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1.
Exp Eye Res ; 224: 109211, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35985532

RESUMO

Retinoblastoma is a rare childhood tumor caused by the inactivation of both copies of the RB1 gene. Early diagnosis and identification of heritable RB1 mutation carriers can improve the disease outcome and management via genetic counseling. We used the Multiplex Ligation-dependent Probe Amplification (MLPA) method to analyze the RB1 gene and flanking regions in blood samples from 159 retinoblastoma patients previously negative for RB1 point mutations via Sanger sequencing. We detected a wide spectrum of germline chromosomal alterations, ranging from partial loss or duplication of RB1 to large deletions spanning RB1 and adjacent genes. Mutations were validated via karyotyping, fluorescent in situ hybridization (FISH), SNP-arrays (Single Nucleotide Polymorphism-arrays) and/or quantitative relative real-time PCR. Patients with leukocoria as a presenting symptom showed reduced death rate (p = 0.013) and this sign occurred more frequently among carriers of two breakpoints within RB1 (p = 0.05). All unilateral cases presented both breakpoints outside of RB1 (p = 0.0075). Patients with one breakpoint within RB1 were diagnosed at earlier ages (p = 0.017). Our findings characterize the mutational spectrum of a Brazilian cohort of retinoblastoma patients and point to a possible relationship between the mutation breakpoint location and tumor outcome, contributing to a better prospect of the genotype/phenotype correlation and adding to the wide diversity of germline mutations involving RB1 and adjacent regions in retinoblastoma.


Assuntos
Neoplasias da Retina , Retinoblastoma , Humanos , Retinoblastoma/diagnóstico , Retinoblastoma/genética , Retinoblastoma/patologia , Hibridização in Situ Fluorescente , Brasil/epidemiologia , Genes do Retinoblastoma/genética , Mutação , Neoplasias da Retina/patologia , Análise Mutacional de DNA
2.
Pediatr Blood Cancer ; 69(1): e29274, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34767315

RESUMO

BACKGROUND: Medulloblastoma (MB),the most common malignant brain tumor of childhood has survival outcomes exceeding 80% for standard-risk and 60% for high-risk patients in high-income countries (HICs). These results have not been replicated in low- and middle-income countries (LMICs), where 80% of children with cancer live. METHODS: This is a retrospective review of 114 children aged 3-18 years diagnosed with MB from 1997 to 2016 at National Cancer Institute (INCA). Sociodemographic, clinical, and treatment data were extracted from the medical records and summarized descriptively. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. RESULTS: The male-to-female ratio was 1.32 and the median age at diagnosis was 8.2 years. Headache (83%) and nausea/vomiting (78%) were the most common presenting symptoms. Five-year OS was 59.1% and PFS was 58.4%. The OS for standard-risk and high-risk patients was 69% and 53%, respectively. The median time to diagnosis interval was 50.5 days and the median time from surgery to radiation therapy initiation was 50.4 days. Patients who lived >40 km from INCA fared better (OS = 68.2% vs. 51.1%, p = .032). Almost 20% of families lived below the Brazilian minimum wage. Forty-five patients (35%) had metastatic disease at admission. Gross total resection was achieved in 57% of the patitents. CONCLUSIONS: Although there are considerable barriers to deliver effective MB treatment in countries like Brazil, the OS seen in the present study demonstrates that good outcomes are not only feasible but can and should be increased with appropriate interventions.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Brasil/epidemiologia , Neoplasias Cerebelares/epidemiologia , Neoplasias Cerebelares/terapia , Criança , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Meduloblastoma/epidemiologia , Meduloblastoma/terapia , Estudos Retrospectivos , Resultado do Tratamento
3.
Support Care Cancer ; 30(5): 4283-4289, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35088149

RESUMO

PURPOSE: In the last few decades, interest in palliative care and advance care planning has grown in Brazil and worldwide. Empirical studies are needed to reduce therapeutic obstinacy and medical futility in the end-of-life care of children with incurable cancer. The aim of this study was to investigate the effects of do-not-resuscitate-like (DNRL) orders on the quality of end-of-life care of children with incurable solid tumors at a cancer center in Brazil. METHODS: A retrospective observational cohort study of 181 pediatric patients with solid tumors followed at the Pediatric Oncology Department of the Brazilian National Cancer Institute, Rio de Janeiro, Brazil, who died due to disease progression from 2009 to 2013. Medical records were reviewed for indicators of quality of end-of-life care, including overtreatment, care planning, and care at death, in addition to documentation of the diagnosis of life-limiting illness and the presence of a DNRL order. Data were summarized using descriptive statistics. Univariate and multivariate logistic regression analyses were used to examine associations between demographics, disease, treatment, and indicators of end-of-life care with a DNRL order. RESULTS: A documented DNRL order was associated with lower odds of dying in the intensive care unit or emergency room (80%), dying within 30 days of endotracheal tube placement (80%), or cardiopulmonary resuscitation (CPR) administration at the time of death (96%). CONCLUSION: Placement of DNRL orders early in the disease process is critical in reducing futile treatment in pediatric patients with incurable cancer.


