Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Hum Gene Ther ; 30(3): 352-364, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30234393

RESUMO

Oncolytic viruses represent a unique type of agents that combine self-amplification, lytic, and immunostimulatory properties against tumors. A local and locoregional clinical benefit has been demonstrated upon intratumoral injections of an oncolytic herpes virus in melanoma patients, leading to its approval in the United States and Europe for patients without visceral disease (up to stage IVM1a). However, in order to debulk and change the local immunosuppressive environment of tumors that cannot be injected directly, oncolyitc viruses need to be administered systemically. Among different viruses, adenovirus has been extensively used in clinical trials but with few evidences of activity upon systemic administration. Preclinical efficacy of a single intravenous administration of our oncolytic adenovirus ICOVIR5, an adenovirus type 5 responsive to the retinoblastoma pathway commonly deregulated in tumors, led us to use this virus in a dose-escalation phase 1 trial in metastatic melanoma patients. The results in 12 patients treated with a single infusion of a dose up to 1 × 1013 viral particles show that ICOVIR5 can reach melanoma metastases upon a single intravenous administration but fails to induce tumor regressions. These results support the systemic administration of armed oncolytic viruses to treat disseminated cancer.


Assuntos
Adenoviridae/genética , Terapia Genética , Vetores Genéticos/genética , Melanoma/genética , Melanoma/terapia , Terapia Viral Oncolítica , Vírus Oncolíticos/genética , Administração Intravenosa , Animais , Biópsia , Citocinas/metabolismo , Ordem dos Genes , Terapia Genética/efeitos adversos , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Humanos , Melanoma/diagnóstico , Camundongos , Terapia Viral Oncolítica/efeitos adversos , Terapia Viral Oncolítica/métodos , Distribuição Tecidual , Resultado do Tratamento , Replicação Viral
2.
Rep Pract Oncol Radiother ; 23(5): 360-368, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30127676

RESUMO

Aim: To evaluate the association between dose-volume histogram (DVH) values in organs at risk (OAR) and patient-reported HRQoL outcomes. Background: Data on the association between DVHs and health-related quality of life (HRQoL) in prostate cancer (PCa) patients are limited. Materials and methods: Five-year follow-up study of 154 patients with organ-confined (stage T1/T2) PCa treated with EBRT between January 2003 and November 2005. HRQoL was evaluated with the Expanded Prostate Cancer Index (EPIC). DVH for OARs (penile bulb, rectum and bladder) were created for all patients for whom data were available (119/154; 77%). The functional data analysis (FDA) statistical method was used. HRQoL data was collected prospectively and data analysis was performed retrospectively. Results: Worsening of urinary incontinence and obstructive symptoms correlated with higher DVH dose distributions at 24 months. Increased rectal bleeding at months 24 and 60 correlated with higher DVH dose distributions in the 40-70 Gy range. Patients with deterioration in rectal incontinence presented a higher DVH distribution range than patients without rectal incontinence. Penile bulb DVH values and erectile dysfunction were not significantly associated. Conclusions: DVH parameters and post-radiotherapy HRQoL appear to be closely correlated, underscoring the importance of assessing DVH values prior to initiating EBRT to determine the risk of developing HRQoL related adverse effects. Advanced treatment modalities may be appropriate in high risk cases to minimize treatment-related toxicity and to improve treatment outcomes and HRQoL. Future studies are needed to better elucidate the association between pre-treatment DVH parameters in organs at risk and subsequent HRQoL.

