Search

Summary: Primary heart tumors are uncommon in children. The majority of them are benign, with only 10% malignant. Among malignant cardiac tumors, sarcoma (rhabdomyosarcoma, angiosarcoma, synovial sarcoma) and lymphoma (Burkitt''s lymphoma, large B-cell lymphoma, lymphoblastic lymphoma) predominate. There are few published pediatric series on malignant primary cardiac tumors. We report here 3 observations of primary malignant cardiac tumors, 2 cases of sarcoma (angiosarcoma and synovial sarcoma) and 1 case of Burkitt''s lymphoma. A precise pathological diagnosis is necessary for the proper management of these patients. For sarcoma, treatment associates surgery and chemotherapy. Surgery should be as complete as possible because of the lack of chemotherapy sensitivity of some sarcomas, mainly angiosarcoma and synovial sarcoma. Therefore, the prognosis of cardiac sarcoma remains poor. For primary cardiac lymphoma, management should not be different from lymphoma in other locations. Chemotherapy is the main treatment, and surgery has to be used only when complications occur. Prognosis depends on histology and not lymphoma location, and so is better than the prognosis for sarcoma. [Copyright &y& Elsevier]

Multidisciplinary health care is necessary to cure patients with Ewing’s sarcoma, which is the second most common primary bone malignancy in children and adolescents. Chemotherapy in association with local therapy can cure from 5% to 65-70% of patients with localized tumors. The choice of surgery has been increasingly made over the years in order to improve local control, and to limit radiation therapy. Radiotherapy remains crucial, either for non-operable tumors or in addition to surgery. Prognostic factors have been identified to tailor the chemotherapy according to the seriousness of the disease. Prognosis of metastatic diseases remains poor and requires evaluating innovative approaches. [ABSTRACT FROM AUTHOR]

Purpose: (1) To improve survival rates in patients with Ewing's sarcoma (ES) or peripheral neuroectodermal tumours (PNET) using semi-continuous chemotherapy and aiming to peform surgery in all; (2) To identify early prognostic factors to tailor therapy for future studies. Patients and methods One hundred and forty-one patients were entered onto the trial between January 1988 and December 1991. Induction therapy consisted of five courses of Cytoxan, 150 mg/m[SUP2] × 7 days, followed by Doxorubicin, 35 mg/m[SUP2] i.v on day 8 given at short intervals. Surgery was recommended whenever possible. The delivery of radiation therapy was based on the quality of resection and the histological response to CT. Maintenance chemotherapy consisted of vincristine + actinomycin and cytoxan + doxorubicin. The total duration of therapy was 10 months. Results After a median follow-up of 8.5 years, the projected overall survival at 5 years was 66% and disease-free survival (DFS) was 58%. In patients treated by surgery, only the histological response to CT had an influence on survival: 75% DFS for patients with a good histological response (less than 5% of cells), 48% for intermediate responders and only 20% for poor responders (≥ 30% of cells), P < 0.0001. The initial tumor volume by itself had no influence on DFS in these patients. In contrast, the tumour volume had a strong impact on DFS in patients treated by radiation therapy alone. Age had no impact on outcome. Conclusion Therapeutic trials for localized Ewing's sarcoma should be based on the histological response to chemotherapy or on the tumour volume according to the modality used for local therapy. [ABSTRACT FROM AUTHOR]

Medulloblastoma is the most common primary malignant central nervous system tumor in childhood, accounting for 16–25% of cases (1). New treatment approaches have led to improved survival rates; however toxicities are still a major concern. Participants were selected from the records of patients who were treated with craniospinal irradiation for medulloblastoma. Between January 2008 and December 2012, 62 patients were diagnosed with medulloblastoma at the national institute of oncology Rabat, 27 patients were still alive at the time of the study, of which n = 16 patients were included in the study. The mean age of patients at the time of the study was 9.6 years. All children were treated with radiation therapy and chemotherapy, according to standard protocols. Median follow-up between treatment and evaluation was 4 years. All the children were assessed with the Wechsler Intelligence Scale for Children - fourth Edition (WISC-IV) three to five years after completion of radiotherapy. The test was administered by two well-trained psychologists in a distraction-free environment. The scoring was then reviewed by a psychologist from Brooklyn College. The mean standard score Full-Scale Intelligence Quotient (FSIQ) (M = 63, SD = 12.6) was found to be in the extremely low range and in the 1st percentile rank (PR), compared to the general population. All the measured primary index scales were below typical performance: verbal comprehension (M = 67.7, SD = 13.1), perceptual reasoning (M = 63.5, SD = 13.8) and processing speed (M = 62.7, SD = 15.5) were all found to be in the extremely low range, while xorking memory (M = 75.5, SD = 10.8) was found to be in the borderline range compared to the general population. To identify factors influencing the results, we performed both univariate and multivariate analyses. Age at the time of radiotherapy, initial clinical stage, total cranial radiotherapy dose, socioeconomic status, and the time of evaluation were identified as significantly impacting cognitive scores in the univariate analysis. In the multivariate analysis, only age at the time of radiotherapy and initial clinical stage remained factors significantly impacting cognitive outcomes with P = 0.001 and P < 0.001 respectively. Our study is evidence that tremendous efforts are still to be made in low-income countries to correctly measure neurocognitive dysfunction in medulloblastoma survivors and to prepare those patients to a typical life after the completion of treatment. [ABSTRACT FROM AUTHOR]

