Explanatory models in real-world clinical interactions at a pediatric cancer center in Guatemala.

Explanatory models (EMs) are used in medical anthropology to characterize individual understandings of illness. This study investigated how interdisciplinary clinical interactions elicited caregiver EMs at a pediatric cancer center in Guatemala. This qualitative study included caregivers of 20 children with newly diagnosed cancer at Unidad Nacional de Oncología Pediátrica (UNOP) in Guatemala City, Guatemala. UNOP's diagnostic process includes social work intake, psychoeducation with a psychologist, and a diagnostic conversation with an oncologist and psychologist. Audio-recordings from the diagnostic process and a semi-structured interview were obtained, transcribed, and translated from Spanish. Transcripts were coded using a priori codes based on the five explanatory model (EM) components (occurrence, causation, pathophysiology, course of sickness, and treatment), as well as disease, and illness accounts. Thematic content analysis explored the EM framework as applied to diagnostic interactions between families and clinicians. All five components of the EM were addressed during the diagnostic process at UNOP. Clinicians, particularly psychologists, initiated conversation about the EM more than caregivers. When prompted, caregivers discussed all aspects of the EM but only rarely mentioned pathophysiology. Disease accounts were primarily described by clinicians, while caregivers used illness accounts to describe cancer causation. Clinicians validated existence of both disease and illness accounts. UNOP's interdisciplinary team elicited families' beliefs and facilitated in-depth discussion of all aspects of the EM, leading to a shared understanding of cancer and its treatment. Utilizing the EM framework in clinical practice may support culturally-competent pediatric cancer care.

Retrospective comparative analysis of two medical evacuation systems for Ukrainian patients affected by war.

INTRODUCTION: Coordinated medical evacuations represent an important strategy for emergency response when healthcare systems are impaired by armed conflict, particularly for patients diagnosed with life-threatening conditions such as cancer. In this study, we compare the experiences of two parallel medical evacuation systems developed to meet the medical needs of Ukrainians affected by war. METHODS: This retrospective study compared outcomes of two medical evacuation systems, developed by the European Union Emergency Response Coordination Centre (ERCC) and Supporting Action for Emergency Response in Ukraine (SAFER Ukraine) collaborative, in the first 10 months after the war's intensification in Ukraine (February 24 to December 21, 2022). Each groups' respective registries served as data sources. Patient demographics and allocation data were summarized descriptively. Median time for patient referral were analyzed statistically. RESULTS: The ERCC pathway evacuated 1385 patients (median age: 36 [0 - 85] years) to 16 European countries; 78.7 % (n = 1091) suffered from trauma-related injuries and 13.4 % (n = 185) from cancer. SAFER Ukraine evacuated 550 patients (median age: 9 [0 - 22] years) to 14 European and North American countries; 97.1 % (n = 534) were children diagnosed with cancer or blood disorders. The median evacuation time for the SAFER Ukraine cohort was shorter than the ERCC cohort (p < 0.001), though comparable (six versus seven days). CONCLUSION: The ERCC and SAFER Ukraine collaborative successfully developed medical evacuation pathways to meet the needs of Ukrainian patients impacted by war. System comparison provides opportunity to identify strategies for parallel system harmonization and a pragmatic example of how to anticipate support of these patients in future armed conflicts.

Pediatric Adrenocortical Carcinoma: The Nuts and Bolts of Diagnosis and Treatment and Avenues for Future Discovery.

Adrenocortical tumors (ACTs) are infrequent neoplasms in children and adolescents and are typically associated with clinical symptoms reflective of androgen overproduction. Pediatric ACTs typically occur in the context of a germline TP53 mutation, can be cured when diagnosed at an early stage, but are difficult to treat when advanced or associated with concurrent TP53 and ATRX alterations. Recent work has demonstrated DNA methylation patterns suggestive of prognostic significance. While current treatment standards rely heavily upon surgical resection, chemotherapy, and hormonal modulation, small cohort studies suggest promise for multi-tyrosine kinases targeting anti-angiogenic pathways or immunomodulatory therapies. Future work will focus on novel risk stratification algorithms and combination therapies intended to mitigate toxicity for patients with perceived low-risk disease while intensifying therapy or accelerating discoveries aimed at improving survival for patients with difficult-to-treat disease.

