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1.
Artigo em Inglês | MEDLINE | ID: mdl-38881401

RESUMO

OBJECTIVE: We evaluated vessel counts in the pharyngeal mucosal margins of patients who underwent salvage laryngectomy to establish whether mucosal vascularity might predict fistula risk. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary Medical Center. METHODS: Patients who underwent salvage total laryngectomy at our institution between 1999 and 2015 were identified. Pharyngeal mucosal margins from laryngectomy specimens were evaluated histologically for each patient, and vessel counts were performed on 5 ×10 images. The primary outcome measure was fistula within 30 days of surgery and mean vessel counts were assessed as the principle explanatory variable. RESULTS: Seventy patients were included and 40% developed a postoperative fistula. There was a large difference in the mean vessel count in patients who did develop fistula (48.6 vessels/×10 field) compared to those who did not (34.7 vessels/×10 field). A receiver operative characteristic curve found that a cutoff value of 33.9 vessels/×10 field provided a sensitivity of 75% and specificity of 62% to predict the likelihood of fistula occurrence (area under the curve = 0.71, 95% confidence interval [CI]: 0.59-0.83). In a binary logistic regression, patients with vessel counts greater than 33.9 had a 5-fold increased risk of developing fistula (95% CI: 1.8-16.45). Histologically, vessels in the pharyngeal mucosa of patients who developed fistulas were more disorganized. CONCLUSION: After salvage laryngectomy, patients with higher mean mucosal margin vessel counts are at increased risk of fistula. The mechanism is unknown, but the disorganization of the vasculature may contribute to poor wound healing. Vessel counting may allow for fistula risk stratification and guide postoperative care.

2.
Oral Oncol ; 156: 106917, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945011

RESUMO

BACKGROUND: Neoadjuvant chemotherapy for induction selection of definitive treatment (IS) protocols have shown excellent outcomes for organ preservation and survival in patients with T3 laryngeal squamous cell carcinoma (LSCC). We seek to evaluate survival and organ preservation outcomes in T4 LSCC patients treated with IS protocols. METHODS: Retrospective cohort of advanced T3 and T4 LSCC patients who underwent IS protocols based upon potential for preserving a functional larynx. Patients received one neoadjuvant cycle of platinum-based chemotherapy with either 5-fluorouracil or docetaxel or with two cycles of platinum-based chemotherapy with docetaxel and a Bcl-2 inhibitor. Patients who achieved ≥ 50 % response as determined by radiographic review and/or endoscopic evaluation received definitive chemoradiation. Patients who had < 50 % response after IS underwent total laryngectomy (TL) followed by post-operative radiation +/- chemotherapy. RESULTS: Amongst T4 patients, 114 met inclusion criteria including 89 who underwent IS protocols and 25 who received an upfront TL. In total, 76.0 % of T3 patients and 71.9 % of T4 patients responded to IS and underwent definitive chemoradiation. There was no significant difference in hazard of death between T4 IS and T4 TL patients (HR: 0.9, p = 0.86). Among responders, there was no significant difference in 5-year laryngectomy-free survival (T3 - 59.6 %, T4 44.3 %, p = 0.15) or laryngeal preservation by T stage (T3 - 72.8 %, T4 - 73.0 %, p = 0.84). CONCLUSIONS: Select T4 patients may benefit from organ preservation using IS protocols with similar response rates to patients with T3 tumors, without compromising survival when compared to upfront TL.

3.
Clin Cancer Res ; 30(14): 2910-2916, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38723280

RESUMO

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 perioperative 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). Postoperatively, intravenous levothyroxine was administered at a weight-based dose (1.3 mcg/kg/d) and transitioned to enteral dosing on day 7. Free T3, T4, and thyroid-stimulating hormones were collected, and dosing was adjusted accordingly. The primary endpoints were rates of fistula formation and fistula requiring reoperation, compared with matched historic controls. All patients were monitored for adverse effects. RESULTS: The rate of postoperative hypothyroidism was 21% compared with 49% in a matched historic cohort. The rate of fistula formation was 18.1%, whereas the rate of fistula requiring reoperation was 4.2%, significantly lower than rates in our historic cohort (34.6% and 14.8%, respectively; P = 0.02 and 0.01). Postoperative hypothyroidism and recurrent clinical stage predicted fistula requiring reoperation in multivariate analysis; other acute phase reactants were not predictive. There were no observed adverse events related to levothyroxine supplementation. CONCLUSIONS: Postoperative intravenous levothyroxine supplementation reduced rates of acute hypothyroidism, fistula formation, and fistula requiring reoperation 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.


