RESUMEN
Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions. The evidence-based and consensus recommendations contained in the NCCN Guidelines are intended to guide clinicians in selecting the most appropriate treatments for their patients with this clinically heterogeneous disease.
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Oncología Médica , Neuroblastoma , Humanos , Neuroblastoma/terapia , Neuroblastoma/diagnóstico , Neuroblastoma/patología , Oncología Médica/normas , Oncología Médica/métodos , Niño , Estadificación de NeoplasiasRESUMEN
Diamond-Blackfan anemia (DBA) is a rare, inherited bone marrow failure syndrome that is both genetically and clinically heterogeneous. The diagnosis of DBA has changed over time, with advancements in our understanding of the varied genetic etiologies and phenotypic manifestations of the disease. We present a rare case of a patient who never developed erythroid precursor hypoplasia, adding to the understanding of atypical manifestations of DBA. Our patient had spontaneous remission followed by subsequent relapse, both atypical and poorly understood processes in DBA. We highlight important considerations in diagnostically challenging cases and review major outstanding questions surrounding DBA.
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Anemia de Diamond-Blackfan , Humanos , Anemia de Diamond-Blackfan/complicaciones , Anemia de Diamond-Blackfan/genética , Anemia de Diamond-Blackfan/diagnóstico , Trastornos de Fallo de la Médula Ósea , Proteínas Ribosómicas/genéticaRESUMEN
Approximately 10% of patients with malignant ovarian germ cell tumors will experience a tumor relapse. Given the rarity of malignant ovarian germ cell tumors, management of these patients is challenging. Secondary cytoreductive surgery can be considered for carefully selected patients with a goal to achieve complete gross or optimal resection. For patients with platinum sensitive disease who have already received platinum-based chemotherapy, standard dose chemotherapy with paclitaxel/ifosfamide/cisplatin or vinblastine/ifosfamide/cisplatin can be considered. High-dose chemotherapy protocols at specialized centers should be explored even for patients with platinum-resistant disease; however, optimal timing is under investigation. A subset of patients with malignant ovarian germ cell tumors harbors potentially actionable genomic alterations. Further research is required to identify novel therapeutic approaches for these patients.
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Recurrencia Local de Neoplasia , Neoplasias de Células Germinales y Embrionarias , Neoplasias Ováricas , Humanos , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/terapia , Neoplasias Ováricas/patología , Femenino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
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.
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Etnicidad , Grupos Minoritarios , Humanos , Niño , Adolescente , Adulto Joven , Estados Unidos/epidemiología , Adulto , Recién Nacido , Lactante , Preescolar , Estudios Retrospectivos , Estudios de Seguimiento , Calidad de VidaRESUMEN
Extracranial germ cell tumors (GCT) are a biologically diverse group of tumors occurring in children, adolescents, and young adults. The majority of patients have excellent outcomes, but treatment-related toxicities impact their quality of survivorship. A subset of patients succumbs to the disease. Current unmet needs include clarifying which patients can be safely observed after initial surgical resection, refinement of risk stratification to reduce chemotherapy burden in patients with standard-risk disease, and intensify therapy for patients with poor-risk disease. Furthermore, enhancing strategies for detection of minimal residual disease and early detection of relapse, particularly in serum tumor marker-negative histologies, is critical. Improving the understanding of the developmental and molecular origins of GCTs may facilitate discovery of novel targets. Future efforts should be directed toward assessing novel therapies in a biology-driven, biomarker-defined, histology-specific, risk-stratified patient population. Fragmentation of care between subspecialists restricts the unified study of these rare tumors. It is imperative that trials be conducted in collaboration with national and international cooperative groups, with harmonized data and biospecimen collection. Key priorities for the Children's Oncology Group (COG) GCT Committee include (a) better understanding the biology of GCTs, with a focus on molecular targets and mechanisms of treatment resistance; (b) strategic development of pediatric and young adult clinical trials; (c) understanding late effects of therapy and identifying individuals most at risk; and (d) prioritizing diversity, equity, and inclusion to reduce cancer health disparities and studying the impacts of social determinants of health on outcomes.
