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1.
Support Care Cancer ; 32(7): 405, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833026

RESUMO

PURPOSE: The Pediatric Oncology Group of Ontario (POGO) supported an effort to implement infection management care pathways based on clinical practice guidelines, to improve the consistency of infection management in pediatric cancer patients. The objective of this qualitative study was to describe the perspective of healthcare professionals (HCPs) following implementation. METHODS: Four tertiary pediatric oncology centers in Ontario, Canada, implemented the pathways. We randomly identified three HCPs per group (clinical pharmacists; nurse case managers, educators or practitioners and physician assistants; pediatric oncology fellows; or pediatric oncology staff physicians) per site and invited them to participate in a qualitative interview. One-on-one interviews were conducted remotely, followed by thematic analysis of interview transcripts. RESULTS: A total of 66 invitations were extended and 42 HCPs participated. Identified themes were: (1) implementation approach, (2) access and navigation, (3) engagement, (4) concerns, (5) workplace benefits, (6) reception, and (7) provincial harmonization. HCPs preferred in-person implementation strategies over e-mail communication. They identified teaching/educational utility and benefits to non-oncology departments and non-tertiary centers participating in shared care of patients. Other positive aspects related to evidence-based practice, safety, supporting oncology HCPs, and benefits to patients and families. Concerns included need to ensure users applied clinical judgement and loss of autonomy. Provincial harmonization of practice was viewed positively, although potential logistical and institutional cultural barriers were raised. CONCLUSIONS: Following infection management care pathway implementation, HCPs described educational utility and benefits to non-oncology departments, oncology HCPs, patients, and families. Our findings may facilitate future infection management care pathway provincial harmonization.


Assuntos
Atitude do Pessoal de Saúde , Procedimentos Clínicos , Pessoal de Saúde , Neoplasias , Pesquisa Qualitativa , Humanos , Neoplasias/terapia , Ontário , Criança , Procedimentos Clínicos/organização & administração , Procedimentos Clínicos/normas , Pessoal de Saúde/psicologia , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Feminino , Masculino , Entrevistas como Assunto , Guias de Prática Clínica como Assunto
2.
Radiol Case Rep ; 19(6): 2381-2389, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38572274

RESUMO

Ewing sarcoma is the second most frequent primary bone tumour of childhood and adolescence. The aim of this report is to describe the imaging, pathology, clinical findings, and treatment of a primary intradural extramedullary Ewing sarcoma with a unique intracranial metastatic component in a pediatric patient. A 14-year-old girl with a history of mood disorders presented to the emergency department with a 3-week history of neck torticollis, cervical pain, paresis, and paresthesia of the upper and lower extremities on the left side. Initially, non-organic causes such as somatization or conversion disorder were suspected. She returned 3 months later when her symptoms worsened. MRI of the head and spine was performed, and demonstrated the presence of a suprasellar, retro-chiasmatic mass lesion. There was also diffuse leptomeningeal enhancement, another well-defined intradural extramedullary lesion the sacral region and several multifocal cauda equina soft tissue nodules. The patient first underwent surgery. The patient was also treated with a combination of chemotherapy (vincristine, doxorubicin and cyclophosphamide alternating with ifosfamide and etoposide (VDC/IE)) and radiation as per the Children's Oncology Group AEWS1221 protocol. Most recent imaging conducted 22 months after the initial mass discovery revealed improvement of the suprasellar mass lesion with residual stable appearance of the prominence and enhancement of the pituitary stalk and tuber cinereum. There was interval improvement of the spinal lesions with no convincing residual. Clinically, at almost three years since initial imaging findings, and 25 months since completing treatment, she is stable from an oncology perspective.