Functions of patient- and family-centered pediatric cancer communication in Pakistan.

Background: Communication is an essential aspect of high-quality patient- and family-centered care. A model for pediatric cancer communication developed in the United States defined eight communication functions. The purpose of this study was to explore the relevance of these functions in Pakistan as part of an effort to understand the role of culture in communication. Materials and methods: Semi-structured interviews were conducted with 20 clinicians and 18 caregivers of children with cancer at two major cancer centers. Interviews were conducted in Urdu or English and transcribed and translated as necessary. Two independent coders used a priori codes related to the communication model as well as novel codes derived inductively. Thematic analysis focused on operationalization of the functional communication model. Results: Clinicians and caregivers in Pakistan discussed the importance of all eight communication functions previously identified including: information exchange, decision-making, managing uncertainty, enabling family self-management, responding to emotions, supporting hope, providing validation, and building relationships. The operationalization of these functions was influenced by Pakistani cultural context. For example, information-exchange included the importance of addressing preconceptions and community myths, while managing uncertainty included strong references to religion and faith-based coping. Essential to all eight functions was trust between the family and the medical team. Discussion: These findings support the use of this functional communication model in diverse pediatric oncology settings and emphasize the importance of trust. Culturally sensitive operationalization of these functions could inform the adaptation of tools to measure communication and interventions aimed at supporting the needs of parents of children with cancer.

Parent-provider communication dynamics during the pediatric oncology diagnostic process in Guatemala: A qualitative study.

BACKGROUND: Effective communication is founded on bidirectional participation from families and healthcare providers. In adult medicine, bidirectional communication promotes treatment adherence and builds the family-provider relationship. However, the relationship between communication styles in pediatrics remains poorly understood, particularly in culturally diverse settings. This study aims to investigate parent-provider communication dynamics and parental involvement during diagnostic cancer communication in Guatemala. PROCEDURE: This qualitative study included 20 families of children with cancer and 10 providers at Unidad Nacional de Oncología Pediátrica in Guatemala. Psychoeducation and diagnostic conversations between parents, psychologists, and oncologists were recorded and thematically analyzed using a priori and novel codes exploring communication behaviors, parental engagement, and interpersonal dynamics. RESULTS: Participating parents had children with various diagnoses. Only 15% of fathers and 5% of mothers reported education beyond primary school. Providers spoke 68% of words during psychoeducation and 85% of words during diagnosis conversations. Providers used supportive communication behaviors providing explanations, demonstrating verbal attentiveness, and soliciting questions and non-supportive behaviors including paternalistic talk. Parental participation was considered active when they asked questions, expressed hopes or concerns, or asserted their opinions, and non-active when participation was limited to brief responses to closed-ended questions. Supportive provider communication often encouraged active participation; non-supportive communication did not. Furthermore, active parental participation prompted supportive communication from providers, while non-active participation did not. CONCLUSIONS: Our findings highlight the bidirectional nature of effective communication, establishing that provider communication styles both influence and are influenced by parental participation, and emphasizing the importance of supportive provider communication for patient-centered care.

Impact of a Regional Pediatric Hematology/Oncology Fellowship Program in Guatemala.

PURPOSE: This study aimed to describe and assess the regional experience of a pediatric hematology/oncology fellowship program based in Guatemala. METHODS: The Unidad Nacional de Oncología Pediátrica (UNOP) in Guatemala City, Guatemala, is the only hospital in Central America dedicated exclusively to childhood and adolescent cancer. To address the regional need for specialists, a fellowship program in pediatric hematology/oncology was launched in 2003. The UNOP fellowship program comprises 3 years of training. Although the program is based at UNOP, it also includes rotations locally and internationally to enhance clinical exposure. The curriculum is based on international standards to cover clinical expertise, research, professionalism, communication, and health advocacy. Trainees are selected according to country or facility-level need for pediatric hematologists/oncologists, with a plan for them to be hired immediately after completing their training. RESULTS: Forty physicians from 10 countries in Latin America have completed training. In addition, there are currently 13 fellows from five countries in training. Of the graduates, 39 (98%) are now practicing in pediatric hematology/oncology in Latin America. Moreover, many of them have leadership positions within their institutions and participate in research, advocacy, and policy making. Graduates from the UNOP program contribute to institutions by providing care for an increasing number of patients with pediatric cancer. The UNOP program is the first pediatric hematology/oncology fellowship program in the world to be accredited by Accreditation Council for Graduate Medical Education-International, an international body accrediting clinical training programs. CONCLUSION: The UNOP program has trained specialists to increase the available care for children with cancer in Latin America. This regional approach to specialist training can maximize resources and serve as a model for other programs and regions.

