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.

SACCSG HL-2018. Barriers and enablers of a harmonized treatment protocol for childhood and adolescent Hodgkin lymphoma in South Africa.

Introduction: Collaborative studies have contributed to improved survival of pediatric Hodgkin lymphoma in well-resourced settings, but few are documented in resource-constrained countries. The South Africa Children's Cancer Study Group initiated harmonization of management protocols in 2015. This article analyzes barriers and enablers of the process. Methods: Clinician-researchers at 11 state-funded pediatric oncology units completed preparatory questionnaires in June 2018. Parameters included infrastructure, access to therapeutic modalities and clinician numbers. A reassessment of 13 sites (two new pediatric oncology unit) in February 2021 ascertained changes in resources and identified challenges to full participation. Questions investigated the presence and quality of diagnostic radiology, availability of surgeons, cytology/pathology options and hematology laboratory facilities. Results: The response rate was 11/11 to survey 1 and 13/13 to survey 2. The anticipated pre-study barriers to participation of pediatric oncology units included time constraints and understaffing. PET-CT was unavailable to two centers. The majority of pediatric oncology units met the minimum criteria to participate. The interim survey confirmed chemotherapy and radiotherapy availability nearly 100% of the time. One site reported improved access to radiotherapy while another reported improved access to PET-CT. Barriers to participation included excessive times to obtain regulatory approvals, time constraints and lack of dedicated research staff. Enablers include the simple management algorithm and communication tools. Conclusion: This study demonstrates that multicenter collaboration and harmonization of management protocols are achievable in a middle-income setting. Minimal funding is required but full participation to run high-quality studies requires more financial investment. Focused funding and increased prioritization of research may address systemic barriers to full participation.

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.

Sex Cord Stromal Tumors in Children and Adolescents: A First Report by The South African Children's Cancer Study Group (1990-2015).

OBJECTIVES: Pediatric sex cord stromal tumors (SCSTs) are extremely rare and there are no reported data from Africa. The authors evaluated the outcomes of children and adolescents with biopsy-proven SCSTs in preparation for the introduction of a national protocol. MATERIALS AND METHODS: Retrospective data were collated from 9 South African pediatric oncology units from January 1990 to December 2015. Kaplan-Meier analysis was performed to estimate overall survival (OS) and event-free survival. RESULTS: Twenty-three patients were diagnosed with SCSTs, 3 male and 20 female individuals, during the study period. Histologies included 1 thecoma, 9 Sertoli-Leydig cell tumors, and 13 juvenile granulosa cell tumors. Stage I tumors predominated (n=14; 60.9%), with 2 stage II (8.7%), 5 stage III (21.7%), and 2 stage IV tumors (8.7%). The upfront resection rate was 91.3% with no reported surgical morbidity or mortality and an OS of 82.1%. Chemotherapy approaches were not standardized. Most children (81.8%), except 2, had recognized platinum-based regimens. Chemotherapy-related toxicity was minimal and acceptable. Assessment of glomerular filtration rate and audiology assessments were infrequent and not standardized. Three patients were lost to follow-up. CONCLUSIONS: Although the numbers in this cohort are small, this study represents the first national cohort in Africa. The 5-year OS of 82.1% was encouraging. Standardized management of rare tumors like SCSTs is critical to improve ensure OS and address potential long-term sequelae.

Treatment outcomes of children with Hodgkin lymphoma between 2000 and 2010: First report by the South African Children's Cancer Study Group.

BACKGROUND: Children with Hodgkin lymphoma (HL) have excellent survival rates in high-income countries, but there are minimal outcome data in South African patients. Differing approaches to treatment are used in centres across South Africa, and the South African Children's Cancer Study Group (SACCSG) embarked on a programme to audit outcomes to improve survival rates. PATIENTS AND METHODS: A multicentre study was conducted to analyse outcomes and prognostic factors of children with HL in South Africa. Ten dedicated South African paediatric oncology units participated in a retrospective data review. All patients with HL treated consecutively between January 2000 and December 2010 were included. Kaplan-Meier curves and Cox regression model were employed to determine survival rates and prognostic factors. RESULTS: Two hundred and ninety-four patients were eligible for inclusion. The median age at presentation was 9.6 years (range 2.9-18.8); 55.4% of the patients presented with Stage III and IV disease and 9.9% were human immunodeficiency virus (HIV) positive. First-line therapy consisted of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) in 158 patients, vincristine, procarbazine/etoposide, prednisone and doxorubicin in 97 and adriamycin, bleomycin, vincristine and dacarbazine-chlorambucil, vinblastine, prednisone and procarbazine in 23 patients. The 5-year overall survival (OS) was 79% (95% confidence interval 73-84%). Multivariate analysis demonstrated that HIV infection (P = 0.018) and Ann Arbor Stage III and IV disease (P = 0.006) conferred a poor prognosis, while treatment with ABVD was associated with higher survival rates (P = 0.028). CONCLUSION: OS rates are encouraging for a middle-income country, although economic disparities continue to impact negatively on outcomes. Study results will form the basis for the development of national protocol and continued advocacy to rectify disparities.