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Recurrencia Local de Neoplasia , Neoplasias de Células Germinales y Embrionarias , Adolescente , Adulto Joven , Niño , Humanos , Neoplasias de Células Germinales y Embrionarias/terapia , Oncología Médica , Biomarcadores de Tumor , Factores de RiesgoRESUMEN
BACKGROUND/OBJECTIVES: Surgery is the mainstay of therapy for children with ovarian immature teratoma (IT), whereas adults receive adjuvant chemotherapy, except those with stage-I, grade-1 disease. In Brazil, children with metastatic ovarian IT received postoperative chemotherapy. This practice variation allowed evaluation of the value of chemotherapy, by comparison of Brazilian patients with those in the United States and United Kingdom. DESIGN/METHODS: From the Malignant Germ Cell International Consortium data commons, data on ovarian IT patients from two recently added Brazilian trials (TCG-99/TCG-2008) were compared with data from US/UK (INT-0106/GC-2) trials. Primary outcome measure was event-free (EFS) and overall survival (OS). RESULTS: Forty-two Brazilian patients were included (stage I: 27, stage II: 4, stage III: 8, stage IV: 3). Twenty-nine patients had surgery alone, whereas 13 patients received postoperative chemotherapy. The EFS and OS for entire cohort was 0.80 (95% CI: 0.64-0.89) and 0.97 (0.84-0.99). There was no difference in relapse risk based on stage, grade, or receipt of chemotherapy. Comparing the Brazilian cohort with 98 patients in US/UK cohort (stage I: 59, stage II: 12, stage III: 27), there was no difference in EFS and OS across all stages, despite 87% of stage II-IV Brazilian patients receiving postoperative chemotherapy compared with only 13% of US/UK patients. The EFS and OS for Brazilian compared with US/UK cohort was stage I: 88% versus 98% (p = .05), stage II-IV EFS: 67% versus 79% (p = .32), stage II-IV OS: 93% versus 97% (p = .44); amongst grade-3 patients, there was no difference in EFS or OS. CONCLUSION: Addition of postoperative chemotherapy did not improve outcome in children with ovarian IT, even at higher grade or stage, compared with surgery alone.
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Neoplasias Ováricas , Teratoma , Adulto , Femenino , Humanos , Niño , Estados Unidos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/patología , Teratoma/tratamiento farmacológico , Teratoma/patología , Quimioterapia AdyuvanteRESUMEN
BACKGROUND: Children with sickle cell anemia (SCA) have substantial medical needs and more unmet basic needs than children with other medical conditions. Despite a recent focus on social determinants of health (SDoH), there remains an incomplete understanding of the processes linking SDoH and disease management, particularly for youth with SCA. This study elucidated these processes and identified ways to mitigate deleterious effects of adverse SDoH on SCA management. METHODS: Parents/primary caregivers (N = 27) of children with SCA (≤12 years old) participated in semi-structured interviews regarding SCA management and SDoH and completed quantitative measures of basic needs. Qualitative data were systematically coded and analyzed using applied thematic analysis. Quantitative data were presented descriptively. RESULTS: Three qualitative themes were identified. First, SCA management is bidirectionally linked with the social environment, whereby challenges of SCA management can hinder basic needs from being met, and unmet basic needs and financial hardship hinder SCA management. Second, due to limited resources, parents/caregivers are faced with difficult choices between prioritizing basic needs versus SCA management. Third, addressing material, emotional, and informational needs may improve SCA management. Quantitatively, 73% of families endorsed ≥1 basic need, including food insecurity (42%), housing instability (62%), and/or energy insecurity 19% (vs. 20%). CONCLUSION: Despite documented associations, there remains a poor understanding of the processes linking SDoH and health. Findings underscore how day-to-day conditions undermine the management of SCA treatments, symptoms, and complications, limiting treatment effectiveness. Understanding these processes may inform family-centered, health equity interventions and policies to improve living conditions, disease management, and health outcomes.
