The Effect of Rapeseed Oil Biopolyols and Cellulose Biofillers on Selected Properties of Viscoelastic Polyurethane Foams.

This paper presents the results of research on polyurethane viscoelastic foams (PUVFs) modified with biomaterials. This investigation looked at the effect of the biomaterials on the foaming processes, as well as the acoustical and selected physical-mechanical properties of the foams. Various types of rapeseed oil biopolyols and microcellulose were used to modify the materials. The analysis of properties covered a reference biopolyol-free sample and materials containing 10 wt.%, 20 wt.%, and 30 wt.% of different types of biopolyols in the mixture of polyol components. The biopolyols differed in terms of functionality and hydroxyl value (OHv). Next, a selected formulation was modified with various microcellulose biofillers in the amount of 0.5-2 wt.%. The PUVFs, with apparent densities of more than 210 kg/m3 and open-cell structures (more than 85% of open cells), showed a slow recovery to their original shape after deformation when the pressure force was removed. They were also characterized by a tensile strength in the range of 156-264 kPa, elongation at break of 310-510%, hardness of 8.1-23.1 kPa, and a high comfort factor of 3.1-7.1. The introduction of biopolyols into the polyurethane system resulted in changes in sound intensity levels of up to 31.45%, while the addition of fillers resulted in changes in sound intensity levels of up to 13.81%.

Performance Characteristics of Incisional and Core Needle Biopsies for Diagnosis in Parotid Gland: Single-Institutional Experience and Assessment of the Value of a Milan System for Reporting Salivary Gland Cytopathology-Like Risk Stratification Model.

CONTEXT.­: Unlike parotid fine-needle aspiration biopsy, standardized reporting for core needle biopsy (CNB) and incisional biopsy (IB) is not established. OBJECTIVE.­: To examine the value of risk stratification by a Milan System for Reporting Salivary Gland Cytopathology (MSRSGC)-like classifier for parotid CNB/IB. DESIGN.­: Five hundred ninety-two parotid biopsy records (CNB = 356, IB = 236) were retrieved (1994-2022) along with clinicopathologic data. Diagnoses were transformed to an MSRSGC-like classifier and compared with end points including risk of malignancy. RESULTS.­: Over time, CNB was progressively more used compared with IB. Overall malignancy call rate was 223 of 592 (37.7%). Common specific diagnoses included Warthin tumor, lymphoma subtypes, and metastatic squamous cell carcinoma for CNB and IB, in addition to pleomorphic adenoma for CNB. Descriptive diagnoses were still frequent. Nondiagnostic rates were higher in CNB (26 of 356; 7.30%) than IB (5 of 236; 2.12%; P <.001). Tissue volumes significantly influenced CNB adequacy, with minimum and optimal volumes of 4.76 mm³ (J index, receiver operating characteristic curve) and 12.92 mm³ (95th percentile of distribution), respectively. One hundred forty-four patients (112 CNBs) had follow-up resections; diagnoses were concordant for 66 of 73 adequate CNBs (90.41%). Our restructured risk grouping of MSRSGC categories performed robustly in terms of risk of malignancy (sensitivity = 85.5%, specificity = 100%, accuracy = 92.3%, area under the curve = 0.9677). CONCLUSIONS.­: Although CNB and IB are amenable to a risk stratification system, there are some differences as compared with fine-needle aspiration biopsy, particularly given the high baseline prevalence of malignancy. Specific diagnoses are often feasible and concordant with resection. CNB tissue volume can inform optimal and minimal sampling recommendations for adequacy.

Long-term outcomes in virtual surgical planning for mandibular reconstruction: A cost-effectiveness analysis.

