Childhood cancer presentation and initial outcomes in Ethiopia: Findings from a recently opened pediatric oncology unit.

There were no pediatric oncology centers in southwest Ethiopia prior to 2016. This study aims to describe presenting diagnoses and initial outcomes at Jimma University Medical Center (JUMC), the first pediatric oncology unit (POU) in southwest Ethiopia, provide initial insights into regional pediatric cancer epidemiology, illustrate the rapid growth of pediatric cancer services, and highlight ongoing challenges. We used a retrospective descriptive approach to assess the epidemiologic pattern and initial treatment outcomes of pediatric cancer at JUMC POU from August 2016 through December 2022. During the study period, 749 children were diagnosed with cancer at JUMC. The mean age was 7.2 years (20 days-18 years). Acute lymphoblastic leukemia was the most common diagnosis (16.4%), followed by non-Hodgkin lymphoma (12.4%), Wilms tumor (11.1%), soft tissue sarcoma (8.8%), Hodgkin lymphoma (8.4%), and retinoblastoma (8.3%). Brain tumors accounted for only 2.7% of the diagnoses. Of the 703 patients that were not referred elsewhere, 42% of the patients abandoned treatment, 29% died, 17% completed treatment, and 7% remained on treatment at the time of this assessment. The findings emphasize the growth in the diagnosis and treatment of children with cancer in the southwest region of Ethiopia. The data suggests a different epidemiologic profile of childhood cancer cases diagnosed at the JUMC POU compared to high-income countries and neighbouring countries in Africa. Treatment abandonment remains a barrier to care. Ongoing areas of focus include establishment of a hospital-based cancer registry, reduction of treatment abandonment, improvement of diagnostic capacity, and increased access to advanced supportive care.

Results of a pre-implementation analysis of Ethiopia's National Pediatric Cancer Registry.

In Ethiopia, cancer accounts for about 5.8% of total national mortality, with an estimated annual incidence of cancer of approximately 60,960 cases and an annual mortality of over 44,000 persons. This is likely an underestimation. Survival rates for pediatric malignancies are likewise suboptimal although exact figures are unknown since a national cancer registry is unavailable. The World Health Organization (WHO) provides recommendations for the creation of cancer registries to track such data. Here we describe our pharmacist-led, pre-implementation assessment of introducing an enhanced national pediatric cancer registry in Ethiopia. Our assessment project had three specific aims around which the methods were designed: 1) characterization of the current spreadsheet-based tool across participating sites, including which variables were being collected, how these variables compared to standards set by the WHO, and a description of how the data were entered and its completeness; 2) assessment of the perceptions of an enhanced registry from hospital staff; and 3) evaluation of workflow gaps regarding documentation. The hospital staff and leadership have generally positive perceptions of an enhanced pediatric cancer registry, which were further improved by our interactions. The workflow assessment revealed several gaps, which were addressed systematically using a three-phase implementation science approach. The assessment also demonstrated that the existing spreadsheet-based tool was missing WHO-recommended variables and had inconsistent completion due to the workflow gaps. A pediatric oncology summary sheet will be implemented in upcoming trips in patient charts to better summarize the patients' journey starting from diagnosis. This document will be used by the data clerks in an enhanced-spreadsheet to have a more complete data set.

Training pediatric hematologist/oncologists for capacity building in Ethiopia.

PURPOSE: A considerable barrier to global pediatric oncology efforts has been the scarcity and even absence of trained professionals in many low- and middle-income countries, where the majority of children with cancer reside. In 2013, no dedicated pediatric hematology-oncology (PHO) programs existed in Ethiopia despite the estimated annual incidence of 6000-12000 cases. The Aslan Project initiative was established to fill this gap in order to improve pediatric cancer care in Ethiopia. A major objective was to increase subspecialty PHO-trained physicians who were committed to practicing locally and empowered to lead programmatic development. METHODS: We designed and implemented a PHO training curriculum to provide a robust educational and clinical experience within the existing resource-constrained environment in Ethiopia. Education relied on visiting PHO faculty, a training attachment abroad, and extraordinary initiative from trainees. RESULTS: Four physicians have completed comprehensive PHO subspecialty training based primarily in Ethiopia, and all have remained local. Former fellows are now leading two PHO centers in Ethiopia with a combined capacity of 64 inpatient beds and over 800 new diagnoses per year; an additional former fellow is developing a pediatric cancer program in Nairobi, Kenya. Two fellows currently are in training. Program leadership, teaching, and advocacy are being transitioned to these physicians. CONCLUSIONS: Despite myriad challenges, a subspecialty PHO training program was successfully implemented in a low-income country. PHO training in Ethiopia is approaching sustainability through human resource development, and is accelerating the growth of dedicated PHO services where none existed 7 years ago.

