Publications by authors named "Gita Naidu"

14 Publications

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

J Pediatr Hematol Oncol 2021 Feb 3. Epub 2021 Feb 3.

Department of Paediatrics and Child Health, Haematology-Oncology Service, Red Cross War Memorial Children's Hospital Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town Burden of Disease Research Unit, South African Medical Research Council Division of Paediatric Haematology-Oncology, Department of Paediatrics and Child Health, Tygerberg Hospital, Faculty of Medicine and Health Sciences, University of Stellenbosch Neurodevelopmental Service, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town Division of Paediatric Haematology-Oncology, Department of Paediatrics and Child Health, Charlotte Maxeke Johannesburg Academic Hospital, University of Witwatersrand, Johannesburg Division of Pediatric Haematology-Oncology, Department of Paediatrics and Child Health, Pietermaritzburg Metropolitan Hospital Complex, University of KwaZulu-Natal, Pietermaritzburg Division of Paediatric Haematology-Oncology, Chris Hani Baragwanath Academic Hospital, University of Witwatersrand, Soweto, Gauteng Division of Paediatric Haematology-Oncology, Department of Paediatrics, Universitas Hospital, University of the Free State, Bloemfontein Division of Paediatric Haematology-Oncology, Department of Paediatrics, Steve Biko Academic Hospital, University of Pretoria, Tshwane Division of Paediatric Haematology-Oncology, Department of Paediatrics and Child Health, Frere Hospital, East London Division of Paediatric Haematology-Oncology, Department of Paediatrics and Child Health, Port Elizabeth Provincial Hospital, Walter Sisulu University, Port Elizabeth, South Africa Paediatric Haematology and Oncology, Department of Paediatrics and Child Health, University of Antwerp, Antwerp University Hospital, Antwerp, Belgium.

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.
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http://dx.doi.org/10.1097/MPH.0000000000002076DOI Listing
February 2021

Age at diagnosis as a prognostic factor in South African children with neuroblastoma.

Pediatr Blood Cancer 2021 Apr 23;68(4):e28878. Epub 2021 Jan 23.

Department of Paediatric Haematology and Oncology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa.

Purpose: Low- and middle-income countries (LMICs) reported a higher median age at diagnosis of neuroblastoma (NB) compared to high-income countries. The aim was to determine if the optimal age at diagnosis, which maximizes the difference in overall survival between younger versus older patients in the South African population was similar to the internationally validated 18 months age cut-point.

Methods: Four hundred sixty NB patients diagnosed between 2000 and 2016 were included. Receiver operating characteristic (ROC) curves were used to predict potential age cut-point values for overall survival in all risk group classifications. Risk ratios, sensitivity, specificity, and positive and negative predictive values at the specific cut-points were estimated with 95% confidence intervals, and time to mortality by age at the specific cut-points was shown with Kaplan-Meier curves and compared using log-rank tests.

Results: The median age at diagnosis for the total cohort was 31.9 months (range 0.2-204.7). For high-risk (HR), intermediate-risk, low-risk, and very low-risk patients, the median age at diagnosis was, respectively, 36 months (range 0.4-204.7), 16.8 months (range 0.7-145.1), 14.2 months (range 2.0-143.5), and 8.7 months (range 0.2-75.6). The ROC curves for the total NB cohort (area under the curve [AUC] 0.696; P < .001) and HR (AUC 0.682; P < .001) were analyzed further. The optimal cut-point value for the total cohort was at 19.1 months (sensitivity 59%; specificity 78%). The HR cohort had potential cut-point values identified at 18.4 months age at diagnosis (sensitivity 45%; specificity 87%) and 31.1 months (sensitivity 67%; specificity 62%). The 19.1 months cut-point value in the total cohort and the 18.4 months cut-point value in HR were as useful in predicting overall survival as 18 months age at diagnosis.

Conclusion: The 18 months cut-point value appears to be the appropriate age for prognostic determination, despite the higher median age at diagnosis in South Africa.
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http://dx.doi.org/10.1002/pbc.28878DOI Listing
April 2021

Burden of Tuberculosis in South African Children During Treatment for Underlying Malignancies: A Single-center Experience in Johannesburg.

Pediatr Infect Dis J 2020 12;39(12):1111-1115

Medical Research Council: Respiratory and Meningeal Pathogens Research Unit.

