18F-DOpA uptake parameters in glioma: Effects of patients’ characteristics and prior treatment history

Objective: In amino acid positron emission tomography brain tumour imaging, tumour-to-background uptake parameters are often used for treatment monitoring. We studied the effects of patients’ characteristics and anticancer treatments on 18F–fluoro-l–phenylalanine uptake of normal brain and tumour lesions, with particular emphasis on temozolomide (TMZ) chemotherapy. Methods: 155 studies from 120 patients with glioma were analysed. Average uptake of normal background (standardized uptake value, SUVbckgr) and basal ganglia (SUVbg), as well as tumour-to-brain ratios (TBR) were compared between positron emission tomography/CT studies acquired before (Group A, n = 48), after (Group B, n = 50) or during (Group C, n = 57) TMZ treatment, using analysis of variance. Results: Overall, mean SUVbckgr and mean SUVbg were 1.06 ± 0.26and 2.12 ± 0.47, respectively. Female had significantly higher SUVbckgr (p = 0.002) and SUVbg (p = 0.012) than male patients. Age showed a positive correlation with SUVbg (p = 0.001). In the overall cohort, there were significant effects of TMZ on SUVbckgr (p = 0.0237) and TBR (p = 0.0138). In particular, SUVbckgr was lower in Group C than in Group B (1.00 ± 0.25 vs 1.14 ± 0.31, p = 0.0173). Significant variations of SUVbckr could be observed in female only. TBR was significantly higher in Group C than in Group B (2.37 ± 0.54 vs 2.06 ± 0.38, p = 0.010). Variations of SUVbg between groups slightly missed significance (p = 0.0504). Conclusion: Temozolomide chemotherapy and patients’ characteristics, including gender and age, affect physiological [18F]–fluoro-l–phenylalanine uptake and, consequently, the calculation of TBRs. Advances in knowledge: For the first time, the effects of past or concurrent temozolomide chemotherapy on brain physiological amino acid uptake have been investigated. Such effects are relevant and should be taken into account when evaluating tumour-to-background ratios

ASSOCIATION OF NEAR-DIPLOID DNA CONTENT AND N-MYC AMPLIFICATION IN NEUROBLASTOMAS

[No abstract available

Prognostic Factors After Relapse in Nonmetastatic Rhabdomyosarcoma: A Nomogram to Better Define Patients Who Can Be Salvaged With Further Therapy

Purpose Previous studies suggest poor outcome in children with relapsed rhabdomyosarcoma (RMS). A better understanding is needed of which patients can be salvaged after first relapse. Patients and Methods The analysis included children with nonmetastatic RMS and embryonal sarcoma enrolled onto the International Society of Paediatric Oncology (SIOP) Malignant Mesenchymal Tumor (MMT) 84, 89, and 95 studies who relapsed after achieving complete local control with primary therapy. All patients included in the analysis had follow-up for >= 3.0 years after the last event. The clinical features, initial treatment characteristics, and features of the relapse were correlated with survival in univariate and multivariate analyses. Results In all, 474 eligible patients were identified for the study. At >= 3.0 years from the last event, 176 (37%) were alive ("cured"). In a full-model multivariate analysis, the factors identified at first relapse that most strongly associated with poor outcome were metastatic relapse (odds ratio [OR], 4.19; 95% CI, 2.0 to 8.5), prior radiotherapy treatment (OR, 3.64; 95% CI, 2.1 to 6.4), initial tumor size > 5 cm (OR, 2.53; 95% CI, 1.5 to 4.1), and time of relapse <18 months from diagnosis (OR, 2.20; 95% CI, 1.3 to 3.6). Unfavorable primary disease site, nodal involvement at diagnosis, alveolar histology, and previous three-or six-drug chemotherapy were also independently associated with poor outcome. To estimate chance of cure for individual patients, a nomogram was developed, which allowed for weighting of these significant factors. Conclusion Some children with relapsed RMS remain curable. It is now possible to estimate the chance of salvage for individual children to direct therapy appropriately toward cure, use of experimental therapies, and/or palliation. J Clin Oncol 29: 1319-1325. (C) 2011 by American Society of Clinical Oncolog

Randomized Comparison of Intensified Six-Drug Versus Standard Three-Drug Chemotherapy for High-Risk Nonmetastatic Rhabdomyosarcoma and Other Chemotherapy-Sensitive Childhood Soft Tissue Sarcomas: Long-Term Results From the International Society of Pediatric Oncology MMT95 Study

