✓ Twelve patients with incompletely resected meningiomas were treated with postoperative radiation therapy. Nine of these patients had previously undergone incomplete surgical resection, and three had suffered one or more postoperative recurrences. The median dose of irradiation was 5490 rads in 6 weeks (range 4800 to 6080 rads). All patients were followed with serial neurological examinations and computerized tomography (CT) scans. Median follow-up period was 54½ months (range 20 to 120 months); 10 of the 12 patients were followed for longer than 42 months posttreatment. Nine patients had no clinical evidence of recurrent disease after radiation therapy, and CT scans confirmed lack of progression or a gradual decrease in tumor size. Three patients had tumor recurrences; two of these lesions appeared at 70 and 112 months after irradiation as extracranial extensions beyond the margin of the irradiation field, and one has exhibited recurrence within the field at 48 months. Three patients who were treated after prior recurrences have demonstrated prolonged progression-free intervals in comparison to the intervals between recurrences prior to irradiation. No significant complications attributable to treatment have been found in any of the patients. These results are discussed in relation to previous reports of the incidence of meningioma recurrence after incomplete resection.
Albert M. Petty, Larry E. Kun and Glenn A. Meyer
Intellectual, emotional, and academic function
Larry E. Kun, Raymond K. Mulhern and J. Jeffrey Crisco
✓ Thirty children with primary brain tumors were evaluated for alterations in intellectual, emotional, and academic functions. Nine were studied following surgery (prior to irradiation) and 21 after postoperative irradiation. Twenty-four patients (80%) showed no serious disabilities on routine medical and neurological examinations. Nineteen patients (63%) had normal intelligence quotient (IQ) levels. Qualitative disabilities on routine examinations were observed in six children: two of nine tested postoperatively, one of six tested after posterior fossa irradiation, and three of 15 tested after cranial irradiation. Subnormal IQ levels were also noted in two of nine children tested prior to irradiation and one of six after posterior fossa irradiation. Of the 15 studied after cranial irradiation, eight had subnormal IQ scores. Serial postirradiation testing in 10 patients revealed improvement in two, stability in five, and further deterioration in three. Ten children were placed in learning disability settings due to achievement delays or problems with selective attending. Social-emotional evaluations detected excessive tendencies toward psychotic symptomatology. Potential etiological factors, including primary tumor site, extent of irradiation, age, and increased intracranial pressure, are discussed. Preliminary findings suggest a greater than normal risk for late neuropsychological alterations among children with supratentorial tumors and/or cranial irradiation.
Evgeny E. Kyrnetskiy, Larry E. Kun, Frederick A. Boop, Robert A. Sanford and Raja B. Khan
Object. The aim of this study was to investigate the cause and outcome of intracranial hemorrhage (ICH) in children with cancer.
Methods. The charts of 51 children who underwent treatment for both cancer and ICH between January 1985 and January 2003 were retrospectively reviewed. Assessment tools included the Karnofsky Performance Scale (KPS), Glasgow Coma Scale (GCS), and the Fisher exact and Student t-tests.
Among the 51 cases, 30 involved brain tumors, 19 leukemia, and two lymphoma. The treatment group (Group 1) comprised 36 patients who suffered ICH during cancer treatment; the posttreatment group (Group 2) consisted of the 15 patients who suffered ICH after the completion of cancer treatment. The types of ICH included 22 cortical, four subcortical, 17 subdural, five brainstem, one subarachnoid, one epidural, and one ventricular. Thrombocytopenia was present in nine patients (25%) in Group 1. More patients in Group 2 (87%) than in Group 1 (44%) underwent cranial radiation treatment. Patients in Group 1 experienced a higher incidence of coagulopathy (37%) and ICH-related death (25%) than those in Group 2 (0 and 7%, respectively). Decrease in KPS and GCS scores of greater than 30 and greater than 3, respectively, at the time of ICH were indicators of increased mortality. Of the 17 children with subdural ICH, 13 suffered the hemorrhage following treatment for hydrocephalus and three patients suffered ICH associated with thrombocytopenia. In the 33 children alive at the 3-month follow-up examination after the ICH, no difference existed in the mean KPS scores pre- and post-ICH.
Conclusions. Treatment for hydrocephalus, coagulopathy, thrombocytopenia, and hemorrhage into the tumor were the most probable causes of ICH among patients in Group 1. Radiation-induced vasculopathy was a possible cause of ICH in the patients in Group 2. Significant decline in the patient's neurological status at the time of ICH is a poor prognostic factor, but those patients who survive cancer and ICH are likely to regain neurological function.