Knowledge and Beliefs About Oncofertility and Associations with Quality of Life Among Adolescent and Young Adult Survivors of Pediatric Cancer.

PURPOSE: Adolescent and young adult (AYA) cancer survivors experience fertility and childrearing challenges in adulthood, but there is limited evidence on awareness, beliefs, and concerns about oncofertility in this population, needs for supportive resources, and associations with quality of life (QoL). METHODS: Participants were 69 AYAs aged 12-25 who were diagnosed with cancer at age 18 years or younger and ≥1 year cancer free, recruited from childhood cancer clinical records and support organizations. Participants completed self-report assessment of oncofertility knowledge and beliefs, information needs, and measures of QoL. Analyses examined associations between oncofertility-related variables and QoL. RESULTS: Knowledge and beliefs about oncofertility options were considerably low in the sample, and participants reported unmet oncofertility resource needs. In multivariable analyses, QoL was associated with beliefs valuing the importance of fertility in childhood cancer (ß = 0.87, p = 0.01) and lower information needs (ß = -1.19, p = 0.022). CONCLUSIONS: Infertility is a well-documented effect of childhood cancer treatment. Our findings indicate that clinical providers are a preferred source of information for AYA patients, and there is a need to address oncofertility concerns and challenges in this group. Research is needed to examine barriers to addressing fertility issues in childhood cancer treatment and ways to promote dialogue between providers and patients and their families.

Safety, Tolerability, and Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Pediatric Patients.

The safety, tolerability, and pharmacokinetics of the liposomal formulation of amphotericin B (L-AMB) were evaluated in 40 immunocompromised children and adolescents. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study with 10 to 13 patients in each of the four dosage cohorts. Each cohort received daily dosages of 2.5, 5.0, 7.5, or 10 mg of amphotericin B in the form of L-AMB per kg of body weight. Neutropenic patients between the ages of 1 and 17 years were enrolled to receive empirical antifungal therapy or treatment of documented invasive fungal infections. The pharmacokinetic parameters of L-AMB were measured as those of amphotericin B by high-performance liquid chromatography and calculated by noncompartmental methods. There were nine adverse-event-related discontinuations, four of which were related to infusions. Infusion-related side effects occurred for 63 (11%) of 565 infusions, with 5 patients experiencing acute infusion-related reactions (7.5- and 10-mg/kg dosage levels). Serum creatinine levels increased from 0.45 ± 0.04 mg/dl to 0.63 ± 0.06 mg/dl in the overall population (P = 0.003), with significant increases in dosage cohorts receiving 5.0 and 10 mg/kg/day. At the higher dosage level of 10 mg/kg, there was a trend toward greater hypokalemia and vomiting. The area under the concentration-time curve from 0 to 24 h (AUC0-24) values for L-AMB on day 1 increased from 54.7 ± 32.9 to 430 ± 566 µg · h/ml in patients receiving 2.5 and 10.0 mg/kg/day, respectively. These findings demonstrate that L-AMB can be administered to pediatric patients at dosages similar to those for adults and that azotemia may develop, especially in those receiving ≥5.0 mg/kg/day.

Tolerance and effectiveness of nivolumab after pediatric T-cell replete, haploidentical, bone marrow transplantation: A case report.

To date, there has been a lack of pediatric experience regarding the efficacy and tolerability of immune checkpoint inhibitors after haploidentical hematopoietic stem cell transplant (HSCT). We present the case of a 22-year-old female with multiple-relapsed Hodgkin lymphoma (HL) who presented with a new relapse after haploidentical (post-haplo) HSCT. Anti-PD-1 therapy with nivolumab resulted in significant objective disease response and clinical improvement without notable side effects, including the absence of a graft-versus-host disease (GVHD). This case report suggests that immune checkpoint inhibition may be safely tolerated even in the setting of haploidentical HSCT, without triggering overt GVHD.

