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BACKGROUND: Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results. METHODS: We included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy. RESULTS: A total of 251 eligible patients were enrolled from 1998 through 2002. The median follow-up was 11.9 years; 55% of the patients died. Patients who received radiation therapy plus chemotherapy had longer median overall survival than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard ratio for death, 0.59; P=0.003). The rate of progression-free survival at 10 years was 51% in the group that received radiation therapy plus chemotherapy versus 21% in the group that received radiation therapy alone; the corresponding rates of overall survival at 10 years were 60% and 40%. A Cox model identified receipt of radiation therapy plus chemotherapy and histologic findings of oligodendroglioma as favorable prognostic variables for both progression-free and overall survival. CONCLUSIONS: In a cohort of patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or older, progression-free survival and overall survival were longer among those who received combination chemotherapy in addition to radiation therapy than among those who received radiation therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00003375.).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Astrocitoma/tratamiento farmacológico , Astrocitoma/radioterapia , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Oligodendroglioma/tratamiento farmacológico , Oligodendroglioma/radioterapia , Adulto , Astrocitoma/mortalidad , Neoplasias Encefálicas/mortalidad , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lomustina/administración & dosificación , Masculino , Clasificación del Tumor , Oligodendroglioma/mortalidad , Procarbazina/administración & dosificación , Análisis de Supervivencia , Vincristina/administración & dosificación , Adulto JovenRESUMEN
AIMS: To determine the efficacy of methylguanine methyltransferase (MGMT) depletion + BCNU [1,3-bis(2-chloroethyl)-1- nitrosourea: carmustine] therapy and the impact of methylation status in adults with glioblastoma multiforme (GBM) and gliosarcoma. METHODS: Methylation analysis was performed on GBM patients with adequate tissue samples. Patients with newly diagnosed GBM or gliosarcoma were eligible for this Phase III open-label clinical trial. At registration, patients were randomized to Arm 1, which consisted of therapy with O(6)-benzylguanine (O(6)-BG) + BCNU 40 mg/m(2) (reduced dose) + radiation therapy (RT) (O6BG + BCNU arm), or Arm 2, which consisted of therapy with BCNU 200 mg/m(2) + RT (BCNU arm). RESULTS: A total of 183 patients with newly diagnosed GBM or gliosarcoma from 42 U.S. institutions were enrolled in this study. Of these, 90 eligible patients received O(6)-BG + BCNU + RT and 89 received BCNU + RT. The trial was halted at the first interim analysis in accordance with the guidelines for stopping the study due to futility (<40 % improvement among patients on the O6BG + BCNU arm). Following adjustment for stratification factors, there was no significant difference in overall survival (OS) or progression-free survival (PFS) between the two groups (one sided p = 0.94 and p = 0.88, respectively). Median OS was 11 [95 % confidence interval (CI) 8-13] months for patients in the O6BG + BCNU arm and 10 (95 % CI 8-12) months for those in the BCNU arm. PFS was 4 months for patients in each arm. Adverse events were reported in both arms, with significantly more grade 4 and 5 events in the experimental arm. CONCLUSIONS: The addition of O(6)-BG to the standard regimen of radiation and BCNU for the treatment patients with newly diagnosed GBM and gliosarcoma did not provide added benefit and in fact caused additional toxicity.
