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1.
Genome Med ; 15(1): 74, 2023 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-37723522

RESUMEN

BACKGROUND: Many families and individuals do not meet criteria for a known hereditary cancer syndrome but display unusual clusters of cancers. These families may carry pathogenic variants in cancer predisposition genes and be at higher risk for developing cancer. METHODS: This multi-centre prospective study recruited 195 cancer-affected participants suspected to have a hereditary cancer syndrome for whom previous clinical targeted genetic testing was either not informative or not available. To identify pathogenic disease-causing variants explaining participant presentation, germline whole-genome sequencing (WGS) and a comprehensive cancer virtual gene panel analysis were undertaken. RESULTS: Pathogenic variants consistent with the presenting cancer(s) were identified in 5.1% (10/195) of participants and pathogenic variants considered secondary findings with potential risk management implications were identified in another 9.7% (19/195) of participants. Health economic analysis estimated the marginal cost per case with an actionable variant was significantly lower for upfront WGS with virtual panel ($8744AUD) compared to standard testing followed by WGS ($24,894AUD). Financial analysis suggests that national adoption of diagnostic WGS testing would require a ninefold increase in government annual expenditure compared to conventional testing. CONCLUSIONS: These findings make a case for replacing conventional testing with WGS to deliver clinically important benefits for cancer patients and families. The uptake of such an approach will depend on the perspectives of different payers on affordability.


Asunto(s)
Síndromes Neoplásicos Hereditarios , Humanos , Estudios Prospectivos , Oncogenes , Pruebas Genéticas , Células Germinativas
2.
Med J Aust ; 189(10): 557-9, 2008 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-19012553

RESUMEN

OBJECTIVE: To measure long-term survival following combined chemotherapy and radiotherapy for inoperable non-small cell lung cancer. DESIGN AND SETTING: Two prospective Phase I/II studies in the multidisciplinary Lung Service of a dedicated cancer hospital in Victoria, commencing in 1996 and 1997-1998. PATIENTS: 33 patients referred for treatment of histologically or cytologically proven inoperable non-small cell lung cancer, who had no evidence of distant metastases, Karnofsky performance status > 70%, weight loss < 10%, and no prior treatment for lung cancer. Patients were followed until death or for a minimum of 9 years. INTERVENTIONS: Patients in both studies were treated concomitantly with chemotherapy and radiotherapy 60 Gy in 30 fractions over 6 weeks. Chemotherapy in the first study (LURTCE) consisted of cisplatin and etoposide; in the second study (LURTCF), chemotherapy consisted of escalating doses of carboplatin and fluorouracil. MAIN OUTCOME MEASURE: Overall survival. RESULTS: Six of 33 patients were still alive 9 years after commencement of treatment. Median survival for the whole group was 2.1 years (95% CI, 1.3-3.1 years), with 18% (95% CI, 8%-35%) of patients still alive at 5 years (plateau). CONCLUSION: Long-term survival can be achieved in some patients with inoperable non-small cell lung cancer treated by radical chemoradiation alone, suggesting the possibility of cure.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Adulto , Anciano , Antineoplásicos/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/uso terapéutico , Etopósido/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante , Tasa de Supervivencia
3.
Eur J Cancer ; 44(15): 2178-84, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18676140

RESUMEN

AIMS: This study reports the symptom and HRQOL results in which standard treatment was compared to standard therapy plus Bec2, an anti-idiotypic antibody that mimics GD3, a ganglioside antigen. METHODS: Five hundred and fifteen LD SCLC patients were randomised to receive five vaccinations of Bec2 (2.5mg)/BCG vaccine arm (VA) or an observational arm (OA) administered over a 10-week period. Survival was the primary end-point; HRQOL was a secondary end-point, assessed using the EORTC QLQ-C30/LC 13. RESULTS: There was no improvement in survival or progression-free survival in the vaccination arm. At baseline patients in both arms demonstrated significantly impaired scores on the global QOL scale, when compared to a normative population. However, HRQOL and symptom scores between the two treatment arms were not statistically different at any time point. CONCLUSION: We found no benefits to patient HRQOL by additional vaccination with Bec2/BCG to LD SCLC for patients who have been undergoing standard therapy.


Asunto(s)
Vacuna BCG/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Canales de Potasio Éter-A-Go-Go/uso terapéutico , Neoplasias Pulmonares/terapia , Proteínas del Tejido Nervioso/uso terapéutico , Carcinoma Pulmonar de Células Pequeñas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Vacuna BCG/efectos adversos , Vacunas contra el Cáncer/efectos adversos , Terapia Combinada , Canales de Potasio Éter-A-Go-Go/efectos adversos , Femenino , Indicadores de Salud , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/efectos adversos , Cooperación del Paciente , Calidad de Vida , Carcinoma Pulmonar de Células Pequeñas/patología , Resultado del Tratamiento , Vacunación/métodos
4.
Int J Colorectal Dis ; 22(8): 887-95, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17235506

