RESUMEN
BACKGROUND: The increasing number of childhood cancer survivors necessitates continued follow-up to monitor for long-term complications. Inequities in loss to follow-up for patients enrolled on pediatric clinical trials have not been well studied. METHODS: This was a retrospective study of 21,084 patients residing in the United States enrolled on phase 2/3 and phase 3 Children's Oncology Group (COG) trials between January 1, 2000 and March 31, 2021. Rates of loss to follow-up to COG were evaluated using log-rank tests and multivariable Cox proportional hazards regression models with adjusted hazard ratios (HRs). Demographic characteristics included age at enrollment, race, ethnicity, and zip code level socioeconomic data. RESULTS: Adolescent and young adult (AYA) patients 15-39 years old at diagnosis had an increased hazard of loss to follow-up compared to patients 0-14 years old (HR, 1.89; 95% confidence interval (CI), 1.76-2.02). In the overall cohort, non-Hispanic Blacks were found to have an increased hazard of loss to follow-up compared to non-Hispanic Whites (HR, 1.56; 95% CI, 1.43-1.70). Among AYAs, the highest loss to follow-up rates were among non-Hispanic Blacks (69.8% ± 3.1%), patients on germ cell tumor trials (78.2% ± 9.2%), and patients living in zip codes with a median household income ≤150% of the federal poverty line at diagnosis (66.7% ± 2.4%). CONCLUSIONS: AYAs, racial and ethnic minority patients, and those living in lower socioeconomic status areas had the highest rates of loss to follow-up among clinical trial participants. Targeted interventions are warranted to ensure equitable follow-up and improved assessment of long-term outcomes. PLAIN LANGUAGE SUMMARY: Little is known about disparities in loss to follow-up for pediatric cancer clinical trial participants. In this study, we found that participants who were adolescents and young adults when treated, those who identified as a racial and/or ethnic minority, or those residing in areas with lower socioeconomic status at diagnosis were associated with higher rates of loss to follow-up. As a result, the ability to assess their long-term survival, treatment-related health conditions, and quality of life is hindered. These findings suggest the need for targeted interventions to improve long-term follow-up among disadvantaged pediatric clinical trial participants.
Asunto(s)
Etnicidad , Grupos Minoritarios , Humanos , Niño , Adolescente , Adulto Joven , Estados Unidos/epidemiología , Adulto , Recién Nacido , Lactante , Preescolar , Estudios Retrospectivos , Estudios de Seguimiento , Calidad de VidaRESUMEN
BACKGROUND: Disparities in survival by race/ethnicity, socioeconomic status (SES), and geography in adolescent and young adult (AYA) patients with central nervous system (CNS) tumors have not been well studied. PROCEDURE: A retrospective cohort study utilizing the Surveillance, Epidemiology, and End Results (SEER) database was conducted for AYA patients diagnosed with primary CNS tumors. Adjusted hazard ratios (aHR) were calculated using a multivariate Cox proportional hazard model to evaluate the association between race/ethnicity, SES, rurality, and hazard of death. RESULTS: All minority groups showed an increased hazard of death with greatest disparities in the high-grade glioma cohort. Lower SES was associated with an increased hazard of death in non-Hispanic White (NHW) patients (aHR 1.12; 95% confidence interval [CI] 1.01-1.24), non-Hispanic Black (NHB) patients (aHR 1.34; 95% CI 1.00-1.80), and patients aged 25-29 years (aHR 1.29; 95% CI 1.07-1.55). Mediation analysis showed an indirect effect of SES on the effect of race/ethnicity on the hazard of death only among NHB patients, with SES accounting for 33.7% of the association between NHB and hazard of death. Rurality was associated with an increased hazard of death for patients in the lowest SES tertile (aHR 1.31; 95% CI 1.08-1.59) and NHW patients (aHR 1.20; 95% CI 1.08-1.34). CONCLUSIONS: Patients identified as a racial/ethnic minority, patients with a lower SES, and patients residing in rural areas had an increased hazard of death. Further studies are needed to understand and address the biological, psychosocial, societal, and economic factors that impact AYA neuro-oncology patients at highest risk of experiencing poorer outcomes.
