Biomedical subjects

Sridharan Gururangan

Publications and source records attributed to Sridharan Gururangan.

At least 19 recordsLinked to original sources

PubMed2006

Phase I trial of intrathecal spartaject busulfan in children with neoplastic meningitis: a Pediatric Brain Tumor Consortium Study (PBTC-004).

PURPOSE: A phase I trial of intrathecal Spartaject Busulfan (SuperGen, Inc., San Ramon, CA) was conducted in children with neoplastic meningitis following recurrent primary brain tumors to describe toxicities, estimate the maximum tolerated dose (MTD), and document evidence of responses to this agent. EXPERIMENTAL DESIGN: The continuous reassessment method was used to assign cohorts of patients to doses of intrathecal Spartaject Busulfan via an Ommaya reservoir and/or lumbar puncture twice weekly for 2 weeks followed by an assessment of toxicity and response. Patients with stable disease or an objective response continued to receive intrathecal Spartaject Busulfan plus systemic chemotherapy at regular intervals. Cerebrospinal fluid and blood were obtained for pharmacokinetic studies in patients with Ommaya reservoirs after the first dose of intrathecal Spartaject Busulfan. Seven evaluable patients were assigned to the starting dose of 5 mg, two patients to 7.5 mg, three patients to 10 mg, seven patients to 13 mg, and four patients to 17 mg. RESULTS: Between September 2000 and May 2003, 28 patients were enrolled in this study. Twenty-three patients (median age, 8.8 years; range, 2.5-19.5 years) were evaluable for estimating the MTD, and dose-limiting toxicities were observed in three and included grade 3 vomiting (n = 1 at 5 mg), grade 3 headache (n = 1 at 17 mg), and grade 3 arachnoiditis (n = 1 at 17 mg). Pharmacokinetic data showed that post-infusion concentrations of busulfan ranged from 50 to 150 microg/mL and declined to <1 microg/mL within 5 hours. CONCLUSIONS: Intrathecal Spartaject Busulfan was well tolerated in children with neoplastic meningitis from brain tumors, and the recommended dose for future phase II studies is 13 mg.

Adolescent↗

PubMed2006

Phase 1 trial of gefitinib plus sirolimus in adults with recurrent malignant glioma.

PURPOSE: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gefitinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among patients with recurrent malignant glioma. PATIENTS AND METHODS: Gefitinib and sirolimus were administered on a continuous daily dosing schedule at dose levels that were escalated in successive cohorts of malignant glioma patients at any recurrence who were stratified based on concurrent use of CYP3A-inducing anticonvulsants [enzyme-inducing antiepileptic drugs, (EIAED)]. Pharmacokinetic and archival tumor biomarker data were also assessed. RESULTS: Thirty-four patients with progressive disease after prior radiation therapy and chemotherapy were enrolled, including 29 (85%) with glioblastoma multiforme and 5 (15%) with anaplastic glioma. The MTD was 500 mg of gefitinib plus 5 mg of sirolimus for patients not on EIAEDs and 1,000 mg of gefitinib plus 10 mg of sirolimus for patients on EIAEDs. DLTs included mucositis, diarrhea, rash, thrombocytopenia, and hypertriglyceridemia. Gefitinib exposure was not affected by sirolimus administration but was significantly lowered by concurrent EIAED use. Two patients (6%) achieved a partial radiographic response, and 13 patients (38%) achieved stable disease. CONCLUSION: We show that gefitinib plus sirolimus can be safely coadministered on a continuous, daily dosing schedule, and established the recommended dose level of these agents in combination for future phase 2 clinical trials.

Administration, Oral↗

PubMed2006

Salvage radioimmunotherapy with murine iodine-131-labeled antitenascin monoclonal antibody 81C6 for patients with recurrent primary and metastatic malignant brain tumors: phase II study results.

