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1.
Lancet Oncol ; 20(11): 1566-1575, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31562043

RESUMO

BACKGROUND: For more than three decades, standard treatment for rhabdomyosarcoma in Europe has included 6 months of chemotherapy. The European paediatric Soft tissue sarcoma Study Group (EpSSG) aimed to investigate whether prolonging treatment with maintenance chemotherapy would improve survival in patients with high-risk rhabdomyosarcoma. METHODS: RMS 2005 was a multicentre, open-label, randomised, controlled, phase 3 trial done at 102 hospitals in 14 countries. We included patients aged 6 months to 21 years with rhabdomyosarcoma who were considered to be at high risk of relapse: those with non-metastatic incompletely resected embryonal rhabdomyosarcoma occurring at unfavourable sites with unfavourable age (≥10 years) or tumour size (>5 cm), or both; those with any non-metastatic rhabdomyosarcoma with nodal involvement; and those with non-metastatic alveolar rhabdomyosarcoma but without nodal involvement. Patients in remission after standard treatment (nine cycles of ifosfamide, vincristine, dactinomycin with or without doxorubicin, and surgery or radiotherapy, or both) were randomly assigned (1:1) to stop treatment or continue maintenance chemotherapy (six cycles of intravenous vinorelbine 25 mg/m2 on days 1, 8, and 15, and daily oral cyclophosphamide 25 mg/m2, on days 1-28). Randomisation was done by use of a web-based system and was stratified (block size of four) by enrolling country and risk subgroup. Neither investigators nor patients were masked to treatment allocation. The primary outcome was disease-free survival in the intention-to-treat population. Secondary outcomes were overall survival and toxicity. This trial is registered with EudraCT, number 2005-000217-35, and ClinicalTrials.gov, number NCT00339118, and follow-up is ongoing. FINDINGS: Between April 20, 2006, and Dec 21, 2016, 371 patients were enrolled and randomly assigned to the two groups: 186 to stop treatment and 185 to receive maintenance chemotherapy. Median follow-up was 60·3 months (IQR 32·4-89·4). In the intention-to-treat population, 5-year disease-free survival was 77·6% (95% CI 70·6-83·2) with maintenance chemotherapy versus 69·8% (62·2-76·2) without maintenance chemotherapy (hazard ratio [HR] 0·68 [95% CI 0·45-1·02]; p=0·061), and 5-year overall survival was 86·5% (95% CI 80·2-90·9) with maintenance chemotherapy versus 73·7% (65·8-80·1) without (HR 0·52 [95% CI 0·32-0·86]; p=0·0097). Toxicity was manageable in patients who received maintenance chemotherapy: 136 (75%) of 181 patients had grade 3-4 leucopenia, 148 (82%) had grade 3-4 neutropenia, 19 (10%) had anaemia, two (1%) had thrombocytopenia, and 56 (31%) had an infection. One (1%) patient had a grade 4 non-haematological toxicity (neurotoxicity). Two treatment-related serious adverse events occurred: one case of inappropriate antidiuretic hormone secretion and one of a severe steppage gait with limb pain, both of which resolved. INTERPRETATION: Adding maintenance chemotherapy seems to improve survival for patients with high-risk rhabdomyosarcoma. This approach will be the new standard of care for patients with high-risk rhabdomyosarcoma in future EpSSG trials. FUNDING: Fondazione Città della Speranza, Association Léon Berard Enfant Cancéreux, Clinical Research Hospital Program (French Ministry of Health), and Cancer Research UK.