3.
Pediatr Exerc Sci ; : 1-11, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38171358

RESUMO

PURPOSE: This study evaluated screening tasks able to identify children with medical conditions or disabilities who may benefit from physical literacy. METHOD: Children completed ≤20 screening tasks during their clinic visit and then the Canadian Assessment of Physical Literacy (2nd edition) at a separate visit. Total Canadian Assessment of Physical Literacy scores <30th percentile were categorized as potentially needing physical literacy support. Receiver operator characteristic curves identified assessment cut points with 80% sensitivity and 40% specificity relative to total physical literacy scores. RESULTS: 223 children (97 girls; 10.1 [2.6] y) participated. Physical activity adequacy, predilection, and physical competence achieved ≥80% sensitivity and ≥40% specificity in both data sets. Adequacy ≤ 6.5 had 86% to 100% sensitivity and 48% to 49% specificity. Daily screen time >4.9 hours combined with Adequacy ≤6.15 had 88% to 10% sensitivity and 53% to 56% specificity. CONCLUSIONS: Activity adequacy, alone or with screen time, most effectively identified children likely to benefit from physical literacy support. Adequacy and screen time questionnaires are suitable for clinical use. Similar results regardless of diagnosis suggest physical competence deficits are not primary determinants of active lifestyles. Research to enhance screening specificity is required.

4.
J Pediatr Hematol Oncol ; 45(8): 436-444, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37807192

RESUMO

Gemtuzumab ozogamicin (GO) is an anti-CD33 antibody that is Food and Drug Administration approved in upfront acute myeloid leukemia (AML) for patients over 1-month old, and for relapsed or refractory AML in patients over 2 years old. GO is now integrated in upfront pediatric AML treatment, and often in CD33+ relapse treatment combined with intensive conventional chemotherapy. Although GO was initially tested as a monotherapeutic agent in relapsed or refractory AML, there are few data in pediatric patients supporting this indication. In this review, we report 4 cases of multiply relapsed pediatric AML patients who were treated with GO monotherapy with palliative intent. Three of 4 patients obtained a complete response with GO reinduction, either as monotherapy or paired with conventional chemotherapy. Three patients remained in remission respectively for 5, 17, and 9 months with GO continuation monotherapy. The literature was reviewed regarding the use of GO in pediatric AML relapse settings.


Assuntos
Gemtuzumab , Leucemia Mieloide Aguda , Criança , Pré-Escolar , Humanos , Lactente , Gemtuzumab/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva
6.
J Med Genet ; 60(12): 1218-1223, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37460202

RESUMO

BACKGROUND: Cancer predisposition syndromes (CPSs) are responsible for at least 10% of cancer diagnoses in children and adolescents, most of which are not clinically recognised prior to cancer diagnosis. A variety of clinical screening guidelines are used in healthcare settings to help clinicians detect patients who have a higher likelihood of having a CPS. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) is an electronic health decision support tool that uses algorithms to help clinicians determine if a child/adolescent diagnosed with cancer should be referred to genetics for a CPS evaluation. METHODS: This study assessed MIPOGG's performance in identifying Li-Fraumeni, DICER1, Constitutional mismatch repair deficiency and Gorlin (nevoid basal cell carcinoma) syndromes in a retrospective series of 84 children diagnosed with cancer and one of these four CPSs in Canadian hospitals over an 18-year period. RESULTS: MIPOGG detected 82 of 83 (98.8%) evaluable patients with any one of these four genetic conditions and demonstrated an appropriate rationale for suggesting CPS evaluation. When compared with syndrome-specific clinical screening criteria, MIPOGG's ability to correctly identify children with any of the four CPSs was equivalent to, or outperformed, existing clinical criteria respective to each CPS. CONCLUSION: This study adds evidence that MIPOGG is an appropriate tool for CPS screening in clinical practice. MIPOGG's strength is that it starts with a specific cancer diagnosis and incorporates criteria relevant for associated CPSs, making MIPOGG a more universally accessible diagnostic adjunct that does not require in-depth knowledge of each CPS.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Síndromes Neoplásicas Hereditárias , Criança , Humanos , Algoritmos , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Estudos Retrospectivos
7.
Br J Cancer ; 129(2): 318-324, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37165200

