Strengthening access to cancer medicines for children in East Africa: policy options to enhance medicine procurement, forecasting, and regulations.

Gaps in access to quality essential medicines remain a major impediment to the effective care of children with cancer in low-and middle-income countries (LMICs). The World Health Organization reports that less than 30% of LMICs have consistent availability of childhood cancer medicines, compared to over 95% in high-income countries. Information provided within this policy brief is drawn from a review of the literature and a mixed-methods study published in the Lancet Oncology that analyzed determinants of cancer medicine access for children in Kenya, Tanzania, Uganda, and Rwanda. Three key policy options are presented to guide strategic policy direction and critical health system planning for strengthening access to cancer medicines for children: pooled procurement, evidence-based forecasting, and regional harmonization of regulatory processes. Enhancing regional pooled procurement to address fragmented markets and improve medicine supply, investing in health information systems for improved forecasting and planning of childhood cancer medicine needs, and promoting regulatory harmonization to streamline medicine approval and quality assurance across East Africa are recommended. This policy brief is intended for policymakers, clinicians, and health-system planners involved in the procurement, supply chain management, policy and financing of childhood cancer medicines.

Inequities in childhood cancer research: A scoping review.

An integral part of understanding and then designing programs to reduce childhood cancer inequities includes adequate representation of people with cancer in research, including children. A scoping review was carried out to understand how cancer research is oriented toward inequities and to identify who has participated in childhood qualitative cancer research. A systematic search identified 119 qualitative studies that met inclusion criteria, with most studies taking place in high-income countries (n=84). Overall, data were lacking on social determinants of health at multiple levels-structural, household, child, and guardian. Only 29 studies reported on race and/or ethnicity, with the majority of those including predominantly or all white children. Six articles included socioeconomic information, and across most articles, attention was absent to the financial ramifications of cancer care. Limited reporting of sociodemographics highlights a broader issue of neglecting key demographics and social factors that contribute to inequities.

Incorporation of patient-reported outcomes in early-phase clinical trials for childhood and adolescent cancer.

INTRODUCTION: The assessment of quality of life (QoL) should be one of the main objectives in paediatric clinical trials. Even though researchers, regulators and advocates support the use of patient-reported outcomes (PROs), this has not been fully implemented. The aim of this study is to assess the measurement of QoL and the usage of PROs, palatability assessments and medication diaries in early-phase clinical trials for childhood and adolescent cancer. METHODS: Early-phase clinical trials for children and adolescents with cancer opened between 2005 and 2022 at the Royal Marsden Hospital (London, UK) and Vall d'Hebron University Hospital (Barcelona, Spain) were interrogated for trial characteristics and the use of QoL questionnaires, PROs, palatability assessments and medication diaries. RESULTS: Overall, 72 clinical trials were analysed: 12 (16.7%) evaluated QoL and eight (11.1%) evaluated PROs. Palatability was tested in 21/40 (52.5%) trials of oral drugs and 23/72 (31.9%) incorporated medication diaries. No studies mentioned patient involvement in the trial protocol. Use of PROs increased from one of 36 (2.8%) to seven of 36 (19.4%) between the first period (2005-2016) and the second period (2017-2022) (p = .02). Implementation of medication diaries increased from seven of 36 (19.4%) to 16/36 (44.4%) in each period, respectively (p = .02). CONCLUSION: Only a minor proportion of the international/multicentric early-phase trials evaluated included QoL/PROs and medication diaries or palatability questionnaires to help assess these, although this trend seems to be increasing over recent years. Greater implementation of QoL/PROs has the potential to improve the patient's wellbeing and facilitate symptom control, to enhance patient/parent involvement in future trial designs and to provide information for drug prioritisation.

Ovarian function in female survivors of high-risk neuroblastoma.

