RESUMEN
OBJECTIVE: Limited availability of authentic human adenoid cystic carcinoma (ACC) cell lines has hindered progress in understanding mechanisms underpinning the biology of this disease and the development of safe and effective therapies. STUDY DESIGN: Surgical human ACC specimens (UM-HACC-6, UM-HACC-14) were dissociated into single cell suspensions and cultured in fibronectin-coated flasks. Alternatively, tumor fragments were transplanted subcutaneously into female immunodeficient (SCID) mice to establish patient-derived xenograft tumors (PDX; UM-PDX-HACC-14). RESULTS: Both ACC cell lines showed continuous growth in monolayers for over 100 passages. Total RNA-Seq, RT-PCR, and FISH analysis revealed that both are MYB-NFIB fusion negative. Western blots revealed passage-dependent expression of E-Cadherin, PCNA, p63, phospho-c-MYB, and NFIB. Both, UM-HACC-14 and UM-HACC-6 cells exhibited tumorigenic potential when injected orthotopically into mouse submandibular glands. CONCLUSION: UM-HACC-14, patient-matching UM-PDX-HACC-14, and the UM-HACC-6 cell line are new, authenticated preclinical models of ACC that are well suited for mechanistic and developmental therapeutics studies.
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Carcinoma Adenoide Quístico , Ratones SCID , Neoplasias de las Glándulas Salivales , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/metabolismo , Animales , Humanos , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/metabolismo , Ratones , Femenino , Línea Celular Tumoral , Western Blotting , Xenoinjertos , Hibridación Fluorescente in SituRESUMEN
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.
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Fístula Cutánea , Hipotiroidismo , Laringectomía , Complicaciones Posoperatorias , Terapia Recuperativa , Tiroxina , Humanos , Masculino , Laringectomía/efectos adversos , Femenino , Persona de Mediana Edad , Terapia Recuperativa/métodos , Anciano , Tiroxina/administración & dosificación , Tiroxina/efectos adversos , Tiroxina/uso terapéutico , Fístula Cutánea/etiología , Fístula Cutánea/prevención & control , Hipotiroidismo/etiología , Hipotiroidismo/tratamiento farmacológico , Complicaciones Posoperatorias/prevención & control , Fístula/etiología , Fístula/prevención & control , Administración Intravenosa , Adulto , Enfermedades Faríngeas/etiología , Enfermedades Faríngeas/prevención & control , Enfermedades Faríngeas/tratamiento farmacológico , Estudios ProspectivosRESUMEN
BACKGROUND: To address the rehabilitative barriers to frequency and precision of care, we conducted a pilot study of a biofeedback electropalatography (EPG) device paired with telemedicine for patients who underwent primary surgery +/- adjuvant radiation for oral cavity carcinoma. We hypothesized that lingual optimization followed by telemedicine-enabled biofeedback electropalatography rehabilitation (TEBER) would further improve speech and swallowing outcomes after "standard-of-care" SOC rehabilitation. METHOD: Pilot prospective 8-week (TEBER) program following 8 weeks of (SOC) rehabilitation. RESULTS: Twenty-seven patients were included and 11 completed the protocol. When examining the benefit of TEBER independent of standard of care, "range-of-liquids" improved by +0.36 [95% CI, 0.02-0.70, p = 0.05] and "range-of-solids" improved by +0.73 [95% CI, 0.12-1.34, p = 0.03]. There was a positive trend toward better oral cavity obliteration; residual volume decreased by -1.2 [95% CI, -2.45 to 0.053, p = 0.06], and "nutritional-mode" increased by +0.55 [95% CI, -0.15 to 1.24, p = 0.08]. CONCLUSION: This pilot suggests that TEBER bolsters oral rehabilitation after 8 weeks of SOC lingual range of motion.
