Phase II Clinical Trial of Intravenous Levothyroxine to Mitigate Pharyngocutaneous Fistula in Euthyroid Patients Undergoing Salvage Laryngectomy.

PURPOSE: Patients undergoing head and neck cancer surgery after prior radiation or chemoradiation are at high risk for wound complications. Hypothyroidism is a known risk factor for wound complications, especially fistulae after salvage total laryngectomy. The purpose of this phase II clinical trial is to investigate the effect of peri-operative intravenous levothyroxine supplementation on wound complications in patients undergoing salvage total laryngectomy. PATIENTS AND METHODS: Euthyroid patients previously treated with radiation/chemoradiation undergoing total laryngectomy were prospectively recruited (n=72). Post-operatively, intravenous levothyroxine was administered at a weight-based dose (1.3 mcg/kg/day) and transitioned to enteral dosing on day 7. Free T3, T4, and thyroid stimulating hormone (TSH) were collected and dosing was adjusted accordingly. The primary endpoints were rates of fistula and fistula requiring re-operation, compared to matched historical controls. All patients were monitored for adverse effects. RESULTS: The rate of post-operative hypothyroidism was 21% compared to 49% in a matched historic cohort. The rate of fistula was 18.1% while the rate of fistula requiring re-operation was 4.2%, significantly lower than rates in our historic cohort (34.6% and 14.8% respectively, p=0.02 and 0.01). Post-operative hypothyroidism and recurrent clinical stage predicted fistula requiring re-operation in multivariate analysis; other acute phase reactants were not predictive. There were no observed adverse events related to levothyroxine supplementation. CONCLUSIONS: Post-operative intravenous levothyroxine supplementation reduced rates of acute hypothyroidism, fistula, and fistula requiring re-operation in patients undergoing salvage total laryngectomy without adverse effects. Intravenous levothyroxine is a viable strategy to reduce wound complications in this high-risk patient population.

Application of Time-Driven Activity-Based Costing for Head and Neck Microvascular Free Flap Reconstruction.

OBJECTIVE: Traditional hospital accounting fails to provide an accurate cost of complex surgical care. Here we describe the application of time-driven activity-based costing (TDABC) to characterize costs of head and neck oncologic procedures involving free tissue transfer. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary academic medical center. METHODS: An analysis of head and neck oncologic procedures involving microvascular free flap reconstruction from 2018 to 2020 (n = 485) was performed using TDABC methodology to measure cost across operative case and postoperative admission, using quantity of time and cost per unit of each resource to characterize resource utilization. Univariate and generalized linear mixed models were used to examine associations between patient and hospital characteristics and cost of care delivery. RESULTS: The total cost of care delivery was $41,905.77 ± 21,870.27 with operating room (OR) supplies accounting for only 10% of the total cost. Multivariable analyses identified significant cost drivers including operative time, postoperative length of stay, number of return trips to the OR, postoperative complication, number of free flaps performed, and patient transfer from another hospital or via emergency department admission (P < .05). CONCLUSION: Operative time and postoperative length of stay, but not operative supplies, were primary drivers of cost of care for head and neck oncology cases involving free tissue transfer. TDABC offers granular cost characterization to inform cost optimization through unused capacity identification and postoperative admission efficiencies.

Implications of Malignancy, Radiation, and Timing of Major Nasal Reconstruction.

Owing to the complex, multilayered anatomy of the nose in the central face, major nasal reconstruction can pose a significant challenge for reconstructive surgeons. It is the responsibility of reconstructive surgeons to have an understanding of the most common cutaneous malignancies and excisional techniques that may lead to complex nasal defects. The purpose of this article is to discuss these malignancies, excisional techniques, and impacts of radiation on tissue that has implications for reconstructive surgeons.

Outcomes of Autologous Versus Irradiated Homologous Costal Cartilage Graft in Rhinoplasty.