OBJECTIVE: This study is an economic evaluation comparing virtual surgical planning (VSP) utilization to free hand mandibular reconstruction (FHR) for advanced oral cavity cancer, for which the cost effectiveness remains poorly understood. The proposed clinical benefits of VSP must be weighed against the additional upfront costs. METHODS: A Markov decision analysis model was created for VSP and FHR based on literature review and institutional data over a 35-year time horizon. Model parameters were derived and averaged from systematic review and institutional experience. VSP cost and surgical time saving was incorporated. We accounted for long-term risks including cancer recurrence and hardware failure/exposure. We calculated cost in US dollars and effectiveness in quality-adjusted-life-years (QALYs). A health care perspective was adopted, discounting costs and effectiveness at 3%/year. Deterministic and probabilistic sensitivity analyses tested model robustness. RESULTS: In the base case scenario, total VSP strategy cost was $49,498 with 8.37 QALYs gained while FHR cost was $42,478 with 8.27 QALY gained. An incremental cost-effectiveness ratio (ICER), or the difference in cost/difference in effectiveness, for VSP was calculated at $68,382/QALY gained. VSP strategy favorability was sensitive to variations of patient age at diagnosis and institutional VSP cost with one-way sensitivity analysis. VSP was less economically favorable for patients >75.5 years of age or for institutional VSP costs >$10,745. In a probabilistic sensitivity analysis, 55% of iterations demonstrated an ICER value below a $100,000/QALY threshold. CONCLUSIONS/RELEVANCE: VSP is economically favorable compared to FHR in patients requiring mandibular reconstruction for advanced oral cancer, but these results are sensitive to the patient's age at diagnosis and the institutional VSP cost. Our results do not suggest if one "should or should not" use VSP, rather, emphasizes the need for patient selection regarding which patients would most benefit from VSP when evaluating quality of life and long-term complications. Further studies are necessary to demonstrate improved long-term risk for hardware failure/exposure in VSP compared to FHR.

Postoperative Radiotherapy and Survival in Oral Cavity Squamous Cell Carcinoma With Mandibulectomy.

Importance: Oral cavity squamous cell carcinoma (SCC) tumors with mandibular invasion are upstaged to pT4a regardless of their size. Even small tumors with boney invasion, which would otherwise be classified as pT1-2, are recommended for the locally advanced treatment pathway to receive administration of postoperative radiotherapy (PORT). Objective: To evaluate the association of PORT with overall survival according to tumor size among patients who received mandibulectomy for pT4aN0 oral cavity SCC. Design, Setting, and Participants: This was a retrospective analysis using data from the US National Cancer Database from January 1, 2004, through December 31, 2019. All patients who received mandibulectomy for treatment-naive pT4aN0 oral cavity SCC with negative surgical margins were included. Data analyses were performed in January 2023 and finalized in July 2023. Exposure: PORT vs no PORT. Main Outcomes and Measures: Entropy balancing was used to balance covariate moments between treatment groups. Weighted multivariable Cox proportional hazards regression was used to measure the association of PORT with overall survival associated with tumor size. Results: Among 3268 patients with pT4aN0 oral cavity SCC (mean [SD] age, 65.9 [12.1] years; 2024 [61.9%] male and 1244 [38.1%] female), 1851 (56.6%) received PORT and 1417 (43.4%) did not receive PORT. On multivariable analysis was adjusted for age, insurance status, Charlson Comorbidity Index score, tumor site, tumor grade, tumor size, and PORT. Findings indicated that PORT was associated with improved overall survival and that this relative survival advantage trended upwards with increasing tumor size. That is, the larger the tumor, the greater the survival advantage associated with the use of PORT. For the 1068 patients with tumors greater than 4 cm, the adjusted hazard ratio (aHR) in favor of PORT was 0.63 (95% CI, 0.48-0.82); for the 1774 patients with tumors greater than 2 cm but less than or equal to 4 cm, the aHR was 0.76 (95% CI, 0.62-0.93); and for 426 patients with tumors less than 2 cm, the aHR was 0.81 (95% CI, 0.57-1.15). Conclusions and Relevance: In this retrospective analysis of patients who received mandibulectomy for pT4aN0 oral cavity SCC, PORT was associated with improved overall survival, the benefit of which improved relatively with increasing tumor size. These findings suggest that tumor size should be considered in guidelines for PORT administration in this patient population.

Co-surgery in head and neck microvascular reconstruction.

PURPOSE: Co-surgery with two attending reconstructive surgeons is becoming increasingly common in breast microvascular reconstruction due to case complexity and the potential for improved outcomes and operative efficiency. The impact of co-surgery on outcomes in head and neck microvascular reconstruction has not been studied. METHODS: Our multidisciplinary head and neck reconstruction team (Otolaryngology, Plastic Surgery) at the University of Pittsburgh transitioned to a practice of co-surgery on head and neck free flaps. In this study, we compare outcomes of two surgeon head and neck reconstruction to single surgeon reconstruction in a prospectively maintained database. RESULTS: 384 patients met our inclusion criteria from 2020 to 2022. Cases were performed by a single surgeon in 77.8 % of cases (299/384) and two surgeons in 22.1 % (85/384). The mean age was 62.5 years. There was no difference between the single surgeon cohort and the co-surgery cohort in terms of flap survival, procedure time, ischemia time, hospital length of stay, recipient site complications, or rates of return to the operating room. Donor site complications were less common in the co-surgery cohort (0 % vs 4.7 %, p = 0.021). For our reconstructive team, the transition to co-surgery has increased total surgeon fee collection per free flap by 28 % and increased surgeon flap related RVU production by 35 %. CONCLUSION: Co-surgery is feasible and safe in head and neck microvascular reconstruction. Benefits may include reduced complications, increased reimbursement, and improved interdisciplinary collaboration.