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Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Gliosarcoma/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/metabolismo , Carmustina/administración & dosificación , Terapia Combinada , Metilación de ADN , Femenino , Glioblastoma/metabolismo , Gliosarcoma/metabolismo , Guanina/administración & dosificación , Guanina/análogos & derivados , Humanos , Masculino , Persona de Mediana Edad , Radioterapia , Adulto JovenRESUMEN
PURPOSE: NRG Oncology/RTOG 9802 (ClinicalTrials.gov Identifier: NCT00003375) is a practice-changing study for patients with WHO low-grade glioma (LGG, grade II), as it was the first to demonstrate a survival benefit of adjuvant chemoradiotherapy over radiotherapy. This post hoc study sought to determine the prognostic and predictive impact of the WHO-defined molecular subgroups and corresponding molecular alterations within NRG Oncology/RTOG 9802. METHODS: IDH1/2 mutations were determined by immunohistochemistry and/or deep sequencing. A custom Ion AmpliSeq panel was used for mutation analysis. 1p/19q codeletion and MGMT promoter methylation were determined by copy-number arrays and/or Illumina 450K array, respectively. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazard model and tested using the log-rank test. Multivariable analyses (MVAs) were performed incorporating treatment and common prognostic factors as covariates. RESULTS: Of the eligible patients successfully profiled for the WHO-defined molecular groups (n = 106/251), 26 (24%) were IDH-wild type, 43 (41%) were IDH-mutant/non-codeleted, and 37(35%) were IDH-mutant/codeleted. MVAs demonstrated that WHO subgroup was a significant predictor of PFS after adjustment for clinical variables and treatment. Notably, treatment with postradiation chemotherapy (PCV; procarbazine, lomustine (CCNU), and vincristine) was associated with longer PFS (HR, 0.32; P = .003; HR, 0.13; P < .001) and OS (HR, 0.38; P = .013; HR, 0.21; P = .029) in the IDH-mutant/non-codeleted and IDH-mutant/codeleted subgroups, respectively. In contrast, no significant difference in either PFS or OS was observed with the addition of PCV in the IDH-wild-type subgroup. CONCLUSION: This study is the first to report the predictive value of the WHO-defined diagnostic classification in a set of uniformly treated patients with LGG in a clinical trial. Importantly, this post hoc analysis supports the notion that patients with IDH-mutant high-risk LGG regardless of codeletion status receive benefit from the addition of PCV.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Glioma/genética , Glioma/terapia , Isocitrato Deshidrogenasa/genética , Adulto , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Ensayos Clínicos Fase III como Asunto , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Femenino , Glioma/tratamiento farmacológico , Glioma/radioterapia , Humanos , Inmunohistoquímica , Lomustina/administración & dosificación , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Procarbazina/administración & dosificación , Regiones Promotoras Genéticas , Modelos de Riesgos Proporcionales , Proteínas Supresoras de Tumor/genética , Vincristina/administración & dosificaciónRESUMEN
Glioblastoma multiforme (GBM) continues to be a difficult therapeutic challenge. Our study was conducted to determine whether improved survival and tumor control could be achieved with modern delivery of fast neutron radiation using three-dimensional treatment planning. Ten patients were enrolled. Eligibility criteria included pathologic diagnosis of GBM, age >or=18 years, and KPS >or=60. Patients underwent MRI and (18)F-fluorodeoxyglucose PET (FDG PET) as part of initial three-dimensional treatment planning. Sequential targets were treated with noncoplanar fields to a total dose of 18 Gy in 16 fractions over 4 weeks. Median and 1-year overall survival were 55 weeks and 60%, respectively. One patient remains alive at last follow-up 255 weeks after diagnosis. Median progression-free survival was 16 weeks, and all patients had tumor progression by 39 weeks. Treatment was clinically well tolerated, but evidence of mild to moderate gliosis and microvascular sclerosis consistent with radiation injury was observed at autopsy in specimens taken from regions of contralateral brain that received approximately 6-10 Gy. Fast neutron radiation using modern imaging, treatment planning, and beam delivery was feasible to a total dose of 18 Gy, but tumor control probability was poor in comparison to that predicted from a dose-response model based on older studies. Steep dose-response curves for both tumor control and neurotoxicity continue to present a challenge to establishing a therapeutic window for fast neutron radiation in GBM, even with modern techniques.
