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2.
J Clin Oncol ; 32(34): 3810-6, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25349290

RESUMO

PURPOSE: Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance. PATIENTS AND METHODS: Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05. RESULTS: Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, -4.7% to 18.7%), significantly lower in comparison with the historical control (P < .001). No decline in QOL scores was observed. Two grade 3 toxicities and no grade 4 to 5 toxicities were reported. Median survival was 6.8 months. CONCLUSION: Conformal avoidance of the hippocampus during WBRT is associated with preservation of memory and QOL as compared with historical series.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana/métodos , Hipocampo/efeitos da radiação , Transtornos da Memória/prevenção & controle , Rememoração Mental/efeitos da radiação , Células-Tronco Neurais/efeitos da radiação , Lesões por Radiação/prevenção & controle , Radioterapia de Intensidade Modulada , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Cognição , Irradiação Craniana/efeitos adversos , Irradiação Craniana/mortalidade , Fracionamento da Dose de Radiação , Feminino , Hipocampo/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/mortalidade , Transtornos da Memória/fisiopatologia , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Qualidade de Vida , Lesões por Radiação/etiologia , Lesões por Radiação/mortalidade , Lesões por Radiação/fisiopatologia , Lesões por Radiação/psicologia , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/mortalidade , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
3.
Biomark Res ; 1(1): 29, 2013 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-24252135

RESUMO

BACKGROUND: Glioblastoma Multiforme (GBM) is the most common primary malignant tumor of the central nervous system. Standard of care includes maximal resection followed by chemoradiotherapy. Tumors need adequate perfusion and neovascularization to maintain oxygenation and for removal of wastes. Vascular endothelial growth factor (VEGF) is a well characterized pro-angiogenic factor. We hypothesized that the increases in urinary VEGF levels would occur early in the course of tumor recurrence or progression. We examine the feasibility of collecting and analyzing urinary VEGF levels in a prospective, multi-institutional trial (Radiation Therapy Oncology Group, RTOG, 0611) as well as the role of VEGF as a marker of tumor recurrence. METHOD: We evaluated VEGF levels in urine specimens collected post-operatively, at the conclusion of radiation therapy (RT) and one month following RT. Urinary VEGF levels were correlated with tumor progression at one year. VEGF levels were measured by enzyme-linked immunosorbant assay in urine specimens and normalized to urinary creatinine levels. Sample size was determined based on a 50% 1-year recurrence rate. With a sensitivity and specificity of 80%, the expected 95% confidence interval was (0.69, 0.91) with 100 patients. A failure was defined as documented disease progression, recurrence or death before one year. RESULTS: 202 patients were enrolled between February-2006 and October-2007. Four patients were ineligible as they did not receive RT. Of the remaining 198 patients, 128 had all three samples collected. In this group, 35 patients (27.3%) did not progress, 89 (69.5%) had progression and 4 (3.1%) died without evidence of progression. Median VEGF levels at baseline were 52.9 pg/mg Cr (range 0.2- 15,034.4); on the last day of RT, 56.6 (range 0-2,377.1); and at one month follow-up, 70.0 (range 0.1-1813.2). In patients without progression at 1-year, both baseline VEGF level and end of RT VEGF level were lower than those of patients who progressed: 40.3 (range 0.2-350.8) vs. 59.7 (range 1.3-15,034.4) and 41.8 (range 0-356.8) vs. 69.7 (range 0-2,377.1), respectively. This did not reach statistical significance. Comparison of the change in VEGF levels between the end of RT and one month following RT, demonstrated no significant difference in the proportions of progressors or non-progressors at 1-year for either the VEGF increased or VEGF decreased groups. CONCLUSION: Urine can be collected and analyzed in a prospective, multi-institutional trial. In this study of patients with GBM a change in urinary VEGF levels between the last day of RT and the one month following RT did not predict for tumor progression by one year.

