Treatment Decision Making at Diagnosis for Children Presenting With Advanced Cancer in Low- and Middle-Income Countries.

INTRODUCTION

Treatment decision making is a core facet of high-quality pediatric cancer communication and integral to culturally adapted, patient-centered care. 1 - 3 At present, most research focused on clinical decision making in pediatrics and pediatric oncology originates in high-income countries (HICs), and its application and relevance in resource-constrained or culturally diverse settings remains understudied. 4 - 7 An estimated 90% of children diagnosed with cancer live in low- and middle-income countries (LMICs), yet research on decision making in these settings is sparse, with a recent review revealing only 11 studies related to decision making in pediatric cancer in LMICs. 8 - 10

CONTEXT

Key Objective

This study aimed to characterize physician decision-making practices for children presenting with advanced cancer in low- and middle-income countries (LMICs), addressing a critical gap in understanding how physicians navigate treatment decisions in resource-constrained and culturally diverse settings.

Knowledge Generated

Physicians in 36 LMICs described diverse approaches to treatment decision making for children with advanced cancer, including both curative- and non–curative-intent therapies. They also reported varied perspectives on family involvement in decision making and treatment goals.

Relevance

These findings highlight the need for context-sensitive, flexible decision-making frameworks, tools, and treatment guidelines that reflect the realities of resource limitations and cultural diversity in LMICs. Applying these insights in clinical practice can help physicians tailor treatment discussions and recommendations, ultimately supporting more equitable and effective care for children presenting with advanced cancer in their settings.

Children with advanced or poor prognosis cancer at diagnosis and their families face particularly challenging circumstances around treatment decision making in LMICs as local centers often lack capacity to provide curative options or access to clinical trials. 9 , 11 - 15 Administration of therapy misaligned with local capacity can worsen treatment-related morbidity and mortality and compromise health system efficiency and effectiveness. 11 , 16 - 18 These challenges are further compounded by inadequate decision-making support, with existing cancer treatment guidelines anchored in data collected in HICs and focused primarily on treatment with curative intent, not accounting for varied resources and contexts. 9 , 17 , 19 - 30

Further investigation of decision-making practices for children with advanced cancer in LMICs is needed to help clinicians, patients, and families make informed choices while navigating barriers to accessing first-line therapies. 7 , 11 , 12 , 16 , 31 , 32 Why, when, or how physicians in LMICs decide to offer treatment with curative versus non curative intent at diagnosis and how local contextual barriers influence and complicate decision making remain poorly understood. 7 , 9 , 15 To address this gap, this qualitative study aimed to characterize physician decision-making practices in LMICs across each of the WHO defined regions. Understanding physician decision-making approaches considerate of local contexts is an essential first step toward developing pragmatic, evidence-based resources and interventions to support decision making and improve outcomes, including survival and quality of life, for children diagnosed with advanced cancer in LMICs.

METHODS

This study was reviewed by the Institutional Review Board at St Jude Children's Research Hospital (SJCRH) and deemed exempt in the context of deidentified data collection with physician participants. Study methods and findings are presented in accordance with the Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist. 33

Settings and Participants

Pediatric oncologists or pediatricians who routinely made treatment decisions for children diagnosed with cancer were eligible if they had more than 5 years of clinical experience or had completed a certified hematology/oncology fellowship, practiced in a LMIC as defined by the World Bank, and spoke English. 34 Eligible participants were identified from the St Jude Global Alliance community, an international network of >300 medical institutions and foundations from >80 countries, dedicated to improving outcomes for children with catastrophic illness. 35 A purposeful sample was recruited to ensure representation across diverse world regions and country income levels, with one participant invited per country. Recruitment continued until analysis of consecutive interviews yielded no new themes or insights, consistent with established standards for achieving saturation in qualitative research. 34 , 36 , 37 Eligible participants were contacted by a member of the research team (M.S.) via e-mail, and verbal informed consent was obtained from each participant before initiating an interview.

