were presented to participating physicians.Participants were asked to mark the anatomic location of each surgical margin using the 3D-model and corresponding radiographic planes for reference.For each individual margin, the 3D coordinates of each participant's marker were used to calculate a mean localization point called the geometric centroid. Mean distance from individual markers to the centroid was compared between participantsand margin types. RESULTS: Amongst 7 surgeons, markers were placed a mean distance of 12.6 mm ([SD] = 7.5) from the centroid.Deep margins were marked with a greater mean distance than mucosal/skin margins (19.6 [24.8] mm vs. 15.3 [14.9] mm, p = 0.034). When asked to relocate a margin following re-resection, surgeons marked a point an average of 20.6 [12.4] mm from their first marker with a range of 3.9- 45.1 mm. CONCLUSIONS: Retrospective localization of conventionally labeled margins is an imprecise process with variability across the care team. Future interventions targeting margin documentation and communication may improve sampling precision.

Postoperative analysis of osseous midface reconstructions: The value of imaging and a novel scoring system for complexity and operative success.

BACKGROUND: Few standardized methods exist for evaluating the postoperative outcomes of osteocutaneous free flaps. We propose an anatomic-based scoring system for midface free flap reconstruction. METHODS: One hundred and twelve patients across four institutions underwent osteocutaneous reconstruction of the midface. Postoperative scans were scored based on the number of independent osseous subunits reconstructed (Subunit Score), the number of different bony appositions with bony contact (Contact Score), and the number of osseous segments in anatomic position (Position Score). These were added together to create a Total Score. RESULTS: Osteocutaneous radial forearm flaps had the lowest Subunit Score (p = 0.001). Fibula flaps had the highest Contact Score (p = 0.0008) and Position Score (p = 0.001). Virtual surgical planning was associated with an increased Subunit Score (p = 0.02) and Total Score (p = 0.04). CONCLUSIONS: We propose a novel scoring system for osseous midface reconstruction based on postoperative imaging scans. This can help guide management decisions and create a common language to compare outcomes.

Effects of Prior Tracheostomy on Total Laryngectomy Outcomes.

OBJECTIVE: To assess whether preoperative tracheostomy (PreOT) increases risk of complications after total laryngectomy (TL) and to determine if timing of tracheostomy creation is associated with an increased risk. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital between 2007 and 2020. METHODS: Inclusion criteria were patients who underwent primary or salvage TL for oncologic treatment. Dependent variables of interest included surgical complications, such as wound dehiscence, infection, hematoma, complete flap failure, fistula formation, and stoma stenosis, as well as medical complications. Categorical variables were compared with chi-square test or Fisher exact test, and continuous variables were compared with an independent t test. Multivariable regression was conducted to assess predictors of complications after laryngectomy. RESULTS: A total of 306 patients were included. Primary TL was performed in 161 (53%) patients and salvage in 145 (47%) patients. Of the patients undergoing primary laryngectomy, 105 (65%) received a PreOT. Of the patients undergoing salvage laryngectomy, 86 (59%) received a PreOT. In both primary and salvage cases, there was no association between PreOT and surgical or medical complications. Additionally, there was no significant association between timing of tracheostomy and surgical complications. On multivariable analysis, the presence of a PreOT was not associated with surgical complications. In salvage cases, those with a PreOT had a significantly longer average length of stay than those without a PreOT (12 vs 9 days, P = .008). CONCLUSION: PreOT in patients undergoing primary and salvage laryngectomies was not associated with surgical or medical complications postlaryngectomy. Timing of tracheostomy in relation to laryngectomy was not found to adversely affect clinical outcomes.

Nasopharyngectomy Without Maxillary Swing via a Combined Open Lateral and Endoscopic Approach.

Nasopharyngeal tumors in the proximity of the internal carotid artery are often difficult to dissect. Here, we describe a combined transcervical and endoscopic endonasal approach that provides improved internal carotid artery protection and confident tumor resection. Laryngoscope, 133:105-108, 2023.

Factors Impacting Discharge Destination Following Head and Neck Microvascular Reconstruction.

OBJECTIVE: Determine which variables impact postoperative discharge destination following head and neck microvascular free flap reconstruction. STUDY DESIGN: Retrospective review of prospectively collected databases. METHODS: Consecutive patients undergoing head and neck microvascular free flap reconstruction between January 2010 and December 2019 (n = 1972) were included. Preoperative, operative and postoperative variables were correlated with discharge destination (home, skilled nursing facility [SNF], rehabilitation facility, death). RESULTS: The mean age of patients discharged home was lower (60 SD ± 13, n = 1450) compared to those discharged to an SNF (68 SD ± 14, n = 168) or a rehabilitation facility (71 SD ± 14, n = 200; p < 0.0001). Operative duration greater than 10 h correlated with a higher percentage of patients being discharged to a rehabilitation or SNF (25% vs. 15%; p < 0.001). Patients were less likely to be discharged home if they had a known history of cardiac disease (71% vs. 82%; p < 0.0001). Patients were less likely to be discharged home if they experienced alcohol withdrawal (67% vs. 80%; p = 0.006), thromboembolism (59% vs. 80%; p = 0.001), a pulmonary complication (46% vs. 81%; p < 0.0001), a cardiac complication (46% vs. 80%; p < 0.0001), or a cerebral vascular event (25% vs. 80%; p < 0.0001). There was no correlation between discharge destination and occurrence of postoperative wound infection, salivary fistula, partial tissue necrosis or free flap failure. Thirty-day readmission rates were similar when stratified by discharge destination. CONCLUSION: There was no correlation with the anatomic site, free flap donor selection, or free flap survival and discharge destination. Patient age, operative duration and occurrence of a medical complication postoperatively did correlate with discharge destination. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:95-104, 2023.