Background: Autologous costal cartilage (ACC) and irradiated homologous costal cartilage (IHCC) are commonly used in septorhinoplasty when there is insufficient septal cartilage for grafting. Objective: To assess the surgical outcomes of patients who underwent septorhinoplasty with either ACC or IHCC as measured by rates of infection, resorption, warping, and revision rate. Methods: A retrospective analysis of patients who underwent rhinoplasty with ACC or IHCC at a single academic institution was performed. Demographic data, surgical details, antibiotic use, and outcomes, including surgical duration, infection, resorption, warping, and revision rate, were analyzed using Fisher's exact test, chi-squared test, and logistic regression. Results: One hundred forty-three patients were identified. The median age was 48 years (interquartile range: 35-57.5) and 62.2% (n = 89) were female, 61 patients (42.7%) underwent ACC, and 82 (57.3%) IHCC. Revision rate in both groups was similar (ACC = 14.8%, IHCC = 14.6%; p = 0.98). There was no difference in infection rate (ACC = 4.9%, IHCC = 3.7%; p = 0.71). Postoperative deformity and nasal obstruction were the most common indications for revision surgery. Surgical time was shorter with IHCC (p < 0.01). Mean follow-up time was 26.5 months (±25) for ACC, and 16 months (±12) for IHCC. Conclusions: ACC and IHCC are similar in terms of effectiveness and safety in septorhinoplasty.

Team-Based Surgical Approach to Head and Neck Microvascular Free Flap Reconstruction.

Importance: Because microvascular free flap reconstruction is increasingly used to restore function in patients with head and neck cancer, there is a growing need for evidence-based perioperative care. Objective: To assess the association of different team-based surgical approaches with intraoperative and postoperative outcomes for patients undergoing head and neck free flap reconstruction. Design, Setting, and Participants: This retrospective cohort study of 733 patients was conducted at an academic tertiary care medical center. Head and neck oncologic procedures involving microvascular free flap reconstruction with available intraoperative data collected from January 1, 2000, to December 31, 2021, were included. Main Outcomes and Measures: Patient characteristics including demographic characteristics and comorbid conditions, operative variables, length of stay, and postoperative outcomes were measured. Descriptive statistics and effect size measures were performed to compare the 3 intraoperative surgical team approaches, specifically single surgeon, separate 2-team approach, and integrated 2-team approach; 1:1 nearest neighbor matching without caliper was performed to compare single- vs 2-team and separate and integrated 2-team approaches. Effect size measures including Cramer V for dichotomous variables, the Kendall W coefficient of concordance for ordinal variables, and η2 for continuous variables were reported with 95% CIs to describe precision. Results: Among 733 cases, there were no clinically significant differences in patient demographic characteristics, clinicopathologic characteristics, and choice of free flap reconstruction based on intraoperative surgical team approach. The mean (SD) age was 58.7 (12.4) years, and 514 were male (70.1%). In terms of operative and postoperative variables, there was a difference in operative times and intraoperative fluid requirements among the 3 different techniques, with the integrated 2-team approach demonstrating a mean reduction in operative time of approximately 2 hours (η2 = 0.871; 95% CI, 0.852-0.887; mean [SD] operative time = 541 [191] minutes for the single-surgeon approach, 399 [175] minutes for the integrated 2-team approach, and 537 [200] minutes for the separate 2-team approach) and lower fluid requirements of greater than 1 L (η2 = 0.790; 95% CI, 0.762-0.817). In both unadjusted analyses and propensity score matching, there were no clinically significant differences in terms of ischemia time, use of pressors, postoperative complications (including free flap failure, number of return trips to the operating room, length of stay, or 30-day readmission) based on intraoperative team approach. Conclusions and Relevance: Findings suggest that the integrated 2-team surgical approach for complex head and neck microvascular reconstruction can be used to safely decrease operative time, with no difference in postoperative outcomes.

Use of neuromuscular blockade for neck dissection and association with iatrogenic nerve injury.