Background: Children with cancer are immunocompromised with increased susceptibility to infections. We evaluated the burden of tuberculosis in children with cancer.

Methods: Children with cancer were enrolled and screened for Mycobacterium tuberculosis infection using the tuberculin skin test and enzyme-linked immune absorbent spot (T-SPOT.TB; Oxford Immunotec Ltd, Oxford, United Kingdom). Children with physician-suspected tuberculosis were investigated for M. tuberculosis using microscopy and culture on sputum or gastric washings.

Results: We enrolled 169 children; 10.7% were living with HIV. The tuberculin skin test was positive in 2.9% of patients, who were treated for tuberculosis and excluded from further analysis. The enzyme-linked immune absorbent spot (T-SPOT.TB) was either negative or indeterminate in the first 100 children screened. The incidence of tuberculosis was 7.6 per 100 child-years; 35.3% were culture-confirmed. Tuberculosis was diagnosed at a mean of 5.5 months from cancer diagnosis. A greater proportion of children living with HIV (44.4%) developed tuberculosis than those without (17.2%; adjusted P = 0.042). Children treated for high-risk acute lymphoblastic leukemia, advanced stage non-Hodgkin lymphoma and acute myeloid leukemia (P = 0.009) and those with a higher exposure-period (per 100 child-years) to corticosteroids courses (350 vs. 29.4; P < 0.001) had a higher incidence of tuberculosis. Twenty-six of 34 children (76.5%) with tuberculosis died; multiple infections were identified at the time of death.

Conclusions: Screening children for tuberculosis infection at cancer diagnosis was of limited value. The high rate of tuberculosis and poor outcomes emphasize the need for a high index of suspicion to diagnose tuberculosis and consideration for antituberculosis treatment, especially for those with identified risk factors.
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http://dx.doi.org/10.1097/INF.0000000000002873DOI Listing
December 2020

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries.