INTRODUCTION: Data on ovarian function in neuroblastoma survivors are limited. We sought to determine the prevalence of ovarian dysfunction in a cohort of high-risk neuroblastoma survivors and compare outcomes among survivors treated with and without autologous stem cell rescue (ASCR) preceded by myeloablative chemotherapy. METHODS: Retrospective review of female survivors of high-risk neuroblastoma ≥5 years from diagnosis, diagnosed between 1982 and 2014, and followed in a tertiary cancer center. Participants were divided into two groups: individuals treated with conventional chemotherapy ± radiation ("non-ASCR") (n = 32) or with chemotherapy ± radiation followed by myeloablative chemotherapy with ASCR ("ASCR") (n = 51). Ovarian dysfunction was defined as follicle-stimulating hormone ≥15 mU/mL, while premature ovarian insufficiency (POI) was defined as persistent ovarian dysfunction requiring hormone replacement therapy. Poisson models were used to determine prevalence ratios of ovarian dysfunction and POI. RESULTS: Among 83 females (median attained age: 19 years [range, 10-36]; median follow-up: 15 years [range, 7-36]), 49 (59%) had ovarian dysfunction, and 34 (41%) developed POI. Survivors treated with ASCR were 3.2-fold more likely to develop ovarian dysfunction (95% CI: 1.8-6.0; p < 0.001) and 4.5-fold more likely to develop POI (95% CI: 1.7-11.7; p = 0.002) when compared with those treated with conventional chemotherapy, after adjusting for attained age. Two participants in the non-ASCR group and six in the ASCR group achieved at least one spontaneous pregnancy. DISCUSSION: Ovarian dysfunction is prevalent in female high-risk neuroblastoma survivors, especially after ASCR. Longitudinal follow-up of larger cohorts is needed to inform counseling about the risk of impaired ovarian function after neuroblastoma therapy.

Neurocognitive outcomes and functional independence in adult survivors of childhood medulloblastoma diagnosed over three decades.

BACKGROUND: Treatment of childhood medulloblastoma has evolved to reduce neurotoxicity while improving survival. However, the impact of evolving therapies on late neurocognitive outcomes and adult functional independence remains unknown. METHODS: Adult survivors of childhood medulloblastoma (n=505; median[minimum-maximum] age, 29[18-46] years) and sibling controls (n=727; 32[18-58] years) from the Childhood Cancer Survivor Study completed surveys assessing neurocognitive problems and chronic health conditions (CHCs). Treatment exposures were categorized as historical (craniospinal irradiation [CSI]≥30 Gy, no chemotherapy), standard-risk (CSI>0 to <30 Gy +chemotherapy) and high-risk (CSI≥30 Gy +chemotherapy) therapy. Latent class analysis identified patterns of functional independence using employment, independent living, assistance with routine/personal care needs, driver's license, marital/partner status. Multivariable models estimated risk of neurocognitive impairment in survivors versus siblings and by treatment exposure group, and associations between neurocognitive impairment, CHCs, and functional independence. RESULTS: Survivors in each treatment exposure group had 4- to 5-fold elevated risk of impaired memory and task efficiency compared to siblings. Contemporary risk-based therapies did not confer lower risk compared to historical therapy. Survivors treated in the 1990s had higher risk of memory impairment (relative risk [RR] 2.24, 95% confidence interval [CI] 1.39-3.60) compared to survivors treated in the 1970s. Sensorimotor, hearing problems and seizures were associated with 33%-34%, 25-26% and 21%-42% elevated risk of task efficiency and memory impairment, respectively. Treatment-related CHCs and neurocognitive impairment were associated with non-independence. CONCLUSIONS: Despite treatment changes, long-term survivors of childhood medulloblastoma remain at risk for neurocognitive impairment, which was associated with CHCs. Neurocognitive surveillance after contemporary regimens is imperative.

Investigating and quantifying obsessive-compulsive and related disorders among childhood cancer survivors: a brief report.

