Health-Related Quality of Life of Adolescent and Young Adult-Aged Childhood Cancer Survivors in a South African Cohort: A Pilot Study Using the Minneapolis-Manchester Quality of Life Instrument.

Purpose: We investigated the health-related quality of life (HRQoL) of an adolescent and young adult (AYA)-aged South African childhood cancer survivor (CCS) cohort. Methods: Participants completed the Minneapolis-Manchester Quality of Life adolescent and adult forms. The overall Cronbach's alpha coefficients were 0.81 (adolescent form) and 0.92 (adult form). The scale-level content validity indexes were acceptable (0.88 and 0.89 for the adolescent and adult forms, respectively). The total domain and overall HRQoL scores were calculated. Results: Sixty-two survivors completed the adolescent form and 30 completed the adult form. The median age was 17.5 years (range 13-34 years), and the median time from diagnosis was 12 years (male:female ratio 1:1.2). Risk factors for poor physical functioning included age at study visit (p = 0.015), solid tumor diagnosis (p = 0.012), radiotherapy (p = 0.021), and surgery (p = 0.006). Six or more late effects impacted most domains negatively; severe late effects (p = 0.020) decreased physical functioning. Lower socioeconomic status was associated with poorer physical (p = 0.006) and cognitive (p = 0.047) functioning. The adult form cohort had poorer psychological (p = 0.014) and social functioning (p = 0.005) and body image (p = 0.016) than the adolescent form cohort. Conclusion: Older age, radiotherapy, surgery, solid tumor diagnosis, and the number and severity of late effects negatively influenced HRQoL in AYA-aged CCSs. A long-term follow-up (LTFU) risk stratification system should include HRQoL status to assist with holistic LTFU care.

Variables included in cerebral palsy registries globally: A scoping review.

AIM: To identify cerebral palsy (CP) variables collected in CP registries from high-income countries (HICs) and low- and middle-income countries (LMICs) to assist with the development of a regional CP registry relevant to the African region. METHOD: A systematic search of online databases to identify peer-reviewed publications and grey literature about CP risk-factor variables, using Ovid MEDLINE, Embase Ovid, CINAHL, and Google Scholar. RESULTS: A total of 197 studies published from global CP registries between 1990 and 2023 were identified. CP registries both from HICs and from LMICs included variables on prenatal CP risk factors. LMIC registries focused more on socioeconomic factors (the physical structure of the family home [21.1%, n = 8, in LMICs vs 1.7%, n = 2, in HICs]). Prenatal modifiable and non-modifiable risk factors were emphasized in HICs. LMIC registries included more postnatal CP risk-factor variables than HIC registries, including history of postnatal jaundice (15.8%, n = 6, in LMICs vs 6.9%, n = 8, in HICs) and postnatal head trauma (10.5%, n = 4, in LMICs vs 5.2%, n = 6, in HICs). INTERPRETATION: CP registries are currently more available in HICs than in LMICs. Differences in CP risk factors account for most of the differences in variables included in HICs and LMICs. Comparing variables used by CP registries in HICs and LMICs suggests the importance of understanding contextually relevant factors for regional registry design.

Marked IDO2 expression and activity related to autophagy and apoptosis in brain tissue of fatal tuberculous meningitis.

In about 1% of tuberculosis (TB) patients, Mycobacterium tuberculosis (M. tuberculosis) can disseminate to the meninges, causing tuberculous meningitis (TBM) with mortality rate up to 60%. Chronic granulomatous inflammation (non-necrotizing and necrotizing) in the brain is the histological hallmark of TBM. The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) and the generated kynurenine metabolites exert major effector functions relevant to TB granuloma functioning. Here we have assessed immunohistochemically IDO1 expression and activity and its effector function and that of its isoform, IDO2, in post-mortem brain tissue of patients that demised with neurotuberculosis. We also related these findings to brain tissue of fatal/severe COVID-19. In this study, IDO1 and IDO2 were abundantly expressed and active in tuberculoid granulomas and were associated with the presence of M. tuberculosis as well as markers of autophagy and apoptosis. Like in fatal/severe COVID-19, IDO2 was also prominent in specific brain regions, such as the inferior olivary nucleus of medulla oblongata and cerebellum, but not associated with granulomas or with M. tuberculosis. Spatially associated apoptosis was observed in TBM, whereas in fatal COVID-19 autophagy dominated. Together, our findings highlight IDO2 as a potentially relevant effector enzyme in TBM, which may relate to the symptomology of TBM.