Authors:
Ido Didi Fabian Andrew W Stacey Allen Foster Tero T Kivelä Francis L Munier Naama Keren-Froim Nir Gomel Nathalie Cassoux Mandeep S Sagoo M Ashwin Reddy Lamis Al Harby Marcia Zondervan Covadonga Bascaran Elhassan Abdallah Shehu U Abdullahi Sahadatou Adamou Boubacar Dupe S Ademola-Popoola Adedayo Adio Ada E Aghaji Silvia Alarcón Portabella Amadou I Alfa Bio Amany M Ali Donjeta B Alia Charlotta All-Eriksson Argentino A Almeida Khalifa M Alsawidi Romanzo Antonino Nicholas J Astbury Rose Atsiaya Julia Balaguer Walentyna Balwierz Honorio Barranco Maja Beck Popovic Sarra Benmiloud Nissrine Bennani Guebessi Rokia C Berete Shelley J Biddulph Eva M Biewald Sharon Blum Nadia Bobrova Marianna Boehme Norbert Bornfeld Gabrielle C Bouda Hédi Bouguila Amaria Boumedane Bénédicte G Brichard Michael Capra L Guilherme Castela Jaume Català-Mora Guillermo L Chantada Violeta S Chernodrinska Faraja S Chiwanga Krzysztof Cieslik Codruta Comsa Maria G Correa Llano Monika Csóka Isac V Da Gama Alan Davidson Patrick De Potter Laurence Desjardins Monica D Dragomir Magritha Du Bruyn Asmaa El Kettani Amal M Elbahi Dina Elgalaly Alaa M Elhaddad Moawia M Ali Elhassan Mahmoud M Elzembely Vera A Essuman Ted Grimbert A Evina Oluyemi Fasina Ana Fernández-Teijeiro Moira Gandiwa David García Aldana Jennifer A Geel Zelalem Gizachew Pernille A Gregersen Koffi M Guedenon Theodora Hadjistilianou Sadiq Hassan Stanislava Hederova Laila Hessissen Diriba F Hordofa Marlies Hummlen Kristina Husakova Russo Ida Vesna R Ilic Helen Jenkinson Theophile B Amani Kabesha Rolande L Kabore Abubakar Kalinaki Noa Kapelushnik Tamar Kardava Pavlin Kroumov Kemilev Tomas Kepak Zaza Khotenashvili Artur Klett Jess Elio Kosh Komba Palet Dalia Krivaitiene Mariana Kruger Alice Kyara Eva S Lachmann Slobodanka Latinović Karin Lecuona Robert M Lukamba Livia Lumbroso Lesia Lysytsia Erika Maka Mayuri Makan Chatonda Manda Nieves Martín Begue Ibrahim O Matende Marchelo Matua Ismail Mayet Freddy B Mbumba Aemero A Mengesha Edoardo Midena Furahini G Mndeme Ahmed A Mohamedani Annette C Moll Claude Moreira Mchikirwa S Msina Gerald Msukwa Kangwa I Muma Gabriela Murgoi Kareem O Musa Hamzah Mustak Okwen M Muyen Gita Naidu Larisa Naumenko Paule Aïda Ndoye Roth Vladimir Neroev Marina Nikitovic Elizabeth D Nkanga Henry Nkumbe Mutale Nyaywa Ghislaine Obono-Obiang Ngozi C Oguego Andrzej Olechowski Alexander Hugo Oscar Peter Osei-Bonsu Sally L Painter Vivian Paintsil Luisa Paiva Ruzanna Papyan Raffaele Parrozzani Manoj Parulekar Katarzyna Pawinska-Wasikowska Sanja Perić Remezo Philbert Pavel Pochop Vladimir G Polyakov Manca T Pompe Jonathan J Pons Léa Raobela Lorna A Renner David Reynders Dahiru Ribadu Mussagy M Riheia Petra Ritter-Sovinz Svetlana Saakyan Azza Ma Said Sonsoles San Román Pacheco Trish A Scanlan Judy Schoeman Stefan Seregard Sadik T Sherief Sidi Sidi Cheikh Sónia Silva Tetyana Sorochynska Grace Ssali Christina Stathopoulos Branka Stirn Kranjc David K Stones Karel Svojgr Fatoumata Sylla Gevorg Tamamyan Alketa Tandili Bekim Tateshi Tuyisabe Theophile Fousseyni Traoré Harba Tyau-Tyau Ali B Umar Steen F Urbak Tatiana L Ushakova Sandra Valeina Milo van Hoefen Wijsard Nevyana V Veleva-Krasteva Maris Viksnins Werner Wackernagel Keith Waddell Patricia D Wade Amina H Wali Nigeria Amelia Dc Wime Charlotte Wolley Dod Jenny M Yanga Vera A Yarovaya Andrey A Yarovoy Ekhtelbenina Zein Shirley Sharabi Katsiaryna Zhilyaeva Othman Ao Ziko Richard Bowman

Br J Ophthalmol 2020 Sep 15. Epub 2020 Sep 15.

Ophthalmology Department, Great Ormond Street Children's Hospital, London, UK.

Background: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe.

Methods: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries.

Results: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease.

Conclusions: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.
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http://dx.doi.org/10.1136/bjophthalmol-2020-316613DOI Listing
September 2020

High Burden of Serious Bacterial Infections in African Children Treated for Cancer.

Pediatr Infect Dis J 2020 10;39(10):943-948

From the Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Paediatric Oncology Unit, Chris Hani Baragwanath Academic Hospital.

Background: Infections in children treated for cancer contribute to morbidity and mortality. There is a paucity of studies on the incidence, etiology, risk factors and outcome of bacterial infections in African children treated for cancer. The aim of the study was to delineate the epidemiology of infectious morbidity and mortality in children with cancer.

Methods: The study enrolled children 1-19 years old with cancer and infections. Children were investigated for infection as part of standard of care.

Results: One hundred sixty-nine children were enrolled, 82 with hematologic malignancies and 87 with solid tumors and 10.7% were HIV infected. The incidence (per 100 child-years) of septic episodes (101) microbiologically confirmed (70.9) septic episodes, Gram-positive (48.5) and Gram-negative (37.6) sepsis was higher in children with hematologic malignancies than in those with solid tumors. The most common Gram-positive bacteria were Coagulase-negative Staphylococci, Streptococcus viridans and Enterococcus faecium, while the most common Gram-negative bacteria were Escherichia coli, Acinetobacter baumannii and Pseudomonas species. The C-reactive protein and procalcitonin was higher in microbiologically confirmed sepsis. The case fatality risk was 40.4%; 80% attributed to sepsis. The odds of dying from sepsis were higher in children with profound [adjusted odds ratio (aOR) = 3.96; P = 0.004] or prolonged neutropenia (aOR = 3.71; P = 0.011) and profound lymphopenia (aOR = 4.09; P = 0.003) and independently associated with pneumonia (53.85% vs. 29.23%; aOR = 2.38; P = 0.025) and tuberculosis (70.83% vs. 34.91%; aOR = 4.3; P = 0.005).