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Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Terapia por Captura de Neutrón/métodos , Tomografía de Emisión de Positrones , Radioterapia Conformacional/métodos , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Supervivencia sin Enfermedad , Femenino , Glioblastoma/mortalidad , Glucosa-6-Fosfato/análogos & derivados , Humanos , Estimación de Kaplan-Meier , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Proyectos Piloto , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
OBJECT: In 1998, the Radiation Therapy Oncology Group initiated a Phase II study of observation for adults < 40 years old with cerebral low-grade glioma who underwent a neurosurgeon-determined gross-total resection (GTR). METHODS: Patient eligibility criteria included the presence of a World Health Organization Grade II astrocytoma, oligodendroglioma, or mixed oligoastrocytoma confirmed histologically; age 18-39 years; Karnofsky Performance Scale score > or = 60; Neurologic Function Scale score < or = 3; supratentorial tumor location; neurosurgeon-determined GTR; and pre- and postoperative MR imaging with contrast enhancement available for central review by the principal investigator. Patients were observed following GTR and underwent MR imaging every 6 months. Prognostic factors analyzed for their contribution to patient overall survival, progression-free survival (PFS), and tumor recurrence included age, sex, Karnofsky Performance Scale score, Neurologic Function Scale score, histological type, contrast enhancement on preoperative MR imaging, preoperative tumor diameter, residual disease based on postoperative MR imaging, and baseline Mini-Mental State Examination score. RESULTS: Between 1998 and 2002, 111 eligible patients were entered into the study. In these 111 patients, the overall survival rates at 2 and 5 years were 99 and 93%, respectively. The PFS rates in these 111 patients at 2 and 5 years were 82 and 48%, respectively. Three prognostic factors predicted significantly poorer PFS in univariate and multivariate analyses: 1) preoperative tumor diameter > or = 4 cm; 2) astrocytoma/oligoastrocytoma histological type; and 3) residual tumor > or = 1 cm according to MR imaging. Review of the postoperative MR imaging results revealed that 59% of patients had < 1 cm residual disease (with a subsequent 26% recurrence rate), 32% had 1-2 cm residual disease (with a subsequent 68% recurrence rate), and 9% had > 2 cm residual disease (with a subsequent 89% recurrence rate). CONCLUSIONS: These data suggest that young adult patients with low-grade glioma who undergo a neurosurgeon-determined GTR have a > 50% risk of tumor progression 5-years postoperatively, warranting close follow-up and consideration for adjuvant treatment.
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Glioma/cirugía , Recurrencia Local de Neoplasia/epidemiología , Procedimientos Neuroquirúrgicos/métodos , Neoplasias Supratentoriales/cirugía , Adolescente , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Análisis Multivariante , Recurrencia Local de Neoplasia/diagnóstico , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: Malignant pleural mesothelioma (MPM) is a deadly disease with varying treatment options. This study retrospectively describes treatment practices at the University of Washington Medical System from 1980 to 2011, and evaluates the impact of trimodality therapy and radiation (photon and neutron) on survival. METHODS: A retrospective study was conducted on patients treated for MPM. Univariate and multivariate methods were utilized to evaluate potential factors associated with survival. Treatments received and baseline characteristics were included. Survival analysis of trimodality therapy was performed using a propensity score method to control for baseline characteristics. RESULTS: Among 78 eligible patients, the median age at diagnosis was 59 years and the median survival was 13.7 months. On multivariate analysis, the significant predictors of improved survival were age, smoking history, location, and receipt of radiation therapy or chemotherapy. In the 48 patients receiving radiation therapy, the difference in survival between neutron therapy and non-neutron therapy patients was not statistically significant: hazard ratio, 1.20 (95% confidence interval, 0.68-2.13), P=0.52. Patients receiving trimodality therapy were more likely to have early-stage disease (60% vs. 30%) and epithelioid histology (86% vs. 58%). In a propensity score-weighted Cox proportional hazards model, trimodality therapy patients had improved overall survival, hazard ratio 0.45, P=0.004, median 14.6 versus 8.6 months. CONCLUSIONS: Trimodality therapy was significantly associated with prolonged survival in patients with MPM, even when adjusting for baseline patient factors. Radiation therapy was associated with improved survival, but the modality of radiation therapy used was not associated with outcome.
