RESUMEN
PURPOSE: Brain radiation is associated with functional deficits in children. The purpose of this study was to examine white matter integrity as measured by diffusion tensor imaging and associations with region-specific radiation dose and neuropsychological functioning in children treated with cranial irradiation. METHODS AND MATERIALS: A total of 20 patients and 55 age- and sex-matched controls were included in the present study. Diffusion tensor imaging and neuropsychological assessments were conducted at baseline and 6, 15, and 27 months after treatment. The neuropsychological assessment included motor dexterity, working memory, and processing speed. White matter regions were contoured, and the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were recorded for each participant. Linear mixed effects regression models were used to prospectively compare the associations among ADC, FA, radiation dose to contoured structures, and performance on the neuropsychological assessments over time. RESULTS: The mean prescription dose was 44 Gy (range 12-54). Across visits, compared with the controls, the patients showed a significantly increased ADC across all selected regions and alterations in FA in the dorsal midbrain and corpus callosum (genu, splenium, body). An increased radiation dose to the genu and body of the corpus callosum was associated with alterations in ADC and FA and reduced neuropsychological performance, most notably motor speed and processing. CONCLUSIONS: These prospective data suggest that subcortical white matter, especially the genu and body of the corpus callosum, could be regions with increased susceptibility to radiation-induced injury, with implications for cognitive function.
Asunto(s)
Encéfalo/efectos de la radiación , Cognición/efectos de la radiación , Cuerpo Calloso/efectos de la radiación , Neuronas/efectos de la radiación , Adolescente , Anisotropía , Conducta , Encéfalo/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Estudios de Casos y Controles , Niño , Preescolar , Cuerpo Calloso/patología , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Neuronas/patología , Pruebas Neuropsicológicas , Estudios Prospectivos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/efectos de la radiaciónRESUMEN
AbstractThe published version of this article unfortunately contained an error. Author "E. Mark Mahone" has been published incorrectly by capturing "Mark Mahone" as family name when it should only be "Mahone". Given in this article is the corrected name.
RESUMEN
PURPOSE/OBJECTIVE(S): Cranial radiation therapy (CRT) may disrupt the corpus callosum (CC), which plays an important role in basic motor and cognitive functions. The aim of this prospective longitudinal study was to assess changes in CC mid-sagittal areas, CC volumes, and performance on neuropsychological (NP) tests related to the CC in children following CRT. MATERIALS/METHODS: Twelve pediatric patients were treated with CRT for primary brain malignancies. Thirteen age-matched healthy volunteers served as controls. Brain MRIs and NP assessment emphasizing motor dexterity, processing speed, visuomotor integration, and working memory (visual and verbal) were performed at baseline and at 6, 15, and 27 months following completion of CRT. Linear mixed effects (LME) analyses were used to evaluate patient NP performance and changes in regional CC volumes (genu, anterior body, mid-body, posterior body, and splenium) and mid-sagittal areas over time and with radiation doses, correcting for age at CRT start. RESULTS: The mean age at CRT was 9.41 (range 1.2-15.7) years. The median prescription dose was 54 (range 18-59.4) Gy. LME analysis revealed a significant decrease in overall CC volumes over time (p < 0.00001), with no overall effect of radiation dose. Analysis of individual CC regions demonstrated a significant decrease in all regional volumes over time (p < 0.00001) in patients, with no effect of radiation dose. Only in the splenium was there a trend toward a dose-dependent effect (p = 0.093). Patients had significantly reduced NP performance across visits-most notably in motor dexterity and visual working memory (both p < 0.0001). CONCLUSIONS: These prospective data demonstrate a significant decrease in CC regional volumes after CRT, with associated decline in neurocognitive function, most notably in manual dexterity, attention, and working memory. Further prospective study of larger cohorts of patients is needed to establish the relationship between CRT dose, neuroanatomical, and functional changes in the CC.
Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Disfunción Cognitiva/diagnóstico por imagen , Cuerpo Calloso/diagnóstico por imagen , Irradiación Craneana/efectos adversos , Pruebas Neuropsicológicas , Adolescente , Neoplasias Encefálicas/psicología , Niño , Preescolar , Cognición/fisiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/psicología , Irradiación Craneana/tendencias , Femenino , Humanos , Lactante , Masculino , Tamaño de los Órganos , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Cranial radiation therapy (RT) is an important component in the treatment of pediatric brain tumors. However, it can result in long-term effects on the developing brain. This prospective study assessed the effects of cranial RT on cerebral, frontal lobe, and temporal lobe volumes and their correlation with higher cognitive functioning. METHODS: Ten pediatric patients with primary brain tumors treated with cranial RT and 14 age- and sex-matched healthy children serving as controls were evaluated. Quantitative magnetic resonance imaging and neuropsychological assessments (language, memory, auditory and visual processing, and vocabulary) were performed at the baseline and 6, 15, and 27 months after RT. The effects of age, the time since RT, and the cerebral RT dose on brain volumes and neuropsychological performance were analyzed with linear mixed effects model analyses. RESULTS: Cerebral volume increased significantly with age in both groups (P = .01); this increase in volume was more pronounced in younger children. Vocabulary performance was found to be significantly associated with a greater cerebral volume (P = .05) and a lower RT dose (P = .003). No relation was observed between the RT dose and the cerebral volume. There was no difference in the corresponding neuropsychological tests between the 2 groups. CONCLUSIONS: This prospective study found significant relations among the RT dose, cerebral volumes, and rate of vocabulary development among children receiving RT. The results of this study provide further support for clinical trials aimed at reducing cranial RT doses in the pediatric population. Cancer 2017;161-168. © 2016 American Cancer Society.
Asunto(s)
Neoplasias Encefálicas/fisiopatología , Neoplasias Encefálicas/radioterapia , Irradiación Craneana/efectos adversos , Lóbulo Frontal/fisiopatología , Lóbulo Frontal/efectos de la radiación , Lóbulo Temporal/fisiopatología , Lóbulo Temporal/efectos de la radiación , Adolescente , Niño , Preescolar , Cognición/efectos de la radiación , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética/métodos , Masculino , Memoria/efectos de la radiación , Pruebas Neuropsicológicas , Estudios ProspectivosRESUMEN
INTRODUCTION: The treatment of pediatric intracranial low-grade gliomas (LGG) generally begins with maximal safe resection. Radiation therapy (RT) and chemotherapy are typically reserved for patients with incomplete resection and/or disease progression. We report long-term treatment outcomes and toxicities in a cohort of pediatric patients with LGG after RT. METHODS: Thirty-four patients <21 years old with intracranial LGG who were treated with RT at the Johns Hopkins Hospital were included in this retrospective analysis. Patients were evaluated for overall survival (OS), progression-free survival (PFS), recurrence patterns, and treatment toxicities using descriptive statistics, Kaplan-Meier curves, and Cox proportional hazard regressions. RESULTS: The mean age at diagnosis was 7.9 years (range 1.2-18.3 years) and mean age at RT was 9.8 years (range 3.0-28.9 years). The median follow-up time was 9.8 years after radiation (range 0.8-33.3 years). The estimated 10-year OS and PFS after RT were 92 and 74 %, respectively. Twelve patients had disease progression after RT, and all recurrences were local. Two patients died due to disease progression 2.3 and 9.1 years after RT. One patient had malignant transformation of LGG to high-grade glioma. No significant predictors of PFS were identified on uni- or multivariate analysis. Late effects of LGG and treatment seen were endocrine deficiencies in 16 patients, visual problems in 10 patients, hearing loss in 4 patients, special education requirements for 5 patients, and a vascular injury/demyelination secondary to RT in 1 patient. CONCLUSION: Our study suggests that the use of radiation in patients with intracranial LGG results in excellent OS and PFS with acceptable toxicity at long-term follow-up.
Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/radioterapia , Manejo de la Enfermedad , Glioma/diagnóstico , Glioma/radioterapia , Adolescente , Adulto , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Estudios Longitudinales , Masculino , Modelos de Riesgos Proporcionales , Adulto JovenRESUMEN
The majority of intermediate-risk rhabdomyosarcoma (RMS) patients have gross residual disease (Group III) after their first operative procedure. It is currently not known if local control rates can be maintained when, following induction chemotherapy, the radiation therapy (RT) dose is decreased after a delayed primary excision (DPE). To answer this question we evaluated patients enrolled on COG D9803 (1999-2005) who had Group III tumors of the bladder dome, extremity or trunk (thorax, abdomen and pelvis) were candidates for DPE at Week 12 if the primary tumor appeared resectable. RT dose was then adjusted by the completeness of DPE: no evidence of disease 36 Gy, microscopic residual 41.4 Gy and gross residual disease (GRD) 50.4 Gy. A total of 161 Group III patients were evaluated (24 bladder dome, 63 extremity and 74 trunk). Seventy-three patients (45%) underwent DPE which achieved removal of all gross disease in 61 (84%) who were then eligible for reduced RT dose (43/73 received 36 Gy, 19/73 received 41.4 Gy). The local 5-year failure rate (0% for bladder dome, 7% for extremity and 20% for trunk) was similar to IRS-IV, which did not encourage DPE and did not allow for DPE adapted RT dose reduction. In conclusion, DPE was performed in 45% of Group III RMS patients with tumors at select anatomic sites (bladder dome, extremity and trunk) and 84% of those who had DPE were eligible for RT dose reduction. Local control outcomes were similar to historic results with RT alone.