Assuntos
Neoplasias , Assistência Terminal , Brasil , Criança , Humanos , Neoplasias/terapia , Cuidados Paliativos , Ordens quanto à Conduta (Ética Médica) , Estudos Retrospectivos
4.
Pediatr Blood Cancer ; 68(11): e29317, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34490992

RESUMO

BACKGROUND: Changesin nutritional status can constitute a risk factor for reduced tolerance and effectiveness of antineoplastic treatment. Knowledge of the nutritional status of pediatric patients is important for implementing interventions to improve outcomes. We aimed to evaluate nutritional status at diagnosis and throughout therapy in pediatric patients with solid tumors. OBJECTIVES: To study the prevalence of malnutrition at diagnosis, compare different assessment tools, and examine longitudinal changes in nutritional status during the treatment of pediatric patients with solid tumors in a Brazilian institution. METHODS: This prospective single-center study enrolled patients with solid tumors (age <19 years) from June 2017 to May 2018. Nutritional evaluations were performed at diagnosis and after 3 and 6 months of treatment. z-Scores for height for age (H/A) and body mass index for age (BMI/A) were calculated using the Anthro/AnthroPlus software and mid-upper arm circumference (MUAC) percentile was used for nutritional classification. RESULTS: The prevalence of nutritional status at diagnosis was 29.3% malnourished, 49.5% adequate, and 21.2% overweight/obese. Nutritional status improved during the first 3 months of treatment, with a reduction in the proportion of malnourished patients and an increased number of patients with adequate nutritional status. CONCLUSIONS: The two combined indices, BMI/A and MUAC, facilitated the diagnosis of a greater number of patients with solid tumors who had nutritional alterations. A high prevalence of malnutrition was present at diagnosis. Nutritional status improved in the first 3 months of treatment and could be related to the multidisciplinary institutional approach following the diagnosis.


Assuntos
Desnutrição , Neoplasias , Adolescente , Antropometria , Índice de Massa Corporal , Criança , Países em Desenvolvimento , Humanos , Desnutrição/diagnóstico , Desnutrição/etiologia , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Estado Nutricional , Estudos Prospectivos , Adulto Jovem
5.
Pediatr Blood Cancer ; 68(1): e28757, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33089657

RESUMO

BACKGROUND: Little is known about socioeconomic status (SES) and its effects in childhood cancer survival. This study aims to discuss the association between SES and survival of patients with retinoblastoma (RB) from a tertiary treatment center. PROCEDURE: A retrospective cohort study was conducted, including all patients with RB referred to the Brazilian National Institute of Cancer in Rio de Janeiro (January 2000-December 2016). RESULTS: Data from 160 patients were analyzed with mean age at diagnosis of 22.85 months (SD ± 14.29). Eighty-three patients (51.9%) had an interval to diagnosis equal to or longer than six months, and 13 children (8.1%) abandoned treatment. Five-year overall survival rate for all patients was 78.8% (95% CI, 72.4%-85.9%). In a multivariate model, patients whose fathers had more than nine years of study had a lower death risk. Patients from families having more than one child under five years had a 213% higher risk of death compared with those living with no other small child. Treatment abandonment also had a profound effect on death risk. CONCLUSION: Childhood cancer is notably important considering the potential years of life lost. RB has even more important elements, as the possibility of vision loss in cases with delayed diagnosis. Family characteristics seem to be highly related to RB survival, especially in low- and middle-income countries, where inequalities are still a public health issue. Strategies to improve survival should focus not only on large-scale settings such as improving national healthcare systems but also on more personalized actions that might help to mitigate disparities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Retina/mortalidade , Retinoblastoma/mortalidade , Classe Social , Centros de Atenção Terciária/estatística & dados numéricos , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Brasil , Pré-Escolar , Atenção à Saúde , Feminino , Seguimentos , Humanos , Lactente , Masculino , Prognóstico , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/economia , Neoplasias da Retina/patologia , Retinoblastoma/tratamento farmacológico , Retinoblastoma/economia , Retinoblastoma/patologia , Estudos Retrospectivos , Taxa de Sobrevida
6.
Lancet Oncol ; 20(11): 1566-1575, 2019 11.
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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Quimioterapia de Manutenção , Rabdomiossarcoma Alveolar/tratamento farmacológico , Rabdomiossarcoma Embrionário/tratamento farmacológico , Vinorelbina/administração & dosagem , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Argentina , Brasil , Criança , Ciclofosfamida/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Europa (Continente) , Feminino , Humanos , Israel , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/mortalidade , Masculino , Indução de Remissão , Rabdomiossarcoma Alveolar/mortalidade , Rabdomiossarcoma Alveolar/patologia , Rabdomiossarcoma Embrionário/mortalidade , Rabdomiossarcoma Embrionário/patologia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Vinorelbina/efeitos adversos , Adulto Jovem
7.
Pediatr Blood Cancer ; 66(7): e27724, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30938082