2.
Pediatr Blood Cancer ; 66(9): e27873, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31207026

RESUMO

INTRODUCTION: In order to describe relapsed B-cell non-Hodgkin lymphoma and mature acute leukemia in children/adolescents treated with the Lymphomes Malins B (LMB) regimen and their outcome in the rituximab era, relapses in the French LMB2001 study were reviewed. METHODS: Between February 2001 and December 2011, 33 patients out of 773 (4.3%) relapsed; 27 had Burkitt lymphoma and six large B-cell histology. Median age at diagnosis was 10.1 years. One patient was initially treated in risk group A, 21 in group B, and 11 in group C. RESULTS: Median time to relapse after diagnosis was 4.5 months (range 2.4-13.6). Thirty-two patients received salvage therapy. Twenty-seven received rituximab mainly in addition to high-dose cytarabine and etoposide (n = 18) and/or ifosfamide, carboplatin, and etoposide (n = 7). First-line salvage chemotherapy response rate was 66% with 47% being complete remission (CR). Twenty-one patients received high-dose chemotherapy (HDC) followed by autologous (n = 13) or allogeneic (n = 8) transplant. With a median follow-up of 6.8 years, the 5-year survival rate after relapse was 36.4% (95% confidence interval [CI] 22-53%). Twelve patients were still alive; all but one (group A) received consolidation treatment. Achieving CR before consolidation was significantly associated with better survival, with a 5-year survival rate of 75% (95% CI 46.8-91.1%) for patients in CR before HDC, 33% (95% CI 9.7-70%) for patients in partial remission, and 0% for nonresponders (P = .033). CONCLUSION: Survival of children/adolescents with mature B-cell lymphoma/leukemia remains poor after relapse with no apparent improvement with rituximab. Response rates to salvage chemo-immunotherapies are insufficient and new drugs are urgently needed to improve disease control.

3.
Int J Pediatr Otorhinolaryngol ; 123: 33-37, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31059930

RESUMO

INTRODUCTION: Desmoid-type fibromatosis (DF) is a rare benign lesion known for its local aggressiveness. The tumor management still remains under debate. Primary head and neck (HN), represents the second most prevalently affected sitein children with DF. This study aims to analyze the specificity of HN-DF in children, focusing on long-term effects of the tumor and therapies. METHODS: This retrospective multicenter study analyzed children treated for a HN-DF between 1993 and 2013. All medical files were reviewed and their outcomes analyzed according to the initial therapies provided. RESULTS: Sixteen children were selected. Mandibular and submandibular areas were the main locations (11 cases). Eight children underwent chemotherapy as first-line therapy with tumor control in 3 cases and 5 cases needing additional treatment. Six children underwent primary surgery: isolated in 3 cases and with additional treatment after tumor progression in 3 cases. A wait-and-see attitude was adopted for 2 children without any additional treatment in 1 case, and followed by additional chemotherapy in the other case. Total burden of treatment to control the disease was a biopsy (1 case), surgery (3 unique cases, 1 multiple case), surgery with chemotherapy (6 cases), and exclusive medical therapies (5 cases). Surgical postoperative sequelae were facial palsy (cases of parotid gland affection), XIth cranial nerve sacrifice or sensory impairment. CONCLUSION: HN-DF is a local and extensive disease that is difficult to control with surgery alone. Sequelae are frequent due to the initial tumor location or therapies. Initial conservative strategies need to be discussed in a multidisciplinary way in order to try to control the disease with the minimal morbidity.


Assuntos
Fibromatose Agressiva/tratamento farmacológico , Fibromatose Agressiva/cirurgia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Mandibulares/tratamento farmacológico , Neoplasias Mandibulares/cirurgia , Adolescente , Antineoplásicos/uso terapêutico , Paralisia de Bell/etiologia , Criança , Pré-Escolar , Terapia Combinada , Progressão da Doença , Feminino , Fibromatose Agressiva/terapia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Lactente , Masculino , Neoplasias Mandibulares/terapia , Glândula Parótida/patologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Conduta Expectante
4.
Pediatr Blood Cancer ; 66 Suppl 3: e27867, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31136081

RESUMO

AIM: We present the preliminary results of robotic-assisted laparoscopic (RAL) total and partial nephrectomy for renal malignant tumors in children. METHODS: This is a prospective study of patients operated with RAL between December 2016 and September 2018. Patients with Wilms tumors were treated according to the SIOP-2001 protocol. Patient and tumor characteristics, type of surgery, surgical-related morbidity, and oncologic outcomes were recorded. Results were compared with a series of patients with similar age- and tumor-related characteristics operated during the same period by an open surgical approach. RESULTS: Ten children underwent RAL nephrectomy with a mean age of five years (3.2-14.1 years). Total nephrectomy was done in six cases for Wilms tumor and in one case for renal sarcoma; three cases were converted. Complete removal of tumor without rupture was achieved in all cases. Postoperative course was uneventful, and patients were discharged between days 2 and 7. Neither recurrence nor medium-term complications occurred. Nine patients are alive with a median follow-up of 16 months (6-27 months) and one female died from complications of central nervous system metastases one year after surgery. When compared with the open surgical approach group, median tumor volume was smaller (P = 0.005), hospital stay was shorter (P = 0.01), and operative time was similar (P = 0.20). CONCLUSIONS: RAL total and partial nephrectomy procedure for renal tumor in children may be an option in carefully selected cases. Indication should be discussed at tumor boards and surgery performed while adhering strictly to oncological surgical rules.