PURPOSE: To assess the efficacy and toxicity of intraresection cavity iodine-131-labeled murine antitenascin monoclonal antibody 81C6 (131I-m81C6) among recurrent malignant brain tumor patients. PATIENTS AND METHODS: In this phase II trial, 100 mCi of 131I-m81C6 was injected directly into the surgically created resection cavity (SCRC) of 43 patients with recurrent malignant glioma (glioblastoma multiforme [GBM], n = 33; anaplastic astrocytoma [AA], n = 6; anaplastic oligodendroglioma [AO], n = 2; gliosarcoma [GS], n = 1; and metastatic adenocarcinoma, n = 1) followed by chemotherapy. RESULTS: With a median follow-up of 172 weeks, 63% and 59% of patients with GBM/GS and AA/AO tumors were alive at 1 year. Median overall survival for patients with GBM/GS and AA/AO tumors was 64 and 99 weeks, respectively. Ten patients (23%) developed acute hematologic toxicity. Five patients (12%) developed acute reversible neurotoxicity. One patient (2%) developed irreversible neurotoxicity. No patients required reoperation for radionecrosis. CONCLUSION: In this single-institution phase II study, administration of 100 mCi of 131I-m81C6 to recurrent malignant glioma patients followed by chemotherapy is associated with a median survival that is greater than that of historical controls treated with surgery plus iodine-125 brachytherapy. Furthermore, toxicity was acceptable. Administration of a fixed millicurie dose resulted in a wide range of absorbed radiation doses to the SCRC. We are now conducting a phase II trial, approved by the US Food and Drug Administration, using patient-specific 131I-m81C6 dosing, to deliver 44 Gy to the SCRC followed by standardized chemotherapy. A phase III multicenter trial with patient-specific dosing is planned.

Adult↗

PubMed2006

Incidence and patterns of neuraxis metastases in children with diffuse pontine glioma.

PURPOSE: We performed a retrospective study of patients with diffuse pontine glioma (DPG) who suffered neuraxis metastasis (NM) and characterized the incidence, clinical features, radiologic findings, and patterns of disease dissemination. METHODS: Magnetic resonance imaging (MRI) of brain and spine was used to assess NM. Some patients also underwent magnetic resonance spectroscopy (MRS) (6 patients) and fluorodeoxyglucose positron emission tomography (FDG-PET) scans (13 patients) to further evaluate areas of metastatic disease. Three patients had histologic confirmation of disease at the site of NM. RESULTS: Between 1986 and 2003, 18 of 96 patients (17.3%) with DPG developed NM. The median age at diagnosis was 8 years (range, 4-17). All patients had adjuvant chemotherapy and/or focal radiotherapy at diagnosis. The NM occurred at a median of 15 months from diagnosis of DPG (range, 3-96). Three patterns of NM were seen on MRI of brain and spine in these patients; 8 (39%) had parenchymal (PM), 4 (22%) leptomeningeal (PM), 2 (11%) subependymal, and in 5 a combination of two or more patterns. The MRS and FDG-PET scan of suspected areas of metastatic disease was consistent with tumor in 6 of 6 and 12 of 13 patients who underwent these procedures respectively. Three patients also had histologic confirmation of malignant glioma at the site of NM. Despite salvage therapy, all 18 patients have died of disease at a median of 5 months (range, 0.5-20) from diagnosis of neuraxis spread. CONCLUSION: Our study emphasizes the need for screening patients with DPG for NM at the time of recurrence.

Adolescent↗

PubMed2006

Novel human IgG2b/murine chimeric antitenascin monoclonal antibody construct radiolabeled with 131I and administered into the surgically created resection cavity of patients with malignant glioma: phase I trial results.