Purpose Irradiation (>3 Gy) to the breast or axillae before 30 years of age increases the risk of secondary breast cancer (SBC). The purpose of this article is to describe the clinical characteristics of SBC and the way of diagnosis in young women (before the age of national screening) in France who had received previous radiotherapy for a childhood or a young adulthood cancer. Patients and methods This retrospective, multicentre study reviewed the medical records of women with SBC before the age of the national screening who had received irradiation (≥3 Gy) on part or all of the breast before 30 years of age, for any type of tumour except BC. Results A total of 121 SBC were detected in 104 women with previous radiotherapy. Twenty percent of SBC were detected during regular breast screening and 16% of the women had a regular radiological follow-up. Conclusion Our results points out that the main proportion of childhood cancer survivors did not benefit from the recommended breast cancer screening. This result is comparable to other previously published studies in other countries. A national screening programme is necessary and should take into account the patient’s age, family history, personal medical history and previous radiotherapy to reduce the number of SBC diagnosed at an advanced stage. [ABSTRACT FROM AUTHOR]

Matériel et Méthodes: Nous avons exploré la fonction testiculaire de 171 patients âgés de plus de 17 ans guéris d’un lymphome par des dosages sériques de FSH. Résultats: Le taux de FSH est élevé chez 42,1% des patients. Trois drogues ont un effet délétère dose-dépendant sur le taux de FSH : cyclophosphamide (CPM) (p < 0,0001), CCNU (p = 0,005), et procarbazine (p = 0,0001). Après maladie de Hodgkin, le taux de FSH augmente avec le nombre de cures de MOPP reçues: 7,5 ± 6,6 UI/l (ffi 3 MOPP), 13,6 ± 8,3 (4-6 MOPP) et 24,3 ± 14 (ffl6 MOPP) (p = 0,001). Après lymphome B, le taux de FSH varie avec l’évolution des protocoles : 12,7 ± 5,7 UI/l pour les protocoles utilisés avant 1984 (CPM 12g/m2, CCNU 104mg/m2), 10,2 ± 7,6 UI/l entre 1984 et 1986 (CPM 7g/m2, CCNU 47mg/m2) et 6 ± 5,1 UI/l après 1986 (CPM 5,5g/m2, CCNU 0) (p < 0,0001). Après lymphome T, le taux de FSH est passé de 9,4 ± 5,7 UI/l pour les protocoles utilisés avant 1989 à 6,8 ± 9,6 UI/l pour les plus récents, ceci semble lié à l’absence de CCNU et de Caryolysine dans les protocoles postérieurs à 1989 (p = 0,035). Conclusion: Les alkylants ont une toxicité testiculaire dose-dépendante. Grâce à la diminution des doses d’alkylants au cours du temps, la toxicité testiculaire des protocoles récents de traitement des lymphomes a significativement diminué. [ABSTRACT FROM AUTHOR]

The prognosis of primary disseminated multifocal metastatic Ewing's sarcoma (PDMES) is poor even if a slight improvement has been achieved with high-dose alkylating agent-containing chemotherapy. To enhance treatment efficacy, we assessed the feasibility, safety and efficacy of a tandem high-dose chemotherapy (HDC) regimen. In a single institution, patients with PDMES received six courses of vincristine/ifosfamide/doxorubicin/etoposide induction therapy, followed by high-dose thiotepa, and then melphalan-busulfan, 8 weeks apart. Surgical resection of primary tumour was carried out between the two HDC regimens and 70 days after the last HDC regimen for post-operative radiotherapy or irradiation alone. From October 2002 to 2009, 13 of the 18 consecutive patients with PDMES (72%) received the full treatment programme. The other five patients experienced early progression and died. Among the 13 patients, 11 relapsed after the end of the treatment programme within 6 months (2.2-11.9) from end of therapy. Only two patients are still alive in first complete remission after 9 years. The 3-year event-free survival (EFS) and overall survival (OS) rates were 11 and 22%, respectively. The median EFS and OS duration from the diagnosis were 13.4 and 17.3 months, respectively. Neither major complications nor treatment-related death occurred. The tandem-HDC regimen was feasible, with expected side effects, but it did not improve the outcome of patients with PDMES. [ABSTRACT FROM AUTHOR]

