Biomedical subjects

L E Kun

Publications and source records attributed to L E Kun.

At least 19 recordsLinked to original sources

PubMed1999

High incidence of secondary brain tumours after radiotherapy and antimetabolites.

BACKGROUND: Brain tumours rarely occur in survivors of childhood acute lymphoblastic leukaemia after cranial radiotherapy. An unusually high frequency of brain tumours seen among children enrolled in one of our leukaemia treatment protocols, Total Therapy Study XII, prompted us to identify the potential causes of this complication. METHODS: We assessed clinical, biological, and pharmacokinetic features in all 52 children who received prophylactic cranial radiotherapy. We compared the cumulative incidence of brain tumours between subgroups, and with that of 421 children who received radiotherapy in previous studies. FINDINGS: The incidence of brain tumours among irradiated children (six of 52, 12.8% [SE 5.0]) was high compared with patients in the same study who did not receive radiotherapy (none of 101; p=0.0008) and with other protocols that included cranial radiotherapy (p<0.0001). Of the six children, four had erythrocyte concentrations of thioguanine nucleotide metabolites higher than the 70th percentile for the entire cohort, and three had a genetic defect in thiopurine catabolism. The 8-year cumulative incidence of brain tumour among children with defective versus wild-type thiopurine methyltransferase phenotype was 42.9% (SE 20.6) versus 8.3% (4.7; p=0.0077). This protocol differed from previous protocols, in that more intensive systemic antimetabolite therapy was given before and during radiotherapy. INTERPRETATION: These data support the elimination of prophylactic radiotherapy for acute lymphoblastic leukaemia except in patients at high risk of central-nervous-system relapse. Underlying genetic characteristics and treatment variables may be associated with an increased risk of radiation-associated brain tumours.

Adolescent↗

PubMed1999

Long-term follow-up of patients treated with primary radiotherapy for supradiaphragmatic Hodgkin's disease at St. Jude Children's Research Hospital.

OBJECTIVE: To assess disease control, patterns of relapse, factors predictive of relapse, and late effects of treatment, we reviewed all cases of supradiaphragmatic (SD) Hodgkin's disease (HD) treated with primary radiation therapy (RT) at our institution. METHODS: We retrospectively reviewed the disease characteristics, treatment history, and long-term outcome of the 106 patients with Stage I and II supradiaphragmatic HD who received definitive irradiation at St. Jude Children's Research Hospital between 1970 and 1995. As of the date of analysis, 95 patients are alive, with a median follow-up of 13.3 years (range, 1.9-24.2 years). RESULTS: The median age at diagnosis was 14.7 years (range, 3.7-22.7). Involved-field RT was given to 13 patients (12%), whereas 37 (35%) had mantle RT, 51 patients (48%) had subtotal nodal irradiation, and 5 (5%) had total nodal irradiation. Relapsed disease developed in 26 patients at a median of 1.8 years (range, 0.2-9.3 years). The 5- and 10-year estimated cumulative incidences of relapse were 20.9% +/- 4.0% and 25.1% +/- 4.3%, respectively. With a median dose of 36 Gy (range, 32-40), in-field failure rate was 6.2%, whereas subdiaphragmatic relapse in sites irradiated prophylactically was 1.5%. There was a trend toward an increased incidence of relapse with higher ESR (p = 0.088) and greater number of sites of disease (p = 0.087). Age, stage, histology, nodal disease > or = 6 cm, the presence of bulky mediastinal disease, and the method of staging did not affect the incidence of relapse. The pattern of failure could not be predicted based on the stage of disease, the extent of subdiaphragmatic staging, the extent of radiation therapy, or the sequence of RT fields-"ping pong" vs. sequential. Subset analysis of Stage II patients revealed significantly more relapses in clinically staged patients. Excluding Stage IA patients with high cervical disease or peripheral nodal disease, nodal extension failures were more common for patients undergoing limited-volume RT, whereas extranodal relapses were likely after STNI or TNI. The estimated 10- and 15-year cumulative incidences of second malignancies were 2.9% +/- 1.6% and 7.9% +/- 3.3%, respectively. Our patients are at increased risk of second malignancies (11-fold), and fatal cardiac (68-fold) and infectious (33-fold) complications. Overall survival at 10 years was 90.8% +/- 3.2%; event-free survival was 72.1% +/- 5.0%. CONCLUSIONS: The current analysis confirms the curative potential of RT for HD in children and adolescents. Despite successful salvage therapy, relapsed disease remained the principal cause of death in our cohort. Excess risk of septic death in asplenic patients, fatal heart disease, and second malignancies may further compromise the ultimate cure of HD in long-term survivors.

