Burden of spousal caregivers of stage II and III esophageal cancer survivors 3 years after treatment with curative intent.

OBJECTIVES: The aim of this study is to examine caregiver burden of spousal caregivers of patients with esophageal cancer after curative treatment with neoadjuvant chemoradiation followed by resection and to assess factors associated with caregiver burden. METHODS: In this exploratory, cross-sectional study, spousal caregivers and patients were eligible if the caregiver was the patient's spouse and the patient had been treated with chemoradiation followed by surgery after esophageal carcinoma diagnosis. Forty-seven couples were included. Spousal caregivers completed a questionnaire, examining caregivers' burden (Self-Perceived Pressure from Informal Care (SPPIC, Dutch)), caregiver unmet needs (SCNS-P&S), anxiety and depression (Hospital Anxiety and Depression Scale (HADS)), and marital satisfaction (Maudsley Marital Questionnaire (MMQ)). Patients completed the latter two questionnaires and a cancer specific quality of life questionnaire (EORTC-QLQ C30 and OES18 (oesophageal module). Logistic regression analysis was performed to identify correlates for caregiver burden. RESULTS: The median time after esophagectomy was 38 months. Thirty-four percent of the spousal caregivers reported moderate or high burden. Spousal caregivers most frequently reported unmet needs were managing concerns about the cancer coming back (43%), dealing with others not acknowledging the impact on your life of caring for a person with cancer (38%), and balancing the needs of the person with cancer and one's own needs. A comparable proportion of spousal caregivers and patients showed symptoms of anxiety (23 vs 17%) and depression (17 vs 17%). Spousal caregivers reported significantly more dissatisfaction than patients on the marital scale (p < 0.01). Factors independently associated with higher caregiver burden were fatigue of the patient (OR = 1.66, 95% CI 1.12-2.47) and depression of the spousal caregiver (OR = 1.44, 95% CI 1.11-1.86). CONCLUSIONS: More than a third of the spousal caregivers of patients with esophageal cancer treated with curative intent report moderate or high burden 3 years after treatment. Fatigue of the patient and depression of the spousal caregiver are associated with caregiver burden. To improve clinical care, identification of spousal caregivers at risk for experiencing higher caregiver burden and implementation of specific interventions is needed.

Transcriptome datasets of oil palm pathogen Ganoderma boninense.

Ganoderma boninense is known to be the causal agent for basal stem rot (BSR) affecting the oil palm industry worldwide thus cumulating to high economic losses every year. Several reports have shown that a compatible monokaryon pair needs to mate; producing dikaryotic mycelia to initiate the infection towards the oil palm. However, the molecular events occurs during mating process are not well understood. We performed transcriptome sequencing using Illumina RNA-seq technology and de novo assembly of the transcripts from monokaryon, mating junction and dikaryon mycelia of G. boninense. Raw reads from these three libraries were deposited in the NCBI database with accession number SRR1745787, SRR1745773 and SRR1745777, respectively.

Human hematopoietic stem cell adherence to cytokines and matrix molecules.

The hematopoietic microenvironment is a complex structure in which stem cells, progenitor cells, stromal cells, growth factors, and extracellular matrix (ECM) molecules each interact to direct the coordinate regulation of blood cell development. While much is known concerning the individual components of this microenvironment, little is understood of the interactions among these various components or, in particular, the nature of those interactions responsible for the regional localization of specific developmental signals. We hypothesized that cytokines act together with ECM molecules to anchor stem cells within the microenvironment, thus modulating their function. In order to analyze matrix-cytokine-stem cell interactions, we developed an ECM model system in which purified stem cell populations and plastic-immobilized individual proteins are used to assess the role of various matrix molecules and/or cytokines in human hematopoietic cell development. Analysis of these interactions revealed that a single ECM protein, thrombospondin, in conjunction with a single cytokine (e.g., c-kit ligand), constitutes a developmental signal that synergistically modulates hematopoietic stem cell function.

[Fibroepithelial tumours of the breast: not always a simple fibroadenoma]. / Fibro-epitheliale tumoren van de borst.

