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BACKGROUND AND AIMS: Tumour rupture (TR) signifies stage III disease and requires treatment intensification, which includes radiotherapy. We studied the associations between radiological, surgical and pathology TR in children with Wilms tumour (WT) in a United Kingdom multicentre clinical study. PATIENTS AND METHODS: The IMPORT (Improving Population Outcomes for Renal Tumours of Childhood) study registered 712 patients between 2012 and 2021. Children with TR on central radiology review (CRR) at diagnosis and/or indication of preoperative TR on surgical forms were included. Correlation between radiology/surgery/pathology findings was made. RESULTS: Total 141 patients had TR identified (69 on CRR, 43 on surgical form and 29 on both), and 124/141 had images available for CRR, and 98/124 had features suggestive of TR on diagnostic CRR (63 magnetic resonance imaging/35 computed tomography). TR was limited to the renal fossa in 47/98 (48%) and intraperitoneal in 51/98 (52%). Three of 98(3%) had upfront surgery, and 87/95 (92%) had TR confirmed on post-chemotherapy preoperative scans. Among 80/98 (82%) cases with TR on CRR and available surgical forms, TR was not confirmed on surgery or pathology in 38/80, giving a false-positive rate of 48%. Preoperative TR was indicated on 72 surgical forms, with images available for CRR in 55. Twenty-six of 55 (47%) were false-negative for TR on CRR and of those 10/26 (38%) had TR confirmed on pathology. CONCLUSIONS: Radiology alone should not be used to define TR, as it does not accurately correlate with surgical or pathology findings, and therefore cannot be relied upon for definitive staging and treatment. A multidisciplinary team should take the decision regarding the final abdominal stage and treatment using a multimodality approach considering clinical, radiological, surgical and pathological findings.
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BACKGROUND: Wilms tumour (WT) is one of the common and curable cancer types targeted by the Global Initiative for Childhood Cancer. Tumour excision is essential for cure. This analysis focuses on surgical outcomes of patients with WT in sub-Saharan Africa. METHODS: We implemented a risk-stratified WT treatment guideline as a multicentre, prospective study across eight hospitals and six countries. Eligibility criteria were age 6 months to 16 years, unilateral WT, surgery performed after preoperative chemotherapy and diagnosed between 1 January 2021 and 31 December 2022. Data collection included a specific surgical case report form (CRF). RESULTS: The study registered 230 patients, among whom 164 (71.3%) had a nephrectomy. Ninety-eight percent of patients had a completed surgical CRF. Out 164 patients, 50 (30.5%) had distant metastases. Median tumour diameter at surgery was 11.0 cm. Lymph node sampling was done in 122 (74.3%) patients, 34 (20.7%) had intraoperative tumour rupture, and for 18 (10.9%), tumour resection involved en bloc resection of another organ. Tumour size at surgery was significantly correlated with tumour rupture (p < .01). With a median follow-up of 17 months (range: 2-33), 23 (14.0%) patients have relapsed. Twenty-two (13.4%) patients abandoned treatment post nephrectomy. Two-year event-free survival was 60.4% ± 4.7% with treatment abandonment as an event. CONCLUSION: Survival post nephrectomy is challenged by treatment abandonment, treatment-related mortality and relapse. Large tumours after preoperative chemotherapy were associated with a higher risk of tumour rupture. Earlier diagnosis and access to radiotherapy are expected to improve survival.