RESUMO

BACKGROUND: High rates of treatment abandonment have been considered one of the major limitations to achieving high cure rates of childhood cancer in developing countries. The aims of this study were to report the prevalence and factors associated with treatment abandonment for children diagnosed with solid tumors in one reference center in Brazil and to describe effective strategies to prevent it. PROCEDURES: A retrospective review was conducted using data from 1139 children (0-18 years) treated for solid tumors at the Brazilian National Cancer Institute, during the period between January 2012 and December 2017. Treatment abandonment was defined as recommended by the International Society of Pediatric Oncology. The impact of implementing a patient-tracking system was evaluated. Descriptive statistics were used to analyze patient characteristics. Chi-square test was used for statistical analysis, with the significance level <0.05. RESULTS: Of 1139 patients, 1.66% refused or abandoned treatment. Although from 2012 to 2013 there was an increase in the abandonment rate, it then decreased by 63.8% from 2013 to 2017 (2.5% to 0.9%). In the multivariate model, only retinoblastoma diagnosis was associated with abandonment (odds ratio = 5.0; 95% confidence interval, 1.2-20.4; P = 0.025). In our cohort, abandonment rates were not associated with increased death. CONCLUSION: Monitoring missed appointments, and early interventions to address issues associated with providing resources to help families during treatment were effective in achieving very low abandonment rates.


Assuntos
Neoplasias da Retina , Retinoblastoma , Recusa do Paciente ao Tratamento , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prevalência , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/epidemiologia , Neoplasias da Retina/terapia , Retinoblastoma/diagnóstico , Retinoblastoma/epidemiologia , Retinoblastoma/terapia , Estudos Retrospectivos , Fatores Socioeconômicos
8.
Eur J Cancer Care (Engl) ; 28(5): e13102, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31184786

RESUMO

INTRODUCTION: This study aims to assess the impact of paediatric benign and malignant solid tumours and its treatment on the health-related quality of life of children and adolescents who were followed up in a Reference Center in Pediatric Oncology in Rio de Janeiro. METHODS: It is a prospective cohort study. Quality of life assessment was performed using the PedsQL™ 4.0 Generic Core Scales and PedsQL™ 3.0 Cancer Module protocols three times: during hospital admission (T1), 6 months after admission (T2) and 1 year after admission (T3). RESULTS: We evaluated 132 patients, 59 men and 73 women, aged 2-17 years. In PedsQL™4.0, the Emotional Functioning scale was the one with the worst scores, while the scores on the Social Functioning scale was the best. In PedsQL™ 3.0, the worst domains were Procedural Anxiety and Worry. Patients with malignant bone tumours had the worst health-related quality of life. The group who received only surgery had better results. Total scores of PedsQL™4.0 and PedsQL™ 3.0 improved between T1 and T3. CONCLUSION: Children and adolescents with malignant and benign neoplasms undergo changes in quality of life as a result of the disease and treatment, but an improvement has been observed over time.


Assuntos
Saúde Mental , Neoplasias/fisiopatologia , Qualidade de Vida , Participação Social , Adolescente , Neoplasias Ósseas/fisiopatologia , Neoplasias Ósseas/psicologia , Neoplasias Ósseas/terapia , Brasil , Neoplasias do Sistema Nervoso Central/fisiopatologia , Neoplasias do Sistema Nervoso Central/psicologia , Neoplasias do Sistema Nervoso Central/terapia , Criança , Pré-Escolar , Estudos de Coortes , Emoções , Feminino , Humanos , Neoplasias Renais/fisiopatologia , Neoplasias Renais/psicologia , Neoplasias Renais/terapia , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/psicologia , Neoplasias Hepáticas/terapia , Masculino , Neoplasias/psicologia , Neoplasias/terapia , Neoplasias Embrionárias de Células Germinativas/fisiopatologia , Neoplasias Embrionárias de Células Germinativas/psicologia , Neoplasias Embrionárias de Células Germinativas/terapia , Neuroblastoma/fisiopatologia , Neuroblastoma/psicologia , Neuroblastoma/terapia , Pais , Estudos Prospectivos , Retinoblastoma/fisiopatologia , Retinoblastoma/psicologia , Retinoblastoma/terapia , Sarcoma/fisiopatologia , Sarcoma/psicologia , Sarcoma/terapia , Instituições Acadêmicas , Neoplasias de Tecidos Moles/fisiopatologia , Neoplasias de Tecidos Moles/psicologia , Neoplasias de Tecidos Moles/terapia , Neoplasias Urogenitais/fisiopatologia , Neoplasias Urogenitais/psicologia , Neoplasias Urogenitais/terapia
9.
Pediatr Hematol Oncol ; 36(2): 55-72, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31014139

