RESUMO
PURPOSE: Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC. METHODS: E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index. RESULTS: Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6]) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented. CONCLUSION: Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC.
Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Cisplatino/uso terapêutico , Inibidor p16 de Quinase Dependente de Ciclina/análise , Neoplasias Orofaríngeas/terapia , Papillomaviridae/isolamento & purificação , Faringectomia , Radioterapia de Intensidade Modulada , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Quimiorradioterapia Adjuvante , Cisplatino/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/química , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Faringectomia/efeitos adversos , Intervalo Livre de Progressão , Estudos Prospectivos , Radioterapia de Intensidade Modulada/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/química , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Fatores de TempoRESUMO
PIK3CA is the most commonly altered oncogene in head and neck squamous cell carcinoma (HNSCC). We evaluated the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on survival in a PIK3CA-characterized cohort of 266 HNSCC patients and explored the mechanism in relevant preclinical models including patient-derived xenografts. Among subjects with PIK3CA mutations or amplification, regular NSAID use (≥6 mo) conferred markedly prolonged disease-specific survival (DSS; hazard ratio 0.23, P = 0.0032, 95% CI 0.09-0.62) and overall survival (OS; hazard ratio 0.31, P = 0.0043, 95% CI 0.14-0.69) compared with nonregular NSAID users. For PIK3CA-altered HNSCC, predicted 5-yr DSS was 72% for NSAID users and 25% for nonusers; predicted 5-yr OS was 78% for regular NSAID users and 45% for nonregular users. PIK3CA mutation predicted sensitivity to NSAIDs in preclinical models in association with increased systemic PGE2 production. These findings uncover a biologically plausible rationale to implement NSAID therapy in PIK3CA-altered HNSCC.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Carcinoma de Células Escamosas , Classe I de Fosfatidilinositol 3-Quinases , Neoplasias de Cabeça e Pescoço , Mutação , Proteínas de Neoplasias , Adulto , Idoso , Animais , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/enzimologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Taxa de Sobrevida , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Pharyngeal stenosis is a complication of head and neck cancer and sleep apnea treatment that results in functional impairment. Due to the location of the stenosis and tendency to recur, surgical management is challenging. Robotic surgery may allow these areas to be treated with surgical technique that would be difficult using traditional approaches. METHODS: A retrospective chart review was performed to identify patients who underwent transoral robotic surgery (TORS) for pharyngeal stenosis at a tertiary hospital system. RESULTS: Five patients were identified, ages 8-75 years. Length of follow-up ranged from 1-12 months. There was one failure, a 74 year old male with a history of chemoradiation to the area who has required additional procedures. CONCLUSION: TORS may offer improved surgical access to the pharynx in patients who require complex reconstruction that would otherwise be very difficult. Appropriate patient selection is necessary and long-term follow-up is warranted for the selected cases.