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Childhood cancer survivors (CCS) require specialized follow-up throughout their lifespan to prevent or manage late effects of cancer treatment. Knowing the size and structure of the population of CCS is crucial to plan interventions. In this scoping review we reviewed studies that reported prevalence of CCS in Europe. We searched Medline, Web of Science, and Embase using permutations of terms referring to childhood, cancer, survivors, prevalence, registries, and Europe. We followed PRISMA-ScR guidelines to select studies and The Joanna Briggs Institute Prevalence Critical Appraisal Tool to evaluate their quality. From 979 unique studies published between 1989 and 2022, 12 were included. Limited-duration prevalence (LDP) for all childhood cancers, assessed in three studies using counting method, varied between 450 and 1240 persons per million. Complete prevalence (CP) of survivors of any childhood cancer except skin carcinomas, reported in three studies using observed data complemented with modelled data for the unobserved period, varied between 730 and 1110 persons per million. CP of survivors of an embryonal tumour was estimated by completeness index method in six studies. In four of them CP ranged from 48 to 95 persons per million for all embryonal tumours, while CP for those occurring in central nervous system was 43 per million in one study and CP for rhabdomyosarcoma was 17 per million in another. Information on prevalence of CCS in Europe is fragmented and inconsistent. The large variations in LDP and CP estimates were linked to differences in data availability, the selection of populations, prevalence measure, statistical method, incidence period, index date, age at diagnosis and prevalence, cancer types, sex, and, for LDP, also the length of follow-up. Standardisation of methodology and reporting are needed to systematically monitor and compare CCS prevalence in Europe and provide data to help address survivors' needs.
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BACKGROUND AND PURPOSE: The optimal utilization rate of radiotherapy (oRUR) serves as a benchmark for assessing service demand and improving access to cancer care. While it is estimated that approximately 50 % of adult cancer patients require external beam radiotherapy during their treatment, there is a scarcity of data regarding the optimal use of radiotherapy in pediatric cancer. In this study, we adopted an established method and developed a model to estimate the oRUR in childhood neuroblastoma. MATERIALS AND METHODS: We developed a decision tree model to calculate the oRUR using indications for radiotherapy and corresponding epidemiological data collected through systematic review and meta-analysis. Sensitivity analyses were performed to evaluate the impact of variations in radiotherapy indications between treatment protocols and variables in the model. We calculated and compared the oRUR for global, high-income, and low- and middle-income settings. RESULTS: The oRUR for pediatric neuroblastoma was 64 % (95 % CI: 58 %-71 %) in the global setting, 50 % in high-income countries, and 68 % in low- and middle-income countries. The impact of variation in radiotherapy indications between major international treatment protocols was negligible. CONCLUSION: The knowledge of oRUR is crucial for evaluating current practices, identifying gaps in access, and planning future radiotherapy services for treating childhood cancer. Based on our results, 64 % of children with neuroblastoma have an indication for radiotherapy. Patients in low- and middle-income countries have more indications for radiotherapy than those in high-income countries, due to a more adverse tumour stage distribution caused by limited access to healthcare resources.
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Neuroblastoma , Criança , Humanos , Árvores de Decisões , Neuroblastoma/radioterapiaRESUMO
BACKGROUND: The Wilms Africa studies implemented an adapted Wilm's tumor (WT) treatment protocol in sub-Saharan Africa in two phases. Phase I began with four sites and provided out-of-pocket costs. Phase II expanded the number of sites, but lost funding provision. Objective is to describe the outcomes of Phase II and compare with Phase I. METHODS: Wilms Africa Phase I (n = 4 sites; 2014-2018) and Phase II (n = 8 sites; 2021-2022) used adapted treatment protocols. Funding for families' out-of-pocket costs was provided during Phase I but not Phase II. Eligibility criteria were age less than 16 years and newly diagnosed unilateral WT. We documented patients' outcome at the end of planned first-line treatment categorized as treatment abandonment, death during treatment, and disease-related events (death before treatment, persistent disease, relapse, or progressive disease). Sensitivity analysis compared outcomes in the same four sites. RESULTS: We included 431 patients in Phase I (n = 201) and Phase II (n = 230). The proportion alive without evidence of disease decreased from 69% in Phase I to 54% in Phase II at all sites (p = .002) and 58% at the original four sites (p = .04). Treatment abandonment increased overall from 12% to 26% (p < .001), and was 20% (p = .04) at the original four sites. Disease-related events (5% vs. 6% vs. 6%) and deaths during treatment (14% vs. 14% vs. 17%) were similar. CONCLUSION: Provision of out-of-pocket costs was important to improve patient outcomes at the end of planned first-line treatment in WT. Prevention of treatment abandonment remains an important challenge.
