Background and Aims

Perinatal and maternal factors have been consistently associated with hepatoblastoma. The aim of our study was to investigate the association between these characteristics and hepatoblastoma in the state of São Paulo, Brazil.

Methods

This is a registry-based case-control study (deterministic linkage based on name, mother’s name, and date of birth) including 71 children <6 years with HB, diagnosed between 2001 and 2019, retrieved from the São Paulo Hospital-based Cancer Registry (FOSP) and 355 controls (5:1, frequency-matched by year and city of birth, gender, and city of birth), identified through birth certificates (SEADE). Crude and adjusted Odds Ratios (OR) (with corresponding 95% CI) were estimated using unconditional logistic regression. Adjusted OR (aOR) (by all other variables) were calculated in the full dataset (treating missing values as categories), complete dataset for the variables gender, maternal age, gestational age, plurality, birthweight) (1), and complete dataset for all variables (2).

Results

Using the full dataset, we have found an Increased risk of HB associated with very low birthweight (<1500g compared to 2500-3999g, crude OR=5.30, 95% CI 1.65-17.04), APGAR score 1 (≤7, crude OR=2.68, 95% CI 1.27-5.65); borderline associations were found for the following variables: maternal education (compared to ≥ 12 years, < 8 years, OR=2.04, 95% CI 0.87-4.79), prematurity (Yes, OR=1.68, 95% CI 0.83-3.41), and mode of delivery (C-section, OR=1.64, (95% CI 0.94-2.88). After adjustment, maternal education (< 8 years, aOR=3.03, 95% CI 1.23-7.48), mode of delivery (C-section, aOR=2.05, 95% CI 1.12-3.75), and APGAR score – 1 (≤7, aOR=2.56, 95% CI 1.11-5.90) remained as independent risk factors for HB. When the analysis was restricted to the complete dataset, results were unchanged.

Conclusions

Our results provide further evidence of associations between APGAR score,very low birthweight and HB, as well as an increased risk for those children born through cesarean, confirming previous data from other continents.

Background and Aims

We previously found maternal use of hormonal contraception associated with leukaemia risk in children. The aim of the present study was to assess associations between maternal use of hormonal contraception and childhood central nervous system tumours.

Methods

In this nationwide cohort study, based on Danish population-based registry data, we followed 1,185,157 children born in Denmark between January 1, 1996 and December 31, 2014, linked with information on maternal use of hormonal contraception and potential confounders. Maternal hormonal contraception use was analysed according to any use, regiment (estrogen and progestin combined or progestin-only products) and route of administration (oral or non-oral), with children born to mothers with no use of hormonal contraception as reference. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated.

Results

After 11,114,299 million person-years of follow-up (mean 9.38 years), 475 children were diagnosed with a central nervous system tumor. The crude incidence rate of central nervous system tumors per 100,000 was 4.5 for children born to mothers with no use of hormonal contraception (n=270,198) and 14.4 for children born to mothers with use of non-oral progestin-only contraception up to pregnancy (n=17,129). The corresponding adjusted HR was 2.69 (95% CI 1.39-5.22; cases=12) in children of mothers who used non-oral progestin-only contraception up to pregnancy. The estimate was mainly driven by maternal use of hormonal injections (HR 10.66, 95% CI 3.34-34.00; cases<5) and intra-uterine devices (HR 2.29; 95% CI 1.06-4.93; cases=8). There were no statistically significant associations with maternal use of other types of hormonal contraception.

Conclusions

Among children born in Denmark, maternal use of non-oral progestin-only hormonal contraception was associated with an increased risk of central nervous system tumors, compared with children born to women with no use of hormonal contraception.

Background and Aims

Childhood cancer is the leading cause of chronic disease-related death among 5 to 14-year-olds worldwide. Approximately 10% of cases are linked to germline mutations associated with hereditary cancer syndromes (HCS). Incidence in Mexico is 6,000 new cases/year. The impact of genetic predisposition is unknown.

Aim: to detect the prevalence of germline mutations in pediatric patients with malignant solid tumors, excluding retinoblastoma.

Methods

103 pediatric patients with malignant solid tumors were included: 39 had osteosarcoma, 22 central nervous system (CNS) tumors, 22 sarcomas, 10 gastrointestinal (GI) tumors, six had thyroid cancer, and 10 had tumors grouped like others; adrenocortical carcinoma (ACC) (3), pleuropulmonary blastoma (PPB) (3), Wilms tumor (2), and one patient each with extra-gonadal germ cell tumor and mucoepidermoid carcinoma). Massive parallel sequencing of 94 genes associated with HCS was performed.

Results

A pathogenic variant was identified in 33% (34/103) of cases. Affected genes included: APC, BMPR1A, CHEK2, DICER1, NBN, MUTYH, PMS2, RECQL4, RET, SUFU, TP53, TSC2, and WT1. TP53 was the most frequently mutated gene (26.47% of positive cases). 30% (31/103) of cases had at least one suspicion criteria for HCS, family history of cancer being the most repeated (51.61%), followed by type of tumor (35.48%). In these, the percentage of mutation-positive cases was significantly higher (54.84%) compared to the group without HCS suspicion criteria (21.79%). The “other tumors“ group had the highest rate of mutation-positive (70%) (7/10), followed by GI 50% (5/10), CNS 45.45% (10/22), thyroid tumors 33% (2/6), osteosarcoma 17.95% (7/39), and soft tissue sarcomas 13.64% (3/22).

Conclusions

Percentage of cases with germline mutations is higher than described elsewhere, especially in cases meeting risk criteria for HCS, (also high for the group without suspicion criteria). Identification of HCS in pediatric patients allows detection of patients at risk for second malignancies, and other relatives at risk, who benefit from risk-adjusted surveillance.