5.
Am J Med Genet A ; 179(7): 1304-1309, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31004414

RESUMO

The spectrum of clinical consequences of variants in the Platelet derived growth factor receptor beta (PDGFRB) gene is wide. Missense variants leading to variable loss of signal transduction in vitro have been reported in the idiopathic basal ganglia calcification (IBGC) syndrome Type 4. In contrast, gain-of-function variants have been reported in infantile myofibromatosis, Penttinen syndrome, and Kosaki overgrowth syndrome. Here, we report a patient harboring a novel postzygotic variant in PDGFRB (c.1682_1684del, p.[Arg561_Tyr562delinsHis]) and presenting severe cerebral malformations, intracerebral calcifications, and infantile myofibromatosis. This observation expands the phenotype associated with PDGFRB variants and illustrates the wide clinical spectrum linked to dysregulation of PDGFRB.

6.
Nat Commun ; 10(1): 1486, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30940805

RESUMO

Immunogenic cell death (ICD) converts dying cancer cells into a therapeutic vaccine and stimulates antitumor immune responses. Here we unravel the results of an unbiased screen identifying high-dose (10 µM) crizotinib as an ICD-inducing tyrosine kinase inhibitor that has exceptional antineoplastic activity when combined with non-ICD inducing chemotherapeutics like cisplatin. The combination of cisplatin and high-dose crizotinib induces ICD in non-small cell lung carcinoma (NSCLC) cells and effectively controls the growth of distinct (transplantable, carcinogen- or oncogene induced) orthotopic NSCLC models. These anticancer effects are linked to increased T lymphocyte infiltration and are abolished by T cell depletion or interferon-γ neutralization. Crizotinib plus cisplatin leads to an increase in the expression of PD-1 and PD-L1 in tumors, coupled to a strong sensitization of NSCLC to immunotherapy with PD-1 antibodies. Hence, a sequential combination treatment consisting in conventional chemotherapy together with crizotinib, followed by immune checkpoint blockade may be active against NSCLC.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Morte Celular/efeitos dos fármacos , Crizotinibe/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Animais , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Linhagem Celular Tumoral , Feminino , Humanos , Interferon gama/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T/imunologia
8.
Pediatr Blood Cancer ; 66(7): e27725, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30920113

RESUMO

OBJECTIVES: To evaluate the impact of local therapies on the outcome of patients with liver-bile duct rhabdomyosarcoma (LBDRMS). METHODS: Data of 30 patients included in the EpSSG-RMS 2005 study were analyzed. RESULTS: The median age at diagnosis was 3 years (11 months-8 years). All patients had non-alveolar histology. Fifteen patients had a tumor > 5 cm and six had enlarged regional lymph nodes on imaging. Eight patients (27%) had primary surgery (1 R0). Six of them received external beam radiotherapy (EBRT). All are in first complete remission (CR1) except one (R1, EBRT+ , local relapse, death). Six patients (20%) received EBRT without surgery: one had local relapse and died. Sixteen patients (53%) underwent delayed surgery, with 12 achieving R0 margins, which were higher than those in the primary surgery group (P = 0.003). Three patients with R0 margins received EBRT; one had a metastatic relapse and died. Nine patients with R0 resection did not receive EBRT, three relapsed locally (two deaths). Four R1 patients received additional EBRT without relapses. Local relapse occurred in two among 19 patients with EBRT and three among 11 without EBRT (P = 0.326). At a median follow-up of 61 months (48-84 months), five patients died; all had a tumor size > 5 cm (P = 0.01). The five-year overall survival was 85% (95% CI, 65-94), and event-free survival was 76% (95% CI, 54-89). CONCLUSION: This analysis did not show any significant difference in outcome between irradiated and nonirradiated patients. Local relapse in LBDRMS is related to initial tumor size and is often fatal.