To retrospectively evaluate the incidence of tumour cell contamination of peripheral blood stem cell (PBSC) collections and to correlate these data with the clinical outcome after high-dose chemotherapy (HDCT) with stem cell rescue in patients with a high-risk Ewing tumour. Peripheral blood stem cell collections obtained from 171 patients were analysed. Tumour contamination was assessed by reverse transcriptase–polymerase chain reaction (RT–PCR). The files of 88 patients who underwent HDCT followed by PBSC reinfusion were reviewed in detail, and their outcome compared to the PBSC RT–PCR results. Seven of 88 PBSC collections (8%) contained tumour cells as detected by RT–PCR. Peripheral blood stem cells were collected after a median of five cycles of chemotherapy. No clinical factor predictive of tumour cell contamination of PBSC harvest could be identified. Event-free survival (EFS) and overall survival (OS) of the whole study population were 45.3 % and 51.8 % at 3 years from the date of the graft, respectively. Forty-five patients relapsed with a median time of 15 months after graft, only four of whom had tumour cell contamination of the PBSC harvest. Tumour cell contamination of PBSC collection is rare and does not seem to be associated with a significantly poorer EFS or OS in this high-risk population.British Journal of Cancer (2006) 95, 1326–1333. doi:10.1038/sj.bjc.6603438 www.bjcancer.com Published online 31 October 2006 [ABSTRACT FROM AUTHOR]

From 1987 to 1995, 22 children with refractory solid tumors entered a phase II study of high-dose thiotepa (HDT) (900 mg/m2) followed by stem cell transplantation (SCT) in the Pediatrics Department of the Institut Gustave Roussy. Tumor types were rhabdomyosarcoma (eight), osteosarcoma (seven), neuroblastoma (three), Ewing’s sarcoma (three) and Burkitt’s lymphoma (one). Before HDT, all had been extensively treated with conventional chemotherapy, surgical resection of the primary tumor (13/22) and of metastases (6/22), and radiotherapy of the primary tumor in three patients. All had measurable disease, at the site of the primary tumor (3 patients), of the metastases (9 patients) or both (10 patients). Toxicity from the HDT was severe but acceptable. No toxicity-related death occurred. The median duration of neutropenia and thrombocytopenia was 18 days (5–37) and 30 days (7–377), respectively. Septicemia was documented in four patients. Severe diarrhea was observed in seven patients. Mild hepatic toxicity occurred 18 times. No CR and 11/22 PR were documented: osteosarcoma 4/7, rhabdomyosarcoma 4/8, Ewing’s sarcoma 2/3; 1/1 Burkitt’s lymphoma progressed. We conclude that at a dose of 900 mg/m2 followed by SCT support in these heavily pretreated children, the main toxicity induced by thiotepa was digestive. The response rate observed, especially in sarcoma, is particularly encouraging. Thiotepa should be further evaluated in HDC regimens either in combination with other alkylating agents or in rapidly cycled courses of HDC with SCT. [ABSTRACT FROM AUTHOR]

With the increase in survival from childhood cancer, research has increasingly focused on the educational and professional achievements of childhood cancer survivors. Yet, if large-scale studies provide an acute description of the current situation of childhood cancer survivors, little is known about their trajectories and the social processes shaping these trajectories. Using a qualitative methodology, drawing from a life course perspective, this study sought to describe the role of childhood cancer and its side effects in educational trajectories, as perceived by the participants. We investigated related processes of social adjustment to cancer, that is to say, choices or decisions that survivors related to the illness in the making of their career plans. Eighty long-term French childhood cancer survivors participating in the Euro2K longitudinal study were interviewed through in-depth, face-to-face interviews undertaken in 2011–2012. There were various types of impact described by respondents of the diagnosis of cancer on their trajectories. These varied according to gender. In women, childhood cancer tended to result in poor educational achievement, or in steering the individual towards a health care or child care occupation. This was justified by a desire to return the support that had been offered to them as patients. In men, however, childhood cancer led to a shift in career plans, because of physical sequelae, or because of concerns about their future health. Paradoxically, this limitation had a positive impact in their occupational achievement, as most of these men disregarded blue-collar jobs and chose more qualified white-collar occupations. Overall, findings suggest that childhood cancer influenced educational trajectories and, thus, socioeconomic status in adulthood, through mechanisms embedded in gender norms. These mechanisms could explain gender inequalities in educational achievement after childhood cancer reported in large-scale cohort studies. [ABSTRACT FROM AUTHOR]

