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A Gajjar

Publications and source records attributed to A Gajjar.

At least 37 records · Page 2Linked to original sources
PubMed1999

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.

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

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

A pilot study of vincristine, ifosfamide, and doxorubicin in the treatment of pediatric non-rhabdomyosarcoma soft tissue sarcomas.

BACKGROUND: Standard therapy for pediatric nonrhabdomyosarcoma soft tissue sarcomas (PNRSTS) consists of surgical resection with or without radiotherapy. The role of chemotherapy in the treatment of these tumors has not yet been defined. We investigated the efficacy and toxicity of an ifosfamide-based regimen in controlling disease in children with high-risk PNRSTS. PATIENTS AND METHODS: Between January 1992 and June 1994 at St. Jude Children's Research Hospital, we treated 11 children and young adults with PNRSTS who were at high risk for treatment failure by using a combined modality regimen that comprised aggressive surgery, radiotherapy, and chemotherapy including vincristine, ifosfamide, and doxorubicin (VID). Nine of these patients had grade 3 disease and one had grade 2 tumor; due to insufficient tissue, the disease grade of the remaining patient could not be established. Metastases were present at diagnosis in 2 children. RESULTS: Therapy was generally well tolerated, with minimal morbidity and no mortality. The most common toxicity was grade 4 neutropenia, which occurred in 51% of evaluable courses. Among 4 patients evaluable for response to chemotherapy alone, 1 child attained a partial response and 3 had stable disease. One child had a response to chemotherapy and concurrent irradiation. At a median follow-up of 30 months, 10 of 11 patients are alive; 8 of 11 patients are alive without evidence of disease. CONCLUSION: Aggressive multimodality therapy for PNRSTS is well tolerated, despite frequent and profound neutropenia. Although adjuvant chemotherapy for this group of cancers remains unproved, the rate of tumor control achieved in this pilot study encourages further investigation in a multi-institutional setting.

Adolescent↗
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

Algorithm for nutritional support: experience of the Metabolic and Infusion Support Service of St. Jude Children's Research Hospital.

The Metabolic and Infusion Support Service (MISS) at St. Jude Children's Research Hospital was established in 1988 to improve the quality of nutritional support given to children undergoing therapy for cancer. This multidisciplinary group, representing each of the clinical services within the hospital, provides a range of services to all patients requiring full enteral or parenteral nutritional support. In 1991, the MISS developed an algorithm for nutritional support which emphasized a demand for a compelling rationale for choosing parenteral over enteral support in patients with functional gastrointestinal tracts. Compliance with the algorithm was monitored annually for 3 years, with full compliance defined as meeting all criteria for initiating support and selection of an appropriate type of support. Compliance rates were 93% in 1992, 95% in 1993 and 100% in 1994. The algorithm was revised in 1994 to include criteria for offering oral supplementation to patients whose body weight was at least 90% of their ideal weight and whose protein stores were considered adequate. Full support was begun if no weight gain occurred. Patients likely to tolerate and absorb food from the gastrointestinal tract were classified into groups defined by the absence of intractable vomiting, severe diarrhea, graft-vs.-host disease affecting the gut, radiation enteritis, strictures, ileus, mucositis and treatment with allogeneic bone marrow transplant. Overall, the adoption of the algorithm has increased the frequency of enteral nutritional support, particularly via gastrostomies, by at least 3-fold. Our current emphasis is to define the time points in therapy at which nutritional intervention is most warranted.

Algorithms↗
PubMed1997

Patterns of failure in children with medulloblastoma: effects of preirradiation chemotherapy.