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Neoplasias Renais , Tumor de Wilms , Humanos , Tumor de Wilms/mortalidade , Tumor de Wilms/terapia , Tumor de Wilms/economia , África Subsaariana/epidemiologia , Feminino , Masculino , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Neoplasias Renais/economia , Pré-Escolar , Taxa de Sobrevida , Criança , Lactente , Adolescente , Prognóstico , Seguimentos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economiaRESUMO
[This corrects the article DOI: 10.3389/fonc.2023.1232451.].
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The Société Internationale d'Oncologie Pédiatrique [International Society of Paediatric Oncology] (SIOP), founded in 1969, aims to improve the lives of children and adolescents with cancer through global collaboration, education, training, research and advocacy. The annual congress provides the opportunity to share late-breaking research, clinical experiences and debate, with experts worldwide. SIOP's six Continental Branches represent their constituent members in North America, Oceania, Latin America, Africa, Europe and Asia and bring best practices and recent research findings of value to their specific patient populations. In 1990, the SIOP Board of Directors addressed the formerly predominantly European/North American society transforming into a global association by establishing a scholarship program to bring low- and middle-income country (LMIC) paediatric oncologists and nurses to SIOP meetings. A major achievement was SIOP's acceptance as a World Health Organisation (WHO) non-state actor in official relations in 2018, joining 220 non-governmental organisations, international business associations and philanthropic foundations with this privilege. SIOP supports advocacy with WHO member states and civil society to highlight the specific needs of cancer in this age-group through key programs especially supporting the WHO Global Initiative for Childhood Cancer. Sustained improvement in childhood cancer outcomes has paralleled the integration of research with care; thus, SIOP launched a Programme for Advancing Research Capacity for funding selected clinical trial groups in LMICs. SIOP supports south-south partnerships, and the principles elegantly expressed in SIOP Africa's checklist for co-branding projects, that include the prioritisation of local needs, cultivation of local expertise and commitment to equitable partnerships. SIOP now counts approximately 3,000 members from over 128 countries; 39% are from more than 60 LMICs. SIOP members have multidisciplinary expertise on all aspects of childhood cancer care working in collaboration with key stakeholders including governments, civil society organisations and funders to improve the lives of children/adolescents with cancer everywhere in all ways.
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BACKGROUND: Completely necrotic Wilms tumor (CN-WT) following preoperative chemotherapy has been regarded as low-risk WT since the International Society of Paediatric Oncology (SIOP) 93-01 study, and patients have been treated with reduced postoperative therapy. The aim of the study was to evaluate whether the omission of adjuvant chemotherapy in patients with localized CN-WT stage I and radiotherapy in stage III was safe. PATIENTS AND METHODS: The retrospective observational study of outcomes of patients diagnosed with localized CN-WT on central pathology review and treated according to the SIOP 93-01 and SIOP-WT-2001 protocols (1993-2022). RESULTS: There were 125 patients with localized CN-WT: 90 with stage I, 10 with stage II, and 25 with stage III. Sixty-two of 125 (49.6%) patients had a discrepant diagnosis and/or staging between the institutional pathologist and central pathology review. In the group of 90 patients with stage I, postoperative chemotherapy was not given to 41 (46%) patients, whereas 49 patients received postoperative chemotherapy-in the latter group, two patients relapsed, and one of them died. One stage I and one stage II patient developed chemotherapy-induced toxicity and died. Nineteen of 25 patients with stage III received no flank radiotherapy. No stage III patient relapsed or died. The overall 5-year event-free survival (EFS) estimate for the entire cohort (stages I-III) was 96.8% [95% confidence interval, CI: 93.6%-99.6%] and the overall survival (OS) was 97.6% [95% CI: 95.0-100%]. The EFS and OS were 97% and 98%, respectively, for stage I, and 100% for stage III. CONCLUSION: Omission of postoperative chemotherapy for patients with CN-WT stage I, and radiotherapy for stage III is safe. Rapid central pathology review is required to assign appropriate treatment and avoid treatment-related side effects.