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Neoplasias del Sistema Nervioso Central , Etnicidad , Adolescente , Neoplasias del Sistema Nervioso Central/epidemiología , Minorías Étnicas y Raciales , Humanos , Grupos Minoritarios , Estudios Retrospectivos , Programa de VERF , Clase Social , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: There are several studies describing the correlation between unsatisfactory tumor marker decline and a poor prognosis for adult patients treated for germ cell tumors. In pediatric patients, the data are limited. Therefore, this study retrospectively analyzed data from Children's Oncology Group (COG) protocol AGCT0132 to determine whether a relationship exists between α-fetoprotein (AFP) decline and outcome. METHODS: One hundred thirty-one patients with germ cell tumors who were enrolled in COG protocol AGCT0132 were eligible for this analysis of AFP decline. The serum AFP half-life was calculated from levels collected postoperatively as a baseline and after the start of chemotherapy. AFP decline was defined as automatically satisfactory (AFP normalized within the first 2 AFP measures after the start of chemotherapy), calculated satisfactory (AFP half-life ≤7 days after the start of chemotherapy), and unsatisfactory. RESULTS: The 3-year cumulative incidence of relapse was 11% (95% confidence interval [CI], 6.0%-18%) for patients with a satisfactory decline and 38% (95% CI, 13%-64%) for patients with an unsatisfactory decline (P = .006). In stratified analyses, this effect was limited to patients who were 11 years of age or older and had standard risk 2 (SR2) disease (P = .004 and P = .007, respectively). Three-year overall survival (OS) for patients with a satisfactory decline versus an unsatisfactory decline was not statistically significant. CONCLUSIONS: This study is the first to show an association between AFP decline and the cumulative incidence of relapse in pediatric patients treated for germ cell tumors. Recognition of patients at high risk for relapse may allow for early intensification of therapy, which could affect future clinical trial design.
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Recurrencia Local de Neoplasia/genética , Neoplasias de Células Germinales y Embrionarias/genética , Pronóstico , alfa-Fetoproteínas/genética , Adolescente , Adulto , Biomarcadores de Tumor/genética , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/patología , Recurrencia , Estudios RetrospectivosRESUMEN
BACKGROUND: Although red blood cell (RBC) transfusion represents an integral component of sickle cell disease (SCD) care, transfusion support for some patients can result in alloimmunization to RBC antigens. Alloimmunized patients with SCD appear to experience worse survival compared to nonalloimmunized patients. While this difference in mortality may in part be due to underlying immunologic differences related to disease severity, it may also reflect direct clinical consequences of RBC alloimmunization. Alloimmunized patients have an increased risk of serious hemolytic transfusion reactions (HTRs) and may not receive adequate RBC transfusion support due to lack of compatible RBC units. CASE REPORT: This study reports on five RBC alloimmunized patients with SCD who died, to illustrate the concept that RBC alloimmunization itself contributes to premature death. RESULTS: The clinical course for each of the reported patients provides insight into the direct and indirect consequences of RBC alloimmunization, where patients experienced delayed HTRs or did not receive needed RBC transfusions. CONCLUSION: Future work examining the clinical impact of RBC alloimmunization should not only consider HTRs but should also address the potential consequences associated with difficulties in obtaining compatible blood.
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Anemia de Células Falciformes/mortalidad , Transfusión de Eritrocitos/efectos adversos , Eritrocitos/inmunología , Isoanticuerpos/sangre , Reacción a la Transfusión/mortalidad , Adolescente , Adulto , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/inmunología , Anemia de Células Falciformes/terapia , Biomarcadores/sangre , Femenino , Humanos , Masculino , Reacción a la Transfusión/sangre , Reacción a la Transfusión/diagnóstico , Reacción a la Transfusión/inmunología , Adulto JovenRESUMEN
Most children with acute immune thrombocytopenic purpura (ITP) respond to first-line therapies including intravenous immunoglobulin, corticosteroids, and Rho(D) immune globulin. However, there is no clear consensus regarding second-line therapies for the treatment of ITP, not responding to first-line therapies in the acute setting. Adapting from the chronic ITP literature, 3 patients with acute refractory ITP were treated with intravenous rituximab and showed immediate and sustained remission. Combined therapy that includes rituximab may be an effective regimen for acute refractory ITP.