Burkitt lymphoma: The effect of age, sex and delay to diagnosis on treatment completion and outcome of treatment in 934 Patients in Cameroon.

INTRODUCTION: The role of age and sex in the presentation and outcome of endemic Burkitt lymphoma (BL) has not been studied recently. This study analysed these factors in 934 patients with BL who had received cyclophosphamide and intrathecal methotrexate as treatment. METHODS: Records of 934 children diagnosed with BL from 2004 to 2015 were obtained from our Paediatric Oncology Networked Database (POND) cancer registry. Age at diagnosis, sex, disease stage, time to diagnosis, delay in diagnosis, completion of treatment, rate of abandonment, and one-year survival rates were recorded and statistically analysed. RESULTS: The male to female ratio of 1.41 for the study population of 934. The median delay from onset of symptoms to diagnosis was 31 days. The St Jude stage distribution was I = 6.4%, II = 5.9%, III = 71.5% and IV = 16.2%. Significantly more patients presented with stage III disease in age groups 5-9 and 10-14 years than 0-4 years. The overall 1-year survival rate was 53.45%, respectively 77.1% for stage I, 67.9% for stage II, 55.1% for stage III and 32.4% for stage IV disease (p<0.001). There was no significant difference in survival by sex and age group. CONCLUSION: Patients aged under 5 years presented with less-advanced disease, but survival was not affected by age. Sex did not influence delay to diagnosis and overall survival. The long delay between the onset of symptoms and diagnosis emphasises the need for interventions to achieve an earlier diagnosis and a better survival rate.

Socioeconomic status significantly impacts childhood cancer survival in South Africa.

BACKGROUND AND AIMS: Significantly discrepant survival rates have been documented in single disease childhood cancer cohorts in South Africa; those from higher socioeconomic groups were shown to have a significantly lower risk of death than those from less affluent households. This study aimed to determine the impact of socioeconomic status (SES) on childhood cancer survival using pooled South African data. METHODS: Five databases spanning January 2000 to December 2021 were interrogated. SES status was assigned based on a public sector annual household income classification. H0 households (formally unemployed) received free healthcare. H1, H2 and H3 (annual income > United States Dollar [USD] 19,000) households paid for healthcare relative to their income. The Spearman test assessed correlations between SES and disease stage in patients with solid tumours. Hazard ratios were determined using Cox regression modelling. The Kaplan-Meier procedure estimated overall survival (OS). RESULTS: A total of 1598 children were eligible for analysis; 1269 had a solid tumour with a negative correlation between SES and stage (Spearman rho = -.178; p < .001). Patients with solid tumours and lower SES showed proportionately higher numbers of stage III and IV disease (p < .01). This proportion decreased with higher SES categories. In the multivariate analyses adjusted for sex, age, tumour type and stage, higher SES was associated with lower mortality risk (p < .001), indicating that the impact of SES on survival was in excess of any effect that could be explained by lower stage disease alone. There was a strong positive correlation between race and SES (Fisher's exact tests, p < .001) across all groups and all SES strata. Five-year OS was 85.3% in children from H3 households versus 46.3% in children from H0 households (p < .001). CONCLUSION: SES significantly impacts childhood cancer survival for children with solid tumours in South Africa. SES is a robust surrogate for race in South Africa as a prognostic metric of disease outcome in childhood cancer. Advocacy to increase social support for impoverished patients is essential to achieve equitable improvements in outcomes treated with standardised national treatment guidelines.

Prevalence of Poverty and Hunger at Cancer Diagnosis and Its Association with Malnutrition and Overall Survival in South Africa.