Asunto(s)
Abdomen/efectos de la radiación , Pelvis/efectos de la radiación , Rabdomiosarcoma/radioterapia , Rabdomiosarcoma/cirugía , Tórax/efectos de la radiación , Vejiga Urinaria/efectos de la radiación , Abdomen/patología , Niño , Preescolar , Ensayos Clínicos como Asunto , Terapia Combinada , Humanos , Lactante , Recién Nacido , Neoplasia Residual , Pelvis/patología , Dosificación Radioterapéutica , Rabdomiosarcoma/patología , Tórax/patología , Insuficiencia del Tratamiento , Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Involved field radiation therapy (IFRT) is integral in curative therapy for Hodgkin lymphoma (HL), although primarily used in patients with intermediate/high-risk HL. We present failure patterns and clinical outcomes in a cohort of pediatric and young adult patients with HL treated with IFRT at the Johns Hopkins Hospital. PROCEDURE: Patients ≤40 years old with intermediate/high-risk HL who received chemotherapy and IFRT from 1997 to 2012 were included in this retrospective analysis. Patients were evaluated for failure patterns, overall survival (OS), and event-free survival (EFS) using Kaplan-Meier curves, descriptive statistics, and Cox proportional hazard regressions. RESULTS: We reviewed 74 patients (45 pediatric and 29 young adult) with a median follow-up of 4.4 years. The mean age at diagnosis was 21.4 years. Patients received a median of 29.75 Gy of IFRT (range 15-39.6 Gy). The majority of pediatric patients received ABVE-PC chemotherapy (n = 25) and <30 Gy of radiation (n = 33) while most young adults received ABVD chemotherapy (n = 24) and ≥30 Gy (n = 25). Estimated 5-year OS and EFS were 96% and 81%, respectively. Thirteen patients had recurrence; eight were pediatric. Distant relapse alone comprised 83% of failures in patients receiving ≥30 Gy. Of the seven patients who received <30 Gy and had recurrence, six had local failure as a component of their recurrence. Caucasian race (P = 0.02) and nodular sclerosing histology (P = 0.01) predicted for increased EFS. Late effects were minimal and all deaths (n = 4) were from HL. CONCLUSIONS: In this series, pediatric and young adult patients were treated with differing chemoradiation and had distinct recurrence patterns.
Asunto(s)
Quimioradioterapia , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/terapia , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Enfermedad de Hodgkin/diagnóstico , Humanos , Masculino , Recurrencia , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
PURPOSE: Previous DTI studies reported microstructural changes in white matter of patients receiving treatment for brain malignancies. The primary aim of this prospective pilot longitudinal study was to examine if DTI can detect microstructural changes in deep gray matter (as evaluated by the apparent diffusion coefficient, ADC) between pediatric patients treated with cranial radiation therapy and typically developing healthy children. The relationship between ADC and neurobehavioral performance was also examined. METHODS: ADC was measured at 1.5 T in the caudate, putamen, globus pallidus, thalamus, and hippocampus in nine patients (mean age 11.8 years) and nine age-matched healthy controls. The study was designed with four visits: baseline, 6-month, 15-month, and 27-month follow-ups. RESULTS: Patients had 24 % higher overall mean ADC in the hippocampus compared with controls (p = 0.003). Post hoc analyses revealed significantly elevated ADC at baseline (p = 0.003) and at the 27-month follow-up (p = 0.006). Nevertheless, patients performed normally on a verbal memory test considered to be a hippocampus-related function. Relative to controls, patients' performance on the tests of the visual-spatial working memory decreased over time (group by visit, p = 0.036). Both patients and controls showed a decline in motor speed with increasing ADC in the globus pallidus and putamen. CONCLUSIONS: Childhood brain malignancies and their treatment may affect gray matter microstructure as measured by water diffusion. Significant findings in the hippocampus but not other regions suggest that differences in tissue sensitivity to disease- and treatment-related injury among gray matter regions may exist. ADC in basal ganglia may be associated with motor performance.