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Biorretroalimentación Psicológica , Neoplasias de la Boca , Telemedicina , Humanos , Proyectos Piloto , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de la Boca/cirugía , Neoplasias de la Boca/rehabilitación , Biorretroalimentación Psicológica/métodos , Anciano , Estudios Prospectivos , Adulto , Resultado del Tratamiento , Trastornos de Deglución/rehabilitación , Trastornos de Deglución/etiología , Electrodiagnóstico , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/rehabilitaciónAsunto(s)
Carcinoma de Células Escamosas , Neoplasias Laríngeas , Disección del Cuello , Humanos , Disección del Cuello/métodos , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Neoplasias Laríngeas/terapia , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/cirugía , Masculino , Persona de Mediana Edad , Femenino , Estadificación de Neoplasias , AncianoRESUMEN
Importance: Patients with unknown primary squamous cell carcinoma (CUP) with cervical metastases typically receive comprehensive radiotherapy (RT) of the pharynx and bilateral neck. Typically, these patients receive comprehensive RT of the pharynx and bilateral neck that may produce treatment-related toxic effects. Objective: To determine whether localization of occult oropharyngeal cancers with transoral robotic surgery (TORS) combined with reduced pharyngeal and neck RT volumes provides acceptable disease control. Design, Setting, and Participants: This phase 2, single-group nonrandomized controlled trial at a single institution accrued 32 prospective participants with p16-positive CUP without a primary squamous cell carcinoma on examination and imaging from 2017 to 2019, and 24-month follow-up. The data analysis was conducted from January 2021 to June 2022. Intervention: Diagnostic- (n = 13) or therapeutic-intent (n = 9) TORS, with pharyngeal-sparing radiotherapy (PSRT) prescribed for negative margins or pT0, and unilateral neck RT (UNRT) prescribed for unilateral lymphadenopathy with lateralized primary tumor or pT0. Main Outcomes and Measures: Out-of-radiation treatment volume failure (<15% was hypothesized to be acceptable) and reports of local and regional recurrence, overall survival, toxic effects, swallowing outcomes (per the MD Anderson Dysphagia Inventory), and videofluoroscopic swallow (per Dynamic Imaging Grade of Swallowing Toxic Effects [DIGEST]) ratings. Results: The study sample comprised 22 patients (mean [SD] age, 59.1 [5.7] years; 3 [14%] females and 19 [86%] male) with CUP. Of these, 19 patients (86%) had tumor stage cN1; 2 (9%), cN2; and 1 (5%), cN3. Five patients (23%), 14 patients (64%), and 3 patients (13%) had 0, 1, or 2 primary tumors, respectively. Twenty patients received RT; of these, 9 patients (45%) underwent PSRT and 10 patients (50%), UNRT. In the diagnostic-intent group, 8 patients (62%) and 5 patients (38%) underwent RT and RT-concurrent chemotherapy, respectively. In the therapeutic-intent group, 6 patients (67%) and 1 patient (11%) received adjuvant RT-concurrent chemotherapy, respectively; 2 patients declined RT. Two-year out-of-radiation treatment volume failure, locoregional control, distant metastasis control, and overall survival were 0%, 100%, 95%, and 100%, respectively. Grade 3 or 4 surgical, acute, and late toxic effects occurred in 2 (9%), 5 (23%), and 1 (5%) patients, respectively. PSRT was associated with lower RT dose to superior constrictors (37 vs 53 Gy; mean difference, 16 Gy; 95% CI, 6.4, 24.9), smaller decline in swallowing scores during treatment (19.3 vs 39.7; mean difference, -20.4; 95% CI, -34.1 to -6.1), and fewer patients with worsening DIGEST grade on findings of videofluoroscopic swallow studies at 2 years (0% vs 60%; difference, 60%; 95% CI, 30% to 90%). Conclusions and Relevance: These findings indicate that TORS for p16-positive CUP allows RT volume deintensification with excellent outcomes and support future investigation in randomized clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT03281499.
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Neoplasias Primarias Desconocidas , Procedimientos Quirúrgicos Robotizados , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Primarias Desconocidas/radioterapia , Neoplasias Primarias Desconocidas/patología , Anciano , Estudios Prospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/cirugía , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/cirugía , Dosificación RadioterapéuticaRESUMEN
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.