Many South African children live in poverty and food insecurity; therefore, malnutrition within the context of childhood cancer should be examined. Parents/caregivers completed the Poverty-Assessment Tool (divided into poverty risk groups) and the Household Hunger Scale questionnaire in five pediatric oncology units. Height, weight, and mid-upper arm circumference assessments classified malnutrition. Regression analysis evaluated the association of poverty and food insecurity with nutritional status, abandonment of treatment, and one-year overall survival (OS). Nearly a third (27.8%) of 320 patients had a high poverty risk, associated significantly with stunting (p = 0.009), food insecurity (p < 0.001) and residential province (p < 0.001) (multinomial regression). Stunting was independently and significantly associated with one-year OS on univariate analysis. The hunger scale was significant predictor of OS, as patients living with hunger at home had an increased odds ratio for treatment abandonment (OR 4.5; 95% CI 1.0; 19.4; p = 0.045) and hazard for death (HR 3.2; 95% CI 1.02, 9.9; p = 0.046) compared to those with food security. Evaluating sociodemographic factors such as poverty and food insecurity at diagnosis is essential among South African children to identify at-risk children and implement adequate nutritional support during cancer treatment.

Prevalence of vitamin and iron deficiencies at cancer diagnosis at two pediatric oncology units in South Africa.

This study investigates the prevalence of vitamin and iron deficiencies at cancer diagnosis. Newly diagnosed children between October 2018 and December 2020 at two South African pediatric oncology units (POUs) were assessed for nutritional and micronutrient status (Vit A, Vit B12, Vit D, folate, and iron). A structured interview with caregivers provided information regarding hunger and poverty risks. There were 261 patients enrolled with a median age of 5.5 years and a male-to-female ratio of 1:0.8. Nearly half had iron deficiency (47.6%), while a third had either Vit A (30.6%), Vit D (32.6%), or folate (29.7%) deficiencies. Significant associations existed between moderate acute malnutrition (MAM) and low levels of Vit A (48.4%; p = .005), Vit B12 (29.6%; p < .001), and folate (47.3%; p = .003), while Vit D deficiency was associated with wasting (63.6%) (p < .001). Males had significantly lower Vit D levels (respectively, 40.9%; p = .004). Folate deficiency was significantly associated with patients born at full term (33.5%; p = .017), age older than five years (39.8%; p = .002), residing in provinces Mpumalanga (40.9%) and Gauteng (31.5%) (P = .032); as well as having food insecurity (46.3%; p < .001), or hematological malignancies (41.3%; p = .004). This study documents the high prevalence of Vit A, Vit D, Vit B12, folate, and iron deficiency in South African pediatric cancer patients, demonstrating the need to include micronutrient assessment at diagnosis to ensure optimal nutritional support for macro-and micronutrients.

The pre-surgical factors that determine the decision to proceed to resection in children diagnosed with high-risk neuroblastoma in a resource limited setting.

Surgical control has prognostic value in neuroblastoma (NB). Advanced NB is common at diagnosis in South Africa. We investigated the pre-surgery factors that influenced decisions to perform surgical resections. We included 204 patients with high-risk NB from a national retrospective study, who completed induction chemotherapy between 2000 and 2016.The median age was 32.4 months (IQR 15.1 - 53.5 months). Primary tumor resection was achieved in 76.9% of patients between 0-18 months of age, 51.8% between 18-60 months and 51.7% older than 60 months (p < 0.001). Only 43.2% of patients with distant metastatic disease had surgery done (p < 0.001). LDH was >750 U/L in 46.8% and ferritin >120 g/dL in 53.1% of those who had surgery (p = 0.005). The majority (80.4%), who had achieved post-induction metastatic complete remission (mCR), were operated, while 28.7% without mCR had surgery (p < 0.001). The long-term overall survival in patients with mCR and primary tumor resection was 36.5% compared to those with mCR without primary tumor resection (25.4%) and without mCR (≤3.0%)(p < 0.001). Age (p < 0.001), stage (p < 0.001), mCR (p < 0.001) and treatment setting (p < 0.001) were of prognostic significance. The tumor site and MYCN-amplification did not significantly predict resection rates. Post-induction mCR and stage were associated with surgical resection and five-year OS (p < 0.001) on multivariate analysis.Patients with high-risk NB who achieved mCR and had primary tumor resections are curable in limited resourced settings. Stage and post-induction mCR were significant variables that led to surgery. These variables should be included as indications in the management of metastatic NB in resource limited settings.