Adolescent↗

PubMed1999

There is no role for hyperfractionated radiotherapy in the management of children with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric Oncology Group phase III trial comparing conventional vs. hyperfractionated radiotherapy.

PURPOSE: In June 1992, POG began accrual to a phase III study, POG-9239, designed to compare the time to disease progression, overall survival, and toxicities observed in children with newly diagnosed brainstem tumor treated with 100 mg/m2 of infusional cisplatin and randomized to either conventional vs. hyperfractionated radiotherapy. METHODS AND MATERIALS: Patients eligible for study were those between 3 and 21 years of age with previously untreated tumors arising in the pons. Histologic confirmation of diagnosis was not mandatory, provided that the clinical and MRI scan findings were typical for a diffusely infiltrating pontine lesion. Treatment consisted of a six-week course of local field radiotherapy with either once a day treatment of 180 cGy per fraction to a total dose of 5400 cGy (arm 1) or a twice a day regimen of 117 cGy per fraction to a total dose of 7020 cGy (the second of the three hyperfractionated dose escalation levels of POG-8495) (arm 2). Because of previously reported poor results with conventional radiotherapy alone, cisplatin was included as a potential radiosensitizer in an attempt to improve progression-free and ultimate survival rates. Based on results of the phase I cisplatin dose escalation trial, POG-9139, 100 mg/m2 was chosen for this trial and was delivered by continuous infusion over a 120-hour period, beginning on the first day of radiotherapy and repeated during weeks 3 and 5. One hundred thirty eligible patients were treated on protocol, 66 on arm 1 and 64 on arm 2. RESULTS: The results we report are from time of diagnosis through October 1997. For patients treated on arm 1, the median time to disease progression (defined as time to off study) was 6 months (range 2-15 months) and the median time to death 8.5 months (range 3-24 months); survival at 1 year was 30.9% and at 2 years, 7.1%. For patients treated on arm 2, the corresponding values were 5 months (range 1-12 months) and 8 months (range 1-23 months), with 1- and 2-year survival rates at 27.0% and 6.7%, respectively. Evaluation of response by MRI at 4 or 8 wks post treatment was available in 108 patients and revealed a complete response in 1 patient of each Rx arm, a partial response (> 50% decrease in size) in 18 patients of arm 1 and 15 patients of arm 2, minimal to no response (stable) in 25 patients of arm 1 and 23 patients of arm 2, and progressive disease in 13 patients of arm 1 and 12 patients of arm 2. The pattern of failure was local in all patients. Morbidity of treatment was similar in both Rx arms, with no significant toxicity (including hearing loss) reported. Autopsy was performed in 6 patients, and confirmed the presence of extensive residual tumor in these cases. CONCLUSION: The major conclusion from this trial is that the hyperfractionated method of Rx 2 did not improve event-free survival (p = 0.96) nor did it improve survival (p = 0.65) over that of the conventional fractionation regimen of Rx 1, and that both treatments are associated with a poor disease-free and survival outcome.

Adolescent↗

PubMed1999

Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist.