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Disección del Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Calidad de Vida , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/virología , Neoplasias Orofaríngeas/mortalidad , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/cirugía , Anciano , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Adulto , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Estadificación de Neoplasias , Quimioradioterapia/métodos , Resultado del Tratamiento , Papillomaviridae/aislamiento & purificaciónRESUMEN
OBJECTIVE: The aim of the study is to describe the factors that influence outcome in adults with head and neck osteosarcoma (HNO) with a specific focus on the margin status. METHODS: Patients with a diagnosis of HNO between the years 1996-2021 were reviewed from the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) Database. Baseline characteristics, pathology, treatment, and outcomes were analyzed. Univariable (UVA) and multivariable (MVA) Cox regression models were performed. 5-year locoregional control rate and overall survival (OS) were estimated using Kaplan-Meier method and Log-Rank test. RESULTS: Of 50 patients with a median age of 40 years (range 16-80), 27 (54%) were male. HNO commonly involved the mandible (n = 21, 42%) followed by maxilla (n = 15, 30%). Thirteen (33.3%) had low-intermediate grade and 26 (66.6%) had high grade tumors. Three patients (6%) had negative resection margins (>5 mm), 24 (48%) had close margins (1-5 mm), 15 (30%) had positive margins (<1mm) and 7 (16%) had unknown margin status. In total, 39 (78%) received chemotherapy - 22 (44%) received neoadjuvant chemotherapy while 17 (34%) received adjuvant chemotherapy. A total of 12 (24%) patients received radiotherapy, of whom 8 (16%) had adjuvant and 3 (6%) had neo-adjuvant. Median follow-up time was 6.3 years (range 0.26-24.9). Disease recurred in 21 patients (42%), of whom 15 (30%) had local recurrence only, 4 (8%) had distant metastasis, and 2 (4%) had both local and distant recurrence. 5-year locoregional control rate and OS was 62% and 79.2% respectively. Resection margins <3 mm was associated with lower 5 years OS and locoregional control rate (Log-Rank p = 0.02, p = 0.01 respectively). CONCLUSION: Osteosarcomas of the head and neck are rare and local recurrence remains a concern. Surgical resection with negative resection margins may improve survival, and a 3 mm resection margin threshold may optimize survival. Radiotherapy and/or chemotherapy should be considered in a multidisciplinary setting based on risk-features.
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Neoplasias Óseas , Osteosarcoma , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Adulto , Masculino , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Márgenes de Escisión , Canadá/epidemiología , Osteosarcoma/patología , Sarcoma/patología , Neoplasias Óseas/patología , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patologíaRESUMEN
OBJECTIVE: The goal was to characterize four clinically distinct glossectomy defects to establish significant quantitative cut points using functional metrics, the MD Anderson Dysphagia Index (MDADI) and speech intelligibility. METHODS: Population included 101 patients treated with surgery, adjuvant radiation per NCCN guidelines, and ≥ 12 months follow-up. RESULTS: Defect groups: subtotal hemiglossectomy (1), hemiglossectomy (2), extended hemiglossectomy (3) and oral glossectomy (4) were compared: All outcomes supported a four defect model. Intergroup comparison of outcomes with subtotal hemiglossectomy as reference (p value): Tongue Protrusion <0.001,<0.001,<0.001; Elevation <0.001,<0.001,<0.001; Open Mouth Premaxillary Contact Elevation <0.001,<0.001,<0.001; Obliteration 0.6,<0.001,<0.001; Normalcy of Diet, <0.3,<0.001,<0.001; Nutritional Mode, <0.9,<0.8,<0.001; Range of Liquids, <0.4,<0.016,<0.02; Range of Solids, <0.5,<0.004,<0.001; Eating in Public, <0.2,<0.002,<0.03; Understandability of Speech, <0.9,<0.001,<0.001; Speaking in Public, <0.4,<0.03,<0.001; MDADI, <0.4,<0.005,<0.01; Single Word Intelligibility, <0.4,<0.1,<0.001; Sentence Intelligibility, <0.5,<0.08,<0.001; Words Per Minute Intelligibility, <0.6,<0.04,<0.001; Sentence Efficiency Ratio, <0.4,<0.03,<0.002. Proportion of patients by 4 defect groups who underwent: tissue transplantation, 51%,93.9%,100%,100%.Radiation,24%,67%,88%,80%.Between hemiglossectomy and extended hemiglossectomy, the defect extends into the contralateral floor of the mouth and/or the anterior tonsillar pillar; resection of these subunits limits tongue mobility with an impact on functional outcome and MDADI. Between extended hemiglossectomy and oral glossectomy, the defect extends to include the tip of the tongue and appears to impact functional outcome and MDADI. CONCLUSIONS: Subtotal hemiglossectomy, hemiglossectomy, extended glossectomy and oral glossectomy are associated with quantitative (elevation, protrusion, open mouth premaxillary contact and obliteration), qualitative (speech and swallowing) and MDADI differences, suggesting that these 4 ordinal defect groups are distinct.
