RESUMO
Subcutaneous patient-derived xenografts (PDXs) are an important tool for childhood cancer research. Here, we describe a resource of 68 early passage PDXs established from 65 pediatric solid tumor patients. Through genomic profiling of paired PDXs and patient tumors (PTs), we observe low mutational similarity in about 30% of the PT/PDX pairs. Clonal analysis in these pairs show an aggressive PT minor subclone seeds the major clone in the PDX. We show evidence that this subclone is more immunogenic and is likely suppressed by immune responses in the PT. These results suggest interplay between intratumoral heterogeneity and antitumor immunity may underlie the genetic disparity between PTs and PDXs. We further show that PDXs generally recapitulate PTs in copy number and transcriptomic profiles. Finally, we report a gene fusion LRPAP1-PDGFRA. In summary, we report a childhood cancer PDX resource and our study highlights the role of immune constraints on tumor evolution.
Assuntos
Neoplasias , Animais , Criança , Humanos , Xenoenxertos , Neoplasias/genética , Neoplasias/patologia , Transcriptoma/genética , Mutação , Modelos Animais de Doenças , Genômica/métodos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Cancers cause significant mortality and morbidity in adolescents and young adults (AYAs), but their biological underpinnings are incompletely understood. Here, we analyze clinical and genomic disparities between AYAs and older adults (OAs) in more than 100,000 cancer patients. We find significant differences in clinical presentation between AYAs and OAs, including sex, metastasis rates, race and ethnicity, and cancer histology. In most cancer types, AYA tumors show lower mutation burden and less genome instability. Accordingly, most cancer genes show less mutations and copy number changes in AYAs, including the noncoding TERT promoter mutations. However, CTNNB1 and BRAF mutations are consistently overrepresented in AYAs across multiple cancer types. AYA tumors also exhibit more driver gene fusions that are frequently observed in pediatric cancers. We find that histology is an important contributor to genetic disparities between AYAs and OAs. Mutational signature analysis of hypermutators shows stronger endogenous mutational processes such as MMR-deficiency but weaker exogenous processes such as tobacco exposure in AYAs. Finally, we demonstrate a panoramic view of clinically actionable genetic events in AYA tumors.
Assuntos
Neoplasias , Criança , Humanos , Adulto Jovem , Adolescente , Idoso , Neoplasias/genética , Genômica , Mutação , OncogenesRESUMO
BACKGROUND: The MAPK pathway is an emerging target across a number of adult and pediatric tumors. Targeting the downstream effector of MAPK, MEK1, is a proposed strategy to control the growth of MAPK-dependent tumors. OBJECTIVE: iMATRIX-cobi assessed the safety, pharmacokinetics, and anti-tumor activity of cobimetinib, a highly selective MEK inhibitor, in children and young adults with relapsed/refractory solid tumors. PATIENTS AND METHODS: This multicenter Phase I/II study enrolled patients aged 6 months to < 30 years with solid tumors with known/expected MAPK pathway involvement. Patients received cobimetinib tablet or suspension formulation on Days 1-21 of a 28-day cycle. Dose escalation followed a rolling 6 design. The primary endpoint was safety; secondary endpoints were pharmacokinetics and anti-tumor activity. RESULTS: Of 56 enrolled patients (median age 9 years [range 3-29]), 18 received cobimetinib tablets and 38 cobimetinib suspension. Most common diagnoses were low-grade glioma (LGG; n = 32, including n = 12 in the expansion cohort) and plexiform neurofibroma within neurofibromatosis type 1 (n = 12). Six patients (11 %) experienced dose-limiting toxicities (including five ocular toxicity events), which established a pediatric recommended Phase II dose (RP2D) of 0.8 mg/kg tablet and 1.0 mg/kg suspension. Most frequently reported treatment-related adverse events were gastrointestinal and skin disorders. Steady state mean exposure (Cmax, AUC0-24) of cobimetinib at the RP2D (1.0 mg/kg suspension) was ~ 50 % lower than in adults receiving the approved 60 mg/day dose. Overall response rate was 5.4 % (3/56; all partial responses in patients with LGG). CONCLUSIONS: The safety profile of cobimetinib in pediatrics was similar to that reported in adults. Clinical activity was observed in LGG patients with known/suspected MAPK pathway activation. Cobimetinib combination regimens may be required to improve response rates in this pediatric population. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02639546, registered December 24, 2015.