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Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Mesotelioma/mortalidad , Mesotelioma/terapia , Pleura/cirugía , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/terapia , Adulto , Factores de Edad , Anciano , Análisis de Varianza , Quimioterapia Adyuvante , Estudios de Cohortes , Terapia Combinada/métodos , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Mesotelioma/patología , Mesotelioma Maligno , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Neoplasias Pleurales/patología , Pronóstico , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante , Estudios Retrospectivos , Medición de Riesgo , Factores Sexuales , Análisis de SupervivenciaRESUMEN
The purpose of this study was to determine factors associated with acute skin toxicity from breast radiation for optimizing forward-planned intensity modulation. Treatment plans in 100 patients who received breast radiation using three-dimensional treatment planning were analyzed. Fifty-two patients were treated with tangent fields using wedges (nonsegmented), and 48 patients were treated with forward-planned fields segmented by a multileaf collimator to modulate intensity. Clinical and dosimetric variables were recorded. Acute skin toxicity was prospectively documented using a standard scale. Body weight, breast target volume, maximum body dose (encompassing 10 mL), and volume of body receiving >50 Gy and 55 Gy (V50Gy, and V55Gy) were associated with acute toxicity. Patients treated with segmented plans had significantly larger breast targets and were treated to lower prescription isodoses, confounding comparison with nonsegmented plans. Consequently, datasets from patients treated with segmented plans were used to design new nonsegmented plans for paired comparison. Segmented plans were superior with respect to dosimetric endpoints predictive of toxicity in this paired comparison. Limitations of 55 Gy for maximum body dose and 1100 mL for V50Gy appeared to be appropriate values to guide forward treatment planning of segmented fields.
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Neoplasias de la Mama/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Piel/efectos de la radiación , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Humanos , Persona de Mediana Edad , Radiografía , RadiometríaRESUMEN
PURPOSE: [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging for brain tumors has been shown to identify areas of active disease. Radiation dose escalation in the treatment of glioblastoma multiforme may lead to improved disease control. Based on these premises, we initiated a prospective study of FDG-PET for the treatment planning of radiation dose escalation for the treatment of glioblastoma multiforme. METHODS AND MATERIALS: Forty patients were enrolled. Patients were treated with standard conformal fractionated radiotherapy with volumes defined by MRI imaging. When patients reached a dose of 45-50.4 Gy, they underwent FDG-PET imaging for boost target delineation, for an additional 20 Gy (2 Gy per fraction) to a total dose of 79.4 Gy (n = 30). RESULTS: The estimated 1-year and 2-year overall survival (OS) for the entire group was 70% and 17%, respectively, with a median overall survival of 70 weeks. The estimated 1-year and 2-year progression-free survival (PFS) was 18% and 3%, respectively, with a median of 24 weeks. No significant improvements in OS or PFS were observed for the study group in comparison to institutional historical controls. CONCLUSIONS: Radiation dose escalation to 79.4 Gy based on FDG-PET imaging demonstrated no improvement in OS or PFS. This study establishes the feasibility of integrating PET metabolic imaging into radiotherapy treatment planning.
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Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Glioblastoma/diagnóstico por imagen , Glioblastoma/radioterapia , Tomografía de Emisión de Positrones/métodos , Estudios de Factibilidad , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radiofármacos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodosRESUMEN
OBJECT: The authors sought to compare the outcomes of patients with arteriovenous malformations (AVMs) treated by Gamma Knife surgery (GKS) with those of patients treated by linear accelerator-based (LINAC) radiosurgery. METHODS: One hundred and eighty-seven patients with AVMs were treated at our institution between 1992 and 2003. Ninety-one patients were treated with GKS and 96 patients were treated with LINAC radiosurgery. Patient and treatment characteristics in the two groups included the following. In the LINAC group, the median age was 33 years (range 9-66 years); the median dose was 16 Gy (70% isodose line); the median treated AVM volume was 5.5 cm3; and 46% of patients in this group were treated after hemorrhage. In the GKS group, the median age was 38 years (range 6-63 years); the median dose was 20 Gy (50% isodose line); the median treated AVM volume was 4.3 cm3; and 44% of patients in this group were treated after hemorrhage. Obliteration of AVMs was determined by performing computed tomography (CT) angiography and/or magnetic resonance (MR) angiography and angiography. Patient follow-up evaluation included obtaining an MR angiogram/MR image or CT angiogram at 6 months, at 1 year, and then annually thereafter. Angiography was performed to confirm obliteration when MR angiography and/or CT angiography no longer revealed evidence of an AVM. The 5-year estimated AVM obliteration rate was 66% in the entire patient group; the LINAC group was 60%; the GKS group was 72%; this difference was not statistically significant (p = 0.97). Twelve patients who underwent treatment with LINAC radiosurgery underwent retreatment with GKS and one was retreated with LINAC radiosurgery. The obliteration rate was 82%. Six patients treated with GKS were retreated with GKS, but the follow-up time is of short duration. Chronic toxicity occurred in 8% of both the GKS and the LINAC groups (p = 0.61). Posttreatment hemorrhage during the time of risk before AVM obliteration was 13% in the GKS group and 6.2% in the LINAC group (p = 0.05). CONCLUSIONS: Treatment of patients with AVMs by using LINAC radiosurgery and GKS treatment produces high obliteration rates with acceptable long-term radiation toxicity in the patients treated.
