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
IMPORTANCE: After surgical resection for oral cavity squamous cell carcinoma, adjuvant radiotherapy may be recommended for patients at higher risk for locoregional recurrence, but it can be difficult to predict whether a particular patient will benefit. OBJECTIVE: To construct a model to predict which patients with oral cavity squamous cell carcinoma would benefit from adjuvant radiotherapy. DESIGN AND SETTING: We constructed several types of survival models using a set of 979 patients with oral cavity squamous cell carcinoma. Covariates were age, sex, tobacco use, stage, grade, margins, and subsite. The best performing model was externally validated on a set of 431 patients. PARTICIPANTS: The model was based on a set of 979 patients with oral cavity squamous cell carcinoma, including 563 from Memorial Sloan Kettering Cancer Center, New York, New York, and 416 from the Hospital AC Camargo, São Paulo, Brazil. The validation set consisted of 431 patients from Princess Margaret Hospital, Toronto, Ontario, Canada. MAIN OUTCOME AND MEASURE: The primary outcome measure of interest was locoregional recurrence-free survival. RESULTS: The lognormal model showed the best performance per the Akaike information criterion. An online nomogram was built from this model that estimates locoregional failure-free survival with and without postoperative radiotherapy. CONCLUSIONS AND RELEVANCE: A web-based nomogram can be used as a decision aid for adjuvant treatment decisions for patients with oral cavity squamous cell carcinoma.
Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Bucais/radioterapia , Nomogramas , Radioterapia Adjuvante , Brasil/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , New York/epidemiologia , Ontário/epidemiologia , Valor Preditivo dos Testes , Fatores de Risco , Fumar/epidemiologia , Taxa de SobrevidaRESUMO
Dos 181 casos de úlcera de córnea admitidos ao Kellogg Eye Center entre 1975 e 1983, 26 ocorreram em olhos que haviam sido submemtidos a ceratoplastia penetrante. Ceratopatia bolhosa foi a indicaçäo mais freqüente para ceratoplastia penetrante. O intervalo médio de tempo entre a ceratoplastia e o início da ulceraçäo foi de 7 meses