High-risk neuroblastoma that achieved post-induction chemotherapy metastatic remission and have undergone resection, is curable, even in limited resource settings.Achieving metastatic complete remission was the only factor that significantly predicated if surgery was done.The age at diagnosis, stage and hospitals with expertise in neuroblastoma surgery were of prognostic significance in South Africa.If a patient with high-risk neuroblastoma achieves metastatic complete remission in a resource limited setting, it should be an indication for resection of the primary tumor.

Psychological distress of adolescent and young adult childhood cancer survivors in a South African cohort.

BACKGROUND: We investigated psychological distress in a South African childhood cancer survivor (CCS) cohort. METHODS: Adult CCSs treated at Tygerberg Hospital, Cape Town, completed the Brief Symptom Inventory-18. Internal consistency was acceptable: Cronbach's alpha values were 0.91 (Global Severity Index (GSI)), 0.85 (depression), 0.83 (somatization), and 0.75 (anxiety). We compared results utilizing different case rules (GSI T scores of ≥50, ≥57, and ≥63) for the identification of psychological distress. RESULTS: Forty CCSs (median age 24 years; median follow-up period 16 years) participated. Most (58%; 23 out of 40) completed school or tertiary education, were unmarried (90%; 36 out of 40), and unemployed (59.5%; 22 out of 37). The diagnoses included hematological malignancies (65%; 26 out of 40) and solid tumors (35%; 14 out of 40). The GSI T scores of ≥63, ≥57, and ≥50 identified 10% (four out of 40), 32.5% (13 out of 40), and 45% (18 out of 40) of survivors with psychological distress, respectively. Radiotherapy (odds ratio (OR) 4.6; p = .035), presence of ≥six late effects (OR 7.5; p = .026), and severe late effects (OR 6.6; p = .024) were significant risk factors (GSI T score ≥57). Follow-up period of 11-20 years (OR 7.3; p = .034) was significant for a GSI T score ≥50. CONCLUSION: This South African CCS cohort had higher levels of psychological distress utilizing the GSI T score ≥50 and ≥57 case rules than reported in the literature. Most were unmarried or unemployed. Significant contributing factors were radiotherapy, number and severity of late effects, and follow-up period. CCSs must be screened for psychological distress.

Outcome of retinoblastoma treatment protocol in Cameroon as per SIOP-PODC recommendation for a low-income setting.

INTRODUCTION: The International Society of Paediatric Oncology-Paediatric Oncology in Developing Countries (SIOP-PODC) group recommended graduated-intensity retinoblastoma treatment for children in low- and middle-income countries with limited local resources. AIM: The aim was to improve outcome of children with retinoblastoma by means of a treatment protocol for low-income settings as recommended by the SIOP-PODC recommendation in Cameroon. METHODS: Children diagnosed with retinoblastoma between 2012 and 2016 were treated in two Baptist Mission hospitals in Cameroon, staging according to the International Retinoblastoma Staging System. Treatment included local therapy and combination chemotherapy (vincristine, cyclophosphamide, and doxorubicin) with or without surgery as per SIOP-PODC guidelines for low-income countries. Endpoint was survival at 24 months. Kaplan-Meier curves with log-rank (Mantel-Cox) chi-square (χ2 ) with respective p-values were prepared. RESULTS: Eighty-two children were included, of whom 79.3% had unilateral disease. The majority were males (61.0%) with median age 24 months (range 1-112 months; standard deviation [SD] 19). Limited disease was diagnosed in 58.5%, metastatic disease in 35.4%, and unknown stage in 6.1%. Overall survival (OS) was 50.0% at 24 months post diagnosis, but 68.8% for limited disease. Estimated cumulative survival at 24 months was 0.528 (standard error [SE] 0.056). Causes of death included disease progression/relapses (60.5%), neutropenic sepsis (15.9%), unknown causes (18.4%), unrelated infection (2.6%), and death post surgery (2.6%). Stage was significantly associated with OS (p < .001). CONCLUSION: Stage was the most significant factor for good OS and demonstrated the efficacy and feasibility of the SIOP-PODC-proposed management guidelines for retinoblastoma in a lower middle-income setting.