RESUMO

BACKGROUND: Studies to date have yielded inconclusive results as to whether maternal medical history during pregnancy, and a child's early-life medical history contribute to the development of childhood brain tumours (CBTs). This study examined associations between maternal and childhood medical history and the risk of CBTs. METHODS: The Childhood Brain Tumour Epidemiology Study of Ontario (CBREO) examined children 0-15 years of age with newly diagnosed CBTs from 1997 to 2003. Multivariable logistic regression analysis determined associations for prenatal medications and childhood medical history, adjusted for child's demographics, and maternal education. Analyses were stratified by histology. A latency period analysis was conducted using 12- and 24-month lead times. RESULTS: Maternal intake of immunosuppressants during the prenatal period was significantly associated with glial tumours (OR 2.73, 95% CI 1.17-6.39). Childhood intake of anti-epileptics was significantly associated with CBTs overall, after accounting for 12-month (OR 8.51, 95% CI 3.35-21.63) and 24-month (OR 6.04, 95% CI 2.06-17.70) lead time before diagnosis. No associations for other medications were found. CONCLUSIONS: This study underscores the need to examine potential carcinogenic effects of the medication classes highlighted and of the indication of medication use. Despite possible reverse causality, increased CBT surveillance for children with epilepsy might be warranted.


Assuntos
Neoplasias Encefálicas , Efeitos Tardios da Exposição Pré-Natal , Criança , Feminino , Gravidez , Humanos , Estudos de Casos e Controles , Ontário/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Família , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/etiologia , Fatores de Risco
8.
J Healthc Leadersh ; 15: 11-18, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36691566

RESUMO

Purpose: The Division Chief at an academic health sciences centre has many leadership roles and responsibilities. There are no data on leadership training needs for Division Chiefs, and so we sought to design and implement a needs assessment for pediatric Division Chiefs at CHEO, a pediatric academic health sciences centre in Eastern Ontario, Canada. Methods: A needs assessment survey was developed with the aim to document demographics, preparedness for the role of Division Chief and desired leadership training for the role. This survey was piloted, revised and then distributed to all the Division Chiefs at our institution. The results of each question were collated, and simple descriptive statistics were calculated. Results: The survey was completed by 22 of 31 Division Chiefs. The majority of respondents were from the Department of Pediatrics (63.6%), followed by Surgery (20%), Psychiatry (3.3%) and Laboratory Medicine (3.3%). Their mean length of time as Division Chief was 5.5 years. Seventy-seven percent had concurrent leadership roles in addition to the role of Division Chief. None felt they were very well prepared for the role, five felt they were somewhat well prepared, nine were neutral, five were somewhat unprepared and three were very unprepared for the role. Half of the respondents received mentoring, either formal or informal, for their role and all but one felt that formal mentoring would have been useful. In terms of desired training, the Division Chiefs felt they had the most knowledge and skills in patient safety. All wanted training in developing divisional budgets, and many desired training in supporting the academic mission of the Division. Conclusion: Overall, this needs assessment identified an unmet need for leadership training and development among Division Chiefs. The findings are being used to optimize onboarding of Division Chiefs and an ongoing leadership development program targeted at this group.