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Neoplasias Renais , Tumor de Wilms , Criança , Humanos , Lactente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/métodos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Estadiamento de Neoplasias , Resultado do Tratamento , Tumor de Wilms/tratamento farmacológico , Tumor de Wilms/radioterapia , Estudos RetrospectivosRESUMO
The modern study of Wilms tumour was prompted nearly 50 years ago, when Alfred Knudson proposed the 'two-hit' model of tumour development. Since then, the efforts of researchers worldwide have substantially expanded our knowledge of Wilms tumour biology, including major advances in genetics - from cloning the first Wilms tumour gene to high-throughput studies that have revealed the genetic landscape of this tumour. These discoveries improve understanding of the embryonal origin of Wilms tumour, familial occurrences and associated syndromic conditions. Many efforts have been made to find and clinically apply prognostic biomarkers to Wilms tumour, for which outcomes are generally favourable, but treatment of some affected individuals remains challenging. Challenges are also posed by the intratumoural heterogeneity of biomarkers. Furthermore, preclinical models of Wilms tumour, from cell lines to organoid cultures, have evolved. Despite these many achievements, much still remains to be discovered: further molecular understanding of relapse in Wilms tumour and of the multiple origins of bilateral Wilms tumour are two examples of areas under active investigation. International collaboration, especially when large tumour series are required to obtain robust data, will help to answer some of the remaining unresolved questions.
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Neoplasias Renais , Tumor de Wilms , Humanos , Neoplasias Renais/terapia , Recidiva Local de Neoplasia , Tumor de Wilms/terapia , Biomarcadores , BiologiaRESUMO
Wilms tumors (WTs) are histologically diverse childhood cancers with variable contributions of blastema, stroma, and epithelia. A variety of cancer genes operate in WTs, including the tripartite-motif-containing-28 gene (TRIM28). Case reports and small case series suggest that TRIM28 mutations are associated with epithelial morphology and WT predisposition. Here, we systematically investigated the prevalence of TRIM28 inactivation and predisposing mutations in a cohort of 126 WTs with >2/3 epithelial cells, spanning 20 years of biobanking in the German SIOP93-01/GPOH and SIOP2001/GPOH studies. Overall, 44.4% (56/126) cases exhibited loss of TRIM28 by immunohistochemical staining. Of these, 48 could be further analyzed molecularly, revealing TRIM28 sequence variants in each case - either homozygous (~2/3) or heterozygous with epigenetic silencing of the second allele (~1/3). The majority (80%) of the mutations resulted in premature stops and frameshifts. In addition, we detected missense mutations and small deletions predicted to destabilize the protein through interference with folding of key structural elements such as the zinc-binding clusters of the RING, B-box-2, and PHD domains or the central coiled-coil region. TRIM28-mutant tumors otherwise lacked WT-typical IGF2 alterations or driver events, except for rare TP53 progression events that occurred with expected frequency. Expression profiling identified TRIM28-mutant tumors as a homogeneous subset of epithelial WTs that mostly present with stage I disease. There was a high prevalence of perilobar nephrogenic rests, putative precursor lesions, that carried the same biallelic TRIM28 alterations in 7/7 cases tested. Importantly, 46% of the TRIM28 mutations were present in blood cells or normal kidney tissue, suggesting germline events or somatic mosaicism, partly supported by family history. Given the high prevalence of predisposing variants in TRIM28-driven WT, we suggest that immunohistochemical testing of TRIM28 be integrated into diagnostic practice as the management of WT in predisposed children differs from that with sporadic tumors. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Neoplasias Renais , Tumor de Wilms , Criança , Humanos , Neoplasias Renais/patologia , Bancos de Espécimes Biológicos , Tumor de Wilms/metabolismo , Rim/patologia , Mutação em Linhagem Germinativa , Suscetibilidade a Doenças/patologia , Proteína 28 com Motivo Tripartido/genéticaRESUMO
Reninomas are exceedingly rare renin-secreting kidney tumours that derive from juxtaglomerular cells, specialised smooth muscle cells that reside at the vascular inlet of glomeruli. They are the central component of the juxtaglomerular apparatus which controls systemic blood pressure through the secretion of renin. We assess somatic changes in reninoma and find structural variants that generate canonical activating rearrangements of, NOTCH1 whilst removing its negative regulator, NRARP. Accordingly, in single reninoma nuclei we observe excessive renin and NOTCH1 signalling mRNAs, with a concomitant non-excess of NRARP expression. Re-analysis of previously published reninoma bulk transcriptomes further corroborates our observation of dysregulated Notch pathway signalling in reninoma. Our findings reveal NOTCH1 rearrangements in reninoma, therapeutically targetable through existing NOTCH1 inhibitors, and indicate that unscheduled Notch signalling may be a disease-defining feature of reninoma.