Stigma in Pediatric Cancer: An Exploratory Study of Osteosarcoma and Retinoblastoma in Guatemala, Jordan, and Zimbabwe.

PURPOSE: Stigma is an understudied barrier to health care acceptance in pediatric oncology. We sought to explore the stigma experience, including its impact on cancer treatment decision making, and identify strategies to mitigate stigma for patients with osteosarcoma and retinoblastoma in Guatemala, Jordan, and Zimbabwe. METHODS: Participants included caregivers, adolescent patients (age 12-19 years), and health care clinicians. A semistructured interview guide based on The Health Stigma and Discrimination Framework (HSDF) was adapted for use at each site. Interviews were conducted in English, Spanish, Arabic, or Shona, audio-recorded, translated, and transcribed. Thematic analysis focused on stigma practices, experiences, outcomes, drivers, mitigators, and interventions. RESULTS: We conducted 56 interviews (28 caregivers, 19 health care clinicians, nine patients; 20 in Guatemala, 21 in Jordan, 15 in Zimbabwe). Major themes were organized into categories used to adapt the HSDF to global pediatric cancer care. Themes were described similarly across all sites, ages, and diagnoses, with specific cultural nuances noted. Pediatric cancer stigma was depicted as an isolating and emotional experience beginning at diagnosis and including internalized and associative stigma. Stigma affected decision making and contributed to negative outcomes including delayed diagnosis, treatment abandonment, regret, and psychosocial fragility. Overcoming stigma led to positive outcomes including resilience, treatment adherence, pride, and advocacy. Identified stigma drivers and mitigators were linked to potential interventions. CONCLUSION: Participants describe a shared stigma experience that transcends geography, cultural context, age, and diagnosis. Stigma manifestations have the potential to impact medical decision making and affect long-term psychological outcomes. Stigma assessment tools and interventions aimed at stigma mitigation including educational initiatives and support groups specific to pediatric cancer should be the focus of future research.

Unification of Efforts to Improve Global Access to Cancer Therapeutics: Report From the 2022/2023 Access to Essential Cancer Medicines Stakeholder Summit.

PURPOSE: There is an urgent need to improve access to cancer therapy globally. Several independent initiatives have been undertaken to improve access to cancer medicines, and additional new initiatives are in development. Improved sharing of experiences and increased collaboration are needed to achieve substantial improvements in global access to essential oncology medicines. METHODS: The inaugural Access to Essential Cancer Medicines Stakeholder Meeting was organized by ASCO and convened at the June 2022 ASCO Annual Meeting in Chicago, IL, with two subsequent meetings, Union for International Cancer Control World Cancer Congress held in Geneva, Switzerland, in October 2022 and at the ASCO Annual Meeting in June of 2023. Invited stakeholders included representatives from cancer institutes, physicians, researchers, professional societies, the pharmaceutical industry, patient advocacy organizations, funders, cancer organizations and foundations, policy makers, and regulatory bodies. The session was moderated by ASCO. Past efforts and current and upcoming initiatives were initially discussed (2022), updates on progress were provided (2023), and broad agreement on resulting action steps was achieved with participants. RESULTS: Summit participants recognized that while much work was ongoing to enhance access to cancer therapeutics globally, communication and synergy across projects and organizations could be enhanced by providing a platform for collaboration and shared expertise. CONCLUSION: The summit resulted in new cross-stakeholder insights and planned collaboration addressing barriers to accessing cancer medications. Specific actions and timelines for implementation and reporting were established.

The transformation of Cure4Kids: Expanding knowledge transfer capacity.