The paper report the results of the first European prospective nonrandomized trial dedicated to pediatric synovial sarcoma. The study included 138 patients treated from 2005 to 2012 with a multimodal therapeutic approach. The overall treatment results were higher than those previously published by pediatric groups.Background To report the results of the first European prospective nonrandomized trial dedicated to pediatric synovial sarcoma. Patients and methods From August 2005 to August 2012, 138 patients <21 years old with nonmetastatic synovial sarcoma were registered in 9 different countries (and 60 centers). Patients were treated with a multimodal therapy including ifosfamide–doxorubicin chemotherapy and radiotherapy, according to a risk stratification based on surgical stage, tumor size and site, and nodal involvement. Results With a median follow-up of 52.1 months (range 13.8–104.4 months), event-free survival (EFS) was 81.9% and 80.7%, and overall survival (OS) was 97.2% and 90.7%, at 3 and 5 years, respectively. The only significant prognostic variable at univariate analysis was the risk group: 3-year EFS was 91.7% for low-risk, 91.2% for intermediate-risk, and 74.4% for high-risk cases. In 24 low-risk patients (completely resected tumor ≤5 cm in size) treated with surgery alone, there were two local relapses and no metastatic recurrences. Among 67 high-risk patients (unresected, or axial tumor or nodal involvement), 66 underwent surgery after neoadjuvant chemotherapy. Response to chemotherapy was 55.2%, including 22.4% cases with complete or major partial remissions, and 32.8% with minor partial remissions. Conclusion This study demonstrates that collaborative prospective studies on rare pediatric sarcomas are feasible even on a European scale, with excellent treatment compliance. The overall results of treatment were satisfactory, with higher survival rates than those previously published by pediatric groups. Nonetheless, larger, international projects are needed, based on a cooperative effort of pediatric and adult oncologists. Clinical Trials number European Union Drug Regulating Authorities Clinical Trials No. 2005-001139-31. [ABSTRACT FROM PUBLISHER]

Parameningeal (PM) site is a well-known adverse prognostic factor in children with rhabdomyosarcoma (RMS). A pooled analysis of data from 1105 patients with PM RMS differentiates those with good prognosis (36% patients with 0-1 risk factor: 10-yr OS 80.9%) from high risk PM patients (28% with 3-4 factors: 10-yr OS 51.1%). Furthermore, this analysis reinforces the necessity for radiotherapy in PM RMS.Background Parameningeal (PM) site is a well-known adverse prognostic factor in children with localized rhabdomyosarcoma (RMS). To identify risk factors associated with outcome at this site, we pooled data from 1105 patients treated in 10 studies conducted by European and North American cooperative groups between 1984 and 2004. Patients and methods Clinical factors including age, histology, size, invasiveness, nodal involvement, Intergroup Rhabdomyosarcoma Study (IRS) clinical group, site, risk factors for meningeal involvement (MI), study group, and application of radiotherapy (RT) were studied for their impact on event-free and overall survival (EFS and OS). Results Ten-year EFS and OS were 62.6 and 66.1% for the whole group. Patients without initial RT showed worse survival (10-year OS 40.8% versus 68.5% for RT treated patients). Multivariate analysis focusing on 862 patients who received RT as part of their initial treatment revealed four unfavorable prognostic factors: age <3 or >10 years, signs of MI, unfavorable site, and tumor size. Utilizing these prognostic factors, patients could be classified into different risk groups with 10-year OS ranging between 51.1 and 80.9%. Conclusions While, in general, PM localization is regarded as an adverse prognostic factor, the current analysis differentiates those with good prognosis (36% patients with 0–1 risk factor: 10-year OS 80.9%) from high-risk PM patients (28% with 3–4 factors: 10-year OS 51.1%). Furthermore, this analysis reinforces the necessity for RT in PM RMS. [ABSTRACT FROM AUTHOR]

Résumé: La curiethérapie est rarement utilisée en cancérologie pédiatrique, et réservée à des institutions spécialisées. Les localisations tumorales les plus fréquemment ainsi traitées sont les rhabdomyosarcomes d’origine gynécologique ou vésicoprostatiques. Les avantages balistiques de la curiethérapie en font une technique de choix en pédiatrie, puisqu’elle permet de protéger sélectivement les tissus sains. Les techniques rapportées, les modalités de la curiethérapie (bas débit de dose, haut débit de dose, débit pulsé), les doses et les indications varient en fonction des centres. Cette revue analyse les techniques, les indications en fonction des deux localisations les plus fréquentes, gynécologique et vésicoprostatique, et les résultats de cette technique qui nécessite une indispensable approche multidisciplinaire. [ABSTRACT FROM AUTHOR]

Background: Rhabdomyosarcomas (RMSs) are primarily paediatric sarcomas that resemble developing skeletal muscle. Our aim was to determine the effects of microRNAs (miRNA) that have been implicated in muscle development on the clinical behaviour of RMSs.Methods: Expression levels of miR-1, miR-206, miR-133a and miR-133b were quantified by RT-PCR in 163 primary paediatric RMSs, plus control tissues, and correlated with clinico-pathological features. Correlations with parallel gene expression profiling data for 84 samples were used to identify pathways associated with miR-206. Synthetic miR-206 was transfected into RMS cell lines and phenotypic responses assessed.Results: Muscle-specific miRNAs levels were lower in RMSs compared with skeletal muscle but generally higher than in other normal tissues. Low miR-206 expression correlated with poor overall survival and was an independent predictor of shorter survival in metastatic embryonal and alveolar cases without PAX3/7-FOXO1 fusion genes. Low miR-206 expression also significantly correlated with high SIOP stage and the presence of metastases at diagnosis. High miR-206 expression strongly correlated with genes linked to muscle differentiation and low expression was associated with genes linked to MAPkinase and NFKappaB pathway activation. Increasing miR-206 expression in cell lines inhibited cell growth and migration and induced apoptosis that was associated with myogenic differentiation in some, but not all, cell lines.Conclusion: miR-206 contributes to the clinical behaviour of RMSs and the pleiotropic effects of miR-206 supports therapeutic potential. [ABSTRACT FROM AUTHOR]