Study and Design

The study protocol was designed in two phases by a research team comprising experts in pediatric oncology, palliative and hospice medicine, and global health. Given the limited existing literature on decision-making approaches at diagnosis for children presenting with advanced cancer in LMICs, phase I involved the conduct of focus groups, with physicians practicing in these settings to explore current practices in up-front treatment decision making for these children. Focus group findings generated key themes to inform the development of a semistructured interview guide (Appendix Table A 1 ) used in the second phase to investigate physician treatment decision-making approaches in greater depth. 15 Interview prompts and probes were pilot tested with physician volunteers and iteratively revised to strengthen question prompts and probes.

Participant interviews were conducted between January 2022 and June 2023 using a secure, online videoconferencing platform that complied with data protection standards. Each interview was led by a trained expert in qualitative data collection (M.S.), lasted 30-90 minutes, and was audio-recorded. Sociodemographic data, including sex, age, country, years of clinical practice, previous training in pediatric hematology/oncology and/or palliative care, and practice setting, were collected from participants via electronic survey.

Data Analysis

Demographic characteristics were summarized descriptively. Interview recordings were transcribed verbatim by trained medical transcriptionists and deidentified to ensure participant confidentiality. Five researchers (M.S., J.Z., A.R., J.C., S.M.) reviewed transcripts, engaged in memo writing, and conducted inductive content analysis that identified a spectrum of recurrent themes. 38 A codebook (Appendix Table A 2 ) was developed through iterative review of eight transcripts, and codes were applied across all transcripts by the research team (M.S., J.Z., A.R., J.C., S.M., L.F., A.C.-S.) using MAXQDA software (WERBI, Berlin, Germany). Coders met to resolve discrepancies by consensus with a third-party adjudicator (E.C.K.).

RESULTS

Thirty-eight physicians were enrolled in the study, and 36 participants completed interviews. Demographic characteristics are summarized in Table 1 . Approximately two thirds of participants were female (n = 24; 67%) and age 36-50 years (n = 22; 61%). Most practiced in a lower-middle–income country (n = 20; 55%), with participants relatively evenly distributed across WHO regions. Most physicians had more than 11 years of clinical experience (n = 28; 77%) and lacked formal pediatric hematology/oncology (n = 22; 61%) or palliative care training (n = 24; 67%). Participants worked in a variety of settings, with most employed at publicly funded hospitals (n = 16; 44%) or hospitals receiving public and private funding (n = 14; 39%). Most participants worked in settings with >100 new childhood cancer cases per year (n = 26; 72%).

Descriptions of Advanced or Poor Prognosis Childhood Cancer

In the context of treatment decision-making approaches, participants described a spectrum of childhood cancers as advanced or poor prognosis at diagnosis. No single diagnosis was consistently described as poor prognosis by most participants. Diagnoses described by at least three participants included leukemias (AML, infant leukemia), sarcomas (Ewing, osteosarcoma, rhabdomyosarcoma), and other solid (neuroblastoma, retinoblastoma) or CNS tumors (diffuse intrinsic pontine glioma [DIPG]). Physicians' designation of advanced or poor prognosis cancers at diagnosis is presented in Table 2 . In addition to naming specific diagnoses, participants also referred to categories of disease, such as advanced solid tumors or brain tumors, or nonspecific diagnoses, like metastatic sarcomas.

Treatment Recommendations and Outcome Pathways

Participants described several treatment recommendations offered at diagnosis to children presenting with advanced cancer in their settings, resulting in a range of decision-making approaches, goals of care, and outcome pathways for treatment that a given patient/family might pursue which are visually presented in Figure 1 . Each component is described in further detail in subsequent sections.

