RESUMEN
To formulate Functional Assessment of Cancer Therapy-Meningioma (FACT-MNG), a web-based tumor site-specific outcome instrument for assessing intracranial meningioma patients following surgical resection or stereotactic radiosurgery. We surveyed the relevant literature available on intracranial meningioma surgery and subsequent outcomes (38 papers), making note of which, if any, QOL/outcome instruments were utilized. None of the surgveyed papers included QOL assessment specific to tumor site. We subsequently developed questions that were relevant to the signs and symptoms that characterize each of 11 intracranial meningioma sites, and incorporated them into a modified combination of the Functional Assessment of Cancer Therapy-Brain (FACT-BR) and SF36 outcome instruments, thereby creating a new tumor site-specific outcome instrument, FACT-MNG. With outcomes analysis of surgical and radiosurgical treatments becoming more important, measures of the adequacy and success of treatment are needed. FACT-MNG represents a first effort to formalize such an instrument for meningioma patients. Questions specific to tumor site will allow surgeons to better assess specific quality of life issues not addressed in the past by more general questionnaires.
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Internet , Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Evaluación de Resultado en la Atención de Salud , Calidad de Vida , Radiocirugia , HumanosRESUMEN
Focal areas of restricted diffusion adjacent to high-grade glioma resection cavities were detected in 70% of patients on immediate postoperative MRI studies. Follow-up studies demonstrated cystic encephalomalacia in 91% of these foci, suggesting the presence of infarction, and the infarcted tissue demonstrated enhancement in 43% of cases. New postoperative deficits correlated well with the anatomic region of infarction in six patients. Enhancement in perioperative infarcts can mimic tumor progression on follow-up imaging studies.
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Infarto Encefálico/etiología , Infarto Encefálico/patología , Neoplasias Encefálicas/cirugía , Glioblastoma/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/irrigación sanguínea , Encéfalo/patología , Encéfalo/fisiopatología , Infarto Encefálico/fisiopatología , Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/fisiopatología , Arterias Cerebrales/lesiones , Arterias Cerebrales/patología , Arterias Cerebrales/fisiopatología , Circulación Cerebrovascular/fisiología , Confusión/etiología , Confusión/patología , Confusión/fisiopatología , Imagen de Difusión por Resonancia Magnética/normas , Femenino , Glioblastoma/irrigación sanguínea , Glioblastoma/fisiopatología , Humanos , Masculino , Microcirculación/lesiones , Microcirculación/patología , Microcirculación/fisiopatología , Persona de Mediana Edad , Paresia/etiología , Paresia/patología , Paresia/fisiopatología , Complicaciones Posoperatorias/fisiopatología , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Patients with a newly detected brain mass and no history of cancer often undergo extensive diagnostic testing in search of a systemic primary neoplasm prior to selection of a biopsy site, potentially leading to unnecessary expense and delay. We sought patterns in the evaluation of these patients to allow rapid selection of a biopsy site. METHODS: We compared the diagnostic evaluation of 176 patients with newly detected brain masses who were ultimately determined to have a metastatic or primary lesion. RESULTS: In 88 patients presenting with brain metastasis, lung cancer was markedly overrepresented as a primary tumor, occurring in 82% of patients. Brain MRI and chest CT together identified the site for diagnostic biopsy in all except for two of the 176 patients. One-half of the patients with metastasis had brain biopsy as the primary diagnostic procedure, with 80% undergoing a craniotomy rather than needle biopsy. The initial management decision in the majority of metastasis patients was whether to perform a craniotomy for resection of tumor. Whereas patients with single and cerebellar lesions were most likely to undergo craniotomy, the extent of systemic disease did not affect the decision to recommend a neurosurgical procedure. The average time to biopsy for patients with metastatic and primary tumors was 4.7 days and 6.0 days. In this retrospective population, we estimated that evaluation with brain MRI and chest CT, followed by an early neurosurgical decision, could reduce the time to diagnosis by at least 10%. CONCLUSIONS: Chest CT and brain MRI, if used together as initial diagnostic studies, would have identified a biopsy site in 97% of patients with a newly detected brain mass.