Assuntos
Azetidinas , Neoplasias , Piperidinas , Adolescente , Adulto , Azetidinas/efeitos adversos , Azetidinas/uso terapêutico , Criança , Pré-Escolar , Inibidores Enzimáticos/uso terapêutico , Glioma/tratamento farmacológico , Humanos , Dose Máxima Tolerável , Recidiva Local de Neoplasia , Neoplasias/tratamento farmacológico , Pediatria , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Comprimidos , Adulto JovemRESUMO
BACKGROUND: Parents of adolescents and young adults (AYAs) with cancer offer primary support to their children and often experience their own high levels of distress, affecting parent-AYA communication and quality of life. OBJECTIVE: To reduce parent distress and improve communication during high-risk cancer treatment, we examined efficacy of a self-care and communication intervention for parents and indirect benefit for AYAs receiving a therapeutic music video (TMV) intervention. METHODS: In this study, we conducted a multisite, randomized controlled trial with AYAs and parents enrolled as dyads (n = 110). Parents were randomized to intervention or low-dose control; all AYAs received TMV. Data collection occurred at baseline, 2 weeks post intervention (T2), and 90 days post intervention (T3). RESULTS: There were no significant between-group differences on primary outcomes for parents or AYAs. We did find significant differences favoring the parent intervention group on parenting confidence at T2 and marginally better outcomes for family adaptability/cohesion at T3. Both groups exhibited significant within-group improvement for parent distress (state anxiety, T3; perceived stress, T2 and T3; mood, T3), state anxiety (T2) intervention only, and family strengths control group only. Qualitative data demonstrate the parent intervention raised self-awareness and parent confidence in the short term. CONCLUSION: Parents found their intervention helpful. Absence of significant results may be due to short intervention duration, need for tailored content, underpowered sample, and potential indirect parent benefit from AYA participation in TMV. The parent intervention did not provide an indirect benefit for AYAs. IMPLICATIONS FOR NURSING: Parents identified their own need for communication and support from nurses. Nurses can optimize AYA care by attending to parent needs through supportive listening and encouraging self-care.
Assuntos
Neoplasias , Autocuidado , Adolescente , Criança , Comunicação , Humanos , Neoplasias/terapia , Poder Familiar , Pais , Qualidade de Vida , Adulto JovemRESUMO
INTRODUCTION: We aimed to create a Spanish-language version of the Pediatric Nausea Assessment Tool (PeNAT) and examine its understandability among Spanish-speaking, Hispanic American children. METHODS: Translation: Forward and backward translations of the PeNAT documents were performed and verified by a bilingual panel. Four monolingual, Spanish-speaking dyads (child/parent) and four bilingual dyads piloted the Spanish-language PeNAT documents. Four additional bilingual dyads read both versions and completed the PeNAT using their preferred version. These were reviewed for errors due to misunderstanding. UNDERSTANDABILITY: Children aged 4-18 years about to receive chemotherapy who spoke Spanish at home and were without impairments precluding PeNAT use were eligible. Participants used the Spanish-language PeNAT during a chemotherapy block. Parents gave feedback on the PeNAT documents. Recruitment continued until 10 consecutive participants offered no substantive suggestions for revision. RESULTS: Translation: All child/parent dyads completed the PeNAT without errors attributable to misunderstanding. The Spanish-language PeNAT was preferred by three of four bilingual dyads. Understandability: Ten cancer patients (mean age: 10.6 years) used the Spanish-language PeNAT. All parents felt their child understood the PeNAT; none felt the documents were hard or very hard to use. CONCLUSION: The Spanish-language PeNAT was understood by Spanish-speaking Hispanic American children. Further psychometric testing is warranted.