Survey of the use of traditional and complementary medicine among children with cancer at three hospitals in Cameroon.

INTRODUCTION: There is lack of diagnostic and treatment resources with variable access to childhood cancer treatment in low- and middle-income countries (LMIC), which may lead to subsequent poor survival. The primary aim of this study was to determine the prevalence and types of traditional and complementary medicine (T&CM) used in Cameroon. Secondarily, we explored determinants of T&CM use, associated costs, perceived benefits and harm, and disclosure of T&CM use to medical team. METHODS: A prospective, cross-sectional survey among parents and carers of children younger than 15 years of age who had a cancer diagnosis and received cancer treatment at three Baptist Mission hospitals between November 2017 and February 2019. RESULTS: Eighty participants completed the survey. Median patient age was 8.1 years (IQR4.1-11.1). There was significant availability (90%) and use (67.5%) of T&CM, whereas 24% thought T&CM would be good for cancer treatment. Common T&CM remedies included herbs and other plant remedies or teas taken by mouth, prayer for healing purposes and skin cutting. Living more than five hours away from the treatment center (P = 0.030), anticipated costs (0.028), and a habit of consulting a traditional healer when sick (P = 0.006) were associated with the use of T&CM. T&CM was mostly paid for in cash (53.7%) or provided free of charge (29.6%). Of importance was the fact that nearly half (44%) did not want to disclose the use of TM to their doctor. CONCLUSION: Pediatric oncology patients used T&CM before and during treatment but were unlikely to disclose its use to the child's health care team.

Assessment of Clinical Outcomes Among Children and Adolescents Hospitalized With COVID-19 in 6 Sub-Saharan African Countries.

IMPORTANCE: Little is known about COVID-19 outcomes among children and adolescents in sub-Saharan Africa, where preexisting comorbidities are prevalent. OBJECTIVE: To assess the clinical outcomes and factors associated with outcomes among children and adolescents hospitalized with COVID-19 in 6 countries in sub-Saharan Africa. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a retrospective record review of data from 25 hospitals in the Democratic Republic of the Congo, Ghana, Kenya, Nigeria, South Africa, and Uganda from March 1 to December 31, 2020, and included 469 hospitalized patients aged 0 to 19 years with SARS-CoV-2 infection. EXPOSURES: Age, sex, preexisting comorbidities, and region of residence. MAIN OUTCOMES AND MEASURES: An ordinal primary outcome scale was used comprising 5 categories: (1) hospitalization without oxygen supplementation, (2) hospitalization with oxygen supplementation, (3) ICU admission, (4) invasive mechanical ventilation, and (5) death. The secondary outcome was length of hospital stay. RESULTS: Among 469 hospitalized children and adolescents, the median age was 5.9 years (IQR, 1.6-11.1 years); 245 patients (52.4%) were male, and 115 (24.5%) had comorbidities. A total of 39 patients (8.3%) were from central Africa, 172 (36.7%) from eastern Africa, 208 (44.3%) from southern Africa, and 50 (10.7%) from western Africa. Eighteen patients had suspected (n = 6) or confirmed (n = 12) multisystem inflammatory syndrome in children. Thirty-nine patients (8.3%) died, including 22 of 69 patients (31.9%) who required intensive care unit admission and 4 of 18 patients (22.2%) with suspected or confirmed multisystem inflammatory syndrome in children. Among 468 patients, 418 (89.3%) were discharged, and 16 (3.4%) remained hospitalized. The likelihood of outcomes with higher vs lower severity among children younger than 1 year expressed as adjusted odds ratio (aOR) was 4.89 (95% CI, 1.44-16.61) times higher than that of adolescents aged 15 to 19 years. The presence of hypertension (aOR, 5.91; 95% CI, 1.89-18.50), chronic lung disease (aOR, 2.97; 95% CI, 1.65-5.37), or a hematological disorder (aOR, 3.10; 95% CI, 1.04-9.24) was associated with severe outcomes. Age younger than 1 year (adjusted subdistribution hazard ratio [asHR], 0.48; 95% CI, 0.27-0.87), the presence of 1 comorbidity (asHR, 0.54; 95% CI, 0.40-0.72), and the presence of 2 or more comorbidities (asHR, 0.26; 95% CI, 0.18-0.38) were associated with reduced rates of hospital discharge. CONCLUSIONS AND RELEVANCE: In this cohort study of children and adolescents hospitalized with COVID-19 in sub-Saharan Africa, high rates of morbidity and mortality were observed among infants and patients with noncommunicable disease comorbidities, suggesting that COVID-19 vaccination and therapeutic interventions are needed for young populations in this region.