OBJECTIVE: Hypothalamic obesity is a rare sequela of cranial insult, for which pathogenesis and treatment remain obscure. In rodents ventromedial hypothalamic damage causes hyperphagia, obesity, hyperinsulinism, and insulin resistance. Reduction of insulin secretion in humans may attenuate weight gain. METHODS: Eight children with intractable obesity after therapy for leukemia or brain tumors underwent oral glucose tolerance testing (OGTT) with simultaneous insulin levels before and after treatment with octreotide for 6 months. RESULTS: In comparison with a 6-month pre-study observation period, patients exhibited weight loss (+6.0 +/- 0.7 kg vs -4.8 +/- 1.8 kg; P =.04) and decrease in body mass index (+2.1 +/- 0.3 kg/m(2) vs -2.0 +/- 0.7 kg/m(2); P =.0001). Recall calorie count decreased during the 6 months of treatment (P =. 015). OGTT demonstrated biochemical glucose intolerance in 5 of 8 patients initially and in 2 of 7 at study end, whereas insulin response was decreased (281 +/- 47 microU/mL vs 114 +/- 35 microU/mL; P =.04). Percent weight change correlated with changes in insulin response (r = 0.72, P =.012) and changes in plasma leptin r = 0.76, P =.0004). CONCLUSIONS: Patients with hypothalamic obesity demonstrate excessive insulin secretion. Octreotide administration promoted weight loss, which correlated with reduction in insulin secretion on OGTT and with reduction in leptin levels. Pre-study biochemical glucose tolerance improved in several patients while they were receiving octreotide. These results suggest that normalization of insulin secretion may be an effective therapeutic strategy in this syndrome.

Adolescent↗

PubMed1999

Topotecan for the treatment of recurrent or progressive central nervous system tumors - a pediatric oncology group phase II study.

Topotecan was studied as a 72 h infusion given every 3 weeks. Treatment began at a dose of 1.0 mg/m2/day and was increased to 1.25 mg/m2/day after the first 6 patients tolerated this higher dose without excessive toxicities. Eighty-eight evaluable children were accrued in 6 strata. There were no complete nor partial responses. Twenty subjects had stable disease (astrocytoma 5/11, malignant glioma 5/13, medulloblastoma 0/12, brain stem tumor 4/19, ependymoma 5/17, and miscellaneous histologies 1/16). Two patients (astrocytoma, ependymoma) completed the maximum 18 topotecan courses. The remaining 68 children developed progressive disease within 2 months. Myelosuppression was the main toxicity. Grade 4 leukopenia, neutropenia, anemia, and thrombocytopenia were observed in 18, 32, 5, and 23 participants, respectively. It was concluded that topotecan as given according to this schedule showed insufficient activity to promote it to frontline protocol usage.

Adult↗

PubMed1999

Diagnostic markers in paediatric medulloblastoma: a Paediatric Oncology Group Study.

AIMS: We have reviewed immunohistochemically 17 paediatric medulloblastomas in order to determine if correlations exist that might be useful in subclassifying these tumours. METHODS AND RESULTS: The patient group included 11 children who had died (mean survival 13 months) and six still alive (followed for up to 10 years). Ten tumours were diffuse and six were nodular (one biopsy had only perivascular tumour). Of the 10 diffuse tumours, three were desmoplastic: of the six nodular tumours, all six were desmoplastic. All 17 tumours were synaptophysin-reactive: three nodular tumours were glial fibrillary acidic protein (GFAP)-reactive in the nodules (two of three S 100-reactive tumours were also GFAP-reactive). MIB-1 labelling indices (LI) ranged from 5 to 80%. Six tumours exhibited at least 1% LI against Tp53 (Mab D07 and/or Mab 1801). Eight cases were 100% bcl2-reactive with nine cases having an LI <80% ('low labelling'). All nine 'low labelling' bcl2 cases were TP53 non-reactive; all six Tp53-reactive cases were bcl2 100% reactive. Six of 10 patients with diffuse medulloblastomas survived 18 months or less while four of 10 are alive up to 10 years. In contrast, five of six patients with nodular neoplasms died within 48 months of diagnosis with one patient followed up for less than 1 year. CONCLUSIONS: Immunohistochemistry is a useful adjunct in characterizing subsets of paediatric medulloblastomas and confirms that larger co-operative studies may be fruitful in identifying a prognostic utility of a combined histochemical/immunohistochemical analysis on these tumours.

Adolescent↗

PubMed1999

High-grade pediatric spinal cord tumors.

