Evaluation of semi-quantitative scoring system for metaiodobenzylguanidine (mIBG) scans in patients with relapsed neuroblastoma

Background The purpose of this study was to determine the accuracy of two semi-quantitative scoring systems to assess response to 131 I-metaiodobenzylguanidine (mIBG) therapy in recurrent neuroblastoma. Procedures Diagnostic mIBG scan pairs (n = 57) were collected for patients who underwent 131 I-mIBG therapy for relapsed neuroblastoma. Two scoring systems were designated: Method 1, which divided the body into nine segments to view osteomedullary lesions with an additional tenth segment to assess soft tissue involvement; and Method 2, which divided the body into seven segments without a corresponding compartment for soft tissue involvement. Four nuclear medicine physicians independently assigned extension and intensity scores utilizing both methods, and separately recorded their impression of whether the post-therapy scan had improved, not changed, or worsened. Inter- and intra-observer concordance and correlation with overall response and progression-free survival (PFS) were performed. Results Method 1 produced the highest inter-observer concordance and was used to calculate the relative extension scores (post-therapy score divided by pre-therapy score), which correlated significantly with overall response. Patients who achieved complete response (CR) or partial response (PR) (n = 21) had lower relative extension scores, compared to those without response ( P  5. Relative extension score did not predict PFS. Conclusion Semi-quantitative scoring of mIBG scans provides a more reliable method of assessing response in patients with relapsed neuroblastoma than qualitative impression. The reproducibility and high inter-observer concordance makes mIBG score an important component of overall response criteria in patients with recurrent neuroblastoma. Pediatr Blood Cancer © 2006 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55847/1/20777_ftp.pd

SIOP CNS GCT 96: final report of outcome of a prospective, multinational nonrandomized trial for children and adults with intracranial germinoma, comparing craniospinal irradiation alone with chemotherapy followed by focal primary site irradiation for patients with localized disease.

We conducted a nonrandomized international study for intracranial germinoma that compared chemotherapy followed by local radiotherapy with reduced-dose craniospinal irradiation (CSI) alone, to determine whether the combined treatment regimen produced equivalent outcome and avoided irradiation beyond the primary tumor site(s). Patients with localized germinoma received either CSI or 2 courses of carboplatin and etoposide alternating with etoposide and ifosfamide, followed by local radiotherapy. Metastatic patients received CSI with focal boosts to primary tumor and metastatic sites, with the option to be preceded with chemotherapy. Patients with localized germinoma (n 190) received either CSI alone (n 125) or combined therapy (n 65), demonstrating no differences in 5-year event-free or overall survival, but a difference in progression-free survival (0.97 0.02 vs 0.88 0.04; P .04). Seven of 65 patients receiving combined treatment experienced relapse (6 with ventricular recurrence outside the primary radiotherapy field), and only 4 of 125 patients treated with CSI alone experienced relapse (all at the primary tumor site). Metastatic patients (n 45) had 0.98 0.023 event-free and overall survival. Localized germinoma can be treated with reduced dose CSI alone or with chemotherapy and reduced-field radiotherapy. The pattern of relapse suggests inclusion of ventricles in the radiation field. Reduced-dose craniospinal radiation alone is effective in metastatic disease

Is neuroblastoma screening evaluation needed and feasible?

Despite the five million children who have been screened for neuroblastoma in Japan through detection of catecholamine metabolites, it is still uncertain whether screening for this disease is beneficial. The Japanese study has clearly indicated that screening at 6 months or earlier leads to heavy overdiagnosis. It is shown in this paper that screening at a later age may give the same reduction in mortality with possibly less overdiagnosis. However, it is estimated that, even with two screens at 12 and 18 months, the reduction in mortality would not greatly exceed 25%, under realistic hypotheses on the length of the preclinical phase of the disease. The evaluation of the efficacy of this screening strategy would need the recruitment of half a million children per year over 5-7 years and the follow-up of an equal number of controls. Such a trial would improve our knowledge of the natural history of the disease and might help to answer some questions raised recently regarding its biological heterogeneity