RESUMO

Retinoblastoma (RB) is the most common intraocular tumor of childhood. In low income countries, Time to diagnosis (TTD: interval between first symptom and diagnosis) has been associated with extraocular disease, metastasis and mortality. However, the relationship between TTD and prognosis is complex and not simply a linear correlation, particularly if TTD is <6 months. This systematic review aims to identify studies reporting TTD of retinoblastoma in Latin America, highlighting factors affecting TTD, alongside proposals and initiatives to obtain shorter intervals. The review also aims to discuss the methodology linked to cancer pathways studies. The study respected PRISMA recommendations, was registered on Prospero, an international database for systematic review registries under number CRD42017076777. MEDLINE/PUBMED, LILACS and SCIELO databases were searched. Studies from Latin America and the Caribbean, published between 1997 and 2017, reporting TTD and age at diagnosis of patients with retinoblastoma were selected. Nine studies were selected, concerning 1560 patients from Argentina, Brazil, Chile, Honduras, Mexico and Peru. The median TTD ranged from 3 to 5 months and the median age at diagnosis ranged from 16.5 to 22.2 months. A prolonged TTD was observed and was associated to damaging results on retinoblastoma outcomes, particularly increasing extraocular disease, and mortality rates. Methodological heterogeneity was observed and reiterates the importance of standardization of TTD studies, allowing more reliable comparisons and greater knowledge about retinoblastoma pathways before diagnosis. Reports on successful initiatives against delayed diagnosis were scarce, emphasizing a need for further studies.


Assuntos
Neoplasias Oculares/diagnóstico , Retinoblastoma/diagnóstico , Fatores Etários , Pré-Escolar , Diagnóstico Tardio , Detecção Precoce de Câncer , Diagnóstico Precoce , Neoplasias Oculares/epidemiologia , Humanos , Lactente , Recém-Nascido , América Latina/epidemiologia , Prognóstico , Retinoblastoma/epidemiologia , Fatores Socioeconômicos , Fatores de Tempo
10.
Cancer ; 124(15): 3201-3209, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29797665

RESUMO

BACKGROUND: Alveolar rhabdomyosarcoma (aRMS) with lymph node involvement (N1 classification) accounts for up to 10% of all cases of RMS. The prognosis is poor, and is comparable to that of distant metastatic disease. In the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS2005 protocol, patients with a histologic diagnosis of aRMS/N1 received intensified chemotherapy with systematic locoregional treatment. METHODS: Patients with aRMS/N1 were enrolled prospectively after primary surgery/biopsy and fusion status was assessed in tumor samples. All patients received 9 cycles of induction chemotherapy and 6 months of maintenance therapy. Local treatment included radiotherapy to the primary site and lymph nodes with or without secondary surgical resection. RESULTS: A total of 103 patients were enrolled. The clinical characteristics of the patients were predominantly unfavorable: 90% had macroscopic residual disease after initial surgery/biopsy, 63% had locally invasive tumors, 77% had a tumor measuring >5 cm, and 81% had disease at unfavorable sites. Fusion genes involving forkhead box protein O1 (FOXO1) were detected in 56 of 84 patients. Events occurred in 52 patients: 43 developed disease recurrence, 7 had disease that was refractory to treatment, and 2 patients developed second neoplasms. On univariate analysis, unfavorable disease site, tumor invasiveness, Intergroup Rhabdomyosarcoma Study group III, and fusion-positive status correlated with worse prognosis. The 5-year event-free survival rate of patients with fusion-positive tumors was 43% compared with 74% in patients with fusion-negative tumors (P = .01). On multivariate analysis, fusion positivity and tumor invasiveness proved to be unfavorable prognostic markers. CONCLUSIONS: Fusion status and tumor invasiveness appear to have a strong impact on prognosis in patients with aRMS/N1. Fusion status will be used to stratify these patients in the next EpSSG RMS study, and treatment will be intensified in patients with fusion-positive tumors. Cancer 2018. © 2018 American Cancer Society.