Global survival disparities among children with cancer and other catastrophic diseases are the driving force behind Cure4Kids' sustained outreach to healthcare professionals. Congruent with this need, Cure4Kids was redesigned to meet the emergent demands of diverse healthcare professionals seeking free, web-based pediatric hematology/oncology education. Herein, we present an overview of each phase of the design and development process for the transformation and describe key features of the new Cure4Kids and future opportunities for expansion.

Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series.

BACKGROUND: Paediatric hepatocellular carcinomas (HCC) traditionally arise in the context of a normal structural and functional liver and carry a dismal prognosis. While chemotherapy is the frontline standard, there is emerging interest in the study of immunotherapies for paediatric patients with relapsed/refractory disease. There is limited data to support whether immunotherapies will be of utility in this patient population. METHODS: Six paediatric patients (median age:16 years, range: 12-17 at the time of treatment) with advanced hepatocellular neosplams, either conventional hepatocellular or fibrolamellar carcinoma, were treated with immunotherapy. Patients were consented to institutional genomic profiling and biobanking protocols. Baseline samples and serial tissue samples, when available, were evaluated for somatic mutation rate, actionable gene mutations, and pan-immune bulk RNA expression profiling. Results were correlated with clinical course. FINDINGS: Three patients responded to checkpoint inhibition: one achieved a complete, durable response and the other two, prolonged stable disease. Three additional patients progressed. Diagnostic tissue from the complete responder demonstrated a higher relative mutational burden and robust immune infiltrate. Pre-treatment samples from the three responders demonstrated decreased expression of genes associated with T-cell dysfunction. INTERPRETATION: A subset of patients with primary paediatric hepatocellular tumours will respond to immunotherapy. Immunotherapies are currently under prospective study for relapsed/refractory liver tumours in paediatric patients. Results from this report support the prospective collection of serial serum and tissue samples which may further identify genomic and immunophenotypic patterns predictive of response. FUNDING: This work was supported by Philanthropic funds (Pan Mass Challenge, Team Angus and Team Perspective).

Langerhans cell histiocytosis: NACHO update on progress, chaos, and opportunity on the path to rational cures.

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by lesions with CD1a-positive/Langerin (CD207)-positive histiocytes and inflammatory infiltrate that can cause local tissue damage and systemic inflammation. Clinical presentations range from single lesions with minimal impact to life-threatening disseminated disease. Therapy for systemic LCH has been established through serial trials empirically testing different chemotherapy agents and durations of therapy. However, fewer than 50% of patients who have disseminated disease are cured with the current standard-of-care vinblastine/prednisone/(mercaptopurine), and treatment failure is associated with long-term morbidity, including the risk of LCH-associated neurodegeneration. Historically, the nature of LCH-whether a reactive condition versus a neoplastic/malignant condition-was uncertain. Over the past 15 years, seminal discoveries have broadly defined LCH pathogenesis; specifically, activating mitogen-activated protein kinase pathway mutations (most frequently, BRAFV600E) in myeloid precursors drive lesion formation. LCH therefore is a clonal neoplastic disorder, although secondary inflammatory features contribute to the disease. These paradigm-changing insights offer a promise of rational cures for patients based on individual mutations, clonal reservoirs, and extent of disease. However, the pace of clinical trial development behind lags the kinetics of translational discovery. In this review, the authors discuss the current understanding of LCH biology, clinical characteristics, therapeutic strategies, and opportunities to improve outcomes for every patient through coordinated agent prioritization and clinical trial efforts.

Identification and characterization of stromal-like cells with CD207+/low CD1a+/low phenotype derived from histiocytic lesions - a perspective in vitro model for drug testing.

