Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 177
Filtrar
1.
Lancet Oncol ; 2019 Sep 24.
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(11): e27932, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31385434

RESUMO

PURPOSE: The presence of pleural effusion or ascites at the time of diagnosis is generally considered a poor prognostic factor for children with rhabdomyosarcoma (RMS), and treatment is usually intensified despite the fact that there are no published studies to support this decision. We investigated the prognostic role of the presence of pleural effusion or ascites at diagnosis in patients with localized RMS consecutively enrolled in the Italian Soft Tissue Sarcoma Committee protocols over a 30-year period. METHODS: We reviewed the radiological reports at diagnosis of 150 children with supradiaphragmatic and infradiaphragmatic RMS, noting any presence of effusion and its extent (minimal, moderate, or massive). All patients received intensive chemotherapy, surgery, and standard or hyperfractionated radiotherapy. RESULTS: Effusion was identified in 32 children (21.3%), 14 with pleural effusion and 18 with ascites. As for its extent, 13 children presented with minimal, 12 with moderate, and 7 with massive effusion. The 5-year progression-free survival (PFS) rate was 49.8% (confidence interval [CI] 31.7-65.5) and 49.5% (CI 40-58.2) for patients with and without effusion, respectively (P = .5). When only patients with moderate or massive effusion were considered, however, their PFS was 36.8% (CI 16.5-57.5) versus 51.2% (CI 42.2-59.5) in patients with minimal or no effusion (P = .01). On the whole, patients with pleural effusion had a very poor outcome with a 5-year PFS of 35.7% (CI 13-59.4). CONCLUSIONS: The presence of moderate or massive effusion seems to be an unfavorable prognostic factor in children with RMS, and justifies their inclusion in experimental studies.

3.
Pediatr Blood Cancer ; 66(10): e27833, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31241238

RESUMO

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are rare tumors of childhood. The role of standard chemotherapy in unresectable MPNST is still unclear. We report the outcome and prognostic factors in the EpSSG risk-adapted prospective study for localized pediatric MPNST. METHODS: Patients were stratified into four treatment groups defined by surgical resection, tumor size, and tumor grade (G): (a) surgery-only group-resected tumors G1; (b) adjuvant radiotherapy group-R0/R1, G2 tumors; (c) adjuvant chemotherapy group-R0/R1, G3 tumors; and (d) neoadjuvant chemotherapy group-R2 resected tumors and/or nodal involvement. Chemotherapy consisted of four courses of ifosfamide-doxorubicin and two courses of ifosfamide concomitant with radiotherapy (50.4-54 Gy). RESULTS: Overall, the study included 51 patients. The 5-year event-free survival (EFS) and overall survival (OS) were 52.9% (95% confidence interval, 38.1-65.8) and 62.1% (46.7-74.3), respectively. The 5-year EFS was 92% (56.6-98.9) for treatment group 1 (N = 13), 33% (0.9-77.4) for treatment group 2 (N = 4), 29% (4.1-61.2) for treatment group 3 (N = 7), and 42% (23.1-60.1) for treatment group 4 (N = 27). Response rate to chemotherapy (partial response + complete response) in patients with measurable disease was 46%. The presence of neurofibromatosis type 1 (NF1; 51% of patients) was an independent poor prognostic factor for OS and EFS. CONCLUSION: The outcome for patients with resectable MPNST was excellent. Standard ifosfamide-doxorubicin for unresectable MPNST rendered the best reported outcome. Children with NF1 disease seem to have worse prognosis.