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Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundario , Carcinoma/diagnóstico , Carcinoma/secundario , Neoplasias Pulmonares/diagnóstico , Biopsia/normas , Encéfalo/patología , Estudios de Cohortes , Craneotomía , Diagnóstico Diferencial , Femenino , Humanos , Incidencia , Pulmón/diagnóstico por imagen , Pulmón/patología , Neoplasias Pulmonares/patología , Imagen por Resonancia Magnética/normas , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/normasRESUMEN
PURPOSE: Recent studies have suggested relative radioresistance in glioblastoma multiforme (GM) tumors in older patients, consistent with their shorter survival. Two common molecular genetic abnormalities in GM are age related: epidermal growth factor receptor (EGFR) overexpression in older patients and p53 mutations in younger patients. We tested whether these abnormalities correlated with clinical heterogeneity in GM response to radiation treatment. METHODS AND MATERIALS: Radiographically assessed radiation response (5-level scale) was correlated with EGFR immunoreactivity, p53 immunoreactivity, and p53 exon 5-8 mutation status in 170 GM patients treated using 2 prospective clinical protocols. Spearman rank correlation and proportional-odds ordinal regression were used for univariate and multivariate analysis. RESULTS: Positive EGFR immunoreactivity predicted poor radiographically assessed radiation response (p = 0.046). Thirty-three percent of tumors with no EGFR immunoreactivity had good radiation responses (>50% reduction in tumor size by CT or MRI), compared to 18% of tumors with intermediate EGFR staining and 9% of tumors with strong staining. There was no significant relationship between p53 immunoreactivity or mutation status and radiation response. Significant relationships were noted between EGFR score and older age and between p53 score or mutation status and younger age. CONCLUSION: The observed relative radioresistance of some GMs is associated with overexpression of EGFR.
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Neoplasias Encefálicas/radioterapia , Receptores ErbB/metabolismo , Genes p53/genética , Glioblastoma/radioterapia , Proteínas de Neoplasias/metabolismo , Neoplasias Supratentoriales/radioterapia , Adolescente , Adulto , Factores de Edad , Anciano , Análisis de Varianza , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Femenino , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Prospectivos , Dosificación Radioterapéutica , Análisis de Regresión , Neoplasias Supratentoriales/genética , Neoplasias Supratentoriales/metabolismoRESUMEN
OBJECTIVE: Hemorrhages from cerebral cavernous malformations (CMs) sometimes seem to occur in closely spaced "clusters" interspersed with long hemorrhage-free intervals. Clustering of hemorrhages could affect retrospective assessments of radiosurgery efficacy in prevention of CM rehemorrhage. However, this empirical observation had not been tested quantitatively. To test whether CM hemorrhages tend to cluster, we reviewed pretreatment rebleeding rates after a first symptomatic hemorrhage in CM patients who later underwent surgery or radiosurgery. METHODS: We performed a retrospective review of 141 patients with CMs who presented with clinically overt hemorrhage, and who subsequently underwent surgery or proton beam radiosurgery during an 18-year period. Statistical models were used to analyze all events per person and identify potential variation in rebleeding risk with time after a previous hemorrhage. RESULTS: Sixty-three of 141 patients experienced a second hemorrhage before treatment; 16 had additional hemorrhages. Five hundred thirty-eight patient years elapsed between first hemorrhages and treatment. The cumulative incidence of a second hemorrhage after the first CM hemorrhage was 14% after 1 year and 56% after 5 years. During the first 2.5 years after a hemorrhage, the monthly rehemorrhage hazard was 2%. The risk then decreased spontaneously to less than 1% per month, which represents a 2.4-fold decline (P < 0.001). Rehemorrhage rates were higher in younger patients (P < 0.01), but not in females or in patients with deep lesions. Shorter intervals between successive hemorrhages did not predict higher subsequent rehemorrhage risk. CONCLUSION: The rehemorrhage rate from untreated CMs is high initially, and it decreases 2 to 3 years after a previous hemorrhage. This hazard pattern generates the observed temporal clustering of hemorrhages from untreated CMs.