Fibroepithelial tumours are the most common type of solid breast tumours. They include the common fibroadenomas and the rare phyllodes tumours. Fibroadenomas usually present in younger patients and are smaller than phyllodes tumours. They are benign and do not require any treatment or follow-up. Further examination (usually ultrasound-guided thick-needle biopsy) is recommended if in doubt about the diagnosis. Phyllodes tumours can be divided into benign, borderline and malignant tumours and are primarily treated with surgery, breast-conserving surgery if possible. In this article, we present three cases and an overview of characteristics, diagnosis, and treatment of fibroepithelial breast tumours.

Secondary brain tumors in children treated for acute lymphoblastic leukemia at St Jude Children's Research Hospital.

PURPOSE: To evaluate the incidence of and potential risk factors for second malignant neoplasms of the brain following treatment for childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: The study population consisted of 1,612 consecutively enrolled protocol patients treated on sequential institutional protocols for newly diagnosed ALL at St Jude Children's Research Hospital (SJCRH) between 1967 and 1988. The median follow-up duration is 15.9 years (range, 5.5 to 29.9 y). RESULTS: The cumulative incidence of brain tumors at 20 years is 1.39% (95% confidence interval [CI], 0.63% to 2.15%). Twenty-two brain tumors (10 high-grade gliomas, one low-grade glioma, and 11 meningiomas) were diagnosed among 21 patients after a median latency of 12.6 years (high-grade gliomas, 9.1 years; meningiomas, 19 years). Tumor type was linked to outcome, with patients who developed high-grade tumors doing poorly and those who developed low-grade tumors doing well. Risk factors for developing any secondary brain tumor included the presence of CNS leukemia at diagnosis, treatment on Total X therapy, and the use of cranial irradiation, which was dose-dependent. Age less than 6 years was associated with an increased risk of developing a high-grade glioma. CONCLUSION: This single-institution study, with a high rate of long-term data capture, demonstrated that brain tumors are a rare, late complication of therapy for ALL. We report many more low-grade tumors than others probably because of exhaustive long-term follow-up evaluation. The importance of limiting cranial radiation is underscored by the dose-dependent tumorigenic effect of radiation therapy seen in this study.

Survival and neurodevelopmental outcome of young children with medulloblastoma at St Jude Children's Research Hospital.

PURPOSE: Young children treated for medulloblastoma are at especially high risk for morbidity and mortality from their disease and therapy. This study sought to assess the relationship, if any, between patient outcome and M stage. Neuropsychologic and endocrine outcomes were also assessed. PATIENTS AND METHODS: Twenty-nine consecutively diagnosed infants and young children were treated for medulloblastoma at St Jude Children's Research Hospital between November 1984 and December 1995. All patients were treated with the intent of using postoperative chemotherapy to delay planned irradiation. RESULTS: The median age at diagnosis was 2.6 years. Six patients completed planned chemotherapy without progressive disease and underwent irradiation at completion of chemotherapy. Twenty-three children experienced disease progression during chemotherapy and underwent irradiation at the time of progression. The 5-year overall survival rate for the entire cohort was 51% +/- 10%. The 5-year progression-free survival rate was 21% +/- 8%. M stage did not impact survival. All patients lost cognitive function during and after therapy at a rate of -3.9 intelligence quotient points per year (P =.0028). Sensory functions declined significantly after therapy (P =.007). All long-term survivors required hormone replacement therapy and had growth abnormalities. CONCLUSION: The majority of infants treated for medulloblastoma experienced disease progression during initial chemotherapy. However, more than half of these patients can be cured with salvage radiation therapy, regardless of M stage. The presence of metastatic disease did not increase the risk of dying from medulloblastoma. All patients treated in this fashion have significant neuropsychologic deficits. Our experience demonstrates that medulloblastoma in infancy is a curable disease, albeit at a significant cost.

Preirradiation chemotherapy with carboplatin and etoposide in newly diagnosed embryonal pediatric CNS tumors.