BACKGROUND: Cranial nerve injury is an uncommon but significant complication of neck dissection. We examined the association between the use of intraoperative neuromuscular blockade and iatrogenic cranial nerve injury during neck dissection. METHODS: This was a single-center, retrospective, electronic health record review. Study inclusion criteria stipulated patients > 18 years who had ≥ 2 neck lymphatic levels dissected for malignancy under general anesthesia with a surgery date between 2008 - 2018. Use of neuromuscular blockade during neck dissection was the primary independent variable. This was defined as any use of rocuronium, cisatracurium, or vecuronium upon anesthesia induction without reversal with sugammadex prior to surgical incision. Univariate tests were used to compare variables between those patients with, and those without, iatrogenic cranial nerve injury. Multivariable logistic regression determined predictors of cranial nerve injury and was performed incorporating Firth's estimation given low prevalence of the primary outcome. RESULTS: Our cohort consisted of 925 distinct neck dissections performed in 897 patients. Neuromuscular blockade was used during 285 (30.8%) neck dissections. Fourteen instances (1.5% of surgical cases) of nerve injury were identified. On univariate logistic regression, use of neuromuscular blockade was not associated with iatrogenic cranial nerve injury (OR: 1.73, 95% CI: 0.62 - 4.86, p = 0.30). There remained no significant association on multivariable logistic regression controlling for patient age, sex, weight, ASA class, paralytic dose, history of diabetes, stroke, coronary artery disease, carotid atherosclerosis, myocardial infarction, and cardiac arrythmia (OR: 1.87, 95% CI: 0.63 - 5.51, p = 0.26). CONCLUSIONS: In this study, use of neuromuscular blockade intraoperatively during neck dissection was not associated with increased rates of iatrogenic cranial nerve injury. While this investigation provides early support for safe use of neuromuscular blockade during neck dissection, future investigation with greater power remains necessary.

Color Match Following Free Flap Surgery in Head and Neck Reconstruction: A Colorimetric and Aesthetic Analysis.

BACKGROUND: Many options for free tissue transfer have been described for head and neck reconstruction. While functional outcomes remain paramount, aesthetic considerations like color match can be equally consequential for patient quality of life. It is important to understand differences in color match based on flap donor site for head and neck reconstruction. METHODS: A retrospective review was performed of patients who underwent head and neck reconstruction with free tissue transfer at a tertiary care academic medical center between November 2012 and November 2020. Patients with documented pictures of their reconstruction and external skin paddles were considered. Patient demographics and surgery specific factors were recorded. Objective differences in color match were obtained by calculating the International Commission on Illumination Delta E 2000 (dE2000) score. Standard univariate descriptive statistics and multivariable statistical analyses were performed. RESULTS: Lateral arm, parascapular, and medial sural artery perforator (MSAP) free tissue transfer performed favorably compared to other donor sites, whereas anterolateral thigh flaps had the highest average dE2000 scores. Differences in dE2000 scores were mitigated by post-operative radiation to the flap site and with increasing time beyond 6 months post-operatively. CONCLUSIONS: We provide an objective assessment of external skin color match in patients undergoing free tissue transfer for head and neck cancer by donor site. MSAP, lateral arm, and parascapular free flaps performed well compared to traditional donor sites. These differences are more significant at the face and mandible when compared to the neck, but diminish 6 months after surgery and with post-operative radiation to the free flap skin paddle.

Patterns of recurrence in head and neck squamous cell carcinoma to inform personalized surveillance protocols.