Assuntos
Proteína Forkhead Box O1/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Rabdomiossarcoma Alveolar/tratamento farmacológico , Rabdomiossarcoma Alveolar/epidemiologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Linfonodos/efeitos dos fármacos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Pediatria , Rabdomiossarcoma Alveolar/genética , Rabdomiossarcoma Alveolar/patologia , Fatores de Risco , Adulto Jovem
11.
Cancer ; 123(6): 1003-1010, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28263383

RESUMO

BACKGROUND: Metronomic chemotherapy (MC) consists of the administration of a low dose of chemotherapy on a daily or weekly basis without a long break to achieve an antitumoral effect through an antiangiogenic effect or stimulation of the immune system. The potential effect of MC with continuous oral cyclophosphamide and methotrexate in patients with high-grade operable osteosarcomas (OSTs) of the extremities was investigated. METHODS: Patients with high-grade OSTs who were 30 years old or younger were eligible for registration at diagnosis. Eligibility for randomization included 1) nonmetastatic disease and 2) complete resection of the primary tumor. The study design included a backbone of 10 weeks of preoperative therapy with methotrexate, adriamycin, and platinum (MAP). After surgery, patients were randomized between 2 arms to complete 31 weeks of MAP or receive 73 weeks of MC after MAP. The primary endpoint was event-free survival (EFS) from randomization. RESULTS: There were 422 nonmetastatic patients registered (May 2006 to July 2013) from 27 sites in 3 countries (Brazil, Argentina and Uruguay), and 296 were randomized to MAP plus MC (n = 139) or MAP alone (n = 157). At 5 years, the EFS cumulative proportions surviving in the MAP-MC group and the MAP-alone group were 61% (standard error [SE], 0.5%) and 64% (SE, 0.5%), respectively, and they were not statistically different (Wilcoxon [Gehan] statistic = 0.724; P =.395). The multivariate analysis showed that necrosis grades 1 and 2, tumor size, and amputation were associated with shorter EFS. CONCLUSIONS: According to the current follow-up, EFS with MAP plus MC is not statistically superior to EFS with MAP alone in patients with high-grade, resectable OSTs of the extremities. Cancer 2017;123:1003-10. © 2016 American Cancer Society.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/tratamento farmacológico , Extremidades/patologia , Osteossarcoma/diagnóstico , Osteossarcoma/tratamento farmacológico , Administração Metronômica , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Ósseas/mortalidade , Criança , Terapia Combinada , Gerenciamento Clínico , Feminino , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Osteossarcoma/mortalidade , Modelos de Riscos Proporcionais , Resultado do Tratamento , Carga Tumoral
12.
J Pediatr Hematol Oncol ; 38(3): e88-96, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26950086

RESUMO

The spectrum of cancers commonly found in adolescents and young adults (AYAs) differs from those in children and adults; therefore, the childhood classification is not appropriate for this population. Here we used a newly proposed classification system to reclassify cases of AYAs from Brazilian population-based cancer registries (PBCRs) in 5 geographic regions of Brazil. We aimed to describe the cancer incidence rates within this age group according to PBCR. Using the world population, incidence rates per million were analyzed in each diagnostic subgroup according to sex and age at diagnosis (15 to 19 y, 20 to 24 y, and 25 to 29 y). The median incidence rate was 232.31 per million for females and 218.07 per million for males. Incidence increased with age, with the highest rate observed for 25- to 29-year-olds in both sexes. Carcinomas, lymphomas, and skin tumors were most frequent among AYAs. High incidence rates of cervix-uterus carcinoma were observed in most PBCRs. AYAs present epidemiological characteristics that differ from those of children, reinforcing the need for a new classification. This study describes, for the first time, the cancer incidence rate in AYAs in Brazil, and we believe that our findings represent the Brazilian profile.


Assuntos
Neoplasias/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Brasil/epidemiologia , Feminino , Humanos , Incidência , Masculino , Sistema de Registros , Distribuição por Sexo , Adulto Jovem
13.
Pediatr Hematol Oncol ; 33(4): 248-58, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27246903

RESUMO

Prognostic markers that can help identifying precocious risk of unfavorable outcomes in patients with childhood adrenocortical tumors (ACTs) are still unclear. This observational and retrospective study aimed to identify clinical and pathology prognostic factors of recurrence and death in a tertiary cancer center population. Clinical, pathology, demographic, staging, and therapy data from patients with childhood ACT (median age: 3.6 years) treated at the Brazilian National Institute of Cancer between 1997 and 2015 were assessed. Univariate and bivariate analyses were used to study the association of clinical and pathology characteristics with recurrence and mortality. Recurrence and disease-related mortality were the main outcomes. Twenty-seven patients were included. Complete tumor resection was performed in 21 cases. The median tumor size was 8.2 cm. Mitotane was the most common adjuvant/palliative therapy (n = 13). Recurrence occurred in 6 patients, after a median time of 7.2 months, and was more common among those with larger tumors (P =.008), higher Weiss score (P =.001), and microscopic tumoral necrosis (P =.002). Ten patients died from the disease. Older age (P =.04), larger tumor size (P =.002), metastatic disease (P =.003), previous recurrence (P =.003), incomplete resection (P =.002), intraoperative tumor spillage (P =.005), higher Weiss score (P =.03), microscopic necrosis (P =.005), and capsular invasion (P =.02) were all associated with increased death risk. Even though complete tumor resection was performed in most cases, a considerable number of cases of childhood ACT resulted in recurrence and death. Early identification of unfavorable outcomes is essential to determine ideal therapy and appropriate surveillance.