4.
Med Phys ; 37(3): 1220-4, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20384259

RESUMO

PURPOSE: A fiducial tracking system based on a novel radioactive tracking technology is being developed for real-time target tracking in radiation therapy. In this study, the authors calculate the radiation dose to the patient, the spouse/caretaker, and the medical staff that would result from a 100 microCi Ir192 radioactive fiducial marker permanently implanted in the prostate of a radiation therapy patient. METHODS: Local tissue dose was calculated by Monte Carlo simulation. The patient's whole body effective dose equivalent was calculated by summing the doses to the sensitive organs. Exposure of the spouse/caretaker was calculated from the NRC guidelines. Exposure of the medical staff was based on estimates of proximity to and time spent with the patient. RESULTS: The local dose is below 40 Gy at 5 mm from the marker and below 10 Gy at 10 mm from the marker. The whole body effective dose equivalent to the patient is 64 mSv. The dose to the spouse/caretaker is 0.25 mSv. The annual exposures of the medical staff are 0.2 mSv for a doctor performing implantations and 0.34 mSv for a radiation therapist positioning patients for therapy. CONCLUSIONS: The local dose is not expected to have any clinically significant effect on the surrounding tissue which is irradiated during therapy. The dose to the patient is small in comparison to the whole body dose received from the therapy itself. The exposure of all other people is well below the recommended limits. The authors conclude that there is no radiation exposure related contraindication for use of this technology in the radiation treatment of prostate cancer.


Assuntos
Carga Corporal (Radioterapia) , Cuidadores , Exposição Ambiental/análise , Corpo Clínico , Neoplasias da Próstata/radioterapia , Próteses e Implantes , Radiometria , Cônjuges , Humanos , Masculino , Medição de Risco
5.
Int J Radiat Oncol Biol Phys ; 77(4): 1240-7, 2010 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-20350794

RESUMO

PURPOSE: To analyze the stability, visibility, and histology of a novel implantable soft-tissue marker (nonradioactive and radioactive) implanted in dog prostate and rabbit liver. METHODS AND MATERIALS: A total of 34 nonradioactive and 35 radioactive markers were implanted in 1 dog and 16 rabbits. Stability was assessed by measuring intermarker distance (IMD) variation relative to IMDs at implantation. The IMDs were measured weekly for 4 months in the dog and biweekly for 2-4 weeks in the rabbits. Ultrasound and X-ray imaging were performed on all subjects. Computed tomography and MRI were performed on the dog. Histologic analysis was performed on the rabbits after 2 or 4 months. RESULTS: A total of 139 measurements had a mean (+/- SD) absolute IMD variation of 1.1 +/- 1.1 mm. These IMD variations are consistent with those reported in the literature as due to random organ deformation. The markers were visible, identifiable, and induced minimal or no image artifacts in all tested imaging modalities. Histologic analysis revealed that all pathologic changes were highly localized and not expected to be clinically significant. CONCLUSIONS: The markers were stable from the time of implantation. The markers were found to be compatible with all common medical imaging modalities. The markers caused no significant histologic effects. With respect to marker stability, visibility, and histologic analysis these implanted fiducials are appropriate for soft-tissue target positioning in radiotherapy.


Assuntos
Fígado/diagnóstico por imagem , Posicionamento do Paciente , Próstata/diagnóstico por imagem , Próteses e Implantes , Algoritmos , Animais , Artefatos , Cães , Radioisótopos de Irídio , Fígado/anatomia & histologia , Imageamento por Ressonância Magnética , Masculino , Platina , Próstata/anatomia & histologia , Implantação de Prótese/métodos , Coelhos , Tomografia Computadorizada por Raios X , Ultrassonografia
6.
J Urol ; 181(3): 1401-6, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19157458

RESUMO

PURPOSE: Hypofractionation schemes and associated higher rectal doses have evoked the need for improved protection of the rectum during prostate cancer irradiation. MATERIALS AND METHODS: An implantable, biodegradable, inflatable, preshaped triangular balloon of commercially used poly(L-lactide-co-epsilon-caprolactone) co-polymer material was developed to provide separation between prostate and rectum. Biocompatibility and degradability of the balloon implanted subcutaneously or perineally, and in the context of transperineal implantation and local irradiation were evaluated in several in vivo studies. RESULTS: The device was found to be biocompatible in subcutaneously implanted rabbits up to 42 days, in a transperineally implanted dog up to 12 months and in 8 transperineally implanted pigs up to 6 months. Upon inflation in situ the balloon separated the tissues, remained inflated for several months and subsequently biodegraded. No systemic or local toxicity was noted, as shown by histopathology. Device insertion into the perineal area using a dedicated introductory kit was convenient and feasible. Three-month followup in irradiated pigs that received 15 Gy in 3 fractions 1 week apart showed a stable balloon position with no local or systemic side effects. CONCLUSIONS: This novel device was safe and effective for its intended use of separating tissues for a desired duration. A clinical study will commence to evaluate the safety and efficacy of this device during irradiation in patients with prostate cancer.


Assuntos
Neoplasias da Próstata/radioterapia , Próteses e Implantes , Proteção Radiológica/instrumentação , Animais , Materiais Biocompatíveis , Modelos Animais de Doenças , Desenho de Equipamento , Masculino , Suínos
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