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Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antineoplásicos/uso terapéutico , Resistencia a Medicamentos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Terapia Recuperativa , Enfermedad Aguda , Preescolar , Femenino , Humanos , Masculino , Púrpura Trombocitopénica Idiopática/patología , Inducción de Remisión , Rituximab , Resultado del TratamientoRESUMEN
Thyroid cancers represent the largest group of pediatric carcinomas. Unlike other cancers of childhood, they have not been prospectively studied; instead adult data has been extrapolated to childhood and adolescent treatment. In this article we review the treatment of both well differentiated thyroid cancer (WDTC), as well as medullary thyroid cancer (MTC). The approach to both cancers relies on a low threshold of suspicion, and a willingness to biopsy suspicious lesions. Surgery remains the primary method of curing these patients, although radioactive iodine (RAI) may offer some benefit in WDTC for selected patients. For patients with MTC new medications, such as Vandetanib, may offer some adjuvant benefit following surgery. Lastly, suppression of thyroid stimulating hormone (TSH) may be one of the most beneficial treatments for WDTC.
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Neoplasias de la Tiroides/terapia , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Isótopos de Yodo/uso terapéutico , Masculino , Piperidinas/uso terapéutico , Quinazolinas/uso terapéutico , Tirotropina/antagonistas & inhibidores , Adulto JovenRESUMEN
Rare tumors are a heterogenous group of infrequent tumors with varied biology and clinical presentation. Although individually rare, in aggregate they account for 15% of all cancers in children younger than 20 years of age. The management of these tumors can be challenging, as there are no pediatric protocols or treatment guidelines. In an effort to improve the management of these rare tumors, the Children's Oncology Group rare tumor committee, brought together a panel of experts to develop therapeutic recommendations for these rare tumors. These recommendations are being presented in this journal issue.
Asunto(s)
Neoplasias/terapia , Enfermedades Raras/terapia , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Neoplasias/epidemiología , Guías de Práctica Clínica como Asunto , Enfermedades Raras/epidemiologíaRESUMEN
Pancreatoblastoma is a very rare childhood tumor originating from the epithelial exocrine cells of the pancreas. It is the most common malignant pancreatic tumor in young children and has a mean age of diagnosis of 5 years. It is slow growing and its presentation is varied and often non-specific. Tumors tend to be quite large and appropriate cross sectional imaging is very important to assess for extent, metastatic disease, and resectability. Biopsy for tissue diagnosis is essential. Complete surgical resection is the goal of therapy although many patients are unresectable at initial diagnosis and require neoadjuvant chemotherapy. Adjuvant chemotherapy is also recommended and chemotherapeutic regimens involve cisplatin and doxorubicin. Even with curative resections, these lesions have a high recurrence rate and patients must be followed closely. Knowledge of this rare tumor is important for the clinician confronted with a large retroperitoneal mass in a young child.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/prevención & control , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Adolescente , Niño , Preescolar , Cisplatino/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Humanos , Masculino , Metástasis de la Neoplasia , Adulto JovenRESUMEN
Oligonucleotide array comparative genomic hybridization, karyotype and fluorescence in situ hybridization analyses were employed to delineate the cytogenetic abnormalities in a case of pediatric acute megakaryoblastic leukemia. Here we present a unique genetic profile that includes bi-allelic deletions within 13q14, where the retinoblastoma tumor suppressor gene (RB1) resides, as well as isolated trisomy 21 without a concomitant mutation in the hematopoietic transcription factor GATA1s and translocation (17;22), that does not involve the megakaryoblastic leukemia 1 (MKL1) gene located on chromosome 22. Alteration of the RB1 gene is most likely the critical leukemogenic event in this patient.