Assuntos
Neoplasias do Córtex Suprarrenal/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Adolescente , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Neoplasias do Córtex Suprarrenal/patologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos
14.
JCO Precis Oncol ; 8: e2300713, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38810175

RESUMO

PURPOSE: Our study aimed to explore real-world treatment scenarios for children and adolescents with neurotrophic tropomyosin receptor kinase (NTRK)-fused tumors, emphasizing access, responses, side effects, and outcomes. PATIENTS AND METHODS: Pooled clinical data from 17 pediatric cases (11 soft-tissue sarcomas, five brain tumors, and one neuroblastoma) treated with larotrectinib and radiologic images for 14 patients were centrally reviewed. Testing for gene fusions was prompted by poor response to treatment, tumor progression, or aggressiveness. RESULTS: Six different NTRK fusion subtypes were detected, and various payment sources for testing and medication were reported. Radiologic review revealed objective tumor responses (OR) in 11 of 14 patients: Complete responses: two; partial responses: nine; and stable disease: three cases. Grades 1 or 2 Common Terminology Criteria for Adverse Events adverse effects were reported in five patients. Regarding the entire cohort's clinical information, 15 of 17 patients remain alive (median observation time: 25 months): four with no evidence of disease and 11 alive with disease (10 without progression). One patient developed resistance to the NTRK inhibitor and died from disease progression while another patient died due to an unrelated cause. CONCLUSION: This real-world study confirms favorable agnostic tumor OR rates to larotrectinib in children with NTRK-fused tumors. Better coordination to facilitate access to medication remains a challenge, particularly in middle-income countries like Brazil.


Assuntos
Inibidores de Proteínas Quinases , Pirazóis , Humanos , Criança , Masculino , Feminino , Adolescente , Pirazóis/uso terapêutico , Pré-Escolar , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Receptor trkA/genética , Receptor trkA/antagonistas & inibidores , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Sarcoma/tratamento farmacológico , Sarcoma/genética , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética , Lactente , Receptor trkB/genética , Receptor trkC/genética , Ensaios Clínicos como Assunto
15.
J Clin Oncol ; 41(13): 2342-2349, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36848614

RESUMO

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The RMS2005 study included two phase III randomized trials for high-risk (HR) and observational trials for low (LR), standard (SR), and very high-risk (VHR) patients who have been partially reported. Herein, we present a comprehensive report of results achieved for the complete unselected nonmetastatic cohort and analyze the evolution of treatment in comparison with previous European protocols. After a median follow-up of 73.1 months, the 5-year event-free survival (EFS) and overall survival (OS) of the 1,733 patients enrolled were 70.7% (95% CI, 68.5 to 72.8) and 80.4% (95% CI, 78.4 to 82.3), respectively. The results by subgroup: LR (80 patients) EFS 93.7% (95% CI, 85.5 to 97.3), OS 96.7% (95% CI, 87.2 to 99.2); SR (652 patients) EFS 77.4% (95% CI, 73.9 to 80.5), OS 90.6% (95% CI, 87.9 to 92.7); HR (851 patients) EFS 67.3% (95% CI, 64.0 to 70.4), OS 76.7% (95% CI, 73.6 to 79.4); and VHR (150 patients) EFS 48.8% (95% CI, 40.4 to 56.7), OS 49.7% (95% CI, 40.8 to 57.9). The RMS2005 study demonstrated that 80% of children with localized rhabdomyosarcoma could be long-term survivors. The study has established the standard of care across the European pediatric Soft tissue sarcoma Study Group countries with the confirmation of a 22-week vincristine/actinomycin D regimen for LR patients, the reduction of the cumulative ifosfamide dose in the SR group, and for HR disease, the omission of doxorubicin and the addition of maintenance chemotherapy.