Developing the Evidence Base in Pediatric Oncology Nursing Practice for Promoting Health-Related Quality of Life in Pediatric Oncology Patients.

Research has shown that self-esteem and hopefulness are positively related among female childhood cancer survivors (CCS) and contribute to their health-related quality of life (HRQOL). HRQOL remains a significant outcome of treatment for CCS. This study examined the relationships among self-esteem, hopefulness, and HRQOL in young adult female CCS to inform the development of evidence-based practice guidelines for pediatric oncology nursing practice. An online survey was conducted with a sample of young adult female CCS from 58 treatment centers across the United States at 4 time points: at baseline and at 6 weeks, 3 months, and 6 months after initial measurement time. The relationships between self-esteem, hopefulness, and HRQOL were statistically significant (Time 1, P = .05; Times 2, 3, and 4, P = .01) across all measurement times. These findings identify hopefulness and self-esteem as determinants of HRQOL and suggest that caring practices among pediatric oncology nurses that support psychosocial adjustment through promoting self-esteem and hopefulness have the potential to support HRQOL among young adult female CCS. These outcomes support the development of evidence-based practice guidelines to influence HRQOL outcomes among these survivors.

Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children.

Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited pharmacokinetic (PK) data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. Our objective was to describe the pharmacokinetics of LAmB in children aged 1 to 17 years with suspected or documented IFD. Thirty-five children were treated with LAmB at doses of 2.5 to 10 mg kg-1 daily. Samples were taken at baseline and at 0.5- to 2.0-h intervals for 24 h after receipt of the first dose (n = 35 patients) and on the final day of therapy (n = 25 patients). LAmB was measured using high-performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored. An evolution in PK was observed during the course of therapy, resulting in a proportion of patients (n = 13) having significantly higher maximum serum concentrations (Cmax) and areas under the concentration-time curve from 0 to 24 h (AUC0-24) later in the course of therapy, without evidence of drug accumulation (trough plasma concentration accumulation ratio of <1.2). The fit of a 2-compartment model incorporating weight and an exponential decay function describing volume of distribution best described the data. There was a statistically significant relationship between mean AUC0-24 and probability of nephrotoxicity (odds ratio, 2.37; 95% confidence interval, 1.84 to 3.22; P = 0.004). LAmB exhibits nonlinear pharmacokinetics. A third of children appear to experience a time-dependent change in PK, which is not explained by weight, maturation, or observed clinical factors.

Use of reprogrammed cells to identify therapy for respiratory papillomatosis.

A patient with a 20-year history of recurrent respiratory papillomatosis had progressive, bilateral tumor invasion of the lung parenchyma. We used conditional reprogramming to generate cell cultures from the patient's normal and tumorous lung tissue. Analysis revealed that the laryngeal tumor cells contained a wild-type 7.9-kb human papillomavirus virus type 11 (HPV-11) genome, whereas the pulmonary tumor cells contained a 10.4-kb genome. The increased size of the latter viral genome was due to duplication of the promoter and oncogene regions. Chemosensitivity testing identified vorinostat as a potential therapeutic agent. At 3 months after treatment initiation, tumor sizes had stabilized, with durable effects at 15 months.

Recruitment and retention of older adolescent and young adult female survivors of childhood cancer in longitudinal research.

PURPOSE/OBJECTIVES: To describe the challenges encountered in the recruitment and retention of a sample of older adolescent and young adult female survivors of childhood cancer for a longitudinal study testing a targeted psychosocial intervention aimed at enhancing hope. DATA SOURCES: Published literature on constructing longitudinal intervention studies and strategies in the recruitment and retention of childhood cancer survivors in research was used to develop the protocol of this study. DATA SYNTHESIS: Using empirical literature to construct the study's design resulted in achieving certain goals for the design, but not in the recruitment and retention of study participants. Using online technology to deliver the intervention and collect data was efficient and effective. Traditional approaches to recruitment and retention of those survivors, however, were not effective. Use of more novel approaches to enroll study participants demonstrated only modest success. CONCLUSIONS: Additional research is needed on strategies to successfully recruit and retain older adolescents and young adult female survivors of childhood cancer in longitudinal intervention studies. IMPLICATIONS FOR NURSING: The improvement in the psychological well-being of female survivors of childhood cancer remains an important outcome in ongoing care. The need to continue to identify creative and effective ways to recruit and retain those survivors is warranted.