OBJECTIVE: Long-term psychological impacts are well--documented among childhood cancer survivors. To our knowledge, however, no research has been conducted to investigate obsessive--compulsive and related disorders (OCRD) among childhood -cancer survivors (CCS). METHODS: Using a large electronic medical record database, relative risk were calculated to examine associations between demographic characteristics and childhood cancer type and OCRDs among childhood cancer survivors. RESULTS: Among 121 survivors of childhood cancer diagnosed with OCRD, 57% were female. The most common childhood cancer diagnoses were leukemia/lymphoma (41%) and central nervous system (CNS) malignancies (38%), and OCRD diagnoses most frequently observed were obsessive-compulsive disorder (OCD; 76%) and excoriation disorder (13%). Female sex (RR= 1.39, 95% confidence interval (CI) 1.17-1.61), White race (RR= 1.28, 95% CI 1.15-1.36) and history of CNS malignancies (RR= 1.36, 95% CI 1.18, 1.92) were associated with OCD. CONCLUSIONS: Numerous factors, including sex, race, and cancer type, were seen as contributors to risk variance for OCRDs, particularly OCD, among CCS, compared to CCS with no OCRD diagnosis. This provides an enhanced understanding of risk factors for OCRD development and may help improve early identification and care for at-risk survivors.

Profile and Outcomes of Pediatric Hematology and Oncology Patients Diagnosed with COVID-19 in the Philippine General Hospital.

Introduction: The coronavirus pandemic has affected millions worldwide. Better understanding of COVID-19 in pediatric hematology-oncology patients in a resource-limited setting is crucial to improve care as the pandemic ensues. Objectives: This study describes the clinical profile and outcomes of pediatric hematology oncology patients with COVID-19 seen at the Philippine General Hospital (PGH). Methods: A retrospective, descriptive review of pediatric hematology oncology patients with COVID-19 seen between March 2020 to March 2021 in PGH was done. Results: Forty patients were identified. Seventeen percent had non-malignant hematologic conditions, 40% had leukemias, and 42.5% had solid tumors. Fever and cough were the most common manifestations. Seventy-six percent were on treatment, 9% were newly diagnosed, and 7% were in relapse or disease progression. Fifty-five percent had mild COVID-19; 5% and 2.5% had severe and critical COVID-19, respectively. Thirty-seven percent were asymptomatic. Cancer-related therapy was placed on hold for most patients. There were two mortalities, none was due to COVID-19. Conclusion: Results suggest that patients with hematologic and oncologic conditions have a mild course, with majority showing recovery from COVID-19. Delays in cancer-related therapy however, may contribute to disease progression and mortality.

Safety of intravitreal chemotherapy in the management of retinoblastoma: A systematic review of the literature.

Intravitreal chemotherapy is used as a salvage therapy for retinoblastoma with persistent or recurrent vitreous seeding after primary treatment. To assess the safety of this technique, we conducted a systematic review of all studies reporting ocular toxicity data. Forty-eight trials involving 2751 eyes were included. The most common complications were cataract, retinal toxicity, and vitreous hemorrhage. However, severe and permanent adverse events were limited, while the risk of extraocular dissemination, a significant concern, was practically eliminated through preventive techniques. Globe salvage rates ranged from 29 % to 100 %. In conclusion, intravitreal chemotherapy seems to improve prognosis of eyes with advanced disease, with an acceptable safety profile. Nevertheless, most relevant studies are retrospective, and no randomized trials have been performed. Recognizing the challenges regarding the conduct of randomized studies for such a rare pediatric cancer, we believe that multicenter trials through international collaborations can significantly enhance the available information.

The impact of clinically relevant health conditions on psychosocial outcomes in survivors of childhood cancer: results of the DCCSS-LATER study.

PURPOSE: Investigate the association between presence, number and type of clinically relevant health conditions and a range of psychosocial outcomes (emotional, social, cognitive, physical) in survivors of childhood cancer (CCS). METHODS: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed between 1963-2001, attained age ≥ 18, diagnosed < 18, ≥ 5 years since diagnosis) completed a questionnaire on health conditions (2013-2014), and questionnaires on psychosocial outcomes (2017-2020): Hospital Anxiety and Depression Scale, Short form 36, TNO-AZL Questionnaire for Adult Health-Related Quality of Life, and the Self-Rating Scale for Post-Traumatic Stress Disorder. Associations among health conditions and psychosocial outcomes were assessed with regression analysis, adjusting for attained age, sex, and time since diagnosis, and adjusting for multiple testing (p < 0.004). RESULTS: A total of 1437 CCS, mean age 36.3 years, 51.1% female, ≥ 15 years since diagnosis, completed questionnaires on health and psychosocial outcomes. CCS with a clinically relevant health condition, and those with more conditions had worse emotional, social, and physical outcomes; regression coefficients were small to moderate. CCS with gastro-intestinal conditions, endocrine, nervous systems, eye, or ear conditions, and especially those with secondary malignant neoplasms, reported worse psychosocial functioning; regression coefficients were small/moderate to large. CONCLUSION AND IMPLICATIONS: Health care professionals should be aware of the increased risk for psychosocial problems among CCS with health conditions, especially for survivors with secondary malignant neoplasms, gastro-intestinal, endocrine, nervous system, eye, and ear conditions. CCS may benefit from psychological interventions to develop coping strategies to manage health conditions and psychosocial consequences of the cancer trajectory.