9.
Eur J Cancer ; 110: 74-85, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30772656

RESUMO

Paediatric Strategy Forums have been created by the multistakeholder organisation, ACCELERATE, and the European Medicines Agency to facilitate dialogue between all relevant stakeholders and suggest strategies in critical areas of paediatric oncology drug development. As there are many medicines being developed for B-cell malignancies in adults but comparatively few in children with these malignancies, a Paediatric Strategy Forum was held to discuss the best approach to develop these products for children. It was concluded that as current frontline therapy is highly successful, despite associated acute toxicity, de-escalation of this or substitution of presently used drugs with new medicines can only be undertaken when there is an effective salvage regimen, which is currently not available. Therefore priority should be given to developing treatment for patients with relapsed and refractory mature B-cell lymphomas. The consensus of the clinicians attending the meeting was that CAR T-cells, T-cell engagers and antibody drug conjugates (excluding those with a vinca alkaloid-like drug) presently have the greatest probability of providing benefit in relapse in view of their mechanism of action. However, as producing autologous CAR T-cells currently takes at least 4 weeks, they are not products which could be quickly employed initially at relapse in rapidly progressing mature B-cell malignancies but only for the consolidation phase of the treatment. Global, industry-supported, academic-sponsored studies testing compounds from different pharmaceutical companies simultaneously should be considered in rare populations, and it was proposed that an international working group be formed to develop an overarching clinical trials strategy for these disease groups. Future Forums are planned for other relevant paediatric oncologic diseases with a high unmet medical need and relevant molecular targets.

10.
Br J Haematol ; 185(6): 1111-1124, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30701541

RESUMO

Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of malignancies. Most NHLs in children, adolescent and young adult patients are aggressive lymphomas that are generally treated with multi-agent chemotherapy or immunochemotherapy regimens. While overall survival is high, the treatment can lead to a high rate of acute and long-term toxicity. However, in the rarer instance of relapsed or refractory disease, outcomes are dismal. Novel therapeutic approaches to the treatment of both T-cell and B-cell NHLs are critical to improve outcomes while also minimising the associated toxicity of current treatment regimes. Potential therapeutic approaches in development include humoral and cellular immunotherapies, small molecule inhibitors of relevant signalling pathways and epigenetic modifying agents. In this review, we will highlight the current state of development of agents of interest with a focus on agents relevant to childhood, adolescent and young adult NHL.

11.
Bull Cancer ; 106(1): 73-83, 2019 Jan.
Artigo em Francês | MEDLINE | ID: mdl-30527817

RESUMO

We describe herein the inaugural manifestations, the radiological and histological diagnosis criteria for and the outcome of epithelioid hemangioendothelioma (EHE). Most of EHE (90%) display a specific reciprocal chromosomic translocation t(1;3)(p36;q23-25), which is associated with the synthesis of fusion protein WWTR1/CAMTA1. EHE are low-grade vascular sarcomas. EHE could be initially localized or multifocal. At localized stage, EHE are best treated with focal treatments. At multifocal stage, the upfront strategy is watchful follow-up. Some multifocal EHE display very indolent course with spontaneous stable disease for years or decades. In case of progressive multifocal EHE, there is no consensual treatment. Diagnostic and clinical management of EHE requires interdisciplinary expertise from labeled centers.


Assuntos
Hemangioendotelioma Epitelioide , Diagnóstico por Imagem/métodos , Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/genética , Hemangioendotelioma Epitelioide/patologia , Hemangioendotelioma Epitelioide/terapia , Humanos , Translocação Genética
12.
J Clin Oncol ; : JCO2018789388, 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30351998