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Carcinoma , Trastornos de Deglución , Neoplasias de la Boca , Procedimientos de Cirugía Plástica , Neoplasias de la Lengua , Humanos , Glosectomía , Neoplasias de la Lengua/cirugía , Neoplasias de la Lengua/etiología , Calidad de Vida , Neoplasias de la Boca/cirugía , Neoplasias de la Boca/etiología , Lengua/cirugía , Inteligibilidad del Habla , Deglución , Trastornos de Deglución/etiología , Medición de Resultados Informados por el Paciente , Carcinoma/cirugíaRESUMEN
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.
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Neoplasias Orofaríngeas , Humanos , Cetuximab/uso terapéutico , Neoplasias Orofaríngeas/patología , Linfocitos T CD8-positivos , Microambiente TumoralRESUMEN
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.
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Colgajos Tisulares Libres , Neoplasias de Cabeza y Cuello , Transferencia de Nervios , Neoplasias de la Lengua , Humanos , Deglución , Estudios Retrospectivos , Neoplasias de la Lengua/cirugía , Neoplasias de la Lengua/patología , Neoplasias de Cabeza y Cuello/cirugíaRESUMEN
PURPOSE: Intensity-modulated radiation therapy (IMRT) has enabled risk-tailored approach to elective mucosal and nodal clinical target volumes (CTVs) in treatment of head and neck carcinoma of unknown primary (HNCUP). This study report outcomes following such approach. METHODS: HNCUP patients treated with definitive IMRT between 2005 and 2018 were reviewed. Local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS) and grade ≥3 late toxicity (LT) were analyzed. Multivariable analysis (MVA) was used to identify OS predictors for entire cohort and cN2-3 subgroup. RESULTS: A total of 203 patients were eligible: cN1 (7%), cN2a (14%), cN2b (46%), cN2c (14%) and cN3 (19%). Among 118 patients with known HPV status (by p16 staining), 81 (68%) were positive. IMRT target volume spared contralateral tonsil (55%), bilateral or contralateral sides of hypopharynx (72%), nasopharynx (72%), larynx (87%) and contralateral uninvolved neck (21%). Median follow-up was 5 years. Five-year LF, RF, DM, OS, and LT were 3%, 14%, 10%, 79%, and 7% respectively. Four patients developed mucosal recurrence: 3 within and 1 at the margin of the elective mucosal CTV. None of ipsilateral neck irradiation patients failed in the contralateral uninvolved neck. MVA identified cN2c-N3, HPV-negative status and older age as predictors for inferior OS. Within cN2-3 subgroup (n = 189): cN2c-N3, HPV-negative status and older age predicted lower OS, while concurrent chemotherapy was associated with better OS. CONCLUSION: Definitive IMRT with risk-adaptive radiation volume de-escalation for HNCUP resulted in high probability of tumor control with acceptable rate of late toxicity.