4.
Laryngoscope ; 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31090942

RESUMO

OBJECTIVE: Primary tracheobronchial tumors (PTTs) are rare heterogeneous lesions arising from any part of the tracheobronchial tree. Nonspecific symptoms may lead to delayed diagnosis that requires more aggressive surgical treatment. An analysis of cases collected by the International Network of Pediatric Airway Team was undertaken to ensure proper insight into the behavior and management of PTTs. METHODS: Patients < 18 years of age with a histological confirmation of PTT diagnosed from 2000 to 2015 were included in this multicenter international retrospective study. Medical records, treatment modalities, and outcomes were analyzed. The patient presentation, tumor management, and clinical course were compared between malignant and benign histotypes. Clinical and surgical variables that might influence event-free survival were considered. RESULTS: Among the 78 children identified, PTTs were more likely to be malignant than benign; bronchial carcinoid tumor (n = 31; 40%) was the most common histological subtype, followed by inflammatory myofibroblastic tumor (n = 19; 25%) and mucoepidermoid carcinoma (n = 15; 19%). Regarding symptoms at presentation, wheezing (P = 0.001) and dyspnea (P = 0.03) were more often associated with benign growth, whereas hemoptysis was more frequently associated with malignancy (P = 0.042). Factors that significantly worsened event-free survival were age at diagnosis earlier than 112 months (P = 0.0035) and duration of symptoms lasting more than 2 months (P = 0.0029). CONCLUSION: The results of this international study provide important information regarding the clinical presentation, diagnostic workup, and treatment of PTTs in children, casting new light on the biological behavior of PTTs to ensure appropriate treatments. LEVEL OF EVIDENCE: NA Laryngoscope, 2019.

5.
Eur J Cancer ; 112: 98-106, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30954717

RESUMO

BACKGROUND: Data on the clinical features, optimal treatment and outcomes of paediatric patients with epithelioid sarcoma (ES) are limited and mostly retrospective. METHODS: A subset analysis of ES patients < 30 years of age enrolled on two international prospective clinical trials conducted between 7/2005 and 11/2015 was performed. Risk-adapted therapy was based on tumour diameter, histologic grade, extent of surgery and presence/absence of metastases and included surgery ± radiotherapy for all patients with the addition of ifosfamide/doxorubicin chemotherapy for intermediate-/high-risk patients. Response to therapy, event-free and overall survival and pattern and predictors of treatment failure were evaluated. RESULTS: Sixty-three ES patients (median age 13.1 years, 52% male) were eligible. Clinical features included the following: 68% extremity, median tumour diameter 3.5 cm, 56% high histologic grade, 14% nodal metastases, 14% distant metastases. Thirty-four low-risk patients underwent surgery (n = 30) or surgery/radiotherapy (n = 4); 16 intermediate-risk and 13 high-risk patients received chemotherapy ± surgery ± radiotherapy. Partial response was observed in 11/22 (50%) patients receiving neoadjuvant therapy. Events were local recurrence (n = 10) and distant recurrence (n = 15); estimated 5-year survival was 86.4%, 63.5% and 0%, respectively, for low-, intermediate- and high-risk patients. Locoregional nodal involvement, invasive tumour, high grade and lesser extent of resection predicted event-free survival in patients without metastases. CONCLUSIONS: Most low-risk ES patients who have undergone an adequate resection fare well without adjuvant therapy. Large tumour size, high histologic grade, tumour invasiveness, inadequate tumour resection and metastatic disease predict poorer outcomes in higher risk ES patients, for whom more effective therapies are needed. CLINICAL TRIAL REGISTRATION: COG ARST0332: ClinicalTrials.gov Identifier NCT00346164, EpSSG NRSTS 2005: European Union Drug Regulating Authorities Clinical Trials No. 2005-001139-31.

6.
Pediatr Blood Cancer ; 66(7): e27695, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30865371

RESUMO

BACKGROUND: Hepatic veno-occlusive (VOD) disease has been described in hematopoietic stem cell transplantation (HSCT), solid tumors, and acute lymphoblastic leukemia. The incidence of VOD in Wilms tumor (WT) ranges from 1.2% to 8%. The diagnosis of VOD is clinical, and there are no validated laboratory biomarkers. PROCEDURE: We prospectively evaluated the specificity and sensitivity of plasminogen-activator inhibitor-1 (PAI-1) and protein C as diagnostic markers of VOD in WT patients. Fifty patients treated from 2008 to 2016 for WT were eligible. VOD was diagnosed according to modified Seattle criteria and retrospectively reclassified according to the recently published criteria for VOD in pediatric HSCT patients. RESULTS: VOD occurred in 6 of 50 patients (12%) after 20 to 97 days from starting chemotherapy. The average duration of VOD was 10 days (range, 4-13 days). PAI-1 levels were elevated in all VOD patients, while a decrease in protein C levels was observed in 33% of patients with VOD. PAI-1 antigen (Ag) values ≥ 26.4 ng/mL demonstrated high sensitivity and specificity for the clinical diagnosis of VOD with sensitivity 100%, specificity 93%; whereas protein C levels below 34.5% had sensitivity 67%, specificity 100%. Both PAI-1 and protein C had an high negative predictive value: PAI-1 Ag 100%; protein C 95%. CONCLUSIONS: PAI-1 Ag and protein C have good sensitivity and specificity for the diagnosis of VOD in WT patients. Their high negative predictive value can be used in the differential diagnosis of liver toxicity, especially in VOD episodes with absent or delayed hyperbilirubinemia.