PURPOSE: To evaluate the effects of preirradiation chemotherapy on patterns of failure in children with medulloblastoma. METHODS AND MATERIALS: Fifty-three patients (pts) with medulloblastoma were given preirradiation chemotherapy as initial postoperative treatment at St. Jude Children's Research Hospital from November 1984 to September 1993. Patients < or = 3 years of age (n = 23) received chemotherapy (CH) with delayed craniospinal irradiation (CSI). Children > or = 3 years with more advanced disease (T3b-T4, M+ or measurable residual after resection) were given CH followed by CSI (30 patients). Chemotherapy regimen depended on protocol, but usually included cis- or carboplatin and etoposide, +/- cyclophosphamide and vincristine. RESULTS: Actuarial overall survival and event-free survival rates are 60% (95% confidence interval [41,79]) and 37% [19,55] at 5 years. Children < or = 3 at diagnosis: six of 23 pts completed CH without progression and received consolidative CSI; all six are alive with no evidence of disease (NED) at 2.4-9.1 years. Seventeen patients progressed during CH and were then given CSI. Sites of progression during CH were posterior fossa (PF) in 11 patients, neuraxis (NEUR) in 4, and PF+NEUR in 2. Following CSI, 7 patients are alive NED at 2.0-8.6 years; 10 patients died of progressive disease. Eleven patients had M0 disease at diagnosis; 8 (73%) progressed during CH, 3 in the neuraxis. Children > or = 3 at diagnosis: 20 of 30 patients completed pre-CSI CH without progression; 15 are alive NED at 1.3-9.2 years, and 5 showed post-CSI progression in the PF (n = 3), in the NEUR (n = 1) and in bone marrow (n = 1). Ten of the 30 (33%) patients progressed on CH (6 in NEUR, 4 in PF); 5 are alive and NED or with stable disease. Seventeen patients had M0 disease at diagnosis; 3 out of 17 (18%) progressed during CH, 2 in NEUR and 1 in an extraneural site. In the total group of 30 patients, 11 have had disease recurrence after completion of XRT. The actuarial rate of failure was 23 +/- 9% for the patients < or = 3 years of age and 21 +/- 8% for the older children when evaluated at 4 months after diagnosis (at the completion of chemotherapy in the older children but during the ongoing chemotherapy in the younger children). CONCLUSIONS: In patients presenting with M0 disease and receiving pre-CSI chemotherapy, the risk of neuraxis progression seems to increase with duration of chemotherapy. The sites of progression during preirradiation chemotherapy are nearly equally divided between posterior fossa and other neuraxis sites. CSI salvage of patients progressing on chemotherapy is possible in approximately 50% of patients. Following CSI, neuraxis progression is more frequent than posterior fossa relapse.

Adolescent↗
PubMed1997

Brain stem involvement in children with neurofibromatosis type 1: role of magnetic resonance imaging and spectroscopy in the distinction from diffuse pontine glioma.

OBJECTIVE: To evaluate the ability of magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) to distinguish neurofibromatosis Type 1 (NF-1) with brain stem enlargement from diffuse pontine glioma (PG) in pediatric patients. METHODS: A chart review was used to identify all patients with NF-1 and diffuse brain stem enlargement who were seen at our institution and who had undergone MRI. Comparison groups were as follows: 1) eight patients who did not have NF-1 but who did have diffuse PG, and 2) seven healthy children. Midsagittal diameters of the pons, midbrain, and medulla were measured in all patients, and the results were statistically analyzed. Two MRS variables were also statistically compared: N-acetyl aspartate and the vector sum of the metabolites choline and creatine/phosphocreatine. RESULTS: In MRI-based measurements, only the pontine midsagittal diameter differed significantly between the NF-1 and PG groups (P = 0.002). Altogether, 21 children underwent MRS, including 6 in the NF-1 group. Measures of both MRS variables were significantly lower in patients with PG than in the others (P < or = 0.007). The two MRS variables classified the 21 children into the three respective groups with 100% accuracy. Of the seven patients with NF-1, four presented with symptoms attributable to brain stem involvement. The brain stems of all seven patients with NF-1 were hyperintense on T2-weighted magnetic resonance images, and five were isointense on T1-weighted images; only one exophytic tumor was identified. Four of the patients with NF-1 were followed up clinically without treatment; all remained alive and neurologically stable for a median of 40 months. All eight patients in the PG group were symptomatic at presentation, and all except one died despite therapy. CONCLUSION: Both MRI measurements and MRS seem to be useful for distinguishing patients with NF-1 and diffuse brain stem enlargement from patients without NF-1 but with diffuse PG. They should be most helpful in differentiating symptomatic patients with NF-1 from patients with PG, thereby minimizing aggressive treatment and its side effects in patients destined to have better outcomes.

Adolescent↗
PubMed1997

Cerebellar pontine angle ependymoma in infants.