Odontogenic Carcinosarcoma: Clinicopathologic and Molecular Features of Three Cases, a Literature Review and Nomenclature Proposal.

BACKGROUND: Odontogenic carcinosarcoma (OCS) is a rare odontogenic malignancy with limited characterization and unexplored molecular features. We report clinicopathologic and molecular findings in 3 additional OCS and review the literature. METHODS: 3 OCS (5.1%) were identified among 59 malignant odontogenic tumors (in our archives from 1992 to 2022). Clinical, radiologic, histopathologic, immunophenotypic, and molecular findings were reviewed. Data from prior case reports and systematic or non-systematic reviews were extracted for analysis. RESULTS: Three mandibular OCS (age range: 66 to 72 years; 1 male, 2 females) were identified. Case 1 had novel clear-cell morphology, multiple recurrences, and a lethal outcome 28 months after resection. EWSR1 rearrangements were negative, but the tumor showed focal nuclear ß-catenin and strong LEF-1 immunoreactivity. Case 2 demonstrated ameloblastic and sclerosing features and encased the inferior alveolar nerve; the patient was disease-free 22 months after resection with adjuvant chemoradiation therapy. LEF-1 was again strongly positive, and next-generation sequencing demonstrated 9p region-(CDKN2A, CDKN2B) copy number loss, and 12q region-(MDM2, CDK4) copy number gain. Case 3 showed clear-cell and markedly sclerosing features; no follow-up information was available. Literature review along with the current cases yielded 20 cases. OCS showed a male predilection (1.5:1), mandibular predominance (80%, typically posterior), and a bimodal age distribution (modes: 27.7 years, 62.7 years). OCS presented as masses (100%), often with pain (55%), and paresthesia (45%). Tumors were typically radiolucent (88.9%), with bone destruction (61.1%), and/or tooth effacement (27.8%). Preoperative biopsy was sensitive for malignancy (85.7%). At least 45% show evidence for a precursor lesion. 3-year DSS and DFS were 58% and 35%, respectively. Regional and distant (usually lung) metastatic rates were 25% and 31.3%, respectively. Increased mitotic rates and presence of tumor necrosis trended toward worse DSS and DFS. CONCLUSION: OCS is a rare but aggressive malignancy, often arising from precursor tumors and may represent a terminal phenotype rather than a distinct entity. We describe novel clear-cell and sclerosing morphologies. Wnt pathway alterations appear important. Mitotic rates and necrosis may be adverse prognosticators. In keeping with nomenclature trends in other sites, OCS may be more appropriately designated as "biphasic sarcomatoid odontogenic carcinomas."

Pretreatment pain predicts perineural invasion in patients with head and neck squamous cell carcinoma.

OBJECTIVES: Perineural invasion (PNI) in head and neck cancer (HNC) is a distinct pathological feature used to indicate aggressive tumor behavior and drive treatment strategies. Our study examined the prevalence and predictors of PNI in HNC patients stratified by tumor site. STUDY DESIGN AND METHODS: A retrospective analysis of head and neck squamous cell carcinoma (HNSCC) patients who underwent surgical resection at the University of Pittsburgh Medical Center between 2015 and 2018 was performed. Pretreatment pain was assessed at least 1 week before surgery using the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N). Demographics, clinical characteristics, and concomitant medications were obtained from medical records. Patients with cancers at the oropharynx and non-oropharynx (i.e., cancer at oral cavity, mandible, larynx) sites were separately analyzed. Tumor blocks were obtained from 10 patients for histological evaluation of intertumoral nerve presence. RESULTS: A total of 292 patients (202 males, median age = 60.94 ± 11.06) were assessed. Pain and PNI were significantly associated with higher T stage (p < 0.001) and tumor site (p < 0.001); patients with non-oropharynx tumors reported more pain and had a higher incidence of PNI compared to oropharynx tumors. However, multivariable analysis identified pain as a significant variable uniquely associated with PNI for both tumor sites. Evaluation of nerve presence in tumor tissue showed 5-fold higher nerve density in T2 oral cavity tumors compared to oropharyngeal tumors. CONCLUSIONS: Our study finds that PNI is associated with pretreatment pain and tumor stage. These data support the need for additional research into the impact of tumor location when investigating targeted therapies of tumor regression.