Assuntos
Idioma , Traduções , Adolescente , Criança , Pré-Escolar , Hispânico ou Latino , Humanos , Náusea , PsicometriaRESUMO
Few studies have explored interventions to improve adolescent and young adult (AYA) cancer care delivery. While many AYAs receive cancer care at NCI Community Oncology Research Program (NCORP) sites, few enroll on clinical trials. Barriers and facilitators to pediatric oncologist activation of and enrollment on an AYA cross-network National Clinical Trials Network (NCTN) supportive care trial were assessed using a survey that was administered to 162 stakeholders representing all 47 children's oncology group (COG) institutions affiliated to an NCORP. Fifty-eight stakeholders participated representing 62% of all sites surveyed. Approximately half of participants (45%) were unaware of the trial. Seven sites had the study open and one enrolled a patient. Reasons for not opening and enrolling on the trial included limited research staff and resources, low anticipated accrual, and lower prioritization of the trial. Enrollment facilitators included having a local "AYA champion," improving communication between pediatric and medical oncology, and having site education on available AYA trials. Interventions focused on increasing site and provider awareness of AYA trials and decreasing local barriers to AYA enrollment are needed.
Assuntos
Neoplasias , Oncologistas , Seleção de Pacientes , Adolescente , Ensaios Clínicos como Assunto , Humanos , Neoplasias/terapia , Adulto JovemRESUMO
OBJECTIVES: To translate a symptom screening tool developed for paediatric patients receiving cancer therapies called Symptom Screening in Pediatrics Tool (SSPedi) into Argentinian Spanish and to evaluate the understandability and cultural relevance of the translated version of SSPedi among children with cancer and paediatric haematopoietic stem cell transplant (HSCT) recipients. METHODS: We conducted a multiphase, descriptive study to translate SSPedi into Argentinian Spanish. Using two translators, forward and backward translations were performed. The translated version was evaluated by Spanish-speaking paediatric patients 8-18 years of age receiving cancer treatments in two centres in Argentina and El Salvador. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was patient self-reported difficulty with understanding of the SSPedi instructions and each symptom using a 5-point Likert scale. Secondary outcomes were incorrect understanding of the SSPedi instructions, symptoms and response scale determined by cognitive interviews with the patients and rated using a 4-point Likert scale. Cultural relevance was assessed qualitatively. RESULTS: There were 30 children enrolled and included in cognitive interviews; 16 lived in Argentina and 14 lived in El Salvador. The most common types of Spanish spoken were Central American (17, 57%) followed by South American (10, 33%) and Castilian (3, 10%). No changes to Argentinian Spanish SSPedi were required based on the outcomes or qualitative comments. No issues with cultural relevance were identified by any of the respondents. CONCLUSIONS: We translated and finalised Argentinian Spanish SSPedi. Future research will focus on its use to describe bothersome symptoms by Argentinian Spanish-speaking children.
Assuntos
Neoplasias , Pediatria , Argentina , Criança , Detecção Precoce de Câncer , El Salvador , Humanos , Neoplasias/terapia , Psicometria , Inquéritos e Questionários , Avaliação de Sintomas , TraduçãoRESUMO
BACKGROUND: Extranodal NK/T cell lymphoma (ENKTL) is an aggressive form of Epstein-Barr virus (EBV)-associated non-Hodgkin's lymphoma which historically has a poor prognosis. When relapse occurs, particularly in the cerebral nervous system (CNS), survival is rare. The immune checkpoint pathway family of proteins is highly expressed in many human tumors, especially in EBV-related malignancies. To the best of our knowledge, there are no reports of immune checkpoint inhibitors used either alone or in combination for the treatment of ENTKL CNS relapse, yet there are promising results in metastatic CNS involvement of other malignancies. CASE PRESENTATION: This is the case of a 29-year-old Hispanic male with ENKTL who was treated at first relapse with 24 doses of the programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor, atezolizumab, over a 17-month period. He remained in remission for 18 months until he experienced an isolated CNS relapse and on-going evidence of chronic EBV infection. Salvage therapy was provided as a combination of triple intrathecal (TIT) chemotherapy, radiation, and atezolizumab. He continues on maintenance atezolizumab and remains alive 1-year post CNS relapse. CONCLUSIONS: The results from this case suggest that atezolizumab should be considered as part of the treatment regimen for relapsed ENKTL. They also demonstrate the benefit of using atezolizumab in combination with TIT chemotherapy and radiation as a viable treatment option for ENKTL CNS relapse and indicate that atezolizumab is an option for long-term maintenance therapy for patients with ENKTL.