PURPOSE: We evaluated the clinical efficacy of preirradiation carboplatin (CARBO) and etoposide (VP-16) in 25 patients with newly diagnosed embryonal CNS tumors. PATIENTS AND METHODS: Sixteen patients with high-risk medulloblastoma and nine with other embryonal tumors were treated with two daily doses of CARBO 350 mg/m2 and VP-16 100 mg/m2 (CARBO/VP) every 21 days for four cycles before standard craniospinal irradiation. Patients with disease progression (PD) before radiation therapy were additionally treated with intensive postirradiation cyclophosphamide (CYCLO) and vincristine (VINC). RESULTS: Among 23 assessable patients, 48% (95% confidence interval, 27% to 69%) had a complete response (CR) or partial response (PR) to CARBO/VP; eight had PD. Among the subgroup of 15 assessable patients with medulloblastoma, 53% had a CR or PR (95% confidence interval, 27% to 79%) and five PD. The toxicity of CARBO/VP was predominantly hematologic; although grade IV neutropenia was common, only five episodes of febrile neutropenia occurred. Only thrombocytopenia was a more common toxicity than in other reported chemotherapy regimens; ototoxicity was less common than in cisplatin (CDDP) regimens. CONCLUSION: The responses and survival associated with neoadjuvant CARBO/VP are similar to those with CDDP-containing and other neoadjuvant drug regimens. Although the rate of progression with this regimen may be higher than with similar CDDP-containing regimens, the numbers of patients in other published studies of these agents are too small to detect meaningful statistical differences. Future studies must balance the apparently comparable efficacy of CARBO and CDDP with their differing toxicities.

Comparison of CSF cytology and spinal magnetic resonance imaging in the detection of leptomeningeal disease in pediatric medulloblastoma or primitive neuroectodermal tumor.

PURPOSE: Leptomeningeal disease (LMD) significantly affects the prognosis and treatment of pediatric patients with medulloblastoma or primitive neuroectodermal tumor (PNET). Examination of CSF for malignant cells, detection of LMD on spinal magnetic resonance imaging (MRI), or both are the methods routinely used to diagnose LMD. A recent study suggested 100% correlation between CSF and MRI findings in children with medulloblastoma. To determine the validity of this hypothesis, we compared the rate of detection of LMD between concurrent lumbar CSF cytology and spinal MRI performed at diagnosis in patients with medulloblastoma or PNET. PATIENTS AND METHODS: As a part of diagnostic staging, 106 consecutive patients newly diagnosed with medulloblastoma or PNET were evaluated with concurrent lumbar CSF cytology and spinal MRI. CSF cytology was examined for the presence of malignant cells and spinal MRI was reviewed independently for the presence of LMD. RESULTS: Thirty-four patients (32%) were diagnosed with LMD based on CSF cytology, spinal MRI, or both. There were 21 discordant results. Nine patients (8.5%) with positive MRI had negative CSF cytology. Twelve patients (11.3%) with positive CSF cytology had negative MRIs. The exact 95% upper bounds on the proportion of patients with LMD whose disease would have gone undetected using either CSF cytology or MRI as the only diagnostic modality were calculated at 14.4% and 17.7%, respectively. CONCLUSION: With the use of either CSF cytology or spinal MRI alone, LMD would be missed in up to 14% to 18% of patients with medulloblastoma or PNET. Thus, both CSF cytology and spinal MRI should routinely be used to diagnose LMD in patients with medulloblastoma or PNET.

Comparison of lumbar and shunt cerebrospinal fluid specimens for cytologic detection of leptomeningeal disease in pediatric patients with brain tumors.