The Incidence of Retinoblastoma in South Africa: Findings from the South African National Cancer Registry (2004-2018).

PURPOSE: To determine the frequency and incidence rate of retinoblastoma in children in South Africa from 2004 to 2018. METHODS: Incident cases of histologically diagnosed retinoblastoma were identified from the South African National Cancer Registry. Crude incidence rates were calculated using national population data on children <15 years and live births. Incidence rates were stratified and compared by age, sex and population group. Direct age-standardised incidence rates and comparative incidence ratios were calculated. RESULTS: The overall age-standardised incidence rate for children <15 years was 3.3 per million or 1 per 21 641 live births. Age-specific rates for children aged 0-4, 5-9 and 10-14 years were 7.7, 0.8 and 0.2 per million, respectively. There was no difference in incidence rates by sex. White children had a significantly higher incidence rate compared to other population groups, but this finding may be due to systemic biases introduced by access to healthcare in South Africa or study methodology. CONCLUSION: This is the largest study to provide population-based, histologically confirmed national estimates of retinoblastoma incidence from an African nation to date and affirms the need for high-quality cancer registries across the African continent.

Malignant extracranial germ cell tumours: A first national report by the South African Children's Cancer Study Group.

OBJECTIVE: To determine the overall survival (OS) and prognostic factors influencing outcomes in children and adolescents with malignant extracranial germ cell tumours (MEGCTs) in preparation for the development of a harmonised national treatment protocol. METHODS: A retrospective folder review was undertaken at nine South African paediatric oncology units to document patient profiles, tumour and treatment-related data and outcomes for all children with biopsy-proven MEGCTs from birth up to and including 16 years of age. RESULTS: Between 1 January 2000 and 31 December 2015, 218 patients were diagnosed with MEGCTs. Female sex (hazard ratio [HR] 0.284, p = .037) and higher socio-economic status (SES) (HR 0.071, p = .039) were associated with a significantly lower risk of death. Advanced clinical stage at diagnosis significantly affected 5-year OS: stage I: 96%; stage II: 94.3%; stage III: 75.5% (p = .017) and stage IV (60.1%; p < .001). There was a significant association between earlier stage at presentation and higher SES (p = .03). Patients with a serum alpha-fetoprotein (AFP) level of more than 33,000 ng/ml at diagnosis had significantly poorer outcomes (p = .002). The use of chemotherapy significantly improved survival, irrespective of the regimen used (p < .001). CONCLUSIONS: The cohort demonstrated a 5-year OS of 80.3% with an event-free survival (EFS) of 75.3%. Stage, the use of chemotherapy and an elevated serum AFP level of more than 33,000 ng/ml were independently predictive of outcome. The relationship between SES and outcome is important as the implementation of the new national protocol hopes to standardise care across the socio-economic divide.

The scope of childhood cancer in South Africa: A response to 'Childhood cancers in a section of the South African private health sector - Analysis of medicines claims data'.

Childhood cancer is an under resourced medical field that is emerging as a great healthcare concern in low- and middle-income countries such as South Africa. Therefore, reporting data in this field that may inform policymakers should be representative of the subject matter. This article aims to discuss why medicines claims as an indicator for incidence, as per an article published in 2020, is not representative of childhood malignancies in the South African setting. Literature to support the commentary were sourced using Pubmed, Google scholar, and data presented by members of the South African Children's Cancer Study Group (SACCSG). Private medical aid coverage in South Africa between 2002 and 2018 varied between 15.5% and 18.2%. Of these, 9.5% were children under 18 years and 3.5% were under the age of six. Only 13.5% of children were treated in private paediatric oncology units during 2015. The limitations in the study were the variable medical aid coverage, the disproportionate age representation, and lack of reliable indicators for measurement and calculation of incidence. Utilising one medicines claims data base to evaluate the incidence of childhood cancer in South Africa is not representative and cannot inform policy. CONTRIBUTION: This article highlights the importance of accurate registration of childhood cancer diagnoses, especially when data and conclusions based on these results inform policy. The study highlights the limitations of extrapolating general conclusions based on data representing only a small sector of the childhood cancer landscape in South Africa.