Discharge Disposition After Head and Neck Reconstruction: Effect on Adjuvant Therapy and Outcomes.

OBJECTIVES: Head and neck cancer patients that require major reconstruction often have advanced-stage disease. Discharge disposition of patients can vary and impact time to adjuvant treatment. We sought to examine outcomes in patients discharged to skilled nursing facilities (SNF) compared to those discharged home, including the impact on adjuvant therapy initiation and treatment package time (TPT). METHODS: Patients with head and neck squamous cell carcinoma treated with surgical resection and microvascular free flap reconstruction from 2019 to 2022 were included. Retrospective review was conducted to evaluate the impact of disposition on time to radiation (RT) and TPT. RESULTS: 230 patients were included, with 165 (71.7%) discharged to home and 65 (28.3%) discharged to SNF. 79.1% of patients were recommended adjuvant therapy. Average time to RT was 59 days for patients discharged to home compared to 70.1 days for patients discharged to SNF. Disposition was an independent risk factor for delays to starting RT (p = 0.03). TPT was 101.7 days for patients discharged to home versus 112.3 days for those who discharged to SNF. Patients discharged to SNF had higher rates of readmission (p < 0.005) compared to patients discharged home in an adjusted multivariate logistic regression. CONCLUSIONS: Patients discharged to an SNF had significantly delayed time to initiation of adjuvant treatment and higher rates of readmission. Timeliness to adjuvant treatment has recently been established as a quality measure, thus identifying delays to adjuvant treatment initiation should be a priority. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2977-2983, 2023.

Functional outcomes of hyoid suspension in anterior oromandibular reconstruction.

BACKGROUND: Hyoid suspension can be considered in major oromandibular reconstruction. The impact of hyoid suspension on flap viability, swallowing outcomes, airway, and long term radiographic hyoid position is unknown. The objective of this study is to describe outcomes after hyoid suspension in anterior mandibular reconstruction with fibular free flaps. We hypothesized hyoid suspension would not affect flap viability and would benefit functional outcomes. METHODS: A retrospective cohort study was conducted in an academic tertiary medical center. The study consisted of 84 adults who underwent anterior mandibular reconstruction from February 2014 to September 2020. The primary outcome studied was the post-suspension flap viability. Secondary outcomes include pre/post-operative hyomental distance on computed-tomography, duration of perioperative tracheostomy, postoperative feeding tube dependence, and post-operative aspiration pneumonia. RESULTS: A total of 84, predominantly male (66.5 %), patients with an average age of 58.9 ± 11.5 were included in the study. Of those that met inclusion criteria, 25 (29.4 %) underwent intraoperative hyoid suspension. Univariable analysis showed no significant association between resuspension and post-operative total flap loss (p = 0.864) or partial flap loss (p = 0.318). There was no association between hyoid suspension and any of the studied postoperative functional outcomes or radiographic measures. CONCLUSIONS: Hyoid suspension is an option during oromandibular reconstruction and does not impact flap viability. The impact on functional outcomes and long-term hyoid position in this patient subset remains unclear.

Venous Thromboembolism Rates After Free Flap Reconstruction of the Head and Neck Region.