BACKGROUND: Histiocytoses are rare disorders manifested by increased proliferation of pathogenic myeloid cells sharing histological features with macrophages or dendritic cells and accumulating in various organs, i.a., bone and skin. Pre-clinical in vitro models that could be used to determine molecular pathways of the disease are limited, hence research on histiocytoses is challenging. The current study compares cytophysiological features of progenitor, stromal-like cells derived from histiocytic lesions (sl-pHCs) of three pediatric patients with different histiocytoses types and outcomes. The characterized cells may find potential applications in drug testing. METHODS: Molecular phenotype of the cells, i.e. expression of CD1a and CD207 (langerin), was determined using flow cytometry. Cytogenetic analysis included GTG-banded metaphases and microarray (aCGH) evaluation. Furthermore, the morphology and ultrastructure of cells were evaluated using a confocal and scanning electron microscope. The microphotographs from the confocal imaging were used to reconstruct the mitochondrial network and its morphology. Basic cytophysiological parameters, such as viability, mitochondrial activity, and proliferation, were analyzed using multiple cellular assays, including Annexin V/7-AAD staining, mitopotential analysis, BrdU test, clonogenicity analysis, and distribution of cells within the cell cycle. Biomarkers potentially associated with histiocytoses progression were determined using RT-qPCR at mRNA, miRNA and lncRNA levels. Intracellular accumulation of histiocytosis-specific proteins was detected with Western blot. Cytotoxicyty and IC50 of vemurafenib and trametinib were determined with MTS assay. RESULTS: Obtained cellular models, i.e. RAB-1, HAN-1, and CHR-1, are heterogenic in terms of molecular phenotype and morphology. The cells express CD1a/CD207 markers characteristic for dendritic cells, but also show intracellular accumulation of markers characteristic for cells of mesenchymal origin, i.e. vimentin (VIM) and osteopontin (OPN). In subsequent cultures, cells remain viable and metabolically active, and the mitochondrial network is well developed, with some distinctive morphotypes noted in each cell line. Cell-specific transcriptome profile was noted, providing information on potential new biomarkers (non-coding RNAs) with diagnostic and prognostic features. The cells showed different sensitivity to vemurafenib and trametinib. CONCLUSION: Obtained and characterized cellular models of stromal-like cells derived from histiocytic lesions can be used for studies on histiocytosis biology and drug testing.

Multiple TP53 p.R337H haplotypes and implications for tumor susceptibility.

The germline TP53 p.R337H mutation is reported as the most common germline TP53 variant. It exists at a remarkably high frequency in the population of southeast Brazil as founder mutation in two distinct haplotypes with the most frequent co-segregating with the p.E134∗ variant of the XAF1 tumor suppressor and an increased cancer risk. Founder mutations demonstrate linkage disequilibrium with neighboring genetic polymorphic markers that can be used to identify the founder variant in different geographic regions and diverse populations. We report here a shared haplotype among Brazilian, Portuguese, and Spanish families and the existence of three additional distinct TP53 p.R337H alleles. Mitochondrial DNA sequencing and Y-STR profiling of Brazilian carriers of the founder TP53 p.R337H allele reveal an excess of Native American haplogroups in maternal lineages and exclusively European haplogroups in paternal lineages, consistent with communities established through male European settlers with extensive intermarriage with Indigenous women. The identification of founder and independent TP53 p.R337H alleles underlines the importance for considering the haplotype as a functional unit and the additive effects of constitutive polymorphisms and associated variants in modifier genes that can influence the cancer phenotype.

A regional virtual case discussion forum in pediatric oncology: Experience of the Pediatric Oncology East and Mediterranean Group.

BACKGROUND: The Pediatric Oncology East and Mediterranean (POEM) group that aims to share expertise among pediatric oncology providers across the Middle East, North Africa, and East Asia region initiated a virtual Case Discussion Forum (CDF) in 2013. METHODS: Meeting records from September 2013 till June 2021 were reviewed. Detailed minutes were available starting August 2016; case data were analyzed including diagnoses, purpose of presentation and recommendations. A 38-item survey assessing perception of benefits, challenges, and opportunities of the forum was distributed to members of the POEM group and results analyzed. RESULTS: A total of 140 cases were presented from 14 countries. After August 2016, 67 cases were presented, and those were analyzed regarding reasons for discussion, barriers, and recommendations. Details are presented in this report, and the most common challenges identified were related to histopathologic/molecular diagnosis (24%), imaging interpretation (18%), resource limitations (12%), and surgical difficulties (9%). A survey was distributed to all POEM members in 28 countries, and 76 responded. The main benefit reported was the provision of recommendations regarding treatment and evaluation, while the main challenges reported were time zone difference and workload. Recognized opportunities included conducting regionally relevant research studies based on clinical problems identified during discussions, and setting guidelines for resource-adapted treatment regimens. CONCLUSIONS: The POEM CDF identified areas for multi-institutional regional studies and led to a twinning project between two centers in the region for improving diagnostic infrastructure. Such forums can identify specific resource limitations in pediatric cancer and direct efforts for targeted capacity building.