Assuntos
Rabdomiossarcoma , Sarcoma , Adolescente , Criança , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dactinomicina , Intervalo Livre de Doença , Rabdomiossarcoma/tratamento farmacológico , Sarcoma/patologia
16.
Pediatr Blood Cancer ; 59(1): 39-43, 2012 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-22180099

RESUMO

BACKGROUND: Retinoblastoma (RB) accounts for 3% of all childhood malignancies, with different incidences around the world. This malignancy results from loss-of-function of both RB1 alleles although other genes, like MDM2 and MDM4, have been proposed to be involved in tumor development. PROCEDURE: We genotyped rs2279744T>G and rs937283A>G in MDM2, and rs4252668T>C and rs116197192G>A in MDM4, in 104 unrelated RB patients and 104 controls. Sixty-month survival Kaplan-Meier curves and χ(2)-tests were performed for estimating the putative effect of MDM2 and MDM4 alleles on disease progression and survival of RB patients. RESULTS: MDM2 rs2279744G was significantly more frequent in controls, indicating an apparently protective effect on RB development. However, survival of patients who carried a constitutional RB1 mutation was significantly lower with rs2279744TG or GG than with rs2279744TT. Presence of rs2279744G and a constitutional RB1 mutation was sixfold more frequent in the 0-12 month age group than other age groups at onset of symptoms (P = 0.0401). MDM4 rs4252668C was present at a significantly higher frequency in controls while the frequency of MDM4 rs116197192G was significantly higher in RB patients, suggesting that this allele might increase the risk of developing RB. CONCLUSION: Our results indicate that MDM2 and MDM4 polymorphisms may influence development and/or survival in RB.


Assuntos
Alelos , Mutação de Sentido Incorreto , Proteínas Nucleares/genética , Polimorfismo Genético , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas/genética , Retinoblastoma/genética , Retinoblastoma/mortalidade , Adulto , Proteínas de Ciclo Celular , Pré-Escolar , Intervalo Livre de Doença , Feminino , Técnicas de Genotipagem , Humanos , Lactente , Recém-Nascido , Masculino , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Retinoblastoma/metabolismo , Estudos Retrospectivos , Taxa de Sobrevida
17.
Genet Mol Biol ; 35(4): 714-24, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23271929

RESUMO

The most frequent epigenetic alterations in Wilms tumor (WT) occur at WT2, assigned to 11p15. WT2 consists of two domains: telomeric domain 1 (DMRH19) that contains the IGF2 gene and an imprinted maternally expressed transcript (H19) and centromeric domain 2 (KvDMR) that contains the genes KCNQ1, KCNQ1OT1 and CDKN1C. In this work, we used pyrosequencing and MS-MLPA to compare the methylation patterns of DMRH19/KvDMR in blood and tumor samples from 40 WT patients. Normal constitutional KvDMR methylation indicated that most of the epigenetic alterations in WT occur at DMRH19. Constitutional DMRH19 hypermethylation (HM DMRH19) was observed in two patients with Beckwith-Wiedemann syndrome. Pyrosequencing and MS-MLPA showed HM DMRH19 in 28/34 tumor samples: 16/34 with isolated HM DMRH19 and 12/34 with concomitant HM DMRH19 and KvDMR hypomethylation, indicating paternal uniparental disomy. With the exception of one blood sample, the MS-MLPA and pyrosequencing findings were concordant. Diffuse or focal anaplasia was present in five tumor samples and was associated with isolated somatic HM DMRH19 in four of them. Constitutional 11p15 methylation abnormalities were present in 5% of the samples and somatic abnormalities in the majority of tumors. Combined analysis of DMRH19/KvDMR by pyrosequencing and MS-MLPA is beneficial for characterizing epigenetic anomalies in WT, and MS-MLPA is useful and reliable for estimation of DNA methylation in a clinical setting.

18.
J Clin Oncol ; 40(32): 3730-3740, 2022 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-35709412

RESUMO

PURPOSE: Outcome for patients with metastatic rhabdomyosarcoma (RMS) is poor. This study presents the results of the MTS 2008 study with a pooled analysis including patients from the concurrent BERNIE study. PATIENTS AND METHODS: In MTS 2008, patients with metastatic RMS received four cycles of ifosfamide, vincristine, and actinomycin D (IVA) plus doxorubicin, five cycles of IVA, and 12 cycles of maintenance chemotherapy (low-dose cyclophosphamide and vinorelbine). The BERNIE study randomly assigned patients to the addition or not of bevacizumab to the same chemotherapy. Local therapy (surgery/radiotherapy) was given to the primary tumor and all metastatic sites when feasible. RESULTS: MTS 2008 included 270 patients (median age, 9.6 years; range, 0.07-20.8 years). With a median follow-up of 50.3 months, 3-year event-free survival (EFS) and overall survival (OS) were 34.9% (95% CI, 29.1 to 40.8) and 47.9% (95% CI, 41.6 to 53.9), respectively. In pooled analyses on 372 patients with a median follow-up of 55.2 months, 3-year EFS and OS were 35.5% (95% CI, 30.4 to 40.6) and 49.3% (95% CI, 43.9 to 54.5), respectively. Patients with ≤ 2 Oberlin risk factors (ORFs) had better outcome than those with ≥ 3 ORFs: 3-year EFS was 46.1% versus 12.5% (P < .0001) and 3-year OS 60.0% versus 26.0% (P < .0001). Induction chemotherapy and maintenance appeared tolerable; however, about two third of patients needed dose adjustments during maintenance. CONCLUSION: Outcome remains poor for patients with metastatic RMS and multiple ORFs. Because of the design of the studies, it was not possible to determine whether the intensive induction regimen and/or the addition of maintenance treatment resulted in apparent improvement of outcome compared with historical cohorts. Further studies, with novel treatment approaches are urgently needed, to improve outcome for the group of patients with adverse prognostic factors.


