RESUMO
PURPOSE: The primary objective of this phase I study was to determine the maximum tolerated dose for pemetrexed, alone and in combination with carboplatin, with concurrent radiotherapy. EXPERIMENTAL DESIGN: Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) or esophageal cancer were treated every 21 days for two cycles. Regimen 1 was pemetrexed (200-600 mg/m(2)); regimen 2 was pemetrexed (500 mg/m(2)) with escalating carboplatin doses (AUC = 4-6). Both regimens included concurrent radiation (40-66 Gy; palliative-intent doses were lower). RESULTS: Thirty patients (18 locally advanced and 12 metastatic with dominant local symptoms) were enrolled, with an Eastern Cooperative Oncology Group performance status of 0/1/2 (n = 8/21/1). All dose levels were tolerable for regimen 1 (n = 18: 15 NSCLC and 3 esophageal cancers) and regimen 2 (n = 12: all NSCLC). In regimen 1, one dose-limiting toxicity (grade 4 esophagitis/anorexia) occurred (500 mg/m(2)). Grade 3 neutropenia (3 of 18 patients) was the main hematologic toxicity. In regimen 2, one dose-limiting toxicity (grade 3 esophagitis) occurred (500 mg/m(2); AUC = 6); grade 3/4 leukopenia (4 of 12 patients) was the main hematologic toxicity. Four complete responses (2 pathology proven) and eight partial responses were observed. When systemically active chemotherapy doses were reached, further dose escalation was discontinued, and a phase II dose-range was established (pemetrexed 500 mg/m(2) and carboplatin AUC = 5-6). CONCLUSIONS: The combination of pemetrexed (500 mg/m(2)) and carboplatin (AUC = 5 or 6) with concurrent radiation is well tolerated, allows for the administration of systemically active chemotherapy doses, and shows signs of activity. To further determine efficacy, safety profile, and optimal dosing, the Cancer and Leukemia Group B study 30407 is currently evaluating this regimen in patients with unresectable stage III NSCLC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Terapia Combinada/métodos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Glutamatos/administração & dosagem , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Guanina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , PemetrexedeRESUMO
UNLABELLED: The American College of Surgeons Oncology Group recently completed a trial evaluating the role of PET with 18F-FDG in patients with documented or suspected non-small cell lung cancer. Subjects underwent standard imaging to exclude metastatic disease before PET. Here, we report the yield of brain PET in evaluating, for potential intracranial metastases, patients who have undergone previous brain CT or MRI with negative findings. METHODS: A total of 287 evaluable patients who had been registered from 22 institutions underwent whole-body 18F-FDG PET, including dedicated PET of the brain, after routine staging procedures had found no suggestion of metastatic disease. Patients were followed postoperatively for disease-free and overall survival, with a minimum follow-up of 6 mo. Patients with specific brain abnormalities identified by PET were further examined, and the findings were evaluated along with the results of CT and MRI, clinical management, and follow-up. RESULTS: In 4 patients, PET found focal 18F-FDG uptake in the brain suggestive of metastatic disease; however, metastatic disease was excluded clinically in all 4 by negative findings on further brain imaging. All 4 patients remained alive at follow-up (mean duration, 10.5 mo; range, 6-16 mo). CONCLUSION: In patients with suspected or proven non-small cell lung cancer considered resectable by standard imaging, including routine preoperative contrast-enhanced CT or MRI of the brain, PET of the brain provides no additional information regarding metastatic disease.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo/patologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Idoso , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Radiografia , Cintilografia , Compostos Radiofarmacêuticos , Imagem Corporal TotalRESUMO
The current national sentinel lymph node (SLN) clinical trials for breast carcinoma address the prognostic and therapeutic utility of SLN dissection (SLND) in women with early-stage, clinically node-negative breast cancer. Following completion of these studies, overall survival, disease-free survival, morbidity, and quality of life of patients will be compared. Surgeon participation is crucial to the ongoing success of clinical trials in the field of breast cancer surgery.