Our institutional experience with high-grade pediatric spinal cord tumors includes 11 children treated during the period of 1981-1997. All patients underwent a biopsy or an attempt at resection and received postoperative radiation therapy. Three patients had a gross-total resection of their primary tumor, 6 patients had a subtotal resection and the remaining 2 were biopsied. Histologically, these tumors were characterized as anaplastic astrocytoma (n = 6), glioblastoma multiforme (n = 3) or anaplastic oligodendroglioma (n = 2). Three patients were treated with craniospinal irradiation (38-48 Gy) in addition to a boost to the residual tumor. The median dose to the primary site for all patients was 48.6 Gy (range 38-55 Gy). The median overall survival was 13 months (range 8-149 months). Only 2 patients were alive at 138 and 149 months following radiation therapy. The median progression-free survival following radiation therapy was 10 months (range 2-80 months). There was no difference in progression-free or overall survival for those diagnosed with glioblastoma multiforme when compared to patients diagnosed with anaplastic astrocytoma or anaplastic oligodendroglioma. The pattern of failure was either diffuse or local. For the patients who failed diffusely (n = 6), the median progression-free survival was 2 months compared to 23 months for those whose failure was entirely local (p < 0.01). The median overall survival was significantly shorter for those who failed diffusely compared to those who failed locally (10 vs. 37 months, p < 0.01). High-grade spinal cord tumors in children have a poor prognosis based on this report. It is important to document the extent of disease accurately prior to the initiation of radiation therapy, since a subset of these patients progress rapidly outside of the field of irradiation.

Child↗

PubMed1999

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.

Adolescent↗

PubMed1999

Infectious meningitis mimicking recurrent medulloblastoma on magnetic resonance imaging. Case report.

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.

Adolescent↗

PubMed1998

The effects of radiation on craniofacial skeletal growth: a quantitative study.

To determine whether radiation delivered to children treated for head and neck cancer causes deformity, we performed a quantitative analysis for craniofacial asymmetry. A total of 42 patients, with either rhabdomyosarcoma or nasopharyngeal carcinoma, treated between 1980 and 1991, were analyzed. Exclusions included 16 subjects, leaving 26 children of mixed race and gender with a median age at diagnosis of 13 years (range: 2-18) and a median age at follow-up of 4 years (range: 3-37). Data from 14 measurements of the cranium and facial skeleton, for which normative data exist, were recorded. Symmetry of the face and head were determined and each measurement was compared to age specific standards. Deviation occurred in the cranial vault, the anterior and mid-interorbital distances and lateral orbital wall length. Asymmetry existed in the medial and lateral orbital wall lengths and the zygomatic arches. We conclude that, children irradiated for head and neck malignancies, have significant alterations in some skeletal measurements indicative of treatment induced asymmetry and potential deformity.

Adolescent↗

PubMed1998

Early intensification of intrathecal chemotherapy virtually eliminates central nervous system relapse in children with acute lymphoblastic leukemia.

Central nervous system (CNS) relapse has been an obstacle to uniformly successful treatment of childhood acute lymphoblastic leukemia (ALL) for many years. We therefore intensified intrathecal chemotherapy (simultaneously administered methotrexate, hydrocortisone, and cytarabine) for 165 consecutive children with newly diagnosed ALL enrolled in Total Therapy Study XIIIA from December 1991 to August 1994. The 64 patients (39%) who had 1 or more blast cells in cytocentrifuged preparations of cerebrospinal fluid at diagnosis, with or without associated higher-risk features, received additional doses of intrathecal chemotherapy during remission induction and the first year of continuation treatment. Patients with higher-risk leukemia, regardless of cerebrospinal fluid findings, also received additional doses of intrathecal chemotherapy during the first year of continuation treatment. Cranial irradiation was reserved for patients with higher-risk leukemia (22% of the total). The 5-year cumulative risk of an isolated CNS relapse among all 165 patients was 1.2% (95% confidence interval, 0% to 2.9%), whereas that of any CNS relapse was 3.2% (0. 4% to 6.0%). The probability of surviving for 5 years without an adverse event of any type was 80.2% +/- 9.2% (SE). Our results suggest that early intensification of intrathecal chemotherapy will reduce the risk of CNS relapse to a very low level in children with ALL, securing a higher event-free survival rate overall.