Summary: Soft tissue tumors account for approximately 25% of neonatal tumors and are most often benign (more than 2/3 of cases). Vascular tumors are the most frequent benign tumors and infantile hemangioma accounts for 32% of these tumors, affecting 1 out of 200 children at birth. Kaposiform hemangioendothelioma (KH) is a rare vascular tumor with locally aggressive behavior. More than 50% of KH are associated with the Kasabach-Merritt phenomenon, a condition characterized by thrombocytopenia and consumptive coagulopathy. Malignant soft tissue tumors are, after neuroblastoma, the second cause of cancer in neonates. Infantile fibrosarcoma (IF) is a rare tumor that most often affects the extremities of children aged 4 years or younger. A recurrent t(12;15) (p13;q25) rearrangement fusing the ETV6 gene with the NTRK3 neurotrophin-3 receptor gene has been identified in IF. Complete conservative surgical resection is usually curative. Chemotherapy is indicated when initial surgical removal cannot be accomplished without unacceptable morbidity. Prognosis of IF is excellent, with reported overall survival rates ranging from 80 to 100%. Neonatal rhabdomyosarcoma (RMS) is a rare tumor (0.5–1% of RMS). The primary tumor predominantly involves the limbs and the genitourinary tract. Treatment is based on age-adapted chemotherapy and surgery. Prognosis of RMS in children less than 1 year old appears to be comparable with that of older children. [Copyright &y& Elsevier]

Abstract: Introduction. – Ifosfamide is an alkylating agent used in the treatment of germ-cell tumors, sarcomas and lymphomas. One of its main side effects is the encephalopathy of which the incidence may reach 30% in the literature, in adults and children just as well. Objectives. – Based on both our experience and a review of the literature, we propose some recommendations for the management of this complication. Patients and methods. – We report 15 encephalopathy cases in non-brain tumor patients, which occurred between January 1987 and March 2002 in children from 2 to 17 years old, treated for solid tumors at the Institut Gustave Roussy. Ifosfamide was administered at a posology between 5.4 and 15 g/m2/course, associated with other antimitotics such as actinomycin D, etoposide or vincristine. Results. – Six patients experienced a grade III neurological toxicity according to the NCI classification, which developed as excess drowsiness lasting up to 36 hours. Six other patients developed grade IV neurotoxicity, including two comas resolving within 4 days and four short generalized convulsions. Three other children experienced grade II drowsiness. Brain MRIs were normal and EEG showed an aspecific encephalopathy tracing. This early central neurotoxicity appeared right from the first administration, and occurred immediately after the first injection or during the second or third day of treatment. It was most often reversible, usually 3 to 5 days after the last ifosfamide administration. Five patients were administered a treatment with Methylene Blue with a demonstrable efficacy in only one case. No death or neurological sequelae have been noted. Ifosfamide has been renewed after the neurological accident in 7 of those patients. Only 1 of those 7 patients developed grade IV neurotoxicity during the next course of treatment. In 2 of those 7 children, Methylene Blue was used in a prophylactic way. No neurological disorders have been noted during the next courses of treatment. Discussion. – In the literature, the following are described as risk factors for ifosfamide encephalopathy: advanced pelvic disease, previous cisplatyl treatment and renal failure. We have not found any of these predisposing factors in our series, but three of the fifteen patients had severe neurotoxicity associated with Vincristin during previous treatments. Conclusion. – Facing a clinical diagnosis of ifosfamide encephalopathy, it is recommended to discontinue administration of ifosfamide and inject by intravenous route 50 mg Methylene Blue every 4 hours until the symptomatology recedes. The re-challenge of Ifosfamide is not contra-indicated and should be performed under prophylactic treatment with Methylene Blue by intravenous route at the dose of 50 mg every 6 hours. [Copyright &y& Elsevier]