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Seno Cavernoso/anomalías , Malformaciones Vasculares del Sistema Nervioso Central/complicaciones , Hemorragia Cerebral/etiología , Adolescente , Adulto , Hemorragia Cerebral/terapia , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
Glioblastoma multiforme (GBM) carries a dismal prognosis. However, a range of survival times exists, and parameters that define prognostic groups may help to optimize treatment. To identify such prognostic groups, we analyzed tumor tissue from 110 cases of newly diagnosed GBM from two clinical protocols. Similar to other studies, we found no association of epidermal growth factor receptor (EGFR) overexpression (as assessed by immunohistochemistry), p53 immunopositivity, or p53 mutation with survival in the entire sample. However, EGFR overexpression showed trends toward worse prognosis in patients younger than the median age, but better prognosis in patients older than the median age. This interaction of EGFR with age group was statistically significant and led us to focus our further analyses on the younger patients. In this group, a statistically significant association of EGFR overexpression with worse survival was identified in the p53-negative but not p53-positive tumors. We found a similar result after screening these cases for mutations in p53: EGFR overexpression was negatively associated with survival only in the p53 wild-type cases. To confirm this unexpected result, this finding was reproduced in a validation sample of an additional 42 tumors from younger patients on the same two clinical protocols. This complex relationship between EGFR and p53 in younger patients remained in a multivariate analysis that incorporated additional prognostic variables. The results suggest that analysis of prognostic markers in GBM is complex, and maximal information may require analysis of subgroups based on age and the status of specific markers such as p53. In addition, they suggest a specific group of patients on which to focus promising therapies targeting EGFR.
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Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Receptores ErbB/biosíntesis , Glioblastoma/genética , Glioblastoma/metabolismo , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/genética , Adulto , Factores de Edad , Anciano , Biomarcadores de Tumor/biosíntesis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Neoplasias Encefálicas/patología , División Celular/fisiología , Femenino , Genes p53 , Glioblastoma/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación , Polimorfismo Conformacional Retorcido-Simple , Pronóstico , Reproducibilidad de los Resultados , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/inmunologíaRESUMEN
OBJECTIVE: Advanced age is a strong predictor of shorter survival in patients with glioblastoma multiforme (GM), especially for those who receive multimodality treatment. Radiographically assessed tumor response to external beam radiation therapy is an important prognostic factor in GM. We hypothesized that older GM patients might have more radioresistant tumors. METHODS: We studied radiographically assessed response to external beam radiation treatment (five-level scale) in relation to age and other prognostic factors in a cohort of 301 GM patients treated on two prospective clinical protocols. A total of 223 patients (74%) were assessable for radiographically assessed radiation response. A proportional odds ordinal regression model was used for univariate and multivariate analysis. RESULTS: Younger age (P = 0.006), higher Karnofsky Performance Scale score before radiotherapy (P = 0.027), and more extensive surgical resection (P = 0.028) predicted better radiation response in univariate analyses. Results were similar when clinical criteria were used to classify an additional 61 patients without radiographically assessed radiation response (stable versus progressive disease). In multivariate analyses, age and extent of resection were significant independent predictors of radiation response (P < 0.05); Karnofsky Performance Scale score was of borderline significance (P = 0.07). CONCLUSION: Older GM patients are less likely to have good responses to postoperative external beam radiation therapy. Karnofsky Performance Scale score before radiation treatment and extent of surgical resection are additional predictors of radiographically assessed radiation response in GM.