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Cromosomas Humanos Par 13/genética , Síndrome de Down/genética , Factor de Transcripción GATA1/genética , Leucemia Megacarioblástica Aguda/genética , Eliminación de Secuencia , Proteínas de Unión al ADN/genética , Femenino , Humanos , Lactante , Proteínas de Fusión Oncogénica/genética , Proteína de Retinoblastoma/genética , Transactivadores , Translocación GenéticaRESUMEN
BACKGROUND: Constipation occurs in children receiving chemotherapy for cancer but there are no data about prevalence, risk factors, and severity of constipation in this group of children. METHODS: We prospectively studied 61 children receiving chemotherapy for cancer. We administered questionnaires to children and parents and collected data on demographics, chemotherapy, and bowel movement pattern during chemotherapy. We used North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition criteria for the diagnosis of constipation. Parental perception of constipation as a problem and impact on lifestyle during chemotherapy were assessed on a 0 to 3 scale with 0 being no problem, 1 minor, 2 significant, and 3 being a major problem. RESULTS: Thirty-five children (57%) had acute constipation lasting for 2 or more weeks during chemotherapy. Several risk factors were analyzed and only combined use of vincristine and opiates emerged as significant risk factor for the development of constipation. In children with constipation, 15 of 35 parents (43%) perceived constipation as a major/significant problem and 8 children and their parents (23%) perceived constipation having a major/significant impact on lifestyle during chemotherapy. CONCLUSIONS: Acute constipation was diagnosed in 57% of children receiving chemotherapy for cancer. Combined use of vincristine and opiates was associated with the development of constipation. Constipation can be a significant problem with a negative impact on lifestyle during chemotherapy and needs aggressive management.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estreñimiento/inducido químicamente , Estreñimiento/complicaciones , Enfermedad Aguda , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Preescolar , Estreñimiento/diagnóstico , Femenino , Humanos , Lactante , Masculino , Estudios Prospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenAsunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/metabolismo , Antidrepanocíticos/uso terapéutico , Hidroxiurea/uso terapéutico , Oxígeno/metabolismo , Adolescente , Adulto , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pronóstico , Estudios Prospectivos , Adulto JovenRESUMEN
Elevated pulmonary artery pressures (PAP) occur in approximately 30% of children with sickle cell disease. In adults, pulmonary hypertension is significantly associated with mortality. There are no data on the long term significance in children. Nineteen children with SS/Sbeta(0) thalassaemia had elevated PAP, defined as tricuspid regurgitant jet velocity (TRV) > or =2.5 m/s on screening echocardiograms. They were prospectively followed for 23 months (range 19-31 months). Patients with initial TRV > or = 3 or TRV > or = 2.5 m/s on repeat echocardiogram had cardiopulmonary evaluation and were offered treatment with hydroxyurea. Associated conditions like asthma and obstructive sleep apnea were treated. 18/19 patients had follow-up echocardiograms. These showed normalization of TRV in 8 patients. Risk factors associated with persistent elevation were higher TRV on initial echocardiogram (P = 0.01), lower haemoglobin (P = 0.003) and lower oxygen saturation (P = 0.03). Five patients with persistently elevated PAP were treated with hydroxyurea. Mean right ventricular pressure dropped from 40.16 to 29.26 (P = 0.017) after 3-6 months and to 23.6 mmHg (P = 0.002) after 9-12 months on treatment. In conclusion (i) At borderline elevation of TRV there is intrapatient variability and echocardiograms should be repeated for confirmation. (ii) Elevated PAP are reversible in children with early detection and treatment with hydroxyurea.
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Hipertensión Pulmonar/fisiopatología , Talasemia/fisiopatología , Adolescente , Adulto , Antidrepanocíticos/uso terapéutico , Niño , Ecocardiografía Doppler , Femenino , Estudios de Seguimiento , Humanos , Hidroxiurea/uso terapéutico , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/etiología , Masculino , Estudios Prospectivos , Arteria Pulmonar/diagnóstico por imagen , Talasemia/complicaciones , Talasemia/diagnóstico por imagen , Resultado del Tratamiento , Adulto JovenRESUMEN
A patient with homozygous hemoglobin SS disease presented with an intracerebral hemorrhage complicating reversible posterior leucoencephalopathy syndrome (RPLS), secondary to hypertension associated with acute post-streptococcal glomerulonephritis (APSGN). Distinguishing potentially reversible causes of central nervous system events from primary cerebral infarction or hemorrhage in patients with sickle cell disease is important because the management and prognosis of these complications is very different. Similarly, because of the difference in prognosis between APSGN and other forms of sickle cell nephropathy, it is also important to differentiate these conditions.