The aim of this study was to determine therapy-related risk factors for the development of melanoma after childhood cancer. Among 4401 3-year survivors of a childhood cancer in eight French and British centres and 25 120 patients younger than 20 years old at first malignant neoplasm (FMN) extracted from the Nordic Cancer Registries, 16 patients developed a melanoma as a second malignant neoplasm (SMN). A cohort study of the French and British cohorts was performed. In a nested case–control study, the 16 patients who developed a melanoma as a SMN (cases) were matched with 3–5 controls in their respective cohort according to gender, age at the first cancer, the calendar year of occurrence of the first cancer and follow-up. Radiotherapy appeared to increase the risk of melanoma for local doses >15 Gy, Odds Ratio (OR)=13 (95% Confidence Interval (CI): 0.94–174). Regarding chemotherapy, we observed an increased OR for both alkylating agents and spindle inhibitors, OR=2.7 (95% CI: 0.5–14). Children treated for a gonadal tumour as a FMN were found to be at a higher risk of melanoma, OR=8.7 (95% CI: 0.9–86). The adjusted OR for the local radiation dose was 1.07 (95% CI: 1.00–1.15). In conclusion, radiotherapy may contribute to an increased risk of melanoma as a SMN, but only at very high doses of low linear energy transfer radiation. Common genetic origins between gonadal tumours and malignant melanomas are likely. [Copyright &y& Elsevier]

Presents a study that examined an intensive chemotherapy regimen and the role of high-dose melphalan in children with metastatic soft tissue sarcoma, including peripheral neuroectodermal tumors (PNET). List of European groups who launched the study; Details on the chromosomal translocation of PNET and Ewing sarcoma; Function of high-dose chemotherapy in stem cell rescue.

From 1984 to 1997, 57 consecutive patients with non-metastatic Ewing''s sarcoma of the ribs were treated according to multimodal French Society of Pediatric Oncology (SFOP) protocols EW 84, EW 88 and EW 93. The results of treatment were reviewed and analysed. Median age was 12 years. 34 patients had large tumours (greatest tumour dimension 8 cm); pleural effusion was noted in 26. A tumour-positive margin after surgery was noted in 15 patients. Histological response after chemotherapy was assessed in 34 patients. 34 patients received radiation therapy. With a median follow-up of 5 years, the projected overall and relapse-free survival rates were 69 and 62%, respectively. The major site of relapse was local. None of the following was significant in predicting relapse: tumour size, gender, age at diagnosis, existence of pleural effusion, level of rib tumour, rib component, type of local control, surgical margin (positive or negative). Response to chemotherapy was the sole significant prognostic factor (P=0.004). Patients with pleural effusion had a higher percentage of relapse if they were treated without local radiation therapy. Our study confirms the prognostic significance of response to initial chemotherapy. Radiation therapy may be withheld in selected cases, but seems necessary in patients with pleural effusion. [Copyright &y& Elsevier]

The prognosis of metastatic malignant mesenchymal tumors (MMT) remains poor. Given the chemosensitivity of these neoplasms, a phase II study of high-dose thiotepa (HDT) was performed to evaluate the efficacy of this drug in this particular subset of pediatric tumors. Between 1986 and 1998, 18 patients, previously treated with conventional therapy for metastatic or refractory MMT, entered the study. Thiotepa was administered at a daily dose of 300 mg/m2 for 3 consecutive days. Hematopoietic stem cell rescue, consisting of bone marrow transplantation or peripheral stem cell transplantation, was performed 2 days after completion of HDT. A response exceeding 50% was observed in 6/18 patients (response rate 33%). Toxicity was severe but never led to death. HDT used at a dose of 900 mg/m2 yields measurable anti-tumor activity in previously treated patients. The next step in these particularly poor prognosis metastatic MMT will be to investigate HDT combined with other drugs, known to be efficient at high doses. Bone Marrow Transplantation (2000) 26, 627–632. [ABSTRACT FROM AUTHOR]

The variation in the risk of solid second malignant neoplasms (SMN) with time since first cancer during childhood has been previously reported. However, no study has been performed that controls for the distribution of radiation dose and the aggressiveness of past chemotherapy, which could be responsible for the observed temporal variation of the risk. The purpose of this study was to investigate the influence of the treatment on the long-term pattern of the incidence of solid SMN after a first cancer in childhood. We studied a cohort of 4400 patients from eight centres in France and the UK. Patients had to be alive 3 years or more after a first cancer treated before the age of 17 years and before the end of 1985. For each patient in the cohort, the complete clinical, chemotherapy and radiotherapy history was recorded. For each patient who had received external radiotherapy, the dose of radiation received by 151 sites of the body were estimated. After a mean follow-up of 15 years, 113 children developed a solid SMN, compared to 12.3 expected from general population rates. A similar distribution pattern was observed among the 1045 patients treated with radiotherapy alone and the 2064 patients treated with radiotherapy plus chemotherapy; the relative risk, but not the excess absolute risk, of solid SMN decreased with time after first treatment; the excess absolute risk increased during a period of at least 30 years after the first cancer. This pattern remained after controlling for chemotherapy and for the average dose of radiation to the major sites of SMN. It also remained when excluding patients with a first cancer type or an associated syndrome known to predispose to SMN. When compared with radiotherapy alone, the addition of chemotherapy increases the risk of solid SMN after a first cancer in childhood, but does not significantly modify the variation of this risk during the time after the first cancer. [ABSTRACT FROM AUTHOR]