Conclusion: The study emphasizes the high burden of sepsis in African children treated for cancer and highlights the association of tuberculosis and pneumonia as independent predictors of death in children with cancer.
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http://dx.doi.org/10.1097/INF.0000000000002758DOI Listing
October 2020

The importance of local control management in high-risk neuroblastoma in South Africa.

Pediatr Surg Int 2020 Apr 28;36(4):457-469. Epub 2020 Feb 28.

Department of Paediatric Surgery, Faculty of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.

Purpose: To investigate the impact of local therapies on high-risk neuroblastoma (HR-NB) outcomes in South Africa.

Methods: Data from 295 patients with HR-NB from nine pediatric oncology units between 2000 and 2014 were analysed. All patients received chemotherapy. Five-year overall (OS) and event free survival (EFS) were determined for patients who had received local therapy, either surgery or radiotherapy or both.

Results: Surgery was performed in only 35.9% (n = 106/295) patients. Surgical excision was done for 34.8% (n = 85/244) of abdominal primaries, 50.0% (n = 11/22) of thoracic primaries; 22.2% (n = 2/9) neck primaries and 66.7% (n = 8/12) of the paraspinal primaries. Only 15.9% (n = 47/295) of all patients received radiotherapy. Children, who had surgery, had an improved five-year OS of 32.1% versus 5.9% without surgery (p < 0.001). Completely resected disease had a five-year OS of 30.5%, incomplete resections 31.4% versus no surgery 6.0% (p < 0.001). Radiated patients had a five-year OS of 21.3% versus 14.2% without radiotherapy (p < 0.001). Patients who received radiotherapy without surgical interventions, had a marginally better five-year OS of 12.5% as opposed to 5.4% (p < 0.001). Patients who underwent surgery had a longer mean overall survival of 60.9 months, while patients, who were irradiated, had a longer mean overall survival of 7.9 months (p < 0.001). On multivariate analysis, complete metastatic remission (p < 0.001), surgical status (p = 0.027), and radiotherapy status (p = 0.040) were significant predictive factors in abdominal primaries.

Conclusion: Surgery and radiotherapy significantly improve outcomes regardless of the primary tumor site, emphasizing the importance of local control in neuroblastoma.
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http://dx.doi.org/10.1007/s00383-020-04627-xDOI Listing
April 2020

Global Retinoblastoma Presentation and Analysis by National Income Level.

Authors:
Ido Didi Fabian Elhassan Abdallah Shehu U Abdullahi Rula A Abdulqader Sahadatou Adamou Boubacar Dupe S Ademola-Popoola Adedayo Adio Armin R Afshar Priyanka Aggarwal Ada E Aghaji Alia Ahmad Marliyanti N R Akib Lamis Al Harby Mouroge H Al Ani Aygun Alakbarova Silvia Alarcón Portabella Safaa A F Al-Badri Ana Patricia A Alcasabas Saad A Al-Dahmash Amanda Alejos Ernesto Alemany-Rubio Amadou I Alfa Bio Yvania Alfonso Carreras Christiane Al-Haddad Hamoud H Y Al-Hussaini Amany M Ali Donjeta B Alia Mazin F Al-Jadiry Usama Al-Jumaily Hind M Alkatan Charlotta All-Eriksson Ali A R M Al-Mafrachi Argentino A Almeida Khalifa M Alsawidi Athar A S M Al-Shaheen Entissar H Al-Shammary Primawita O Amiruddin Romanzo Antonino Nicholas J Astbury Hatice T Atalay La-Ongsri Atchaneeyasakul Rose Atsiaya Taweevat Attaseth Than H Aung Silvia Ayala Baglan Baizakova Julia Balaguer Ruhengiz Balayeva Walentyna Balwierz Honorio Barranco Covadonga Bascaran Maja Beck Popovic Raquel Benavides Sarra Benmiloud Nissrine Bennani Guebessi Rokia C Berete Jesse L Berry Anirban Bhaduri Sunil Bhat Shelley J Biddulph Eva M Biewald Nadia Bobrova Marianna Boehme H C Boldt Maria Teresa B C Bonanomi Norbert Bornfeld Gabrielle C Bouda Hédi Bouguila Amaria Boumedane Rachel C Brennan Bénédicte G Brichard Jassada Buaboonnam Patricia Calderón-Sotelo Doris A Calle Jara Jayne E Camuglia Miriam R Cano Michael Capra Nathalie Cassoux Guilherme Castela Luis Castillo Jaume Català-Mora Guillermo L Chantada Shabana Chaudhry Sonal S Chaugule Argudit Chauhan Bhavna Chawla Violeta S Chernodrinska Faraja S Chiwanga Tsengelmaa Chuluunbat Krzysztof Cieslik Ruellyn L Cockcroft Codruta Comsa Zelia M Correa Maria G Correa Llano Timothy W Corson Kristin E Cowan-Lyn Monika Csóka Xuehao Cui Isac V Da Gama Wantanee Dangboon Anirban Das Sima Das Jacquelyn M Davanzo Alan Davidson Patrick De Potter Karina Q Delgado Hakan Demirci Laurence Desjardins Rosdali Y Diaz Coronado Helen Dimaras Andrew J Dodgshun Craig Donaldson Carla R Donato Macedo Monica D Dragomir Yi Du Magritha Du Bruyn Kemala S Edison I Wayan Eka Sutyawan Asmaa El Kettani Amal M Elbahi James E Elder Dina Elgalaly Alaa M Elhaddad Moawia M Ali Elhassan Mahmoud M Elzembely Vera A Essuman Ted Grimbert A Evina Zehra Fadoo Adriana C Fandiño Mohammad Faranoush Oluyemi Fasina Delia D P G Fernández Ana Fernández-Teijeiro Allen Foster Shahar Frenkel Ligia D Fu Soad L Fuentes-Alabi Brenda L Gallie Moira Gandiwa Juan L Garcia David García Aldana Pascale Y Gassant Jennifer A Geel Fariba Ghassemi Ana V Girón Zelalem Gizachew Marco A Goenz Aaron S Gold Maya Goldberg-Lavid Glen A Gole Nir Gomel Efren Gonzalez Graciela Gonzalez Perez Liudmira González-Rodríguez Henry N Garcia Pacheco Jaime Graells Liz Green Pernille A Gregersen Nathalia D A K Grigorovski Koffi M Guedenon D Sanjeeva Gunasekera Ahmet K Gündüz Himika Gupta Sanjiv Gupta Theodora Hadjistilianou Patrick Hamel Syed A Hamid Norhafizah Hamzah Eric D Hansen J William Harbour M Elizabeth Hartnett Murat Hasanreisoglu Sadiq Hassan Shadab Hassan Stanislava Hederova Jose Hernandez Lorelay Marie Carcamo Hernandez Laila Hessissen Diriba F Hordofa Laura C Huang G B Hubbard Marlies Hummlen Kristina Husakova Allawi N Hussein Al-Janabi Russo Ida Vesna R Ilic Vivekaraj Jairaj Irfan Jeeva Helen Jenkinson Xunda Ji Dong Hyun Jo Kenneth P Johnson William J Johnson Michael M Jones Theophile B Amani Kabesha Rolande L Kabore Swathi Kaliki Abubakar Kalinaki Mehmet Kantar Ling-Yuh Kao Tamar Kardava Rejin Kebudi Tomas Kepak Naama Keren-Froim Zohora J Khan Hussain A Khaqan Phara Khauv Wajiha J Kheir Vikas Khetan Alireza Khodabande Zaza Khotenashvili Jonathan W Kim Jeong Hun Kim Hayyam Kiratli Tero T Kivelä Artur Klett Jess Elio Kosh Komba Palet Dalia Krivaitiene Mariana Kruger Kittisak Kulvichit Mayasari W Kuntorini Alice Kyara Eva S Lachmann Carol P S Lam Geoffrey C Lam Scott A Larson Slobodanka Latinovic Kelly D Laurenti Bao Han A Le Karin Lecuona Amy A Leverant Cairui Li Ben Limbu Quah Boon Long Juan P López Robert M Lukamba Livia Lumbroso Sandra Luna-Fineman Delfitri Lutfi Lesia Lysytsia George N Magrath Amita Mahajan Abdul Rahim Majeed Erika Maka Mayuri Makan Emil K Makimbetov Chatonda Manda Nieves Martín Begue Lauren Mason John O Mason Ibrahim O Matende Miguel Materin Clarissa C D S Mattosinho Marchelo Matua Ismail Mayet Freddy B Mbumba John D McKenzie Aurora Medina-Sanson Azim Mehrvar Aemero A Mengesha Vikas Menon Gary John V D Mercado Marilyn B Mets Edoardo Midena Divyansh K C Mishra Furahini G Mndeme Ahmed A Mohamedani Mona T Mohammad Annette C Moll Margarita M Montero Rosa A Morales Claude Moreira Prithvi Mruthyunjaya Mchikirwa S Msina Gerald Msukwa Sangeeta S Mudaliar Kangwa I Muma Francis L Munier Gabriela Murgoi Timothy G Murray Kareem O Musa Asma Mushtaq Hamzah Mustak Okwen M Muyen Gita Naidu Akshay Gopinathan Nair Larisa Naumenko Paule Aïda Ndoye Roth Yetty M Nency Vladimir Neroev Hang Ngo Rosa M Nieves Marina Nikitovic Elizabeth D Nkanga Henry Nkumbe Murtuza Nuruddin Mutale Nyaywa Ghislaine Obono-Obiang Ngozi C Oguego Andrzej Olechowski Scott C N Oliver Peter Osei-Bonsu Diego Ossandon Manuel A Paez-Escamilla Halimah Pagarra Sally L Painter Vivian Paintsil Luisa Paiva Bikramjit P Pal Mahesh Shanmugam Palanivelu Ruzanna Papyan Raffaele Parrozzani Manoj Parulekar Claudia R Pascual Morales Katherine E Paton Katarzyna Pawinska-Wasikowska Jacob Pe'er Armando Peña Sanja Peric Chau T M Pham Remezo Philbert David A Plager Pavel Pochop Rodrigo A Polania Vladimir G Polyakov Manca T Pompe Jonathan J Pons Daphna Prat Vireak Prom Ignatius Purwanto Ali O Qadir Seema Qayyum Jiang Qian Ardizal Rahman Salman Rahman Jamalia Rahmat Purnima Rajkarnikar Rajesh Ramanjulu Aparna Ramasubramanian Marco A Ramirez-Ortiz Léa Raobela Riffat Rashid M Ashwin Reddy Ehud Reich Lorna A Renner David Reynders Dahiru Ribadu Mussagy M Riheia Petra Ritter-Sovinz Duangnate Rojanaporn Livia Romero Soma R Roy Raya H Saab Svetlana Saakyan Ahmed H Sabhan Mandeep S Sagoo Azza M A Said Rohit Saiju Beatriz Salas Sonsoles San Román Pacheco Gissela L Sánchez Phayvanh Sayalith Trish A Scanlan Amy C Schefler Judy Schoeman Ahad Sedaghat Stefan Seregard Rachna Seth Ankoor S Shah Shawkat A Shakoor Manoj K Sharma Sadik T Sherief Nandan G Shetye Carol L Shields Sorath Noorani Siddiqui Sidi Sidi Cheikh Sónia Silva Arun D Singh Niharika Singh Usha Singh Penny Singha Rita S Sitorus Alison H Skalet Hendrian D Soebagjo Tetyana Sorochynska Grace Ssali Andrew W Stacey Sandra E Staffieri Erin D Stahl Christina Stathopoulos Branka Stirn Kranjc David K Stones Caron Strahlendorf Maria Estela Coleoni Suarez Sadia Sultana Xiantao Sun Meryl Sundy Rosanne Superstein Eddy Supriyadi Supawan Surukrattanaskul Shigenobu Suzuki Karel Svojgr Fatoumata Sylla Gevorg Tamamyan Deborah Tan Alketa Tandili Fanny F Tarrillo Leiva Maryam Tashvighi Bekim Tateshi Edi S Tehuteru Luiz F Teixeira Kok Hoi Teh Tuyisabe Theophile Helen Toledano Doan L Trang Fousseyni Traoré Sumalin Trichaiyaporn Samuray Tuncer Harba Tyau-Tyau Ali B Umar Emel Unal Ogul E Uner Steen F Urbak Tatiana L Ushakova Rustam H Usmanov Sandra Valeina Milo van Hoefen Wijsard Adisai Varadisai Liliana Vasquez Leon O Vaughan Nevyana V Veleva-Krasteva Nishant Verma Andi A Victor Maris Viksnins Edwin G Villacís Chafla Vicktoria Vishnevskia-Dai Tushar Vora Antonio E Wachtel Werner Wackernagel Keith Waddell Patricia D Wade Amina H Wali Yi-Zhuo Wang Avery Weiss Matthew W Wilson Amelia D C Wime Atchareeya Wiwatwongwana Damrong Wiwatwongwana Charlotte Wolley Dod Phanthipha Wongwai Daoman Xiang Yishuang Xiao Jason C Yam Huasheng Yang Jenny M Yanga Muhammad A Yaqub Vera A Yarovaya Andrey A Yarovoy Huijing Ye Yacoub A Yousef Putu Yuliawati Arturo M Zapata López Ekhtelbenina Zein Chengyue Zhang Yi Zhang Junyang Zhao Xiaoyu Zheng Katsiaryna Zhilyaeva Nida Zia Othman A O Ziko Marcia Zondervan Richard Bowman

JAMA Oncol 2020 05;6(5):685-695

International Centre for Eye Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale.

Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis.

Design, Setting, And Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017.

Main Outcomes And Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis.

Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]).

Conclusions And Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.
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http://dx.doi.org/10.1001/jamaoncol.2019.6716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047856PMC
May 2020

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

Pediatr Hematol Oncol 2020 May 19;37(4):300-313. Epub 2020 Feb 19.

Paediatric Haematology and Oncology, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa.

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%;  = 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%) ( = 0.010). The 2-year EFS of treatment with NB84 was 37% compared to OPEC/OJEC (35%) and rCOJEC (18%) ( = 0.008). OPEC/OJEC had the least treatment-related deaths (1.6%) compared to rCOJEC (7.1%) and NB84 (7.5%) ( = 0.037). On multivariate analysis LDH ( = 0.023), ferritin ( = 0.002) and INSS stage ( = 0.006) were identified as significant prognostic factors for OS. The induction chemotherapy was not significant for OS ( = 0.18), but significant for EFS ( = 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.
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http://dx.doi.org/10.1080/08880018.2020.1717698DOI Listing
May 2020

Overall survival for neuroblastoma in South Africa between 2000 and 2014.

Pediatr Blood Cancer 2019 11 31;66(11):e27944. Epub 2019 Jul 31.

Paediatric Haematology and Oncology, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa.

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.
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http://dx.doi.org/10.1002/pbc.27944DOI Listing
November 2019

Cancer in adolescents and young adults living with HIV.

Curr Opin HIV AIDS 2018 05;13(3):196-203

MRC CTU, University College London Institute of Clinical Trials and Methodology.

Purpose Of Review: Adults living with HIV have an increased risk of malignancy yet there is little data for adolescents and young adults. We reviewed recently published cancer epidemiology, treatment, and outcome data for adolescents and young adults living with HIV (AYALHIV) aged 10 to less than 25 years between 2016 and 2017.

Recent Findings: AYALHIV are at increased risk of developing cancer compared to their uninfected peers. Kaposi sarcoma and non-Hodgkin lymphoma occur most frequently with variation by geographical region. Increased cancer risk is associated with HIV-related immunosuppression and coinfection with oncogenic viruses. Published data, particularly on posttreatment outcomes, remain limited and analyses are hampered by lack of data disaggregation by age and route of HIV transmission.

Summary: Although data are sparse, the increased cancer risk for AYALHIV is the cause for concern and must be modified by improving global access and uptake of antiretroviral therapy, human papilloma virus (HPV) and hepatitis B virus (HBV) vaccination, screening for hepatitis B and C infection, and optimized cancer screening programs. Education aimed at reducing traditional modifiable cancer risk factors should be embedded within multidisciplinary services for AYALHIV.
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http://dx.doi.org/10.1097/COH.0000000000000460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047517PMC
May 2018

HIV-associated malignancies in children.

Curr Opin HIV AIDS 2017 01;12(1):77-83

aNational Cancer Registry, National Health Laboratory Service bPaediatric Haematology Oncology, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa cCentre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa dInstitute of Social and Preventive Medicine, University of Bern, Switzerland.

Purpose Of Review: HIV-infected children are at an increased risk of developing cancer. Many of the cancers in HIV-infected children are linked to immunosuppression and oncogenic coinfections. Worldwide most HIV-infected children live in sub-Saharan Africa, but cancer data for this population are scarce. In this article, we review the current literature on the epidemiology and prevention of cancer in HIV-infected children.

Recent Findings: Combined antiretroviral therapy (cART) reduces the risk of developing cancer in HIV-infected children. Cancer risk remains increased in children who start cART at older ages or more advanced immunosuppression as compared with children who start cART at younger age and with mild immunosuppression. Starting cART before severe immunosuppression develops is key to prevent cancer in HIV-infected children but most children in low-income countries start cART at severe immunosuppression levels. Vaccination against high-risk variants of human papillomavirus may protect again human papillomavirus-associated cancer later in life. However, tailoring of human papillomavirus vaccination guidelines for HIV-infected children and young women awaits answers to determine the best vaccination strategies.

Summary: Better data on the short-term and long-term risks of developing cancer and the effects of preventive measures in HIV-infected children from regions with high burden of HIV/AIDS are urgently needed.
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http://dx.doi.org/10.1097/COH.0000000000000331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340073PMC
January 2017

Do Not Forget the Glycophorin A: An Unusual Case of Myeloid Sarcoma.

J Pediatr Hematol Oncol 2016 07;38(5):e173-6

Departments of *Anatomical Pathology ∥Molecular Medicine and Hematology #Pediatrics, Division of Pediatric Oncology †National Health Laboratory Services ‡Chris Hani Baragwanath Academic Hospital §Faculty of Health Sciences, University of the Witwatersrand ¶Charlotte Maxeke Academic Hospital, Soweto, Johannesburg, South Africa.

Acute erythroid leukemia is rare, with isolated reports on presentation as an extramedullary tumor mass (myeloid sarcoma). We describe a case of pure erythroid leukemia presenting as an orbital mass in a 1-year, 9-month-old girl. This is only the second case described in a child. Tissue biopsy of the tumor mass showed medium-sized cells that were glycophorin A positive and negative with conventional myeloid markers. Flow cytometry, bone marrow aspirate, and trephine confirmed the diagnosis of pure erythroid leukemia.
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http://dx.doi.org/10.1097/MPH.0000000000000543DOI Listing
July 2016

The Saint Siluan warning signs of cancer in children: impact of education in rural South Africa.

Pediatr Blood Cancer 2011 Feb;56(2):314-6

Division of Paediatric Haematology and Oncology, Department of Paediatrics, Chris Hani-Baragwanath Hospital, University of the Witwatersrand, Soweto, Johannesburg, South Africa.

Two thirds of children with cancer never reach a specialist centre for treatment in South Africa. The majority of those who present have advanced disease. A campaign was undertaken to educate the public and the primary health workers on the Saint Siluan early warning signs of cancer in children. There was a statistically significant increase in the number of new patients referred in the 6 years following the campaign (P = 0.001), but did not succeed in achieving the referral of patients at earlier stages of disease. This list of the warning signs appears to be useful in promoting awareness of cancer.
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http://dx.doi.org/10.1002/pbc.22853DOI Listing
February 2011

Paroxysmal nocturnal hemoglobinuria arising from Fanconi anemia.

J Pediatr Hematol Oncol 2003 Feb;25(2):167-8

University of the Witwatersrand, Chris-Hani-Baragwanath Hospital, Johannesburg, South Africa.

The progress of a female child with African type Fanconi anemia that evolves in time into paroxysmal nocturnal hemoglobinuria is described. Modern diagnostic methods are used to confirm this process. A discussion of possible mechanisms ensues.
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http://dx.doi.org/10.1097/00043426-200302000-00017DOI Listing
February 2003