RESUMO

PURPOSE: Treatment recommendations for localized paratesticular rhabdomyosarcoma (PT RMS) differ in North America and Europe. We conducted a pooled analysis to identify demographic features and treatment choices that affect outcome. PATIENTS AND METHODS: We retrospectively analyzed the effect of nine demographic variables and four treatment choices on event-free survival (EFS) and overall survival (OS) from 12 studies conducted by five cooperative groups. RESULTS: Eight hundred forty-two patients with localized PT RMS who enrolled from 1988 to 2013 were included. Patients age ≥ 10 years were more likely than younger patients to have tumors that were > 5 cm, enlarged nodes (N1), or pathologically involved nodes ( P ≤ .05 each). With a median follow-up of 7.5 years, Kaplan-Meier estimates for 5-year EFS and OS were 87.7% and 94.8%, respectively. Of demographic variables, cooperative group, era of enrollment, age category, tumor size, Intergroup Rhabdomyosarcoma Study group, and T stage affected EFS ( P ≤ .05 each). Surgical assessment of regional nodes, which was performed in 23.5% of patients-usually in those age ≥ 10 years or with suspicious or N1 nodes-was the only treatment variable associated with EFS by univariable and multivariable analyses ( P ≤ .05 each) in patients age ≥ 1 year. A variable selection procedure on a proportional hazards regression model selected era of enrollment, age, tumor size, and surgical assessment of regional nodes as significant ( P ≤ .05 each) in the EFS model, and era of enrollment, age, tumor size, and histology ( P ≤ .05 each) in the OS model. CONCLUSION: Localized PT RMS has a favorable prognosis. Age ≥ 10 years at diagnosis and tumor size larger than 5 cm are unfavorable prognostic features. Surgical assessment of regional nodes is important in patients age ≥ 10 years and in those with N1 nodes as it affects EFS.

13.
Lancet Oncol ; 19(8): 1061-1071, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29941280

RESUMO

BACKGROUND: Rhabdomyosarcoma is an aggressive tumour that can develop in almost any part of the body. Doxorubicin is an effective drug against rhabdomyosarcoma, but its role in combination with an established multidrug regimen remains controversial. Therefore, we aimed to evaluate the possible benefit of early dose intensification with doxorubicin in patients with non-metastatic rhabdomyosarcoma. METHODS: We did a multicentre, open-label, randomised controlled, phase 3 trial involving 108 hospitals from 14 countries. We included patients older than 6 months but younger than 21 years with a pathologically proven diagnosis of rhabdomyosarcoma. We assigned each patient to a specific subgroup according to the EpSSG stratification system. Those with embryonal rhabdomyosarcoma incompletely resected and localised at unfavourable sites with or without nodal involvement, or those with alveolar rhabdomyosarcoma without nodal involvement were considered at high risk of relapse. These high-risk patients were randomly assigned (1:1) to receive either nine cycles of IVA (ifosfamide 3 g/m2 given as a 3-h intravenous infusion on days 1 and 2, vincristine 1·5 mg/m2 weekly during the first 7 weeks then only on day 1 of each cycle [given as a single intravenous injection], and dactinomycin 1·5 mg/m2 on day 1 given as a single intravenous injection) or four cycles of IVA with doxorubicin 30 mg/m2 given as a 4-h intravenous infusion on days 1 and 2 followed by five cycles of IVA. The interval between cycles was 3 weeks. Randomisation was done using a web-based system and was stratified (block sizes of four) by enrolling country and risk subgroup. Neither investigators nor patients were masked to treatment allocation. The primary endpoint was 3-year event-free survival assessed by the investigator at each centre in the intention-to-treat population. Patients who received at least one dose of study treatment were considered in the safety analysis. In agreement with the independent data monitoring committee, the study was closed to patient entry on Dec 16, 2013, after futility analysis. This trial is registered with EudraCT, number 2005-000217-35, and is currently in follow-up. FINDINGS: Between Oct 1, 2005, and Dec 16, 2013, 484 patients were randomly assigned to receive each chemotherapy regimen (242 in the IVA group and 242 in the IVA plus doxorubicin group). Median follow-up was 63·9 months (IQR 44·6-78·9). The 3-year event-free survival was 67·5% (95% CI 61·2-73·1) in the IVA plus doxorubicin group and 63·3% (56·8-69·0) in the IVA group (hazard ratio 0·87, 95% CI 0·65-1·16; p=0·33). Grade 3-4 leucopenia (232 [93%] of 249 patients in the IVA plus doxorubicin group vs 194 [85%] of 227 in the IVA group; p=0·0061), anaemia (195 [78%] vs 111 [49%]; p<0·0001), thrombocytopenia (168 [67%] vs 59 [26%]; p<0.0001), and gastrointestinal adverse events (78 [31%] vs 19 [8%]; p<0·0001) were significantly more common in the IVA plus doxorubicin group than in the IVA group. Grade 3-5 infections (198 [79%] vs 128 [56%]; p<0·0001) were also significantly more common in the IVA plus doxorubicin group than in the IVA group, in which one patient had grade 5 infection. Two treatment-related deaths were reported (one patient developed septic shock and one affected by Goldenhar syndrome developed intractable seizures) in the IVA plus doxorubicin group, both occurring after the first cycle of treatment, and none were reported in the IVA group. INTERPRETATIONS: The addition of dose-intensified doxorubicin to standard IVA chemotherapy did not show a significant improvement in the outcome of patients with high-risk non-metastatic rhabdomyosarcoma. Therefore, the IVA chemotherapy regimen should remain the standard of care for patients with localised rhabdomyosarcoma in Europe. FUNDING: Fondazione Città della Speranza, Italy, and the Association Léon Berard Enfant Cancéreux, France.