9.
BMC Cancer ; 22(1): 730, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35787263

RESUMO

BACKGROUND: Symptom Screening in Pediatrics Tool (SSPedi) was developed for symptom screening by children 8-18 years. Objectives were to evaluate the reliability and validity of proxy-SSPedi and self-report mini-SSPedi for younger children. METHODS: This multi-center study enrolled guardians of children 2-7 years receiving cancer treatments (proxy-SSPedi) and their children 4-7 years (mini-SSPedi). The two populations were: (1) More symptomatic group where children were receiving active cancer treatment and were in hospital or clinic for four consecutive days; and (2) Less symptomatic group where children were receiving maintenance therapy for acute lymphoblastic leukemia or had completed cancer therapy. Proxy-SSPedi or mini-SSPedi were completed with measures of mucositis, nausea, pain, quality of life and overall symptoms. Respondents in the more symptomatic group repeated proxy-SSPedi/mini-SSPedi and a global symptom change scale 3 days later. RESULTS: There were 402 guardians and 326 children included in the analysis. Test re-test reliability of proxy-SSPedi showed intraclass correlation coefficient (ICC) 0.83 (95% confidence interval (CI) 0.72-0.90). Mean difference in proxy-SSPedi between more and less symptomatic groups was 9.7 (95% CI 8.3-11.1). Proxy-SSPedi was responsive to change and hypothesized relationships between measures were observed. With a priori threshold ≥0.6, inter-rater ICC among all dyads and those 6-7 years were 0.54 (95% CI 0.45-0.62) and 0.62 (95% CI 0.50-0.71) respectively. Among participating children, other hypothesized reliability and validity thresholds were generally met. CONCLUSIONS: Proxy-SSPedi is reliable, valid and responsive in children 2-7 years old receiving cancer treatments. Mini-SSPedi can be used for children 6-7 years of age.


Assuntos
Neoplasias , Pediatria , Diretivas Antecipadas , Instituições de Assistência Ambulatorial , Criança , Pré-Escolar , Humanos , Neoplasias/tratamento farmacológico , Qualidade de Vida , Reprodutibilidade dos Testes
10.
J Pediatr Hematol Oncol Nurs ; 39(6): 366-378, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35759365

RESUMO

Background: There is a lack of self-management tools for adolescents with cancer (AWC). This study evaluated the feasibility of Teens Taking Charge Cancer, a web-based self-management program. Methods: A pilot randomized control trial (RCT) was conducted across 4 pediatric oncology clinics. AWC (12-18 years) and their caregivers were randomized to either the intervention or control group. All were asked to complete 12 website modules over 12 weeks (at their own pace) and received monthly calls from health coaches. The intervention website was based on cognitive behavioral principals, designed as an interactive self-guided online program, while the control consisted of education and included links to 12 general cancer websites. Outcome assessments occurred at enrollment and 12 weeks post-intervention. The primary outcomes included rate of accrual and retention, adherence to the protocol, acceptability and satisfaction with intervention using questionnaire and semi-structured interviews, adverse events and engagement with the intervention. Results: Eighty-one teen-caregiver dyads were enrolled with a retention rate of 33%. In the intervention group 46% (n = 18) logged in at least once over the 12-week period. A mean of 2.4 of 12 modules (SD 3.0) were completed; and no one completed the program. Thirty-three percent of caregivers in the intervention logged into the website at least once and none completed the full program. Discussion: The results from this pilot study suggest that the current design of the Teens Taking Charge Cancer RCT lacks feasiblity. Future web-based interventions for this group should include additional features to promote uptake and engagement with the program.


Assuntos
Neoplasias , Autogestão , Criança , Adolescente , Humanos , Projetos Piloto , Inquéritos e Questionários , Neoplasias/terapia , Internet
11.
Cancers (Basel) ; 14(12)2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35740650