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Rayos gamma , Malformaciones Arteriovenosas Intracraneales/cirugía , Aceleradores de Partículas , Radiocirugia/instrumentación , Adolescente , Adulto , Anciano , Niño , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/diagnóstico , Hemorragias Intracraneales/etiología , Masculino , Persona de Mediana Edad , Radiocirugia/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: Malignant pleural mesothelioma (MPM) is a fatal disease lacking standardized treatment. We describe the use of fast neutron radiation therapy in MPM patients referred to the Department of Radiation Oncology at the University of Washington Medical Center. MATERIALS AND METHODS: Retrospective chart review of MPM patients receiving neutron radiotherapy treatment from 1980 to 2012. RESULTS: A total of 30 MPM patients received fast neutron radiotherapy as part of their treatment regimen. Median age at diagnosis was 59.6 years (range, 46.6 to 72.3 y). Eighteen patients received fast neutron radiotherapy as a component of trimodality treatment. Median overall survival was 20.3 months (range, 5.5 to 73.3 mo) with 1 patient censored at 34.8 months and all other patients with confirmed dates of death. One patient receiving radiotherapy alone as a palliative measure died during radiation treatment. One patient was unable to tolerate radiotherapy and stopped before completing prescribed treatment. On univariate analysis, Brigham Stage at presentation was a significant predictor of survival (P<0.01). No significant differences in survival were observed when comparing patients who received trimodality treatment compared to those who did not. CONCLUSIONS: Fast neutron radiotherapy may be utilized in the management of MPM patients. However, treatment with fast neutron radiotherapy did not significantly improvement outcome, even when used in a trimodality regimen.
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Neutrones Rápidos/uso terapéutico , Neoplasias Pulmonares/radioterapia , Mesotelioma/radioterapia , Neoplasias Pleurales/radioterapia , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Quimioradioterapia Adyuvante/métodos , Cisplatino/administración & dosificación , Estudios de Cohortes , Femenino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/terapia , Mesotelioma Maligno , Metotrexato/administración & dosificación , Persona de Mediana Edad , Neoplasias Pleurales/terapia , Neumonectomía , Radioterapia Adyuvante/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Vinblastina/administración & dosificaciónRESUMEN
PURPOSE: Progesterone receptors are expressed in approximately 70% of meningiomas. Mifepristone is an oral antiprogestational agent reported to have modest activity in a phase II study. This multicenter, prospective, randomized, placebo-controlled phase III trial conducted by SWOG was planned to define the role of mifepristone in the treatment of unresectable meningioma. PATIENTS AND METHODS: Eligible patients were randomly assigned to receive either mifepristone or placebo for 2 years unless disease progressed. Patients who were stable or responding to protocol therapy after 2 years had the option to continue with the same blinded therapy. Serial follow-up allowed assessment of efficacy and toxicity. Time to treatment failure and overall survival were ascertained for all randomly assigned patients. On progression, patients receiving placebo could cross over and receive active drug. RESULTS: Among 164 eligible patients, 80 were randomly assigned to mifepristone and 84 to placebo. Twenty-four patients (30%) were able to complete 2 years of mifepristone without disease progression, adverse effects, or other reasons for discontinuation. Twenty-eight patients (33%) in the placebo arm completed the 2-year study. There was no statistical difference between the arms in terms of failure-free or overall survival. CONCLUSION: Long-term administration of mifepristone was well tolerated but had no impact on patients with unresectable meningioma.