Recommendations for Age-Appropriate Testing, Timing, and Frequency of Audiologic Monitoring During Childhood Cancer Treatment: An International Society of Paediatric Oncology Supportive Care Consensus Report.

IMPORTANCE: Ototoxicity is an irreversible direct and late effect of certain childhood cancer treatments. Audiologic surveillance during therapy as part of the supportive care pathway enables early detection of hearing loss, decision-making about ongoing cancer treatment, and, when applicable, the timely use of audiologic interventions. Pediatric oncologic clinical practice and treatment trials have tended to be driven by tumor type and tumor-specific working groups. Internationally accepted standardized recommendations for monitoring hearing during treatment have not previously been agreed on. OBJECTIVE: To provide standard recommendations on hearing loss monitoring during childhood cancer therapy for clinical practice. METHODS: An Ototoxicity Task Force was formed under the umbrella of the International Society of Paediatric Oncology, consisting of international audiologists, otolaryngologists, and leaders in the field of relevant pediatric oncology tumor groups. Consensus meetings conducted by experts were organized, aimed at providing standardized recommendations on age-directed testing, timing, and frequency of monitoring during cancer treatment based on literature and consensus. Consensus statements were prepared by the core group, adapted following several videoconferences, and finally agreed on by the expert panel. FINDINGS: The consensus reached was that children who receive ototoxic cancer treatment (platinum agents, cranial irradiation, and/or brain surgery) require a baseline case history, monitoring of their middle ear and inner ear function, and assessment of tinnitus at each audiologic follow-up. As a minimum, age-appropriate testing should be performed before and at the end of treatment. Ideally, audiometry with counseling before each cisplatin cycle should be considered in the context of the individual patient, specific disease, feasibility, and available resources. CONCLUSIONS AND RELEVANCE: This is an international multidisciplinary consensus report providing standardized supportive care recommendations on hearing monitoring in children undergoing potentially ototoxic cancer treatment. The recommendations are intended to improve the care of children with cancer and facilitate comparative research on the timing and development of hearing loss caused by different cancer treatment regimens.

Reporting Incidences of Neuroblastoma in Various Resource Settings.

PURPOSE: The incidences of neuroblastoma (NB) differ significantly between various resource settings because of varying quality of cancer registries and underdiagnoses. This study aimed to evaluate current regional variations as reported by international cancer registries and the theoretical and reported differences in international NB incidences and to evaluate South Africa (SA) as a case for variable reporting. METHODS: A comprehensive literature review on registries reporting on NB was performed to construct incidence tables. The SEER Program incidence of 10.5/million children was used to calculate the expected number of NB cases for each country. Registry data of NB cases between 2000 and 2016 were requested from The South African National Cancer registry (SA-NCR) and the South African Children's Tumour Registry (SACTR) for comparison and to perform a probabilistic linkage study. RESULTS: Internationally, incidences varied between -97.1% and +80% compared with the SEER program. SA under-reported NB cases by an estimated 74.2%. Between 2000 and 2016, the SA-NCR reported between 23 and 51 cases/year, whereas the SACTR reported between 18 and 57 cases/year for the same period. The incidence reported by the SA-NCR varied between 1.5 and 2.8/million children under 15-year per year, whereas the SACTR reported 1.74-2.6 cases/million children. Both registries reported incidences less than high-income country. A probabilistic record linkage of the two registries resulted in a combined incidence of 2.9 cases/million children. CONCLUSION: As with most low- and middle-income countries, SA has either a lower incidence or underdiagnoses of NB cases. The reasons for under-reporting are not clear, but can be due to undiagnosed NB cases with spontaneous regression, missed possible cases because of lack of autopsies, and diagnosed cases not recorded in registries.