Improved survival of children and adolescents with classical Hodgkin lymphoma treated on a harmonised protocol in South Africa

Funding: CANSA, Wits Faculty Research Committee Individual Research Grant, Carnegie Corporation Research Funding, Crowdfunding through Doit4Charity Backabuddy and the Ride Joburg Cycle Race.Background Historic South African 5-year overall survival (OS) rates for Hodgkin lymphoma (HL) from 2000 to 2010 were 46% and 84% for human immunodeficiency virus (HIV)-positive and HIV-negative children, respectively. We investigated whether a harmonised treatment protocol using risk stratification and response-adapted therapy could increase the OS of childhood and adolescent HL. Methods Seventeen units prospectively enrolled patients less than 18 years, newly diagnosed with classical HL onto a risk-stratified, response-adapted treatment protocol from July 2016 to December 2022. Low- and intermediate-risk patients received four and six courses of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), respectively. High-risk patients received two courses of ABVD, followed by four courses of cyclophosphamide, vincristine, prednisone, and dacarbazine (COPDac). Those with a slow early response and bulky disease received consolidation radiotherapy. HIV-positive patients could receive granulocyte colony-stimulating factor and less intensive therapy if stratified as high risk, at the treating clinician's discretion. Kaplan–Meier survival analysis was performed to determine 2-year OS and Cox regression to elucidate prognostic factors. Results  The cohort comprised 132 patients (19 HIV-positive, 113 HIV-negative), median age of 9.7 years, with a median follow-up of 2.2 years. Risk grouping comprised nine (7%) low risk, 36 (27%) intermediate risk and 87 (66%) high risk, with 71 (54%) rapid early responders and 45 (34%) slow early responders, and 16 (12%) undocumented. Two-year OS was 100% for low-risk, 93% for intermediate-risk, and 91% for high-risk patients. OS for HIV-negative (93%) and HIV-positive (89%) patients were similar (p = .53). Absolute lymphocyte count greater than 0.6 × 109 predicted survival (94% vs. 83%, p = .02). Conclusion In the first South African harmonised HL treatment protocol, risk stratification correlated with prognosis. Two-year OS of HIV-positive and HIV-negative patients improved since 2010, partially ascribed to standardised treatment and increased supportive care. This improved survival strengthens the harmonisation movement and gives hope that South Africa will achieve the WHO Global Initiative for Childhood Cancer goals.Publisher PDFPeer reviewe

Current childhood cancer survivor long-term follow-up practices in South Africa

Background: The number of childhood cancer survivors (CCSs) is increasing due to improved survival. Most suffer at least one treatment-related late effect, even decades after treatment, thus lifelong long-term follow-up (LTFU) care is a necessity. Currently no standardized LTFU programme for CCSs exists in South Africa. Study purpose: This study investigated current LTFU care of CCSs in South Africa. Methods: A survey was conducted amongst 31 South African paediatric oncologists using the SurveyMonkeyTM online tool. Information obtained included: training/experience, LTFU practices, late effects knowledge and opinion regarding the importance of a standardized LTFU programme. Results: The response rate was 74% (23/31). Respondents had an average of 9 years’ experience. All (22/23; 96%) regarded LTFU as important. Only half (12/23; 52%) discussed late effects at diagnosis. Infertility and second malignancy risks were discussed by a third. Less than half (48%) used LTFU guidelines; the majority (9/11; 82%) adjusted them to the local context. Most survivors were followed by a paediatric oncologist (17/23; 74%). About half of respondents (47.8%) shared LTFU with colleagues in private practice (50%), secondary (66.7%) or primary care facilities (25%). Almost half of respondents (10/23; 43.5%) regarded their late effects knowledge and LTFU experience as good, 8/23 (34.8%) as adequate and 3/23 (13%) as inadequate. All agreed that a national LTFU programme would be very important (87%) or important (13%). Almost half of the respondents (48%) understood what a Survivorship Passport was. Conclusion: It is essential to develop a national standardized LTFU programme for CCSs in South Africa to ensure appropriate care for all survivors