BACKGROUND: Development of evidence-based post-treatment surveillance guidelines in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is limited by comprehensive documentation of patterns of recurrence and metastatic spread. METHODS: A retrospective analysis of patients diagnosed with R/M HNSCC at a National Cancer Institute-designated cancer center between 1998- 2019 was performed (n = 447). Univariate and multivariate analysis identified patterns of recurrence and predictors of survival. RESULTS: Median overall survival (mOS) improved over time (6.7 months in 1998-2007 to 11.8 months in 2008-2019, p = .006). Predictors of worse mOS included human papillomavirus (HPV) negativity (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.2-2.6), high neutrophil/lymphocyte ratio (HR, 2.1 [1.4-3.0], disease-free interval (DFI) ≤6 months (HR, 1.4 [1.02-2.0]), and poor performance status (Eastern Cooperative Oncology Group, ≥2; HR, 1.91.1-3.4). In this cohort, 50.6% of recurrences occurred within 6 months of treatment completion, 72.5% occurred within 1 year, and 88.6% occurred within 2 years. Metachronous distant metastases were more likely to occur in patients with HPV-positive disease (odds ratio [OR], 2.3 [1.4-4.0]), DFI >6 months (OR, 2.4 [1.5-4.0]), and body mass index ≥30 (OR, 2.3 [1.1-4.8]). Oligometastatic disease treated with local ablative therapy was associated with improved survival over polymetastatic disease (HR, 0.36; 95% CI, 0.24-0.55). CONCLUSION: These data regarding patterns of distant metastasis in HNSCC support the clinical utility of early detection of recurrence. Patterns of recurrence in this population can be used to inform individualized surveillance programs as well as to risk-stratify eligible patients for clinical trials. PLAIN LANGUAGE SUMMARY: After treatment for head and neck cancer (HNC), patients are at risk of recurrence at prior sites of disease or at distant sites in the body. This study includes a large group of patients with recurrent or metastatic HNC and examines factors associated with survival outcomes and recurrence patterns. Patients with human papillomavirus (HPV)-positive HNC have good survival outcomes, but if they recur, this may be in distant regions of the body and may occur later than HPV-negative patients. These data argue for personalized follow-up schedules for patients with HNC, perhaps incorporating imaging studies or novel blood tests.

Initial Feasibility and Acute Toxicity Outcomes From a Phase 2 Trial of 18F-Fluorodeoxyglucose Positron Emission Tomography Response-Based De-escalated Definitive Chemoradiotherapy for p16+ Oropharynx Cancer: A Planned Interim Analysis.

PURPOSE: 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) parameters are prognostic of oncologic outcomes in human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). We used FDG-PET imaging biomarkers to select patients for de-escalated chemoradiotherapy (CRT), hypothesizing that acute toxicity will be improved with de-escalation. METHODS AND MATERIALS: This is a planned interim initial feasibility and acute toxicity report from a phase 2, prospective, nonrandomized study, which enrolled patients with stage I-II p16+ OPSCC. All patients started definitive CRT to 70 Gy in 35 fractions, and those who met de-escalation criteria on midtreatment FDG-PET at fraction 10 completed treatment at 54 Gy in 27 fractions. We report the acute toxicity and patient-reported outcomes for 59 patients with a minimum follow-up of 3 months. RESULTS: There were no statistically significant differences between baseline patient characteristics in the standard and de-escalated cohorts. There were 28 of 59 (47.5%) patients who met FDG-PET de-escalation criteria and collectively received 20% to 30% less dose to critical organs at risk known to affect toxicity. At 3 months posttreatment, patients who received de-escalated CRT lost significantly less weight (median, 5.8% vs 13.0%; P < .001), had significantly less change from baseline in penetration-aspiration scale score (median, 0 vs 1; P = .018), and had significantly fewer aspiration events on repeat swallow study (8.0% vs 33.3%, P = .037) compared with patients receiving standard CRT. CONCLUSIONS: Approximately half of patients with early-stage p16+ OPSCC are selected for de-escalation of definitive CRT using midtreatment FDG-PET biomarkers, which resulted in significantly improved rates of observed acute toxicity. Further follow-up is ongoing and will be required to determine whether this de-escalation approach preserves the favorable oncologic outcomes for patients with p16+ OPSCC before adoption.

Tumor immune microenvironment alterations using induction cetuximab in a phase II trial of deintensified therapy for p16-positive oropharynx cancer.