14.
Pediatr Blood Cancer ; 65(9): e27096, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29781567

RESUMO

BACKGROUND: Vaginal/uterine rhabdomyosarcoma (VU RMS) is one of the most favorable RMS sites. To determine the optimal therapy, the experience of four cooperative groups (Children's Oncology Group [COG], International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor Group [MMT], Italian Cooperative Soft Tissue Sarcoma Group [ICG], and European pediatric Soft tissue sarcoma Study Group [EpSSG]) was analyzed. PROCEDURE: From 1981 to 2009, 237 patients were identified. Median age (years) at diagnosis differed by tumor location; it was 1.9 for vagina (n = 160), 2.7 for uterus corpus (n = 26), and 13.5 for uterus cervix (n = 51). Twenty-eight percent of patients received radiation therapy (RT) as part of primary therapy (23% COG, 27% MMT, 46% ICG, and 42% EpSSG), with significant differences in the use of brachytherapy between the cooperative groups (23% COG, 76% MMT, 64% ICG, and 88% EpSSG). RESULTS: Ten-year event-free (EFS) and overall survival (OS) were 74% (95% CI, 67-79%) and 92% (95% CI, 88-96%), respectively. In univariate analysis, OS was inferior for patients with uterine RMS and for those with regional lymph node involvement. Although EFS was slightly lower in patients without initial RT (71% without RT vs. 81% with RT; P = 0.08), there was no difference in OS (94% without RT vs. 89% with RT; P = 0.18). Local control using brachytherapy was excellent (93%). Fifty-one (51.5%) of the 99 survivors with known primary therapy and treatment for relapse were cured with chemotherapy with or without conservative surgery. CONCLUSIONS: About half of all patients with VU RMS can be cured without systematic RT or radical surgery. When RT is indicated, modalities that limit sequelae should be considered, such as brachytherapy.

15.
J Pediatr Surg ; 53(7): 1428-1431, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29753523

RESUMO

BACKGROUND/PURPOSE: Fertility preservation is a major goal in treatment of children with cancer. We describe a new technique of testicular transposition (TT) in patients treated with pulse-dose-rate (PDR) brachytherapy as part of the multimodal conservative treatment of bladder neck and/or prostate rhabdomyosarcoma (BP RMS). METHODS: Medical records of consecutive patients treated between September 2016 and August 2017 were studied. These patients underwent a TT performed during BP RMS surgery by the same suprapubic incision. The external oblique aponeurosis was not incised. The spermatic cord was mobilized up to the external inguinal ring, and the gubernaculum attachments were severed from the scrotum. The testis was then flipped over with care taken to avoid injury of the vessels or the vas, wrapped in a silicone material and sutured under the abdominal skin with a transfixing stitch facing the anterior superior iliac spine. At the end of brachytherapy, the testis was relocated in the scrotum and during the same general anesthesia, plastic tubes and stents were removed. Surgical outcome and dosimetric parameters were examined. RESULTS: Eight patients were identified. Median age was 24 months (range 11-80 months). All had embryonal BP RMS and received chemotherapy according to RMS 2005 protocol prior to local treatment. All patients underwent conservative surgery followed by brachytherapy (60 Gy) and had testicular transposition of one testis. None had surgical complications. After converting doses to biologically equivalent doses in 2-Gy fractions (EQD2), the dose delivered to 75% of the transposed testis was 1.5 GyEQD2 (1-3 GyEQD2), versus 5.4 GyEQD2 (3.9-9.4 Gy EQD2) for the untransposed testis (p < 0.001). CONCLUSION: Testicular transposition is feasible in order to potentially preserve fertility and future quality of life in children undergoing brachytherapy for BP RMS. TYPE OF STUDY: Level IV Treatment Study: Case Study with no Comparison Group.