UNLABELLED: Results from animal experiments have shown that human IgG2/mouse chimeric antitenascin 81C6 (ch81C6) monoclonal antibody exhibited higher tumor accumulation and enhanced stability compared with its murine parent. Our objective was to determine the effect of these differences on the maximum tolerated dose (MTD), pharmacokinetics, dosimetry, and antitumor activity of (131)I-ch81C6 administered into the surgically created resection cavity (SCRC) of malignant glioma patients. METHODS: In this phase I trial, eligible patients received a single injection of (131)I-ch81C6 administered through a Rickham catheter into the SCRC. Patients were stratified as newly diagnosed and untreated (stratum A), newly diagnosed after external beam radiotherapy (XRT) (stratum B), and recurrent (stratum C). (131)I-ch81C6 was administered either before (stratum A) or after (stratum B) conventional XRT for newly diagnosed patients. In addition, chemotherapy was prescribed for all patients after (131)I-ch81C6 administration. Dose escalation was performed independently for each stratum. Patients were observed for toxicity and response until death or progressive disease. RESULTS: We treated 47 patients with (131)I-ch81C6 doses up to 4.44 GBq (120 mCi), including 35 with newly diagnosed tumors (strata A and B) and 12 with recurrent disease (stratum C). Dose-limiting hematologic toxicity defined the MTD to be 2.96 GBq (80 mCi) for all patients, regardless of treatment strata. Neurologic dose-limiting toxicity developed in 3 patients; however, none required further surgery to debulk radiation necrosis. Median survival was 88.6 wk and 65.0 wk for newly diagnosed and recurrent patients, respectively. CONCLUSION: The MTD of (131)I-ch81C6 is 2.96 GBq (80 mCi) because of dose-limiting hematologic toxicity. Although encouraging survival was observed, (131)I-ch81C6 was associated with greater hematologic toxicity, probably due to the enhanced stability of the IgG2 construct, than previously observed with (131)I-murine 81C6.

Adult↗

PubMed2005

Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.

PURPOSE: We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). PATIENTS AND METHODS: Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). RESULTS: Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. CONCLUSION: Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

Administration, Oral↗

PubMed2005

Phase I trial of irinotecan plus temozolomide in adults with recurrent malignant glioma.

BACKGROUND: The authors determined the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of irinotecan (CPT-11), a topoisomerase I inhibitor, when administered with temozolomide among patients with recurrent malignant glioma (MG). METHODS: Patients with MG at any recurrence received temozolomide (TMZ) at a dose of 200 mg/m(2)/day on Days 1-5 plus CPT-11 administered as a 90-minute intravenous infusion during Weeks 1, 2, 4, and 5 of each 6-week cycle. Patients were stratified based on concurrent administration of CYP3A4-inducing anticonvulsants (enzyme-inducing antiepileptic drugs [EIAEDs]). The CPT-11 dose was escalated in successive cohorts of patients independently for each stratum. RESULTS: CPT-11, at doses ranging from 40 mg/m(2) to 375 mg/m(2), was administered with TMZ to 107 patients. Ninety-one patients (85%) had recurrent glioblastoma multiforme (GBM) and 16 (15%) had recurrent anaplastic glioma. Sixty-eight patients (64%) were given EIAEDs. The MTD of CPT-11 for patients concurrently receiving and not receiving EIAEDs was 325 mg/m(2) and 125 mg/m(2), respectively. The DLTs were hematologic, gastrointestinal, and hepatic. Fifteen patients (14%) achieved either a radiographic complete (n = 5) or partial (n = 10) response across a wide range of CPT-11 dose levels. Patients with recurrent GBM who achieved radiographic response had a median time to disease progression of 54.9 weeks. CONCLUSIONS: The current study built on preclinical observations designed to increase the clinical activity of topoisomerase I inhibitors. CPT-11, administered at full dose levels, was well tolerated in combination with TMZ. Furthermore, durable responses were observed in this recurrent population. Ongoing Phase II studies will evaluate the efficacy of this regimen and its application to other malignancies.

Adult↗

PubMed2005

Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.