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Neoplasias Renais , Renina , Humanos , Renina/metabolismo , Neoplasias Renais/metabolismo , Sistema Justaglomerular/metabolismo , Sistema Justaglomerular/patologia , Glomérulos Renais/patologia , Transdução de Sinais/genética , Receptor Notch1/genéticaRESUMO
Introduction: Variation in stage at diagnosis of childhood cancers (CC) may explain differences in survival rates observed across geographical regions. The BENCHISTA project aims to understand these differences and to encourage the application of the Toronto Staging Guidelines (TG) by Population-Based Cancer Registries (PBCRs) to the most common solid paediatric cancers. Methods: PBCRs within and outside Europe were invited to participate and identify all cases of Neuroblastoma, Wilms Tumour, Medulloblastoma, Ewing Sarcoma, Rhabdomyosarcoma and Osteosarcoma diagnosed in a consecutive three-year period (2014-2017) and apply TG at diagnosis. Other non-stage prognostic factors, treatment, progression/recurrence, and cause of death information were collected as optional variables. A minimum of three-year follow-up was required. To standardise TG application by PBCRs, on-line workshops led by six tumour-specific clinical experts were held. To understand the role of data availability and quality, a survey focused on data collection/sharing processes and a quality assurance exercise were generated. To support data harmonization and query resolution a dedicated email and a question-and-answers bank were created. Results: 67 PBCRs from 28 countries participated and provided a maximally de-personalized, patient-level dataset. For 26 PBCRs, data format and ethical approval obtained by the two sponsoring institutions (UCL and INT) was sufficient for data sharing. 41 participating PBCRs required a Data Transfer Agreement (DTA) to comply with data protection regulations. Due to heterogeneity found in legal aspects, 18 months were spent on finalizing the DTA. The data collection survey was answered by 68 respondents from 63 PBCRs; 44% of them confirmed the ability to re-consult a clinician in cases where stage ascertainment was difficult/uncertain. Of the total participating PBCRs, 75% completed the staging quality assurance exercise, with a median correct answer proportion of 92% [range: 70% (rhabdomyosarcoma) to 100% (Wilms tumour)]. Conclusion: Differences in interpretation and processes required to harmonize general data protection regulations across countries were encountered causing delays in data transfer. Despite challenges, the BENCHISTA Project has established a large collaboration between PBCRs and clinicians to collect detailed and standardised TG at a population-level enhancing the understanding of the reasons for variation in overall survival rates for CC, stimulate research and improve national/regional child health plans.
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BACKGROUND: In the United Kingdom, healthcare data is collected on all patients receiving National Health Service (NHS) care, including children and young people (CYP) with cancer. This data is used to inform service delivery, and with special permissions used for research. The use of routinely collected health data in research is an advancing field with huge potential benefit, particularly in CYP with cancer where case numbers are small and the impact across the life course can be significant. Patient and public involvement (PPI) exercise aims: Identify current barriers to trust relating to the use of healthcare data for research. Determine ways to increase public and patient confidence in the use of healthcare data in research. Define areas of research importance to CYP and their carers using healthcare data. METHODS: Young people currently aged between 16 and 25 years who had a cancer diagnosis before the age of 20 years and carers of a young person with cancer were invited to take part via social media and existing networks of service users. Data was collected during two interactive online workshops totalling 5 h and comprising of presentations from health data experts, case-studies and group discussions. With participant consent the workshops were recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: Ten young people and six carers attended workshop one. Four young people and four carers returned for workshop two. Lack of awareness of how data is used, and negative media reporting were seen as the main causes of mistrust. Better communication and education on how data is used were felt to be important to improving public confidence. Participants want the ability to have control over their own data use. Late effects, social and education outcomes and research on rare tumours were described as key research priorities for data use. CONCLUSIONS: In order to improve public and patient trust in our use of data for research, we need to improve communication about how data is used and the benefits that arise.