RESUMO

Oral metronomic topotecan represents a novel approach to chemotherapy delivery which, in preclinical models, may work synergistically with pazopanib in targeting angiogenesis. A phase I and pharmacokinetic (PK) study of this combination was performed in children with relapsed/refractory solid tumors. Oral topotecan and pazopanib were each administered daily without interruption in 28-day cycles at five dose levels (0.12 to 0.3 mg/m2 topotecan and 125 to 160 mg/m2 pazopanib powder for oral suspension (PfOS)), with dose escalation in accordance with the rolling-six design. PK studies were performed on day 1 and at steady state. Thirty patients were enrolled, with 26 evaluable for dose-limiting toxicity (DLT), with median age 12 years (3-20). Toxicities were generally mild; the most common grade 3/4 adverse events related to protocol therapy were neutropenia (18%), thrombocytopenia (11%), lymphopenia (11%), AST elevation (11%), and lipase elevation (11%). Only two cycle 1 DLTs were observed on study, both at the 0.3/160 mg/m2 dose level comprising persistent grade 3 thrombocytopenia and grade 3 ALT elevation. No AEs experienced beyond cycle 1 required treatment discontinuation. The best response was stable disease in 10/25 patients (40%) for a median duration of 6.4 (1.7-45.1) months. The combination of oral metronomic topotecan and pazopanib is safe and tolerable in pediatric patients with solid tumors, with a recommended phase 2 dose of 0.22 mg/m2 topotecan and 160 mg/m2 pazopanib. No objective responses were observed in this heavily pre-treated patient population, although 40% did achieve stable disease for a median of 6 months. While this combination is likely of limited benefit for relapsed disease, it may play a role in the maintenance setting.

12.
Pediatr Blood Cancer ; 69(8): e29585, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35147285

RESUMO

BACKGROUND: Central nervous system (CNS) relapse in pediatric acute lymphoblastic leukemia (ALL) patients is uncommon. The cerebrospinal fluid (CSF) of patients with ALL is routinely sampled at each intrathecal chemotherapy treatment to screen for CNS relapse. The analysis of CSF is both time consuming and resource intensive and must be completed approximately 20 times per patient throughout treatment. Our objective was to examine the expense of routine screening on all CSF samples for CNS relapse in ALL patients, and to identify if CNS relapse can be detected clinically. METHODS: We identified all patients diagnosed with ALL at the Children's Hospital of Eastern Ontario (CHEO) between January 2001 and June 2021. We collected the total number of CSF samples in these patients and the number of CSF samples positive for CNS relapse. An in-depth chart review on the patients who relapsed in the CNS was completed to identify symptoms at relapse. RESULTS: Over the study period, 351 patients were diagnosed with ALL and underwent a total of 6515 lumbar punctures (LPs), each of which examined the CSF. The cost of CSF sample analysis is $14.32 (Canadian dollars [CDN]); thus, the total cost for the study sample was $93,294.80 (CDN). There were 14 CNS relapses and although symptoms including headache, vomiting, and fatigue were common, two patients were asymptomatic at relapse. CONCLUSIONS: Given the marginal cost of routine CSF screening and the lack of specific and sensitive symptoms for CNS relapse, we conclude that the routine practice of sending all CSF samples for analysis of CNS relapse in ALL patients is relatively inexpensive and beneficial.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Punção Espinal , Sistema Nervoso Central , Líquido Cefalorraquidiano , Criança , Humanos , Ontário/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquidiano , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva
13.
J Pediatr Hematol Oncol ; 44(1): e255-e259, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33448719

RESUMO

Embryonal tumor with multilayered rosettes is a rare and highly malignant early childhood brain tumor. We report a case of embryonal tumor with multilayered rosettes in the parietooccipital region of a 2-year-old girl. Histopathology of the tumor demonstrated amplification of the 19q13.42 locus and strong positivity for LIN28A. Treatment was multimodal and included 3 surgical resections, adjuvant chemotherapy with autologous stem cell rescue, and focal radiotherapy. The use of the agents vorinostat and isotretinoin, and the addition of focal radiation have not been extensively described in this patient population, but may attribute to our patient's sustained remission at 2.5-years follow-up.