PURPOSE: We conducted a two-phase clinical trial in patients with progressive malignant glioma (MG). The first phase of this trial was designed to determine the dose of O6-BG effective in producing complete depletion of tumor AGT activity for 48 hours. The second phase of the trial was designed to define the maximum tolerated dose (MTD) of a single dose of temozolomide when combined with O6-BG. In addition, plasma concentrations of O6-BG and O6-benzyl-8-oxoguanine were evaluated after O6-BG. PATIENTS AND METHODS: For our first phase of the clinical trial, patients were scheduled to undergo craniotomy for AGT determination after receiving a 1-hour O6-BG infusion at 120 mg/m2 followed by a continuous infusion at an initial dose of 30 mg/m2/d for 48 hours. The dose of the continuous infusion of O6-BG escalated until tumor AGT was depleted. Once the O6-BG dose was established a separate group of patients was enrolled in the second phase of clinical trial, in which temozolomide, administered as a single dose at the end of the 1-hour O6-BG infusion, was escalated until the MTD was determined. RESULTS: The O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. On enrolling 38 patients in six dose levels of temozolomide, the MTD was established at 472 mg/m2 with dose-limiting toxicities limited to myelosuppression. CONCLUSION: This study provides the foundation for a phase II trial of O6-BG plus temozolomide in temozolomide-resistant MG.

Adult↗

PubMed2005

Chemotherapy and novel therapeutic approaches in malignant glioma.

Glial neoplasms represent 0.5-1% of all cancers in most Western countries. Malignant gliomas are among the most devastating cancers, leading to death in most cases. They present unique challenges due to their location, aggressive biological behavior and diffuse infiltrative growth. Notwithstanding the development of new surgical and radiation techniques in the last thirty years, a cure for malignant gliomas remains elusive. In this article, we will review the standard and new therapies used for malignant gliomas. As standard therapies, surgery, radiation therapy and systemic chemotherapy, are in a continuous process of evolution. Multiple chemotherapies have been used in malignant gliomas, as single agents, in combination, or with different modes of administration, including high-dose chemotherapy with stem cell rescue and intra-arterial chemotherapy. The last decade has been noticeable for the advent of a better understanding of the biology of malignant gliomas. This has stimulated active research in multiples areas and the advent of new treatment strategies. Techniques to circumvent the resistance mechanisms to chemotherapy have been evaluated, tyrosine kinase inhibitors have shown activity in malignant primary brain tumors and radioimmunotherapy remains an area of active research. In this article, we review the past, present and future treatments of malignant gliomas with a special interest on chemotherapy, resistance mechanisms and tyrosine kinase inhibitors.

Antineoplastic Agents↗

PubMed2005

Phase II trial of irinotecan plus celecoxib in adults with recurrent malignant glioma.

BACKGROUND: In the current study, the authors report a Phase II trial of irinotecan (CPT-11), a topoisomerase I inhibitor active against malignant glioma (MG), with celecoxib, a selective COX-2 inhibitor, among MG patients with recurrent disease. METHODS: Patients with MG at any type of recurrence received CPT-11, administered as a 90-minute intravenous infusion on Weeks 1, 2, 4, and 5 of each 6-week cycle plus celecoxib, which was administered continuously at a dose of 400 mg twice a day. CPT-11 was given at a dose of 350 mg/m(2) for patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) and at a dose of 125 mg/m(2) for those patients not receiving EIAEDs. Assessments were performed after every cycle. The primary endpoint was radiographic response and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and therapeutic safety. RESULTS: Thirty-four of the 37 patients enrolled in the current study (92%) were diagnosed with recurrent GBM and 3 patients (8%) were diagnosed with recurrent anaplastic astrocytoma (AA). Twenty-one patients were receiving EIAEDs and 16 patients were not. The median follow-up time was 76.9 weeks. Concomitant CPT-11 plus celecoxib was found to be well tolerated and safe. Hematologic toxicities of >/= Grade 3 (according the second version of the Common Toxicity Criteria of the National Cancer Institute) reportedly complicated 8.6% of treatment courses. Grade 3 diarrhea, the most commonly reported nonhematologic toxicity, occurred with equal frequency (8%), regardless of whether the patient was receiving EIAED. Six patients (16%), all whom were diagnosed with recurrent GBM, achieved an objective radiographic response whereas an additional 13 patients (35%) achieved stable disease. The median PFS was 11.0 weeks and the 6-month PFS was reported to be 25.1%. The median OS was 31.5 weeks. CONCLUSIONS: The results of the current study confirm that CPT-11 plus celecoxib can be safely administered concurrently at full dose levels, and that this regimen has encouraging activity among heavily pretreated patients with recurrent MG.