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Carcinoma , Neoplasias de Cabeza y Cuello , Neoplasias Primarias Desconocidas , Infecciones por Papillomavirus , Radioterapia de Intensidad Modulada , Humanos , Neoplasias Primarias Desconocidas/radioterapia , Neoplasias Primarias Desconocidas/patología , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/etiología , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodosRESUMEN
IMPORTANCE: Patient-derived xenografts (PDXs) offer the opportunity to identify patients with oral cavity squamous cell carcinoma (OSCC) who are at risk for recurrence and optimize clinical decision-making. OBJECTIVE: To develop and validate a prediction score for locoregional failure (LRF) and distant metastases (DM) in OSCC that incorporates PDX engraftment in addition to known clinicopathological risk factors. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, PDX models were generated from patients with OSCC treated with curative intent at Princess Margaret Cancer Centre (Toronto, Canada) between 2006 and 2018. The cohort included 288 patients (aged ≥18 years) with a new diagnosis of nonmetastatic (M0) OSCC whose tumor samples were available for engraftment under the skin of xenograft mice. Patients were scored as a nonengrafter if PDX formation did not occur within 6 months. Data analysis was performed between August 2006 and May 2018. INTERVENTIONS: All patients received up-front curative-intent surgery followed by either observation or postoperative radiation with or without concurrent chemotherapy based on institutional guidelines. MAIN OUTCOMES AND MEASURES: Main outcomes were LRF, DM, and overall survival (OS). Multivariable analysis (MVA) was used to identify predictors of LRF and DM. Factors retained in the final MVA were used to construct a prediction score and classify patients into risk groups. RESULTS: Overall, 288 patients (mean [SD] age at diagnosis, 63.3 [12.3] years; 112 [39%] women and 176 [61%] men) with OSCC were analyzed. The MVA identified pT3-4, pathologic extranodal extension, and engraftment as predictors of LRF and DM. Patients whose tumors engrafted (n = 198) were more likely to develop LRF (hazard ratio [HR], 1.98; 95% CI, 1.24-3.18) and DM (HR, 2.64; 95% CI, 1.21-5.75) compared with nonengrafters. A prediction score based on the aforementioned variables identified patients at high risk and low risk for LRF (43.5% vs 26.5%), DM (38.2% vs 8.4%), and inferior OS (34% vs 66%) at 5 years. Additionally, rapid engraftment was shown to be similarly prognostic, with rapid engrafters demonstrating higher rates of relapse and poor OS. CONCLUSIONS: In this cohort study, a prediction score using OSCC PDX engraftment, in conjunction with pT3-4 and pathologic extranodal extension, was associated with improved prognostic utility of existing clinical models and predicted patients at risk for LRF, DM, and poor survival.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Adolescente , Adulto , Animales , Carcinoma de Células Escamosas/cirugía , Estudios de Cohortes , Extensión Extranodal , Femenino , Xenoinjertos , Humanos , Masculino , Ratones , Neoplasias de la Boca/cirugía , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
The current standard for the treatment of oropharynx cancers is radiation therapy. However, patients are frequently left with dysphagia characterized by penetration-aspiration (impaired safety) and residue (impaired efficiency). Although thickened liquids are commonly used to manage dysphagia, we lack evidence to guide the modification of liquids for clinical benefit in the head and neck cancer population. The objective of this study was to assess the impact of slightly and mildly thick liquids on penetration-aspiration and residue in 12 patients with oropharyngeal cancer who displayed penetration-aspiration on thin liquid within 3 to 6 months after completion of radiotherapy. Significantly fewer instances of penetration-aspiration were seen with slightly and mildly thick liquids as compared with thin (P < .05). No differences were found across stimuli in the frequency of residue. Patients with oropharyngeal cancers who present with post-radiation therapy dysphagia involving penetration-aspiration on thin liquids may benefit from slightly and mildly thick liquids without risk of worse residue.
