RESUMO
BACKGROUND: Concurrent inhibition of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) is an active and well tolerated regimen in recurrent head and neck cancer (HNC). In the current phase 1 trial, the authors sought to determine the maximum tolerated dose (MTD) and efficacy of concurrent erlotinib and celecoxib as a radiosensitizing regimen. METHODS: Fourteen patients with previously irradiated HNC with no distant metastases who required reirradiation were eligible. Treatment consisted of daily erlotinib 150 mg and twice daily celecoxib (escalated from 200 mg to 600 mg using a 3 + 3 design with an expanded cohort at the MTD) starting on Day 1 and was continued during radiation. Daily radiation was started on Day 15, and maintenance erlotinib was recommended. RESULTS: The recommended phase 2 dose of celecoxib was 400 mg. Three dose-limiting toxicities included late in-field orocutaneous fistula (Dose Level 2), osteonecrosis (Dose Level 3), and trismus (Dose Level 3). Acute grade ≥ 3 toxicities were uncommon and included mucositis (21%) and dermatitis (14%). At a median follow-up of 11 months, the 1-year locoregional control, progression-free survival, and overall survival rates were 60%, 37%, and 55%, respectively. CONCLUSIONS: Concurrent erlotinib, celecoxib, and reirradiation was a feasible and clinically active regimen in a population of patients with recurrent HNC who had a poor prognosis.
Assuntos
Receptores ErbB/antagonistas & inibidores , Neoplasias de Cabeça e Pescoço/radioterapia , Pirazóis/administração & dosagem , Quinazolinas/administração & dosagem , Radiossensibilizantes/uso terapêutico , Sulfonamidas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Celecoxib , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Intervalo Livre de Doença , Receptores ErbB/administração & dosagem , Cloridrato de Erlotinib , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , RetratamentoRESUMO
Fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has evolved to be an essential imaging modality in the evaluation of laryngeal carcinoma. Although the modality has limited utility in assessing the extent of the primary tumor, FDG PET has proved to be superior to anatomic modalities in the detection of lymph node and distant metastases. The role of FDG PET in the evaluation of patients with laryngeal tumors that are clinically classified as N0 has not shown consistent usefulness because of the innate resolution limitations of the camera. In the posttherapy setting, however, FDG PET has consistently demonstrated a high negative predictive value in the identification of recurrent disease, both during the course of therapy and during long-term follow-up. In addition, contrast material-enhanced computed tomography (CT) in conjunction with FDG PET has demonstrated a complementary role by allowing for superior anatomic coregistration and therefore more definitive diagnosis. There is sufficient evidence that with further advances in PET technology, this modality will likely become more useful in the detection of small lesions and occult nodal disease, as well as in guiding the management of laryngeal carcinoma.
Assuntos
Fluordesoxiglucose F18 , Aumento da Imagem/métodos , Neoplasias Laríngeas/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Técnica de Subtração , Tomografia Computadorizada por Raios X/métodos , Humanos , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: Lack of access to primary care physicians (PCPs) may be an important contributor to mortality differences attributed to race/ethnicity. This study examined the effects of primary care access on mortality of lung cancer patients in an underserved community. METHODS: Medical records of all newly diagnosed patients with primary lung cancer from 2012 to 2016 at a National Cancer Institute (NCI)-designated center in Bronx, New York were reviewed. Demographic data, PCP status, and residence in primary care shortage areas (PCSAs) were collected. Survival data from time of first imaging to death or the end of follow-up on January 1, 2018 were recorded. Survival analysis was performed using Kaplan-Meier and Cox hazards modeling. RESULTS: Among 1062 patients, 874 (82%) were PCSA residents, 314 (30%) were Hispanic, and 445 (42%) were African American. PCSA residents were likely Hispanics (P<0.001), African Americans (P<0.001), of lower income (P<0.001), and had advanced disease at diagnosis (P=0.01). Patients without established PCPs had more comorbidities (P=0.04), more advanced disease (P<0.001), and less in-network cancer treatment (P<0.001). PCSA residence (P=0.03, hazard ratio [HR]=1.27) and no established PCP (P<0.001, HR=1.50) were associated with increased mortality. In multivariable modeling, lack of established PCP remained a predictor of increased mortality (P=0.02, HR=1.25). DISCUSSION: Among newly diagnosed lung cancer patients, lack of established PCP is associated with increased mortality. Hispanics and African Americans increasingly resided in PCSAs, suggesting race/ethnicity mortality differences may be mediated by primary care shortage. Patients without PCPs had worse health outcomes. Effective health policy efforts to reduce mortality in lung cancer patients must include approaches to improve primary care access.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Neoplasias Pulmonares/mortalidade , Atenção Primária à Saúde/estatística & dados numéricos , Carcinoma de Pequenas Células do Pulmão/mortalidade , Adenocarcinoma/epidemiologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , New York/epidemiologia , Prognóstico , Características de Residência , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Carcinoma de Pequenas Células do Pulmão/patologia , Fatores Socioeconômicos , Taxa de SobrevidaRESUMO
