Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 11 appraisals
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
A systematic review of long-term outcomes (>10-year follow-up) of paediatric craniopharyngioma
PURPOSE: Adamantinomatous craniopharyngiomas (ACP) in children are rare benign tumours. Relatively few publications have addressed the long-term impact of this tumour and its treatment. We undertake a systemic review of the existing literature aiming to define the outcome of ACP beyond 10 years' follow-up. METHODS: Ovid MEDLINE, Embase and Google Scholar were used to search the literature. The search criteria were children (aged under 18 at diagnosis), any intervention for and outcomes of ACP. Publications with less than 10 years' follow-up and single case reports were excluded. RESULTS: Twenty-one studies were included reporting on 1152 children, with a mean age of 8.8 years at diagnosis. Mean follow-up was 14 years. The most common presenting symptom was headache. The mean overall survival at 5, 10, 15 and 20 years post-diagnosis was 91.6%, 84.4%, 77.5% and 68.0%, respectively. In children undergoing gross total resection only or radiotherapy only, survival was higher than with combined treatments. Seventy-five percent of children had endocrine dysfunction after intervention; the most prevalent was hypothyroidism (81.9%). The prevalence of endocrinopathies was similar across all treatment groups. Lower QoL was reported than the general population, predominantly related to the effects of hypothalamic injury. One in ten patients suffered a late complication related to radiotherapy with vasculopathy being the most prevalent. CONCLUSIONS: The long-term morbidity and mortality for paediatric ACP remain high. The impact from hypothalamic injury cannot be understated and is likely the cause for this finding. As surgical treatment advances, less hypothalamic injury may arise and improved outcomes may follow. Gross total resection, if felt achievable without hypothalamic injury, should form the mainstay of treatment due to the late radiotherapy-related complications that arise.
10 July 2026
Read appraisal →Journal of neuro-oncology
Feasibility evaluation of tumor treating fields for brainstem gliomas
PURPOSE: Tumor treating fields (TTFields) are FDA-approved for supratentorial glioblastoma, but feasibility in infratentorial tumors remains poorly defined. This simulation study evaluated TTFields dose in brainstem gliomas using patient-specific modeling with scalp-only transducer arrays. METHODS: MRI and CT imaging from seven patients with brainstem gliomas were used for TTFields planning with MAXPOINT® (Novocure, Switzerland). Clinical target volume (CTV) was defined as enhancing tumor on T1 post-contrast MRI (Gross tumor volume, GTV) plus a 3 mm peritumoral expansion. The platform optimized scalp-only array layouts, and finite element calculations generated maps of local minimum field intensity (LMiFI, V/cm) and local minimum power density (LMiPD, mW/cm³). Values were compared against a standard, unplanned layout using one-sided paired t-tests, with LMiFI ≥ 1.0 V/cm as a therapeutic reference. RESULTS: MAXPOINT-optimized layouts achieved significantly higher LMiFI than the standard layout across all regions (all p ≤ 0.019). GTV median LMiFI was 1.1 vs. 1.0 V/cm (p = 0.019). CTV median LMiFI was 1.1 vs. 1.0 V/cm (p = 0.002). Brainstem median LMiFI was 1.3 vs. 1.1 V/cm (p = 0.002). Posterior fossa showed the largest difference: median LMiFI 1.5 vs. 1.2 V/cm (p < 0.001). All optimized LMiFI values met or exceeded the therapeutic reference. LMiPD was also significantly higher with MAXPOINT® across all regions (all p ≤ 0.006). CONCLUSION: This simulation study demonstrates that patient-specific modeling can achieve favorable TTFields intensities in brainstem gliomas using scalp-only arrays, supporting prospective clinical evaluation for infratentorial tumors.