Everyday data is collected on all patients treated within the National Health Service, including children and young people with cancer (CYP). This data is used routinely to improve how services are run and with special permissions, can also be used for research. Negative reporting in the media about this use of data can lead to mistrust and some people choosing not to share their data. This can reduce the quality and accuracy of research looking at rare diseases or populations with small numbers. In addition, many barriers exist to researchers when trying to access this data such as laws around data sharing, making it difficult and sometimes impossible to carry out such research. We invited CYP and carers to two workshops to: Learn about how healthcar e data is used for research. Consider ways to increase public and patient confidence in this use of healthcare data. Describe areas of research importance to CYP and their carers using healthcare data. Ten young people and six carers attended the first workshop. Four young people and four carers returned for workshop two. Workshops consisted of interactive presentations, case studies and group discussions. Overall participants felt that lack of awareness and negative media reporting led to mistrust in data use for research. It was believed that greater education about how the data is used, including positive examples of the benefits of the research, was needed to improve public confidence. Key research priorities for data use included late-effects, social and educational outcomes and rare tumours.
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BACKGROUND: The COVID-19 pandemic had global catastrophic effects on the management of non-communicable diseases including paediatric cancers. Restrictions during the start of 2020 complicated timely referrals of patients to specialized centres. We aimed to evaluate the pandemic's impact on the number of new diagnoses, disease characteristics and management delay for paediatric renal tumour patients included in the SIOP-RTSG-UMBRELLA study, as compared with data from a historical SIOP-RTSG trial (2005-2009). METHODS: The number of intensive care admissions, population mobility rates and national lockdown periods/restrictions were used as proxies of the pandemic's severity and impact on societies. Clinical and tumour data were extracted from the SIOP-RTSG-UMBRELLA study and from historical SIOP-RTSG trials. RESULTS: During the first lockdown in Europe, the number of newly diagnosed patients decreased following restrictions and population immobilisation. Additionally, there was a higher proportion of advanced disease (37% vs. 17% before and after COVID-9, p < 0.001) and larger median tumour volume (559 cm3 vs. 328 and 434 cm3 before and after, p < 0.0001). Also in Brazil, the proportion of advanced disease was higher during the national decrease in mobilisation and start of restrictions (50% and 24% vs. 11% and 18% before and after, p < 0.01). Tumour volume in Brazil was also higher during the first months of COVID-19 (599 cm3 vs. 459 and 514 cm3 ), although not significant (p = 0.17). We did not observe any delays in referral time nor in time to start treatment, even though COVID-19 restrictions may have caused children to reach care later. CONCLUSION: The COVID-19 pandemic briefly changed the tumour characteristics of children presenting with renal tumours. The longer-term impact on clinical outcomes will be kept under review.
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COVID-19 , Neoplasias Renais , Criança , Humanos , Pandemias , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Neoplasias Renais/diagnóstico , Neoplasias Renais/epidemiologia , Neoplasias Renais/terapia , CintilografiaRESUMO
BACKGROUND: The Global Registry of COVID-19 in Childhood Cancer (GRCCC) seeks to describe the natural history of SARS-CoV-2 in children with cancer across the world. Here, we report the disease course and management of coronavirus disease 2019 (COVID-19) infection in the subset of children and adolescents with central nervous system (CNS) tumors who were included in the GRCCC until February 2021, the first data freeze. PROCEDURE: The GRCCC is a deidentified web-based registry of patients less than 19 years of age with cancer or recipients of a hematopoietic stem cell transplant and laboratory-confirmed SARS-CoV-2 infection. Demographic data, cancer diagnosis, cancer-directed therapy, and clinical characteristics of SARS-CoV-2 infection were collected. Outcomes were collected at 30 and 60 days post infection. RESULTS: The GRCCC included 1500 cases from 45 countries, including 126 children with CNS tumors (8.4%). Sixty percent of the cases were from middle-income countries, while no cases were reported from low-income countries. Low-grade gliomas, high-grade gliomas, and CNS embryonal tumors were the most common CNS cancer diagnoses (67%, 84/126). Follow-up at 30 days was available for 107 (85%) patients. Based on the composite measure of severity, 53.3% (57/107) of reported SARS-CoV-2 infections were asymptomatic, 39.3% (42/107) were mild/moderate, and 6.5% (7/107) were severe or critical. One patient died from SARS-CoV-2 infection. There was a significant association between infection severity and absolute neutrophil count less than 500 (p = .04). Of 107 patients with follow-up available, 40 patients (37.4%) were not receiving cancer-directed therapy. Thirty-four patients (50.7%) had a modification to their treatment due to withholding of chemotherapy or delays in radiotherapy or surgery. CONCLUSION: In this cohort of patients with CNS tumors and COVID-19, the frequency of severe infection appears to be low, although severe disease and death do occur. We found that greater severity was seen in patients with severe neutropenia, although treatment modifications were not associated with infection severity or cytopenias. Additional analyses are needed to further describe this unique group of patients.