We discuss the surgical approach used for and outcome in 11 infants (< or =3 years) who were treated at our institution for ependymomas arising in the cerebellar-pontine (C-P) angle. The median age of the group was 19 months (range: 6-26 months). Of these 11 patients, the initial surgery for 8 was performed at our center and achieved a gross total resection (GTR) in 4 patients and a subtotal resection (STR) in the remaining 4. The 3 patients who had tumor debulking performed elsewhere were subsequently referred to our institution and had definitive surgery after receiving 3-4 courses of chemotherapy; one of these children had a GTR, whereas the remaining 2 had an STR. During the immediate postoperative period, 9 patients had cranial nerve deficits that necessitated placement of a tracheostomy and a gastrostomy feeding tube; these were discontinued in 6 of the 9 patients as the deficits resolved. The majority of the permanent cranial nerve deficits involved the sixth and seventh cranial nerves. Of the 11 patients, 4 have died (progressive disease, n = 1; accidental death, n = 2; withdrawal of life support, n = 1); the remaining 7 patients are alive, with a median follow-up of 37 months (range: 20-73 months). Aggressive surgical resection for tumors arising in the C-P region is associated with postoperative deficits, which resolve over time with appropriate supportive care. This approach may increase the number of children in whom GTR is achieved, thereby potentially increasing the cure rate for these patients.

Antineoplastic Agents↗
PubMed1997

Low-grade astrocytoma: a decade of experience at St. Jude Children's Research Hospital.

PURPOSE: To evaluate the impact of primary tumor site, age at diagnosis, extent of resection, and histology on progression-free survival (PFS) in pediatric low-grade astrocytoma. PATIENTS AND METHODS: Medical, pathologic, and imaging information were reviewed for 142 children (ages 2 months to 19 years) with low-grade astrocytoma treated between January 1984 and July 1994. Gross total resection (GTR) was attempted for cerebellar and cerebral hemisphere tumors, with biopsy or less aggressive resection used predominantly for tumors in other sites. Surgery was followed by observation in 107 cases, radiation therapy in 31, and chemotherapy in four. RESULTS: The overall survival rate was 90% +/- 3% (SE) at 4 years. PFS was significantly better for patients with cerebellar and cerebral hemisphere tumors (n = 75) than those with tumors in all other sites (P = .0006). Within the former group, there was no significant difference in PFS for patients in whom GTR was achieved versus those with incomplete resections (4-year estimates, 89% and 77%, respectively). Histology (juvenile pilocytic v astrocytoma not otherwise specified [NOS]) was not related to PFS in an analysis that controlled for tumor site and patient age. Patients younger than 5 years at diagnosis had a significantly poorer PFS than older children, regardless of histology (P < .03) or tumor site (P < .002). Treatment for progressive/recurrent disease was effective in a majority of patients, but appeared more successful in patients with hemispheric than thalamic or hypothalamic tumors. CONCLUSION: The overall survival in this series of pediatric low-grade astrocytomas is excellent. Age at diagnosis and tumor location, but not histology, had a significant impact on PFS. Efforts to improve treatment outcome should focus on young patients (< 5 years) and on those with central midline tumors. The majority of patients with completely resected hemispheric tumors were monitored without further therapy, which supports attempted GTR of cerebral and cerebellar hemisphere low-grade astrocytoma.

Adolescent↗
PubMed1997

Ependymomas.

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Adolescent↗
PubMed1996

Overt testicular disease at diagnosis is associated with high risk features and a poor prognosis in patients with childhood acute lymphoblastic leukemia.

BACKGROUND: The impact of overt testicular disease on survival was assessed among patients treated at the study institution for childhood acute lymphoblastic leukemia (ALL) over a 15-year period. To the authors' knowledge, the frequency of overt testicular involvement at diagnosis of ALL and its impact on treatment outcome have not been reported previously. METHODS: The medical records of all 651 boys with ALL enrolled on St. Jude Total Therapy Studies X-XIIIA (May 1979 to December 1993) were reviewed to determine the frequency of overt testicular involvement at diagnosis. The log rank test and sequential Cox regression analyses, adjusted for known adverse features, were used to compare event free and overall survival for patients with and without testicular leukemia. A matched-pairs analysis was then conducted for both outcome measures. RESULTS: Thirteen of the 651 male patients (1.9%) presented with overt testicular leukemia. Compared with the other patients, these 13 boys had a significantly higher frequency of infant or adolescent age at diagnosis, hyperleukocytosis, splenomegaly, and mediastinal mass; a poorer 5-year event free survival (38% [95% confidence interval (CI), 15.4-61.4%] vs. 58% [95% CI, 53.6-61.7%], P = 0.06, log rank test); and a significantly poorer 5-year overall survival (37% [95% CI, 14-60.4%] vs. 75% [95% CI, 71.3-78.4%], P = 0.002). The difference in overall, but not event free, survival was supported by sequential Cox regression analyses and by the matched-pairs analysis (P = 0.04). CONCLUSIONS: Overt testicular involvement with leukemia at diagnosis was associated with an adverse survival in boys with ALL. Testicular irradiation may not be necessary in those patients who present with overt testicular involvement. This finding merits prospective evaluation in a larger sample of similarly treated patients.