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Antagonistas de Hormonas/uso terapéutico , Neoplasias Meníngeas/tratamiento farmacológico , Meningioma/tratamiento farmacológico , Mifepristona/uso terapéutico , Progestinas/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Masculino , Neoplasias Meníngeas/mortalidad , Neoplasias Meníngeas/patología , Meningioma/mortalidad , Meningioma/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
UNLABELLED: The use of (18)F-FDG PET for brain tumors has been shown to be accurate in identifying areas of active disease. Radiation dose escalation in the treatment of glioblastoma multiforme (GBM) may lead to improved disease control. On the basis of these premises, we initiated a pilot study to investigate the use of (18)F-FDG PET for the guidance of radiation dose escalation in the treatment of GBM. METHODS: Patients were considered eligible to participate in the study if they had a diagnosis of GBM, were at least 18 y old, and had a score of at least 60 on the Karnofsky Scale. Patients were treated with standard conformal fractionated radiotherapy (1.8 Gy per fraction, to 59.4 Gy), with volumes defined by MRI. At a dose of 45-50.4 Gy, patients underwent (18)F-FDG PET for boost target delineation. Final noncoplanar fields (3-4) were designed to treat the volume of abnormal (18)F-FDG uptake plus a 0.5-cm margin for an additional 20 Gy (2 Gy per fraction), to a total dose of 79.4 Gy. If no abnormal (18)F-FDG uptake was observed, treatment was stopped after the conventional course of 59.4 Gy. Age, Karnofsky score, MRI-based volumes, and (18)F-FDG PET volume were analyzed as prognostic variables for time to tumor progression (TTP) and overall survival. (18)F-FDG PET volumes and MRI-based volumes were compared to assess concordance. RESULTS: For the 27 patients who could be evaluated, median actuarial TTP was 43 wk, and median actuarial survival was 70 wk. On univariate analysis, (18)F-FDG PET, T1-weighted MRI gadolinium enhancement (excluding nonenhancing resection cavity), and T2-weighted MRI volumes were significantly predictive of TTP. On multivariate analysis, only (18)F-FDG PET volume retained significance for predicting TTP. Similar results were obtained on analysis of these variables as prognostic factors for survival. When (18)F-FDG PET-based volumes were compared with MRI-based volumes, a difference of at least 25% was detected in all patients, with all but 2 having smaller (18)F-FDG PET volumes. Of patients in whom (18)F-FDG uptake was initially present but treatment subsequently failed, 83% demonstrated the first tumor progression within the region of abnormal (18)F-FDG uptake. CONCLUSION: In comparison with MRI, (18)F-FDG PET defined unique volumes for radiation dose escalation in the treatment of GBM. (18)F-FDG PET volumes were predictive of survival and time to tumor progression in the treatment of patients with GBM.