8 July 2026
Read appraisal →Journal of pediatric surgery
Artificial intelligence in rare pediatric solid tumor research and clinical care: A scoping review
BACKGROUND: Clinical and research advances for children with solid tumors are limited by their rare nature. Artificial intelligence (AI) and machine learning (ML) hold potential for advancing diagnosis, risk stratification, and treatment in rare diseases where individual patients contribute high-dimensional data. This review characterizes current AI/ML applications in rare pediatric solid tumors. METHODS: PubMed, Embase, and Web-of-Science Core Collection databases were queried for relevant articles published before February 10, 2025. Eligible studies applied AI/ML methods to study rare tumors in pediatric populations (≤19 years). Articles were evaluated for tumor diagnosis, AI/ML methods, clinical applications, comparators, effectiveness, and interpretability. RESULTS: Twenty-three studies (2009-2025) were included. Hepatoblastoma (12/23) and pediatric thyroid cancers (4/23) were most frequently studied. Supervised learning predominated (20/23), followed by unsupervised (9/23), deep learning (4/23), and hybrid/ensemble models (6/23). Applications included diagnosis (12/23), prognosis (10/23), and risk stratification (9/23). Twenty studies reported effectiveness measures, with many models achieving AUCs >0.85. In comparative analysis (17/23), AI/ML often equaled or exceeded expert consensus, traditional models, or alternative algorithms. Eight studies reported external validation. CONCLUSIONS: Current AI/ML research in rare pediatric extra-cranial solid tumors focuses on diagnosis, risk stratification, and prognosis, often outperforming traditional methods. Future work should prioritize external validation and clinical applicability.
1 July 2026
Read appraisal →Blood advances
Pediatric-inspired regimens and HSCT for adolescents and young adults with acute lymphoblastic leukemia
The best frontline treatment for acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYAs) is unclear. To support a clinical practice guideline, we systematically reviewed and meta-analyzed evidence on (1) asparaginase-based (pediatric) vs non-asparaginase-based (adult) regimens and (2) allogeneic hematopoietic stem cell transplantation (HSCT) vs no HSCT for AYAs (aged 15-39 years) with ALL in first complete remission. Data sources were PubMed, CINAHL, and PsycINFO from inception to 29 November 2023. Eligible studies compared regimens or the use of HSCT and reported survival, remission, toxicity, or quality of life in AYAs. We included 19 studies (14 comparative, 5 single-group; N = 3607) comparing regimens and 7 studies (N = 7492) comparing HSCT and no HSCT. Studies were mostly of poor quality, with sparse randomized controlled trials (RCTs), yielding low-certainty findings. Pediatric regimens were associated with higher 5-year overall survival (OS; relative risk [RR], 1.40; 95% confidence interval [CI], 1.18-1.65), event-free survival (RR, 1.80; 95% CI, 1.13-2.85), disease-free survival (DFS; RR, 1.55; 95% CI, 1.32-1.82), and lower treatment-related mortality (TRM; RR, 0.29; 95% CI, 0.09-0.90). HSCT was associated with lower 5-year OS (RR, 0.72; 95% CI, 0.61-0.84) and DFS (RR, 0.78; 95% CI, 0.68-0.90) and higher nonrelapse mortality (RR, 2.70; 95% CI, 1.18-6.18) and TRM (hazard ratio, 6.88; 95% CI, 3.02-15.70). Relapse risk varied by time point. In AYAs with Philadelphia chromosome-negative ALL, pediatric regimens may improve survival; toxicity-related evidence remains limited. HSCT may lead to inferior OS and DFS. With a dearth of RCTs, low-certainty evidence highlights the need for high-quality studies and subanalyses of AYAs.
26 May 2026
Read appraisal →Journal of neuro-oncology
Therapeutic effects of selumetinib on diffuse neurofibroma and optic pathway glioma in neurofibromatosis type 1.
PURPOSE: Selumetinib is approved for the treatment of inoperable plexiform neurofibromas (PN) in patients with neurofibromatosis type 1 (NF1). However, its efficacy in treating NF1-associated diffuse neurofibromas (NF1-DN) or optic pathway gliomas (NF1-OPG) remains unclear. We evaluated the efficacy and safety of selumetinib in these subgroups. METHODS: This was a sub-analysis of a Korean phase II open-label trial focusing on non-target treatment effects on NF1-DN and NF1-OPG. A total of 88 pediatric and adult patients with NF1-PN (59 children and 29 adults) in this trial had been treated for at least 2 years (~ 26 cycles, 28-day cycle) with oral selumetinib (20 or 25 mg/m², or 50 mg/dose every 12 h). Tumor volume, quality of life (QoL), and visual acuity were assessed. RESULTS: Among the 88 included patients, NF1-DN was diagnosed in 25 (28%), and NF1-OPG in 3 (3%). All NF1-DN patients exhibited disfigurement, two experienced pain, and a partial response (PR; ≥20% tumor reduction at a single time) was achieved in 9 of these cases (36%). The median time to PR was 6 cycles (range, 6-12), and the median time to best response was 18 cycles (range, 6-26), with a median volume change of - 11.9% (range, - 55.4% to + 36.3%). Confirmed PR (cPR; PR sustained for > 6 cycles) was observed in 6 NF1-DN patients (24%), stable disease (SD) was observed in 9 of these patients (36%), and progressive disease (PD) in 10 cases (40%). In a paired comparison, cPR was significantly lower for NF1-DN than for NF1-PN (24% vs. 88%, P < 0.001), and the median best volume reduction was also smaller (- 11.9% vs. -42.1%, P < 0.001). For the 3 NF1-OPG patients, visual impairment was present in all cases at baseline. One patient achieved PR at cycle 12 (- 36.1% from baseline) and complete response (CR) at cycle 26 but the visual acuity did not improve in this case. SD was maintained in the other two patients. Within these subgroups, QoL improved in 16 patients (57%) by cycle 26. No serious adverse events or treatment discontinuations were reported. CONCLUSIONS: Selumetinib shows therapeutic potential against NF1-DN, although with a lower response than that observed against NF1-PN. The NF1-OPG findings herein for this drug were exploratory only because of the small number of cases, but they may provide an additional clinical context for evaluating the broader effects of selumetinib across NF1-associated lesions. TRIAL REGISTRATION INFORMATION: KCT0003700, cris.nih.go.kr/cris/search/detailSearch.do/19,080, first submission March 4, 2019; first patient enrolled May 14, 2019.