Treatment Recommendations

Physicians most often recommended treatment with noncurative intent for children with advanced cancer at diagnosis, with a focus on optimizing quality of life, prolonging life, and alleviating suffering. However, physicians also described offering treatment with curative intent even in the context of very low survival odds. For example, if a child's disease had favorable clinical or diagnostic features, physicians might recommend treatment with curative intent, even if the disease burden otherwise suggested incurability. Physicians described cognitive tension between uncertainty of a child's treatment response versus known statistics associated with a given diagnosis. Some participants reported a moral and ethical obligation to treat each child with curative intent therapy regardless of diagnosis or prognosis. Others described referring patients within the country or abroad to a center with greater capacity to offer curative treatment options. Finally, some physicians described offering a limited trial of chemotherapy, at full or reduced dosing, with reassessment before transitioning to noncurative goals. Quotes illustrating these various treatment recommendations are presented in Table 3 .

Approaches to Decision Making

Four main approaches to decision making were described by participants, including clinician-led, family-led, participatory or shared, and decision making influenced by a party external to the physician-family dyad. Some physicians reported that they carried the burden of making treatment decisions at diagnosis on behalf of the patient and family. Physician-led decision making was described across varying clinical scenarios, for example, when only one medically reasonable option existed (eg, lack of available treatment with curative intent) or when a contextual factor, such as a physician's assessment of the family's ability to afford treatment, influenced which treatment options the physician offered to the family. Physicians also inferred that certain families preferred to have the physician guide them in decision making.

Some participants described participatory or shared approaches to decision making with the family, where the physician-family dyad would discuss the child's diagnosis and treatment options, consider the salient contextual factors affecting treatment provision, and subsequently decide together. In some contexts, families consulted with community or spiritual leaders to guide decision making. By contrast, other physicians described sharing all available treatment options, leaving treatment decision making in the hands of the family and acknowledging their inability to predict a family's wishes or available resources.

Finally, a small group of physicians described how decision making was influenced by an external group of decision-makers (eg, politicians or hospital administrators), independent of the medical team's treatment recommendations. Outcomes described by participants in these circumstances were typically poor, including risk of patient harm and moral injury to the medical team. Quotations describing various approaches to treatment recommendations are presented in Table 4 .

Goals of Care

Physicians often described the importance of optimizing prognostic outcomes for children presenting with advanced cancer. Few expressed an imperative to offer curative treatment to all children presenting with advanced disease; rather, most discussed their goal to stabilize or slow disease progression to prolong a child's life.

Diverse goals were listed under the auspices of prioritizing care of the child as an individual, with frequent references to optimizing quality of life and addressing suffering through management of pain and other cancer-related symptoms. Other common goals included maintaining a child's dignity and enabling a peaceful death. Many physicians described the importance of offering each child the best treatment possible, considering locally available resources, while minimizing treatment toxicity. At times, striving for this balance involved time-limited trials of cancer-directed treatment even when odds of cure were slim, in part to build therapeutic rapport with the family and lessen the risk of treatment abandonment or pursuit of alternative care. Physicians weighed treatment options through the lens of avoiding therapeutic cruelty (eg, not offering toxic therapies that were unlikely to achieve cure) or risking the overall health of the family (eg, anticipated financial toxicity because of staggering costs related to relocation or treatment, inability to work).

Finally, participants described a profound commitment to all children diagnosed with cancer, verbalizing the importance of treating all children equally irrespective of differences in patient/family circumstances. However, participants recognized nuances within this commitment with respect to allocating limited resources to children with a higher likelihood of achieving cure. Appendix Figure A 1 visually summarizes physician perspectives on goals of care, and illustrative quotes are presented in Appendix Table A 3 ).

Treatment Outcome Pathways

Participants described seven potential treatment outcome pathways for children diagnosed with advanced cancer at diagnosis based on a family's response to various options (Fig 1 ). Quotes illustrating these treatment outcome pathways are presented in Table 5 . Physicians described how families often agreed with their recommendation for noncurative treatment in inpatient, outpatient, and home settings, with specific options summarized in Appendix Figure A 2 . Descriptions of treatment with noncurative intent included chemotherapy (also described as metronomic or palliative chemotherapy), pain management, palliative care, radiation, surgery, and supportive care. Physicians also described families that opted for treatment with curative intent when physicians offered this option, resulting in a wide spectrum of outcomes including cure, disease control, and death from treatment toxicities.