Maryam Fouladi, Richard Heideman, James W. Langston, Larry E. Kun, Stephen J. Thompson and Amar Gajjar
✓ This report and the accompanying review of the literature address the challenges, when using surveillance magnetic resonance (MR) imaging, of establishing the origin of newly detected central nervous system lesions. Routine surveillance MR imaging in a 16-year-old boy, whose medulloblastoma had been successfully treated, demonstrated asymptomatic nodular leptomeningeal enhancement of the brain and spinal cord, which was consistent with recurrent disease. Examination of the cerebrospinal fluid, however, led to the diagnosis of bacterial meningitis. Two weeks after completion of antibiotic therapy, the original MR imaging findings were seen to have resolved. This case illustrates the importance of considering clinical and laboratory data, including results from a complete examination of the cerebrospinal fluid, when interpreting the origin of new lesions revealed by MR imaging.
Joseph F. Cusick, Khang-Cheng Ho, Thad C. Hagen and Larry E. Kun
✓ Granular-cell pituicytomas of the neurohypophysis have a controversial histogenesis and oncological behavior. The occurrence of such a tumor in a patient whose father and daughter had endocrine neoplasms suggests a neuroectodermal origin for these tumors. Although all of the conditions considered in this report are unusual clinical entities, their correlation offers considerations in understanding the importance of genetic factors in tumor development.
Thomas E. Merchant, Erin N. Kiehna, Larry E. Kun, Raymond K. Mulhern, Chenghong Li, Xiaoping Xiong, Frederick A. Boop and Robert A. Sanford
A Phase II trial of conformal radiation therapy (CRT) for craniopharyngioma was conducted to determine whether the irradiated volume could be safely reduced to decrease effects on cognitive function.
Between July 1997 and January 2003, 28 pediatric patients (median age 7.3 ± 4.12 years) received CRT in whom doses (54–55.8 Gy) were administered to the gross tumor volume (solid and cystic components) surrounded by a 1-cm clinical target volume margin. Patients were evaluated serially with neuropsychometric testing. Statistical analyses were performed to determine the effect of clinical factors and radiation dosimetry on intelligence quotient (IQ).
The median follow-up period was 36.6 months (range 24.4–80 months). The estimated 3-year progression-free survival rate was 90.3 ± 7.3%. Three patients experienced local disease progression. Cognitive outcome for patients was adversely affected by the following factors: age younger than 7.4 years (p = 0.001), an interval between symptoms and diagnosis of more than 73 days (p = 0.06), more extensive surgery (p = 0.014), multiple surgical procedures (p = 0.002), diabetes insipidus (p = 0.02), hydrocephalus at diagnosis (p = 0.009), a cerebrospinal fluid shunt (p = 0.005), shunt revisions (p = 0.01), Ommaya reservoir laterality (p = 0.005), and cyst aspirations (p = 0.02). The percentage of total brain, supratentorial brain, or left temporal lobe volumes receiving a dose in excess of 45 Gy had a significant impact on longitudinal IQ.
The use of CRT with a 1-cm margin for clinical target volume results in tumor control equivalent to that achieved using conventionally planned radiation therapy. Surgical morbidity and a volume-receiving dose more than 45 Gy are factors affecting longitudinal IQ after CRT in patients treated for craniopharyngioma.
Amar Gajjar, Ravi Bhargava, Jesse J. Jenkins, Richard Heideman, Robert A. Sanford, James W. Langston, Andrew W. Walter, John F. Kuttesch, Michael Muhlbauer and Larry E. Kun
✓ Little is known about low-grade astrocytoma with neuraxis dissemination at diagnosis. A review of medical records identified this phenomenon in eight of 150 pediatric patients evaluated between 1985 and 1994 for histologically confirmed low-grade astrocytoma. These patients (five male and three female) ranged in age from 5 months to 20 years (median 8 years). Symptoms of neuraxis disease were minimal or absent. Primary tumor sites were the hypothalamus in four cases, brainstem/spinal cord in three, and temporal lobe in one. Patterns of dissemination (evaluated by computerized tomography and/or magnetic resonance imaging techniques) appeared to be related to the primary site: hypothalamic tumors metastasized along the ventricular cerebrospinal fluid pathways, and tumors in other locations disseminated along subarachnoid pathways. Following initial treatment with chemotherapy (in three), partial resection (in one), radiation therapy (in three), and chemotherapy plus irradiation (in one), four patients required salvage therapy for progressive or recurrent disease. Seven of the eight patients are alive with stable or progressive disease 6 to 105 months postdiagnosis (median 15 months). Low-grade astrocytoma with initial neuraxis dissemination is responsive to chemotherapy and radiation, a proportion showing periods of stable disease. The optimum therapy or combination of therapies remains unclear.
Paul Klimo Jr., Atmaram S. Pai Panandiker, Clinton J. Thompson, Frederick A. Boop, Ibrahim Qaddoumi, Amar Gajjar, Gregory T. Armstrong, David W. Ellison, Larry E. Kun, Robert J. Ogg and Robert A. Sanford
Whereas diffuse intrinsic pontine gliomas generally have a short symptom duration and more cranial nerve involvement, focal brainstem gliomas are commonly low grade, with fewer cranial neuropathies. Although these phenotypic distinctions are not absolute predictors of outcome, they do demonstrate correlation in most cases. Because there is a limited literature on focal brainstem gliomas in pediatric patients, the objective of this paper was to report the management and outcome of these tumors.