7.
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.

8.
J Clin Oncol ; 37(9): 723-730, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30702969

RESUMO

PURPOSE: To evaluate the clinical significance of indeterminate pulmonary nodules at diagnosis (defined as ≤ 4 pulmonary nodules < 5 mm or 1 nodule measuring ≥ 5 and < 10 mm) in patients with pediatric rhabdomyosarcoma (RMS). PATIENTS AND METHODS: We selected patients with supposed nonmetastatic RMS treated in large pediatric oncology centers in the United Kingdom, France, Italy, and the Netherlands, who were enrolled in the European Soft Tissue Sarcoma Study Group (E pSSG) RMS 2005 study. Patients included in the current study received a diagnosis between September 2005 and December 2013, and had chest computed tomography scans available for review that were done at time of diagnosis. Local radiologists were asked to review the chest computed tomography scans for the presence of pulmonary nodules and to record their findings on a standardized case report form. In the E pSSG RMS 2005 Study, patients with indeterminate pulmonary nodules were treated identically to patients without pulmonary nodules, enabling us to compare event-free survival and overall survival between groups by log-rank test. RESULTS: In total, 316 patients were included; 67 patients (21.2%) had indeterminate pulmonary nodules on imaging and 249 patients (78.8%) had no pulmonary nodules evident at diagnosis. Median follow-up for survivors (n = 258) was 75.1 months; respective 5-year event-free survival and overall survival rates (95% CI) were 77.0% (64.8% to 85.5%) and 82.0% (69.7% to 89.6%) for patients with indeterminate nodules and 73.2% (67.1% to 78.3%) and 80.8% (75.1% to 85.3%) for patients without nodules at diagnosis ( P = .68 and .76, respectively). CONCLUSION: Our study demonstrated that indeterminate pulmonary nodules at diagnosis do not affect outcome in patients with otherwise localized RMS. There is no need to biopsy or upstage patients with RMS who have indeterminate pulmonary nodules at diagnosis.

9.
Eur J Cancer ; 110: 120-126, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30785015

RESUMO

Although all tumours are rare in childhood, there are some particularly rare paediatric cancers which have not benefited from advances made by the international paediatric oncology network. To establish a shared definition and produce a list of these entities, the European Union Joint Action on Rare Cancers (JARC) promoted a consensus effort. The definition was based on the incidence rates estimated using the information network on rare cancers (RARECAREnet) database, pooling data from 94 population-based cancer registries and 27 countries. The RARECAREnet list of cancers was used to estimate the incidence rates. This list groups cancers by combining the International Classification of Diseases for Oncology, third edition, morphology and topography codes. According to the consensus, very rare paediatric cancers were identified as those with an annual incidence <2/1000000 and corresponded to 11% of all cancers in patients aged 0-14 years. Two subgroups were identified: tumour types typical of childhood (i.e. hepatoblastoma, pleuropulmonary blastoma, pancreatoblastoma) and those typical of adult age (i.e. carcinomas, melanoma). The threshold of 2/1000000 could also be adopted in populations aged 0-19 years: in this case, three tumour types had an incidence rate which was >2/1000000 (i.e. thyroid and testicular cancers and skin melanoma), but the consensus experts considered them as 'very rare' according to their clinical needs (e.g. shortage of knowledge and clinical expertise as the other rare paediatric cancers). The JARC consensus produced a definition and a list of very rare paediatric cancers which may represent a starting point for prioritising research on these tumours, based on data and patients' clinical needs.