Purpose MMT95 was the fourth of a series of International Society of Pediatric Oncology (SIOP) collaborations for children with high-risk nonmetastatic soft tissue sarcoma (STS). The principal objective was to explore survival advantage for an intensified chemotherapy strategy in a randomized trial. Patients and Methods From July 1995 to June 2003, 457 previously untreated patients with incompletely resected embryonal rhabdomyosarcoma (RMS), undifferentiated sarcoma, and soft tissue primitive neuroectodermal tumor at all sites except paratesticular, vagina, and uterus, or with alveolar RMS were randomly assigned to receive either ifosfamide, vincristine, and dactinomycin (IVA) or a six-drug combination (IVA plus carboplatin, epirubicin, and etoposide) both delivered over 27 weeks. Cumulative doses were as follows: ifosfamide 54 g/m(2) (both arms), epirubicin 450 mg/m(2), etoposide 1,350 mg/m(2) (six-drug regimen). Poor responders after three courses of IVA were to be switched to the other arm. Delivery of radiotherapy was determined according to site and/or response to chemotherapy with or without surgery. Results Overall survival (OS) for all patients was 81% (95% CI, 77% to 84%) at 3 years. No significant difference in outcome in either OS or event-free survival was noted between the two arms (3-year OS: 82% [95% CI, 76% to 86%] for IVA and 80% [95% CI, 74% to 85%] for the six-drug arm). Toxicity was significantly greater (infection, myelosuppression, and mucositis) in the six-drug arm. Overall burden of local therapy was consistent with data from previous SIOP studies and showed no difference between the two chemotherapy regimens. Conclusion Intensification of chemotherapy for nonmetastatic RMS and other chemotherapy-sensitive STS provides no survival advantage or reduction in the intensity of local therapy and adds toxicit

Prognostic stratification for children with hepatoblastoma: The SIOPEL experience

Purpose: To identify factors relevant to long-term outcome in newly diagnosed hepatoblastoma, and define subgroups for clinical research on tailoring treatment to the individual patient. Patients and methods: Between 1995 and 2006 the SIOPEL group conducted two clinical trials which established risk-adapted therapy for hepatoblastoma patients. Patients were stratified into high-risk (AFP 1,200,000 ng/mL, patient age, platelet count and histology were further explored. The outcome measure was event-free survival (EFS). Results: In 541 patients, reduced EFS correlated significantly with AFP = 1.2 x 10(6) ng/mL (2.48, 1.47-4.17), metastatic disease (3.02, 2.05-4.44), PRETEXT IV (2.15, 1.19-3.87), multifocality (1.59, 1.01-2.50), age>5 years (2.76, 1.68-4.53); borderline with small cell undifferentiated (SCU) histology (2.29, 95% confidence interval 0.91-5.77); but not with PRETEXT III, age 30-60 months, platelet count or V+/P+/E+. By using the significant factors and SCU to stratify the population, we have identified three distinct prognostic groups: PRETEXT I/II/III, and no other factors, have 3 year EFS of 90%, PRETEXT IV and/or multifocal tumour and/or age > 5 years and/or AFP > 1.2 x 10(6) have 3 year EFS of 71% and SCU and/or AFP <100 ng/mL and/or metastatic have a 3 year EFS of 49%. Conclusion: Prognostic stratification for clinical research on newly diagnosed hepatoblastoma should take into consideration PRETEXT, metastatic disease, AFP, multifocality, age and SCU histology. (C) 2011 Elsevier Ltd. All rights reserve

Successful treatment of childhood high-risk hepatoblastoma with dose-intensive multiagent chemotherapy and surgery: final results of the SIOPEL-3HR study

The primary objective was to determine the efficacy of a newly designed preoperative chemotherapy regimen in an attempt to improve the cure rate of children with high-risk hepatoblastoma

Hepatocellular cardinoma in children : does modified platinum and Doxorubicin based chemotherapy increase tumor resectability and change outcome ? Lessons lerned from the SIOPEL 2 and 3 studies

INTRODUCTION : The aim of this article is to present an experience of two prospective studies from the International Childhood Liver Tumor Strategy Group (SIOPEL 2 [S2] and SIOPEL [S3]) trials and to evaluate whether modified platinum- and doxorubicin-based chemotherapy is capable of increasing tumor resectability and changing patient outcomes. METHODS : Between 1995 and 2006, 20 patients with hepatocellular carcinoma (HCC) were included in the S2 trial and 70 were included in the S3 trial. Eighty-five patients remained evaluable. RESULTS : Response to preoperative chemotherapy was observed in 29 of 72 patients (40%) who did not have primary surgery, whereas 13 patients underwent upfront surgery. Thirty-three patients had a delayed resection. Thirty-nine tumors never became resectable. Complete tumor resection was achieved in 34 patients (40%), including seven of those treated with liver transplantation (LTX). After a median follow-up period of 75 months, 63 patients (74%) had an event (a progression during treatment, a relapse after treatment, or death from any cause). Sixty patients died. Twenty-three of 46 patients (50%) who underwent tumor resection died. Eighteen of 27 patients (63%) with complete tumor resection (without LTX) and 20 of 34 patients (59%) with LTX survived. Only one of seven patients (14%) with microscopically involved margins survived. Overall survival at 5 years was 22%. CONCLUSION : Survival in pediatric HCC is more likely when complete tumor resection can be achieved. Intensification of platinum agents in the S2 and S3 trials has not resulted in improved survival. New treatment approaches in pediatric HCC should be postulated