A multi-institutional feasibility study of intra-arterial chemotherapy in children with retinoblastoma. A Children's Oncology Group study (COG ARET12P1).

BACKGROUND: Intra-arterial chemotherapy (IA) as a treatment to salvage the eye with advanced retinoblastoma is increasingly utilized based on successes reported by institutions around the world mainly through retrospective studies. OBJECTIVE: To study the feasibility of delivering melphalan directly into the ophthalmic artery in a multi-institutional prospective study in children with newly diagnosed unilateral group D retinoblastoma. METHODS: The Children's Oncology Group (COG) initiated study ARET12P1 in 2014 and was open to nine institutions. Eligible patients older than six months of age were enrolled. The feasibility of delivering three injections of melphalan into the ophthalmic artery every 28 days was assessed. RESULTS: Nine institutions participated in this trial. Fourteen patients were enrolled, two of whom were unevaluable for feasibility. Four patients experienced a feasibility failure. In two patients, the ophthalmic artery could not be accessed for the second IA injection, in one the artery could not be accessed for the first injection, and one patient experienced grade 4 hypotension during the procedure. CONCLUSION: Delivery of prescribed therapy within the context of this study did not meet the feasibility goals of the study with only a 67% feasibility success rate. These results should caution centers that plan to initiate this treatment and suggest investment in training to achieve technical expertise or referral to centers with expertise.

Barriers and Facilitators of Quality Family-Centered Communication in Pakistan.

PURPOSE: Communication is a fundamental aspect of patient- and family-centered care. Unfortunately, there is a dearth of evidence regarding pediatric cancer communication in low- and middle-income countries, where over 90% of all children with childhood cancer live. The purpose of this study was to explore barriers and facilitators of quality communication within two pediatric cancer centers in Pakistan. METHODS: Semistructured interviews were conducted with 20 multidisciplinary pediatric cancer clinicians and 18 caregivers of children with cancer at Children's Hospital of Lahore and Indus Hospital in Karachi, Pakistan. Interviews were conducted in English or Urdu, audio-recorded, transcribed, and translated to English. Two researchers coded each transcript using an inductively derived codebook. Thematic content analysis focused on barriers and facilitators of high-quality communication. RESULTS: Pakistani clinicians and caregivers identified factors that affected the quality of patient-centered cancer communication. These included structural factors including setting, available interpreters, documentation, patient volume, teamwork, and financial support. Clinician-level communication barriers and facilitators included communication training, clinician distress/boundaries, and the ability to have recurrent conversations. Patient or family characteristics affecting communication included education, income status, primary language, and geography; the child's specific disease type; and relational elements such as social support, empowerment, and split decision makers. Participants identified existing or potential interventions related to each factor. CONCLUSION: Multilevel factors serve as either barriers or facilitators for pediatric cancer communication in Pakistan. Identification of these elements of communication is an essential step toward interventions aimed at improving patient- and family-centered care in resource limited settings.

Rare Tumors: Opportunities and challenges from the Children's Oncology Group perspective.

While all childhood cancers are rare, tumors that are particularly infrequent or underrepresented within pediatrics are studied under the umbrella of the Children's Oncology Group Rare Tumor committee, divided into the Retinoblastoma and Infrequent Tumor subcommittees. The Infrequent Tumor subcommittee has traditionally included an emphasis on globally rare tumors such as adrenocortical carcinoma, nasopharyngeal carcinoma, or those tumors that are rare in young children, despite being common in adolescents and young adults, such as colorectal carcinoma, thyroid carcinoma, and melanoma. Pleuropulmonary blastoma, gonadal stromal tumors, pancreatic tumors including pancreatoblastoma, gastrointestinal stromal tumor, nonmelanoma skin cancers, neuroendocrine tumors, and desmoplastic small round cell tumors, as well as other carcinomas are also included under the heading of the Children's Oncology Group Rare Tumor committee. While substantial challenges exist in rare cancers, inclusion and global collaboration remain key priorities to ensure high quality research to advance care.