Physicians often described tension in decision making when families challenged their recommendation for treatment with noncurative intent. Multiple scenarios were described where negotiations occurred between the family and their child's medical team. In some circumstances, physicians would explore the families' wishes but not change the offered treatment given low odds of survival. Other times, physicians changed their recommendation at the family's behest, either because the child could tolerate chemotherapy even if it was likely to be ineffective or because of potential for inaccurate prognostication.

In addition, physicians described how well-resourced families may pursue care at centers with access to more comprehensive treatment options, either guided by the physician or driven by the family independently. Participants worried about outside centers offering unrealistic chances of cure, resulting in excessive morbidity or mortality, financial exploitation, and other harms to the family. Physicians also described families that sought care from traditional healers because of cultural familiarity of offered treatments, closer proximity, or lower costs. Children were often lost to follow-up but sometimes would return in crisis with disease progression and fewer options for disease control. Some families declined treatment all together, with decisions influenced by low health literacy or socioeconomic constraints. Physicians described the logistical challenges of financing the transport of a child's body or planning a child's burial far from home, leading some families to request to return home instead of pursuing cancer-directed therapy.

Finally, one physician described a clinical scenario in which the treatment recommendation changed from noncurative to curative during the intraoperative period, because of worry that the initial prognostication was inaccurate. Retroactively, the physician reflected that the patient's odds of cure likely had not changed with treatment, and the decision to pursue a curative approach resulted in a higher risk for treatment-related morbidity and mortality.

DISCUSSION

This qualitative study characterized treatment decision-making approaches among physicians practicing in 36 LMICs for children with advanced or poor prognosis cancer at diagnosis, revealing a diverse spectrum of treatment recommendations and pathways (Fig 1 , Tables 3 - 5 ). Up-front treatment with noncurative intent was commonly endorsed although consensus was lacking on which diagnoses warranted this approach (Table 2 ). Physicians also had divergent perceptions of how much or often families should participate in the treatment decision-making process (Table 4 ). When physicians and families disagreed about treatment options, physicians reported that subsequent negotiations risked families pursuing care elsewhere or declining treatment all together (Table 5 ). Finally, physicians described the importance of balancing goals for up-front treatment, anchored in optimizing outcomes and offering equitable care to all children with advanced cancer (Appendix Fig A 1 , Appendix Table A 3 ).

These findings suggest that approaches to up-front treatment decision making for children presenting with advanced cancer differ in LMICs compared with HICs. Of the eight cancers most often described as advanced or poor prognosis by participants, seven would be offered treatment with curative intent at diagnosis in HICs (excluding DIPG, which remains incurable globally). 39 - 46 In LMICs, delays in diagnosing pediatric cancer and resource limitations often prevent centers from offering curative treatment at diagnosis to all children presenting with cancer, exacerbating outcome disparities. 11 , 47 Context-sensitive approaches are needed to support decision making for children presenting with advanced cancer, empowering physicians to offer the best available treatment options—whether curative or noncurative—and identify areas for health care system strengthening. Similarly, future childhood cancer treatment guidelines should reflect local decision making realities faced in LMICs as described in this study. 9 , 17 Collaborative efforts are underway to address existing guideline limitations by building on previous initiatives to develop guidelines for resource-limited settings. This includes the Adapted Resource and Implementation Application, which aims to provide pragmatic, resource-adapted guidelines tailored to local care delivery settings. 48 Guided approaches are also needed to help support teams facing complex decision making for children with extremely low odds of cure at diagnosis, including recommendations for provision of non–curative-intent therapy or guidance on choosing between multiple reasonable treatment approaches.