BACKGROUND: We sought to characterize early changes in CD8+ tumor-infiltrating lymphocytes and tumor transcriptomes after induction cetuximab in a cohort with p16-positive oropharyngeal cancer on a phase II clinical de-escalation trial. METHODS: Tumor biopsies were obtained before and 1 week after a single cetuximab loading dose in eight patients enrolled in a phase II trial of cetuximab and radiotherapy. Changes in CD8+ tumor-infiltrating lymphocytes and transcriptomes were assessed. RESULTS: One week after cetuximab, five patients (62.5%) had an increase in CD8+ cell infiltration with a median (range) fold change of +5.8 (2.5-15.8). Three (37.5%) had unchanged CD8+ cells (median [range] fold change of -0.85 [0.8-1.1]). In two patients with evaluable RNA, cetuximab induced rapid tumor transcriptome changes in cellular type 1 interferon signaling and keratinization pathways. CONCLUSIONS: Within 1 week, cetuximab induced measurable changes in pro-cytotoxic T-cell signaling and immune content.

Neurotization of the radial forearm free flap improves swallowing outcomes in hemiglossectomy defects.

BACKGROUND: We examined the effect of free tissue neurotization on speech and swallowing outcomes for patients undergoing reconstruction of hemiglossectomy defects with a radial forearm free flap (RFFF). METHODS: A retrospective study was performed in patients with oral cavity squamous cell carcinoma undergoing a hemiglossectomy and reconstruction with a RFFF. Functional outcomes including nutritional mode, range of liquids and solids, and speech understandability were analyzed 1-year post-treatment. RESULTS: Eighty-four patients were included in this analysis, 41 of whom had neurotized flaps (49%). No significant differences in demographic or clinical variables were seen between the neurotized and non-neurotized groups. On multivariate analysis controlling for BMI, flap area, and N-classification, patients with neurotized flaps were significantly more likely to have normal range of liquids and solids and less likely to have a G-tube. CONCLUSIONS: Neurotization of RFFF reconstructing hemiglossectomy defects results in decreased G-tube dependence and improved range of liquids and solids.

Prognostic value of CD103+ tumor-infiltrating lymphocytes and programmed death ligand-1 (PD-L1) combined positive score in recurrent laryngeal squamous cell carcinoma.

OBJECTIVES: In an evolving era of immunotherapeutic options for persistent or recurrent laryngeal squamous cell carcinoma (LSCC), there is a need for improved biomarkers of treatment response and survival to inform optimal treatment selection and prognostication. Herein, our primary objective was to explore correlations between tumor infiltrating lymphocytes (TILs) and PD-L1 Combined Positive Score (CPS). Secondarily, we sought to explore their combined association with survival outcomes in patients with persistent or recurrent LSCC treated with salvage surgery. MATERIALS AND METHODS: This was a retrospective cohort study at a single academic medical center. Immunohistochemistry staining for TILs and PD-L1 was performed on a tissue microarray of persistent or recurrent LSCC pathologic specimens. Correlations between TIL subsets and PD-L1 CPS were examined using Pearson's correlation coefficient and survival outcomes were analyzed with the Kaplan-Meier method and log-rank tests. RESULTS: Only CD103+ TILs showed a statistically significant, weakly-positive correlation with PD-L1 CPS (r2 = 0.264, p < 0.015). No other TIL subsets correlated with PD-L1 CPS in our cohort. The most favorable survival outcomes were seen in patients with pathologic N0 tumors showing high CD103+ TILs and/or high PD-L1 CPS staining. CONCLUSION: Among patients with persistent or recurrent LSCC, CD103+ TILs only modestly correlated with PD-L1 CPS. A combined biomarker score incorporating CD103+ TILs and PD-L1 CPS greatly enhanced survival discrimination. This model may have additional utility in predicting the clinical benefit of immunotherapies in persistent or recurrent LSCC in the future.