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Anemia de Células Falciformes/complicaciones , Hemorragia Cerebral/etiología , Glomerulonefritis/etiología , Síndrome de Leucoencefalopatía Posterior/etiología , Infecciones Estreptocócicas/complicaciones , Niño , Glomerulonefritis/fisiopatología , Humanos , Hipertensión/etiología , Imagen por Resonancia Magnética , Masculino , Síndrome de Leucoencefalopatía Posterior/fisiopatología , Infecciones Estreptocócicas/fisiopatología , Tomografía Computarizada por Rayos XRESUMEN
Nuclear imaging techniques such as bone scans, metaiodobenzylguanidine (MIBG) scans, and (111)In-diethylenetriaminepentaacetic acid-octreotide scans have greatly increased the sensitivity and specificity of both diagnostic and follow-up protocols for pediatric solid tumors. Molecular targets that are specific for certain pediatric tumors are now being developed. Targets include cell membrane receptors targeted by specific ligands, subcellular organelles targeted by false transmitters, and cellular proteins targeted by antibodies. This review focuses on the use of MIBG (which is a false transmitter) and octreotide (which is a ligand for G protein receptor) in the diagnosis and treatment of solid tumors that affect children and young adults.
Asunto(s)
3-Yodobencilguanidina/uso terapéutico , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/radioterapia , Octreótido/análogos & derivados , Ácido Pentético/análogos & derivados , 3-Yodobencilguanidina/efectos adversos , Animales , Niño , Preescolar , Ensayos Clínicos como Asunto , Humanos , Lactante , Recién Nacido , Selección de Paciente , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/tendencias , Traumatismos por Radiación/etiología , Traumatismos por Radiación/prevención & control , Cintigrafía , Radiofármacos/efectos adversos , Somatostatina/análogos & derivados , Resultado del TratamientoRESUMEN
OBJECTIVES: The objectives of this study were (1) to determine the prevalence and risk factors of elevated pulmonary artery pressures in children with homozygous SS or Sbeta(0) thalassemia using Doppler echocardiography and (2) to determine a correlation between abnormal transcranial Doppler examinations and elevated pulmonary artery pressures. METHODS: Screening echocardiograms were prospectively performed during an annual comprehensive clinic visit on children who were older than 6 years and had homozygous SS or Sbeta(0) thalassemia. Detailed history, examination, and laboratory tests were done, and transcranial Doppler examinations were obtained in children 2 to 14 years of age. Pulmonary hypertension was defined as pulmonary artery systolic pressure of at least 30 mmHg corresponding to a peak tricuspid regurgitant jet velocity of > or = 2.5 m/second. Mild pulmonary hypertension was defined as tricuspid regurgitant jet velocity > or = 2.5 to 2.9 m/second. Moderate pulmonary hypertension was defined as tricuspid regurgitant jet velocity > or = 3 m/second. Patients with pulmonary stenosis or right outflow obstruction were excluded. Characteristics were compared between patients with mild, moderate, and no pulmonary hypertension using 1-way analysis of variance for continuous variable and Fisher's exact test for categorical variables. RESULTS: Of the 75 patients who had homozygous SS/Sbeta(0) thalassemia and were older than 6 years, echocardiograms were obtained for 62 (82.6%). Thirty percent (19 of 62) of patients had elevated tricuspid regurgitant jet velocity > or = 2.5 m/second. One third of these patients had tricuspid regurgitant jet velocity > or = 3 m/second. All patients with elevated tricuspid regurgitant jet velocity had SS disease. A high reticulocyte count, low oxygen saturation, and a high platelet count were significantly associated with elevated pulmonary artery pressures. There was no difference in age, gender, history of acute chest syndrome, hydroxyurea therapy, chronic blood transfusion, stroke, hemoglobin, and bilirubin between patients with and without elevated pulmonary artery pressures. A total of 47% patients with elevated tricuspid regurgitant jet velocity and 57% without elevated tricuspid regurgitant jet velocity had screening transcranial Doppler examinations. Transcranial Doppler examinations were normal for all patients. CONCLUSIONS: High pulmonary artery pressures do occur in children with sickle cell disease. Screening by echocardiography can lead to early detection and intervention that may potentially reverse this disease process. There was no correlation between elevated pulmonary artery pressures and abnormal transcranial Doppler examination in our study.