3.
Oncologist ; 22(8): 934-943, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28487465

RESUMO

BACKGROUND: The challenge when selecting elderly patients with colorectal cancer (CRC) for adjuvant therapy is to estimate the likelihood that death from other causes will preclude cancer events from occurring. The aim of this paper is to evaluate whether comprehensive geriatric assessment (CGA) can predict survival and cancer-specific mortality in elderly CRC patients candidates for adjuvant therapy. MATERIAL AND METHODS: One hundred ninety-five consecutive patients aged ≥75 with high-risk stage II and stage III CRC were prospectively included from May 2008 to May 2015. All patients underwent CGA, which evaluated comorbidity, polypharmacy, functional status, geriatric syndromes, mood, cognition, and social support. According to CGA results, patients were classified into three groups-fit, medium-fit, and unfit-to receive standard therapy, adjusted treatment, and best supportive care, respectively. We recorded survival and cause of death and used the Fine-Gray regression model to analyze competing causes of death. RESULTS: Following CGA, 85 (43%) participants were classified as fit, 57 (29%) as medium-fit, and 53 (28%) as unfit. The univariate 5-year survival rates were 74%, 52%, and 27%. Sixty-one (31%) patients died due to cancer progression (53%), non-cancer-related cause (46%), and unknown reasons (1%); there were no toxicity-related deaths. Fit and medium-fit participants were more likely to die due to cancer progression, whereas patients classified as unfit were at significantly greater risk of non-cancer-related death. CONCLUSION: CGA showed efficacy in predicting survival and discriminating between causes of death in elderly patients with high-risk stage II and stage III resected CRC, with potential implications for shaping the decision-making process for adjuvant therapies. IMPLICATIONS FOR PRACTICE: Adjuvant therapy in elderly patients with colorectal cancer is controversial due to the high risk for competing events among these patients. In order to effectively select older patients for adjuvant therapy, we have to weigh the risk of cancer-related mortality and the potential survival benefits with treatment against the patient's life expectancy, irrespective of cancer. This prospective study focused on the prognostic value of geriatric assessment for survival using a competing-risk analysis approach, providing an important contribution on the treatment decision-making process and helping clinicians to identify elderly patients who might benefit from adjuvant chemotherapy among those who will not.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Avaliação Geriátrica , Prognóstico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Terapia Combinada/efeitos adversos , Tomada de Decisões , Feminino , Humanos , Masculino , Fatores de Risco
4.
J Thorac Oncol ; 11(7): 1101-11, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27103512

RESUMO

OBJECTIVES: The long-term impact of stereotactic body radiotherapy (SBRT) on respiratory function in patients with inoperable non-small cell lung cancer (NSCLC) has not been well studied. The aim of this phase II trial was to assess local control, survival, and lung function at 36 months after treatment. METHODS: From July 2008 to February 2012, 42 patients in whom inoperable NSCLC with peripheral lesions was diagnosed were consecutively enrolled. Lung function testing included measurement of forced expiratory vital capacity, forced expiratory volume in 1 second, and diffusing capacity for carbon monoxide. All lung function parameters were registered at baseline and evaluated prospectively after SBRT every 6 months for 2 years and annually thereafter. RESULTS: Of the 42 initial patients, four were excluded. At 36 months after SBRT, 22 patients were still evaluable (12 deaths and four patients lost to follow-up). At 36 months, the rate of local control was 94%. At 1, 2, and 3 years, respectively, overall survival rates were 92%, 75%, and 66%. Median overall survival was 57 months. Grade (G) 3 acute toxicity was observed in four patients (10%). Chronic G1 toxicity was observed in all 38 cases (100%), with the most common type being pneumonitis (26 patients [68%]). The mean lung function parameters at baseline and at 36 months after treatment were as follows: forced expiratory vital capacity 83% versus 79%; forced expiratory volume in 1 second 62% versus 57%; and diffusing capacity for carbon monoxide 54% versus 54%. These changes were not significant. CONCLUSIONS: In this trial, local control and survival rates after SBRT were very good. Treatment with SBRT had no significant impact on lung function at 36 months. These findings provide further support for the use of SBRT as a radical treatment for NSCLC. Lung toxicity is minimal, even in patients with poor pulmonary function before treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Pulmão/efeitos da radiação , Radiocirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Feminino , Volume Expiratório Forçado/efeitos da radiação , Humanos , Pulmão/fisiopatologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonite por Radiação/etiologia , Radiocirurgia/efeitos adversos
5.
Radiat Oncol ; 10: 176, 2015 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-26289071