BACKGROUND: Venous thromboembolism (VTE) is a major concern for the postoperative hospitalized patient, especially after long and complex procedures. Cancer itself also contributes to the hypercoagulable state, further complicating the management of patients. Despite prophylaxis, breakthrough events can occur. We aimed to assess our institutional VTE and bleeding rates after free flap reconstruction of the head and neck (H&N) region and the factors associated with VTE events. METHODS: A retrospective review of the patients who underwent H&N free flap reconstruction at an academic center from 2012 to 2021 was performed from a prospectively maintained database. Data regarding patient demographics, medical history, surgical details, and overall outcomes were collected. Outcomes studied included postoperative 30-day VTE rates and major bleeding events. Patients who had a VTE event were compared with the rest of the cohort to identify factors associated with VTE. RESULTS: Free flap reconstruction of the H&N region was performed in 949 patients. Reconstruction after cancer extirpation for squamous cell carcinoma was the most common etiology (79%). The most common flap was thigh based (50%), followed by the fibula (29%). The most common postoperative VTE chemoprophylaxis regimen was enoxaparin 30 mg twice daily (83%). The VTE and bleeding rates over the 10-year period were 4.6% (n = 44) and 8.7% (n = 83), respectively. Body mass index (28.7 ± 5.8 vs 26.2 ± 6.6, P = 0.013) and pulmonary comorbidities were found to be significantly higher in patients who had a VTE event (43% vs 27%, P = 0.017). Patients with a VTE event had a prolonged hospital stay of 8 more days (19.2 ± 17.4 vs 11 ± 7, P = 0.003) and a higher incidence of bleeding events (27% vs 8%, P < 0.001). CONCLUSIONS: Postoperative VTE is a significant complication associated with increased length of hospitalization in patients undergoing free flap reconstruction of the H&N region. Institutional measures should be implemented on an individualized basis based on patient comorbidities to improve the postoperative VTE rates, while balancing the bleeding events.

Head and Neck Reconstruction in Patients with Polycythemia Vera: Case Series and Literature Review.

Background Polycythemia vera (PV) is a myeloproliferative disease with overproduction of erythrocytes, leukocytes, and platelets causing an increased risk of both thrombosis and hemorrhage. There are limited reports and no established guidelines for managing such patients undergoing reconstructive surgery. Methods We present four patients with PV and head and neck cancer who required reconstruction after resection and provide a review of the current literature. Results Preoperatively, patients on cytoreductive therapy continued with their treatment throughout their hospital course and had hematologic parameters normalized with phlebotomy or transfusions if needed. Two patients who underwent free flap surgery (cases 1 and 2) had postoperative courses complicated by hematoma formation and persistent anemia, requiring multiple transfusions. Cases 3 and 4 (JAK2+ PV and JAK2- PV, respectively) underwent locoregional flap without postoperative complications. Conclusion Concomitant presentation of PV and head and neck cancer is uncommon and presents unique challenges for the reconstructive surgeon. Overall, we recommend that patients should have hematologic parameters optimized prior to surgery, continue ruxolitinib or hydroxyurea, and hold antiplatelet/anticoagulation per established department protocols. It is essential to engage a multidisciplinary team involving hematology, head and neck and reconstructive surgery, anesthesia, and critical care to develop a standardized approach for managing this unique subset of patients.

Association between venous thromboembolism rates and different prophylactic anticoagulation regimens in patients undergoing free flap reconstruction of the head and neck region.

BACKGROUND: Venous Thromboembolism (VTE) is a serious complication after free tissue transfer to the head and neck (H&N). However, an optimal antithrombotic prophylaxis protocol is not defined in the literature. Enoxaparin 30 mg twice daily (BID) and heparin 5000 IU three times daily (TID) are among the most commonly used regimens for chemoprophylaxis. However, no studies compare these two agents in the H&N population. METHODS: A cohort study of patients who underwent free tissue transfer to H&N from 2012 to 2021 and received either enoxaparin 30 mg BID or Heparin 5000 IU TID postoperatively. Postoperative VTE and hematoma events were recorded within 30 days of index surgery. The cohort was divided into two groups based on chemoprophylaxis. VTE and hematoma rates were compared between the groups. RESULTS: Out of 895 patients, 737 met the inclusion criteria. The mean age and Caprini score were 60.6 [SD 12.5] years and 6.5 [SD 1.7], respectively. 234 [31.88%] were female. VTE and hematoma rates among all patients were 4.47% and 5.56%, respectively. The mean Caprini score between the enoxaparin (n = 664) and heparin (n = 73) groups was not statistically significant (6.5 ± 1.7 vs.6.3 ± 1.3, p = 0.457). The VTE rate in the enoxaparin group was significantly lower than in the heparin group (3.9% vs. 9.6%; OR: 2.602, 95% CI: 1.087-6.225). Hematoma rates were similar between the two groups (5.5% vs. 5.6%; OR: 0.982, 95% CI: 0.339-2.838). CONCLUSIONS: Enoxaparin 30 mg BID was associated with a lower VTE rate while maintaining a similar hematoma rate compared to heparin 5000 units TID. This association may support the use of enoxaparin over heparin for VTE chemoprophylaxis in H&N reconstruction.