Childhood Cancer Awareness Program in Bungoma County, Kenya.

BACKGROUND: Awareness could play a key role in reducing underdiagnosis and accelerating referral of childhood cancer in low- and middle-income countries and ultimately improve outcomes. This study describes the implementation of a childhood cancer awareness program in Bungoma County in Kenya, containing five components: (1) baseline data collection of primary healthcare facilities; (2) live training session for healthcare providers (HCP); (3) early warning signs posters; (4) online SMS course for HCP; and (5) radio campaign. METHODS: This study was conducted between January and June 2023. All 144 primary healthcare facilities (level 2 and 3 health facilities) within Bungoma County were visited by the field team. RESULTS: All 125 level 2 (87%) and 19 level 3 (13%) facilities participated in the study. National Health Insurance Fund (NHIF) failed to cover services in 37 (26%) facilities. HCP were more often reported absent at level 3 (89%) than level 2 (64%) facilities (P = 0.034). The 144 live training sessions were attended by over 2000 HCP. Distribution of 144 early warning signs posters resulted in 50 phone calls about suspected childhood cancer cases. Sixteen children were later confirmed with childhood cancer and treated. Online SMS learning was completed by 890 HCP. Knowledge mean scores improved between pre-test (7.1) and post-test (8.1; P < 0.001). Finally, 540 radio messages about childhood cancer and a live question-and-answer session were broadcasted. CONCLUSION: This study described the implementation of a childhood cancer awareness program in Kenya involving both HCP and the general public. The program improved HCP's knowledge and increased the number of referrals for children with cancer.

Prevention of cardiotoxicity in childhood cancer survivors: in physical exercise, we trust.

In recent years, the mean survival rate of children after a cancer diagnosis has significantly improved. At the same time, a growing interest in short and long-term cardiovascular (CV) complications of cancer therapy, as well as long-term CV risk in childhood cancer survivors (CCS) developed, along with proposals of protocols for the diagnosis, management, and prevention of cancer therapy-related CV toxicity (CTR-CVT) in this population. Many clinical and individual risk factors for CTR-CVT have been identified, and a non-negligible prevalence of traditional CV risk factors has been described in this population, potentially associated with a further worsening in both CTR-CVT and long-term CV risk. Physical exercise (PE) represents a promising, free-of-cost and free-of-complications, helpful therapy for primary and secondary prevention of CTR-CVT in CCS. The present narrative review aims to summarize the most critical evidence available about CTR-CVT in CCS, focusing on the role of PE in this clinical scenario.

Identifying causes of balance impairment and exploring sensory contributions to balance in pediatric oncology: A scoping review.

PURPOSE: To identify causes of balance impairment in children undergoing treatment for cancer and childhood cancer survivors. METHODS: A systematic search was performed according to PRISMA guidelines. Studies were included if participants were 0-19 years of age with a current/past diagnosis of cancer, an objective balance measure was reported, and a cause of balance impairment was either stated or implied. RESULTS: The 64 full text studies included identified balance impairments as sequelae secondary to CNS tumors, and/or as an effect of medical treatment including chemotherapy, radiation, and/or surgery. Cancer treatment can result in damage to the visual, vestibular and/or somatosensory systems which in turn can contribute to balance dysfunction. CONCLUSIONS: Balance impairments were caused by the cancer itself or the result of medical treatment. Oncology professionals are integral in recognition and treatment of factors affecting balance impairments in childhood cancer; however, further research is needed to identify interventions targeting specific causes of balance impairment.