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COVID-19 , Neoplasias do Sistema Nervoso Central , Glioma , Leucopenia , Humanos , Adolescente , Criança , COVID-19/complicações , COVID-19/epidemiologia , SARS-CoV-2 , Progressão da Doença , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/terapiaRESUMO
BACKGROUND: Measurement of faecal haemoglobin using faecal immunochemistry testing is recommended in patients presenting with symptoms suspicious for colorectal cancer, to aid in triage and prioritization of definitive investigations. While its role in colorectal cancer has been extensively investigated, the ability of faecal immunochemistry testing to detect adenomas in symptomatic patients is unclear. METHODS: A multicentre prospective observational study was conducted between April 2017 and March 2019, recruiting adults from 24 hospitals across England and 59 general practices in London who had been urgently referred with suspected colorectal cancer symptoms. Each patient provided a stool sample for faecal immunochemistry testing, in parallel with definitive investigation. A final diagnosis for each patient was recorded, including the presence, size, histology, and risk type of colonic polyps. The outcome of interest was the sensitivity of faecal immunochemistry testing in detecting the presence of adenomas. RESULTS: Of 3496 patients included in the analysis, 553 (15.8 per cent) had polyps diagnosed. Sensitivity of faecal immunochemistry testing for polyp detection was low across all ranges; with a cut-off for faecal haemoglobin of 4â µg/g or lower, sensitivity was 34.9 per cent and 46.8 per cent for all polyp types and high-risk polyps respectively. The area under the receiver operating characteristic curve in detection probability was relatively low for both intermediate-risk (0.63) and high-risk polyps (0.63). CONCLUSION: While faecal immunochemistry testing may be useful in prioritizing investigations to diagnose colorectal cancer, if used as a sole test, the majority of polyps would be missed and the opportunity to prevent progression to colorectal cancer may be lost.
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Adenoma , Neoplasias Colorretais , Adulto , Humanos , Sensibilidade e Especificidade , Estudos Prospectivos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Hemoglobinas/análiseRESUMO
BACKGROUND: Patients treated with preoperative chemotherapy with stage I intermediate-risk Wilms tumor (IR-WT) represent the largest group of patients with Wilms tumor (WT), and they have excellent outcomes. METHODS: The authors performed a retrospective analysis of patients with stage I epithelial (ET-WT) or stromal type WT (ST-WT) treated pre- and postoperatively according to the International Society of Paediatric Oncology-WT-2001 protocol in the UK Children's Cancer and Leukaemia Group and Gesellschaft für Pädiatrische Onkologie und Hämatologie groups' participation in the relevant WT trials and studies (2001-2020). RESULTS: There were 880 patients with stage I IR-WT, including 124 with ET-WT, 156 with ST-WT, and 600 with other IR-WT (oIR-WT). Patients with stage I ET-WT or ST-WT were significantly younger than patients with oIR-WT, represented a large proportion of stage I WTs in their groups, and tumors showed poor histologic response to preoperative chemotherapy. The 5-year event-free survival (EFS) estimates for patients with stage I ET-WT (96.8% ± 1.8 SE) or ST-WT (96.8% ± 1.6 SE) were significantly better than for patients with oIR-WT (90.3% ± 1.3 SE) (p = .014 and p = .009, respectively). A multivariate analysis showed that histologic type (ET-WT or ST-WT) remained a significant factor for EFS when adjusted for age and gender (p = .032 and p = .022, respectively). In both groups, relapses occurred in 3.2% of patients, and the overall survival was 99.2%. CONCLUSIONS: The results suggest that stage I ET-WT or ST-WT could be regarded as low-risk WT, for which omission of postoperative chemotherapy should be considered. PLAIN LANGUAGE SUMMARY: Patients with pretreated intermediate-risk Wilms tumor (WT) represent the largest group of patients with WT. This study reports the outcomes of patients with stage I epithelial type (ET-WT) or stromal type WT (ST-WT). These patients were significantly younger and had a larger proportion of stage I cases than patients with other intermediate-risk WT (oIR-WT). The event-free survival for patients with stage I ET-WT and ST-WT was significantly better than for patients with oIR-WT. Rare relapses were curable resulting in 99.2% overall survival.