Assuntos
Neoplasias Encefálicas , Cromossomos Humanos Par 19/genética , Loci Gênicos , Isotretinoína/administração & dosagem , Neoplasias Embrionárias de Células Germinativas , Transplante de Células-Tronco , Vorinostat/administração & dosagem , Autoenxertos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Quimiorradioterapia Adjuvante , Pré-Escolar , Feminino , Humanos , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia
14.
J Pediatr Hematol Oncol ; 44(3): e788-e791, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33902061

RESUMO

Sinusoidal obstruction syndrome (SOS), formerly veno-occlusive disease (VOD), in pediatric cancer patients often presents as a complication of hematopoietic stem cell transplantation, and less commonly secondary to nontransplant-associated chemotherapy. Therapy with defibrotide is well-described as standard care for transplant-associated SOS/VOD, but the treatment of nontransplant-associated SOS/VOD is less clear. We report a 3-year-old with relapsed Wilms tumor and recurrent SOS/VOD, with successful use of defibrotide during chemotherapy. A review of pediatric cancer patients with nontransplant-associated SOS/VOD treated with defibrotide revealed 83 patients, and 66 were in remission. This review supports early treatment with defibrotide in patients with nontransplant-associated SOS/VOD.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Neoplasias Renais , Criança , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Polidesoxirribonucleotídeos/uso terapêutico
15.
Int J Cancer ; 150(5): 795-801, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34520575

RESUMO

Head trauma in early childhood has been hypothesized as a potential risk factor for childhood brain tumours (CBTs). However, head trauma has not been extensively studied in the context of CBTs and existing studies have yielded conflicting results. A population-based and hospital-based case-control study of children 0 to 15 years with newly diagnosed CBTs from 1997 to 2003 recruited across Ontario through paediatric oncology centres was conducted. Controls were frequency-matched with cases by age, sex and geographical region. The association was assessed based on multivariable logistic regressions, accounting for child's age, sex, ethnicity, highest level of maternal education and maternal pack-years of smoking during the pregnancy. Analyses were conducted separately based on age of first head trauma, sex and histology. A latency period analysis was conducted. Overall, based on 280 cases and 919 controls, CBTs were not significantly associated with previous history of head trauma (OR 1.34, 95% CI 0.96, 1.86), head trauma severity, number of head injuries, or head or neck X-rays or computed tomography (CT) examinations. Results were consistent across sexes and histological subtypes. However, head trauma within the first year of life was significantly associated with CBTs (OR 2.00, 95% CI 1.01, 3.98), but the association diminished when adjusted for X-ray or CT occurring during the same time period (OR 1.62, 95% CI 0.75, 3.49), albeit limited sample size. Overall, no association was observed between head trauma and CBTs among all children, while head trauma occurring within first year of life may warrant further investigation in future research.


Assuntos
Neoplasias Encefálicas/etiologia , Traumatismos Craniocerebrais/complicações , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Fatores de Risco
16.
Can Oncol Nurs J ; 32(3): 381-386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-38919683

RESUMO

Goal: This study aims to explore how healthcare professionals perceive home-based pediatric cancer care provided in French. Methodology: A qualitative descriptive study was conducted using semi-directed individual interviews of 22 healthcare professionals. A thematic analysis of the transcribed interviews was carried out independently by two members of the research team. Findings: Pediatric cancer care is readily available in French in Quebec, but access to French-language services in Ontario is limited. The possible causes and effects of this lack of access and potential solutions are discussed in this paper. Conclusion: The perceptions compiled in this study should be taken into account to help provide quality home-based pediatric cancer care in French.