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Neoplasias Encefálicas/radioterapia , Irradiación Craneana , Glioblastoma/radioterapia , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/cirugía , Estudios de Cohortes , Terapia Combinada , Fraccionamiento de la Dosis de Radiación , Glioblastoma/diagnóstico por imagen , Glioblastoma/mortalidad , Glioblastoma/cirugía , Humanos , Oportunidad Relativa , Radiografía , Radioterapia Adyuvante , Tasa de Supervivencia , Resultado del TratamientoAsunto(s)
Neoplasias Hipofisarias/cirugía , Acromegalia/diagnóstico , Acromegalia/mortalidad , Acromegalia/cirugía , Adenoma/diagnóstico , Adenoma/mortalidad , Adenoma/cirugía , Adulto , Anciano , Craneofaringioma/diagnóstico , Craneofaringioma/mortalidad , Craneofaringioma/cirugía , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/mortalidad , Síndrome de Cushing/cirugía , Femenino , Estudios de Seguimiento , Humanos , Hipofisectomía , Masculino , Persona de Mediana Edad , Síndromes Paraneoplásicos Endocrinos/diagnóstico , Síndromes Paraneoplásicos Endocrinos/mortalidad , Síndromes Paraneoplásicos Endocrinos/cirugía , Neoplasias Hipofisarias/diagnóstico , Neoplasias Hipofisarias/mortalidad , Prolactinoma/diagnóstico , Prolactinoma/mortalidad , Prolactinoma/cirugía , Reoperación , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE/HYPOTHESIS: In specific clinical situations, endoscopes offer better visualization than the microscope during acoustic neuroma (vestibular schwannoma) surgery and can therefore decrease the incidence of the postoperative complications of cerebrospinal fluid (CSF) leakage and recurrence of tumor. This study was undertaken to determine if the use of adjunctive endoscopy provides complementary information to the operating surgeon during surgery for acoustic neuromas. METHOD: Seventy-eight patients with acoustic neuromas underwent tumor excision by two neurotologists (PAW., D.S.P.), together with their respective neurosurgical partners, via a retrosigmoid (suboccipital) approach (n = 68), translabyrinthine approach (n = 7), or middle cranial fossa approach (n = 3). Endoscopy with a rigid glass lens endoscope was used during tumor removal to examine posterior fossa neurovascular structures, and after tumor excision to inspect the internal auditory canal (IAC), inner ear, and middle ear, depending on the approach used. One of the authors (D.S.P.) has not used adjunctive endoscopy during resections via the translabyrinthine and middle cranial fossa approaches, and therefore, these cases were excluded from the data collection and analysis. RESULTS: Complete tumor excision was achieved in 73 patients. Endoscopy allowed improved identification of tumor and adjacent neurovascular relationships in all cases. In addition, residual tumor at the fundus of the IAC (n = 11) and exposed air cells (n = 24) not seen with the microscope during retrosigmoid approaches were identified endoscopically. In one of the translabyrinthine cases, the endoscope allowed identification of open air cells not visualized with the microscope. None of the 78 patients developed CSF rhinorrhea. Incorporating the endoscope did not significantly increase operative time. CONCLUSIONS: Endoscopy can be performed safely during surgery to remove acoustic neuromas. The adjunctive use of endoscopy may offer some advantages including improved visualization, more complete tumor removal, and a lowered risk of CSF leakage.
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Neoplasias de los Nervios Craneales/cirugía , Endoscopía/métodos , Neuroma Acústico/cirugía , Adolescente , Adulto , Anciano , Otorrea de Líquido Cefalorraquídeo/prevención & control , Neoplasias de los Nervios Craneales/diagnóstico , Craneotomía/métodos , Oído Interno/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroma Acústico/diagnóstico , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios , Estudios Prospectivos , Hueso Temporal/cirugíaRESUMEN
Radiosurgery is being used more routinely to treat patients with inoperable, recurrent, or multiple brain metastases from systemic cancer. Results in > 2000 treated patients have been published during the past 8 years. These results indicate that permanent local control can be obtained in > 80% of treated lesions with complications in < 10% of patients. Success is independent of the histology, ie, melanoma vs adenocarcinoma, of the treated lesion or number of lesions treated. The long-term results of radiosurgery compare favorably with those seen following surgical resection. The cost-effectiveness of radiosurgery compared to surgical resection favors an expanded role for this technology in the treatment of selected patients with brain metastases.