Assuntos
Braquiterapia/métodos , Tratamento Conservador , Neoplasias da Próstata/radioterapia , Rabdomiossarcoma/radioterapia , Neoplasias da Bexiga Urinária/radioterapia , Pré-Escolar , Humanos , Lactente , Masculino , Planejamento da Radioterapia Assistida por Computador/métodos , Rabdomiossarcoma/cirurgia , Testículo/cirurgia
16.
Bull Cancer ; 105(5): 523-536, 2018 May.
Artigo em Francês | MEDLINE | ID: mdl-29576221

RESUMO

Desmoplastic small round cell tumor (DSRCT) is a rare sarcoma that typically affects pediatric and young adult patients with a median age in the general and in the pediatric population of 24.6 years (range 4-58 years) and 15.0 years (range 0-21 years) respectively, with a strong male predominance. This tumor is characterized by a specific t(11;22)(p13;q12) that results in fusion of EWS and WT1 genes which can be demonstrated by RT-PCR or by FISH. DSRCT most frequently presents as an intra-abdominal primary mass associated with peritoneal seeding and a highly aggressive pattern of spread. Generally, all tumors showed the typical histologic findings of variably sized clusters of poly-phenotypic small, round, or spindled cells lying in a desmoplastic stroma. Treatment of this malignancy remains a challenge. The combination of polychemotherapy regimens and aggressive surgery followed by whole abdomen radiation therapy represents nowadays a classical protocol for DSRCT. The survival rate of DSRCT patients is still disappointing around 20 %. However, the survival of patients who had complete resection of the tumor appears better. Hopes are turning to targeted therapeutics against this simple genomic sarcoma. Authors summarize medical knowledge of this rare tumor.


Assuntos
Tumor Desmoplásico de Pequenas Células Redondas , Doenças Raras , Adolescente , Criança , Pré-Escolar , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 22 , Tumor Desmoplásico de Pequenas Células Redondas/genética , Tumor Desmoplásico de Pequenas Células Redondas/mortalidade , Tumor Desmoplásico de Pequenas Células Redondas/patologia , Tumor Desmoplásico de Pequenas Células Redondas/terapia , Feminino , Humanos , Masculino , Proteínas de Fusão Oncogênica/genética , Prognóstico , Doenças Raras/genética , Doenças Raras/mortalidade , Doenças Raras/patologia , Doenças Raras/terapia , Translocação Genética , Adulto Jovem
17.
Cancer Med ; 7(4): 1384-1393, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29533008

RESUMO

A genomic index (GI) tool using array comparative genomic hybridization (aCGH) on tumor cells has emerged as independent prognostic factor associated with the risk of metastatic relapse in synovial sarcoma (SS). The aim was to assess GI in pediatric patients with SS, to determine its value as a prognostic factor. All pediatric/adolescent/young adults' (<25 years) with localized SS prospectively included in the European EpSSG-NRSTS05 protocol with a contributive aCGH were selected. Definition of GI was A2 /C, where A is the total number of alterations (segmental gains and losses) and C is the number of involved chromosomes on aCGH results. GI1 group corresponds to cases with no copy number alterations (flat profile, GI = 0) and GI2 group cases with at least one or more copy number alterations (rearranged profile; GI ≥ 1). Samples were available from 61 patients. The median age of the cohort was 13 years (range: 4-24). Overall, 55.7% were GI1 group, and 44.3% GI2 . After a median follow-up of 62 months (range: 0.1-112), 10 tumor events occurred and five patients died. Respectively, for GI1 versus GI2 groups, five-year event-free survival (EFS) was 93.8 ± 4.2% versus 64.9 ± 10.1% (P < 0.006) and five-year Metastatic-Free Survival (MFS) 93.8 ± 4.2% versus 72.9 ± 9.5% (P < 0.04). In multivariate analysis, GI status as adjusted for IRS group, patient age, site, and tumor size remain independent prognostic for EFS with a relative risk (RR) of 6.4 [1.3-31.9] (P < 0.01) and RR for MFS is 4.8 [0.9-25.7] (P < 0.05). Genomic complexity evaluated through GI may explain the metastatic behavior of pediatric SS.