10.
Methods Mol Biol ; 1909: 165-175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30580430

RESUMO

Rhabdomyosarcoma is an aggressive solid tumor that may disseminate hematogenously giving metastasis which represents the most important prognostic factor. Chances of an effective cure in childhood cancer rely on the capacity to make an early and accurate diagnosis, detect metastatic disease or relapse, and predict the response to treatment.Liquid biopsy is a very promising blood test for cancer detection and noninvasive disease monitoring. This method has a great advantage to use blood and plasma, a more accessible biological material, quick and easy to obtain with minimal pain and risk for patients. In particular, circulating free DNA (cfDNA) represents a tumor biomarker detected in plasma that gives information on biology and genetic background of tumor.Moreover, cfDNA mutation detection could be a reliable method to monitor the efficacy of treatment and to discover novel targets for a personalized treatment in pediatric solid tumor. Here, we describe an optimized protocol to cfDNA isolation from small amount of plasma, as well as a method to assess the quantity and quality of cfDNA. Finally, we propose ddPCR as a reliable method to detect mutations at low frequency in cfDNA obtained from pediatric rhabdomyosarcoma samples.


Assuntos
Ácidos Nucleicos Livres/genética , Análise Mutacional de DNA/métodos , Rabdomiossarcoma/genética , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/isolamento & purificação , Criança , Fluorometria/métodos , Humanos , Mutação , Reação em Cadeia da Polimerase/métodos , Rabdomiossarcoma/sangue
11.
Pediatr Blood Cancer ; 66(1): e27472, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30270493

RESUMO

INTRODUCTION: The treatment paradigm in desmoid-type fibromatosis (DF) has changed in recent years from a surgery-based strategy to a multidisciplinary approach that includes systemic therapies. Among various medical therapies, hydroxyurea has been considered of potential interest. This case series summarizes the experience gained at four centers using hydroxyurea in relapsing DF. METHODS: Eligibility requirements were age < 21 years, histologically confirmed DF, and progressive or recurrent disease after at least one line of systemic therapy. Hydroxyurea was given orally at an initial dose of 20 mg/kg/day (escalated up to 30 mg/kg/day as necessary, if well tolerated). RESULTS: The series included 16 patients treated between 2008 and 2016. Hydroxyurea was the second systemic therapy in nine cases, and the third (at least) in seven. There was no reported G3-G4 hematological toxicity, and one case of G3 diarrhea. Dose reductions were reported in three cases (due to G2 neutropenia). The response rate was 18.7% major partial remissions, 37.5% considering any amount of shrinkage, 68.7% considering symptom response or signs of tissue response as well. In patients with no progression, the treatment was continued for 9-24 months. CONCLUSION: This is the first published series on the efficacy of hydroxyurea in pediatric DF. The response rate was moderate, but similar to that reported for other medical therapies currently considered as treatment options in this disease. Though further, larger series are needed to confirm as much, hydroxyurea has potential as an effective alternative therapy for DF.

12.
Pediatr Blood Cancer ; : e27519, 2018 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-30362240

RESUMO

BACKGROUND: Solid pseudopapillary pancreatic tumors (SPPT) are an extremely rare entity in pediatric patients. Even if the role of radical surgical resection as primary treatment is well established, data about follow-up after pancreatic resection in children are scant. METHODS: A retrospective review of data from the Italian Pediatric Rare Tumor Registry (TREP) was performed. Short-term (<30 days) and long-term complications of different surgical resections, as well as long-term follow-up were evaluated. RESULTS: From January 2000 to present, 43 patients (male:female = 8:35) were enrolled. The median age at diagnosis was 13.2 years (range, 7-18). Nine children had an incidental diagnosis, whereas 26 complained of abdominal pain and 4 of palpable mass. Tumors arose either from the head of pancreas (n = 14) or from body/tail (n = 29): only one patient presented with metastatic disease. Resection was complete in all patients (cephalic duodenopancreatectomy vs distal resection). At follow-up (median, 8.4 years; range, 0-17 years), one recurrence occurred in a patient with intraoperative rupture. All patients are alive. Three pancreatic fistulas occurred in the body/tail group, whereas four complications occurred in the head group (one ileal ischemia, two stenosis of the pancreatic duct, and one chylous fistula). CONCLUSION: Surgery is the best therapeutic option for these tumors; hence, complete resection is mandatory. Extensive resections, including cephalic duodenopancreatectomy, are safe when performed in specialized centers. Long-term follow-up should be aimed to detect tumor recurrence and to evaluate residual pancreatic function.