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Neoplasias Encefálicas/secundario , Neoplasias Encefálicas/cirugía , Radiocirugia , Humanos , Radiocirugia/efectos adversosRESUMEN
BACKGROUND: Untreated Cushing disease historically has a high mortality rate, but the long-term survival of patients with Cushing disease after transsphenoidal surgery has not been reported. OBJECTIVE: To determine long-term mortality rate in patients who are treated for Cushing disease with current management techniques. DESIGN: Retrospective case series. SETTING: Tertiary care center. PATIENTS: 161 patients (32 men and 129 women; mean age, 38 years) who were treated for Cushing disease between 1978 and 1996. INTERVENTION: Transsphenoidal adenomectomy and as-needed adjunctive therapy. MEASUREMENT: Record review with follow-up interview. RESULTS: The cure rate for patients with microadenomas who had no previous therapy was 90% (123 of 137). No perioperative deaths occurred (0 of 193 procedures [95% CI, 0.0% to 1.9%]). Follow-up data (mean, 8.7 years) were obtained for 99% of patients (159 of 161). Six patients died. The 5- and 10-year survival rates were 99% (CI, 97% to 100%) and 93% (CI, 88% to 99%), respectively. Survival was similar to that seen in an age- and sex-matched sample that was based on U.S. population data (standardized mortality ratio, 0.98 [CI, 0.44 to 2.2]; P > 0.2). CONCLUSION: Survival of patients treated for Cushing disease with current management techniques between 1978 and 1996 was better than the poor survival historically associated with this disorder.
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Adenoma/cirugía , Neoplasias de las Glándulas Suprarrenales/cirugía , Síndrome de Cushing/mortalidad , Síndrome de Cushing/cirugía , Adenoma/complicaciones , Adenoma/metabolismo , Adolescente , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/metabolismo , Adulto , Anciano , Niño , Síndrome de Cushing/etiología , Femenino , Estudios de Seguimiento , Humanos , Hidrocortisona/sangre , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Estadística como Asunto , Tasa de Supervivencia , Factores de TiempoRESUMEN
OBJECTIVE/HYPOTHESIS: In some instances endoscopes offer better visualization than the microscope and frequently allow less invasive surgery. This study was undertaken to determine whether endoscopy is safe and effective during neurectomy of the vestibular nerve. METHOD: Ten patients with intractable unilateral Meniere's disease underwent a retrosigmoid craniotomy for neurectomy of the vestibular nerve. Endoscopy with a Hopkins telescope was used during each procedure to study posterior fossa anatomic relationships and to assist the neurectomy. Preoperative and postoperative audiometric evaluation was performed in all patients undergoing vestibular neurectomy. Nine of these patients had preoperative electronystagmography, and four patients completed postoperative electronystagmography. The 1995 American Academy of Otolaryngology-Head and Neck Surgery's Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of therapy in Meniere's disease were used. RESULTS: Complete neurectomy was achieved in all 10 patients. Endoscopy allowed improved identification of the nervus intermedius and the facial, cochlear, and vestibular nerves and adjacent neurovascular relationships without the need for significant retraction of the cerebellum or brainstem. In addition, endoscopic identification of the cleavage plane between the cochlear and vestibular nerves medial to or within the internal auditory canal (n = 3) was not made with the 0-degree endoscope; however, identification was made with the 30- or 70-degree endoscope in all cases. In all patients with Meniere's disease, elimination of the recurrent episodes of vertigo (n = 10) or otolithic crisis of Tumarkin (n = 1) was achieved. CONCLUSIONS: Posterior fossa endoscopy can be performed safely. Endoscope-assisted neurectomy of the vestibular nerve may offer some advantages over standard microsurgery including increased visualization, more complete neurectomy, minimal cerebellar retraction, and a lowered risk of cerebrospinal fluid leakage.