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Trastornos de Deglución , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Deglución , Trastornos de Deglución/etiología , Humanos , Neoplasias Orofaríngeas/complicaciones , Neoplasias Orofaríngeas/radioterapiaRESUMEN
OBJECTIVES/HYPOTHESIS: Despite considerable effort being dedicated to contouring reconstruction plates, there remains limited evidence demonstrating an association between contour and reconstructive outcomes. We sought to evaluate whether optimizing mandibular reconstruction plate contouring is associated with reduced postoperative hardware complications. STUDY DESIGN: Retrospective cohort study. METHODS: A cohort study was performed with adult patients (age ≥18 years) who underwent mandibulectomy and osseous free flap reconstruction following oncologic ablation at the University Health Network in Toronto, Canada, between January 1, 2003 and December 31, 2014. Patients with computed tomography scans performed within 1 year of reconstruction were included. Computer-based three-dimensional models were generated and used to calculate the mean plate-to-bone gap (mm). The primary outcome was plate exposure. Secondary outcome included a composite of plate exposure or intraoral dehiscence. Logistic regression models were fitted for each outcome accounting for other patient and surgical characteristics associated with the primary outcome. RESULTS: Ninety-four patients met inclusion criteria, with a mean age of 60.4 (standard deviation [SD] 14.9). The mean follow-up time was 31.4 months (range 3-94). Reconstruction was performed with fibular (57%) and scapular free flaps (43%). In the multivariable model, small mean plate-to-bone gap (<1 mm) was independently associated with 86% reduced odds of plate exposure (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.02-0.55). Mean plate-to-bone gap less than 1 mm was also independently associated with reduced odds of developing a composite of plate exposure or intraoral dehiscence (OR, 0.29; 95%CI, 0.11-0.75). CONCLUSION: Optimizing plate contouring during mandibular reconstruction may decrease the development of postoperative hardware complications. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:61-66, 2022.
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Placas Óseas , Reconstrucción Mandibular/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Placas Óseas/efectos adversos , Femenino , Colgajos Tisulares Libres/cirugía , Humanos , Masculino , Osteotomía Mandibular/métodos , Reconstrucción Mandibular/efectos adversos , Reconstrucción Mandibular/instrumentación , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: Despite increasing recognition of the importance of functional outcomes for patients with head and neck cancer, post-treatment neck fibrosis remains poorly understood. We sought to develop and validate a patient reported outcome measure for head and neck cancer patients with neck fibrosis. STUDY DESIGN: Prospective multiphase cross-sectional study. METHODS: To guide instrument development, we employed the World Health Organization International Classification of Functioning, Disability and Health as our conceptual framework. Items were generated using a composite strategy consisting of patient focus groups, literature review, and expert opinion from a multidisciplinary group. Candidate items were reduced through the item impact method. Preliminary psychometric properties of the finalized instrument were evaluated through measures of internal consistency, test-retest reliability, and construct validity. RESULTS: Four in person focus groups were held with 13 head and neck cancer patients. The process of item generation led to 221 relevant citations and 68 unique items. An additional 17 items were identified from review of existing neck disability questionnaires and expert opinion. A draft instrument with 25 candidate items was generated and reduced to its final 15-item scale using item impact method. Early psychometric testing revealed excellent internal consistency (Cronbach's alpha = 0.95) and test-retest reliability [ICC = 0.95]. Internal consistency at the item level was good (>0.7) for 11/15 individual items. Four separate constructs were evaluated. Three of the four constructs matched our a priori hypotheses. CONCLUSION: The Neck Fibrosis Scale demonstrates preliminary reliability and validity for discriminate use. Further research is needed to confirm dimensionality and assess responsiveness. LEVEL OF EVIDENCE: NA Laryngoscope, 132:1015-1021, 2022.
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Reproducibilidad de los Resultados , Estudios Transversales , Fibrosis , Humanos , Estudios Prospectivos , Psicometría , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Symptom burden is common in head and neck cancer patients though it frequently remains undetected and untreated. The Edmonton Symptom Assessment System - revised version (ESAS-r) is a generic symptom scale deployed in many outpatient settings worldwide. The ESAS-r is meant to improve symptom detection and management. We sought to review the ESAS-r and its psychometric properties in a head and neck oncology population. METHODS: Narrative Review. RESULTS: Over the past 30 years, the ESAS-r has emerged as one of the most used symptom scales for cancer patients. Its psychometric properties in a heterogenous cancer population are well supported, proving to be reliable and valid in a variety of settings. The linking of ESAS-r scores with Ontario administrative health data has led to a detailed assessment of validity in head and neck cancer. The ESAS-r can discriminate between high and low levels of symptom burden and is responsive to change over time in this patient population. ESAS-r scores have also been shown to be a strong predictor of future emergency department use and unplanned hospitalization in head and neck cancer patients. CONCLUSIONS: The ESAS-r is reliable and valid in the head and neck cancer population and may serve as a useful clinical endpoint in research studies.