25 May 2026
Read appraisal →Physics in medicine and biology
A novel deep-learning approach for monitoring gastrointestinal air variation during radiotherapy in young patients using radiographs
Objective.To develop deep-learning (DL) predictive models of internal gastrointestinal (GI) gas from radiographs, a surrogate for dose degradation in abdominal proton beam therapy (PBT).Approach.DL architectures (convolutional neural networks and U-Nets) were trained to predict GI air local path length and/or global volume from radiographs. Frontal/lateral radiographs with paired volume and path length labels were simulated from CTs and GI gas segmentations using the Tomographic Iterative GPU-based Reconstruction (TIGRE) toolbox. CTs from The Cancer Imaging Archive Paediatric-CT-SEG dataset (N= 349, 0-16 year, North America) were used for model development and internal evaluation; variation in GI filling, organ motion and body size were simulated for augmentation. External evaluation utilised data from two international radiotherapy institutions: one consisting mostly of children and young people (CYP) (N= 21, 2-19 year, Europe); the other predominantly of teenagers and young adults (TYAs) (N= 14, 10-24 year, Asia). Finally, real-life use case was demonstrated on two subjects treated with PBT.Main results.The optimal configuration was the dual U-Net, accurately predicting both volume (mean absolute error (MAE) = 24.0 ± 32.9 ml) and path length (MAE = 0.80 ± 0.59 mm) on the held-out Paediatric-CT-SEG dataset, while also generalising well to external radiotherapy datasets (volume MAE = {18.9 ± 22.4, 34.6 ± 35.2} ml, and path length MAE = {0.52 ± 0.38, 0.67 ± 0.55} mm on the CYP and TYA datasets, respectively). We found a lower Dice similarity coefficient for gas segmentations in TYA vs Paediatric-CT-SEG and CYP (0.56 ± 0.24 vs 0.87 ± 0.09 and 0.84 ± 0.16, respectively), reflecting cohort-specific gas morphology differences. When applied longitudinally, the network detected both monotonic and realistic intrasubject GI gas variation. Proof-of-concept evaluation on clinical radiographs showed promising performance (volume MAE = 29.5 ± 25.9 ml, and path length MAE = 1.10 ± 0.75 mm).Significance.DL-powered radiographs quantified internal GI gas changes with promising performance and generalisability to diverse ages and demographics. This was the first step towards a novel personalised image-guided radiotherapy traffic-light workflow for abdominal PBT with the goal of reducing the need for CBCT to required fractions.