Objectifs: En 2003 la SFCE a proposé des recommandations MDH03 de prise en charge des lymphomes de Hodgkin de l’enfant. 3 groupes: GMH1stades favorables, GMH2 intermédiaires et GMH3 avancés. Les patients étaient évalués par TDM après 4 cures. En cas de réponse < 75 %, chimiothérapie complémentaire. Pour tous, radiothérapie complémentaire 20Gy IF ± boost. Patients et méthodes: Enregistrement prospectif. 470 patients dont 407 ayant des données exploitables. Age médian 14 ans, 191 filles. Stades IA n = 19;IB n = 8;IIA n = 131;IIB n = 58;IIIA n = 41; IIIB n = 42;IVA n = 45; IVB n = 63;13 %E. Résultats: GMH1 n = 89(22 %), GMH2 n = 181(45 %), GMH3 n = 137(33 %). GMH1: 88 % de bons répondeurs (BR) après 4xVBVP. GMH2:83 % BR après 4xCOPP/ABV. GMH3:94 %BR après 3xOPPA. 4 % des pts ont eu un boost. Recul médian de 32 mois (0-67), 9/407 pts sont décédés. OS à 5 ans 96 %(+/-2 %) (GMH1 100 %, GMH2 94 %, GMH3 95 %). EFS 86 %(+/-2 %) (GMH1 97 %, GMH2 81 %, GMH3 86 %). 2 % des pts réfractaires. Conclusion: Les recommandations MDH03 ont été largement appliquées, avec des résultats encourageants. 60 % des pts ont reçu < 160mg/m2 d’anthracyclines et irradiation 20Gy. Depuis 2008, la SFCE est associée au protocole EURONET PHL-C1 qui évalue l’abstention de radiothérapie pour les BR à 2 cures et randomise la dacarbazine/procarbazine. [ABSTRACT FROM AUTHOR]

Les enfants suivis en oncologie ont un risque infectieux augmenté en particulier de bactériémies et fongémies, cause majeure de morbidité qui peut mettre en jeu le pronostic vital. Nous avons étudié rétrospectivement toutes les hémocultures positives entre 2000 et 2007 du département de pédiatrie de l’Institut Gustave Roussy, afin de décrire les caractéristiques épidémiologiques des patients à risque et de déterminer l’évolution de ces épisodes. Nous avons recensé 1091 hémocultures positives, soit 345 épisodes bactériémiques chez 290 patients ; 47 % ont eu lieu chez des patients neutropéniques et 13 % après une autogreffe. Les germes mis en évidence étaient des cocci gram positif dans 42,3 % des cas puis des bacilles gram négatifs (BGN) dans 35,7 % des cas. Les infections étaient polymicrobiennes dans 15,6 % des cas et il y a eu 2,3 % de fongémies. Dans 50 % des cas, la voie veineuse centrale a été retirée. En outre, l’infection a été compliquée d’un choc septique dans 9 % des cas et d’un transfert en USI dans 5,2 %, surtout en cas de BGN ; seulement deux décès ont été constatés. L’amélioration des connaissances sur les bactériémies en oncologie pédiatrique va permettre d’optimiser leur prise en charge en terme de gestion des voies d’abord et de l’antibiothérapie. [ABSTRACT FROM AUTHOR]

Les séquelles endocriniennes après allogreffe de moelle osseuse et irradiation corporelle totale (TBI) pour hémopathie sont bien connues, contrairement à celles des autogreffes de moelle sans TBI. 88 enfants ayant reçu une chimiothérapie à haute dose et une autogreffe de moelle sans TBI pour une tumeur solide (52 % de neuroblastomes) à un âge moyen de 6 ± 4.4 ans, ont été étudiés à un âge moyen de 16 ± 5.7 ans et un recul de 10 ± 3.6 ans post-greffe. 57 % ont reçu un conditionnement contenant du Busulfan. L’étude de la croissance montre une perte moyenne de presque 1 DS entre le diagnostic de tumeur et le bilan actuel, corrélée à l’utilisation de la radiothérapie du squelette. La taille finale est inférieure à –2DS dans 22 % des cas. 11 enfants avaient un déficit en hormone de croissance, secondaire à une irradiation craniale chez seulement 5 d’entre eux. La puberté s’est déroulée normalement chez la plupart des garçons (87 %), mais 89 % ont une atteinte tubulaire testiculaire (FSH > 14 UI/l pour 62 %, volume testiculaire < 10 ml pour 86 %). Seulement 2 garçons ont une atteinte Leydigienne après irradiation testiculaire, mais 22 % ont des taux de LH > 8 UI/l. 66 % des filles ont une atteinte ovarienne dont l’incidence est liée à l’utilisation du Busulfan, l’âge et le stade pubertaire au moment de la greffe. 86 % ont un examen et une fonction thyroïdienne normale. Des anomalies thyroïdiennes ne sont observées qu’après irradiation cervicale ou traitement d’un neuroblastome : élévation de la TSH > 6 mUI/l (8 %), nodules thyroïdiens (6.8 %). La fonction surrénalienne est normale chez tous les patients. Conclusions: 1/L’insuffisance ovarienne et l’atteinte tubulaire testiculaire sont les principales séquelles endocriniennes de la chimiothérapie à haute dose avec autogreffe de moelle avec une fréquence équivalente à celle des conditionnements avec TBI. 2/La croissance est moins altérée après conditionnement par chimiothérapie seule qu’avec TBI. 3/L’irradiation cervicale et le neuroblastome (ou sa prise en charge) sont les principaux facteurs de risque d’atteinte thyroïdienne dans cette population. [Copyright &y& Elsevier]