Adolescent↗

PubMed1998

Carboplatin and etoposide with hyperfractionated radiotherapy in children with newly diagnosed diffuse pontine gliomas: a phase I/II study.

BACKGROUND: Diffuse pontine gliomas remain one of the most lethal of pediatric malignancies despite the use of increasingly intensive therapies. We delivered intensive chemotherapy during and following 70.2 Gy of hyperfractionated radiation therapy in an attempt to improve survival. PROCEDURE: Nine consecutive children with diffuse pontine gliomas were treated on this single arm study. Carboplatin, given in combination with fixed dose etoposide, was escalated in successive cohorts to determine its maximum tolerated systemic exposure (AUC). Outcome was coded based on imaging characteristics and clinical status. RESULTS: Eight of the nine children on this study died of their disease at a median of 44 weeks, essentially the same survival as those treated on a previous Pediatric Oncology Group study using hyperfractionated radiation therapy alone. Toxicity was almost exclusively hematologic and not associated with significant morbidity. CONCLUSIONS: The use of concurrent carboplatin and etoposide with hyperfractionated radiation therapy did not appear to improve the survival in this group of children with diffuse pontine gliomas. The toxicity of this chemotherapy during radiation therapy was primarily hematologic and well tolerated. New approaches to the treatment of these tumors need to be investigated.

Antineoplastic Agents, Phytogenic↗

PubMed1998

Second malignancies in young children with primary brain tumors following treatment with prolonged postoperative chemotherapy and delayed irradiation: a Pediatric Oncology Group study.

Between 1986 and 1990, the Pediatric Oncology Group conducted a study in which 198 children younger than 3 years of age with malignant brain tumors were treated with prolonged postoperative chemotherapy in an effort to delay irradiation and reduce long-term neurotoxicity. Children younger than 2 years of age received 24 months of chemotherapy followed by irradiation, and those between 2 and 3 years of age received 12 months of chemotherapy plus irradiation. Chemotherapy was given in 28-day cycles (AAB, AAB), with cycle A = vincristine (0.065 mg/kg) intravenously on days 1 and 8 and cyclophosphamide (65 mg/kg) intravenously on day 1, and cycle B = cisplatinum (4 mg/kg) intravenously on day 1 and etoposide (6.5 mg/kg) intravenously on days 3 and 4. Five of the 198 children developed second malignancies, with a cumulative risk at 8 years of 11.3% (95% confidence interval [CI], 0-39%). Four of the five second malignancies occurred in children younger than 2 years of age at diagnosis, with a cumulative risk at 8 years of 18.9% (CI, 0-70%). Initial diagnoses were choroid plexus carcinoma (2 children), ependymoma (1 child), desmoplastic infantile ganglioglioma (2 children), and medulloblastoma (1 child). Duration from diagnosis of initial tumor to second malignancy was 33, 35, 57, 66, and 92 months. Three children younger than 2 years of age developed lymphoproliferative disease, that is, myelodysplastic syndrome (2 children), both with monosomy 7 deletions, and acute myelogenous leukemia (1 child), after 24 to 26 cycles of chemotherapy, including 8 cycles of etoposide. Two of 3 received craniospinal irradiation (2,560/3,840 cGy) and (3,520/5,320 cGy). Time to second malignancy was 7 years 8 months, 4 years 9 months, and 2 years 9 months. Two children developed solid tumors, at 5 years 6 months and 2 years 11 months, respectively, after initiation of treatment. A sarcoma developed after 26 cycles of chemotherapy and no irradiation, and a meningioma developed after 12 cycles of chemotherapy and local craniospinal irradiation. Potential causative factors for this high rate of secondary malignancies include prolonged use of alkylating agents and etoposide with or without irradiation.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Multiple causes of cerebrovascular events in children with tumors of the parasellar region.