Assuntos
Segunda Neoplasia Primária , Rabdomiossarcoma , Sarcoma , Criança , Humanos , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/patologia , Sarcoma/tratamento farmacológico , Ifosfamida , Vincristina , Ciclofosfamida , Dactinomicina , Doxorrubicina , Segunda Neoplasia Primária/etiologia
19.
BMC Cancer ; 11: 160, 2011 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-21545722

RESUMO

BACKGROUND: Childhood cancer differs from most common adult cancers, suggesting a distinct aetiology for some types of childhood cancer. Our objective in this study was to test the difference in incidence rates of 4 non-CNS embryonic tumours and their correlation with socioeconomic status (SES) in Brazil. METHODS: Data was obtained from 13 Brazilian population-based cancer registries (PBCRs) of neuroblastoma (NB), Wilms'tumour (WT), retinoblastoma (RB), and hepatoblastoma (HB). Incidence rates by tumour type, age, and gender were calculated per one million children. Correlations between social exclusion index (SEI) as an indicator of socioeconomic status (SES) and incidence rates was investigated using the Spearman's test. RESULTS: WT, RB, and HB presented with the highest age-adjusted incidence rates (AAIRs) in 1 to 4 year old of both genders, whereas NB presented the highest AAIR in ≤11 month-olds. However, differences in the incidence rates among PBCRs were observed. Higher incidence rates were found for WT and RB, whereas lower incidence rates were observed for NB. Higher SEI was correlated with higher incidences of NB (0.731; p = 0.0117), whereas no SEI correlation was observed between incidence rates for WT, RB, and HB. In two Brazilian cities, the incidence rates of NB and RB were directly correlated with SEI; NB had the highest incidence rates (14.2, 95% CI, 8.6-19.7), and RB the lowest (3.5, 95% CI, 0.7-6.3) in Curitiba (SEI, 0.730). In Natal (SEI, 0.595), we observed just the opposite; the highest incidence rate was for RB and the lowest was for NB (4.6, 95% CI, 0.1-9.1). CONCLUSION: Regional variations of SES and the incidence of embryonal tumours were observed, particularly incidence rates for NB and RB. Further studies are necessary to investigate risk factors for embryonic tumours in Brazil.


Assuntos
Hepatoblastoma/epidemiologia , Neuroblastoma/epidemiologia , Retinoblastoma/epidemiologia , Classe Social , Tumor de Wilms/epidemiologia , Adolescente , Fatores Etários , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Sistema de Registros
20.
J Pediatr (Rio J) ; 97(3): 302-308, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32505617

RESUMO

OBJECTIVE: To evaluate the performance of risk stratification protocols for febrile neutropenia specific to the pediatric population. METHODS: Retrospective study of a cohort of pediatric patients undergoing cancer treatment with episodes of neutropenia due to chemotherapy and fever, treated at the emergency department of a tertiary cancer hospital from January 2015 to June 2017. Patients who were bone marrow transplant recipients and patients with neutropenia due to causes other than chemotherapy were excluded. Six protocols were applied to all patients: Rackoff, Alexander, Santolaya, Rondinelli, Ammann 2003, and Ammann 2010. The following outcomes were assessed: microbiological infection, death, ICU admission, and need for more than two antibiotics. The performance of each protocol was analyzed for sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operator characteristic (ROC) curve. RESULTS: This study evaluated 199 episodes of febrile neutropenia in 118 patients. Microbiological infection was identified in 70 samples from 45 distinct episodes (22.6%), 30 patients used more than two antibiotics during treatment (15%), eight required ICU admission (4%), and one patient died (0.8%). Three protocols achieved high sensitivity indices and NPV regarding the outcomes of death and ICU admission: Alexander, Rackoff, and Ammann 2010; however, Rackoff showed higher sensitivity (0.82) and NPV (0.9) in relation to the microbiological infection outcome. CONCLUSION: The Rackoff risk rating showed the best performance in relation to microbiological infection, death, and ICU admission, making it eligible for prospective evaluation.


Assuntos
Neutropenia Febril , Neoplasias , Antibacterianos/uso terapêutico , Criança , Neutropenia Febril/tratamento farmacológico , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco
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