13.
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.

14.
Urol Oncol ; 36(11): 502.e7-502.e13, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30249520

RESUMO

OBJECTIVES: We report the results of an Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) study on the treatment of testicular germ cell tumors (TGCT) with a pediatric PEB (pPEB) regimen (cisplatin 25 mg/m2 daily on days 1-4; etoposide 100 mg/m2 daily on days 1-4; bleomycin 15 mg/m2 on day 2, once per cycle). METHODS AND MATERIALS: Male patients under 18 years old with malignant TGCT were enrolled for a second national prospective protocol. All patients underwent orchiectomy at diagnosis. Those with Stage I received no chemotherapy; those with Stage II-III disease received three cycles of pPEB; and those with Stage IV received four cycles. After chemotherapy, resection of radiologically-evident residual disease was recommended. The main study end-points were overall survival and relapse-free survival. RESULTS: Ninety-nine boys from 0.5 to 17.8 years old (median 15.4 years) were evaluable, and staged as follows: 58 Stage I (59%), 7 Stage II (7%), 14 Stage III (14%), and 20 Stage IV (20%). With a median follow-up of 59 months (range 4-165 months), 5-year relapse-free survival (95% CI) was 73% (65%-83%) for the whole sample, 65% (53%-79%) for Stage I patients, and 86% (75%-98%) for Stage II-IV patients. Five-year overall survival (95% CI) was 99% (97%-100%). CONCLUSIONS: We confirmed a good prognosis for malignant TGCT in children and adolescents. Reducing the number of chemotherapy cycles for Stage II-III disease does not seem to negatively affect survival outcomes.

15.
Tumori ; : 300891618792479, 2018 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-30131003

RESUMO

INTRODUCTION: From 2002 to 2011, the Italian Soft Tissue Sarcoma Committee explored a combination of topotecan and carboplatin as a second-line strategy for children with resistant or relapsing rhabdomyosarcoma. METHODS: Patients received two blocks of topotecan 2 mg/m2 on days 1, 2, and 3, and carboplatin 250 mg/m2 on days 4 and 5, followed by alternating blocks of topotecan-cyclophosphamide and carboplatin-etoposide for a total of six courses with 3-week intervals. Tumor response was assessed after two cycles, and local control was implemented when feasible. RESULTS: A total of 38 patients were included in this study: 18/38 had alveolar rhabdomyosarcoma (RMS), 10/38 had metastatic disease at diagnosis, 8/38 had tumor progression during first-line chemotherapy, 21/38 had locoregional relapses, and 9/38 had distant relapses. Thirty-two patients could be assessed for tumor response to topotecan-carboplatin, and 9 (28%) showed a complete or partial response. Twenty-four patients experienced grade IV hematologic toxicity, while transient grade 1 tubulopathy, grade 3 mucositis, transient grade 2 nephrotoxicity, and a grade 2 decline in cardiac function occurred in one patient each. The 5-year overall and progression-free survival rates were 17% and 14%, respectively. CONCLUSION: the prognosis for children with resistant or relapsing RMS remains unsatisfactory. The topotecan-carboplatin regimen was well-tolerated. Though in case of late relapse the response rate was similar to those reported for other regimes, the result achieved remains unsatisfactory. New approaches, possibly including target agents, seem more attractive for future studies.