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Endoscopía , Enfermedad de Meniere/cirugía , Nervio Vestibular/cirugía , Adulto , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoAsunto(s)
Leucemia de Células Pilosas/diagnóstico , Púrpura Trombocitopénica/diagnóstico , Neoplasias del Bazo/diagnóstico , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Leucemia de Células Pilosas/patología , Leucemia de Células Pilosas/fisiopatología , Púrpura Trombocitopénica/patología , Púrpura Trombocitopénica/fisiopatología , Neoplasias del Bazo/patología , Neoplasias del Bazo/fisiopatologíaRESUMEN
To analyze the long term outcome after multimodality therapy for acromegaly, a retrospective review was performed on 162 patients who underwent transsphenoidal surgery at Massachusetts General Hospital between 1978 and 1996. The surgical cure rate for microadenomas was 91%, that for macroadenomas was 48%, and it was 57% overall. The surgical cure rate was significantly dependent on tumor size, but was not dependent on age or sex. An improvement in the surgical cure rate was noted over the course of the review, from 45% before 1987 to 73% since 1991. Long term follow-up was obtained in 99% of U.S. residents (149 of 151), with a mean follow-up period of 7.8 yr. Adjuvant radiation and/or pharmacological therapy was given to 61 patients. Of the entire group, 83% (124 of 149) were in biochemical remission as determined by normalization of serum insulin-like growth factor I levels or by GH suppression after oral glucose tolerance testing at last contact or at death. The recurrence rate was 6% at 10 yr and 10% at 15 yr after surgery in those patients who initially met the criteria for surgical cure. The 10-yr survival rate was 88%, and there were 12 deaths at postoperative intervals of 2-12 yr, with the most common cause of death being cardiovascular disease. A Cox proportional hazards model showed that patient-years with persistent disease carried a 3.5-fold [95% confidence interval (CI), 1.0-12; P = 0.02] relative mortality risk compared to those patient-years in remission. A Poisson person-years regression analysis showed no significant difference in survival between those 86 patients cured at operation and an age- and sex-matched sample from the U.S. population [standardized mortality ratio (SMR), 0.84; 95% CI, 0.3-2.2; P = 0.35]. A similar analysis on the entire group of 149 patients showed no significant difference in survival from that in a control sample (SMR, 1.16; 95% CI, 0.66-2.0; P = 0.3). Mortality risk for patient-years with persistent active disease after unsuccessful treatment vs. that in the U.S. population sample remained increased (SMR, 1.8; 95% CI, 0.9-3.6; P = .05). This analysis suggests that the decreased survival previously reported to be associated with acromegaly can be normalized by successful surgical and adjunctive therapy.
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Acromegalia/mortalidad , Acromegalia/cirugía , Acromegalia/terapia , Adulto , Anciano , Enfermedad Crónica , Terapia Combinada , Personas con Discapacidad , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Morbilidad , Complicaciones Posoperatorias/epidemiología , Recurrencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine the selection factors for and results of second resections performed to treat recurrent glioblastoma multiforme (GM), we studied 301 patients with GM who were treated from the time of diagnosis using two prospective clinical protocols. METHODS: The patients were prospectively followed from the time of diagnosis, using clinical and radiographic criteria after maximal surgical resection and external beam radiotherapy with or without adjuvant chemotherapy. Resection of recurrent GM was performed at the recommendation of the treating clinicians. The results of the second resections were retrospectively reviewed and analyzed using multivariate logistic regression, Kaplan-Meier-Turnbull survival analysis, Cox regression, and propensity score stratification. RESULTS: Forty-six patients underwent second resections during the study period. The actuarial rate of the second resections was 15% of the patients 1 year after diagnosis and 31% 2 years after diagnosis. Younger age (P = 0.01) and more extensive initial resection (P = 0.02), but not Karnofsky Performance Scale (KPS) score at the time of diagnosis or recurrence, predicted a higher chance of selection for reoperation after initial tumor recurrence. Twenty-eight percent of the patients had improved KPS scores after undergoing reoperation, 49% were stable, and 23% had declines in KPS scores of 10 to 30 points. There was no operative mortality. After reoperation, 85% of the patients received chemotherapy, 11% received brachytherapy or underwent stereotactic radiosurgery, and 17% underwent third resections. The median survival period after reoperation was 36 weeks. Higher preoperative KPS scores predicted longer survival periods after reoperation (P = 0.03). Age and interval since diagnosis were not significant prognostic factors. The median high-quality survival period (KPS score, > or =70) was 18 weeks. The median survival period after first tumor progression was 23 weeks for 130 patients treated using the same protocols who did not undergo reoperations. Patients who did undergo reoperations experienced clinically and statistically significantly longer survival periods. However, this was determined to be partially because of selection bias. CONCLUSION: Survival after resection of recurrent GM remains poor despite advances in imaging, operative technique, and adjuvant therapies. High-quality survival after resection of recurrence to treat GM seems to have increased significantly since an earlier report from our institution.
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Neoplasias Encefálicas/fisiopatología , Neoplasias Encefálicas/cirugía , Glioblastoma/fisiopatología , Glioblastoma/cirugía , Adolescente , Adulto , Anciano , Neoplasias Encefálicas/radioterapia , Estudios de Cohortes , Terapia Combinada , Femenino , Glioblastoma/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Periodo Posoperatorio , Pronóstico , Estudios Prospectivos , Reoperación , Estadística como Asunto , Análisis de SupervivenciaRESUMEN
Chemotherapeutic regimens in present use for recurrent glioma have substantial toxicity. Activity against recurrent gliomas has been reported for both tamoxifen and interferon alpha, agents that have more acceptable toxicity profiles and that can be administered in an outpatient setting. We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial. Eligible patients had radiographically measurable recurrent gliomas of any grade after initial radiation therapy. Interferon-alpha [6 x 10(6) U subcutaneously three times per week] and tamoxifen (240 mg/m2/day orally) were administered continuously. Treatment response was assessed at 6 week intervals using clinical and radiographic criteria. Eighteen patients (11 males and 7 females) were enrolled. Median age was 41 years (range 23-61 years). All patients had gliomas that progressed after radiation therapy and nitrosourea chemotherapy. The histologic diagnosis of the original tumor was glioblastoma multiforme in 8 patients, anaplastic astrocytoma in 5 patients, astrocytoma in 4 patients and mixed malignant glioma in 1 patient. Reversible moderate to severe neurological toxicity manifested by dizziness and unsteady gait was seen at tamoxifen doses of 240 mg/m2/day. Although the initial tamoxifen dose was reduced to 120 mg/m2/day, moderate neurotoxicity was noted at this dose as well and the trial was closed early. The combination of oral tamoxifen (120 to 240 mg/m2/day) and subcutaneous interferon-alpha [6 x 10(6) U three times per week] was associated with significant neurotoxicity in this group of recurrent glioma patients, resulting in early study closure. Of 16 evaluable patients, 12 had progressive disease after one cycle of treatment, 3 had stable disease, and there was one minor response. Gradual dose escalation may be required if similar patients are to be treated with high dose tamoxifen in conjunction with interferon.