Assuntos
Infecções por Vírus Epstein-Barr , Linfoma Extranodal de Células T-NK , Adulto , Anticorpos Monoclonais Humanizados , Herpesvirus Humano 4 , Humanos , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/radioterapia , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Sistema NervosoRESUMO
OBJECTIVES: Symptom screening is important to achieving symptom control. Symptom Screening in Paediatrics Tool (SSPedi) is validated for English-speaking children. Objectives were to translate SSPedi into Spanish, and to evaluate the understandability and cultural relevance of the translated version among Spanish-speaking children with cancer and paediatric haematopoietic stem cell transplant recipients. METHODS: We conducted a multiphase, descriptive study to translate SSPedi into Spanish. The first step was to determine whether one Spanish version would be appropriate for both North America and Argentina. Once this decision was made, forward and backward translations were performed. The translated version was evaluated by Spanish-speaking children 8-18 years of age receiving cancer treatments. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was child self-reported difficulty with understanding of the entire instrument and each symptom using a 5-point Likert scale. Secondary outcomes were incorrect understanding of SSPedi items identified by cognitive interviews with the children using a 4-point Likert scale and cultural relevance, which was assessed qualitatively. RESULTS: This report focuses on North American Spanish as a separate version will be required for Argentinian Spanish SSPedi based on different common vocabulary and grammatical structure. There were 20 children from Toronto and San Antonio included in cognitive interviews. The most common types of Spanish spoken were Mexican (13, 65%), Central American (2, 10%) and South American (2, 10%). No child reported that it was hard or very hard to complete Spanish SSPedi. Changes to the instrument itself were not required based on understanding or cultural relevance. CONCLUSIONS: We translated and finalised Spanish SSPedi appropriate for use in North America. Future research will translate and evaluate SSPedi for use in Argentina and other Spanish-speaking countries.
Assuntos
Neoplasias , Pediatria , Argentina , Criança , Detecção Precoce de Câncer , Humanos , Neoplasias/terapia , América do Norte , Psicometria , Inquéritos e Questionários , Avaliação de Sintomas , TraduçãoRESUMO
PURPOSE: Clinical trial participation leads to progress in cancer care. Principal investigators (PIs) and clinical research associates (CRAs) play key roles in the provision and maintenance of clinical trial portfolios at their sites. Previous studies have evaluated the educational and resource needs of adult oncology providers, but nothing to date has focused on providers of pediatric oncology care. We aimed to identify the educational needs and clinical trial participation barriers at National Cancer Institute Community Oncology Research Program (NCORP) Children's Oncology Group (COG) sites to improve the quality of site investigator engagement. METHODS: Quality improvement surveys of pediatric clinical research staff at NCORP sites were performed. The first was a web-based inquiry of NCORP COG PIs and lead CRAs to assess their general understanding of NCORP organizational structure and needs. The second survey of COG PIs was conducted by one-on-one telephone interviews aimed at identifying specific barriers to physician engagement and patient enrollment in clinical trial research. RESULTS: The majority of NCORP COG PIs and CRAs (63%) reported an incomplete understanding of NCORP structure, with approximately half expressing interest in developing stronger collaborations and engagement. Most NCORP COG PIs reported at least one shared barrier to clinical trial enrollment (78%), with inadequate protected time and research support (39% each) being the most frequently cited barriers. CONCLUSIONS: Contributions to pediatric cancer clinical research at COG NCORP sites could be enhanced through improved education, resources, and time allocation.