Wide variations in decision-making approaches, as seen in these data, further underscore the complexity of caring for children with poor prognosis cancer in LMICs. Pediatric-focused research conducted in HICs advocates for a shared decision-making (SDM) model, an approach that is relevant when more than one medically reasonable option exists. 4 , 5 In this model, clinicians and families collaborate, reviewing treatment options, preferences, and priorities. SDM was described by a subset of physicians in this study when several treatment options were felt to be reasonable at diagnosis. However, SDM is less relevant when physicians recommended only one treatment option or, conversely, perceive all options as futile. While useful in certain applications, the SDM model is not immune to bias, does not account for public health considerations (ie, resource limitations), and is anchored to Western cultural norms, suggesting the need for thoughtful consideration and exploration of how best to use this model in LMICs. 5 A recent study exploring pediatric cancer decision making in Guatemala revealed that most families appreciated SDM while also wanting their medical team to guide decision making rather than providing multiple treatment pathways without a clear recommendation. 49 Similar to Pakistan, families emphasized the importance of SDM and wanted to know the risks and benefits associated with treatment. 3 Ongoing analyses are underway to better understand how contextual factors influence up-front decision making from the perspectives of children and young people presenting with advanced cancer, their families, and their multidisciplinary clinicians in LMICs. Findings from this study, along with evidence from other research on patient-centered communication, can help adapt existing decision-making frameworks developed in HICs or contribute to the creation of new models that are better suited to the unique resource and cultural contexts of LMICs.

These findings should be interpreted in the context of limitations. Data were collected from one physician per country, and study findings may not reflect the experiences of other physicians within each country. Participants were conversant in English which may exclude perspectives of non–English-speaking physicians. While not intentional, more than two thirds of participants practiced at higher-volume cancer centers; their decision-making perspectives may differ from clinicians practicing in smaller centers. As recruitment was limited to members of the St Jude Global Alliance, the participant sample may not fully represent the diversity of perspectives among physicians providing care to children diagnosed with cancer in LMICs. We sought maximum variation by including participants from diverse regions, income levels, and backgrounds. Countries were categorized by World Bank income groupings, which may obscure important differences between low-, lower-middle–, and upper-middle–income countries. In addition, 14% of participants were from low-income countries. While this reflects the global country income-level distribution according to the World Bank, it should be considered while interpreting study findings. 34 Cultural norms and values influencing treatment decision making also vary across regions, independent of national income levels. This study was not designed to examine regional or cultural variations in-depth, representing an additional limitation. Physicians described decision-making approaches in the context of clinical vignettes rooted in their professional experiences and offered local examples of cancers considered advanced at diagnosis rather than using a standardized definition. Patient-level data were not collected to further characterize these cases. Future research should explore these distinctions as resource availability, health care infrastructure, and decision-making processes can vary substantially across LMICs. This analysis focuses on decision-making approaches; analysis of key contextual factors influencing these processes is ongoing. Finally, the perspectives of patients, caregivers, and nonphysician clinicians were not explored in this study. Future work will characterize the experiences and perspectives of these groups to complement these data and inform the design of future interventions to support clinical decision making.

In summary, physicians who care for children with advanced cancer at diagnosis in LMICs navigate complex, nuanced, context-specific treatment decision making. Although physicians aim to offer treatment with curative intent to all children presenting with cancer, current resource limitations may necessitate consideration of treatments with noncurative intent focused on relieving suffering, optimizing quality of life, and facilitating a peaceful death. Physicians face challenging decision making in their day-to-day practice as they strive to balance resource allocation with curative approaches for as many children as possible. These findings will support the development of pragmatic, evidence-based guidelines and interventions to guide treatment decision making for children presenting with advanced cancer, flexible to local constraints, and elevating the voices of key community members, including patients and families. This foundational work will also inform adaptation of existing decision-making frameworks considerate of diverse resource and cultural contexts. Ultimately, these interventions aim to improve patient outcomes and reduce suffering in synergy with efforts to optimize equitable and compassionate care for children with cancer globally.