Randomized Phase II Study of Physiologic MRI-Directed Adaptive Radiation Boost in Poor Prognosis Head and Neck Cancer.

PURPOSE: We conducted a randomized phase II multicenter clinical trial to test the hypothesis that physiologic MRI-based radiotherapy (RT) dose escalation would improve the outcome of patients with poor prognosis head and neck cancer. PATIENTS AND METHODS: MRI was acquired at baseline and at RT fraction 10 to create low blood volume/apparent diffusion coefficient maps for RT boost subvolume definition in gross tumor volume. Patients were randomized to receive 70 Gy (standard RT) or 80 Gy to the boost subvolume (RT boost) with concurrent weekly platinum. The primary endpoint was disease-free survival (DFS) with significance defined at a one-sided 0.1 level, and secondary endpoints included locoregional failure (LRF), overall survival (OS), comparison of adverse events and patient reported outcomes (PRO). RESULTS: Among 81 randomized patients, neither the primary endpoint of DFS (HR = 0.849, P = 0.31) nor OS (HR = 1.19, P = 0.66) was significantly improved in the RT boost arm. However, the incidence of LRF was significantly improved with the addition of the RT boost (HR = 0.43, P = 0.047). Two-year estimates [90% confidence interval (CI)] of the cumulative incidence of LRF were 40% (27%-53%) in the standard RT arm and 18% (10%-31%) in the RT boost arm. Two-year estimates (90% CI) for DFS were 48% (34%-60%) in the standard RT arm and 57% (43%-69%) in the RT boost arm. There were no significant differences in toxicity or longitudinal differences seen in EORTC QLQ30/HN35 subscales between treatment arms in linear mixed-effects models. CONCLUSIONS: Physiologic MRI-based RT boost decreased LRF without a significant increase in grade 3+ toxicity or longitudinal PRO differences, but did not significantly improve DFS or OS. Additional improvements in systemic therapy are likely necessary to realize improvements in DFS and OS.

Imaging response assessment for predicting outcomes after bioselection chemotherapy in larynx cancer: A secondary analysis of two prospective trials.

BACKGROUND AND PURPOSE: Bioselection with induction chemotherapy in larynx cancer is associated with excellent larynx preservation and disease-specific survival but requires visual inspection of the primary tumor. We retrospectively compare clinical and imaging response in bioselected patients to develop predictive models of surgeon-assessed response (SR), laryngectomy-free survival (LFS), and overall survival (OS) in bioselected patients. MATERIALS AND METHODS: In a secondary analysis of patients on two single-institution bioselection trials, model building used a regularized regression model (elastic-net) and applied nested cross-validation. Logistic regression-based model was used to predict SR and Cox proportional hazard-based models were used to predict LFS and OS. RESULTS: In 115 patients with a median age of 57 years, most patients had supraglottic tumors (73.0%) and T3/T4 disease (94.8%). Definitive treatment was chemoradiation in 76.5% and laryngectomy in 23.5%. Change in primary tumor (OR = 5.78, p < 0.001) and N-classification (OR = 1.64, p = 0.003) predicted SR (AUC 0.847). Change in tumor volume (HR = 0.58, p < 0.001) predicted LFS (c-index 0.724). N-classification (HR = 1.48, p = 0.04) and pre-chemotherapy tumor volume (HR = 1.30, p = 0.174) predicted OS (c-index 0.552). CONCLUSIONS: Imaging offers a non-invasive opportunity to evaluate response to induction chemotherapy, complementary to surgeon assessment. Further evaluation of approaches to bioselection that optimize generalizability of this paradigm are needed, and clinical trials utilizing imaging to predict outcomes including LFS are warranted.

Impact of Completion Lymphadenectomy on Quality of Life for Head and Neck Cutaneous Melanoma.