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Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos/administración & dosificación , Neoplasias Encefálicas/terapia , Glioma/terapia , Interferón-alfa/administración & dosificación , Tamoxifeno/administración & dosificación , Administración Oral , Adulto , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/uso terapéutico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inyecciones Subcutáneas , Interferón alfa-2 , Interferón-alfa/efectos adversos , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Proteínas Recombinantes , Análisis de Supervivencia , Tamoxifeno/efectos adversos , Tamoxifeno/uso terapéutico , Resultado del TratamientoRESUMEN
Human non-gravid myometrium differentiates in response to ovarian sex steroids into a subendometrial layer or junctional zone and an outer myometrial layer. Compared to the outer myometrial layer, the junctional zone myocytes are characterized by higher cellular density and lower cytoplasmic-nuclear ratio. These structural differences allow in-vivo visualization of the myometrial zonal anatomy by T2-weighted magnetic resonance (MR) imaging. The human myometrium is also functionally polarized. Video-vaginosonography studies have shown that propagated myometrial contractions in the non-pregnant uterus originate only from the junctional zone and that the frequency and orientation of these contraction waves are dependent on the phase of the menstrual cycle. The mechanisms underlying zonal myometrial differentiation are not known, but growing evidence suggests that ovarian hormone action may be mediated through cytokines and uterotonins locally released by the basal endometrial layer and endometrio-myometrial T-lymphocytes. Irregular thickening of the junctional zone due to inordinate proliferation of the inner myometrium, junctional zone hyperplasia, is a common MR finding in women suffering from menstrual dysfunction. Preliminary data suggest that junctional zone hyperplasia is further characterized by loss of normal inner myometrial function. Although irregular thickening of the junctional zone has been associated with diffuse uterine adenomyosis, the precise relationship between subendometrial smooth muscle proliferation and myometrial invasion by endometrial glands and stroma remains to be established.
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Miometrio/citología , Miometrio/fisiología , Útero/citología , Útero/fisiología , Diferenciación Celular , Polaridad Celular , Femenino , Hormonas Esteroides Gonadales/fisiología , Humanos , Hiperplasia , Imagen por Resonancia Magnética , Útero/patologíaRESUMEN
BACKGROUND: It is often assumed that a cerebral lesion that is nonenhancing on a magnetic resonance imaging study with gadolinium contrast is a low grade tumor. Some physicians recommend observation rather than biopsy for such lesions. METHODS: The authors prospectively evaluated the incidence of anaplastic tumor histology in a consecutive series of patients who presented to a neuro-oncology service with a nonenhancing mass of the cerebral hemisphere. RESULTS: During a 5-month period, the authors evaluated 31 patients who had a nonenhancing lesion in the cerebral hemisphere on initial magnetic resonance images. Thirty patients underwent stereotactic biopsy (27%) or open resection (73%). The median patient age was 36 years (range, 6-63 years). There was no mortality or permanent neurologic morbidity from surgery. Twenty-eight patients had pathologic confirmation of diagnosis while their lesions were still nonenhancing. Of these patients, 9 (32%) had Grade 3 lesions (anaplastic astrocytoma or oligoastrocytoma), 13 (43%) had Grade 2 lesions (astrocytoma, oligodendroglioma, or oligoastrocytoma), and 2 (7%) had Grade 1 lesions (dysembryoplastic neuroepithelial tumors). Two additional patients (ages 33 and 59 years) who developed enhancement within their lesions during preoperative periods of observation had glioblastomas at surgery. Logistic regression was used to relate patient age to the risk of anaplasia in a nonenhancing cerebral mass lesion. Older age predicted a significantly higher risk of anaplasia (P = 0.025). The model predicted that nonenhancing cerebral masses in patients older than 44 years were more likely to be anaplastic tumors than low grade tumors. There was no "safe" age below which low grade histology could be confidently assumed. CONCLUSIONS: Magnetic resonance-nonenhancing cerebral lesions may be histologically anaplastic, even in young patients. The risk of anaplasia in magnetic resonance-nonenhancing lesions increases significantly with patient age.