RESUMO

BACKGROUND: To compare thermoplastic masks (TMP) and vacuum cushion system (VCS) to assess differences in interfraction set up accuracy in patients treated with stereotactic radiotherapy (SBRT) for oligometastatic lung cancer. Secondarily, to survey radiotherapy technologists to assess their satisfaction with the two systems. METHODS: Retrospective study of patients treated with lung SBRT between 2008 to 2012 at our institution. Immobilization was performed for 73 treatment sessions (VCS = 40; TMP = 33). A total of 246 cone-beams were analysed. Patients considered ineligible for surgery with a life expectancy ≥6 months and performance status > 1 were included. Target lesion location was verified by cone beam computed tomography (CBCT) prior to each session, with displacements assessed by CBCT simulation prior to each treatment session. Couch shifts were registered prospectively in vertical, longitudinal, and latero-lateral directions to obtain Kernel coordinates (3D representation). Technologists were surveyed to assess their satisfaction with indexing, positioning, and learning curve of the two systems. Setup displacements were obtained in all patients for each treatment plan and for each session. To assess differences between the immobilization systems, a t-test (Welch) was performed. RESULTS: Mean displacements for the TMP and VC systems, respectively, were as follows: session one, 0.64 cm vs 1.05 cm (p = 0.0002); session two, 0.49 cm vs 1.02 cm (p < 0.0001), and session three, 0.56 vs 0.97 cm (p = 0.0011). TMP resulted in significantly smaller shifts vs. VCS in all three treatment sessions. Technologists rated the learning curve, set up, and positioning more highly for TMP versus VCS. CONCLUSIONS: Due to the high doses and steep gradients in lung SBRT, accurate and reproducible inter-fraction set up is essential. We found that thermoplastic masks offers better reproducibility with significantly less interfractional set up displacement than vacuum cushions. Moreover, radiotherapy technologists rated the TMP system higher. Taken together, these two findings suggest that TMP may be preferable to VCS. However, more research is needed to determine both inter- and intrafraction error to identify the optimal immobilisation system for use in lung SBRT.


Assuntos
Neoplasias Pulmonares/cirurgia , Radiocirurgia/instrumentação , Restrição Física/instrumentação , Humanos , Máscaras , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Estudos Retrospectivos
6.
Oral Oncol ; 51(8): 795-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26051499

RESUMO

BACKGROUND: Multimodal treatment for locally advanced head and neck carcinomas (LAHNC) has been reported to improve survival. However, it is less clear to what extent this survival gain is given at the expense of an impact on the quality of life of our patients. Our aim is to analyze the ongoing late toxic effects among long survivors, to determine how much these impairments affect their QoL, and if there is any factor that clearly impacts on this toxicity. METHODS: 152 Patients diagnosed with LAHNC were treated radically in our clinical practice, either with concomitant chemoradiotherapy or bioradiotherapy, with or without induction chemotherapy. We prospectively assessed these patients' treatment-related late toxicities according to the Radiation Therapy Oncology Group scoring system, and patients answered a QoL question to subjectively evaluate the degree of impact caused by these sequelae in their daily life. Multivariate logistic regressions were performed to detect factors that could influence in toxicity. RESULTS: 21.9% Patients experienced grade 3-4 toxicity. Concomitant chemoradiation with cisplatin was found to be a risk factor of moderate and severe late toxicity compared to concomitant cetuximab in the adjusted analysis by RT fractionation. OR for moderate toxicity 0.292 (CI: 0.125-0.680, p=0.004); OR for severe toxicity: 0.299 (CI: 0.0909-0.999, p=0.05). Induction chemotherapy was found to be a protective factor for moderate late toxicity compared to concomitant treatment alone. CONCLUSION: Patients treated with concomitant chemoradiation with cisplatin have significantly more late toxicity compared to bioradiotherapy, whereas induction chemotherapy prevents from developing moderate late toxicity.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/terapia , Cetuximab/efeitos adversos , Cisplatino/efeitos adversos , Terapia Combinada/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Cetuximab/administração & dosagem , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Inquéritos e Questionários , Resultado do Tratamento
7.
BMC Cancer ; 15: 59, 2015 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-25886275