Validation of a milk consumption stage of change algorithm among adolescent survivors of childhood cancer.

OBJECTIVE: To assess the construct validity of a milk consumption Stages of Change (SOC) algorithm among adolescent survivors of childhood cancer ages 11 to 21 years (n = 75). METHODS: Baseline data from a randomized controlled trial designed to evaluate a health behavior intervention were analyzed. Assessments included a milk consumption SOC algorithm and hypothesized theoretical and behavioral predictors of SOC. RESULTS: Compared with survivors who expressed no readiness to change, those expressing readiness to change behavior for both 2 and 4 daily servings of milk reported more frequent milk consumption (P < .001), greater dietary calcium intake (P = .006), and were more likely to meet age-specific recommendations for daily calcium intake (P = .01). CONCLUSIONS AND IMPLICATIONS: Results provide support for the construct validity of the milk consumption SOC algorithm relative to behavioral criteria. Research is needed to further examine algorithm validity with respect to theoretical predictors of SOC.

Late effects in cancer survivors: "the shared care model".

Advances continue to be made in the field of pediatric oncology ever since treatment for childhood cancer began in 1948. Since then, there has been exponential progress in the care for children with cancer as reflected in the current survival rates, which approach 90%. With such incredible survival rates, the number of childhood cancer survivors has increased significantly, with present estimates being above 300,000 in the United States alone. This success has, however, not been without cost. Long-term studies of cancer survivors have brought to light specific adverse effects of therapy, which often present years after treatment is finished, termed "late effects." Over the years, it has become apparent that monitoring for and treating these late effects of treatment is essential for the continuing health of young cancer survivors. It is now well recognized that childhood cancer survivors require long-term follow-up care given by an integrated team of qualified and invested specialty-care providers in collaboration with their primary caregivers. These teams deliver care using a risk-based approach, following a systematic plan for lifelong screening,surveillance, and prevention that incorporates risks based on the previous cancer, cancer therapy, genetic predispositions,lifestyle behaviors, and co-morbid health conditions.

Can we overcome the effect of conflicts in rendering palliative care? An introduction to the Middle Eastern Cancer Consortium (MECC).

The Middle East has been experiencing an ongoing political conflict for the past several decades. This situation has been characterized by hostility often leading to violence of all sources. At times, such a conflict led to the outbreak of a military war, which was followed by an enmity between religious, ethnic, cultural, and national populations. In such environmental situations, palliative care professionals often confront major challenges including bias, mistrust, and mutual suspicion between patients and their treating clinicians. In order to overcome such obstacles, while rendering palliative care services, all professionals involved need careful planning and execution of their treatment plans. The latter is however possible, and sometimes successful even across lines of conflict, thereby promoting understanding, mutual respect, and tolerance between the involved communities and individuals.

Survey of consumer informatics for palliation and hospice care.

CONTEXT: Palliation in patient care is under-utilized in part because many patients have insufficient knowledge about this management option. Information technology can improve awareness by providing access to numerous sources of trustworthy information. EVIDENCE ACQUISITION: To estimate what a patient interested in palliation might find online, online resources were searched in July 2010, using terms relevant to palliation. PubMed was searched for publications relevant to discussed topics. EVIDENCE SYNTHESIS: Search engines returned vast numbers of hits, and identifying trustworthy sites was difficult. Products judged as trustworthy were classified as information, decision tool, or extended interaction tool. Sites with useful educational material were relatively plentiful; decision guides or interactive tools were much rarer. Available consumer informatics did not address some terminal illnesses very well, and some subpopulations such as children, nor was there sufficient attention to literacy levels or principles of instructional design. Online or published information about usage numbers, effectiveness, and cost/benefit considerations was scant. Many sectors, including commercial, government, healthcare, research, and wellness/advocacy groups, have created consumer informatics for palliation. CONCLUSIONS: Online information about palliation is available, although identifying trustworthy sources can be problematic. General information sites are relatively plentiful, but more tools for decision making, and interaction would increase value of web resources. More attention to literacy levels, instructional principles, and needs of special populations would improve products. Research to measure usage of such tools, ability to influence behavior, and cost/benefit issues is needed.