PURPOSE: Leptomeningeal disease (LMD) significantly affects the prognosis and treatment of pediatric patients with primary CNS tumors. Cytologic examination of lumbar CSF is routinely used to detect LMD. To determine whether examination of CSF obtained from ventricular shunt taps is a more sensitive method of detecting LMD in these patients, we designed a prospective study to compare the findings of cytologic examinations of CSF obtained from concurrent lumbar and ventriculoperitoneal (VP) shunt taps. PATIENTS AND METHODS: As a part of diagnostic staging, follow-up testing, or both, 52 consecutive patients underwent concurrent lumbar and shunt taps on 90 separate occasions, ranging from the time of diagnosis to treatment follow-up. CSF from both sites was examined cytologically for malignant cells. RESULTS: The median age of the 28 males and 24 females was 7.5 years (range, 0.6 to 21.4 years). The primary CNS tumors included medulloblastoma (n = 29), astrocytoma (n = 10), ependymoma (n = 5), germinoma (n = 3), atypical teratoid rhabdoid tumor (n = 2), choroid plexus carcinoma (n = 2), and pineoblastoma (n = 1). Each site yielded a median CSF volume of 1.0 mL. Fourteen of 90 paired CSF test results were discordant: in 12, the cytologic findings from shunt CSF were negative for malignant cells, but those from lumbar CSF were positive; in two, the reverse was true. Malignant cells were detected at a higher rate in lumbar CSF than in shunt CSF (P =.0018). When repeat analyses were excluded, examination of lumbar CSF remained significantly more sensitive in detecting malignant cells (P =.011). Analysis of the subset of patients with embryonal tumors showed similar results (P =.0008). CONCLUSION: Cytologic examination of lumbar CSF is clearly superior to cytologic examination of VP shunt CSF for detecting leptomeningeal metastases in pediatric patients with primary CNS tumors.

Direct translation of a protracted irinotecan schedule from a xenograft model to a phase I trial in children.

PURPOSE: In a preclinical model of neuroblastoma, administration of irinotecan daily 5 days per week for 2 consecutive weeks ([qd x 5] x 2) resulted in greater antitumor activity than did a single 5-day course with the same total dose. We evaluated this protracted schedule in children. PATIENTS AND METHODS: Twenty-three children with refractory solid tumors were enrolled onto a phase I study. Cohorts received irinotecan by 1-hour intravenous infusion at 20, 24, or 29 mg/m(2) (qd x 5) x 2 every 21 days. RESULTS: The 23 children (median age, 14.1 years; median prior regimens, two) received 84 courses. Predominant diagnoses were neuroblastoma (n = 5), osteosarcoma (n = 5), and rhabdomyosarcoma (n = 4). The dose-limiting toxicity was grade 3/4 diarrhea and/or abdominal cramps in six of 12 patients treated at 24 mg/m(2), despite aggressive use of loperamide. The maximum-tolerated dose (MTD) on this schedule was 20 mg/m(2)/d. Five patients had partial responses and 16 had disease stabilization. On day 1, the median systemic exposure to SN-38 (the active metabolite of irinotecan) at the MTD was 106 ng-h/mL (range, 41 to 421 ng-h/mL). CONCLUSION: This protracted schedule is well tolerated in children. The absence of significant myelosuppression and encouraging clinical responses suggest compellingly that irinotecan be further evaluated in children using the (qd x 5) x 2 schedule, beginning at a dose of 20 mg/m(2). These results imply that data obtained from xenograft models can be effectively integrated into the design of clinical trials.

Long-term results with radiation therapy for pediatric desmoid tumors.

PURPOSE: To retrospectively review the treatment and outcome of pediatric patients with desmoid tumor who received radiation therapy at a single institution. MATERIALS AND METHODS: Thirteen pediatric patients received radiation therapy for desmoid tumor at St. Jude Children's Research Hospital between 1962 and 1998. Only 2 of the patients reviewed received treatment prior to 1976. The median dose of external beam irradiation was 50 Gy. RESULTS: At the time of this report, 10 of 13 patients have had tumors that recurred after radiation therapy and 3 have died from their disease. One additional patient was harboring a recurrence, and 1 had not been followed long enough to suggest that the patient had achieved disease control. One patient remained locally controlled after radiation therapy with long-term follow-up (196 months). The median time to recurrence following radiation therapy was 19 months (range, 3-135 months). Eight of the 13 patients suffered substantial tumor and treatment-related morbidity. CONCLUSIONS: Desmoid tumors in pediatric patients are locally aggressive tumors that are likely to recur after radiation therapy. Alternatives to radiation therapy should be sought for the treatment of these tumors, and efforts should focus on low-morbidity therapies aimed at inhibiting the growth of these unique tumors.

Low-grade astrocytoma with neuraxis dissemination at diagnosis.