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Anemia de Células Falciformes , Determinantes Sociales de la Salud , Adolescente , Niño , Humanos , Padres , Investigación Cualitativa , Anemia de Células Falciformes/terapia , Encuestas y CuestionariosRESUMEN
BACKGROUND: Adolescents with extracranial metastatic germ cell tumors (GCTs) are often treated with regimens developed for children, but their clinical characteristics more closely resemble those of young adult patients. This study was designed to determine event-free survival (EFS) for adolescents with GCTs and compared them with children and young adults. METHODS: An individual patient database of 11 GCT trials was assembled: 8 conducted by pediatric cooperative groups and 3 conducted by an adult group. Male patients aged 0 to 30 years with metastatic, nonseminomatous, malignant GCTs of the testis, retroperitoneum, or mediastinum who were treated with platinum-based chemotherapy were included. The age groups were categorized as children (0 to <11 years), adolescents (11 to <18 years), and young adults (18 to ≤30 years). The study compared EFS and adjusted for risk group by using Cox proportional hazards analysis. RESULTS: From a total of 2024 individual records, 593 patients met the inclusion criteria: 90 were children, 109 were adolescents, and 394 were young adults. The 5-year EFS rate was lower for adolescents (72%; 95% confidence interval [CI], 62%-79%) than children (90%; 95% CI, 81%-95%; P = .003) or young adults (88%; 95% CI, 84%-91%; P = .0002). The International Germ Cell Cancer Collaborative Group risk group was associated with EFS in the adolescent age group (P = .0020). After adjustments for risk group, the difference in EFS between adolescents and children remained significant (hazard ratio, 0.30; P = .001). CONCLUSIONS: EFS for adolescent patients with metastatic GCTs was similar to that for young adults but significantly worse than for that children. This finding highlights the importance of coordinating initiatives across clinical trial organizations to improve outcomes for adolescents and young adults. LAY SUMMARY: Adolescent males with metastatic germ cell tumors (GCTs) are frequently treated with regimens developed for children. In this study, a large data set of male patients with metastatic GCTs across different age groups has been built to understand the outcomes of adolescent patients in comparison with children and young adults. The results suggest that adolescent males with metastatic GCTs have worse results than children and are more similar to young adults with GCTs. Therefore, the treatment of adolescents with GCTs should resemble therapeutic approaches for young adults.
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Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Metástasis Linfática/tratamiento farmacológico , Neoplasias del Mediastino/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias Retroperitoneales/tratamiento farmacológico , Neoplasias Testiculares/tratamiento farmacológico , Adolescente , Adulto , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Masculino , Supervivencia sin Progresión , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To describe medication utilization patterns by pediatric inpatients with cancer during their last week of life. METHODS: This retrospective study used data from the Vizient Clinical Database/Resource Manager, a national compilation of clinical and resource use data from over 100 academic medical centers and affiliates. Patients (0-21 years) with malignancy who died during hospitalization (2010-2017) were included (N = 1659). Medications were categorized as opioid, benzodiazepine, gastrointestinal related, chemotherapy, anti-infectives, or vasopressors. Exposure to each group was ascertained for all patients at 1 week and 1 day prior to death. Factors associated with exposure were examined using generalized estimating equations, and summarized using adjusted odds ratios (aORs). RESULTS: Over the last week of life, there was increased use of opioids (76% to 82%, aOR = 1.55, P < .001) and benzodiazepines (53% to 66%, aOR = 1.36, P = .02), while gastrointestinal-related medication use decreased (92% to 89%, aOR = 0.69, P = .001). Patients had decreased exposure to chemotherapy (10% to 5%, aOR = 0.46, P < .001) and anti-infectives (82% to 73%, aOR = 0.41, P = .002). Vasopressor use increased as death approached (15% to 28%, aOR = 1.67, P = .04). Factors significantly associated with exposure varied with medication category, and included age, race, length of stay, malignancy type, death in the intensive care unit, history of hematopoietic stem cell transplant, and do-not-resuscitate status. CONCLUSION: During the week preceding death, administration of symptom management medications increased for children with cancer, but use was not universal. Potentially life-sustaining medications were often continued. Variability in utilization suggests differences in provider/family decision making that warrant further study to develop an evidence-based approach to end-of-life care.