Asunto(s)
Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Hipocampo/patología , Hipocampo/efectos de la radiación , Adolescente , Niño , Preescolar , Irradiación Craneana/efectos adversos , Imagen de Difusión Tensora , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Estudios Longitudinales , Masculino , Proyectos PilotoRESUMEN
PURPOSE: Pediatric intramedullary spinal cord tumors are exceedingly rare; in the United States, 100 to 200 cases are recognized annually, of these, most are astrocytomas. The purpose of this study is to report the outcomes in pediatric patients with spinal cord astrocytomas treated at a tertiary care center. METHODS AND MATERIALS: An institutional review board-approved retrospective single-institution study was performed for pediatric patients with spinal cord astrocytomas treated at our hospital from 1990 to 2010. The patients were evaluated on the extent of resection, progression-free survival (PFS), and development of radiation-related toxicities. Kaplan-Meier curves and multivariate regression model methods were used for analysis. RESULTS: Twenty-nine patients were included in the study, 24 with grade 1 or 2 (low-grade) tumors and 5 with grade 3 or 4 (high-grade) tumors. The median follow-up time was 55 months (range, 1-215 months) for patients with low-grade tumors and 17 months (range, 10-52 months) for those with high-grade tumors. Thirteen patients in the cohort received chemotherapy. All patients underwent at least 1 surgical resection. Twelve patients received radiation therapy to a median radiation dose of 47.5 Gy (range, 28.6-54.0 Gy). Fifteen patients with low-grade tumors and 1 patient with a high-grade tumor exhibited stable disease at the last follow-up visit. Acute toxicities of radiation therapy were low grade, whereas long-term sequelae were infrequent and manageable when they arose. All patients with low-grade tumors were alive at the last follow-up visit, compared with 1 patient with a high-grade tumor. CONCLUSION: Primary pediatric spinal cord astrocytomas vary widely in presentation and clinical course. Histopathologic grade remains a major prognostic factor. Patients with low-grade tumors tend to have excellent disease control and long-term survival compared to those with high-grade tumors. This experience suggests that radiation therapy may enhance tumor control with an acceptably low risk of long-term sequelae in this sensitive patient population.
Asunto(s)
Astrocitoma/radioterapia , Neoplasias de la Médula Espinal/radioterapia , Adolescente , Astrocitoma/mortalidad , Astrocitoma/patología , Astrocitoma/cirugía , Baltimore , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Traumatismos por Radiación/complicaciones , Traumatismos por Radiación/patología , Dosificación Radioterapéutica , Análisis de Regresión , Estudios Retrospectivos , Neoplasias de la Médula Espinal/mortalidad , Neoplasias de la Médula Espinal/patología , Neoplasias de la Médula Espinal/cirugía , Centros de Atención Terciaria , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Neurocognitive toxicity from radiation therapy (RT) for brain tumors may be related to damage to neural progenitor cells that reside in the subventricular zone and hippocampus. This prospective study examines the relationship between RT dose to neural progenitor cell niches, temporal lobes, and cerebrum and neurocognitive dysfunction following cranial irradiation. METHODS: Standardized assessments of motor speed/dexterity, verbal memory, visual perception, vocabulary, and visuospatial working memory were conducted in 19 pediatric patients receiving cranial RT and 55 controls at baseline and 6, 15, and 27 months following completion of RT. Prescription doses ranged from 12 Gy to 59.4 Gy. Linear mixed effects regression model analyses were used to examine the relationships among neuropsychological performance, age, and radiation dose to the subventricular zone, hippocampus, temporal lobes, and cerebrum. RESULTS: Performance on all neuropsychological tests, except vocabulary, was significantly reduced in patients relative to controls, particularly among younger children. Performance on motor speed/dexterity decreased with increasing dose to hippocampus (P < .05) and temporal lobes (P < .035). There was also a significant relationship between (i) reduced performance on verbal learning and increasing dose to the cerebrum (P = .022) and (ii) reduced performance on visual perception and increasing dose to the left temporal lobe (P = .038). There was no association between radiation dose to evaluated structures and performance on vocabulary or visuospatial working memory. CONCLUSIONS: These prospective data demonstrate a significant association between increasing RT dose to hippocampus and temporal lobes and decline in neurocognitive skills following cranial irradiation. These findings have important implications for trials, including RTOG 0933 (hippocampal-sparing whole brain radiation therapy for brain metastases).