OBJECTIVE: Recent randomized data suggest that completion lymph node dissection after a positive sentinel lymph node biopsy (SLNB) improves locoregional control but does not improve survival for melanoma patients. Locoregional recurrences of head and neck cutaneous melanoma (HNCM) may result in significant morbidity. A better understanding of morbidity is thus important to inform decisions about whether to pursue completion neck dissection (ND). STUDY DESIGN: Cross-sectional study. SETTING: Academic tertiary care hospital. METHODS: Clinical data were collected for patients with HNCM seen between 2016 and 2019 who were at least 1-year disease free. Each patient completed the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (SLANSS), Neck Dissection Impairment Index, and SF-36 (Short Form-36). Scores were compared by surgical treatment: wide local excision (WLE) only, SLNB, and ND. Univariate and multivariable regression was performed. RESULTS: Of 474 patients, 140 returned questionnaires (29.5% response rate; WLE, n = 49; SLNB, n = 76; ND, n = 15). No significant differences in SLANSS or Neck Dissection Impairment Index scores were found between the WLE and SLNB groups. SLANSS scores differed by 2 SD (P = .001) in the ND cohort, which had a 36% rate of neuropathy. Neck impairment was worse by 1 SD (P = .01) in the ND cohort. No differences were found in SF-36 domains. CONCLUSION: Neuropathy and neck impairment are components of morbidity after ND. These risks must be balanced with potential morbidity of locoregional recurrence in HNCM.

Lateral border and scapular tip free flaps: Old school versus new school.

Free tissue transfer from the subscapular system provides a wide array of options for both soft tissue and bony reconstruction. When bone stock is required for head and neck reconstruction, both the lateral scapular border free flap (LSBFF), supplied by the circumflex scapular artery, and the scapular tip free flap (STFF), supplied by the angular artery, are excellent options. Issues with positioning had previously prevented the widespread use of these bony subscapular system flaps. However, through the use of a Spider Limb Positioner, current clinical practice patterns allow for two team approaches in both of these free flaps. The following pictorial essay compares and contrasts the specific positioning and harvesting technique used for both the LSBFF and STFF, while discussing the clinical advantages and drawbacks of each. Both the lateral border scapula and scapular tip free flaps provide excellent bone stock for head and neck reconstruction. By positioning with currently available technology, both of these free flaps can be harvested through a two team approach.

Tumor-Infiltrating Lymphocytes in Patients With Advanced Laryngeal Cancer Undergoing Bioselection.

OBJECTIVE: Bioselection to assess tumor response after induction chemotherapy has been introduced as an alternative treatment strategy to total laryngectomy for patients with advanced larynx squamous cell carcinoma (LSCC). Tumor-infiltrating lymphocytes (TILs) have proven to serve as prognostic biomarkers in head and neck cancer but have not been evaluated as a way to select patients for treatment paradigms. The aim of this study is to evaluate the role of pretreatment TILs in patients with advanced LSCC undergoing the bioselection paradigm. STUDY DESIGN: Retrospective study. SETTING: Tertiary care hospital. METHODS: Patients with advanced LSCC treated with bioselection and available tissue were included (N = 76). Patients were stratified into CD8-low and CD8-high cohorts by using the median TIL count. Kaplan-Meier survival analysis and multivariate cox regression were performed with SPSS version 26 (IBM). RESULTS: After controlling for tobacco use, tumor site, and stage, a high CD8 TIL count was an independent predictor of improved 5-year disease-specific survival (hazard ratio, 0.17 [95% CI, 0.03-0.84]; P = .03). CD8 TIL counts did not predict response to induction chemotherapy; however, subgroup analysis of patients treated with chemoradiation therapy revealed that CD8 TIL count was significantly associated with degree of response (P = .012). CONCLUSION: These findings support prior data published by our group showing that TILs are predictive of disease-specific survival in patients with head and neck cancer. CD8 TIL counts were significantly associated with degree of clinical response after induction chemotherapy. These results suggest that pretreatment assessment of tumor-infiltrating CD8 cells could be useful in selecting patients.