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Neoplasias , Cuidados Paliativos/métodos , Cuidado Terminal/métodos , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Pacientes Internos , Masculino , Estudios Retrospectivos , Adulto JovenRESUMEN
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
FA is the most common cause of inherited BMF syndromes. The only cure for BMF in FA remains HSCT. Due to DNA instability in FA, RIC has been used to decrease immediate and late complications of HSCT. Most FA conditioning regimens in mismatched and unrelated donor transplants rely on TBI, which increases the risk of secondary malignancies. Most of the non-TBI conditioning regimens use an ex vivo T-cell depletion approach, but this is not feasible at all pediatric stem cell transplant programs. To evaluate the success of HSCT in patients with FA using non-TBI conditioning regimens with in vivo T-cell depletion approach. HSCT using non-TBI based conditioning was performed on two siblings with FA. The first sibling underwent matched unrelated donor transplant with a BM graft using fludarabine, alemtuzumab, busulfan, and cyclophosphamide conditioning and cyclosporine and mycophenolate as GVHD prophylaxis. The second sibling underwent MSD transplant with UCB and BM grafts using similar approach, but without busulfan and mycophenolate. Both siblings had engraftment without signs of acute or chronic GVHD. Acute post-transplant complications included brief viral reactivations. At last follow-up, both siblings continued to have full immune reconstitution with stable chimerism. Conditioning regimens without radiation and inclusion of alemtuzumab can lead to successful engraftment without development of GVHD and reduce risk of developing secondary neoplasms, even with unrelated donor transplants.
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Trasplante de Médula Ósea , Anemia de Fanconi/terapia , Depleción Linfocítica/métodos , Agonistas Mieloablativos/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Vidarabina/análogos & derivados , Niño , Quimioterapia Combinada , Anemia de Fanconi/inmunología , Humanos , Hermanos , Linfocitos T/inmunología , Vidarabina/uso terapéuticoRESUMEN
In the wake of the Children's Oncology Group (COG) ANBL00P2 trial and the ongoing ANBL1232 trial, an increasing number of children with neonatal neuroblastoma are being managed nonoperatively. We report the case of a patient with low-risk, non-MYCN amplified, neuroblastoma that was diagnosed and resected in the neonatal period but subsequently developed pulmonary metastases by the age of 7 months. Though rare, the possibility of low-risk disease metastasizing during surveillance should be recognized and may not be identified by current protocols.