Adult↗

PubMed2005

Intracranial Ewing sarcoma.

The occurrence of primary extraosseous Ewing sarcoma (EES) of the central nervous system (CNS) has only rarely been reported in the literature. It is important to distinguish this entity from the more common central primitive neuroectodermal tumor (PNET) of brain, since the management of these tumors is different from that of EES. We present the clinical, radiologic, and pathologic features of two cases of EES occurring in the brain. The diagnosis was further confirmed by detection of a rearrangement of the FLI1 and/or EWS gene loci in tumors from both patients using fluorescent in situ hybridization (FISH). Although rare, the possibility of EES should be considered particularly when tumors that arise near the meningeal surface of the brain and have the pathologic appearance of a PNET. Demonstration of t(11;22)(q24;q12) by molecular analysis essentially confirms the diagnosis and enables the oncologist to choose appropriate therapy.

Brain Neoplasms↗

PubMed2004

Short-term efficacy of methylphenidate: a randomized, double-blind, placebo-controlled trial among survivors of childhood cancer.

PURPOSE: Children surviving acute lymphoblastic leukemia (ALL) and malignant brain tumors (BTs) have a higher incidence of attention and learning problems in school than do their healthy peers. The present study tests the hypothesis that the psychostimulant methylphenidate (MPH) improves cognitive and social functioning among these patients. PATIENTS AND METHODS: We report on 83 long-term survivors of ALL and BT identified as having attentional deficits on behavioral testing and parent or teacher report, and problems with academic achievement. The 47 male and 36 female patients ranged from 0.6 to 14.3 years (median, 5.4 years) of age at diagnosis and 6.7 to 17.9 years (median, 11.9 years) of age at participation. The patients (40 ALL, 43 BT) participated in a randomized, double-blind, 3-week home cross-over trial of placebo (bid), low-dose MPH (0.3 mg/kg; maximum dose, 10 mg bid), and moderate-dose MPH (0.6 mg/kg; maximum dose, 20 mg bid). The primary end points were weekly teacher and parent reports on the Conners' Rating Scales and Social Skills Rating System. RESULTS: Compared to placebo, significant improvement with MPH was reported by teachers and parents on the Conners' Rating Scales and by teachers on the Social Skills Rating System. However, no consistent advantage of moderate dose over low dose was observed. Of those participating, 66 (79.5%) of the 83 patients continued on best clinical management. CONCLUSION: Treatment with MPH can at least temporarily reduce some attentional and social deficits among survivors of childhood ALL and BT. Long-term follow-up will reveal those subsets of patients who are more likely to benefit from MPH.

Adolescent↗

PubMed2004

Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma.

In preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, plus CPT-11 (irinotecan) exhibits schedule-dependent, synergistic activity against malignant glioma (MG). We previously established the maximum tolerated dose of CPT-11 when administered for 4 consecutive weeks in combination with BCNU administered on the first day of each 6-week cycle. We now report a phase 2 trial of BCNU plus CPT-11 for patients with MG. In the current study, BCNU (100 mg/m2) was administered on day 1 of each 6-week cycle. CPT-11 was administered on days 1, 8, 15, and 22 at 225 mg/m2 for patients receiving CYP3A1- or CYP3A4-inducing anticonvulsants and at 125 mg/m2 for those not on these medications. Newly diagnosed patients received up to 3 cycles before radiotherapy, while recurrent patients received up to 8 cycles. The primary end point of this study was radiographic response, while time to progression and overall survival were also assessed. Seventy-six patients were treated, including 37 with newly diagnosed tumors and 39 with recurrent disease. Fifty-six had glioblastoma multiforme, 18 had anaplastic astrocytoma, and 2 had anaplastic oligodendroglioma. Toxicities (grade > or =3) included infections (13%), thromboses (12%), diarrhea (10%), and neutropenia (7%). Interstitial pneumonitis developed in 4 patients. Five newly diagnosed patients (14%; 95% CI, 5%-29%) achieved a radiographic response (1 complete response and 4 partial responses). Five patients with recurrent MG also achieved a response (1 complete response and 4 partial responses; 13%; 95% CI, 4%-27%). More than 40% of both newly diagnosed and recurrent patients achieved stable disease. Median time to progression was 11.3 weeks for recurrent glioblastoma multiforme patients and 16.9 weeks for recurrent anaplastic astrocytoma/ anaplastic oligodendroglioma patients. We conclude that the activity of BCNU plus CPT-11 for patients with MG appears comparable to that of CPT-11 alone and may be more toxic.