Phase I trial and pharmacological study of a 3-hour paclitaxel infusion in children with refractory solid tumours: a SFOP study

The maximum tolerated dose of paclitaxel administered by 24-hour continuous infusion in children is known. Short infusion might offer equivalent antitumour efficacy and reduced haematological toxicity, without increasing the allergic risk. Our aims were to determine the maximum tolerated dose and the pharmacokinetics of paclitaxel in children when administered in 3-h infusion every 3 weeks. Patients older than 6 months, younger than 20 years with refractory malignant solid tumours were eligible when they satisfied standard haematological, renal, hepatic and cardiologic inclusion criteria with life expectancy exceeding 8 weeks. Paclitaxel was administered as a 3-hour infusion after premedication (dexamethasone, dexchlorpheniramine). Pharmacokinetic analysis and solvent assays (ethanol, cremophor) were performed during the first course. 20 courses were studied in 17 patients; 4 dosage levels were investigated (240 to 420 mg/m2). No dose-limiting haematological toxicity was observed. Severe acute neurological and allergic toxicity was encountered. One treatment-related death occurred just after the infusion at the highest dosage. Delayed peripheral neurotoxicity and moderate allergic reactions were also encountered. Pharmacokinetic analysis showed dose-dependent clearance of paclitaxel and elevated blood ethanol and Cremophor EL levels. Although no limiting haematological toxicity was reached, we do not recommend this paclitaxel schedule in children because of its acute neurological toxicity. © 2001 Cancer Research Campaign http://www.bjcancer.co

Desmoplastic small round cell tumor of the stomach mimicking a gastric cancer in a child

Intra-abdominal desmoplastic small round cell tumor (DSRCT) is a highly malignant tumor of uncertain histogenesis. Here we report a case of DSRCT involving the stomach, initially misdiagnosed as gastric cancer. A 12-year-old boy presented with upper abdominal pain developed 1 month prior. On gastroscopy, a 7-cm mass was noted involving the esophago-gastric junction to the fundus, and positron emission tomography showed multiple hot uptakes suggesting distant metastasis. Gastroscopic biopsy showed poorly differentiated malignant cells. We diagnosed as stage IV gastric cancer and treated with 6 cycles of chemotherapy. Laparotomy revealed a huge gastric mass along with peritoneal disseminations. Palliative proximal gastrectomy was performed. Pathological examination revealed transmural involvement of DSRCT, and t(11;22)(p12;q12) was demonstrated on fluorescence in situ hybridization test. The chemotherapeutic regimen was changed and the patient underwent 8 additional cycles of post-operative chemotherapy. The patient is now alive and the residual tumor shows no significant changes after chemotherapy

Rare Primary Central Nervous System Tumors in Adults: An Overview

Overall, tumors of primary central nervous system (CNS) are quite common in adults with an incidence rate close to 30 new cases/100,000 inhabitants per year. Significant clinical and biological advances have been accomplished in the most common adult primary CNS tumors (i.e., diffuse gliomas). However, most CNS tumor subtypes are rare with an incidence rate below the threshold defining rare disease of 6.0 new cases/100,000 inhabitants per year. Close to 150 entities of primary CNS tumors have now been identified by the novel integrated histomolecular classification published by the World Health Organization (WHO) and its updates by the c-IMPACT NOW consortium (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy). While these entities can be better classified into smaller groups either by their histomolecular features and/or by their location, assessing their treatment by clinical trials and improving the survival of patients remain challenging. Despite these tumors are rare, research, and advances remain slower compared to diffuse gliomas for instance. In some cases (i.e., ependymoma, medulloblastoma) the understanding is high because single or few driver mutations have been defined. The European Union has launched European Reference Networks (ERNs) dedicated to support advances on the clinical side of rare diseases including rare cancers. The ERN for rare solid adult tumors is termed EURACAN. Within EURACAN, Domain 10 brings together the European patient advocacy groups (ePAGs) and physicians dedicated to improving outcomes in rare primary CNS tumors and also aims at supporting research, care and teaching in the field. In this review, we discuss the relevant biological and clinical characteristics, clinical management of patients, and research directions for the following types of rare primary CNS tumors: medulloblastoma, pineal region tumors, glioneuronal and rare glial tumors, ependymal tumors, grade III meningioma and mesenchymal tumors, primary central nervous system lymphoma, germ cell tumors, spinal cord tumors and rare pituitary tumors