Assuntos
Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela , Neoplasias da Mama/cirurgia , Ensaios Clínicos como Assunto , Humanos , Excisão de Linfonodo , Metástase Linfática/diagnóstico , Estados UnidosRESUMO
OBJECTIVES: The American College of Surgeons Oncology Group undertook a trial to ascertain whether positron emission tomography with 18F-fluorodeoxyglucose could detect lesions that would preclude pulmonary resection in a group of patients with documented or suspected non-small cell lung cancer found to be surgical candidates by routine staging procedures. METHODS: A total of 303 eligible patients registered from 22 institutions underwent positron emission tomography after routine staging (computed tomography of chest and upper abdomen, bone scintigraphy, and brain imaging) had deemed their tumors resectable. Positive findings required confirmatory procedures. RESULTS: Positron emission tomography was significantly better than computed tomography for the detection of N1 and N2/N3 disease (42% vs 13%, P =.0177, and 58% vs 32%, P =.0041, respectively). The negative predictive value of positron emission tomography for mediastinal node disease was 87%. Unsuspected metastatic disease or second primary malignancy was identified in 18 of 287 patients (6.3%). Distant metastatic disease indicated in 19 of 287 patients (6.6%) was subsequently shown to be benign. By correctly identifying advanced disease (stages IIIA, IIIB, and IV) or benign lesions, positron emission tomography potentially avoided unnecessary thoracotomy in 1 of 5 patients. CONCLUSIONS: In patients with suspected or proven non-small cell lung cancer considered resectable by standard staging procedures, positron emission tomography can prevent nontherapeutic thoracotomy in a significant number of cases. Use of positron emission tomography for mediastinal staging should not be relied on as a sole staging modality, and positive findings should be confirmed by mediastinoscopy. Metastatic disease, especially a single site, identified by positron emission tomography requires further confirmatory evaluation.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada de Emissão , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios XRESUMO
Since the introduction of the pneumonectomy as a technically feasible strategy for the treatment of lung cancer, surgical resection has played a pivotal role in the management of early stage non-small cell lung carcinoma (NSCLC). In the last two decades, surgical, medical, and radiation oncologists have produced a growing body of evidence to support the combination of neoadjuvant or adjuvant treatments with standard surgical resection, to improve disease-free and overall survival for specific patient subgroups. Furthermore, alternatives to aggressive surgical management have evolved for patients who are medically inoperable due to compromised pulmonary function or other comorbidities. In this review, surgical options and multimodal treatment strategies are discussed, as well as completed and ongoing clinical trials addressing the surgical management of NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Ensaios Clínicos como Assunto , Humanos , Neoplasias Pulmonares/diagnóstico , PneumonectomiaRESUMO
BACKGROUND: Desmoplastic melanoma (DM) has been associated with higher local recurrence rates than other types of cutaneous melanoma. Current controversies regarding locoregional treatment strategies warrant further investigation. METHODS: Retrospective review of a prospectively maintained melanoma database identified 129 patients with DM out of >12,500 melanoma patients referred for treatment from 1980 to 2003. Clinical and histopathologic characteristics, recurrence, and survival were analyzed. RESULTS: The median follow-up was 4.0 years. Of the 129 patients identified, 82 (63.6%) were male, and the median age was 55.2 years. American Joint Committee on Cancer staging was I, II, and III in 25.6%, 68.0%, and 6.4% of patients, respectively, and the mean tumor thickness was 4.42 mm. Overall survival was 76% at 5 years and 64% at 10 years; median survival was 13.0 years. A total of 51 patients (39.5%) experienced disease recurrence, with a median time to recurrence of 1.3 years. The first recurrence was local in 18 patients (14.0%), nodal in 18 patients (14.0%), and distant in 15 patients (11.6%), with median survivals of 6.7, 7.8, and 1.8 years, respectively. Statistically significant predictors of recurrence were a final positive margin status and stage, and predictors of overall survival were patient age and stage. CONCLUSIONS: Compared with other types of melanoma, DMs do demonstrate a tendency toward local recurrence, thus suggesting that narrower excision margins may not be appropriate in this population. Scrutiny of final surgical margins is critical to the local management of DM. In addition, the potential for regional nodal involvement must be considered at the time of diagnosis and during surveillance for disease recurrence.
Assuntos
Melanoma/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Taxa de SobrevidaRESUMO
BACKGROUND: American College of Surgeons Oncology Group Z0010 is a prospective multicenter trial designed to evaluate the prognostic significance of micrometastases in the sentinel lymph nodes and bone marrow aspirates of women with early-stage breast cancer. Surgical complications associated with the sentinel lymph node biopsy surgical procedure are reported. METHODS: Eligible patients included women with clinical T1/2N0M0 breast cancer. Surgical outcomes were available at 30 days and 6 months after surgery for 5327 patients. Patients who had a failed sentinel node mapping (n=71, 1.4%) or a completion lymph node dissection (n=814, 15%) were excluded. Univariate and multivariate analyses were performed to identify predictors for the measured surgical complications. RESULTS: In patients who received isosulfan blue dye alone (n=783) or a combination of blue dye and radiocolloid (n=4192), anaphylaxis was reported in .1% of subjects (5 of 4975). Other complications included axillary wound infection in 1.0%, axillary seroma in 7.1%, and axillary hematoma in 1.4% of subjects. Only increasing age and an increasing number of sentinel lymph nodes removed were significantly associated with an increasing incidence of axillary seroma. At 6 months, 8.6% of patients reported axillary paresthesias, 3.8% had a decreased upper extremity range of motion, and 6.9% demonstrated proximal upper extremity lymphedema (change from baseline arm circumference of >2 cm). Significant predictors for surgical complications at 6 months were a decreasing age for axillary paresthesias and increasing body mass index and increasing age for upper extremity lymphedema. CONCLUSIONS: This study provides a prospective assessment of the sentinel lymph node biopsy procedure, as performed by a wide range of surgeons, demonstrating a low complication rate.