Asunto(s)
Neoplasias Encefálicas/complicaciones , Irradiación Craneana/efectos adversos , Neuronas/efectos de la radiación , Nicho de Células Madre/efectos de la radiación , Células Madre/efectos de la radiación , Lóbulo Temporal/efectos de la radiación , Adolescente , Neoplasias Encefálicas/psicología , Neoplasias Encefálicas/radioterapia , Niño , Preescolar , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Memoria/efectos de la radiación , Trastornos de la Memoria/etiología , Trastornos de la Memoria/psicología , Neuronas/patología , Pruebas Neuropsicológicas , Pronóstico , Estudios Prospectivos , Dosificación Radioterapéutica , Células Madre/patología , Lóbulo Temporal/patologíaRESUMEN
INTRODUCTION: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE. METHODS: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves and descriptive statistics were used for analysis. RESULTS: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT. CONCLUSIONS: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.
Asunto(s)
Ependimoma/radioterapia , Enfermedades Raras/radioterapia , Neoplasias de la Columna Vertebral/radioterapia , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Ependimoma/mortalidad , Ependimoma/cirugía , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia , Dosificación Radioterapéutica , Radioterapia Adyuvante/métodos , Enfermedades Raras/mortalidad , Enfermedades Raras/cirugía , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/mortalidad , Neoplasias de la Columna Vertebral/cirugía , Adulto JovenRESUMEN
PURPOSE: Postoperative radiation therapy (RT) is recommended for patients with rhabdomyosarcoma having microscopic disease. Sometimes RT dose/volume is reduced or omitted in an attempt to avoid late effects, particularly in young children. We reviewed operative bed recurrences to determine if noncompliance with RT protocol guidelines influenced local-regional control. METHODS AND MATERIALS: All operative bed recurrences among 695 Group II rhabdomyosarcoma patients in Intergroup Rhabdomyosarcoma Study Group (IRS) I through IV were reviewed for deviation from RT protocol. Major/minor dose deviation was defined as >10% or 6-10% of the prescribed dose (40-60 Gy), respectively. Major/minor volume deviation was defined as tumor excluded from the RT field or treatment volume not covered by the specified margin (preoperative tumor volume and 2- to 5-cm margin), respectively. No RT was a major deviation. RESULTS: Forty-six of 83 (55%) patients with operative bed recurrences did not receive the intended RT (39 major and 7 minor deviations). RT omission was the most frequent RT protocol deviation (19/46, 41%), followed by dose (17/46, 37%), volume (9/46, 20%), and dose and volume deviation (1/46, 2%). Only 7 operative bed recurrences occurred in IRS IV (5% local-regional failure) with only 3 RT protocol deviations. Sixty-three (76%) patients with recurrence died of disease despite retrieval therapy, including 13 of 19 nonirradiated children. CONCLUSION: Over half of the operative bed recurrences were associated with noncompliance; omission of RT was the most common protocol deviation. Three fourths of children die when local-regional disease is not controlled, emphasizing the importance of RT in Group II rhabdomyosarcoma.
Asunto(s)
Adhesión a Directriz , Recurrencia Local de Neoplasia/radioterapia , Rabdomiosarcoma Alveolar/radioterapia , Rabdomiosarcoma Embrionario/radioterapia , Adolescente , Factores de Edad , Niño , Preescolar , Protocolos Clínicos , Humanos , Lactante , Recurrencia Local de Neoplasia/mortalidad , Neoplasia Residual , Dosificación Radioterapéutica , Rabdomiosarcoma Alveolar/mortalidad , Rabdomiosarcoma Alveolar/patología , Rabdomiosarcoma Alveolar/cirugía , Rabdomiosarcoma Embrionario/mortalidad , Rabdomiosarcoma Embrionario/patología , Rabdomiosarcoma Embrionario/cirugía , Carga TumoralRESUMEN
PURPOSES: The aims of the study were to compare results of clinical/radiographic studies before second-look procedures (SLP) with SLP specimens from patients with gross residual sarcoma at diagnosis and to relate tumor viability to outcome. PATIENTS: Seventy-three patients underwent SLP before completing chemotherapy, with (n = 59) or without (n = 14) radiotherapy. Tumor sites were bladder/prostate (n = 27), head/orbit/parameningeal (n = 22), extremity/trunk (n = 14), and retroperitoneum/pelvis (n = 10). RESULTS: Of 14 patients, 1 (7%) with clinical/radiographic complete response (CR) had viable tumor. Of 59 patients, 35 (59%) without CR had viable tumor. Five-year failure-free survival (FFS) rates were 81% in 37 patients without viable tumor and 53% in 36 patients with viable tumor (Cox proportional hazards adjusted P = .05). Five-year FFS rates were 67% in 15 patients with clear margins and 43% in 21 patients with tumor-involved margins (n = 18) or viable gross tumor (n = 3) (Cox proportional hazards adjusted P = .04). Five-year survival was 78% to 79% among 73 patients with and 333 patients without SLP during treatment. CONCLUSIONS: Second-look procedures can show whether viable tumor is present and may be beneficial in selected patients with rhabdomyosarcoma. Disappearance of tumor (CR) usually correlated with no viable tumor at SLP. However, 41% of patients without CR had no viable tumor. Those without viable tumor had increased FFS but not survival compared to those with viable tumor.