Nephroblastoma - a 25 year review of a South African unit

CITATION: Visser, Y. T., et al. 2014. Nephroblastoma - a 25 year review of a South African unit. Journal of medicine and life, 7(3):445–449.The original publication is available at http://www.medandlife.ro/Rationale: To determine the outcome of patients with nephroblastoma in a South African hospital. Objective: To determine if there is a difference in the outcome of patients with nephroblastoma comparing two treatment protocols SIOP (Société International D’Oncologie Pédiatrique Protocol) versus NWTS (National Wilms’ Tumour Study Protocol). Methods and results: A retrospective audit of 25 years (1983-2007), of children diagnosed with nephroblastoma in Tygerberg Hospital. One hundred and seven patients were included in the study and 98 were analyzed. The average age at diagnosis was 3.8 years. Most patients (37%) presented with stage 1 of the disease, followed by patients with stage 3 (27%). Most patients were treated according to the SIOP protocol (61%). Gender and race did not influence the outcome. Patients with stage 1 and 2 of the disease had the best outcome (76% versus 43% for stages 3 and 4). The SIOP group had a better outcome than the NWTS group (p value 0.001). The two groups had an equal distribution of the stage of presentation. The tumor volumes were bigger in the NWTS group (1004cm3 compared to 613cm3). Nutritional status did not influence the outcome although more patients were underweight for age in the SIOP group. The statistical methods used were: Kaplan Meier, Gehan’s Wilcoxon Test, Chi –square test and the Fisher exact test.http://www.medandlife.ro/archive/31-vol-vii-iss-3-july-september-2014/special-articles/74-nephroblastoma-a-25-year-review-of-a-south-african-unitPost prin

High prevalence of long-term and late effects in a South African childhood cancer survivor cohort

Purpose: We documented the prevalence of late effects in a South African childhood cancer survivor (CCS) cohort. Patients and methods: CCSs at Tygerberg Hospital, Cape Town, were evaluated for clinical abnormalities, whereafter late effects were identified, graded according to the Common Terminology Criteria for Adverse Events (CTCAE), and classified as significant or insignificant. Results: The cohort comprised 160 CCSs (median age 13 years (interquartile range 9.9 – 17.8 years); follow-up period eight years (range 5–37.2 years)). There were 89 (55.6%) hematological and 71 (44.4%) solid malignancies. Most CCSs (146/160; 91.3%) had at least one late effect; the majority were of Grade 1 CTCAE severity (73.7%). Common late effects were gastrointestinal (13.3%), metabolic (12.9%), hematological (9.2%), musculoskeletal (9.1%), and neurological (8.8%) disorders. Significant risk factors for late effects were cancer diagnosis (p = 0.005), chemotherapy (moderate intensity [incidence rate ratio (IRR) 1.84; p = 0.036]; high intensity [IRR 2.8; p = 0.001]), and radiotherapy (IRR 1.44) (p = < 0.001). Late effects severity was significantly associated with radiotherapy (IRR 1.54; p = 0.004). Solid tumor survivors were more likely to develop Grade 2 (IRR 2.4; p = < 0.001) and 3 late effects (IRR 2.8; p = 0.011). Conclusion: This is the first prospective study of a CCS cohort in South Africa. Most CCSs developed mild or moderate long-term and late effects, significantly associated with cancer diagnosis, chemotherapy intensity, and radiotherapy. It is crucial to develop long-term surveillance plans for CCSs in South Africa to ensure early detection of late effects