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Neoplasias de Cabeza y Cuello , Neoplasias , Servicio de Urgencia en Hospital , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/diagnóstico , Hospitalización , Humanos , Neoplasias/diagnóstico , Cuidados Paliativos , Psicometría , Encuestas y Cuestionarios , Evaluación de SíntomasRESUMEN
BACKGROUND: Of interest is the long-term neck and shoulder impairment of patients treated with primary chemoradiotherapy (CRT). This is important for counseling patients regarding treatment decisions when discussing primary CRT. METHODS: A cross-sectional study to identify factors that contribute to neck and shoulder dysfunction in patients treated with primary CRT. We utilized the neck dissection impairment index (NDII). Eighty-seven patients treated between 2003 and 2010, who were free of disease, responded; 24 of these 87 underwent post-CRT neck dissection. Mean interval since completion of CRT was over 5 years (62.7 months). Mean age, 63.5 years, male:female 75:12. RESULTS: Mean NDII score was 87.4 (SD 22.1, range 5-100). Multiple linear regression revealed worse NDII scores for patients with larger pre-CRT gross tumor nodal volume (GTVnodal), controlled for age, sex, body mass index (BMI), and the presence of neck dissection (p = 0.02). There were significant associations with increasing GTVnodal and "low" scores for components of the NDII that assessed neck pain (p = 0.02), neck stiffness (p = 0.01), lifting heavy objects (p = 0.02), reaching overhead (p = 0.02), and ability to do work (p = 0.02). Physical therapy (PT) was evaluated as an "anchor" but it was prescribed "as needed." Regression revealed participation in PT was associated with higher GTVnodal, lower BMI, presence of neck dissection, and female sex (p = 0.00007). CONCLUSION: GTVnodal was an independent predictor of neck and shoulder impairment. High GTVnodal was associated with increased pain and stiffness, and increased difficulty lifting heavy objects, reaching overhead, overall ability to perform work-related tasks and was associated with participation in post-treatment PT.
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Neoplasias de Cabeza y Cuello , Disección del Cuello , Quimioradioterapia/efectos adversos , Estudios Transversales , Femenino , Neoplasias de Cabeza y Cuello/terapia , Humanos , Masculino , Persona de Mediana Edad , Hombro , Carcinoma de Células Escamosas de Cabeza y Cuello , SobrevivientesRESUMEN
PURPOSE: To determine the outcomes of oral cavity squamous cell cancer (OSCC) patients treated with non-surgical approach i.e. definitive intensity-modulated radiation therapy (IMRT). METHODS: All OSCC patients treated radically with IMRT (without primary surgery) between 2005-2014 were reviewed in a prospectively collected database. OSCC patients treated with definitive RT received concurrent chemotherapy except for early stage patients or those who declined or were unfit for chemotherapy. The 5-year local, and regional, distant control rates, disease-free, overall, and cancer-specific survival, and late toxicity were analyzed. RESULTS: Among 1316 OSCC patients treated with curative-intent; 108 patients (8%) received non-operative management due to: medical inoperability (n = 14, 13%), surgical unresectability (n = 8, 7%), patient declined surgery (n = 15, 14%), attempted preservation of oral structure/function in view of required extensive surgery (n = 53, 49%) or extensive oropharyngeal involvement (n = 18, 17%). Sixty-eight (63%) were cT3-4, 38 (35%) were cN2-3, and 38 (35%) received concurrent chemotherapy. With a median follow-up of 52 months, the 5-year local, regional, distant control rate, disease-free, overall, and cancer-specific survival were 78%, 92%, 90%, 42%, 50%, and 76% respectively. Patients with cN2-3 had higher rate of 5-year distant metastasis (24% vs 3%, p = 0.001), with detrimental impact on DFS (p = 0.03) and OS (p < 0.02) on multivariable analysis. Grade ≥ 3 late toxicity was reported in 9% of patients (most common: grade 3 osteoradionecrosis in 6%). CONCLUSIONS: Non-operative management of OSCC resulted in a meaningful rate of locoregional control, and could be an alternative curative approach when primary surgery would be declined, unsuitable or unacceptably delayed.