Nosocomial outbreak of hepatitis B virus infection in a pediatric hematology and oncology unit in South Africa: Epidemiological investigation and measures to prevent further transmission.

BACKGROUND: Hospital-acquired hepatitis B virus (HBV) infection has been well described and continues to occur worldwide. Recent nosocomial outbreaks have been linked to unsafe injection practices, use of multi-dose vials, and poor staff compliance with standard precautions. This report describes a nosocomial outbreak that occurred in a pediatric hematology and oncology unit of a large academic hospital, the epidemiological investigation of the outbreak, and preventive measures implemented to limit further in-hospital transmission. METHODS: Outbreak investigation including contact tracing and HBV screening were initially carried out on all patients seen by the unit during the same period as the first three cases. Routine screening for the entire patient population of the unit was initiated in February 2013 when it was realized that numerous patients may have been exposed. RESULTS: Forty-nine cases of HBV infection were confirmed in 408 patients tested between July 2011 and October 2013. Phylogenetic analysis of the HBV preC/C gene nucleotide sequences revealed that all tested outbreak strains clustered together. Most (67%) patients were HBeAg positive. The cause of transmission could not be established. Preventive measures targeted three proposed routes. HBV screening and vaccination protocols were started in the unit. CONCLUSIONS: The high number of HBeAg positive patients, together with suspected lapses in infection prevention and control measures, are believed to have played a major role in the transmission. Measures implemented to prevent further in-hospital transmission were successful. On-going HBV screening and vaccination programs in pediatric hematology and oncology units should become standard of care.

Malignancies in South African children with HIV.

OBJECTIVES: In 2008 the South African Children's Cancer Study Group decided to review the epidemiology, management, and chemotherapy response of HIV-positive children with malignancy. METHODS: This is a retrospective analysis of data collected from the records of HIV-positive children diagnosed with malignancy at 7 university-based pediatric oncology units serving 8 of the 9 provinces in South Africa. RESULTS: Two hundred eighty-eight HIV-positive children were diagnosed with 289 malignancies between 1995 and 2009. Age at diagnosis ranged from 17 days to 18.64 years; median 5.79 years. Of the 220 HIV-associated malignancies, there were 97 Kaposi sarcomas, 61 Burkitt lymphomas, 47 other B-cell lymphomas including 2 primary central nervous system lymphomas, 12 Hodgkin lymphomas, and 3 leiomyosarcomas. Sixty-nine patients presented with non-AIDS-defining malignancies. More than 80% presented with advanced disease. Most patients (76.7%) were naive to antiretroviral therapy; 22.2% did not have access because it only became available in public hospitals in 2004. One hundred ninety-seven children were treated with curative intent; 91 received palliative care due to advanced malignancy and/or advanced HIV disease. Nearly one third had coexisting pathology, mostly tuberculosis. Overall survival for the whole group was 33.7%, but was 57.8% for those treated with antiretroviral therapy and chemotherapy. CONCLUSIONS: The study shows more Kaposi sarcoma and fewer primary central nervous system lymphomas among HIV-positive children than that is reported in the developed world, but confirms a higher incidence of non-Burkitt B-cell lymphoma than in HIV-negative children. The high number of non-AIDS-defining malignancies underscores the prevalence of HIV-AIDS in South Africa. The overall survival should improve with universal access to antiretrovirals and earlier diagnosis.

Implemented nutritional intervention algorithm in pediatric oncology compared to standard nutritional supportive care outcomes.