Targeting pediatric solid tumors in the new era of RNA therapeutics.

Despite substantial progress in pediatric cancer treatment, poor prognosis remained for patients with recurrent or metastatic disease, given the limitations of approved targeted treatments and immunotherapies. RNA therapeutics offer significant potential for addressing a broad spectrum of diseases, including cancer. Advances in manufacturing and delivery systems are paving the way for the rapid development of therapeutic RNAs for clinical applications. This review summarizes therapeutic RNA classifications and the mechanisms of action, highlighting their potential in manipulating major cancer-related pathways and biological effects. We also focus on the pre-clinical investigation of RNA molecules with efficient delivery systems for their therapeutic potential targeting pediatric solid tumors.

Children's voices on their values and moral dilemmas when being cared and treated for cancer- a qualitative interview study.

BACKGROUND: Childhood cancers affect about 350 children every year in Sweden and are life-threatening diseases. During the treatment period, situations arise that can become morally challenging for the child. When knowing children's values and morally challenging situations in childhood cancer care, targeted ethics support could be developed and used in care. AIM: To explore children's values and moral dilemmas ​​when undergoing cancer treatment. METHODS: This is a qualitative study based on empirical data. The data collection was conducted through three focus group interviews and six individual interviews with children between 10 and 18 years (n = 16). A content analysis methodology was used to generate themes. Children who were/have been treated for cancer at three childhood cancer centres in Sweden were invited to participate. The study was approved by the Swedish Ethical Review Authority. The children's participation was based on voluntariness and consent/assent. FINDINGS: During the analysis, five themes of values emerged: Personal relationships, Bodily ease and identity, Feeling in control and being involved, Positive distractions and Right care that is needed. Their moral dilemmas were thematized into: Should I consider others or not? Should I rest or not? and Should I refuse treatment or not? CONCLUSION: Children undergoing cancer treatment want to have personal relationships with healthcare professionals. Their moral dilemmas were about questioning their own physical and psychological well-being against their expectations, the values of others and the treatment required. Further research is needed to understand how to deal with moral dilemmas in children undergoing cancer treatment.

Profiles of Posttraumatic Growth and Posttraumatic Stress Symptoms in Childhood Cancer Survivors.

The experience of childhood cancer (CC) could be a traumatic event that produces long-term emotional responses such as posttraumatic stress symptoms (PTSS) and posttraumatic growth (PTG) in survivors. The relationship between both PTSS and PTG is not clear in CC survivors. Assessing challenges to core beliefs and rumination could give information regarding the different paths that lead to traumatic responses. Thus, this study aims to identify childhood cancer survivors' profiles from PTSS and PTG measures and to examine the pathways of relationships between PTSS and PTG, rumination, and challenge to core belief. Sixty-two CC survivors completed surveys on their childhood cancer experience, PTSS, PTG, challenge to core beliefs, and rumination. High PTG scores among childhood cancer survivors (Cluster 1), High PTSS scores among childhood cancer survivors (Cluster 2), and Childhood cancer survivors without changes (Cluster 3). Network analysis found that the challenge to core beliefs is the central point in the relationship between the variables, in a direct and positive relationship with PTG. We found an indirect path from challenge to core beliefs to PTSS, mediated by intrusive and deliberative ruminations. The combined findings suggested that there are different profiles related to trauma in CC survivors and the relationship between PTSS and PTG is mediated by the challenge to core beliefs and deliberative and intrusive rumination.

Nutritional status, body composition and diet quality in children with cancer.