Assuntos
Ensaios Clínicos como Assunto , Oncologia , Neoplasias , Oncologistas , Adulto , Criança , Pesquisa sobre Serviços de Saúde , Humanos , National Cancer Institute (U.S.) , Neoplasias/terapia , Estados UnidosRESUMO
Desmoid tumors are a manifestation of familial adenomatous polyposis (FAP), associated with mutation of the APC gene. Although considered benign tumors, desmoids can be aggressive and cause considerable morbidity. Known risk factors for desmoid tumor growth include location of mutations within the APC gene, family history of desmoid tumors, previous surgery, female gender, and pregnancy. Desmoids occur at diverse sites, commonly within the abdomen or at sites of previous surgery; thoracic desmoids are relatively uncommon. Reported here is a highly desmoid tumor-prone FAP family with a truncating mutation in the APC gene at codon 1550 (c.4648G>T) in which female siblings developed remarkably similar thoracic desmoids with highly aggressive tumor behavior during the onset of puberty, throughout adolescence, and in one sibling during and following pregnancy. Both siblings had a fatal outcome. This case underscores the potential for aggressive behavior of desmoids during adolescence and the need for close vigilance during the adolescent and young adult (AYA) age range in desmoid-prone FAP kindreds.
Assuntos
Polipose Adenomatosa do Colo/genética , Fibromatose Agressiva/genética , Genes APC , Irmãos , Neoplasias Torácicas/genética , Polipose Adenomatosa do Colo/complicações , Adolescente , Pré-Escolar , Terapia Combinada/métodos , Evolução Fatal , Feminino , Fibromatose Agressiva/patologia , Fibromatose Agressiva/terapia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Mutação , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Linhagem , Gravidez , Complicações Neoplásicas na Gravidez/genética , Complicações Neoplásicas na Gravidez/patologia , Fatores de Risco , Neoplasias Torácicas/patologia , Neoplasias Torácicas/terapia , Adulto JovemRESUMO
BACKGROUND: Little is known regarding risk factors for chemotherapy-induced nausea (CIN) in pediatric patients. PROCEDURE: A secondary analysis was conducted of a previously published multicenter, prospective, randomized, single-blind, sham-controlled trial assessing the efficacy of acupressure in preventing CIN in pediatric patients receiving highly emetogenic chemotherapy. The primary outcome was nausea severity, self-reported using the Pediatric Nausea Assessment Tool. The relationships between acute and delayed nausea severity and patient- (sex, race, age, and cancer diagnosis) and treatment-related (chemotherapy, antiemetic prophylaxis, CIN, and vomiting control) factors were analyzed by a proportional odds generalized estimating equation approach. The acute phase started with administration of the first and continued for 24 hours after the last chemotherapy dose. The delayed phase started at the end of the acute phase and continued until the next chemotherapy block (maximum seven days). RESULTS: In the acute and delayed phases, 165 and 144 patients provided data for analysis, respectively. Nonwhite race was significantly associated with higher acute phase nausea severity (OR, 1.7; 95% CI, 1.1-2.6). Poor CIN control in the acute phase (OR, 16; 95% CI, 4.0-64.6), diagnosis of a cancer other than a central nervous system (CNS) tumor (OR, 2.5; 95% CI, 1.2-5.3), and cisplatin administration (OR, 3.7; 95% CI, 2.1-6.0) were significantly associated with higher delayed phase nausea severity. CONCLUSION: Acute phase CIN was associated with nonwhite race. Delayed phase CIN was associated with poor acute phase CIN control, diagnosis of non-CNS cancer, and receipt of cisplatin. These findings will inform future antiemetic trial design.