Assuntos
Axila/patologia , Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela , Fatores Etários , Anafilaxia/etiologia , Índice de Massa Corporal , Neoplasias da Mama/cirurgia , Feminino , Hematoma/etiologia , Humanos , Cooperação Internacional , Parestesia/etiologia , Estudos Prospectivos , Corantes de Rosanilina/efeitos adversos , Biópsia de Linfonodo Sentinela/efeitos adversos , Seroma/etiologia , Infecção da Ferida Cirúrgica/etiologiaRESUMO
OBJECTIVE: Marked variations in sentinel lymph node dissection (SLND) technique have been identified, and definitive qualifications for SLND performance remain controversial. Based on previous reports and expert opinion, we predicted that 20 to 30 cases of SLND with axillary lymph node dissection (ALND) would enable surgeons to identify sentinel lymph nodes (SLN). SUMMARY BACKGROUND DATA: In 1999, the American College of Surgeons Oncology Group initiated a prospective trial, Z0010, to evaluate micrometastatic disease in the SLN and bone marrow of women with early-stage breast cancer. Eligible patients included women with biopsy-proven T1/T2 breast cancer and clinically negative lymph nodes who were candidates for lumpectomy and SLND. METHODS: Participating surgeons were required to document 20 to 30 SLNDs followed by immediate ALND with failure rates less than 15%. Prior fellowship or residency training in SLND provided exemption from skill requirements. Data for 5237 subjects and 198 surgeons were available for analysis. RESULTS: Surgeons from academic (48.4%), community (28.6%), or teaching-affiliated (19.8%) institutions qualified with 30 SLND + ALND cases (64.6%), 20 cases (22.2%), or exemption (13.1%). Participants used blue dye + radiocolloid in 79.4%, blue dye alone in 14.8%, and radiocolloid alone in 5.7% of cases, achieving a 98.7% SLN identification rate. Patient factors associated with increased SLND failure included increased body mass index and age, whereas tumor location, stage, and histology, presence of nodal metastases, and number of positive nodes were not. Surgeon accrual of fewer than 50 patients was associated with increased SLND failure; however, SLND technique, specific skill qualification, and institution type were not. CONCLUSIONS: Using a standard skill requirement, surgeons from a variety of institutions achieved an acceptably low SLND failure rate in the setting of a large multicenter trial, validating the incorporation of SLND into clinical practice.
Assuntos
Neoplasias da Mama , Cirurgia Geral/normas , Excisão de Linfonodo/normas , Padrões de Prática Médica/normas , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Diagnóstico Diferencial , Feminino , Seguimentos , Cirurgia Geral/educação , Humanos , Internato e Residência , Metástase Linfática , Mastectomia Segmentar , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Resultado do TratamentoRESUMO
Pulmonary xenotransplantation is one potential solution to the paucity of donors but is currently limited by rapid failure of the graft. Unlike cardiac and renal xenotransplants, pulmonary xenografts release large quantities of swine von Willebrand factor (vWF). Swine vWF binds xenoreactive antibodies and is capable of activating primate platelets. The contribution of swine vWF to lung xenograft dysfunction is not entirely clear. To probe the role vWF plays in xenograft dysfunction, we traced the fate of xenoantibodies in vWF+ and von Willebrand factor-deficient (vWFD) swine lungs. These studies showed that the vast majority of xenoantibodies bind the vWF released from the vWF+ swine lung, and thus do not remain bound on lung endothelium. The vWF complexed to xenoantibody remained capable of aggregating primate platelets. With this information, we performed swine-to-baboon lung transplants using vWF+ and vWFD donors. Without vWF present to complex xenoantibodies, a picture of hyperacute rejection more typical of heart and kidney xenografts, with antibody deposition along the graft endothelium, interstitial hemorrhage, and edema occurred. These findings suggest that porcine vWF plays a major role in the pathogenesis of pulmonary xenograft dysfunction, and suggests promising strategies to treat lung xenograft dysfunction.