Response to Neoadjuvant Targeted Therapy in Operable Head and Neck Cancer Confers Survival Benefit.

PURPOSE: Neoadjuvant targeted therapy provides a brief, preoperative window of opportunity that can be exploited to individualize cancer care based on treatment response. We investigated whether response to neoadjuvant therapy during the preoperative window confers survival benefit in patients with operable head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: A pooled analysis of treatment-naïve patients with operable HNSCC enrolled in one of three clinical trials from 2009 to 2020 (NCT00779389, NCT01218048, NCT02473731). Neoadjuvant regimens consisted of EGFR inhibitors (n = 83) or anti-ErbB3 antibody therapy (n = 9) within 28 days of surgery. Clinical to pathologic stage migration was compared with disease-free survival (DFS) and overall survival (OS) while adjusting for confounding factors using multivariable Cox regression. Circulating tumor markers validated in other solid tumor models were analyzed. RESULTS: 92 of 118 patients were analyzed; all patients underwent surgery following neoadjuvant therapy. Clinical to pathologic downstaging was more frequent in patients undergoing neoadjuvant targeted therapy compared with control cohort (P = 0.048). Patients with pathologic downstage migration had the highest OS [89.5%; 95% confidence interval (CI), 75.7-100] compared with those with no stage change (58%; 95% CI, 46.2-69.8) or upstage (40%; 95% CI, 9.6-70.4; P = 0.003). Downstage migration remained a positive prognostic factor for OS (HR, 0.22; 95% CI, 0.05-0.90) while adjusting for measured confounders. Downstage migration correlated with decreased circulating tumor markers, SOX17 and TAC1 (P = 0.0078). CONCLUSIONS: Brief neoadjuvant therapy achieved pathologic downstaging in a subset of patients and was associated with significantly better DFS and OS as well as decreased circulating methylated SOX17 and TAC1.

A phase â ¡ prospective trial of photobiomodulation therapy in limiting oral mucositis in the treatment of locally advanced head and neck cancer patients.

Objective: This study aimed to compare the historical incidence rate of severe oral mucositis (OM) in head and neck cancer patients undergoing definitive concurrent chemoradiation therapy (CRT) versus a prospective cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with prophylactic photobiomodulation therapy (PBMT). Methods: This US-based, institutional, single-arm, phase Ⅱ prospective clinical trial was initiated in 50 patients (age ≥ 18 years, Karnofsky Performance Scale Index > 60, with locally advanced HNSCC (excluding oral cavity) receiving definitive or adjuvant radiation therapy (RT) with concurrent platinum-based chemotherapy (CT). PBMT was delivered three times per week throughout RT utilizing both an intraoral as well extraoral delivery system. Primary outcome measure was incidence of severe OM utilizing both the National Cancer Institute Common Toxicity Criteria, version 4.0 (NCI-CTCAE) Grade ≥3 and the World Health Organization Mucositis Grading Scale (WHO) Grade ≥3 versus historical controls; secondary outcome measures included time to onset of severe OM following therapy initiation. Results: At baseline, all patients included in final analysis (N = 47) had OM Grade 0. Average RT and CT dose was (66.3 ± 5.1) Gy and (486.1 ± 106.8) mg/m2, respectively. Severe OM was observed in 11 of 47 patients (23%, confidence interval: 12, 38). OM toxicity grade trended upward during treatment, reaching a maximum at 7 weeks (WHO: 1.8 vs. NCI-CTCAE: 1.7). Subsequently, OM grade returned to baseline 3 months following completion of RT. The mean time to onset of severe OM was (35 ± 12) days. The mean time to resolution of severe OM was (37 ± 37) days. Conclusions: Compared to historical outcomes, PBMT aides in decreasing severe OM in patients with locally advanced HNSCC. PBMT represents a minimally invasive, prophylactic intervention to decrease OM as a major treatment-related side effect.

Assessment of BMI and Venous Thromboembolism Rates in Patients on Standard Chemoprophylaxis Regimens After Undergoing Free Tissue Transfer to the Head and Neck.