Background and Aims

Kaposi sarcoma (KS) is the most common pediatric HIV-associated malignancy in Sub-Saharan Africa (SSA). Optimizing recognition and management of KS remains critical for pediatric and adolescent/young adult (AYA) patients. Previous descriptions of pediatric/AYA KS from SSA have not included sites in Tanzania. We describe the clinical experience of children/AYAs treated at an outpatient KS treatment center in southwest Tanzania without local oncology sub-specialists.

Methods

Patients diagnosed with KS at Baylor-Tanzania Children’s Foundation Mbeya between March 2011-December 2017 were included. Kaplan-Meier and Anderson-Gill methodologies were applied to estimate overall (OS) and event free survival (EFS), respectively. Events included failure to achieve complete remission (CR) with up-front chemotherapy; relapse; and/or death.

Results

Sixty-one patients were identified; 97% were HIV-positive. The median diagnosis age was 12.6 years. Clinical features included lymphadenopathy (69%), hyperpigmented skin lesions (67%), oral lesions (56%), woody edema (41%), and visceral disease (23%). At diagnosis severe immunosuppression was found in 62%, and severe acute malnutrition in 44%. Fifty-eight patients received chemotherapy (3 died prior). The up-front regimen included bleomycin/vincristine (34 patients), while 23 received intensified treatment with bleomycin/vincristine/doxorubicin. Fourteen patients received Paclitaxel. At 1-year OS was 76% and EFS was 51%. EFS was significantly lower for patients with woody edema (40%; P=0.01), visceral and/or disseminated skin/oral disease (32%; P=0.01), and severe immunosuppression (43%; P=0.05). Survival patterns varied by phenotype: 73% of patients with mild/moderate skin/oral disease or primarily lymphadenopathic KS achieved CR, 28% of patients with woody edema achieved CR and 50% stable partial response (SPR), and 35% of patients with visceral and/or disseminated skin/oral disease achieved CR and 18% achieved SPR.

Conclusions

In a cohort of complex pediatric patients with advanced-stage disease and severe immunosuppression, relatively high survival was achieved in a resource-limited setting through a standardized treatment approach implemented by a team of pediatricians with remote sub-specialized oncology support.

Background and Aims

BACKGROUND: Poor adherence to oral 6-mercaptopurine (6 MP) in children and adolescents during acute lymphoblastic leukemia (ALL) treatment is a continuous challenge. We aimed to assess the feasibility of monitoring adherence to 6 MP intake using a daily “selfie” picture made by cell phone

Methods

METHODS: From September 2017 to December 2019, 57 patients < 18 years of age with ALL, treated according IC BFM 2009 in Santa Marcelina/TUCCA Pediatric Oncology Center in São Paulo, Brazil, were included in the study. Parents and patients were interviewed and oriented by multidisciplinary team. A specific cellular number was provided. We have calculated the percentage of adherence (dividing the number of received selfies by the expected number of pictures), the duration of participation (days) and the percentage who had discontinued (non-compliance). Patients were followed-up from day 1 of the maintenance until the end of treatment, interruption, relapse or death. Kaplan-Meier method was use to estimate the probability of compliance to the strategy.

Results

Results: All patients (100%) initially agreed in participate, but 2 (3.5%) had never sent pictures. Most patients were males (65.5%), with a median age of 5.3 years, presenting intermediate risk ALL (63.6%). Adherence ranged between 2.5% and 100% (median=71%). Only 6 patients (10.9%) presented adherence ³95%. Sixteen patients (29.1%) interrupted the participation. After 12 months, the probability of compliance was 76.1% and 44.4% for patients with low/intermediate (n=38) or high-risk ALL (n=17), respectively (p=0.037). None of the socioeconomic variables was significantly associated with discontinuation. Among those who had the chance of completing the maintenance (n=27), 18 (66.7%) kept compliant until the end of the follow-up (median percentage of pictures=67.6%). Only 4 relapses were observed and only among those with adherence <=95%.

Conclusions

Conclusions: Our results demonstrate that this strategy is feasible and can be cost-effective in improving 6-MP adherence in a fun way.

Background and Aims

The Abbreviated Version of the Pediatric Oncology Facility Integrated Local Evaluation (PrOFILE) tool includes a subset of the questions and activities of the Full Version. It aims to illustrate the PHO resource landscape for a national or regional group of facilities, guide conversations about collective strengths and opportunities, and help set priorities for collaborative work among stakeholders to improve PHO care.

Methods

During the preparation phase, relevant stakeholders and a liaison are identified. In the assessment phase, local teams collect and enter data into an electronic platform. Facility-based and aggregated data analysis are conducted during the interpretation and action phase. Final score-based and descriptive reports are generated for each participating facility. The 6-8-week implementation process concludes with site visits and/or a multi-site workshop. Structured exercises are used to meet workshop goals and set priorities. Data entry and analysis are conducted using the CDC Epi Info software.

Results

A total of 44 facilities providing PHO care implemented the tool since its inception in April 2019, representing seven countries in four global regions (Morocco, Brazil, Ukraine, Uganda, Pakistan, Zambia, and Lebanon). The largest cohort was comprised of 15 PHO facilities (Brazil). The average implementation process duration was 79 days (range 24-137). During the interpretation phase, seven facility-based workshops were conducted, and four regional workshops were held. A total of 173 (range 27-70) stakeholders participated during in-country prioritization exercises. Some of the most critical areas of opportunity identified included PHO nursing specialization, nursing empowerment, prospective data collection (registry), and development of cancer workforce training opportunities.

Conclusions

PrOFILE Abbreviated Version assists facilities and multi-site collaborations to prioritize solutions and take practical actions to improve PHO care locally and regionally. Access to this free tool is available through the St. Jude Global Alliance and is being translated to other languages (Spanish and Russian).