Le traitement des tumeurs malignes du petit bassin de l’enfant nécessite souvent un traitement lourd et multimodal dont le recours à la radiothérapie dans le contrôle tumoral local. L’irradiation peut générer elle même des complications sur les organes en développement de l’enfant. L’exclusion pelvienne chirurgicale permet de déplacer les organes intra pelviens hors du champs d’irradiation. Entre 1987 et 2008, 20 enfants suivis à l’IGR ont bénéficié d’une exclusion des viscères intrapelviens par mise en place d’une prothèse d’expansion associée ou non à une compartimentation abdominale complémentaire. La durée moyenne d’exclusion était de 97 jours. La tolérance était bonne dans 85 % des cas. 2 patients ont présenté une complication lors de l’intervention de mise en place. La radiothérapie externe a pu être réalisée dans 90 % des cas avec une dose moyenne de 50,6 Gy. 2 Patients ont eu une entérite aiguë rapidement résolutive et un seul patient a présenté des complications digestives sévères à long terme. La mise en place d’une prothèse d’expansion en vue de protéger les viscères intrapelviens est une technique sûre et reproductible chez l’enfant. Elle permet d’éloigner les organes à risque du champ d’irradiation sans surmortalité et au prix d’une morbidité faible et acceptable. [ABSTRACT FROM AUTHOR]

Objectifs: colliger des observations de MM pédiatriques afin d’améliorer notre connaissance de cette pathologie. Méthode: étude rétrospective des MM pris en charge par la SFCE. Résultats: 12 patients (6 garçons) d’âge médian de 12 ans ont été identifiés. La localisation était péritonéale (7 cas), vaginale testiculaire (1 cas), péricardique (1 cas), multi sérique (3 cas). 6 cas étaient métastatiques dans au diagnostic. Le délai moyen diagnostique était de 200 jours. Le traitement initial était multimodal chez 9 patients. Une chirurgie a été réalisée chez 7 patients au diagnostic et chez 3 patients après chimiothérapie. 9 patients ont reçu de la chimiothérapie durant leur traitement de première ligne. Les agents utilisés étaient variés. Une CHIP a été réalisée chez 5 patients. À l’issue de la première ligne de traitement ; 5 RC, 2 RP, 0 MS et 4 MP ont été observées. 1 patient a été perdu de vue. 66 % des patients ont nécessité plusieurs lignes de traitement (jusqu’à 5). La SSE à 2 et 5 ans est de 38 and 30 %. La SG à 2 et 5 ans est respectivement de 90 and 80 %. Conclusion: MM est une tumeur extrêmement rare de l’enfant qui semble différente de la maladie observée chez l’adulte (moins de localisation pleurale et un pronostic supérieur malgré de fréquentes rechutes). [ABSTRACT FROM AUTHOR]

Objectifs: L’esthésioneuroblastome (ENB) est une tumeur rare développée aux dépend de l’épithélium de la cavité nasale supérieure et de l’ethmoïde. Nous avons revu l’expérience de l’Institut Gustave Roussy sur les ENB des enfants et adolescents. Matériels et Méthodes: Onze enfants et adolescents ont pris en charge sur une période de 20 ans. 9 patients ont reçu un traitement par chimiothérapie initiale suivie de chirurgie et de radiothérapie. Un patient a été traité par chirurgie et radiothérapie sans chimiothérapie ; un autre patient en rémission complète après chimiothérapie n’a pas eu de chirurgie avant la radiothérapie. Résultats: 10 patients étaient évaluables pour la réponse au traitement, parmi lesquels 7 ont été mis en rémission complète ou partiale par la chimiothérapie. Seul un patient a rechuté localement et sous forme métastatique 9 mois après le diagnostic. Il est décédé en quelques semaines. Les 10 autres sont vivants en première rémission. Avec un suivi médian de 8,8 ans (extrêmes : 9,9-16,4), la survie sans évènement et la survie globale à 5 ans sont de 91 % (95 % IC : 62 % – 98 %). Conclusions: Ces résultats montrent la chimiosensibilité des ENB et l’efficacité d’un traitement combinant chimiothérapie, chirurgie et radiothérapie. [Copyright &y& Elsevier]