14 May 2026
Read appraisal →European journal of clinical pharmacology
The impact of gene polymorphisms on the response of methotrexate-based treatments
PURPOSE: Methotrexate (MTX) is a long-standing drug used to treat leukemia (at high doses to inhibit DNA/RNA synthesis) and rheumatoid arthritis (at low doses for anti-inflammatory effects). Its characteristic narrow therapeutic range, in terms of efficacy and safety associated with MTX, are important factors to consider when deciding whether to prescribe it. A major challenge in its use is interindividual variability which is largely attributed to germline genetic polymorphisms in genes encoding proteins that control the pharmacokinetics or pharmacodynamics of MTX. METHODS: This study updates a previous 2018 review using a systematic literature search in PubMed/MEDLINE, Scopus, and SciELO. The search, conducted according to the PRISMA protocol, employed predefined keywords to identify studies published up to June 2025. RESULTS: This systematic review identified that, to date, only a few genetic polymorphisms influence clinical decision-making. Specifically, the MTHFR 677T allele and the MTHFR 677T-1298 A haplotype (rs1801133- rs1801131) have been associated with toxicity in both adults and children. Furthermore, the 677T-1298 A haplotype has been linked with reduced event-free survival in Caucasian patients with either adult RA or pediatric ALL. Regarding other markers, the TYMS rs34743033 3R allele has been implicated with reduced efficacy in adult patients receiving low-dose MTX, while the FPGS rs1544105 T allele has shown an association with diverse toxicities in ALL pediatric patients. CONCLUSION: Although considerable research has been conducted and numerous results have been obtained, the available evidence remains predominantly of moderate quality. Consequently, current guidelines from CPIC and the DPWG do not recommend routine MTX dose adjustments based solely on single gene variants. It is, therefore, imperative to develop and validate multifactorial risk prediction tools that integrate a range of other clinical factors. Accordingly, the establishment of a comprehensive pharmacogenetics-guided dosing guideline for MTX remains an elusive goal.
13 May 2026
Read appraisal →Clinical & experimental metastasis
All-site radiotherapy for metastatic ewing's sarcoma: a short-term analysis of feasibility, response, and safety.
BACKGROUND: Metastatic Ewing sarcoma (EWS) has a poor prognosis. While metastasis-directed therapy benefits oligometastatic disease, the role of comprehensive all-site radiotherapy in widespread disease remains underexplored. This study aimed to preliminarily assess its short-term efficacy and safety. METHODS: This retrospective analysis included 21 consecutive metastatic EWS patients treated with helical tomotherapy (Aug 2024-Jun 2025). All known metastases and unresected primary tumors received radiotherapy (45-55 Gy in 20 fractions for most sites; 12-45 Gy for lung/pleural metastases). Concurrent systemic therapies included chemotherapy, tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), or combinations. Primary endpoints were local objective response rate (ORR, RECIST 1.1) at 2 months post-radiotherapy and acute toxicity (CTCAE 5.0). Systemic therapy subgroup analyses were exploratory. RESULTS: Median follow-up was 6 months (range 2-11). Among 77 target lesions, ORR was 61.0% (CR 48.1%), and disease control rate (DCR) was 97.4%. Soft tissue lesions had a significantly higher CR rate than bone metastases (78.3% vs 3.2%, p < 0.001), potentially influenced by RECIST 1.1 limitations and treatment heterogeneity. Median progression-free survival (PFS) was 6.0 months (95% CI: 2.30-9.70), and median overall survival (OS) was 8.0 months (95% CI: 6.69-9.31). Combination systemic therapy was associated with improved PFS (HR 3.94, 95%CI 1.32-11.78; p = 0.014), with chemotherapy-based regimens yielding the best PFS (8.5 months). TKI-containing regimens were linked to shorter PFS (4.0 vs 8.5 months, p = 0.048) due to selection bias. Acute toxicity was manageable, with grade 3 thrombocytopenia (19.0%) and pneumonitis (4.7%) resolving with treatment. CONCLUSION: All-site radiotherapy achieves promising short-term local control with manageable toxicity in metastatic EWS, demonstrating feasibility and a lesion site-specific response warranting further investigation. Systemic therapy, particularly chemotherapy, correlates with improved PFS. Given high systemic progression rates, long-term outcomes may benefit from integration with more effective systemic therapies, supporting future prospective trials.