Assuntos
Fístula Cutânea , Hipotireoidismo , Laringectomia , Complicações Pós-Operatórias , Terapia de Salvação , Tiroxina , Humanos , Masculino , Laringectomia/efeitos adversos , Feminino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Idoso , Tiroxina/administração & dosagem , Tiroxina/efeitos adversos , Tiroxina/uso terapêutico , Fístula Cutânea/etiologia , Fístula Cutânea/prevenção & controle , Hipotireoidismo/etiologia , Hipotireoidismo/tratamento farmacológico , Complicações Pós-Operatórias/prevenção & controle , Fístula/etiologia , Fístula/prevenção & controle , Administração Intravenosa , Adulto , Doenças Faríngeas/etiologia , Doenças Faríngeas/prevenção & controle , Doenças Faríngeas/tratamento farmacológico , Estudos Prospectivos
4.
Otolaryngol Head Neck Surg ; 171(1): 73-80, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38643408

RESUMO

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.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Humanos , Retalhos de Tecido Biológico/irrigação sanguínea , Retalhos de Tecido Biológico/economia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/economia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/economia , Procedimentos de Cirurgia Plástica/métodos , Idoso , Duração da Cirurgia , Custos e Análise de Custo , Tempo de Internação/economia
5.
Head Neck ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38680087

RESUMO

BACKGROUND: Post-treatment surveillance recommendations for oropharyngeal cancer do not vary with p16 status despite the differences in outcomes. The optimal algorithm personalizing follow-up for these patients remains undefined. Here, we evaluate the feasibility and utility of incorporating electronic patient-reported outcomes (ePROs) and circulating tumor DNA (ctDNA) into routine surveillance for patients treated for p16+ oropharynx cancer. METHODS: A prospective registry was developed in which ePROs and ctDNA were incorporated into routine surveillance among patients with oropharynx cancer. ePROs were emailed monthly for 1 year and blood HPV ctDNA testing was performed every 3-6 months. The primary objective was to assess patient compliance with ePRO-based surveillance with adequate compliance defined as ≥85% of patients completing monthly ePROs. Sensitivity, specificity, and positive/negative predictive values to detect recurrence were calculated for ePROs, HPV ctDNA, or the combination. RESULTS: Of 122 patients who initially expressed interest, 76 completed the electronic consent process and 44/76 (58%) were compliant with monthly surveys over 1 year; thus adequate compliance was not achieved. Technical difficulties associated with ePRO receipt through email largely limited participation. Provider feedback was significantly associated with heightened ePRO compliance. One hundred and six patients had ctDNA testing with a mean number of three tests per patient. Sensitivity to detect recurrence was 75% for the combination of ePROs and ctDNA. CONCLUSION: Despite lower than anticipated compliance with ePROs, our findings show promise for incorporation of HPV ctDNA into surveillance paradigms for HPV-related oropharynx cancer with suggestions of methods to optimize ePRO formats for personalized surveillance.

6.
Clin Cancer Res ; 30(11): 2393-2401, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38517480

RESUMO

PURPOSE: Locoregionally advanced HPV+ oropharyngeal squamous cell carcinoma (OPSCC) has excellent cure rates, although current treatment regimens are accompanied by acute and long-term toxicities. We designed a phase II deescalation trial for patients with HPV+ OPSCC to evaluate the feasibility of an upfront neck dissection to individualize definitive treatment selection to improve the quality of life without compromising survival. PATIENTS AND METHODS: Patients with T1-3, N0-2 HPV+ OPSCC underwent an upfront neck dissection with primary tumor biopsy. Arm A included patients with a single lymph node less than six centimeters, with no extracapsular spread (ECS) and no primary site adverse features underwent transoral surgery. Arm B included patients who had two or more positive lymph nodes with no ECS, or those with primary site adverse features were treated with radiation alone. Arm C included patients who had ECS in any lymph node and were treated with chemoradiation. The primary endpoint was quality of life at 1 year compared with a matched historical control. RESULTS: Thirty-four patients were enrolled and underwent selective neck dissection. On the basis of pathologic characteristics, 14 patients were assigned to arm A, 10 patients to arm B, and 9 to arm C. A significant improvement was observed in Head and Neck Quality of Life (HNQOL) compared with historical controls (-2.6 vs. -11.9, P = 0.034). With a median follow-up of 37 months, the 3-year overall survival was 100% and estimated 3-year estimated progression-free survival was 96% [95% confidence interval (CI), 76%-99%]. CONCLUSIONS: A neck dissection-driven treatment paradigm warrants further research as a deintensification strategy.