17.
JAMA Oncol ; 7(12): 1806-1814, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34617981

RESUMO

IMPORTANCE: Prompt recognition of a child with a cancer predisposition syndrome (CPS) has implications for cancer management, surveillance, genetic counseling, and cascade testing of relatives. Diagnosis of CPS requires practitioner expertise, access to genetic testing, and test result interpretation. This diagnostic process is not accessible in all institutions worldwide, leading to missed CPS diagnoses. Advances in electronic health technology can facilitate CPS risk assessment. OBJECTIVE: To evaluate the diagnostic accuracy of a CPS prediction tool (McGill Interactive Pediatric OncoGenetic Guidelines [MIPOGG]) in identifying children with cancer who have a low or high likelihood of having a CPS. DESIGN, SETTING, AND PARTICIPANTS: In this international, multicenter diagnostic accuracy study, 1071 pediatric (<19 years of age) oncology patients who had a confirmed CPS (12 oncology referral centers) or who underwent germline DNA sequencing through precision medicine programs (6 centers) from January 1, 2000, to July 31, 2020, were studied. EXPOSURES: Exposures were MIPOGG application in patients with cancer and a confirmed CPS (diagnosed through routine clinical care; n = 413) in phase 1 and MIPOGG application in patients with cancer who underwent germline DNA sequencing (n = 658) in phase 2. Study phases did not overlap. Data analysts were blinded to genetic test results. MAIN OUTCOMES AND MEASURES: The performance of MIPOGG in CPS recognition was compared with that of routine clinical care, including identifying a CPS earlier than practitioners. The tool's test characteristics were calculated using next-generation germline DNA sequencing as the comparator. RESULTS: In phase 1, a total of 413 patients with cancer (median age, 3.0 years; range, 0-18 years) and a confirmed CPS were identified. MIPOGG correctly recognized 410 of 412 patients (99.5%) as requiring referral for CPS evaluation at the time of primary cancer diagnosis. Nine patients diagnosed with a CPS by a practitioner after their second malignant tumor were detected by MIPOGG using information available at the time of the first cancer. In phase 2, of 658 children with cancer (median age, 6.6 years; range, 0-18.8 years) who underwent comprehensive germline DNA sequencing, 636 had sufficient information for MIPOGG application. When compared with germline DNA sequencing for CPS detection, the MIPOGG test characteristics for pediatric-onset CPSs were as follows: sensitivity, 90.7%; specificity, 60.5%; positive predictive value, 17.6%; and negative predictive value, 98.6%. Tumor DNA sequencing data confirmed the MIPOGG recommendation for CPS evaluation in 20 of 22 patients with established cancer-CPS associations. CONCLUSIONS AND RELEVANCE: In this diagnostic study, MIPOGG exhibited a favorable accuracy profile for CPS screening and reduced time to CPS recognition. These findings suggest that MIPOGG implementation could standardize and rationalize recommendations for CPS evaluation in children with cancer.


Assuntos
Testes Genéticos , Neoplasias , Criança , Pré-Escolar , Detecção Precoce de Câncer , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Síndrome
18.
J Clin Oncol ; 39(29): 3207-3216, 2021 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-34383599

RESUMO

PURPOSE: Childhood cancer survivors (CCS) are at risk of developing subsequent malignant neoplasms (SMNs) resulting from exposure to prior therapies. CCS with underlying cancer predisposition syndromes are at additional genetic risk of SMN development. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) tool identifies children with cancer at increased likelihood of having a cancer predisposition syndrome, guiding clinicians through a series of Yes or No questions that generate a recommendation for or against genetic evaluation. We evaluated MIPOGG's ability to predict SMN development in CCS. METHODS: Using the provincial cancer registry (Ontario, Canada), and adopting a nested case-control approach, we identified CCS diagnosed and/or treated for a primary malignancy before age 18 years (1986-2015). CCS who developed an SMN (cases) were matched, by primary cancer and year of diagnosis, with CCS who did not develop an SMN (controls) over the same period (1:5 ratio). Potential predictors for SMN development (chemotherapy, radiation, and MIPOGG output) were applied retrospectively using clinical data pertaining to the first malignancy. Conditional logistic regression models estimated hazard ratios and 95% CIs associated with each covariate, alone and in combination, for SMN development. RESULTS: Of 13,367 children with a primary cancer, 317 (2.4%) developed an SMN and were matched to 1,569 controls. A MIPOGG output recommending evaluation was significantly associated with SMN development (hazard ratio 1.53; 95% CI, 1.06 to 2.19) in a multivariable model that included primary cancer therapy exposures. MIPOGG was predictive of SMN development, showing value in nonhematologic malignancies and in CCS not exposed to radiation. CONCLUSION: MIPOGG has additional value for SMN prediction beyond treatment exposures and may be beneficial in decision making for enhanced individualized SMN surveillance strategies for CCS.