ACKNOWLEDGMENT

We thank the physicians who invested time as participants in this study. In addition, we acknowledge the contributions of Drs Katerina Trkova and Anjali Chandra in aspects of the qualitative data analysis. A list of CATALYST Advisory Group participants is provided in Appendix 1.

APPENDIX 1. CATALYST ADVISORY GROUP

Justin N. Baker, MD (Stanford University, Stanford, CA); Mae Concepcion J. Dolendo, MD, FPPS, FPSPO (Southern Philippines Medical Center, Children's Cancer Institute, Davao City, Philippines); Diego Figueredo, MD (Hospital de Clinicas, National University of Asunción, Asuncion, Paraguay); Lisa M. Force, MD, MPH (University of Washington, Seattle, WA); Paola Friedrich, MD, MPH (St Jude Children's Research Hospital, Memphis, TN); Fadhil Geriga, MBChB, MMed (Uganda Cancer Institute, Kampala, Uganda); Sanjeeva Gunasekera, MD (National Cancer Institute, Maharagama, Sri Lanka); Jean M. Hunleth, MPH, PhD (Washington University in St Louis, St Louis, MO); Roman Kizyma MD (Clinical Center of Children's Healthcare, Lviv, Ukraine); Essy Maradiege, MD (Cancer Prevention and Control Directorate - Ministry of Health, Lima, Peru); Hoa Thi Kim Nguyen, MD, PhD (Hue Central Hospital, Hue, Vietnam); Irene Nzamu, MBChB, MMed, FPHO (Kenyatta National Hospital, Nairobi, Kenya); Muhammad Rafie Raza, MD (Indus Hospital & Health Network, Karachi, Pakistan); Khilola Rustamova, MD, PhD (The Scientific and Practical Center of Pediatric Oncology, Hematology, and Immunology, Tashkent, Uzbekistan); Nur Melani Sari, MD (Dr Hasan Sadikin General Hospital/Faculty of Medicine Universitas Padjadjaran, Bandung, Indonesia); Paul H. Wise, MD, MPH (Stanford University, Stanford, CA)

Marta Salek

Other Relationship: Conquer Cancer, the ASCO Foundation

No other potential conflicts of interest were reported.

PRIOR PRESENTATION

Presented at the International Society of Pediatric Oncology (SIOP) Annual Congress, Ottawa, Canada, October 11-14, 2023.

SUPPORT

M.S. supported by the ASCO, Conquer Cancer Foundation. E.C.K. supported by the National Cancer Institute (K08CA266935). Supported by the American Lebanese Syrian Associated Charities (ALSAC).

Contributor Information

on behalf of the CATALYST Advisory Group:

CATALYST Advisory Group, Justin N. Baker , Mae Concepcion J. Dolendo , Diego Figueredo , Lisa M. Force , Paola Friedrich , Fadhil Geriga , Sanjeeva Gunasekera , Jean M. Hunleth , Roman Kizyma , Essy Maradiege , Hoa Thi Kim Nguyen , Irene Nzamu , Muhammad Rafie Raza , Khilola Rustamova , Nur Melani Sari , and Paul H. Wise

AUTHOR CONTRIBUTIONS

Conception and design: Marta Salek, Carlos Rodriguez-Galindo, Dylan Graetz, Nickhill Bhakta, Erica C. Kaye

Administrative support: Erica C. Kaye

Provision of study materials or patients: Nickhill Bhakta

Collection and assembly of data: Marta Salek, Joanne Canedo, Alaina Rule

Data analysis and interpretation: Marta Salek, Ana Caceres-Serrano, Joanne Canedo, Lucia Fuentes, Shoshana Mehler, Alaina Rule, Jamie Zeal, Dylan Graetz, Erica C. Kaye

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/go/authors/author-center .

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians ( Open Payments ).

Marta Salek

Other Relationship: Conquer Cancer, the ASCO Foundation

No other potential conflicts of interest were reported.

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