Assuntos
Acupressão , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Náusea , Neoplasias , Adolescente , Antineoplásicos/administração & dosagem , Criança , Cisplatino/administração & dosagem , Feminino , Humanos , Masculino , Náusea/induzido quimicamente , Náusea/epidemiologia , Náusea/terapia , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Chemotherapy-induced nausea and vomiting remain common, distressing side effects of chemotherapy. It has been reported that acupressure prevents chemotherapy-induced nausea in adults, but it has not been well studied in children. METHODS: In this multicenter, prospective, randomized, single-blind, sham-controlled trial, the authors compared acute-phase nausea severity in patients ages 4 to 18 years who were receiving highly emetic chemotherapy using standard antiemetic agents combined with acupressure wrist bands, the most common type of acupressure, versus sham bands. Patients wore acupressure or sham bands continuously on each day of chemotherapy and for up to 7 days afterward. Chemotherapy-induced nausea severity in the delayed phase and chemotherapy-induced vomiting control in the acute and delayed phases also were compared. RESULTS: Of the 187 patients randomized, 165 contributed nausea severity assessments during the acute phase. Acupressure bands did not reduce the severity of chemotherapy-induced nausea in the acute phase (odds ratio [OR], 1.33; 95% confidence limits, 0.89-2.00, in which an OR <1.00 favored acupressure) or in the delayed phase (OR, 1.23; 95% CL, 0.75-2.01). Furthermore, acupressure bands did not improve daily vomiting control during the acute phase (OR, 1.57; 95% CL, 0.95-2.59) or the delayed phase (OR, 0.84; 95% CL, 0.45-1.58). No serious adverse events were reported. CONCLUSIONS: Acupressure bands were safe but did not improve chemotherapy-induced nausea or vomiting in pediatric patients who were receiving highly emetic chemotherapy. Cancer 2018;124:1188-96. © 2017 American Cancer Society.
Assuntos
Acupressão/métodos , Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Náusea/terapia , Neoplasias/tratamento farmacológico , Acupressão/instrumentação , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Masculino , Náusea/induzido quimicamente , Náusea/diagnóstico , Estudos Prospectivos , Índice de Gravidade de Doença , Método Simples-Cego , Resultado do TratamentoRESUMO
PURPOSE: The use of radiographic response as the primary end point in phase II osteosarcoma trials may limit optimal detection of treatment response because of the calcified tumor matrix. We performed this study to determine if time to progression could be used as an end point for subsequent studies. PATIENTS AND METHODS: We performed a retrospective analysis of outcome for patients with recurrent/refractory osteosarcoma enrolled in one of seven phase II trials conducted by the Children's Oncology Group and predecessor groups from 1997 to 2007. All trials used RECIST or WHO radiographic response criteria and the primary end point of response rate. The following potential prognostic factors-age, trial, number of prior chemotherapy regimens, sex, and race/ethnicity-were evaluated for their impact on event-free survival (EFS). We used data from a phase II study (AOST0221) of patients with osteosarcoma who were given inhaled granulocyte-macrophage colony-stimulating factor with first pulmonary recurrence who had an EFS as well as biologic end point to determine the historical disease control rate for patients with fully resected disease. RESULTS: In each included trial, the drugs tested were determined to be inactive on the basis of radiographic response rates. The EFS for 96 patients with osteosarcoma and measurable disease was 12% at 4 months (95% CI, 6% to 19%). There was no significant difference in EFS across trials according to number of prior treatment regimens or patient age, sex, and ethnicity. The 12-month EFS for the 42 evaluable patients enrolled in AOST0221 was 20% (95% CI, 10% to 34%). CONCLUSION: The EFS was uniformly poor for children with recurrent/refractory osteosarcoma in these single-arm phase II trials. We have now constructed baseline EFS outcomes that can be used as a comparison for future phase II trials for recurrent osteosarcoma.
Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Ensaios Clínicos Fase II como Assunto/métodos , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Adolescente , Criança , Intervalo Livre de Doença , Determinação de Ponto Final , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Stagnant outcomes for adolescents and young adults (AYAs; 15 to 39 years old) with cancer are partly attributed to poor enrollment onto clinical trials. The National Cancer Institute (NCI) Community Clinical Oncology Program (CCOP) was developed to improve clinical trial participation in the community setting, where AYAs are most often treated. Further, many CCOP sites had pediatric and medical oncologists with collaborative potential for AYA recruitment and care. For these reasons, we hypothesized that CCOP sites enrolled proportionately more AYAs than non-CCOP sites onto Children's Oncology Group (COG) trials. METHODS: For the 10-year period 2004 through 2013, the NCI Division of Cancer Prevention database was queried to evaluate enrollments into relevant COG studies. The proportional enrollment of AYAs at CCOP and non-CCOP sites was compared and the change in AYA enrollment patterns assessed. All sites were COG member institutions. RESULTS: Although CCOP sites enrolled a higher proportion of patients in cancer control studies than non-CCOP sites (3.5% v 1.8%; P < .001), they enrolled a lower proportion of AYAs (24.1% v 28.2%, respectively; P < .001). Proportional AYA enrollment at CCOP sites decreased during the intervals 2004 through 2008 and 2009 through 2013 (26.7% v 21.7%; P < .001). CONCLUSION: Despite oncology practice settings that might be expected to achieve otherwise, CCOP sites did not enroll a larger proportion of AYAs in clinical trials than traditional COG institutions. Our findings suggest that the CCOP (now the NCI Community Oncology Research Program) can be leveraged for developing targeted interventions for overcoming AYA enrollment barriers.