Adult↗

PubMed2004

Phase 1 trial of irinotecan plus BCNU in patients with progressive or recurrent malignant glioma.

Irinotecan is a topoisomerase I inhibitor previously shown to be active in the treatment of malignant glioma. We now report the results of a phase 1 trial of irinotecan plus BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, for patients with recurrent or progressive MG. Irinotecan dose escalation occurred independently within 2 strata: patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) and patients not receiving EIAEDs. BCNU was administered at a dose of 100 mg/m2 over 1 h every 6 weeks on the same day as the first irinotecan dose was administered. Irinotecan was administered intravenously over 90 min once weekly. Treatment cycles consisted of 4 weekly administrations of irinotecan followed by a 2-week rest with dose escalation in cohorts of 3 to 6 patients. Seventy-three patients were treated, including 49 patients who were on EIAEDs and 24 who were not on EIAEDs. The maximum tolerated dose for patients not on EIAEDs was 125 mg/m2. The maximum tolerated dose for patients on EIAEDs was 225 mg/m2. Dose-limiting toxicity was evenly distributed among the following organ systems: pulmonary, gastrointestinal, cardiovascular, neurologic, infectious, and hematologic, without a clear predominance of toxicity involving any one organ system. There was no evidence of increasing incidence of toxicity involving one organ system as irinotecan dose was escalated. On the basis of these results, we conclude that the recommended doses of irinotecan for a phase 2 clinical trial when given in combination with BCNU (100 mg/m2) are 225 mg/m2 for patients on EIAEDs and 125 mg/m2 for patients not on EIAEDs.

Adult↗

PubMed2004

[18F]fluorodeoxyglucose-positron emission tomography in patients with medulloblastoma.

OBJECTIVE: We evaluated the [(18)F]fluorodeoxyglucose (FDG) accumulation during positron emission tomography (PET) in patients with medulloblastoma and examined the relationship of intensity of uptake with patient outcome after the initial scan. METHODS: Magnetic resonance imaging and FDG-PET scans of brain and spine were used to assess FDG uptake by visual grade (qualitative analysis) and metabolic activity ratios (T(max)/G(mean) and T(max)/W(mean)). Patients were divided into two groups based on either confirmation of tumor by biopsy and/or death resulting from progressive disease after the initial FDG-PET scan (Group A) or no intervention for the suspected lesion shown on magnetic resonance imaging after the initial FDG-PET scan but currently alive without evidence of disease (Group B). RESULTS: Twenty-two patients with either recurrent (n = 21) or newly diagnosed (n = 1) medulloblastoma underwent brain (n = 18) or whole-body (n = 4) FDG-PET scans after magnetic resonance imaging evidence of suspected tumor. The median qualitative analysis was 3 (range, 0-4) in 17 Group A patients compared with 0 (range, 0-1) in 5 Group B patients (P = 0.0003). The mean T(max)/G(mean) and T(max)/W(mean) ratios for 16 Group A patients were 1.3 (range, 0.1-3.8) and 2.10 (range, 0.4-5.2), respectively, compared with 0.80 (range, 0.20-1.5) and 1.3 (range, 0.5-1.9) in 5 Group B patients (P = 0.2 for both parameters, not significant). There was a significant negative correlation between increased FDG uptake and survival. Higher qualitative analysis and T(max)/W(mean) were associated with significantly poorer 2-year overall survival after the initial scan (71% versus 15% for qualitative analysis grade of <3 versus > or =3, P = 0.001; 46% versus 0% for T(max)/W(mean) < or =2.5 versus >2.5, P = 0.004). CONCLUSION: Increased FDG uptake is observed in medulloblastoma and is correlated negatively with survival.