Asunto(s)
Antineoplásicos/uso terapéutico , Diagnóstico por Imagen/métodos , Fraccionamiento de la Dosis de Radiación , Rabdomiosarcoma/diagnóstico , Segunda Cirugía/métodos , Niño , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estadificación de Neoplasias , Neoplasia Residual , Estudios Retrospectivos , Rabdomiosarcoma/epidemiología , Rabdomiosarcoma/terapia , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Real-time stereovision-guidance has been introduced for efficient and convenient fractionated stereotactic radiotherapy (FSR) and image-guided intensity-modulated radiation therapy (IMRT). This first pilot study is to clinically evaluate its accuracy and precision as well as impact on treatment doses. Sixty-one FSR patients wearing stereotactic masks (SMs) and nine IMRT patients wearing flexible masks (FMs), were accrued. Daily target reposition was initially based-on biplane-radiographs and then adjusted in six degrees of freedom under real-time stereovision guidance. Mean and standard deviation of the head displacements measured the accuracy and precision. Head positions during beam-on times were measured with real-time stereovisions and used for determination of delivered doses. Accuracy ± ± precision in direction with the largest errors shows improvement from 0.4 ± 2.3 mm to 0.0 ± 1.0 mm in the inferior-to-superior direction for patients wearing SM or from 0.8 ± 4.3 mm to 0.4 ± 1.7 mm in the posterior-to-anterior direction for patients wearing FM. The image-guidance increases target volume coverage by >30% for small lesions. Over half of head position errors could be removed from the stereovision-guidance. Importantly, the technique allows us to check head position during beam-on time and makes it possible for having frameless head refixation without tight masks.
Asunto(s)
Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Neuroma Acústico/radioterapia , Neuroma Acústico/cirugía , Radiocirugia/métodos , Radioterapia de Intensidad Modulada/métodos , Cirugía Asistida por Computador/métodos , Adulto , Anciano , Anciano de 80 o más Años , Sistemas de Computación , Femenino , Cabeza/diagnóstico por imagen , Humanos , Masculino , Meningioma/radioterapia , Meningioma/cirugía , Persona de Mediana Edad , Posicionamiento del Paciente/métodos , Proyectos Piloto , Radiografía , Planificación de la Radioterapia Asistida por Computador/métodos , Adulto JovenRESUMEN
BACKGROUND: Samarium-153 ethylenediamine tetramethylene phosphoric acid (153Sm-EDTMP) is a radiopharmaceutical that has been used to treat osteosarcoma. The authors conducted a phase 2 study to test safety and response of high-risk osteosarcoma to tandem doses of 153Sm-EDTMP and to determine correlation between radiation delivered by low and high administered activities. METHODS: Patients with recurrent, refractory osteosarcoma detectable on standard 99mTc bone scan received a low dose of 153Sm-EDTMP (37.0-51.8 MBq/kg), followed upon count recovery by a second, higher dose (222 MBq/kg). Fourteen days later, patients were rescued with autologous hematopoietic stem cells. The authors assessed response to therapy, performed dosimetry to determine the relationship between administered activity and tumor absorbed dose, and investigated whether changes in 2-(fluorine-18) fluoro-2-deoxy-d-glucose (18F-FDG) tumor uptake upon hematologic recovery reflected disease response. RESULTS: Nine patients were given tandem doses of 153Sm-EDTMP; 2 received only the initial dose because of disease progression. Six patients experienced radiographic disease stabilization, but this was not considered a response, so the study was terminated early. There was a linear relationship between administered activity and tumor absorbed dose, but there was no correlation between change in 18F-FDG positron emission tomography tumor uptake and tumor absorbed dose or time to progression. The median time to progression for the entire group was 79 days. CONCLUSIONS: Tandem doses of 153Sm-EDTMP were safe for this cohort of heavily pretreated patients with very high-risk disease. The strong correlation between absorbed dose and administered activity within each evaluable patient provides a methodology to individually tailor tandem doses of this agent.