Assuntos
Esvaziamento Cervical , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Qualidade de Vida , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/cirurgia , Idoso , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Adulto , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estadiamento de Neoplasias , Quimiorradioterapia/métodos , Resultado do Tratamento , Papillomaviridae/isolamento & purificação
7.
Laryngoscope Investig Otolaryngol ; 9(2): e1217, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38525113

RESUMO

Objective: Gaps in gender-based equity persist in academic otolaryngology. Here we present a needs-based assessment of otolaryngology faculty and trainees regarding facilitators and barriers to professional satisfaction and career development in academic medicine. Methods: A qualitative study of otolaryngology faculty, trainees, and administrators who identify as women at an academic tertiary care center was performed from 2020 to 2021 using focus groups and semi-structured interviews. Five confidential, virtual focus group sessions moderated by a third-party executive coach were audio-taped, transcribed, and reviewed for thematic content. Results: Of 48 women invited, 77% participated (18 faculty/administrative leaders, 10 residents/fellows, 4 audiologists). Participants noted direct patient care, support from colleagues who identify as women, and the transition to virtual meetings as facilitators of current professional satisfaction. Five themes emerged as barriers to workplace satisfaction and career development including (1) limited professional schedule flexibility, (2) competing commitments such as childcare exacerbated by pandemic, (3) lack of visible departmental leadership who identify as women, (4) perceived lack of organic sponsorship within subspecialty divisions, and (5) frequent identity-associated microaggressions from patients and staff outside the department. Strategies identified for improving gender-based equity included (1) promoting department-wide awareness of workplace gender-based differences, (2) implicit bias training within established programming such as grand rounds conferences, and (3) novel faculty programming such as leadership development training and formal junior faculty mentorship. Conclusion: Confidential needs-based assessment of otolaryngology faculty and trainees identified both persistent gaps and strategies to enhance recruitment, support career development, and grow professional satisfaction of women within academic otolaryngology. Level of Evidence: 3.

8.
JAMA Otolaryngol Head Neck Surg ; 149(11): 1021-1026, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37796525

RESUMO

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.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cabeça/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/complicações , Pescoço/cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Idoso
9.
BMC Anesthesiol ; 23(1): 254, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37507689

RESUMO

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.


Assuntos
Anestésicos , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Humanos , gama-Ciclodextrinas/farmacologia , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Estudos Retrospectivos , Sugammadex , Doença Iatrogênica , Androstanóis
10.
Plast Reconstr Surg ; 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37285194

RESUMO

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.

11.
Cancer ; 129(18): 2817-2827, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37162461

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações , Infecções por Papillomavirus/complicações , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/complicações
12.
Head Neck ; 45(5): 1281-1287, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36932871

RESUMO

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.


Assuntos
Neoplasias Orofaríngeas , Humanos , Cetuximab/uso terapêutico , Neoplasias Orofaríngeas/patologia , Linfócitos T CD8-Positivos , Microambiente Tumoral
13.
Int J Radiat Oncol Biol Phys ; 117(1): 171-180, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36931572

RESUMO

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.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Humanos , Fluordesoxiglucose F18 , Estudos de Viabilidade , Estudos Prospectivos , Tomografia por Emissão de Pósitrons , Neoplasias Orofaríngeas/diagnóstico por imagem , Neoplasias Orofaríngeas/terapia , Quimiorradioterapia/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço
14.
Otolaryngol Head Neck Surg ; 168(3): 384-391, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35639485

RESUMO

OBJECTIVE: To explore challenges and opportunities for supporting midcareer women otolaryngologists in the areas of negotiation and sponsorship. STUDY DESIGN: Qualitative approach using semistructured interviews. SETTING: Online multi-institutional interviews. METHODS: This study was performed from June to August 2021. Women otolaryngologists representing diverse subspecialties, training, and practice environments were recruited via a purposive criterion-based sampling approach. Semistructured interviews were transcribed, coded, and analyzed via an inductive-deductive approach to produce a thematic content analysis. RESULTS: Among the 12 women interviewees, who represented 7 subspecialties, the majority were Caucasian (58%) and in academic practice (50%). The median residency graduation year was 2002 (range, 1982-2013). Participants expressed several challenges that women otolaryngologists face with respect to negotiation, including the absence of systematic formal negotiation training, gendered expectations that women experience during negotiations, and a perceived lack of power in negotiations. Obstacles to effective sponsorship included difficulty in the identification of sponsors and the influence of gender and related systemic biases that hindered sponsorship opportunities. CONCLUSION: Notable gender disparities exist for negotiation and sponsorship in the midcareer stage for women otolaryngologists. Women start at a disadvantage due to a lack of negotiation training and access to sponsors, which is exacerbated by systemic gender bias and power differentials as women advance in their careers. This study highlights opportunities to improve negotiation and sponsorship for women, with the goal of promoting a more diverse workforce.