Assuntos
Sobreviventes de Câncer , Detecção Precoce de Câncer/métodos , Segunda Neoplasia Primária/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Modelos Logísticos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
19.
JCO Oncol Pract ; 17(6): e827-e839, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33914620

RESUMO

PURPOSE: Although the hospital remains the dominant site for delivering most pediatric cancer care, home-based care is increasingly provided. To effectively deliver comprehensive, relevant, and acceptable care in children's homes, the voices of these key informants must be considered. We examined the views of children with cancer, their family caregivers, and clinicians on home-based cancer care to identify necessary strategies to improve the delivery of care. METHODS: Children with cancer, their family caregivers, and multiprofessional clinicians who provide care at a tertiary pediatric care center or in the community participated in audio-recorded, semistructured interviews in French and English. Interviews were conducted until data saturation in each participant group was achieved. Interviews were transcribed, coded, and analyzed using thematic analysis. RESULTS: Thirteen children, 20 family caregivers, and 22 clinicians participated. Home-based care was endorsed as a means to improve child health-, family social- and financial-, and system-level outcomes. The success of a home-based model is built on care that addresses child and family informational, treatment and care, material, and psychosocial needs. Mechanisms to improve care include enhanced homecare agency-hospital-family communication, training for homecare nurses in pediatric cancer care, virtual solutions, and an expanded breadth of services provided in-home. Child-, family-, and system-related factors affect the delivery of optimal home-based care. CONCLUSION: Children, families, and clinicians value a model of pediatric cancer care that incorporates home-based services. The insights of these key informants should be reflected in the principles that become the basis of home-based cancer care best practices.


Assuntos
Serviços de Assistência Domiciliar , Neoplasias , Cuidadores , Criança , Comunicação , Família , Humanos , Neoplasias/terapia
20.
Pediatr Dev Pathol ; 24(4): 309-317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33749384

RESUMO

INTRODUCTION: The World Health Organization currently classifies medulloblastoma (MB) into four molecular groups (WNT, SHH, Group 3 and Group 4) and four histologic subtypes (classic, desmoplastic nodular, MB with extensive nodularity, and large cell/anaplastic). "Classic" MB is the most frequent histology, but unfortunately it does not predict molecular group or patient outcome. While MB may exhibit additional histologic features outside of the traditional WHO subtypes, the clinical significance of such features, in a molecular context, is unclear. METHODS: The clinicopathologic features of 120 pediatric MB were reviewed in the context of NanoString molecular grouping. Each case was evaluated for five ancillary histologic features, including: nodularity without desmoplasia (i.e., "biphasic", B-MB), rhythmic palisades, and focal anaplasia. Molecular and histological features were statistically correlated to clinical outcome using Chi-square, log-rank, and multivariate Cox regression analysis. RESULTS: While B-MB (N = 32) and rhythmic palisades (N = 12) were enriched amongst non-WNT/SHH MB (especially Group 4), they were not statistically associated with outcome. In contrast, focal anaplasia (N = 12) was not associated with any molecular group, but did predict unfavorable outcome. CONCLUSION: These data nominate B-MB as a surrogate marker of Groups 3 and particularly 4 MB, which may earmark a clinically significant subset of cases.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Cerebelares/patologia , Proteínas Hedgehog/metabolismo , Meduloblastoma/patologia , Proteínas Wnt/metabolismo , Canadá , Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/mortalidade , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Meduloblastoma/diagnóstico , Meduloblastoma/metabolismo , Meduloblastoma/mortalidade , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Análise Serial de Tecidos
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