Pediatric palliative care and eHealth opportunities for patient-centered care.

BACKGROUND: Pediatric palliative care currently faces many challenges including unnecessary pain from insufficiently personalized treatment, doctor-patient communication breakdowns, and a paucity of usable patient-centric information. Recent advances in informatics for consumer health through eHealth initiatives have the potential to bridge known communication gaps, but overall these technologies remain under-utilized in practice. PURPOSE: This paper seeks to identify effective uses of existing and developing health information technology (HIT) to improve communications and care within the clinical setting. METHODS: A needs analysis was conducted by surveying seven pediatric oncology patients and their extended support network at the Lombardi Pediatric Clinic at Georgetown University Medical Center in May and June of 2010. Needs were mapped onto an existing inventory of emerging HIT technologies to assess what existing informatics solutions could effectively bridge these gaps. RESULTS: Through the patient interviews, a number of communication challenges and needs in pediatric palliative cancer care were identified from the interconnected group perspective surrounding each patient. These gaps mapped well, in most cases, to existing or emerging cyberinfrastructure. However, adoption and adaptation of appropriate technologies could improve, including for patient-provider communication, behavioral support, pain assessment, and education, all through integration within existing work flows. CONCLUSIONS: This study provides a blueprint for more optimal use of HIT technologies, effectively utilizing HIT standards-based technology solutions to improve communication. This research aims to further stimulate the development and adoption of interoperable, standardized technologies and delivery of context-sensitive information to substantially improve the quality of care patients receive within pediatric palliative care clinics and other settings.

Development of palliative-care services in a developing country: Pakistan.

Palliative care services are poorly developed in most resource-poor countries. With the increase in the number of cancer cases being diagnosed in these countries, most of whom present in advanced stages, an urgent need for palliative care is emerging. Pakistan is an example of a resource-poor country where palliative care services are in the initial phase of development.

Acute promyelocytic leukemia following chemotherapy for EBV-associated hemophagocytic lymphohistiocytosis.

We report a case of chemotherapy-related acute promyelocytic leukemia (APL) following therapy with VP-16/etoposide for EBV-associated hemophagocytic lymphohistiocytosis (HLH). A 17-month-old male presented with fever and lymphadenopathy. Bone marrow and liver biopsies showed hemophagocytosis. He responded well to chemotherapy including dexamethasone, VP-16/etoposide, and cyclosporine. One and a half year later, he developed fever and pancytopenia. Clinical work-up revealed APL with t(15;17)(q22;q12);PML-RARα translocation. He underwent chemotherapy for APL and is in remission 8 years after diagnosis. Alternative non-leukemogenic agents to effectively treat HLH would be desirable.

Improving short-term sun safety practices among adolescent survivors of childhood cancer: a randomized controlled efficacy trial.

INTRODUCTION: Skin cancer is one of the most common secondary neoplasms among childhood cancer survivors. However, little evidence exists for effective interventions to promote sun safety behaviors within this population. METHODS: This small-scale randomized controlled trial examined the efficacy of the Survivor Health and Resilience Education (SHARE) Program intervention, a multiple health behavior change intervention designed to increase sun safety practices among adolescent survivors of childhood cancer. Adolescent survivors of childhood cancer (11-21 years) were randomly allocated to a group-based behavioral intervention (n = 38) or wait-list control (n = 37). Self-reported sun safety behaviors were assessed using a valid, 8-item scale at baseline and 1-month post-intervention. RESULTS: Controlling for baseline sun safety, gender, and seasonal influences, intervention participants reported significantly more sun safety practices (e.g., using sunscreen, reapplying sunscreen regularly) at 1-month post-intervention than control participants (B = 2.64, 95% CI = 1.02, 4.27, p = 0.002). CONCLUSIONS: The results suggest that SHARE was efficacious in producing improvements in short-term self-reported sun safety practices among adolescent survivors of childhood cancer. Future research is needed to build upon this work by incorporating objective measures of sun safety behaviors and examining intervention durability. IMPLICATIONS FOR CANCER SURVIVORS: Behavioral interventions addressing lifestyle factors, including sun safety behaviors, among adolescent survivors of childhood cancer should be integrated into long-term care to reduce the risk for secondary malignancies and diseases.