Overall survival for neuroblastoma in South Africa between 2000 and 2014

BACKGROUND : Outcome data for neuroblastoma in sub‐Saharan Africa are minimal, whereas poor outcome is reported in low‐ and middle‐income countries. A multi‐institutional retrospective study across South Africa was undertaken to determine outcome. METHODS : Patients treated between January 2000 and December 2014 in nine South African pediatric oncology units were included. Kaplan–Meier curves and Cox regression models were employed to determine two‐year survival rates and to identify prognostic factors. RESULTS : Data from 390 patients were analyzed. The median age was 39.9 months (range, 0–201 months). The majority presented with stage 4 disease (70%). The main chemotherapy regimens were OPEC/OJEC (44.8%), St Jude NB84 protocol (28.96%), and Rapid COJEC (22.17%). Only 44.4% had surgery across all risk groups, whereas only 16.5% of high‐risk patients received radiotherapy. The two‐year overall survival (OS) for the whole cohort was 37.6%: 94.1%, 81.6%, and 66.7%, respectively, for the very‐low‐risk, low‐risk, and intermediate‐risk groups and 27.6% for the high‐risk group (P < 0.001, 95% CI). The median survival time for the whole group was 13 months (mean, 41.9 months; range, 0.1–209 months). MYCN‐nonamplified patients had a superior two‐year OS of 51.3% in comparison with MYCN‐amplified patients at 37.3% (P = 0.002, 95% CI). CONCLUSIONS : Limited disease had an OS comparable with high‐income countries, but advanced disease had a poor OS. South Africa should focus on early diagnosis and implementation of a national protocol with equitable access to treatment.Supporting Information Figure S1: Flow diagram: Patient cohort between 2000 and 2014Supporting Information Table S1: Clinical characteristics at presentationSupporting Information Table S2: Staging investigationsSupporting Information Table S3: Staging and risk classificationsSupporting Information Table S4: Lactate dehydrogenase and ferritin levelsSupporting Information Table S5: AnthropometrySupporting Information Table S6: Autologous stem cell transplant cohortSupporting Information Table S7: OutcomesSupporting Information Table S8: Survival durationThe VZW Kinderkankerfonds, Belgium.http://wileyonlinelibrary.com/journal/pbc2020-11-01hj2019Paediatrics and Child Healt

The evaluation of induction chemotherapy regimens for high-risk neuroblastoma in South African children

Achieving remission after induction therapy in high-risk neuroblastoma (HR-NB) is of significant prognostic importance. This study investigated remission after induction-chemotherapy using three standard neuroblastoma protocols in the South African (SA) setting. Retrospective data of 261 patients with HR-NB diagnosed between January 2000 and December 2016, who completed induction chemotherapy with standard treatment protocols were evaluated. The treatment protocols were either OPEC/OJEC or the St Jude NB84 protocol (NB84) or rapid COJEC (rCOJEC). The postinduction metastatic complete remission (mCR) rate, 2-year overall survival (OS) and 2-year event free survival (EFS) were determined as comparative denominators. The majority (48.3%; n = 126) received OPEC/OJEC, while 70 patients received (26.8%) rCOJEC and 65 (24.9%) NB84. Treatment with NB84 had the best mCR rate (36.9%), followed by OPEC/OJEC (32.5%) and rCOJEC (21.4%). The 2-year OS of treatment with NB84 was 41% compared to OPEC/OJEC (35%) and rCOJEC (24%) (p = 0.010). The 2-year EFS of treatment with NB84 was 37% compared to OPEC/OJEC (35%) and rCOJEC (18%) (p = 0.008). OPEC/OJEC had the least treatment-related deaths (1.6%) compared to rCOJEC (7.1%) and NB84 (7.5%) (p = 0.037). On multivariate analysis LDH (p = 0.023), ferritin (p = 0.002) and INSS stage (p = 0.006) were identified as significant prognostic factors for OS. The induction chemotherapy was not significant for OS (p = 0.18), but significant for EFS (p = 0.08) Treatment with NB84 achieved better mCR, OS and EFS, while OPEC/OJEC had the least treatment-related deaths. In resource-constrained settings, OPEC/OJEC is advised as induction chemotherapy in HR-NB due to less toxicity as reflected in less treatment-related deaths.Kinderkankerfonds, Belgiumhttps://www.tandfonline.com/loi/ipho202021-02-19hj2020Paediatrics and Child Healt

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.The National Research Foundation of South Africahttp://journals.lww.com/jpho-online/pages/default.aspx2022-07-01hj2021Paediatrics and Child Healt