RESUMO

BACKGROUND: To evaluate whether the addition of bevacizumab (BVZ) to capecitabine-based chemoradiotherapy in the preoperative treatment of locally advanced rectal cancer (LARC) improves efficacy measured by the pathological complete response (pCR) rate. METHODS: A phase II two-step design was performed. Patients received four cycles of therapy consisting of: BVZ 10 mg/kg in first infusion on day 1 and 5 mg/kg on days 15, 29, 43, capecitabine 1800 mg/m(2)/day 5 days per week during radiotherapy, which consisted of external-beam irradiation (45 Gy in 1.8 Gy dose per session over 5 sessions/week for 5 weeks). Six to eight weeks after completion of all therapies surgery was undergone. To profile the biological behaviour during BVZ treatment we measured molecular biomarkers before treatment, during BVZ monotherapy, and during and after combination therapy. Microvessel density (MVD) was measured after surgery. RESULTS: Forty-three patients were assessed and 41 were included in the study. Three patients achieved a pathological complete response (3/40: 7.5%) and 27 (67.5%) had a pathological partial response, (overall pathological response rate of 75%). A further 8 patients (20%) had stable disease, giving a disease control rate of 95%. Downstaging occurred in 31 (31/40: 77.5%) of the patients evaluated. This treatment resulted in an actuarial 4-year disease-free and overall survival of 85.4 and 92.7% respectively. BVZ with chemoradiotherapy showed acceptable toxicity. No correlations were observed between biomarker results and efficacy variables. CONCLUSION: BVZ with capecitabine and radiotherapy seem safe and active and produce promising survival results in LARC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00847119 . Trial registration date: February 18, 2009.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Quimiorradioterapia Adjuvante/métodos , Neoplasias Retais/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Capecitabina/uso terapêutico , Fracionamento da Dose de Radiação , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Neoplasias Retais/patologia , Análise de Sobrevida , Resultado do Tratamento
8.
Lung Cancer ; 52(2): 149-54, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16516336

RESUMO

BACKGROUND: Radiation therapy (RT) alone is frequently used in elderly patients with medically inoperable early stage (I/II) non-small cell lung cancer (NSCLC). We retrospectively investigated the effectiveness of RT alone in this patient population treated in our institution. MATERIAL AND METHODS: Between 1995 and 1999, a total of 33 patients were treated with RT alone in our institution, all being males. RT doses ranged 66-78 Gy (median, 70 Gy) using standard fractionation (2.0 Gy per fraction). The age range was 71-97 years (median, 75 years) with 11 patients being >or=80 years old. Twenty-two (67%) patients had a squamous cell carcinoma. There were 24 (73%) stage I and nine (27%) stage II patients. RESULTS: Radiographic objective response rate was observed in 23 (70%) patients. The median survival time was 37.4 months and 3-year survival time was 50%, while the median cause-specific survival time was 48.1 months and a 3-year cause-specific survival rate was 55.3%. The median time to local recurrence was 36.8 months and a 3-year local recurrence-free survival rate was 50.2%, while the median time to distant metastasis was not achieved yet, the 3-year distant metastasis-free survival rate being 71.4%. One (3%) patient died of RT-induced acute lung toxicity, while only two (6%) patients experienced late grade 3 lung toxicity. No other high-grade toxicity was observed during this study. CONCLUSIONS: RT alone was effective and low toxic in elderly with early stage (I/II) NSCLC and could be considered as treatment of choice in this patient population.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
9.
Río Piedras, P.R; U.P.R., R.C.M., Escuela Graduada de Salud Pública; 1992. xii, 130 p p. tablas.
Tese | Porto Rico | ID: por-15023
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...