Assuntos
Internato e Residência , Otorrinolaringologistas , Humanos , Masculino , Feminino , Negociação , Sexismo , Recursos Humanos
16.
Head Neck ; 45(4): 798-805, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36579434

RESUMO

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.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Transferência de Nervo , Neoplasias da Língua , Humanos , Deglutição , Estudos Retrospectivos , Neoplasias da Língua/cirurgia , Neoplasias da Língua/patologia , Neoplasias de Cabeça e Pescoço/cirurgia
17.
Oral Oncol ; 135: 106226, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36323071

RESUMO

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.


Assuntos
Neoplasias de Cabeça e Pescoço , Linfócitos do Interstício Tumoral , Humanos , Linfócitos do Interstício Tumoral/patologia , Antígeno B7-H1 , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/patologia , Biomarcadores Tumorais
18.
Clin Cancer Res ; 28(23): 5049-5057, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36107219

RESUMO

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.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Dosagem Radioterapêutica , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Intervalo Livre de Doença , Imageamento por Ressonância Magnética
19.
Am J Crit Care ; 31(6): 452-460, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35953441

RESUMO

BACKGROUND: Tracheostomies are highly aerosolizing procedures yet are often indicated in patients with COVID-19 who require prolonged intubation. Robust investigations of the safety of tracheostomy protocols and provider adherence and evaluations are limited. OBJECTIVES: To determine the rate of COVID-19 infection of health care personnel involved in COVID-19 tracheostomies under a multidisciplinary safety protocol and to investigate health care personnel's attitudes and suggested areas for improvement concerning the protocol. METHODS: All health care personnel involved in tracheostomies in COVID-19-positive patients from April 9 through July 11, 2020, were sent a 22-item electronic survey. RESULTS: Among 107 health care personnel (80.5%) who responded to the survey, 5 reported a positive COVID-19 test result (n = 2) or symptoms of COVID-19 (n = 3) within 21 days of the tracheostomy. Respondents reported 100% adherence to use of adequate personal protective equipment. Most (91%) were familiar with the tracheostomy protocol and felt safe (92%) while performing tracheostomy. Suggested improvements included creating dedicated tracheostomy teams and increasing provider choices surrounding personal protective equipment. CONCLUSIONS: Multidisciplinary engagement in the development and implementation of a COVID-19 tracheostomy protocol is associated with acceptable safety for all members of the care team.


Assuntos
COVID-19 , Humanos , Traqueostomia/efeitos adversos , SARS-CoV-2 , Equipamento de Proteção Individual , Atenção à Saúde
20.
Curr Probl Cancer ; 46(5): 100894, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35989105

RESUMO

Translational research describes the process of applying observations and scientific discoveries made in the laboratory to clinical applications that can improve the health of individual patients, most often through clinical trials. To apply the findings of translational research studies to the broader population, the study population must accurately reflect the group of patients afflicted by a particular disease. Yet, it is well known that significant disparities exist for underrepresented groups and lower socioeconomic populations in clinical trials. In fact, only 20% of randomized controlled studies published in high-impact oncology journals include subgroup analyses to assess differences in outcomes based on race or ethnicity.1 If effective interventions to decrease health disparities in research are to be implemented, it is critical to understand the multifactorial influences that create such differences. These are complex and include individual patient factors, family and social support, provider and organizational factors, as well as policy and community factors. Patient access to tertiary or quaternary care academic centers or designated cancer centers with the funding and resources to carry out translational research and knowledge of ongoing available research endeavors is often critical. Active community engagement and outreach and deep understanding of a particular health system's catchment area are necessary to increase both awareness and participation in clinical trials. Without significant progress in biomedical research patient recruitment, existing racial and ethnic health disparities will be challenging to overcome.


Assuntos
Pesquisa Biomédica , Acessibilidade aos Serviços de Saúde , Etnicidade , Humanos , Seleção de Pacientes , Pesquisa Translacional Biomédica , Estados Unidos
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