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Neoplasias Pulmonares/secundario , Proteína Proto-Oncogénica N-Myc/genética , Neuroblastoma/cirugía , Procedimientos Neuroquirúrgicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Amplificación de Genes , Humanos , Lactante , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/etiología , Masculino , Neuroblastoma/genética , Neuroblastoma/patología , PronósticoRESUMEN
The management of ovarian immature teratoma (IT) presents several challenges. It occurs both in children and adults and therefore is managed by pediatric oncologists as well as adult and gynecologic oncologists. Treatment approach; however, varies significantly. Unlike pediatric patients in whom surgery is considered the mainstay of treatment, adult providers routinely prescribe postoperative chemotherapy. Management of recurrent IT can be challenging. Growing teratoma syndrome may occur after treatment of recurrent IT. We report the development and management of this phenomenon in a pediatric patient who had several recurrences of her IT.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Teratoma/tratamiento farmacológico , Teratoma/patología , Adolescente , Femenino , Humanos , Recurrencia Local de Neoplasia/cirugía , Neoplasias Ováricas/cirugía , Síndrome , Teratoma/cirugíaRESUMEN
Children with recurrent hepatoblastoma have a poor prognosis and limited treatment options. The authors describe a child with metastatic hepatoblastoma who had multiple relapses. He was treated with surgical resection and adjuvant chemotherapy at first relapse. At second relapse, he had progressive disease postresection. He was treated with ifosfamide/carboplatin/etoposide chemotherapy followed by maintenance irinotecan and achieved long-term disease-free survival. Irinotecan as maintenance should be explored in recurrent hepatoblastoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hepatoblastoma/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Camptotecina , Carboplatino , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Etopósido , Hepatoblastoma/patología , Humanos , Ifosfamida , Lactante , Irinotecán/administración & dosificación , Neoplasias Hepáticas/patología , Masculino , Recurrencia Local de Neoplasia/patología , Inducción de RemisiónRESUMEN
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: Bleomycin, etoposide, and cisplatin (BEP) chemotherapy administered every 3 weeks for 4 cycles remains the standard first line treatment for patients with intermediate- and poor-risk metastatic germ cell tumours (GCTs). Administering standard chemotherapy 2-weekly rather than 3-weekly, so-called 'accelerating chemotherapy', has improved cure rates in other cancers. An Australian multicentre phase 2 trial demonstrated this regimen is feasible and tolerable with efficacy data that appears promising. The aim of this trial is to determine if accelerated BEP is superior to standard BEP as first line chemotherapy for adult and paediatric male and female participants with intermediate and poor risk metastatic GCTs. METHODS: This is an open label, randomised, stratified, 2-arm, international multicentre, 2 stage, phase 3 clinical trial. Participants are randomised 1:1 to receive accelerated BEP or standard BEP chemotherapy. Eligible male or female participants, aged between 11 and 45 years with intermediate or poor-risk metastatic GCTs for first line chemotherapy will be enrolled from Australia, the United Kingdom and the United States. Participants will have regular follow up for at least 5 years. The primary endpoint for stage 1 of the trial (n = 150) is complete response rate and for the entire trial (n = 500) is progression free survival. Secondary endpoints include response following treatment completion (by a protocol-specific response criteria), adverse events, health-related quality of life, treatment preference, delivered dose-intensity of chemotherapy (relative to standard BEP), overall survival and associations between biomarkers (to be specified) and their correlations with clinical outcomes. DISCUSSION: This is the first international randomised clinical trial for intermediate and poor-risk metastatic extra-cranial GCTs involving both adult and pediatric age groups open to both males and females. It is also the largest, current randomised trial for germ cell tumours in the world. Positive results for this affordable intervention could change the global standard of care for intermediate and poor risk germ cell tumours, improve cure rates, avoid the need for toxic and costly salvage treatment, and return young adults to long, healthy and productive lives. TRIAL REGISTRATION: ACTRN 12613000496718 on 3rd May 2013 and Clinicaltrials.gov NCT02582697 on 21st October 2015.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos Clínicos , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/patología , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/efectos adversos , Bleomicina/uso terapéutico , Niño , Preescolar , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Ensayos Clínicos Fase III como Asunto , Etopósido/efectos adversos , Etopósido/uso terapéutico , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Adulto JovenRESUMEN