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Neoplasias Encefálicas/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Glioblastoma/diagnóstico por imagen , Radiofármacos , Tomografía Computarizada de Emisión , Adulto , Anciano , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Dosis de RadiaciónAsunto(s)
Aorta Torácica/cirugía , Quimioradioterapia/efectos adversos , Procedimientos Endovasculares/métodos , Neoplasias Esofágicas/terapia , Hematemesis/prevención & control , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/patología , Carboplatino/administración & dosificación , Procedimientos Endovasculares/instrumentación , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/patología , Hematemesis/etiología , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/diagnóstico por imagen , Paclitaxel/administración & dosificación , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radioterapia de Intensidad Modulada/efectos adversos , Stents , Resultado del TratamientoRESUMEN
PURPOSE: The addition of PCV (procarbazine, lomustine, and vincristine) chemotherapy to radiotherapy (RT) for patients with WHO grade 2 glioma improves progression-free survival (PFS). The effect of therapy intensification on cognitive function (CF) remains a concern in this population with substantial long-term survival. PATIENTS AND METHODS: A total of 251 patients with WHO grade 2 glioma age ≥ 40 years with any extent of resection or age < 40 years with subtotal resection/biopsy were randomly assigned to RT (54 Gy) or RT plus PCV. We observed 111 patients age < 40 years with gross total resection. CF was assessed by Mini-Mental State Examination (MMSE) at baseline and years 1, 2, 3, and 5. RESULTS: Overall, few patients experienced significant decline in MMSE score. There were no significant differences in the proportion of patients experiencing MMSE score decline between the randomized study arms at any time point. Both study arms experienced a significant gain in average MMSE score longitudinally over time, with no difference between arms. CONCLUSION: The MMSE is a relatively insensitive tool, and subtle changes in CF may have been missed. However, the addition of PCV to RT did not result in significantly higher rates of MMSE score decline than RT alone through 5 years of follow-up. Patients in both randomly assigned arms experienced a statistically significant average MMSE score increase over time, with no difference between arms. The addition of PCV chemotherapy to RT improves PFS without excessive CF detriment over RT alone for patients with low-grade glioma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Cognición/efectos de los fármacos , Cognición/efectos de la radiación , Glioma/tratamiento farmacológico , Glioma/radioterapia , Adulto , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/psicología , Quimioradioterapia Adyuvante , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/etiología , Supervivencia sin Enfermedad , Femenino , Glioma/patología , Glioma/psicología , Humanos , Lomustina/administración & dosificación , Masculino , Clasificación del Tumor , Procarbazina/administración & dosificación , Estudios Prospectivos , Tasa de Supervivencia , Vincristina/administración & dosificaciónRESUMEN
A substantial, but uncertain, number of patients with cancer develop brain metastases. Risk of brain metastasis is recognized to vary with type of primary cancer. Within specific types of primary cancer, prognostic factors for development of brain metastases are being recognized. Recent data suggest that molecular biomarkers that relate to cellular function can predict risk of developing brain metastases. Such information could optimize surveillance standards and/or be used to select patients for preventive interventions. Though average survival for patients with brain metastases is typically less than 6 months, it is well-recognized that subgroups of patients have significant probability of longer survival. Multiple prognostic models have been proposed, validated, and compared without clearly demonstrating superiority of one model over another. However, some factors show consistency as predictive variables across models, and performance status is almost universally significant. Application of predictive models to specific treatments has been difficult. Tumor-specific prognostic models are evolving, and combinations of biological and clinical factors may be used to optimize models for particular primary tumor types.
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BACKGROUND: Patients with recurrent malignant gliomas have a uniformly poor prognosis. However, further treatment is often warranted at the time of recurrence. Low-activity implanted brachytherapeutic devices, such as iodine-125 seeds, and implantable chemotherapeutic devices such as 1, 3-bis (2-chloroethyl)-nitrosourea (BCNU) impregnated polymer wafers (Gliadel(®)) have been shown to be safe and modestly effective, but a comparison of combination therapy versus Gliadel(®) implantation alone has not been performed. METHODS: We retrospectively examined 24 patients following re-resection of recurrent glioblastoma, with 17 patients undergoing implantation of both Gliadel(®) and iodine-125 seeds, and 7 patients undergoing implantation of Gliadel(®) only. Outcomes examined included adverse events, survival after re-resection (SAR), and time to tumor progression after re-resection (PAR). RESULTS: Implantation of both Gliadel(®) and low activity iodine-125 seeds is safe with only two wound infections noted, a complication rate comparable to previous reports. The combination appears to confer a median SAR benefit if the activity per tumor resection volume exceeds 0.8 mCi/mL (60 versus 31 weeks, P = 0.02), and this benefit remained significant on multivariate analysis (HR =0.26 [CI:0.07-0.93], P = 0.03). Gross total resection of tumor was also significantly associated with longer time to PAR (HR =5.4 [CI: 1.13-26.0], P = 0.03). CONCLUSIONS: The concomitant use of Gliadel(®) and low activity iodine-125 seeds following re-resection of recurrent glioblastoma is safe. Our study demonstrated a significant benefit in SAR if the iodine-125 activity per tumor volume is greater than 0.8 mCi/mL. While our sample size is small, our results are in agreement with previous studies demonstrating the efficacy of combination treatment.