Cerebrovascular arterial occlusion is a rare but devastating event causing long-term morbidity in children with tumors in the parasellar region. While usually associated with radiation therapy, there are a variety of host, tumor and treatment factors which predispose patients to significant vasculopathy. Case reports of 5 patients from St. Jude Children's Research Hospital with tumors in the parasellar region who presented with or developed vascular occlusive disease are summarized. Multiple factors are identified in these cases which probably impacted on the development of cerebral arterial occlusion with or without moyamoya syndrome. These include, but are not limited to, neurofibromatosis, tumor encasement of major cerebral vessels, surgical alterations, and radiation therapy. The literature supports multiple, potentially interactive etiologies for the development of vascular events in these patients, suggesting that their development is not simply a phenomenon related to radiation therapy.

Brain Neoplasms↗

PubMed1998

Atypical teratoid/rhabdoid tumor of the central nervous system: a highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma: a Pediatric Oncology Group study.

Fifty-five patients with atypical teratoid/rhabdoid tumors of the central nervous system were studied to define the clinical and pathologic features of this newly described neoplasm. The lesion occurred primarily in children younger than 2 (mean age at diagnosis, 17 months). The neoplasms were located in the posterior fossa (36 patients) and the supratentorial compartment (17 patients) or were multifocal in both compartments (2 patients) at presentation. Histologically, the tumors were composed of small cells and large, pale cells in a jumbled architectural arrangement. The small cell component resembled medulloblastoma and occasionally had cords of cells in a mucinous background, simulating chordoma. The cytoplasm of the larger cells was conspicuous with a somewhat "rhabdoid" appearance, although rhabdoid features were not always prominent. Epithelioid features in the form of poorly formed glands or Flexner-Wintersteiner rosettes were noted in a minority of lesions. The neoplasms showed striking polyphenotypic immunoreactivity, including that for vimentin, glial fibrillary acidic protein, epithelial membrane antigen, cytokeratins, synaptophysin, chromogranin, and smooth muscle actin. Using a probe for chromosome 22, seven of eight scorable cases showed a solitary signal by fluorescence in situ hybridization (FISH) consistent with monosomy 22. The eighth scorable case showed three signals by fluorescence in situ hybridization and had a translocation involving chromosome 22 reported by conventional cytogenetics. In contrast to patients with medulloblastoma, the neoplasm with which these lesions are often confused, the outcome of the patients was uniformly poor. The mean postoperative survival of patients with atypical teratoid/rhabdoid tumors was only 11 months. Local recurrence, seeding of the cerebrospinal fluid pathways, or both, were common terminal events. This study underscores the distinctive clinical, histopathologic, immunohistochemical, and cytogenetic character of this unusually aggressive tumor.

Brain Neoplasms↗

PubMed1998

Prognostic factors in infants and very young children with intracranial ependymomas.

The Pediatric Oncology Group (1986-1990) conducted a study in which 48 children <3 years of age with intracranial ependymomas were treated with prolonged postoperative chemotherapy (CT) and delayed RT. Thirty-one children, 0-23 months of age at diagnosis (Gp A) received 2 years of CT followed by RT; while 17 children, 24-36 months of age at diagnosis (Gp B) received CT for 1 year followed by radiation. One-year survivals were 87% (Gp A) and 94% (Gp B) and 2-year survivals were 67% (Gp A) and 82% (Gp B). In subsequent years a significant divergence in survivals according to age has been noted (p = 0.04). Five-year survivals were 25.7% (Gp A) vs. 63.3% (Gp B). The curves began to diverge 1 year following diagnosis. Other than age, the only significant prognostic factor was degree of surgical resection: 5-year survivals were 66% (total resection) vs. 25% (subtotal resection). Neither the presence of metastases, degree of anaplasia nor the degree of surgical resection varied significantly according to age at diagnosis. The most likely reason for the difference in survivals between the two age groups relates to the timing of radiation following CT, i.e., 1-year delay in children 24-36 months of age compared to a 2-year delay in children 0-23 months of age. An alternative but less likely hypothesis is that ependymomas in the younger children have a more aggressive biology. In contrast, survivals in the 24- to 36-month group are much better than previous reports in the literature suggesting that prolonged postoperative CT may allow both a delay in CRT as well as provide improved survivals. Based on these results, future treatment trials should emphasize maximal surgical resection and a delay in radiation of no more than 1 year.