Asunto(s)
Neoplasias Óseas/radioterapia , Neoplasias Óseas/cirugía , Trasplante de Células Madre Hematopoyéticas/métodos , Compuestos Organometálicos/uso terapéutico , Compuestos Organofosforados/uso terapéutico , Osteosarcoma/radioterapia , Osteosarcoma/cirugía , Radiofármacos/uso terapéutico , Adolescente , Adulto , Femenino , Humanos , Masculino , Compuestos Organometálicos/efectos adversos , Compuestos Organofosforados/efectos adversos , Radiometría , Radiofármacos/efectos adversos , Trasplante AutólogoRESUMEN
Intracranial tumors are the most common neoplasms of childhood, accounting for approximately 20% of all pediatric malignancies. Radiation therapy has led directly to significant increases in survival of children with certain types of intracranial tumors; however, given the aggressive nature of this therapy, children are at risk for exhibiting changes in brain structure, neuronal biochemistry, and neurocognitive functioning. In this case report, we present neuropsychological, magnetic resonance imaging, proton magnetic resonance spectroscopic imaging, and diffusion tensor imaging data for two adolescents (one patient with ependymal spinal cord tumor with intracranial metastases, and one healthy, typically developing control) from three time points as defined by the patient's radiation schedule (baseline before the patient's radiation therapy, 6 months following completion of the patient's radiation, and 27 months following the patient's radiation). In the patient, there were progressive decreases in gray and white matter volumes as well as early decreases in mean N-acetyl aspartate/choline (NAA/Cho) ratios and fractional anisotropy (FA) in regions with normal appearance on conventional MRI. At the last follow-up, NAA/Cho and FA tended to change in the direction to normal values in selected regions. At the same time, the patient had initial reduction in language and motor skills, followed by return to baseline, but later onset delay in visuospatial and visual perceptual skills. Results are discussed in terms of sensitivity of the four techniques to early and late effects of treatment, and avenues for future investigations.
Asunto(s)
Mapeo Encefálico , Cognición/fisiología , Ependimoma/cirugía , Radiocirugia/métodos , Neoplasias de la Columna Vertebral/cirugía , Adolescente , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Lenguaje , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos , Masculino , Memoria/fisiología , Pruebas Neuropsicológicas , Pediatría , Terapia de Protones , Desempeño Psicomotor/fisiología , Percepción Visual/fisiologíaRESUMEN
To characterize a population of pediatric high-grade astrocytoma (HGA) patients by confirming the proportion with a correct diagnosis, and determine prognostic factors for survival in a subset diagnosed with uniform pathologic criteria. Sixty-three children diagnosed with HGA were treated at the Johns Hopkins Hospital between 1977 and 2004. A single neuropathologist (P.C.B.) reviewed all available histologic samples (n = 48). Log-rank analysis was used to compare survival by patient, tumor, and treatment factors. Median follow-up was 16 months for all patients and 155 months (minimum 54 months) for surviving patients. Median survival for all patients (n = 63) was 14 months with 10 long-term survivors (survival >48 months). At initial diagnosis, 27 patients were grade III (43%) and 36 grade IV (57%). Forty-eight patients had pathology slides available for review, including seven of ten long-term surviving patients. Four patients had non-HGA pathology, all of whom were long term survivors. The remaining 44 patients with confirmed HGG had a median survival of 14 months and prognostic analysis was confined to these patients. On multivariate analysis, five factors were associated with inferior survival: performance status (Lansky) <80% (13 vs. 15 months), bilaterality (13 vs. 19 months), parietal lobe location (13 vs. 16 months), resection less than gross total (13 vs. 22 months), and radiotherapy dose <50 Gy (9 vs. 16 months). Among patients with more than one of the five adverse factors (n = 27), median survival and proportion of long-term survivors were 12.9 months and 0%, compared with 41.4 months and 18% for patients with 0-1 adverse factors (n = 17). In an historical cohort of children with HGA, the potential for long term survival was confined to the subset with less than two of the following adverse prognostic factors: low performance status, bilaterality, parietal lobe site, less than gross total resection, and radiotherapy dose <50 Gy. Pathologic misdiagnosis should be suspected in patients who are long term survivors of a pediatric high grade astrocytoma.