Adolescent↗
PubMed1996

DNA index of glial tumors in children. Correlation with tumor grade and prognosis.

BACKGROUND: Although DNA index (DI) has prognostic significance in a variety of pediatric malignancies, there are few data regarding its utility in central nervous system (CNS) tumors. We have previously shown that patients with hyperdiploid medulloblastoma have a significantly better survival than those whose tumors are diploid. Here, we examine the effect of DI and tumor grade on the progression free survival (PFS) of 57 patients with a variety of glial neoplasms. METHODS: DI was determined by flow cytometry on freshly obtained tumor tissue from the initial diagnostic specimens; a DI = 1.0 was defined as diploid (DIP), 1.0 < DI < 1.1 as near diploid (NDIP), and DI > 1.1 as hyperdiploid (HYP). Tumors were histologically graded according to the World Health Organization classification. RESULTS: There were 21 Grade I tumors, 20 Grade II, 8 Grade III, and 8 Grade IV. Among the 41 low grade tumors (Grade I-II), 39 were DIP or NDIP, and 2 were HYP. Among the 16 high grade tumors (Grade III-IV), 9 were DIP, 2 NDIP, and 5 HYP. The 4-year PFS of low grade tumors was 70% (standard deviation [SD] 12%) versus 8% (SD 7%) for high grade tumors. There was a significant correlation between low grade tumor histology and a DIP/NDIP DI (P = 0.015), and univariate analysis suggested improved PFS was associated with DIP/NDIP tumors (P = 0.05). However, DI did not remain a significant prognostic factor after being stratified by tumor grade (P = 0.87). CONCLUSIONS: Unlike medulloblastoma, DI is not an independent prognostic factor in pediatric glial tumors.

Adolescent↗
PubMed1996

Topoisomerase I interactive drugs in children with cancer.

Topotecan, irinotecan, and 9-aminocamptothecin (9-AC) are analogs of the plant alkaloid 20(S)-camptothecin (CMT), the prototypical DNA topoisomerase I interactive agent. These agents interact with the topoisomerase I-DNA complex and prevent resealing topoisomerase I-mediated DNA single-strand breaks. This eventual leads to double-strand DNA breaks and apoptosis or cell death. Topotecan, irinotecan, and 9-AC have shown significant activity in mice bearing pediatric solid tumor xenografts; the greatest antitumor responses were found with protracted continuous schedules. Preclinical data also suggest that maintenance of an exposure-duration threshold (EDT) may be required to achieve optimal cytotoxicity. Pediatric Phase I trials have evaluated the toxicity and safety to camptothecin analogs in children with relapsed solid tumors and relapsed acute leukemia. The primary dose-limiting toxicity (DLT) for the CMT analogs in children has been myelosuppression, except for mucositis observed with the 120-hr continuous topotecan infusion schedule. Pharmacodynamic relationships with these analogs have been reported between systemic exposure, and myelosuppression and mucositis. Although not a primary objective of the early Phase I studies, antitumor responses have been reported. In this review, the pharmacokinetic and pharmacodynamics of the CMT analogs studied in children are summarized, and future studies of these agents are discussed.

Animals↗
PubMed1996

Cerebrospinal fluid pharmacokinetics and penetration of continuous infusion topotecan in children with central nervous system tumors.