OBJECTIVE: Dysgerminoma is the most common malignant ovarian germ cell tumor (GCT) with peak incidence during adolescence and young adulthood. Current standard of care for patients with disease that has spread outside of the ovary (advanced-stage) utilizes platin-based chemotherapy regimens. The study objective was to compare clinical outcomes between platin-based (carboplatin versus cisplatin) strategies across all age groups (childrenâ¯<â¯11â¯years (y), adolescentsâ¯=â¯11-25â¯y and young adult womenâ¯>â¯25â¯y) for advanced-stage dysgerminoma. METHODS: The Malignant Germ Cell Tumor International Consortium (MaGIC) pooled data from six GCT trials (3â¯=â¯pediatric, 3â¯=â¯adult) conducted internationally by pediatric and gynecologic oncology clinical trial organizations (CTOs) between 1983 and 2009. Newly diagnosed patients, with advanced-stage (FIGO IC-IV) dysgerminoma, who received either carboplatin- or cisplatin-based chemotherapy were eligible for analysis. RESULTS: 126 eligible patients were identified; 56 patients (38â¯=â¯pediatric, 18â¯=â¯adult) received carboplatin-based and 70 patients (50â¯=â¯pediatric, 20â¯=â¯adult) received cisplatin-based chemotherapy. Mean age was 20â¯y (rangeâ¯=â¯6-46â¯y). The median follow-up was 10.3â¯y (rangeâ¯=â¯0.17-21.7â¯y). The five-year event-free survival (EFS5) and overall survival (OS5) was 0.94 (95%CI, 0.88-0.97) and 0.96 (95%CI, 0.91-0.99) respectively. Survival outcomes were comparable between carboplatin-(EFS5â¯=â¯0.96 (95%CI, 0.85-0.99), OS5â¯=â¯0.96 (95%CI, 0.85-0.99)) and cisplatin-(EFS5â¯=â¯0.93 (95%CI, 0.83-0.97), OS5â¯=â¯0.96 (95%CI, 0.87-0.99)) based regimens. Across three age groups, comparison of the EFS5 (<11â¯yâ¯=â¯0.1, 11-25â¯yâ¯=â¯0.91 (95%CI, 0.82-0.96), >25â¯yâ¯=â¯0.97 (95%CI, 0.81-0.99)) and OS5 (<11â¯yâ¯=â¯0.1, 11-25â¯yâ¯=â¯0.95 (95%CI, 0.87-0.99), >25â¯yâ¯=â¯0.97 (95%CI, 0.81-0.99)) did not demonstrate any statistically significant differences in outcomes. CONCLUSIONS: Patients diagnosed with dysgerminoma have an excellent OS, across all ages, even in the context of metastatic disease. Data from three large CTOs supports the investigation of carboplatin-based regimens in the frontline treatment of all patients with advanced-stage dysgerminoma to minimize treatment-related toxicities.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Disgerminoma/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adolescente , Adulto , Carboplatino/administración & dosificación , Niño , Cisplatino/administración & dosificación , Ensayos Clínicos como Asunto , Disgerminoma/patología , Femenino , Humanos , Estadificación de Neoplasias , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Ováricas/patología , Pronóstico , Adulto JovenRESUMEN
BACKGROUND: Paclitaxel, ifosfamide, cisplatin (TIP) is commonly used as salvage for malignant germ cell tumors (MGCT) in adults; however, additional administration of cisplatin at a young age could cause significant short- and long-term toxicities in a group of patients with high expected salvage. Because carboplatin has been shown to be effective in pediatric MGCT with less toxicity, the TIP regimen was modified by substituting carboplatin for cisplatin. METHODS: The Children's Oncology Group conducted a phase II trial between November 2007 and June 2011 evaluating "TIC" (paclitaxel 135 mg/m2 /day Day 1, ifosfamide 1,800 mg/m2 /dose Days 1-5 and carboplatin with AUC 6.5 Day 1) in children < 21 years with relapsed MGCT. The endpoint of the trial was response after two cycles, incorporating RECIST response and marker decline. RESULTS: Twenty patients (12 male, median age 13.5 years) were enrolled. Seventeen patients had tumor markers ≥10 times above normal. After two cycles, by RECIST criteria, 8 patients achieved a partial response (response rate 40%), 10 had stable disease, and 2 had progressive disease. A ≥ 1 log reduction was achieved in 10/17 patients (58.8%) with elevated markers. By study defined criteria, combining response by RECIST and marker decline, the response rate was 44%. CONCLUSION: TIC is active in relapsed pediatric MGCT and should be considered for salvage therapy in children. In adolescents and older adults with relapse MGCT, TIP or high-dose chemotherapy with stem cell remain the standard therapy.