18.
J Craniomaxillofac Surg ; 46(2): 201-206, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29275074

RESUMO

OBJECTIVES: Melanotic neuroectodermal tumor of infancy (MNTI) of the head and neck is a rare entity with uncertain clinical behavior. Radical surgical resection is the current recommended treatment, however this can cause severe aesthetic and functional sequelae. The aim of this study was to clinically characterize MNTIs and to stratify risk factors that may influence locoregional recurrence. METHODS: A retrospective multicenter study, including 11 patients from eight centers with a confirmed diagnosis of MNTI, was conducted. Epidemiological, clinical, radiological, pathological, and immunohistochemical examinations were reviewed. A statistical analysis using a t-test was conducted to calculate parameters correlating with tumor recurrence. RESULTS: MNTIs mainly occurred in the maxilla, with a mean age at diagnosis of 3.18 months (range: 0-6 months). Primary surgery was performed on 10 patients, with a clear margin resection on two patients. Overall recurrence rate was 27% with a survival of 100% at time of follow-up. No statistical correlation between recurrence rate, age at diagnosis, localization, resection margins, and pathological and immunohistochemical characteristics could be established. CONCLUSION: In our study, locoregional tumor recurrence did not seem to correlate with resection margins, so a conservative surgical approach may need to be considered to avoid functional and aesthetic sequelae.


Assuntos
Neoplasias de Cabeça e Pescoço/etiologia , Tumor Neuroectodérmico Melanótico/etiologia , Feminino , França/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Lactente , Recém-Nascido , Imagem por Ressonância Magnética , Masculino , Neoplasias Mandibulares/epidemiologia , Neoplasias Mandibulares/etiologia , Neoplasias Mandibulares/patologia , Neoplasias Mandibulares/cirurgia , Neoplasias Maxilares/epidemiologia , Neoplasias Maxilares/etiologia , Neoplasias Maxilares/patologia , Neoplasias Maxilares/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Tumor Neuroectodérmico Melanótico/epidemiologia , Tumor Neuroectodérmico Melanótico/patologia , Tumor Neuroectodérmico Melanótico/cirurgia , Neoplasias Orbitárias/epidemiologia , Neoplasias Orbitárias/etiologia , Neoplasias Orbitárias/patologia , Neoplasias Orbitárias/cirurgia , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
20.
Cancer ; 124(5): 1016-1024, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29211298

RESUMO

BACKGROUND: Early response to induction chemotherapy is used in current European guidelines to evaluate the efficacy of chemotherapy and subsequently to adapt treatment in pediatric patients with rhabdomyosarcoma (RMS). However, existing literature on the prognostic value of early radiologic response on survival is contradictory; here the prognostic value is analyzed with data from the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor 95 (MMT-95) study. METHODS: This study examined 432 Intergroup Rhabdomyosarcoma Study Grouping III (macroscopic residue) patients enrolled in the SIOP MMT-95 study with a response assessment after 3 courses of chemotherapy (a 2-dimensional assessment). Patients with progressive disease (PD) after 3 courses of chemotherapy were excluded (n = 7). Failure-free survival (FFS) and overall survival (OS), calculated with the Kaplan-Meier method, were compared for 3 groups (complete response [CR]/partial response [PR], objective response [OR], and no response [NR]). The prognostic impact of early response was assessed through the calculation of Cox proportional hazards. RESULTS: After 3 courses of chemotherapy, 85.2% of the patients had CR/PR, 8.6% had OR, and 6.3% had NR. For all patients, the 5-year FFS and OS rates were 60% (95% confidence interval [CI], 56%-65%) and 74% (95% CI, 70%-78%), respectively. However, a Cox proportional hazards regression analysis revealed no significant difference in FFS or OS between the response groups. The adjusted hazard ratios for an OR and NR were 1.09 (95% CI, 0.63-1.88) and 0.81 (95% CI, 0.39-1.67), respectively, for FFS and 0.91 (95% CI, 0.47-1.76) and 1.27 (95% CI, 0.61-2.64), respectively, for OS. CONCLUSIONS: No evidence was found for the idea that early radiologic response to chemotherapy is prognostic for survival for patients with RMS. Treatment adaptation based on early response (except for patients with PD) should, therefore, no longer be incorporated into future studies. Cancer 2018;124:1016-24. © 2017 American Cancer Society.

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