AIM: To implement a childhood cancer-specific nutritional algorithm adapted for the South African context for interventions at time-set intervals to evaluate differences in the nutritional status of newly diagnosed children with cancer. METHOD: Children with newly diagnosed cancer were assessed for stunting, underweight, wasting, and moderate to severe malnutrition (MUAC < -2SD and < - 3 SD) between October 2018 and December 2020 in a longitudinal nutritional assessment study with monthly assessments. Two pediatric oncology units (POUs) served as the intervention group that implemented the nutritional algorithm-directed intervention and three other POUs formed the control group that implemented standard supportive nutritional care. RESULTS: A total of 320 patients were enrolled with a median age of 6.1 years (range three months to 15.3 years) and a male-to-female ratio of 1.1:1. The malnourished patients in the intervention group showed significant improvement at six months after diagnosis for stunting (P = 0.028), underweight (P < 0.001), and wasting until month five (P = 0.014). The improvements in the control group were not significant. Moderate acute malnutrition (MAM) significantly improved over the first six months of cancer treatment in the intervention group (P < 0.001), while MAM improvement was only significant in the control group for the children under five years of age (P = 0.004). The difference in mean z-scores over time for the nutritional parameters between the intervention and control groups was insignificant. CONCLUSION: We established that the nutritional algorithm adapted for South Africa as an intervention tool for childhood cancer assisted in optimizing nutritional interventions and improved nutritional outcomes over the first six months of cancer treatment.

Machine Learning to Predict Interim Response in Pediatric Classical Hodgkin Lymphoma Using Affordable Blood Tests.

PURPOSE: Response assessment of classical Hodgkin lymphoma (cHL) with positron emission tomography-computerized tomography (PET-CT) is standard of care in well-resourced settings but unavailable in most African countries. We aimed to investigate correlations between changes in PET-CT findings at interim analysis with changes in blood test results in pediatric patients with cHL in 17 South African centers. METHODS: Changes in ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), albumin, total white cell count (TWC), absolute lymphocyte count (ALC), and absolute eosinophil count were compared with PET-CT Deauville scores (DS) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine in 84 pediatric patients with cHL. DS 1-3 denoted rapid early response (RER) while DS 4-5 denoted slow early response (SER). Missing values were imputed using the k-nearest neighbor algorithm. Baseline and follow-up blood test values were combined into a single difference variable. Data were split into training and testing sets for analysis using Python scikit-learn 1.2.2 with logistic regression, random forests, naïve Bayes, and support vector machine classifiers. RESULTS: Random forest analysis achieved the best validated test accuracy of 73% when predicting RER or SER from blood samples. When applied to the full data set, the optimal model had a predictive accuracy of 80% and a receiver operating characteristic AUC of 89%. The most predictive variable was the differences in ALC, contributing 21% to the model. Differences in ferritin, LDH, and TWC contributed 15%-16%. Differences in ESR, hemoglobin, and albumin contributed 11%-12%. CONCLUSION: Changes in low-cost, widely available blood tests may predict chemosensitivity for pediatric cHL without access to PET-CT, identifying patients who may not require radiotherapy. Changes in these nonspecific blood tests should be assessed in combination with clinical findings and available imaging to avoid undertreatment.

The Utility of Metabolic Parameters on Baseline F-18 FDG PET/CT in Predicting Treatment Response and Survival in Paediatric and Adolescent Hodgkin Lymphoma.

Lymphoma is the third most common paediatric cancer. Early detection of high-risk patients is necessary to anticipate those who require intensive therapy and follow-up. Current literature shows that residual tumor avidity on PET (Positron Emission Tomography) following chemotherapy corresponds with decreased survival. However, the value of metabolic parameters has not been adequately investigated. In this retrospective study, we aimed to evaluate the prognostic value of metabolic and other parameters in paediatric and adolescent Hodgkin lymphoma. We recorded tMTV (total Metabolic Tumor Volume), TLG (Total Lesion Glycolysis), and SUVmax (maximum Standard Uptake Value) on baseline PET, as well the presence of bone marrow or visceral involvement. HIV (human immunodeficiency virus) status and baseline biochemistry from clinical records were noted. All patients received stage-specific standard of care therapy. Response assessment on end-of-treatment PET was evaluated according to the Deauville criteria. We found that bone marrow involvement (p = 0.028), effusion (p < 0.001), and treatment response (p < 0.001) on baseline PET, as well as HIV status (p = 0.036) and baseline haemoglobin (p = 0.039), were significantly related to progression-free survival (PFS), whereas only effusion (p = 0.017) and treatment response (p = 0.050) were predictive of overall survival (OS). Only baseline tMTV predicted treatment response (p = 0.017). This confirms the value of F-18 FDG PET/CT (Fluoro-deoxy-glucose Positron Emission Tomography/Computed Tomography) in prognostication in paediatric and adolescent Hodgkin lymphoma; however, further studies are required to define the significance of metabolic parameters.