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PURPOSE: A prior Radiation Therapy Oncology Group (RTOG) clinical trial in anaplastic oligodendroglioma suggested a progression-free survival benefit for procarbazine, lomustine, and vincristine (PCV) chemotherapy in addition to radiation therapy (RT), as have smaller trials in low-grade glioma (LGG). PATIENTS AND METHODS: Eligibility criteria included supratentorial WHO grade 2 LGG, age 18 to 39 years with subtotal resection/biopsy, or age ≥ 40 years with any extent resection. Patients were randomly assigned to RT alone or RT followed by six cycles of PCV. Survival was compared by using the modified Wilcoxon and log-rank tests. RESULTS: In all, 251 patients were accrued from 1998 to 2002. Median overall survival (OS) time and 5-year OS rates for RT versus RT + PCV were 7.5 years versus not reached and 63% versus 72%, respectively (hazard ratio [HR]; 0.72; 95% CI, 0.47 to 1.10; P = .33; log-rank P = .13). Median progression-free survival (PFS) time and 5-year PFS rates for RT versus RT + PCV were 4.4 years versus not reached and 46% versus 63%, respectively (HR, 0.6; 95% CI, 0.41 to 0.86; P = .06; log-rank P = .005). OS and PFS were similar for all patients between years 0 and 2. After 2 years, OS and PFS curves separated significantly, favoring RT + PCV. For 2-year survivors (n = 211), the probability of OS for an additional 5 years was 74% with RT + PCV versus 59% with RT alone (HR, 0.52; 95% CI, 0.30 to 0.90; log-rank P = .02). CONCLUSION: PFS but not OS was improved for adult patients with LGG receiving RT + PCV versus RT alone. On post hoc analysis, for 2-year survivors, the addition of PCV to RT conferred a survival advantage, suggesting a delayed benefit for chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia Adyuvante , Glioma/terapia , Neoplasias Supratentoriales/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia Adyuvante/efectos adversos , Distribución de Chi-Cuadrado , Supervivencia sin Enfermedad , Glioma/mortalidad , Glioma/patología , Humanos , Estimación de Kaplan-Meier , Lomustina/administración & dosificación , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Procarbazina/administración & dosificación , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo , Neoplasias Supratentoriales/mortalidad , Neoplasias Supratentoriales/patología , Factores de Tiempo , Resultado del Tratamiento , Vincristina/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: The poor prognosis reported for patients with high-grade glial neoplasms indicates a need for the development of multimodality therapeutic approaches. The addition of chemotherapy has contributed variably to increased survival. The objective of the current study (Southwest Oncology Group [SWOG] 9016) was to determine whether concurrent radiotherapy and chemotherapy with the combination of carmustine and cisplatin could be given safely in a cooperative group setting. Additional objectives included the estimation of response rate, the rate of disease stabilization, and the probability of 1-year survival. METHODS: SWOG 9016 study included 59 eligible patients with grade III or IV astrocytoma who received radiotherapy concurrently with carmustine/cisplatin chemotherapy. Patients were required to have either measurable or evaluable disease. The therapeutic endpoints were comprised of complete response (CR), partial response (PR), or progressive disease (PD). RESULTS: Six patients achieved a CR (CR rate of 10%; 95% confidence interval [95% CI], 4-21%), 4 achieved a PR (PR rate of 7%; 95% CI, 2-16%), and 2 patients (3%) experienced an unconfirmed response. Twenty-four patients (41%; 95% CI, 28-54%) had stable disease and 10 patients (17%) demonstrated PD. The overall disease stabilization rate (CR + PR + stable disease, excluding unconfirmed response) was 58% (95% CI, 44-70%). CONCLUSIONS: Despite the presence of a cohort of long-term survivors, the results of the current study do not appear to support the additional study or routine use of concurrent cisplatin and carmustine.