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.

Anemia associated with exposure to lindane.

A recent case of severe, but reversible, hypoplastic anemia was associated temporally with lindane exposure. A series of 46 cases of hematotoxicity associated with lindane is reviewed, and the weaknesses in the indictment of lindane as the causative agent are pointed out. A more rational policy for control of agents suspected of damaging bone marrow awaits improved understanding of pathogenetic mechanisms.

A simple method for the preparation of furosine and pyridosine reference material.

After heating N alpha-acetyllysine and glucose for 4 h at 90 degrees C in the dry state and subsequent acid hydrolysis with 7.8 N HCl, preparative fractionation of the dihydrochlorides of furosine and pyridosine was achieved by cation-exchange chromatography. The lysine derivatives could be prepared with high yield and sufficient purity for the use as reference material.

Studies on the formation of lysinomethylalanine and histidinomethylalanine in milk products.

From reaction mixtures consisting of N-acetyldehydroaminobutyric acid methyl ester and N alpha-acetyl-L-lysine or N alpha-acetyl-L-histidine, respectively, distinct amounts of the cross-link amino acids N epsilon-(2-amino-2-carboxy-1-methyl-ethyl)-L-lysine (lysinomethylalanine, LMeAL) and N tau-(2'-amino-2'-carboxy-1'-methyl-ethyl)-L-histidine (histidinomethylalanine, HMeAL) were isolated via preparative ion-exchange chromatography and identified by 1H- and 13C-nuclear magnetic resonance. In the amino acid chromatogram, both compounds eluted clearly separated from other basic amino acids. However, neither LMeAL nor HMeAL could be detected in numerous acid hydrolysates of a range of milk products. In model studies, threonine showed a significantly lower tendency for an alkali-induced beta-elimination reaction compared to serine. The reactivity of the resulting dehydroaminobutyric acid towards nucleophiles was more than tenfold lower as compared to dehydroalanine. Thus, the formation of LMeAL as well as of HMeAL during food processing is negligible.

Detection and identification of the cross-linking amino acids N tau- and N pi-(2'-amino-2'-carboxy-ethyl)-L-histidine ("histidinoalanine", HAL) in heated milk products.

An unknown ninhydrin positive compound, X, was detected in acid hydrolysates of heated skim milk samples by amino acid analysis, eluting between phenylalanine and pyridosine in the chromatogram. The formation of X correlated with heating time and temperature. preparative ion-exchange chromatography enabled the isolation of X and a second minor compound from a milk protein hydrolysate and from a model mixture consisting of N alpha-acetylhistidine and methyl-2-acetamidoacrylate (acetyldehydroalaninemethylester), in a relative abundance of 8 to 1. By 1H-NMR spectroscopy, the two compounds could be identified as the N tau- and N pi-isomers of N-(2'-amino-2'-carboxy-ethyl)-L-histidine (histidinoalanine), a cross-link amino acid that has not been described in food proteins up to now. In a number of foods containing milk protein, the N tau-histidinoalanine contents were between 50 and 1800 mg/kg protein, which is in a concentration range comparable to the potential nephrotoxic cross-link lysinoalanine, which was determined simultaneously.

Gorlin syndrome associated with midline nasal dermoid cyst.

Gorlin syndrome is an autosomal dominant multisystem disorder characterised by multiple basal cell naevi, cysts of the jaw, pits of the palms and soles, skeletal anomalies, and various other defects. Patients with Gorlin syndrome have a predisposition to basal cell carcinomas and other neoplasms. This is the first report to describe the coexistence of Gorlin syndrome and a nasal dermoid cyst. A 4 year old girl was diagnosed with medulloblastoma and treated with surgery and radiation therapy. A genetic evaluation was sought because of the brain tumour, multiple small naevi localised mostly on the upper torso, and rib abnormalities. Biopsies of several naevi showed naevoid basal cell carcinoma. Past medical history was significant for a midline nasal punctum noted at birth. The significance of this finding was unrecognised until the dermoid cyst enlarged, just before the diagnosis of her brain tumour. A common tissue of origin exists between basal cell naevi, cysts of the jaw, and dermoid cysts. We propose that the association of these two rare conditions in one patient is not a chance occurrence.