Prognostic factors affecting survival in children and adolescents with HIV and Hodgkin lymphoma in South Africa.

South African children with Hodgkin lymphoma (HL) and human immunodeficiency virus (HIV) have low 5-year overall survival (OS) rates. In this retrospective multicenter study, 271 South African pediatric patients with HL were studied to determine OS and prognostic factors in those with HIV and HL. Univariate risk factor analysis was performed to analyze prognostic factors. The 29 HIV-infected patients were younger (p = .021), more likely to present with wasting (0.0573), stunting (0.0332), and Stage IV disease (p = .000) than HIV-uninfected patients. The 5- and 10-year OS of HIV-infected patients of 49% and 45% versus 84% and 79%, respectively for HIV-uninfected patients (p = .0001) appeared to be associated with hypoalbuminemia (<20 g/dL) and CD4 percentage of <15%. Causes of death in the HIV-infected group included disease progression (6/14), infection (4/14), unknown (3/14), and second malignancy (1/14). HIV-infected pediatric patients with HL experience increased mortality due to post-therapy opportunistic and nosocomial infections.

Does radiotherapy prior to surgery improve long term prognosis in pediatric colorectal cancer in lower- and upper-middle income countries with limited resources? Our experience and literature review.

Colorectal carcinoma in children and adolescents is extremely rare, with an annual incidence <0.3 cases per million, most frequently reported in the second decade of life. It accounts for severe morbidity and poor prognosis owing to the low index of suspicion, delayed diagnosis, advanced stage at presentation and the aggressive tumor nature. Patients present with abdominal pain, vomiting, constipation, abdominal distension, rectal tenesmus, iron-deficiency anemia, change in bowel habit and weight loss. Rectal bleeding is an uncommon presentation in children. Bowel obstruction presents frequently in children compared to adults. In 90% of pediatric cases, colorectal carcinoma occurs sporadically. In 10%, predisposing conditions and syndromes are identified. We present a case study of a 12-year-old female with advanced colorectal cancer without a predisposing disease or syndrome, who received radio-chemotherapy ten weeks prior to radical abdominopelvic surgery, followed by radio-chemotherapy postoperatively, with a positive outcome.

Investigating hepatitis B immunity in patients presenting to a paediatric haematology and oncology unit in South Africa.

BACKGROUND: Hepatitis B is an important public health concern in South Africa (SA). The hepatitis B virus (HBV) vaccine was introduced into the South African Expanded Programme on Immunisation (EPI-SA) in 1995. There is no 'catch-up' programme in place. The duration of protection after hepatitis B vaccination in the SA population is unknown. Waning of vaccine-induced immunity leaves people at risk of acquiring hepatitis B infection in settings where the prevalence of infection is high and horizontal transmission is likely. OBJECTIVE: To assess immunity to HBV in patients at presentation to a paediatric haematology and oncology unit. METHODS: An audit of hepatitis profiles was done of all new patients seen in the unit from January 2012 to December 2013. Patients were classified as immune (antibody levels to hepatitis B surface antigen (anti-HBs) >100 mIU/ml), low immune (anti-HBs 10 - 100 mIU/ml) and not immune (anti-HBs <10 mIU/ml). RESULTS: Of the 210 patients included (median age 6.5 years), 84 (40.0%) had no immunity to hepatitis B despite presumed vaccination as part of the EPI schedule. Six patients tested positive for hepatitis B core antibody (anti-HBc), consistent with previous infection. No patients had active hepatitis B infection (hepatitis B surface antigen-positive). Most human immunodeficiency virus (HIV)-infected patients were not immune to HBV (80.0%). CONCLUSION: A significant number of children in SA are not immune to hepatitis B despite vaccination being part of the EPI-SA. Combined passive-active immunisation should be considered for all oncology patients in settings where exposure to HBV is possible. Consideration should also be given to offering booster vaccination to the population as a whole.

Unusual variant of scimitar syndrome associated with an absent right pulmonary artery, stenosis of the inferior vena cava, hemi-azygous continuation and the VACTERL association.

We report on a two-month-old infant with an unusual form of scimitar syndrome, associated with an absent right pulmonary artery, obstructed inferior vena cava, hemi-azygous continuation and the VACTERL association. The infant posed a major management problem and eventually died from a lower respiratory tract infection.