Adolescent↗

PubMed2004

Trilateral retinoblastoma: clinical and radiologic progression.

OBJECTIVE: The purpose of this study was to assess the clinical and radiologic features of tumor progression in children with trilateral retinoblastoma. MATERIALS AND METHODS: Clinical records of eight children with trilateral retinoblastoma were reviewed for the patient's age at the time of diagnosis of the ocular tumor, time interval from diagnosis of ocular retinoblastoma to discovery of the intracranial tumor, time interval from diagnosis of retinoblastoma to death, and time interval from diagnosis of the intracranial tumor to death. CT or MRI studies were reviewed for the appearance of the primary intracranial neoplasm, intracranial metastases, and spinal metastases. RESULTS: The mean age of the patients at diagnosis of bilateral retinoblastoma was 4.5 months, and the mean age at diagnosis of the intracranial midline tumor was 26 months. The mean interval from the time of diagnosis of retinoblastoma to discovery of the intracranial tumor was 21.5 months. Two children had spinal leptomeningeal metastases at the time of discovery of the midline intracranial mass although no intracranial metastases were seen on imaging. In the other children, intracranial and spinal leptomeningeal metastases frequently developed within months of the diagnosis of retinoblastoma despite lack of progression in the midline intracranial lesion. Six children died of leptomeningeal spread of tumor. The mean interval from diagnosis of the ocular tumor to death was 46 months and from diagnosis of the intracranial tumor to death was 17 months. One child developed metastatic retinoblastoma in the ulna 10 years after the diagnosis of the intracranial tumor. CONCLUSION: Children typically died of leptomeningeal tumor dissemination despite lack of progression in the midline intracranial mass. Effective treatment of trilateral retinoblastoma may require close evaluation of these children for leptomeningeal dissemination.

Brain Neoplasms↗

PubMed2003

High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas.

PURPOSE: We evaluated the usefulness of a treatment regimen that included high-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) in patients with newly diagnosed pineoblastoma (PBL). PATIENTS AND METHODS: Twelve patients with PBL were initially treated with surgery and induction chemotherapy. All but two patients underwent radiotherapy. Subsequently, all patients received HDC using cyclophosphamide (CTX) + melphalan (MEL) or busulfan (Bu) + MEL regimens and ASCR. RESULTS: A total of six children and six adults with median ages of 4.2 (range, 0.3 to 19.8 years) and 23 years (range, 23 to 43.7 years), respectively, were treated according to this strategy. Four patients had metastatic disease confined to the neuraxis. Five of 12 patients (42%) had a complete tumor resection at diagnosis. Ten patients received radiotherapy at median doses of 36.0 and 59.4 Gy to the neuraxis and pineal region, respectively. Eleven patients received HDC with CTX + MEL, and one patient received BU + MEL followed by ASCR. Nine patients are alive with no evidence of disease recurrence at a median of 62 months from diagnosis (range, 28 to 125 months), including three patients with metastatic disease and two infants who did not receive any radiotherapy. Three patients have died of progressive disease at 19, 32, and 37 months from diagnosis, respectively. The actuarial 4-year progression-free and overall survivals are 69% (95% confidence interval [CI], 39% to 99%) and 71% (95% CI, 43% to 99%), respectively. CONCLUSION: The use of HDC in addition to radiotherapy seems to be an effective treatment for patients with newly diagnosed pineoblastoma.

Adolescent↗

PubMed2003

Phase II trial of temozolomide in patients with progressive low-grade glioma.

PURPOSE: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma. PATIENTS AND METHODS: Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m(2)/d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity. RESULTS: Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to infinity months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced > or = grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death. CONCLUSION: Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.

Adolescent↗