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Neoplasias Renais , Tumor de Wilms , Criança , Humanos , Lactente , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia , Tumor de Wilms/tratamento farmacológico , Tumor de Wilms/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Reino Unido/epidemiologiaRESUMO
Stage III Wilms' tumour (WT) represents a heterogeneous group which includes different criteria, but all stage III patients are treated according to the same study regiment. The aim of the study was to retrospectively analyse outcomes in patients with stage III due to positive resection margins (RM) only, sub-grouped in RM with viable (RM-v) and nonviable (RM-nv) tumour. Patients were treated pre- and postoperatively according to the SIOP-WT-2001 protocol in the UK-CCLG and GPOH WT trials and studies (2001-2020). There were 197 patients, including 134 with localised, abdominal stage III and 63 with overall stage IV, but abdominal stage III. Stage III due to RM-v had 126 patients, and due to RM-nv 71 patients. The overall 5-year local-relapse-free survival (RFS), event-free (EFS) and overall survival (OS) estimates for all patients with abdominal stage III RM were 95.7% (±SE1.5%), 85.1 (±SE2.6%) and 90.3% (±SE2.2%), respectively. Patients with stage III RM-nv had significantly better RFS and EFS than patients with RM-v (P = .027 and P = .003, respectively). A multivariate analysis showed that RM-v remained a significant factor for EFS when adjusted for age, presence of metastasis at diagnosis, histological risk group and overall stage in Cox regression analysis (P = .006). Patients with stage III due to RM-nv only exhibited no local recurrence and have a significantly better RFS and EFS than patients with RM-v. The results suggest that exclusion of RM-nv as a stage III criterion in the UMBRELLA staging system and consequent treatment reduction is warranted.
Assuntos
Neoplasias Renais , Tumor de Wilms , Humanos , Lactente , Neoplasias Renais/patologia , Estudos Retrospectivos , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Tumor de Wilms/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Reino Unido/epidemiologia , Estadiamento de NeoplasiasRESUMO
The objective of this study was to understand global caregiver concerns about SARS-CoV-2 vaccination for children with cancer and to provide healthcare providers with guidance to support parental decision-making. A co-designed cross-sectional mixed-methods survey was distributed to primary caregivers of children with cancer globally between April and May 2021 via several media. Caregivers were asked to rate the importance of vaccine-related questions and the median scores were ranked. Principal Component Analysis was conducted to identify underlying dimensions of caregiver concerns by World Bank income groups. Content analysis of free-text responses was conducted and triangulated with the quantitative findings. 627 caregivers from 22 countries responded to the survey with 5.3% (n = 67) responses from low-and-middle-income countries (LMIC). 184 caregivers (29%) provided free-text responses. Side effects and vaccine safety were caregivers' primary concerns in all countries. Questions related to logistics were of concern for caregivers in LMIC. A small minority of caregivers (n = 17) did not consider the survey questions important; free-text analysis identified these parents as vaccine hesitant, some of them quoting safety and side effects as main reasons for hesitancy. Healthcare providers and other community organizations globally need to provide tailored information about vaccine safety and effectiveness in pediatric oncology settings. Importantly, continued efforts are imperative to reduce global inequities in logistical access to vaccines, particularly in LMIC.