Age Distribution↗

PubMed1998

Bithalamic involvement predicts poor outcome among children with thalamic glial tumors.

Clinical features and treatment of 36 consecutive pediatric patients with thalamic glial tumors confirmed by histology and characterized by neuroimaging were reviewed to identify prognostic factors. The median age at diagnosis was 10 years (range 1-18 years). Twenty-four patients had low-grade tumors (juvenile pilocytic astrocytoma n = 9, fibrillary astrocytoma n = 6, astrocytomas not otherwise specified n = 6, ganglioglioma n = 2 and oligodendroglioma n = 1) and 12 patients had high-grade tumors (glioblastoma multiforme n = 7, anaplastic astrocytoma n = 4 and unclassified malignant tumor n = 1). With a median follow-up of 4.3 years among survivors, estimates of 4-year progression-free survival (PFS) and overall survival (OS) for the entire group are 28+/-10 and 37 +/- 10%, respectively. Low-grade tumors were associated with a significantly better 4-year PFS (36 +/- 12 vs. 0% for the high-grade group; p = 0.03) and OS (52 +/- 12 vs. 0%; p < 0.001). This review identified that bithalamic involvement, characterized by neuroimaging, exerted an independent and significant negative impact on PFS and OS for patients with low-grade tumors. Estimates of 4-year PFS and OS among patients with tow-grade bithalamic versus monothalamic tumors were 58 +/- 15 vs. 0% and 85 +/- 11 vs. 0% (p < 0.00001), respectively. The presence of bithalamic involvement did not affect outcome among patients with high-grade tumors. Additionally, age at diagnosis, enhancement with neuroimaging contrast, extension beyond the thalamus and extent of surgical resection did not correlate with overall outcome. Because treatment approaches varied during the study period, the impact of radiation therapy or chemotherapy could not be assessed. This contemporary, single-institution series of pediatric thalamic glial tumors demonstrates, for the First time, the statistical significance of bithalamic involvement as a marker of poor prognosis among patients with low-grade glial lesions.

Adolescent↗

PubMed1998

Increased mortality after successful treatment for Hodgkin's disease.

PURPOSE: To determine the impact of treatment toxicity on long-term survival in pediatric Hodgkin's disease. PATIENTS AND METHODS: We studied late events in 387 patients treated for pediatric Hodgkin's disease on four consecutive clinical trials at St Jude Children's Research Hospital from 1968 to 1990. Relative risks, actuarial risks, and absolute excess risks for cause-specific deaths were calculated. RESULTS: As of April 1997, 316 (82%) of patients were alive, with a median follow-up of 15.1 (range, 2.9 to 28.6) years. In this cohort, which represented 5,623 person-years of follow-up, 71 fatal events resulted from Hodgkin's disease (n=36), second malignancies (n=14), infections (n=7), accidents (n=7), cardiac disease (n=6), and asphyxiation (n=1). The 5-year estimated event-free survival (EFS) for the entire cohort was 79.6%+/-2.1 %, which declined to 63.1%+/-4.4% by 20 years. Cumulative incidences of cause-specific deaths at 25 years were 9.8%+/-1.6% for Hodgkin's disease, 8.1%+/-2.6% for second malignancy, 4.0%+/-1.8% for cardiac disease, 3.9%+/-1.5% for infection, and 2.1%+/-0.8% for accidents. Standardized incidence ratios showed excess risk for all second malignancies (12; 95% confidence interval [CI], 8 to 17), acute myeloid leukemia (81; 95% CI, 16 to 237), solid tumors (11; 95% CI, 7 to 16), and breast cancer (33; 95% CI, 12 to 72). Standardized mortality ratios also showed excess mortality from cardiac disease (22; 95% CI, 8 to 48) and infection (18; 95% CI, 7 to 38). CONCLUSION: Compared with age- and sex-matched control populations, survivors of pediatric Hodgkin's disease who were treated before 1990 face an increased risk of early mortality related to second cancers, cardiac disease, and infection.

Adolescent↗