Assuntos
Ensaios Clínicos como Assunto , Oncologia , Seleção de Pacientes , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Serviços de Saúde Comunitária , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The Children's Oncology Group (COG) has endorsed a clinical practice guideline (CPG) for acute chemotherapy-induced nausea and vomiting (CINV) prophylaxis in children with cancer. This project aims to describe current acute CINV prophylaxis practice at COG sites and the gap between this practice and CPG recommendations. PROCEDURE: Two surveys were developed. The first survey, sent to 94 cancer control and supportive care responsible individuals (CCL RIs) at 94 COG institutions, asked if the institution had a standardized approach to practice and focused on antiemetic agent choice. The second survey, sent to 54 pharmacists at COG sites where the CCL RI indicated that there was a standardized approach to CINV prophylaxis practice, focused on antiemetic dosing. Survey results were described and analyzed for consistency with the CPG recommendations. RESULTS: Among the 69 respondents to the first survey, 54 (78%) stated that their institutions have a standardized approach to CINV prophylaxis practice. However, antiemetic choice varied widely among respondents. Results from the 36 respondents to the second survey also demonstrated significant antiemetic dosing practice variability. Frequent sources of deviation from CPG recommendations were as follows: antiemetic choice when corticosteroids are contraindicated, dexamethasone dosing, aprepitant use in children less than 12 years, and aprepitant use in the presence of a known or suspected drug interaction. CONCLUSIONS: There is a great diversity in the CINV prophylaxis provided to children with cancer at COG sites. Concerted strategies are required to improve awareness of the current CINV prophylaxis CPG and to facilitate CPG-consistent CINV prophylaxis.
Assuntos
Antieméticos/administração & dosagem , Náusea/prevenção & controle , Neoplasias/tratamento farmacológico , Inquéritos e Questionários , Vômito/prevenção & controle , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Vômito/induzido quimicamenteRESUMO
BACKGROUND: Osteosarcoma is the most common bone malignancy in children, adolescents, and young adults. Most study cohorts have 10% to 15% Hispanic patients that encompass many different Hispanic backgrounds. This study characterizes the effect of mainly Mexican American ethnicity on the outcome of children, adolescents, and young adults with osteosarcoma. METHODS: A retrospective analysis of demographics, tumor characteristics, response to treatment, and survival outcome of all localized osteosarcoma of the extremity patients below 30 years of age was performed. A Kaplan-Meier estimates with log-rank tests and Cox proportional hazard regression models were used. RESULTS: Fifty patients (median age, 15; range, 2 to 28 y) with localized high-grade osteosarcoma of the extremity were diagnosed between January 2000 and December 2010. The cohort was 70% Mexican Americans. With a median follow-up of 39 months (range, 5 to 142 mo), patients had a 5-year overall survival and event-free survival of 65% and 48%, respectively. We observed a significantly decreased 5-year event-free survival in patients diagnosed before age 12 relative to patients diagnosed between ages 12 and 29 (11% vs. 57%, P<0.001). We also found that tumor necrosis was not predictive of outcome in our patients. CONCLUSIONS: The preadolescent patients of predominately Mexican American ethnicity had an increased rate of relapse when compared with previous studies. Tumor necrosis is not directly predictive of outcome in this population.