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Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Radioterapia de Intensidad Modulada , Terapia Combinada , Humanos , Neoplasias de la Boca/terapia , Radioterapia de Intensidad Modulada/efectos adversos , Estudios RetrospectivosRESUMEN
BACKGROUND: We aimed to compare unstimulated saliva flow using 3-minute modified Schirmer test (MST) following bilateral vs unilateral radiotherapy (RT) in oropharyngeal carcinoma (OPC). METHODS: We reviewed OPC patients treated with definitive intensity-modulated radiation therapy (IMRT) between 2011 and 2017. MST was measured at baseline, 1-/6-/12-/24-month post-RT. MST values were compared between bilateral-RT vs unilateral-RT groups. Multivariable logistic regression analysis (MVA) identified predictors of hyposalivation (MST < 25 mm). RESULTS: Total 498 bilateral-RT and 36 unilateral-RT patients were eligible. The MST values at 1-/6-/12-/24-month post-RT were all significantly reduced from baseline for the entire cohort. Baseline unilateral-RT and bilateral-RT MST values (in mm) were similar (P = .2), but much higher for unilateral-RT 1-month (mean: 19.1 vs 13.0, P = .03), 6-month (20.5 vs 9.3, P < .001), 12-month (20.1 vs 11.9, P < .01), and 24-month post-RT (22.2 vs 13.9, P = .04). MVA confirmed that unilateral RT reduced the likelihood of hyposalivation vs bilateral RT (OR 2.36, P = .006). CONCLUSION: Unilateral RT reduces unstimulated salivary flow in OPC patients.
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Carcinoma , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Radioterapia de Intensidad Modulada , Xerostomía , Humanos , Neoplasias Orofaríngeas/radioterapia , Saliva , Xerostomía/etiologíaRESUMEN
INTRODUCTION: Advanced oral cancer and its ensuing treatment engenders significant morbidity and mortality. Patients are often elderly with significant comorbidities. Toxicities associated with surgical resection can be devastating and they are often highlighted by patients as impactful. Given the potential for suboptimal oncological and functional outcomes in this vulnerable patient population, promotion and performance of shared decision making (SDM) is crucial.Decision aids (DAs) are useful instruments for facilitating the SDM process by presenting patients with up-to-date evidence regarding risks, benefits and the possible postoperative course. Importantly, DAs also help elicit and clarify patient values and preferences. The use of DAs in cancer treatment has been shown to reduce decisional conflict and increase SDM. No DAs for oral cavity cancer have yet been developed.This study endeavours to answer the question: Is there a patient or surgeon driven need for development and implementation of a DA for adult patients considering major surgery for oral cancer? METHODS AND ANALYSIS: This study is the first step in a multiphase investigation of SDM during major head and neck surgery. It is a multi-institutional convergent parallel mixed-methods needs assessment study. Patients and surgeon dyads will be recruited to complete questionnaires related to their perception of the SDM process (nine-item Shared Decision-Making Questionnaire, SDM-Q-9 and SDM-Q-Doc) and to take part in semistructured interviews. Patients will also complete questionnaires examining decisional self-efficacy (Ottawa Decision Self-Efficacy Scale) and decisional conflict (Decisional Conflict Scale). Questionnaires will be completed at time of recruitment and will be used to assess the current level of SDM, self-efficacy and conflict in this setting. Thematic analysis will be used to analyse transcripts of interviews. Quantitative and qualitative components of the study will be integrated through triangulation, with matrix developed to promote visualisation of the data. ETHICS AND DISSEMINATION: This study has been approved by the research ethics boards of the Nova Scotia Health Authority (Halifax, Nova Scotia) and the University Health Network (Toronto, Ontario). Dissemination to clinicians will be through traditional approaches and creation of a head and neck cancer SDM website. Dissemination to patients will include a section within the website, patient advocacy groups and postings within clinical environments.