During cancer treatment, nutritional status disorders such as malnutrition or obesity affect the tolerance of cancer treatment, quality of life, but also the pharmacokinetics of drugs. It is hypothesized that changes in fat and lean body mass can modify chemotherapy volume distribution, metabolism and clearance. In children with cancer, lean body mass decreases or remains low during treatment and fat mass increases. Body composition is influenced by the cancer itself, aggressive multimodal-therapies, changes in metabolism, unbalanced diet and reduced physical activity. Due to the side effects of treatment, including changes in the sense of taste and smell, nausea, vomiting, diarrhea, and stress, eating according to recommendation for macronutrients and micronutrients is difficult. Research indicates that throughout cancer treatment, the consumption of fruits, vegetables, and dairy products tends to be insufficient, whereas there is an elevated intake of sugar and unhealthy snacks. Children exhibit a preference for high-carbohydrate, salty, and strongly flavored products. This review revealed the importance of body composition and its changes during cancer treatment in children, as well as eating habits and diet quality.

Unveiling perspectives on the psychosocial impacts of childhood cancer survival on young adult survivors' reassimilation journey: A qualitative exploration.

Background: Approximately 82% of children with childhood cancer survive more than five years after diagnosis. Living as a cancer survivor elicits a new reality that can include psychosocial impacts. These psychosocial impacts interact collectively, especially regarding reassimilation, and are rarely explored. Objective: To explore the psychosocial impacts of surviving childhood cancer and reassimilation back into society in young adult survivors of childhood cancer. Methodology: Individual in-depth semi-structured interviews were conducted with childhood cancer survivors and explored psychosocial aspects associated with returning to work, school, and social environments after remission. Interpretive phenomenological analysis was conducted once interviews were manually transcribed. A group interview with survivors was held to discuss the study's findings and interpretation. Results: Individual interviews and the group interview revealed three major themes: outlook on reassimilating, outlook on coping, and outlook on cancer. Conclusions: This work is a first step to understanding how survivors' personal outlook on coping and healthcare system barriers play influential roles in reassimilation following cancer treatment. Survivors expressed the need for reliable survivorship information and improved communication with healthcare providers regarding what to expect, so they could feel prepared for life post-cancer. These aspects need to be explored more deeply through other qualitative studies.

Enhancing sibling support in oncology: Collaborative care for families facing cancer in young people.

Purpose: This study investigates the support systems and needs of siblings of young people with cancer, shedding light on the emotional and informational challenges siblings face. This topic area has had relatively little attention. Design and methods: Qualitative interviews were conducted, and thematic analysis was employed to gain in-depth insights into the experiences and perspectives of siblings. While the study's relatively small sample size and participant homogeneity are acknowledged limitations, the approach offers several strengths, including relevance and participant diversity across age cohorts. Results: The findings underscore the essential role of healthcare professionals, particularly nurses, in providing emotional and informational support to siblings. Family-centred care, psychosocial support, tailored interventions, and ongoing research and education are recommended to address the unique needs of siblings effectively. Conclusion: Overall, this study highlights the importance of recognizing and addressing the support needs of siblings in pediatric oncology care, emphasizing their role as a vital component of the family system and advocating for holistic support throughout the cancer journey and beyond.

Extracellular Vesicles for Childhood Cancer Liquid Biopsy.

Liquid biopsy involves the utilization of minimally invasive or noninvasive techniques to detect biomarkers in biofluids for disease diagnosis, monitoring, or guiding treatments. This approach is promising for the early diagnosis of childhood cancer, especially for brain tumors, where tissue biopsies are more challenging and cause late detection. Extracellular vesicles offer several characteristics that make them ideal resources for childhood cancer liquid biopsy. Extracellular vesicles are nanosized particles, primarily secreted by all cell types into body fluids such as blood and urine, and contain molecular cargos, i.e., lipids, proteins, and nucleic acids of original cells. Notably, the lipid bilayer-enclosed structure of extracellular vesicles protects their cargos from enzymatic degradation in the extracellular milieu. Proteins and nucleic acids of extracellular vesicles represent genetic alterations and molecular profiles of childhood cancer, thus serving as promising resources for precision medicine in cancer diagnosis, treatment monitoring, and prognosis prediction. This review evaluates the recent progress of extracellular vesicles as a liquid biopsy platform for various types of childhood cancer, discusses the mechanistic roles of molecular cargos in carcinogenesis and metastasis, and provides perspectives on extracellular vesicle-guided therapeutic intervention. Extracellular vesicle-based liquid biopsy for childhood cancer may ultimately contribute to improving patient outcomes.