The purpose of this study was to describe the cerebrospinal fluid (CSF) penetration of topotecan in humans, to generate a pharmacokinetic model to simultaneously describe topotecan lactone and total concentrations in the plasma and CSF, and to characterize the CSF and plasma pharmacokinetics of topotecan administered as a continuous infusion (CI). Plasma and CSF samples were collected from 17 patients receiving 5.5 or 7.5 mg/m2 per day as a 24-h CI (5 patients, 7 courses), or 0.5 to 1.25 mg/m2 per day as a 72-h CI (12 patients, 12 courses). CSF samples were obtained from either a ventricular reservoir (VR) or a lumbar puncture (LP). Topotecan lactone and total (lactone plus hydroxy acid) concentrations were determined by HPLC and fluorescence detection. Using MAP-Bayesian modelling, a three-compartment model was fitted simultaneously to topotecan lactone and total concentrations in the plasma and CSF. The penetration of topotecan into the CSF was determined from the ratio of the CSF to the plasma area under the concentration-time curve. The median CSF ventricular lactone concentrations, obtained prior to the end of infusion (EOI), were 0.86, 1.4, 0.73, 5.3, and 4.6 ng/ml for patients receiving 0.5, 1.0, 1.25, 5.5, and 7.5 mg/m2 per day, respectively. EOI CSF lumbar lactone concentrations measured in three patients were 0.44, 1.1, and 1.7 ng/ml for topotecan doses of 1.0, 5.5, and 7.5 mg/m2 per day, respectively. In two patients receiving 1.25 mg/m2 per day, EOI CSF concentrations were obtained simultaneously from a VR and LP; the lumbar lactone concentrations were 30% and 49% lower than the ventricular concentrations. During a 24-h and a 72-h CI, the median CSF penetration of topotecan lactone was 0.29 (range 0.10 to 0.59) and 0.42 (range 0.11 to 0.86), respectively. A three-compartment model adequately described topotecan lactone and total concentrations in the plasma and CSF. Topotecan was therefore found to significantly penetrate into the CSF in humans. The pharmacokinetic model presented may be useful in the design of clinical studies of topotecan to treat CNS tumors.

Adolescent↗
PubMed1996

Medulloblastoma with brain stem involvement: the impact of gross total resection on outcome.

We studied the impact of gross total resection on progression-free survival (PFS) and postoperative morbidity in 40 children with locally advanced medulloblastoma characterized by tumor invading the brain stem. These patients represented 40% of children treated for newly diagnosed medulloblastoma at a pediatric oncology center over a 10-year period. All patients underwent aggressive initial surgical resection. Review of surgical and neuroimaging findings documented gross total resection in 13 cases, near-total resection (< 1.5 cm2 residual tumor on imaging) in 14 cases, and subtotal resection (> than 50% resection with > or = 1.5 cm2 residual) in 13 cases. Overall, 85% of patients had a > 90% resection. Subsequent therapy comprised craniospinal irradiation in all cases and chemotherapy on institutional or cooperative group protocols in 35 cases. At a median follow-up of 4 years, postirradiation PFS is 61% (SE = 10%). There was no difference in PFS for patients who underwent gross total resection compared to those with any detectable residual tumor (p > 0.70). The posterior fossa syndrome occurred in 25% of cases, and had no apparent relationship to the extent of resection (p > 0.5, exact test). In this series, true gross total resection was not associated with a PFS advantage when compared to strictly defined near-total and subtotal resection. Although there was no operative mortality, the frequency of the posterior fossa syndrome is of concern and emphasizes the need for careful consideration of the risk/benefit ratio in the surgical approach to this subgroup of patients.

Brain Neoplasms↗
PubMed1996

Response of recurrent medulloblastoma to low-dose oral etoposide.

PURPOSE: The outcome for patients with recurrent medulloblastoma has historically been poor, with most patients dying of disseminated disease. Here, we report on seven patients with recurrent medulloblastoma, most heavily pretreated with a variety of chemotherapeutic agents, including parenteral etoposide (VP-16), who showed responses to the administration of repeated courses of low-dose oral VP-16. PATIENTS AND METHODS: Seven patients age 4 to 16 years were treated with VP-16 after neuroradiographic and clinical evidence of tumor progression. Six had received prior irradiation. All seven had been pretreated with a variety of chemotherapeutic agents and schedules, including parenteral VP-16. VP-16 was administered orally as repeated 21-day courses at 50 mg/m2/d with a 7-day interval between courses. Evaluation consisted of neuroradiographic and clinical examination after completion of every two courses of therapy. Complete blood cell counts were performed weekly. RESULTS: The major toxicity of oral VP-16 was hematologic, with two patients requiring platelet transfusions due to thrombocytopenia and two requiring RBC transfusions. All seven patients developed treatment-related neutropenia. Two patients were supported with granulocyte colony-stimulating factor (G-CSF) between courses. One patient developed infectious epididymitis after course 2 and required intravenous antibiotics; this illness was complicated by Clostridium difficile colitis. There was one episode of fever associated with neutropenia. There were no treatment-related deaths. Of seven patients assessed, six have demonstrated partial responses (PRs) and the remaining patient had stable disease (SD). CONCLUSION: This report demonstrates the activity of oral VP-16 in the treatment of a small cohort of pretreated patients with recurrent medulloblastoma. This form of administration of oral VP-16 was well tolerated and produced modest toxicity.

Administration, Oral↗