RESUMEN

BACKGROUND AND AIMS: There is considerable uncertainty as to whether adjuvant 5-fluorouracil-based chemotherapy provides survival benefit for colon cancer patients with stage II disease. Consequently, the current rates of chemotherapy use for this disease are low despite 5-year survival rates of only 70-80%. The aim of the present study is to compare the survival rate of stage II colon cancer patients treated by surgery alone with that of patients also treated by chemotherapy. PATIENTS AND METHODS: A population-based observational study was conducted on the survival of stage II colon cancer patients (n = 812) diagnosed in Western Australia from 1993 to 2003. The study was restricted to patients aged < or =75 years, of whom 18% (n = 142) were treated with chemotherapy. Only 0.9% of patients older than 75 years received chemotherapy. RESULTS: Patients who received chemotherapy were significantly younger (mean age 6 years) than those treated by surgery alone (65 years, P < 0.001), and their tumors were more often positive for vascular invasion (P = 0.007). Multivariate analysis that included all prognostic factors revealed adjuvant chemotherapy was associated with improved survival (HR = 0.62, 95% CI [0.39-0.98], P = 0.043), with women gaining more benefit (HR = 0.48, 95% CI [0.20-1.22], P = 0.09) than men (HR = 0.94, 95% CI [0.54-1.64], P = 0.8). CONCLUSIONS: In view of the apparent survival benefit from chemotherapy for stage II colon cancer, the present study raises concerns about the current low rates of adjuvant treatment for this disease in the community, particularly for female patients.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo , Fluorouracilo/uso terapéutico , Adulto , Distribución por Edad , Factores de Edad , Anciano , Quimioterapia Adyuvante , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Vigilancia de la Población , Modelos de Riesgos Proporcionales , Factores Sexuales , Factores de Tiempo , Resultado del Tratamiento , Australia Occidental
5.
J Clin Oncol ; 23(28): 6854-64, 2005 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-16192577

RESUMEN

PURPOSE: Bec2 is an anti-idiotypic antibody that mimics GD3, a ganglioside that is expressed on the surface of tumor cells and is of neuroectodermal origin. We assessed whether Bec2/bacille Calmette-Guerin (BCG) vaccination prolongs survival in patients with limited-disease small-cell lung cancer (SCLC) after a major response to chemotherapy and chest radiation. PATIENTS AND METHODS: Patients were randomly assigned to receive five vaccinations of Bec2 (2.5 mg)/BCG vaccine or follow-up. Vaccination was given over a 10-week period. The sample size was targeted to detect an increase in median survival of 40% after random assignment, and stratification was by performance status, response, and institution. Quality of life was assessed by using the European Organisation for Research and Treatment of Cancer instrument. Humoral response was assessed in patients who received vaccination. RESULTS: A total of 515 patients were randomly assigned. The primary toxicities of vaccination were transient skin ulcerations and mild flu-like symptoms. There was no improvement in survival, progression-free survival, or quality of life in the vaccination arm. Median survival from randomization was 16.4 and 14.3 months in the observation and vaccination arms (P = .28), respectively. Among vaccinated patients, a trend toward prolonged survival was observed in those (one third) who developed a humoral response (P = .085). Multivariate analysis showed a positive impact on survival by prior treatment with concomitant chemoradiotherapy, prophylactic cranial irradiation, female sex, low lactate dehydrogenase, and normal platelets. CONCLUSION: Vaccination with Bec2/BCG has no impact on outcome of patients with limited-disease SCLC responding to combined-modality treatment. Vaccination strategies in SCLC may still be warranted using vaccines that produce a better immunologic response.


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Vacuna BCG/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas del Tejido Nervioso/inmunología , Canales de Potasio con Entrada de Voltaje/inmunología , Adyuvantes Inmunológicos/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Formación de Anticuerpos , Carcinoma de Células Pequeñas/cirugía , Supervivencia sin Enfermedad , Esquema de Medicación , Canales de Potasio Éter-A-Go-Go , Femenino , Humanos , Inmunoterapia , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Calidad de Vida
6.
Lung Cancer ; 49(3): 401-12, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15923057

RESUMEN

PURPOSE: Pemetrexed and vinorelbine are active antineoplastic agents in non-small cell lung cancer (NSCLC). Phase I objectives include maximum tolerated dose (MTD) and recommended phase II dose determination, and pharmacokinetics of the pemetrexed-vinorelbine doublet in locally advanced or metastatic solid tumor patients (pts). Phase II objectives include tumor response evaluation, efficacy, and toxicity for first-line treatment of advanced NSCLC. EXPERIMENTAL DESIGN: Phase I pts received pemetrexed (day 1, 300-700 mg/m2) and vinorelbine (days 1 and 8, 15-30 mg/m2) every 21 days. Pharmacokinetics determined at cycle 1. Beginning with dose-level 3, folic acid and Vitamin B12 supplementation were given. RESULTS: Thirty-one phase I pts were enrolled. MTD was pemetrexed 700 mg/m2 and vinorelbine 30 mg/m2; and recommended phase II dose was pemetrexed 500 mg/m2 and vinorelbine 30 mg/m2. When administered in combination, pemetrexed and vinorelbine pharmacokinetics were consistent with single-agent administration. Thirty-seven (36 chemonaive) phase II NSCLC pts received pemetrexed-vinorelbine. Evaluable tumor response was 40%, with intent-to-treat 38%. One drug-related death occurred from febrile neutropenia with Staphylococcal infection. Grade 3/4 hematologic toxicities were neutropenia (65%) and febrile neutropenia (11%), while prevalent grade 3/4 non-hematologic toxicity was fatigue (27%). CONCLUSION: The pemetrexed-vinorelbine combination is well tolerated and shows activity as first-line treatment in advanced NSCLC patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Glutamatos/administración & dosificación , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Vinblastina/análogos & derivados , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Creatinina/metabolismo , Suplementos Dietéticos , Femenino , Glutamatos/farmacocinética , Guanina/administración & dosificación , Guanina/farmacocinética , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Pemetrexed , Factores de Tiempo , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/farmacocinética , Vinorelbina , Vitamina B 12/farmacología
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