Importance: Venous thromboembolism (VTE) is a severe complication after free tissue transfer to the head and neck (H&N). Enoxaparin 30 mg twice daily (BID) is a common regimen for chemoprophylaxis. However, differences in enoxaparin metabolism based on body weight may influence its efficacy and safety profile. Objective: To assess the association between BMI and postoperative VTE and hematoma rates in patients treated with prophylactic enoxaparin 30 mg BID. Design, Setting, and Participants: This was a retrospective review of a prospectively collected cohort from 2012 to 2022. Postoperative VTE, hematoma, and free flap pedicle thrombosis were recorded within 30 days of index surgery. The setting was a tertiary academic referral center. Participants included patients undergoing H&N reconstruction with free flaps that received fixed-dose subcutaneous enoxaparin 30 mg BID postoperatively. Statistical analysis was conducted from April to May 2022. Main Outcomes and Measures: Outcomes include incidence of VTE, hematoma, and flap pedicle thrombosis events within 30 days of the surgery. Univariate and multivariable regression models were used to evaluate associations between BMI and other patient factors with these outcomes. Results: Among the 765 patients included, 262 (34.24%) were female; mean (SD) age was 60.85 (12.64) years; and mean (SD) BMI was 26.36 (6.29). The rates of VTE and hematoma in the cohort were 3.92% (30 patients) and 5.09% (39 patients), respectively. After adjusting for patient factors, BMI was the only factor associated with VTE (OR, 1.07; 95% CI, 1.015-1.129). Obesity (BMI >30) was associated with increased odds of VTE (OR, 2.782; 95% CI, 1.197-6.564). Hematoma was not associated with BMI (OR, 0.988; 95% CI, 0.937-1.041). Caprini score of at least 9 was not associated with VTE (OR, 1.259; 95% CI, 0.428-3.701). Conclusions and Relevance: This cohort study found that obesity was associated with an increased risk of VTE in patients after microvascular H&N reconstruction and while on standard postoperative chemoprophylaxis regimens. This association may suggest insufficient VTE prophylaxis in this group and a potential indication for weight-based dosing.

Anatomic Considerations of Microvascular Free Tissue Transfer in Endoscopic Endonasal Skull Base Surgery.

Objective Though microvascular free tissue transfer is well established for open skull base reconstruction, normative data regarding flap design and inset after endoscopic endonasal skull base surgery (ESBS) is lacking. We aim to describe anatomical considerations of endoscopic endonasal inset of free tissue transfer of transclival (TC) and anterior cranial base resection (ACBR) defects. Design and Setting Radial forearm free tissue transfer (RFFTT) model. Participants Six cadaveric specimens. Main Outcome Measures Pedicle orientation, pedicle length, and recipient vessel intraluminal diameter. Results TC and ACBR defects averaged 17.2 and 11.7 cm 2 , respectively. Anterior and lateral maxillotomies and endoscopic medial maxillectomies were prepared as corridors for flap and pedicle passage. Premasseteric space tunnels were created for pedicle tunneling to recipient facial vessels. For TC defects, the RFFTT pedicle was oriented cranially with the flap placed against the clival defect (mean pedicle length 13.1 ± 0.6 cm). For ACBR defects, the RFFTT pedicle was examined in three orientations with respect to anterior-posterior axis of the RFFTT: anteriorly, posteriorly, and laterally. Lateral orientation offered the shortest average pedicle length required for anastomosis in the neck (11.6 ± 1.29 cm), followed by posterior (13.4 ± 0.7cm) and anterior orientations (14.4 ± 1.1cm) ( p < 0.00001, analysis of variance). Conclusions In ACBR reconstruction using RFFTT, our data suggests lateral pedicle orientation shortens the length required to safely anastomose facial vessels and protects the frontal sinus outflow anteriorly while limiting pedicle exposure through a maxillary corridor within the nasal cavity. With greater understanding of anatomical factors related to successful preoperative flap planning, free tissue transfer may be added to the ESBS reconstruction ladder.

Standard Fixed Enoxaparin Dosing for Venous Thromboembolism Prophylaxis Leads to Low Peak Anti-Factor Xa Levels in Both Head and Neck and Breast Free Flap Patients.