BACKGROUND: The landmark National Lung Screening Trial demonstrated significant reduction in lung cancer-related mortality. However, European lung cancer screening (LCS) trials have not confirmed such benefit. We examined LCS patterns and determined the impact of LCS-led diagnosis on the mortality of newly diagnosed patients with lung cancer in an underserved community. PATIENTS AND METHODS: Medical records of patients diagnosed with primary lung cancer in 2013 through 2016 (n = 855) were reviewed for primary care provider (PCP) status and LCS eligibility and completion, determined using United States Preventative Services Task Force guidelines. Univariate analyses of patient characteristics were conducted between LCS-eligible patients based on screening completion. Survival analyses were conducted using Kaplan-Meier and multivariate Cox regression. RESULTS: In 2013 through 2016, 175 patients with primary lung cancer had an established PCP and were eligible for LCS. Among them, 19% (33/175) completed screening prior to diagnosis. LCS completion was associated with younger age (P = .02), active smoking status (P < .01), earlier stage at time of diagnosis (P < .01), follow-up in-network cancer treatment (P = .03), and surgical management (P < .01). LCS-eligible patients who underwent screening had improved all-cause mortality compared with those not screened (P < .01). Multivariate regression showed surgery (hazard ratio, 0.31; P = .04) significantly affected mortality. CONCLUSION: To our knowledge, this is the first study to assess LCS patterns and mortality differences on patients with screen-detected lung cancer in an urban underserved setting since the inception of United States Preventative Services Task Force guidelines. Patients with a LCS-led diagnosis had improved mortality, likely owing to cancer detection at earlier stages with curative treatment, which echoes the finding of prospective trials.
Assuntos
Técnicas de Apoio para a Decisão , Detecção Precoce de Câncer/estatística & dados numéricos , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/mortalidade , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Área Carente de Assistência Médica , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/terapia , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , População UrbanaRESUMO
Preliminary results demonstrated that concurrent sunitinib and stereotactic body radiation therapy (SBRT) is an active regimen for metastases limited in number and extent. This analysis was conducted to determine the long-term survival and cancer control outcomes for this novel regimen. Forty-six patients with oligometastases, defined as five or fewer clinical detectable metastases from any primary site, were treated on a phase I/II trial from February 2007 to September 2010. The majority of patients were treated with 37.5 mg sunitinib (days 1-28) and SBRT 50 Gy (days 8-12 and 15-19) and maintenance sunitinib was used in 39 % of patients. Median follow up for surviving patients is 3.6 years. The 4-year estimates for local control, distant control, progression-free and overall survival were 75 %, 40 %, 34 % and 29 %, respectively. At last follow-up, 26 % of patients were alive without evidence of disease, 7 % were alive with distant metastases, 48 % died from distant metastases, 2 % died from local progression, 13 % died from comorbid illness, and 4 % died from treatment-related toxicities. Patients with kidney and prostate primary tumors were associated with a significantly improved overall survival (hazard ratio = 0.25, p = 0.04). Concurrent sunitinib and SBRT is a promising approach for the treatment of oligometastases and further study of this novel combination is warranted.
Assuntos
Antineoplásicos/administração & dosagem , Quimiorradioterapia , Terapia Combinada/métodos , Indóis/administração & dosagem , Metástase Neoplásica/terapia , Pirróis/administração & dosagem , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , SunitinibeRESUMO
A phase II trial was conducted to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) into a well-described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. Patients with stage IVa-IVb or high-risk stage III squamous cell carcinomas were enrolled. Prior organ-conserving surgery or induction chemotherapy was allowed. IMRT was administered in 1.5 Gy fractions twice daily on days 1-5 of weeks 1, 3, 5, 7±9 for a total dose of 60-73.5 Gy. Concurrent systemic therapy consisted of 5-FU (600 mg/m2), HU (500 mg BID) and cetuximab (250 mg/m2). p16INK4A expression was assessed by immunohistochemistry. From January 2007 to January 2010, 65 patients (61 with stage IV disease; 31 with oropharyngeal primaries) were enrolled. At a median follow-up of 28 months, 2-year locoregional control, distant control, progression-free survival, event-free survival and overall survival were 79, 83, 72, 63 and 80%, respectively. In 48 patients with available pre-treatment tissue, p16 overexpression was associated with significantly increased distant control (p=0.03), progression-free survival (p=0.02), event-free survival (p=0.007) and overall survival (p=0.03). The most common grade 3-4 toxicities were mucositis (46%), leukopenia (18%), anemia (18%) and dermatitis (17%). Concurrent 5-FU, HU, cetuximab and SIB-IMRT is a highly active regimen, particularly in patients with p16-positive disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Radioterapia de Intensidade Modulada , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cetuximab , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Hidroxiureia/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Radioterapia de Intensidade Modulada/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Preclinical data suggest that sunitinib enhances the efficacy of radiotherapy. We tested the combination of sunitinib and hypofractionated image-guided radiotherapy (IGRT) in a cohort of patients with historically incurable distant metastases. METHODS: Twenty five patients with oligometastases, defined as 1-5 sites of active disease on whole body imaging, were enrolled in a phase II trial from 2/08 to 9/10. The most common tumor types treated were head and neck, liver, lung, kidney and prostate cancers. Patients were treated with the recommended phase II dose of 37.5 mg daily sunitinib (days 1-28) and IGRT 50 Gy (days 8-12 and 15-19). Maintenance sunitinib was used in 33% of patients. Median follow up was 17.5 months (range, 0.7 to 37.4 months). RESULTS: The 18-month local control, distant control, progression-free survival (PFS) and overall survival (OS) were 75%, 52%, 56% and 71%, respectively. At last follow-up, 11 (44%) patients were alive without evidence of disease, 7 (28%) were alive with distant metastases, 3 (12%) were dead from distant metastases, 3 (12%) were dead from comorbid illness, and 1 (4%) was dead from treatment-related toxicities. The incidence of acute grade ≥ 3 toxicities was 28%, most commonly myelosuppression, bleeding and abnormal liver function tests. CONCLUSIONS: Concurrent sunitinib and IGRT achieves major clinical responses in a subset of patients with oligometastases. TRIAL REGISTRATION: ClinicalTrials.gov NCT00463060.