Complications of the nevoid basal cell carcinoma syndrome: a case report.

PURPOSE: We report that patients with nevoid basal cell carcinoma syndrome (Gorlin syndrome) are at risk for developing neoplasms, especially basal cell carcinomas and rarely medulloblastoma. METHODS: A case report is presented of a 5-year-old child with medulloblastoma and multiple basal cell carcinomas who was diagnosed with nevoid basal cell carcinoma syndrome. Genetic analyses were performed on tumor DNA from the patient's medulloblastoma and basal cell carcinoma as well as germline DNA from the patient and unaffected family members. RESULTS: After radiation therapy for medulloblastoma, the patient developed thousands of additional basal cell carcinomas. Analysis of tumor DNA revealed the characteristic defect of nevoid basal cell carcinoma syndrome, loss of heterozygosity at 9q22. Photodynamic therapy was successfully used to control the majority of her cutaneous tumors. CONCLUSION: DNA analysis confirmed the presence of the distinctive genetic lesion of nevoid basal cell carcinoma syndrome in both medulloblastoma and basal cell carcinoma. Omitting or limiting radiation therapy for children with nevoid basal cell carcinoma syndrome and medulloblastoma should be considered.

Interleukin-4 mediates STAT6 activation in 3T3-L1 preadipocytes but not adipocytes.

STAT6 is abundantly expressed in 3T3-L1 preadipocytes and adipocytes but activating ligands are not well defined. In this report, we provide evidence that interleukin 4 (IL-4) induced JAK2-mediated STAT6 tyrosine phosphorylation and DNA binding in 3T3-L1 preadipocytes but not in 3T3-L1 adipocytes. Loss of IL-4-mediated STAT6 tyrosine phosphorylation occurred 2 days after preadipocytes were induced to differentiate into adipocytes but when cells remained phenotypically preadipocytes. 3T3-L1 adipocytes were still responsive to IL-4 through tyrosine phosphorylation of other cellular proteins. We conclude that IL-4 signals through STAT6 in 3T3-L1 preadipocytes but not in 3T3-L1 adipocytes. This differentiation-dependent loss of STAT6 activation may be critical for distinct biological effects of IL-4 in 3T3-L1 preadipocytes and adipocytes.

Supratentorial malignant gliomas in childhood: a single institution perspective.

BACKGROUND: A retrospective study evaluated the clinical characteristics, prognostic factors, and outcome of patients with newly diagnosed supratentorial malignant gliomas treated with preirradiation chemotherapy. METHODS: Of 41 patients with supratentorial malignant gliomas accrued between 1984-1994, all had neuroimaging documentation of the extent of resection and 37 had complete neuraxis staging prior to treatment; 80% were treated with one of a variety of neoadjuvant chemotherapy regimens. RESULTS: Thirteen patients had anaplastic astrocytoma (AA), 25 had glioblastoma multiforme (GBM), and 3 had anaplastic oligodendroglioma. Gross total resection (GTR) was performed in 10 patients, subtotal resection (STR) in 22 patients, and biopsy (Bx) alone in 9 patients. For the entire group the 3-year overall and progression free survivals were 35 +/- 8% and 18 +/- 6%, respectively. Tumor recurrence was dominantly local. However, 9 patients with initially local disease failed at a distant neuraxis site, giving a 26 +/- 7% actuarial risk of dissemination at 3 years. The only significant prognostic factor was extent of tumor resection: patients who underwent GTR survived longer than those who underwent STR or Bx (P = 0.004). Histology (GBM vs. AA), age, and the use of enhanced local dose radiation therapy (brachytherapy or stereotactic irradiation) did not affect survival. CONCLUSIONS: Neoadjuvant chemotherapy was not associated with a survival rate significantly different from that observed in adjuvant chemotherapy studies. Systematic neuraxis staging at diagnosis and recurrence revealed a rate of neuraxis dissemination as a component of recurrence that was higher than previously reported; the utility of craniospinal irradiation in preventing isolated dissemination remains uncertain.