BACKGROUND: Venous thromboembolism (VTE) is a serious complication, particularly in cancer patients undergoing free flap reconstruction. Subcutaneous enoxaparin is the conventional prophylaxis for VTE prevention, and serum anti-factor Xa (afXa) levels are being increasingly used to monitor enoxaparin activity. In this study, free flap patients receiving standard enoxaparin prophylaxis were prospectively followed to investigate postoperative afXa levels and 90-day VTE and bleeding-related complications. METHODS: Patients undergoing free tissue transfer during an 8-month period were identified and prospectively followed. Patients received standard fixed enoxaparin dosing at 30 mg twice daily in head and neck (H&N) and 40 mg daily in breast reconstructions. Target peak prophylactic afXa range was 0.2 to 0.5 IU/mL. The primary outcome was the occurrence of 90-day postoperative VTE- and bleeding-related events. Independent predictors of afXa level and VTE incidence were analyzed for patients that met the inclusion criteria. RESULTS: Seventy-eight patients were prospectively followed. Four (5.1%) were diagnosed with VTE, and six (7.7%) experienced bleeding-related complications. The mean afXa levels in both VTE patients and bleeding patients were subprophylactic (0.13 ± 0.09 and 0.11 ± 0.07 IU/mL, respectively). Forty-six patients (21 breast, 25 H&N) had valid postoperative peak steady-state afXa levels. Among these, 15 (33%) patients achieved the target prophylactic range: 5 (33%) H&N and 10 (67%) breast patients. The mean afXa level for H&N patients was significantly lower than for breast patients (p = 0.0021). Patient total body weight was the sole negative predictor of afXa level (R 2 = 0.47, p < 0.0001). CONCLUSION: Standard fixed enoxaparin dosing for postoperative VTE prophylaxis does not achieve target afXa levels for the majority of our free flap patients. H&N patients appear to be a particularly high-risk group that may require a more personalized and aggressive approach. Total body weight is the sole negative predictor of afXa level, supporting a role for weight-based enoxaparin dosing.

Definitive local therapy to head and neck squamous cell carcinoma with distant metastasis.

Objectives: Data on the efficacy of including definitive local therapy to the primary site for head and neck squamous cell carcinoma (HNSCC) patients with synchronous distant metastasis are lacking. In multiple different solid tumor types, there has been benefit when using systemic therapy followed by local consolidative therapy (stereotactic ablative radiotherapy or surgery) directed at metastases. We proposed to retrospectively evaluate patients at our institution that received definitive treatment to the primary. Methods: Single institution retrospective study evaluating 40 patients with metastatic HNSCC treated with definitive surgery (55%) or chemoradiation (45%) to the primary site from 2000 to 2020. The major endpoints were overall survival (OS) and progression-free survival (PFS) for the total population and multiple sub-groups. Some variables were evaluated with multiple covariates Cox model. Results: The median PFS was 8.6 months (95% CI, 6.4-11.6), and OS was 14.2 months (95% CI, 10.9-27.5). In 28% of patients that received induction therapy, there was a twofold increase in median overall survival to 27.5 months. In the 33% of patients that received anti-PD-1 mAb as part of their treatment course, the median OS was significantly increased to 41.7 months (95% CI, 8.7-NR) versus 12.1 months (95% CI, 8.4-14.4) with a 5-year OS of 39%. Multivariate analysis for OS showed significance for age at diagnosis, use of IO, and number of metastatic sites. Conclusion: We observed impressive survival outcomes in metastatic HNSCC patients treated with definitive local therapy to the primary site in addition to induction and/or immunotherapy. Further study is warranted.Level of Evidence: 3.

Poor treatment tolerance in head and neck cancer patients with low muscle mass.

BACKGROUND: We ascertain the role of a low cervical paraspinal skeletal muscle index (CPSMI) as a biomarker for poor treatment tolerance in patients with operable mucosal head and neck squamous cell carcinoma (HNSCC). METHODS: A prospective cohort of patients with operable HNSCC requiring microvascular reconstruction was evaluated. Low CPSMI was calculated using preoperative CT neck imaging. Poor treatment tolerance, a composite measure of incomplete therapy or severe morbidity/mortality during treatment, was the primary outcome. RESULTS: One hundred and twenty-seven patients underwent extirpative surgery with a mean age was 60.5. Poor treatment tolerance occurred in 71 (56%) patients with 21 not completing recommended adjuvant therapy and 66 having severe treatment-related morbidity. A low CPSMI was independently associated with poor treatment tolerance (OR 2.49, 95%CI 1.10-5.93) and delay to adjuvant therapy (OR 4.48, 95%CI 1.07-27.6) after adjusting for multiple confounders. CONCLUSION: Low CPSMI was independently associated with poor treatment tolerance in patients with operable HNSCC.