Comparison of 123 I-metaiodobenzylguanidine (MIBG) and 131 I-MIBG semi-quantitative scores in predicting survival in patients with stage 4 neuroblastoma: A report from the Children's Oncology Group

Background 123 I-metaiodobenzylguanidine (MIBG) scans are preferable to 131 I-MIBG for neuroblastoma imaging as they deliver less patient radiation yet have greater sensitivity in disease detection. Both 123 I-MIBG and 131 I-MIBG scans were used for disease assessments of neuroblastoma patients enrolled on Children's Oncology Group (COG) high-risk study A3973. The hypothesis was that 123 I-MIBG and 131 I-MIBG scans were sufficiently similar for clinical purposes in terms of ability to predict survival. Procedure Patients enrolled on COG A3973 with stage 4 disease who completed 123 I-MIBG or 131 I-MIBG scans at diagnosis, post-induction, post-transplant, or post-biotherapy were analyzed. The performance of the Curie score for each MIBG scan type in predicting survival was evaluated. At each time point, survival curves for 123 I-MIBG versus 131 I-MIBG were compared using the log-rank test. Results Of the 413 patients on A3973 with at least one MIBG scan, 350 were stage 4. The 5-year event-free survival (EFS) and overall survival (OS) rates were 33.4 ± 3.6% and 45.6 ± 4.0% (N = 350). At post-induction, EFS ( P  = 0.3501) and OS ( P  = 0.5337) for 123 I-MIBG versus 131 I-MIBG were not significantly different. Similarly, comparisons at the three other time points were non-significant. Conclusions We found no evidence of a statistically significant difference in outcome by type of scan. For future survival analyses of MIBG Curie scores, 123 I-MIBG and 131 I-MIBG results may be combined and analyzed overall, without adjustment for scan type. Pediatr Blood Cancer 2011;56:1041–1045. © 2011 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83739/1/22991_ftp.pd

European Organization for Research and Treatment of Cancer (EORTC) open label phase II study on glufosfamide administered as a 60-minute infusion every 3 weeks in recurrent glioblastoma multiforme

Background: Glufosfamide is a new alkylating agent in which the active metabolite of isophosphoramide mustard is covalently linked to β-d-glucose to target the glucose transporter system and increase intracellular uptake in tumor cells. We investigated this drug in a multicenter prospective phase II trial in recurrent glioblastoma multiforme (GBM). Patients and methods: Eligible patients had recurrent GBM following surgery, radiotherapy and no more than one prior line of chemotherapy. Patients were treated with glufosfamide 5000 mg/m2 administered as a 1-h intravenous infusion. Treatment success was defined as patients with either an objective response according to Macdonald's criteria or 6 months progression-free survival. Toxicity was assessed with the Common Toxicity Criteria (CTC) version 2.0. Results: Thirty-one eligible patients were included. Toxicity was modest, the main clinically relevant toxicities being leukopenia (CTC grade >3 in five patients) and hepatotoxicity (in three patients). No responses were observed; one patient (3%; 95% confidence interval 0 to 17%) was free from progression at 6 months. Pharmacokinetic analysis showed a 15% decrease in area under the curve and glufosfamide clearance in patients treated with enzyme-inducing antiepileptic drugs, but no effect of these drugs on maximum concentration and plasma half-life. Conclusion: Glufosfamide did not show significant clinical antitumor activity in patients with recurrent GB