Accrual-Monitoring Practices for Various Disease Trials among AACI Member Cancer Centers.

Progress in the management of rare diseases, including rare cancers, is dependent upon clinical trials; however, as many as 32% of rare-disease trials go uncompleted or unpublished due to insufficient accrual. Monitoring practices may differ between institutions. We sought to survey the regulatory standards for various trial types among major U.S. cancer centers. A 10-question survey was designed using Qualtrics assessment software. The survey was sent via email to an internal server of member institutions of the Association of American Cancer Institutes (AACI). Of 103 AACI centers, 31% completed the survey (n = 32). Respondents differed in their definitions of a rare disease, minimum expectations for rare tumor studies, and frequency of accrual monitoring by their institutional Protocol Review and Monitoring Committee. Seventy-three percent of respondents did not close trials based on low accrual. Strategies to optimize accrual included investigator incentives for high accrual and penalties for low accrual in 37% and 13% of respondents, respectively.

Recurrence of premalignant oral cavity and oropharynx lesions after pulsed diode laser treatment.

PURPOSE: Leukoplakia is common with a 1 % incidence in the population and may harbor preneoplastic changes. Diode lasers provide both precision and coagulation for excision of superficial lesions in clinical and operative settings with little damage to deeper tissue. We aim to determine the rate of oral and oropharyngeal hyperkeratosis and dysplasia recurrence after treatment with diode laser. MATERIALS AND METHODS: Patients with oral or oropharyngeal hyperkeratotic or mild dysplastic lesions treated with pulsed diode laser between 2013 and 2020 at a tertiary academic institution were analyzed. The main outcome measure was recurrence of hyperkeratosis and dysplasia after treatment. RESULTS: Fourteen patients received diode laser treatment for hyperkeratotic or mild dysplastic lesions of the oral cavity or oropharynx. Demographic features included 9 (64.3 %) females and mean age of 66.6 years. In these 14 patients, 18 distinct lesions were identified. Eleven (61.1 %) lesions were located on the oral tongue, 4 (22.2 %) on the buccal mucosa, 2 (11.1 %) on the hard palate, and 1 (5.6 %) on the soft palate. Average time from lesion clinical diagnosis to the first diode laser treatment was 8.3 months with an average number of 1.4 treatments per lesion. Three (16.7 %) lesions experienced recurrence after the most recent treatment. None of the lesions underwent malignant transformation. None of the patients experienced bleeding, tethering, or dysarthria after treatment. One patient developed pyogenic granuloma and reported chronic tongue pain. CONCLUSIONS: Pulsed diode laser treatment of leukoplakia was well tolerated with low complication rates and reasonable control of precancerous lesions.

Analysis of cost and outcomes in bony versus soft tissue midface free flap reconstruction.

BACKGROUND: Outcomes and cost of soft tissue versus bony midface free flap reconstruction (MR) with and without virtual surgical planning (VSP) were evaluated. METHODS: Retrospective review of MR including ischemic time (IT), operative duration (OD), length of stay (LOS), and total cost (TC). Eighty-one soft tissue and 76 bony MR (VSP = 23) were reviewed. RESULTS: Bony MR was used for higher complexity defects (p = 0.003) and was associated with higher IT (p < 0.001), OD (p < 0.001), LOS (p = 0.032), and TC (p < 0.001). VSP was associated with a mean 111.2 ± 37.9 minute reduction in OD (p = 0.004) compared to non-VSP bony flaps. VSP was associated with higher itemized cost, but no increase in TC (p = 0.327). CONCLUSIONS: Bony MR was used for higher complexity MR and was associated with increased TC, LOS, OD, and IT. VSP shortened OD with no significant increase in TC.

Occult Metastases During Salvage Oral Cavity and Oropharyngeal Free Flaps: Oncologic Outcomes.

OBJECTIVES: To define rates of occult metastases in salvage oral cavity and oropharyngeal cancer resection requiring free flap, to examine the location of occult metastases, and to determine associations between occult metastasis and survival. STUDY DESIGN: Retrospective cohort study. SETTING: Two tertiary care referral centers. METHODS: We identified previous cases of irradiation with recurrent or second primary oral cavity or oropharyngeal squamous cell carcinoma that had no evidence of regional metastasis and required free tissue transfer reconstruction of the primary site. Patients who underwent elective neck dissection or exploration were reviewed. The main outcome measures were the presence and location of occult nodal metastasis. Disease-free survival and overall survival were measured. Odds ratios and hazard ratios were used for analysis. RESULTS: A total of 83 patients were included: 52 with oral cavity primary tumors and 31 with oropharynx. An overall 78 (94%) underwent elective salvage neck dissection. Occult metastases were found in 9 (11.5%) patients. The most common nodal station for occult metastasis was level 2. Neither elective neck dissection nor the presence of occult metastasis was significantly associated with regional disease-free or overall survival. Oropharyngeal primary tumors were associated with higher risk of occult metastasis (odds ratio, 1.38; P < .01) and worse overall survival (hazard ratio, 2.09; P = .01). CONCLUSION: There is a low incidence of occult metastasis in postradiated recurrent or second primary oral cavity and oropharyngeal tumors. Elective neck dissection and occult nodal metastases were not associated with regional or overall survival. This series may help surgeons make decisions regarding the extent of neck surgery after prior radiation, especially when free flap reconstruction is required.