Assuntos
Antineoplásicos/uso terapêutico , Quimiorradioterapia , Indóis/uso terapêutico , Neoplasias/terapia , Pirróis/uso terapêutico , Radioterapia Guiada por Imagem , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias/patologia , Prognóstico , Sunitinibe , Taxa de SobrevidaRESUMO
BACKGROUND: The objective of this phase 2 study was to evaluate the tolerability and efficacy of incorporating cetuximab and simultaneous integrated-boost (SIB), intensity-modulated radiation therapy (IMRT) into a well described 5-fluorouracil (5-FU) and hydroxyurea (HU)-based chemoradiation regimen. METHOD: Patients with stage IVA and IVB or high-risk stage III squamous cell carcinomas of the head and neck were enrolled on a phase 2 trial. Prior organ-conserving surgery or induction chemotherapy was allowed off protocol. SIB-IMRT was prescribed to low-risk volumes (43.2 gray [Gy] to 48 Gy) and intermediate-risk volumes (54-63 Gy). A separate IMRT cone-down plan was targeted to macroscopic disease (72 Gy). The median radiation dose was 72 Gy (range, 60-72 Gy) administered in 1.5 Gy fractions twice daily during Weeks 1, 3, 5, 7 and 9. Concurrent systemic therapy consisted of 5-FU (600 mg/m²), HU (500 mg twice daily), and cetuximab (250 mg/m²). RESULTS: From January 2007 through April 2008, 33 patients were enrolled. At a median follow-up of 24 months, the 2-year rates of locoregional control, distant control, disease-free survival, and overall survival were 83%, 79%, 69%, and 86%, respectively. Grade 3 toxicity consisted of mucositis in 33% of patients, radiation dermatitis in 15%of patients, anemia in 18% of patients, leukopenia in 18% of patients, neutropenia in 12% of patients, and thrombocytopenia in 3% of patients. Most patients (64%) were able to tolerate treatment without a feeding tube, and there were no acute or late grade ≥4 adverse events. CONCLUSIONS: The current results indicated that concurrent 5-FU, HU, and cetuximab plus SIB-IMRT is a promising and reasonably well tolerated approach to incorporating molecularly targeted therapy into curative therapy for patients with locally advanced head and neck cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Cetuximab , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Hidroxiureia/administração & dosagem , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Radioterapia de Intensidade ModuladaRESUMO
OBJECTIVES/HYPOTHESIS: To evaluate the patterns of failure, survival, and functional outcomes for patients treated with transoral robotic surgery (TORS) and compare these results with those from a cohort of patients treated with concurrent chemoradiation (CRT). STUDY DESIGN: Prospective non-randomized case control study. METHODS: Between April 2007 and April 2009, 30 patients with head and neck squamous cell carcinoma were treated with primary TORS and adjuvant therapy as indicated on an institutional review board-approved protocol. Patients were evaluated before treatment, after treatment, and at subsequent 3-month intervals after completing treatment to determine their disease and head and neck-specific functional status using the Performance Status Scale for Head and Neck Cancer and the Functional Oral Intake Score (FOIS). Functional scores were compared to a matched group of head and neck patients treated with primary CRT. RESULTS: The TORS patient population included 73% stage III-IV and 23% nonsmokers. The median follow-up was 20.4 months (range, 12.8-39.6 months). The 18-month locoregional control, distant control, disease-free survival, and overall survival were 91%, 93%, 78%, and 90%, respectively. Compared to the primary CRT group, TORS was associated with better short-term eating ability (72 vs. 43, P = .008), diet (43 vs. 25, P = .01), and FOIS (5.5 vs. 3.3, P < .001) at 2 weeks after completion of treatment. In contrast to TORS patients who returned to baseline, the CRT group continued to have decreased diet (P = .03) and FOIS (P = .02) at 12 months. CONCLUSIONS: Our early experience in treating selected head and neck cancers with TORS is associated with excellent oncologic and functional outcomes that compare favorably to primary CRT.