16.
Cancer Treat Rev ; 68: 94-101, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29940525

RESUMO

We review and summarize the highlights of almost five decades of cooperative group trials in rhabdomyosarcoma on both sides of the Atlantic, concentrating on chemotherapy regimens, what has been learned, and where remaining challenges are. The most important achievements have been to decrease or omit the dose of alkylator therapy for many patients, to clarify after much controversy that doxorubicin does not improve the outcome of patients even in the highest risk groups, and to show that high dose chemotherapy and stem cell rescue do not improve the outcome of the highest risk patients. In North America, vincristine/actinomycin/cyclophosphamide (VAC) remains an important part of therapy, whereas in Europe the alkylating agent of choice is ifosfamide. The highest risk patients, namely those with the poorest prognostic score, have had no improvement in outcome since the first cooperative group trial in 1972 and remain the greatest challenge. Philosophical differences between European and North American strategies still revolve somewhat around the total burden of therapy received, that is should certain groups of patients be spared aggressive local control in order to reduce late effects, recognizing that it is not possible to identify priori the children that can be cured with this approach exposing the whole population to a higher risk of relapse. Collaboration and joining resources may help answer some difficult questions.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Rabdomiossarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Criança , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dactinomicina/administração & dosagem , Dactinomicina/efeitos adversos , Europa (Continente) , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Internacionalidade , América do Norte , Ensaios Clínicos Controlados Aleatórios como Assunto , Vincristina/administração & dosagem , Vincristina/efeitos adversos
17.
Ther Adv Urol ; 10(6): 189-196, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29899760

RESUMO

The latest multimodal protocols for treatment of bladder/prostate rhabdomyosarcoma (RMS) have shifted the goal of treatment from patient survival to bladder preservation. Consistently, partial resections, such as radical prostatectomy (RP), are favoured when surgery is deemed necessary. We sought to determine the oncological risks - that is, failure to achieve disease control - and the possible benefits in terms of urinary continence associated with RP in RMS patients based on a review of our experience and the data reported in the literature. We identified 18 children undergoing RP for RMS (3 at our institution, 15 in the literature). In five cases, a pubectomy/symphisiotomy was performed to improve surgical exposure. Two cases experienced local relapse, suggesting that this approach can be viable to achieve local control. No clear-cut indications could be extrapolated from the literature, however, to determine how to select the patients most suitable for this approach. We offered this treatment to patients with evidence of disease localized only within the prostate on radiological and endoscopic re-assessment after chemo-/radio-therapy. Eight of the 18 cases (44%) eventually required lower urinary tract reconstruction, suggesting that often this approach does not allow for the preservation of urinary continence with volitional voiding. Finally, data about additional interesting outcomes such as erectile function and fertility in RMS patients undergoing RP are extremely sparse.

18.
Eur J Cancer ; 100: 27-34, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29936064

RESUMO

BACKGROUND: nab-Paclitaxel has demonstrated efficacy in adults with solid tumours and preclinical activity in paediatric solid tumour models. Results from phase I of a phase I/II study in paediatric patients with recurrent/refractory solid tumours treated with nab-paclitaxel are reported. PATIENTS AND METHODS: Patients with recurrent/refractory extracranial solid tumours received nab-paclitaxel on days 1, 8 and 15 every 4 weeks at 120, 150, 180, 210, 240, or 270 mg/m2 (rolling-6 dose-escalation) to establish the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). RESULTS: Sixty-four patients were treated. Dose-limiting toxicities were grade 3 dizziness at 120 mg/m2 and grade 4 neutropenia >7 days at 270 mg/m2. The most frequent grade 3/4 adverse events were haematologic, including neutropenia (36%), leukopenia (36%) and lymphopenia (25%). Although the MTD was not reached, 270 mg/m2 was declared non-tolerable due to grade 3/4 toxicities during cycles 1-2 (neutropenia, n = 5/7; skin toxicity, n = 2/7; peripheral neuropathy, n = 1/7). Of 58 efficacy-evaluable patients, complete response occurred in one patient (2%; Ewing sarcoma) and partial responses in four patients (7%; rhabdomyosarcoma, Ewing sarcoma, renal tumour with pulmonary metastases [high-grade, malignant] and sarcoma not otherwise specified); all responses occurred at ≥210 mg/m2. Thirteen patients (22%) had stable disease (5 lasting ≥16 weeks) per RECIST. CONCLUSIONS: nab-Paclitaxel 240 mg/m2 qw3/4 (nearly double the adult recommended monotherapy dose for this schedule in metastatic breast cancer) was selected as the RP2D based on the tolerability profile, pharmacokinetics and antitumour activity. Phase II is currently enrolling patients with recurrent/refractory neuroblastoma, rhabdomyosarcoma and Ewing sarcoma. CLINICALTRIALS.GOV: NCT01962103. EUDRACT: 2013-000144-26.

19.
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.

20.
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.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA