Vincristine exposure in Kenyan children with cancer: CHAPATI feasibility study.

The low incidence of vincristine-induced peripheral neuropathy (VIPN) in Kenyan children may result from low vincristine exposure. We studied vincristine exposure in Kenyan children and dose-escalated in case of low vincristine exposure (NCT05844670). Average vincristine exposure was high. Individual vincristine exposure was assessed with a previously developed nomogram. A 20% dose increase was recommended for participants with low exposure and no VIPN, hyperbilirubinemia, or malnutrition. None of the 15 participants developed VIPN. Low vincristine exposure was seen in one participant: a dose increase was implemented without side effects. In conclusion, the participants did not develop VIPN despite having high vincristine exposure.

Influence of health-insurance on treatment outcome of childhood cancer in Western Kenya.

BACKGROUND: Few governments in low and middle-income countries (LMIC) have responded favourably to the international plea for Universal Health Coverage. Childhood cancer survival in LMIC is often below 20%. Limited health-insurance coverage may contribute to this poor survival. Our study explores the influence of health-insurance status on childhood cancer treatment outcomes in a Kenyan academic hospital. METHODS: This was a retrospective medical records review of all children diagnosed with cancer at Moi Teaching and Referral Hospital between 2010 and 2016. Socio-demographic and clinical data was collected using a structured data collection form. Fisher's exact test, chi-squared test, Kaplan-Meier method, log-rank test and Cox proportional hazard model were used to evaluate relationships between treatment outcomes and patient characteristics. Study was approved by Institutional Research Ethics Committee. FINDINGS: From 2010-2016, 879 children were newly diagnosed with cancer. Among 763 patients whose records were available, 28% abandoned treatment, 23% died and 17% had progressive/relapsed disease resulting in 32% event-free survival. In total 280 patients (37%) had health-insurance at diagnosis. After active enrolment during treatment, total health-insurance registration level reached 579 patients (76%). Treatment outcomes differed by health-insurance status (P < 0.001). The most likely treatment outcome in uninsured patients was death (49%), whereas in those with health-insurance at diagnosis and those who enrolled during treatment it was event-free survival (36% and 41% respectively). Overall survival (P < 0.001) and event-free survival (P < 0.001) were higher for insured versus uninsured patients. The hazard-ratio for treatment failure was 0.30 (95% CI:0.22-0.39; P < 0.001) for patients insured at diagnosis and 0.32 (95% CI:0.24-0.41; P < 0.001) for patients insured during treatment in relation to those without insurance. INTERPRETATION: Our study highlights the need for Universal Health Coverage in LMIC. Children without health-insurance had significantly lower survival. Childhood cancer treatment outcomes can be ameliorated by strategies that improve health-insurance access.

Outcomes of Wilms tumor treatment in western Kenya.

BACKGROUND/OBJECTIVES: Wilms tumor (WT) is a curable type of cancer with 5-year survival rates of over 90% in high-income countries, whereas this is less than 50% in low- and middle-income countries. We assessed treatment outcomes of children with WT treated at a large Kenyan teaching and referral hospital. DESIGN/METHODS: We conducted a retrospective record review of children diagnosed with WT between 2013 and 2016. Treatment protocol consisted of 6 weeks of preoperative chemotherapy and surgery, and 4-18 weeks of postoperative chemotherapy depending on disease stage. Probability of event-free survival (pEFS) and overall survival (pOS) was assessed using Kaplan-Meier method with Cox regression analysis. Competing events were analyzed with cumulative incidences and Fine-Gray regression analysis. RESULTS: Of the 92 diagnosed patients, 69% presented with high-stage disease. Two-year observed EFS and OS were, respectively, 43.5% and 67%. Twenty-seven percent of children died, 19% abandoned treatment, and 11% suffered from progressive or relapsed disease. Patients who were diagnosed in 2015-2016 compared to 2013-2014 showed higher pEFS. They less often had progressive or relapsed disease (p = .015) and borderline significant less often abandonment of treatment (p = .09). Twenty-nine children received radiotherapy, and 2-year pEFS in this group was 86%. CONCLUSION: Outcome of children with WT improved over the years despite advanced stage at presentation. Survival probabilities of patients receiving comprehensive therapy including radiation are approaching those of patients in high-income countries. Additional improvement could be achieved by ensuring that patients receive all required treatment and working on earlier diagnosis strategies.

An evaluation of the disparities affecting the underdiagnosis of pediatric cancer in Western Kenya.

INTRODUCTION: Western Kenya is home to approximately 24 million people, with 10 million children under the age of 15 years.1 Based on estimates of cancer incidence in similar populations from around the world, approximately 1500 patients should be diagnosed with pediatric cancer each year. This article describes the international collaboration that investigates potential barriers preventing the effective diagnosis of pediatric patients with cancer. METHODS: Here, we describe a multidisciplinary and sequential approach to better evaluate the complex factors affecting the lack of appropriate diagnosis of pediatric cancer in Western Kenya. RESULTS: Internal review at a large tertiary hospital noted 200-250 patients were diagnosed annually, suggesting the remaining 75%-80% of patients go undiagnosed and do not receive treatment. Following our screening process at a local referring hospital, 41 malaria slides demonstrated both morphologic and genetic evidence of leukemia. Knowledge assessments of local providers at referring institutions suggested a lack of education and training as the factors that contribute to lower rates of diagnosis. DISCUSSION: Through a multi-step approach, our teams were better able to isolate potential issues impeding the appropriate and timely diagnosis of pediatric cancer in Kenya.

Childhood acute lymphoblastic leukemia treatment in an academic hospital in Kenya: Treatment outcomes and health-care providers' perspectives.

BACKGROUND: Early deaths and treatment nonadherence are major reasons for low childhood acute lymphoblastic leukemia (ALL) survival in low- and middle-income countries. This study assessed treatment outcomes of children presenting with ALL and evaluated perspectives of health-care providers (HCP) on ALL treatment at a Kenyan academic hospital. METHODS: This was a combined retrospective medical records and cross-sectional questionnaire study. Treatment outcomes of 136 children diagnosed with ALL between 2010 and 2016 were collected. Questionnaires were completed by 245 HCP (response rate, 86%) between September and October 2016. RESULTS: Childhood ALL treatment outcomes were death (30%), progressive or relapsed disease (26%), abandonment (24%), and event-free survival (20%). Of all deaths, 80% were early deaths (prior or during induction), whereas 20% occurred in remission. Probability of event-free survival at three years was 18%. Only 57% of HCP believed childhood ALL can be cured, with more doctors (96%) than other HCP (45%) believing in curability of ALL (P < 0.001). The majority of HCP (96%) thought that experienced doctors should put more time and effort into making parents understand the diagnosis and necessity to complete treatment. According to HCP, reasons for protocol nonadherence included parental financial difficulties (94%) and use of alternative treatment (79%). CONCLUSIONS: Event-free survival for ALL in Kenya is low. The primary reason for treatment failure is early death from treatment-related complications. More efforts should be directed toward improving supportive care strategies. In the opinion of HCPs, improved communication with parents and supervision of junior staff will improve ALL treatment outcomes.

Influence of health insurance status on childhood cancer treatment outcomes in Kenya.

BACKGROUND: Survival of childhood cancer in high-income countries is approximately 80%, whereas in low-income countries, it is less than 10%. Limited access to health insurance in low-income settings may contribute to poor survival rates. This study evaluates the influence of health insurance status on childhood cancer treatment in a Kenyan academic hospital. METHODS: This was a retrospective study. All children diagnosed with a malignancy from 2010 until 2012 were included. Data on treatment outcomes and health insurance status at diagnosis were abstracted from patient charts. RESULTS: Of 280 patients, 34% abandoned treatment, 19% died, and 18% had progressive or relapsed disease resulting in 29% event-free survival. The majority of patients (65%) did not have health insurance at diagnosis. Treatment results differed significantly between patients with different health insurance status at diagnosis; 37% of uninsured versus 28% of insured patients abandoned treatment, and 24% of uninsured versus 37% of insured patients had event-free survival. The event-free survival estimate was significantly higher for patients with health insurance at diagnosis compared with those without (P = 0.004). Of patients without health insurance at diagnosis, 77% enrolled during treatment. Among those patients who later enrolled in health insurance, frequency of progressive or relapsed disease and deaths was significantly lower (P = 0.013, P < 0.001, respectively), while the event-free survival estimate was significantly higher (P < 0.001) compared with those who never enrolled. CONCLUSION: Childhood cancer event-free survival was 29% at a Kenyan hospital. Children without health insurance had significant lower chance of event-free survival. Childhood cancer treatment outcomes could be ameliorated by strategies that prevent treatment abandonment and improve access to health insurance.

Health-care providers' perspectives on traditional and complementary alternative medicine of childhood cancer in Kenya.

PURPOSE: Traditional and complementary alternative medicine (TCAM) use is rising globally. In many African countries, TCAM has been a way of life as the first and last resort remedy for many ailments, including cancer. Health-care providers (HCP) should address this need properly. This study explores HCP perspectives on TCAM in Kenya. METHODS: This cross-sectional study used questionnaires. HCP involved in the care of children with cancer at a Kenyan academic hospital were interviewed. RESULTS: In total, 155 HCP (response rate 79%) participated. Only 18% of HCP were positive about TCAM use. However, most HCP (85%) use TCAM themselves. More doctors (90%) than other HCP (56%) think that chemotherapy can cure cancer (P < 0.001).Thirty-three percent of HCP believe a combination of TCAM and chemotherapy is the best way to cure cancer, while 56% think that usefulness of TCAM is underestimated in conventional medicine. Self-prayer is regarded as most effective (58%) and safe (76%). Most harmful is witchcraft (80%). Most HCP (71%) think their knowledge about safety and efficacy of TCAM is inadequate. HCP think that their cancer patients use TCAM (97%) and that it is important that parents inform them about this (97%). However, only 5% of HCP always openly discuss TCAM with parents. CONCLUSIONS: HCP need to improve their knowledge of TCAM and facilitate open communication about TCAM with families so parents feel safe to discuss their interest in it.

CYP3A5 genotype and its impact on vincristine pharmacokinetics and development of neuropathy in Kenyan children with cancer.

BACKGROUND: Vincristine (VCR) is a critical part of treatment in pediatric malignancies and is associated with dose-dependent peripheral neuropathy (vincristine-induced peripheral neuropathy [VIPN]). Our previous findings show VCR metabolism is regulated by the CYP3A5 gene. Individuals who are low CYP3A5 expressers metabolize VCR slower and experience more severe VIPN as compared to high expressers. Preliminary observations suggest that Caucasians experience more severe VIPN as compared to nonCaucasians. PROCEDURE: Kenyan children with cancer who were undergoing treatment including VCR were recruited for a prospective cohort study. Patients received IV VCR 2 mg/m2 /dose with a maximum dose of 2.5 mg as part of standard treatment protocols. VCR pharmacokinetics (PK) sampling was collected via dried blood spot cards and genotyping was conducted for common functional variants in CYP3A5, multi-drug resistance 1 (MDR1), and microtubule-associated protein tau (MAPT). VIPN was assessed using five neuropathy tools. RESULTS: The majority of subjects (91%) were CYP3A5 high-expresser genotype. CYP3A5 low-expresser genotype subjects had a significantly higher dose and body surface area normalized area under the curve than CYP3A5 high-expresser genotype subjects (0.28 ± 0.15 hr·m2 /l vs. 0.15 ± 0.011 hr·m2 /l, P = 0.027). Regardless of which assessment tool was utilized, minimal neuropathy was detected in this cohort. There was no difference in the presence or severity of neuropathy assessed between CYP3A5 high- and low-expresser genotype groups. CONCLUSION: Genetic factors are associated with VCR PK. Due to the minimal neuropathy observed in this cohort, there was no demonstrable association between genetic factors or VCR PK with development of VIPN. Further studies are needed to determine the role of genetic factors in optimizing dosing of VCR for maximal benefit.

Corruption in health-care systems and its effect on cancer care in Africa.

At the government, hospital, and health-care provider level, corruption plays a major role in health-care systems in Africa. The returns on health investments of international financial institutions, health organisations, and donors might be very low when mismanagement and dysfunctional structures of health-care systems are not addressed. More funding might even aggravate corruption. We discuss corruption and its effects on cancer care within the African health-care system in a sociocultural context. The contribution of high-income countries in stimulating corruption is also described. Corrupt African governments cannot be expected to take the initiative to eradicate corruption. Therefore, international financial institutions, health organisations, and financial donors should use their power to demand policy reforms of health-care systems in Africa troubled by the issue of corruption. These modifications will ameliorate the access and quality of cancer care for patients across the continent, and ultimately improve the outcome of health care to all patients.

Impact of Physician Dual Practices on a Pediatric-Oncology Outreach-Program.

OBJECTIVE: Physician dual practices (PDP) can be defined as 'doctors combining clinical work in public and private health-sector.' This study explores the impact of PDP on a long-term pediatric-oncology outreach-program between large referral hospitals in the Netherlands, Indonesia and Kenya. METHODS: This cross-sectional descriptive study used a self-administered semi-structured survey.  The most senior doctor from each partner site was interviewed in June 2022. The survey contained 70 closed-ended and 7 open-ended questions and took 30-45 minutes to complete. Closed-ended questions were evaluated on 2-5 point rating scales. Informed consent was acquired and respondents endorsed the final report. RESULTS: In the Netherlands an estimated 0-20% of senior doctors combine work in public and private-sector, while 60-80% do so in Indonesia and Kenya according to the respondents. In Indonesia and Kenya, most of doctors are involved in PDP to augment low government salaries. Impact of PDP on pediatric-oncology care is minimal in the Netherlands, but detrimental in Indonesia and Kenya: shortage of experienced doctors, limited supervision of junior staff, slow diagnostics and delays in chemotherapy administration ultimately lead to undermining of the quality of care and adverse patient outcomes. CONCLUSIONS: PDP adversely impact patient care at the Indonesian and Kenyan partner sites of a pediatric-oncology outreach-program. Strategies addressing PDP in resource-poor settings are required to improve treatment outcomes and survival of children with cancer.

Treatment outcomes of pediatric acute myeloid leukemia in Western Kenya before and after the implementation of the SIOP PODC treatment guideline.

PURPOSE: The Pediatric Oncology in Developing Countries (PODC) committee of the International Society of Pediatric Oncology (SIOP) published a pediatric acute myeloid leukemia (AML)-specific adapted treatment guideline for low- and middle-income countries. We evaluated the outcomes of children with AML at a large Kenyan academic hospital before (period 1) and after (period 2) implementing this guideline. PATIENTS AND METHODS: Records of children (≤17 years) newly diagnosed with AML between 2010 and 2021 were retrospectively studied. In period 1, induction therapy comprised two courses with doxorubicin and cytarabine, and consolidation comprised two courses with etoposide and cytarabine. In period 2, a prephase with intravenous low-dose etoposide was administered prior to induction therapy, induction course I was intensified, and consolidation was adapted to two high-dose cytarabine courses. Probabilities of event-free survival (pEFS) and overall survival (pOS) were estimated using the Kaplan-Meier method. RESULTS: One-hundred twenty-two children with AML were included - 83 in period 1 and 39 in period 2. Overall, 95 patients received chemotherapy. The abandonment rate was 19% (16/83) in period 1 and 3% (1/39) in period 2. The early death, treatment-related mortality, complete remission, and relapse rates in periods 1 and 2 were 46% (29/63) versus 44% (14/32), 36% (12/33) versus 47% (8/17), 33% (21/63) versus 38% (12/32), and 57% (12/21) versus 17% (2/12), respectively. The 2-year pEFS and pOS in periods 1 and 2 were 5% versus 15% (p = .53), and 8% versus 16% (p = .93), respectively. CONCLUSION: The implementation of the SIOP PODC guideline did not result in improved outcomes of Kenyan children with AML. Survival of these children remains dismal, mainly attributable to early mortality.

Barriers to and facilitators of effective management of fever episodes in hospitalised Kenyan children with cancer: protocol for convergent mixed methods study.

INTRODUCTION: Febrile neutropenia is an oncological emergency in children with cancer, associated with serious infections and complications. In low-resourced settings, death from infections in children with cancer is 20 times higher than in high-resourced treatment settings, thought to be related to delays in antibiotic administration and management. The barriers to effective management of fever episodes in children with cancer have not previously been described. This convergent mixed-methods study will provide the evidence to develop fever treatment guidelines and to inform their effective implementation in children with cancer at Moi Teaching and Referral Hospital (MTRH), a level 6 referral hospital in western Kenya. METHODS AND ANALYSIS: Prospective data collection of paediatric patients with cancer with new fever episodes admitted to MTRH will be performed during routine treatment. Clinical variables will be collected from 50 fever episodes, including cancer diagnosis and infectious characteristics of the fever episode, and elapsed time from fever onset to various milestones in the management workflow. Semistructured qualitative interviews with healthcare providers (estimated 20 to reach saturation) will explore the barriers to and facilitators of appropriate management of fever episodes in children with cancer. The interview guide was informed by a theoretical framework and Consolidated Framework for Implementation Research. A mixed-methods analysis use of joint display tables and process mapping will link and integrate the two types of data with meta-inferences. ETHICS AND DISSEMINATION: Institutional review board approval was obtained from the MTRH (0004273) and the University of Michigan (HUM0225674), and the study was registered with National Commission for Science Technology and Innovation (P/23/22885). Written consent will be obtained from all participants. Results will be formally shared with local and national policy leadership and local end users, presented at relevant national academic conferences and submitted for publication in a peer-reviewed journal.

Outcomes of pediatric acute myeloid leukemia treatment in Western Kenya.

BACKGROUND: Pediatric acute myeloid leukemia (AML) is a challenging disease to treat in low- and middle-income countries (LMICs). Literature suggests that survival in LMICs is poorer compared with survival in high-income countries (HICs). AIMS: This study evaluates the outcomes of Kenyan children with AML and the impact of sociodemographic and clinical characteristics on outcome. METHODS AND RESULTS: A retrospective medical records study was performed at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya, between January 2010 and December 2018. Sociodemographic and clinical characteristics, and treatment outcomes were evaluated. Chemotherapy included two "3 + 7" induction courses with doxorubicin and cytarabine and two "3 + 5" consolidation courses with etoposide and cytarabine. Supportive care included antimicrobial prophylaxis with cotrimoxazole and fluconazole, and blood products, if available. Seventy-three children with AML were included. The median duration of symptoms before admission at MTRH was 1 month. The median time from admission at MTRH to diagnosis was 6 days and to the start of AML treatment 16 days. Out of the 55 children who were started on chemotherapy, 18 (33%) achieved complete remission, of whom 10 (56%) relapsed. The abandonment rate was 22% and the early death rate was 46%. The 2-year probabilities of event-free survival and overall survival were 4% and 7%, respectively. None of the sociodemographic and clinical characteristics were significantly associated with outcome. CONCLUSION: Survival of Kenyan children with AML is dismal and considerably lower compared with survival in HICs. Strategies to improve survival should be put in place including better supportive care, optimization of the treatment protocol, and reduction of the abandonment rate and time lag to diagnosis with sooner start of treatment.

Wilms Tumor Treatment Outcomes: Perspectives From a Low-Income Setting.

PURPOSE: Wilms tumor is the commonest renal malignancy in childhood. Survival in high-income countries is approximately 90%, whereas in low-income countries, it is less than 50%. This study assessed treatment outcomes of patients with Wilms tumor at a Kenyan academic hospital. PATIENTS AND METHODS: We conducted a retrospective medical record review of all children diagnosed with Wilms tumor between 2010 and 2012. Data on treatment outcomes and various sociodemographic and clinical characteristics were collected. RESULTS: Of the 39 patients with Wilms tumor, 41% had event-free survival, 31% abandoned treatment, 23% died, and 5% had progressive or relapsed disease. Most patients presented at an advanced stage: stage I (0%), II (7%), III (43%), IV (40%), or V (10%). The most likely treatment outcome in patients with low-stage (I to III) disease was event-free survival (67%), whereas in those with high-stage (IV to V) disease, it was death (40%). No deaths or instances of progressive or relapsed disease were recorded among patients with low-stage disease; their only reason for treatment failure was abandonment of treatment. Stage of disease significantly affected treatment outcomes (P = .014) and event-free survival estimates (P < .001). Age at diagnosis, sex, duration of symptoms, distance to hospital, and health insurance status did not statistically significantly influence treatment outcomes or event-free survival estimates. CONCLUSION: Survival of patients with Wilms tumor in Kenya is lower compared with that in high-income countries. Treatment abandonment is the most common cause of treatment failure. Stage of disease at diagnosis statistically significantly affects treatment outcomes and survival.

Influence of health insurance status on paediatric non-Hodgkin's lymphoma treatment in Kenya.

OBJECTIVE: Non-Hodgkin's lymphoma (NHL) is the most common childhood malignancy in sub-Saharan Africa. Survival rates for NHL are higher than 80% in high-income countries.This study explores treatment outcomes of children with NHL in Kenya, a sub-Saharan low-income country, and the association between health insurance status at diagnosis and treatment outcomes. DESIGN: This was a retrospective medical records study. All children diagnosed with NHL in 2010, 2011 and 2012 were included. Data on treatment outcomes and health insurance status at diagnosis were collected. RESULTS: Of all 63 patients with NHL, 35% abandoned treatment, 22% had progressive or relapsed disease, 14% died and 29% had event-free survival. Most patients (73%) had no health insurance at diagnosis. Treatment outcomes in children with or without health insurance at diagnosis differed significantly (p=0.005). The most likely treatment outcome in children with health insurance at diagnosis was event-free survival (53%), whereas in children without health insurance at diagnosis it was abandonment of treatment (44%). Crude HR for treatment failure was 3.1 (95% CI 1.41 to 6.60, p=0.005) for uninsured versus insured children. The event-free survival estimate was significantly higher in children with health insurance at diagnosis than in patients without health insurance at diagnosis (p=0.003). Stage of disease at diagnosis was identified as a confounder of this association (adjusted HR=2.4, 95% CI 0.95 to 6.12, p=0.063). CONCLUSIONS: Survival of children with NHL in Kenya is much lower compared with high-income countries. Abandonment of treatment is the most common cause of treatment failure. Health insurance at diagnosis was associated with better treatment outcomes and survival.