Diagnostic challenges and treatment barriers in the management of diffuse intrinsic pontine glioma in low- and lower-middle-income countries: a systematic review.
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INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor with a poor prognosis. In low- and middle-income countries (LMICs), challenges to diagnosis and treatment are exacerbated by limited resources and health system constraints. OBJECTIVE: To evaluate diagnostic delays, access to imaging, biopsy and molecular testing, as well as treatment availability, including availability of standard treatment, palliative care and psychosocial support, in DIPG management across LMICs, alongside system-level barriers and survival outcomes. METHODS: A systematic review was conducted according to PRISMA 2020 guidelines. Searches were performed across PubMed/MEDLINE, Scopus, CINAHL, and clinicaltrials.gov for studies up to December 2024. Two independent reviewers screened 2034 records. Data analysis and descriptive statistics were conducted using R version 4.5.0. RESULTS: This systematic review synthesized data from sixteen studies across six LMICs, encompassing 1527 DIPG cases, predominantly from South Asia (n = 8) and North Africa (n = 5). Significant diagnostic challenges were identified, with median delays of 1 to 6 months, largely attributed to inefficient referral pathways. While neuroimaging was available in most settings (14/16 studies), access to biopsies was limited. Although biopsy utilization reached 100% in a single retrospective molecular study, utilization in clinical series was significantly lower (ranging from 0 to 53%). However, where performed, diagnostic yields were consistently high, exceeding 90% in nearly all reported cohorts. Furthermore, molecular testing was reported in only six centers, primarily within retrospective or restricted contexts rather than routine clinical practice. Therapeutic resources were similarly constrained; radiotherapy access was documented in only six studies and utilized inconsistently. Palliative care and multidisciplinary team involvement were both reported in just 18.8% of centers, respectively. The most common clinical presentations included cranial nerve palsies (45.8-88%), headache (51.4-77.8%), and ataxia (48-77.8%). Prognosis was poor, with median survival ranging from 6.0 to 9.7 months and follow-up abandonment rates reaching as high as 71.4%. CONCLUSIONS: DIPG care in LMICs is fundamentally compromised by significant barriers, including diagnostic delays and restricted access to biopsy, molecular profiling, and essential therapies. Combined with inadequate palliative and multidisciplinary support, these deficiencies lead to poor outcomes. Our findings present a clear mandate for strengthening referral networks, improving infrastructure, and developing integrated neuro-oncology programs in resource-limited settings.