Asunto(s)
Neoplasias Encefálicas/diagnóstico , Encéfalo/patología , Neoplasias Neuroepiteliales/diagnóstico , Pediatría , Adolescente , Factores de Edad , Neoplasias Encefálicas/mortalidad , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Estimación de Kaplan-Meier , Masculino , Análisis Multivariante , Neoplasias Neuroepiteliales/mortalidad , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: The purpose of this study was to compare the outcome of patients with intermediate-risk rhabdomyosarcoma (RMS) treated with standard VAC (vincristine, dactinomycin, and cyclophosphamide) chemotherapy to that of patients treated with VAC alternating with vincristine, topotecan, and cyclophosphamide (VAC/VTC). PATIENTS AND METHODS: Patients were randomly assigned to 39 weeks of VAC versus VAC/VTC; local therapy began after week 12. Patients with parameningeal RMS with intracranial extension (PME) were treated with VAC and immediate x-ray therapy. The primary study end point was failure-free survival (FFS). The study was designed with 80% power (5% two-sided alpha level) to detect an increase in 5-year FFS from 64% to 75% with VAC/VTC. RESULTS: A total of 617 eligible patients were entered onto the study: 264 were randomly assigned to VAC and 252 to VAC/VTC; 101 PME patients were nonrandomly treated with VAC. Treatment strata were embryonal RMS, stage 2/3, group III (33%); embryonal RMS, group IV, less than age 10 years (7%); alveolar RMS or undifferentiated sarcoma (UDS), stage 1 or group I (17%); alveolar RMS/UDS (27%); and PME (16%). At a median follow-up of 4.3 years, 4-year FFS was 73% with VAC and 68% with VAC/VTC (P = .3). There was no difference in effect of VAC versus VAC/VTC across risk groups. The frequency of second malignancies was similar between the two treatment groups. CONCLUSION: For intermediate-risk RMS, VAC/VTC does not significantly improve FFS compared with VAC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Rabdomiosarcoma/tratamiento farmacológico , Niño , Preescolar , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Dactinomicina/administración & dosificación , Dactinomicina/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Estimación de Kaplan-Meier , Masculino , Estadificación de Neoplasias , Rabdomiosarcoma/mortalidad , Rabdomiosarcoma/patología , Topotecan/administración & dosificación , Topotecan/efectos adversos , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
BACKGROUND: Samarium-153 ethylenediaminetetramethylene phosphonic acid ((153)Sm-EDTMP) has been used to treat patients with high-risk osteosarcoma. The purpose of the current study was to determine the maximally tolerated dose of (153)Sm-EDTMP that permits hematopoietic recovery within 6 weeks. METHODS: Patients with recurrent or refractory osteosarcoma with bone metastases were enrolled in this study. Subjects were treated with increasing doses of (153)Sm-EDTMP, beginning with 1.0 millicuries (mCi)/kg and followed initially with 40% increment dose level escalations, using a continual reassessment method for dose escalation and de-escalation with a target dose-limiting toxicity (DLT) rate of 30%. Complete blood counts were monitored weekly, and the primary DLT was defined as failure to achieve an absolute neutrophil count >750/mm(3) and a platelet count >75,000/mm(3) within 6 weeks of treatment. In addition to assessing toxicity, dosimetry measurements were made to estimate the radiation dose delivered to target lesions. RESULTS: The maximally tolerated dose of (153)Sm-EDTMP was 44.8 megabecquerel (MBq)/kg (1.21 mCi/kg). DLTs were confined to hematologic toxicities, particularly delayed platelet recovery in 2 patients treated at a dose of 51.8 MBq/kg (1.4 mCi/kg). Grade 2 and 3 pulmonary toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) as reported in 2 patients (at administered activities of 44.8 MBq/kg and 51.8 MBq/kg) was attributable to progressive pulmonary disease. No other significant nonhematologic toxicities were observed. CONCLUSIONS: Patients with osteosarcoma who have previously been heavily treated with chemotherapy can be safely administered (153)Sm-EDTMP with rapid hematologic recovery. The data from the current study support the development of a future trial to assess the efficacy of combining targeted radiotherapy with cytotoxic chemotherapy as a treatment option for patients with high-risk osteosarcoma.