The authors reviewed the records of all children diagnosed with radiographically confirmed low-grade focal brainstem gliomas from 1986 to 2010. Each patient underwent biopsy or resection for tissue diagnosis. Event-free survival (EFS) and overall survival were evaluated. Univariate analysis was conducted to identify demographic and treatment variables that may affect EFS.
Fifty-two patients (20 girls, 32 boys) with follow-up data were identified. Median follow-up was 10.0 years, and the median age at diagnosis was 6.5 years (range 1–17 years). The tumor locations were midbrain (n = 22, 42%), pons (n = 15, 29%), and medulla (n = 15, 29%). Surgical extirpation was the primary treatment in 25 patients (48%). The 5- and 10-year EFS and overall survival were 59%/98% and 52%/90%, respectively. An event or treatment failure occurred in 24 patients (46%), including 5 deaths. Median time to treatment failure was 3.4 years. Disease progression in the other 19 patients transpired within 25.1 months of diagnosis. Thirteen of these patients received radiation, including 11 within 2 months of primary treatment failure. Although children with intrinsic tumors had slightly better EFS at 5 years compared with those with exophytic tumors (p = 0.054), this difference was not significant at 10 years (p = 0.147). No other variables were predictive of EFS.
Surgery suffices in many children with low-grade focal brainstem gliomas. Radiation treatment is often reserved for disease progression but offers comparable disease control following biopsy. In the authors' experience, combining an assessment of clinical course, imaging, and tumor biopsy yields a reasonable model for managing children with focal brainstem tumors.
Kathleen J. Helton, James K. Weeks, Nicholas S. Phillips, Ping Zou, Larry E. Kun, Raja B. Khan, Amar Gajjar, Maryam Fouladi, Alberto Broniscer, Frederick Boop, Chin-Shang Li and Robert J. Ogg
Diffusion tensor (DT) imaging has been used to predict postoperative motor function in patients with supratentorial tumors. The authors sought to determine whether DT imaging and white matter tractography could detect axonal degeneration in patients with brainstem tumors.
A cross-sectional, retrospective study of 7 patients with brainstem tumors and 8 healthy volunteers was performed. The DT imaging data were normalized and regions of interest (ROIs) with the highest probability of sensory and motor connections were selected using the Talairach Atlas to identify the 3D millimetric coordinates of white matter tracts. An iterative process involving fractional anisotropy (FA), apparent diffusion coefficients (ADCs), and color maps was developed to precisely select ROIs in the bilateral sensory and motor tracts. The FA and ADC values were calculated for each ROI.
The FA values of sensory and motor tracts significantly differed between the patient and healthy volunteer groups (p < 0.05), whereas no significant changes were found in the splenium or genu of the corpus callosum. The FA values were altered proximal and distal to the brainstem tumors with a bimodal peak of antegrade decreased FA involving second- and third-order sensory axons and retrograde decreased FA of motor axons.
This study demonstrates changes in diffusion properties of sensory and motor tracts consistent with degeneration to further characterize brainstem tumors in children, and the results warrant the planning of prospective trials. The rigorous methods the authors describe may provide valuable information when planning biopsies or debulking of unusual brainstem tumors, as well as improve prognostication of the possible functional tract recovery following therapy.
Proceedings from the National Institutes of Health workshop
Elizabeth B. Claus, May Abdel-Wahab, Peter C. Burger, Herbert H. Engelhard, David W. Ellison, Nicholas Gaiano, David H. Gutmann, Daniel A. Heck Jr., Eric C. Holland, George I. Jallo, Carol Kruchko, Larry E. Kun, Bernard L. Maria, Zoran Rumboldt, Daniela Seminara, Giovanna M. Spinella, Linda Stophel, Robert Wechsler-Reya, Margaret Wrensch and Richard J. Gilbertson
The relative rarity of spinal cord tumors has hampered the study of these uncommon nervous system malignancies. Consequently, the understanding of the fundamental biology and optimal treatment of spinal cord tumors is limited, and these cancers continue to inflict considerable morbidity and mortality in children and adults. As a first step to improving the outcome of patients affected with spinal cord tumors, the National Institutes of Health Office of Rare Diseases Research in cooperation with the National Cancer Institute and the National Institute of Neurological Disorders and Stroke convened a workshop to discuss the current status of research and clinical management of these tumors. The overall goal of this meeting was to initiate a process that would eventually translate fundamental basic science research into improved clinical care for this group of patients. Investigational priorities for each of these areas were established, and the opportunities for future multidisciplinary research collaborations were identified.