2 May 2026
Read appraisal →BMJ open
Patients' experiences of the path to sarcoma diagnosis: a qualitative systematic review and thematic synthesis
OBJECTIVE: To explore existing qualitative research on patients' experiences from the onset of symptoms to the diagnosis of sarcoma, with the purpose of identifying patient-perceived barriers at both patient and healthcare system levels and to highlight opportunities for improvement. DESIGN: Systematic review of qualitative studies using thematic synthesis. METHODS: We systematically searched Medline [Ovid], Embase [Ovid], PsycINFO [EBSCOhost] and CINAHL [EBSCOhost] from database inception to 11 April 2025 for qualitative studies reporting sarcoma patients' experiences during their diagnostic trajectory. The final search was conducted on 11 April 2025. All articles were screened against predefined inclusion and exclusion criteria and methodological quality was appraised using the Critical Appraisal Skills Programme qualitative checklist. Six studies conducted in Australia, the Netherlands and the UK were included. Data were analysed using a thematic synthesis approach guided by Thomas and Harden (2008). Confidence in the synthesised findings was assessed using the Grading of Recommendations Assessment, Development and Evaluation - Confidence in the Evidence from Reviews of Qualitative Research (GRADE-CERqual) approach. RESULTS: Four overarching themes emerged: patients' experience and interpretation of symptoms, diagnostic pathways, healthcare system factors, and reflections and recommendations. Key contributors to delayed diagnosis were symptom normalisation, misattribution by both patients and healthcare professionals, limited continuity of care and communication challenges. These findings were consistent across multiple countries, indicating relevance and validity in many settings. Patients emphasised the importance of disease awareness, persistence of patients and coordinated care. CONCLUSIONS: Diagnostic delays in sarcoma are influenced by both patient and healthcare systemic factors. Addressing these factors requires increased disease awareness among healthcare professionals and the public, improved coordination within the healthcare system, and targeted research to guide future interventions. This review provides cross-country insights into barriers to early sarcoma diagnosis, informing future priorities in clinical practice and research. PROSPERO REGISTRATION NUMBER: CRD420251030726.
18 Apr 2026
Read appraisal →Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Transitioning to adolescent and young adult or adult cancer survivorship care: A systematic review of contemporary guidelines and trials
BACKGROUND: Health service transitions of child, adolescent, and young adult cancer survivors between paediatric and adult cancer care services are pervasively fragmented, resulting in poor coordination, reduced satisfaction, and adverse outcomes for cancer survivors and significant others (e.g., caregivers and family members). Numerous trials and clinical guidelines have been developed to support care transitions, but their convergence, divergence, and methodological quality remain unclear. To advance clinical practice and quality research about care transitions, a synthesis of trials and guidelines on child, adolescent, and young adult care transition across age-appropriate cancer services is required to inform future research, practice, guideline, and policy development. METHODS: A systematic review (CRD420251029796) was conducted. Studies were identified from searches of six bibliographic databases, four trial registers, and grey literature. Inclusion criteria focused on clinical guidelines or trials published between January 2020 and April 2025 that addressed age-related transitional cancer care. RESULTS: A total of 3706 records were identified. After screening, 18 records met the inclusion criteria: 10 clinical guidelines, 4 completed trials, and 4 ongoing trials with registrations. While general recommendations between guidelines were consistent, they diverged in detail relating to their local contexts. Only two ongoing trials, and no completed studies, included independent control groups. CONCLUSION: Completed trials were limited and highly variable in approach, components, and outcome measures, suggesting regionally specific guidelines enhance relevance, applicability, and transition practices. Future research should develop core outcome sets for care transition trials to facilitate comparison of outcomes and should develop robust study designs, including control groups.
9 Apr 2026
Read appraisal →Cancer research
Multicenter Histology Image Integration and Multiscale Deep Learning Support Machine Learning-Enabled Pediatric Sarcoma Classification
UNLABELLED: Pediatric sarcomas present diagnostic challenges due to their rarity and diverse subtypes, often requiring specialized pathology expertise and costly genetic tests. To overcome these barriers, we developed a computational pipeline leveraging deep learning methods to accurately classify pediatric sarcoma subtypes from digitized histology slides. To ensure classifier generalizability and minimize center-specific artifacts, a dataset comprising 867 whole-slide images (WSI) from three medical centers and the Children's Oncology Group was collected and harmonized. Multiple convolutional neural network and vision transformer (ViT) architectures were systematically evaluated as feature extractors for SAMPLER-based WSI representations, and input parameters, such as tile size combinations and resolutions, were tested and optimized. The analysis showed that advanced ViT foundation models (UNI and CONCH) significantly outperformed earlier approaches, and incorporating multiscale features enhanced classification accuracy. The optimized models achieved high performance, distinguishing rhabdomyosarcoma (RMS) from non-RMS soft-tissue sarcomas (NRSTS) with an AUC of 0.969 and differentiating RMS subtypes (alveolar vs. embryonal) with an AUC of 0.961. Additionally, a two-stage pipeline effectively identified scarce Ewing sarcoma images from other NRSTS (AUC = 0.929). Compared with conventional transformer-encoder architectures used for WSI representations, these SAMPLER-based classifiers were three orders of magnitude faster to train, despite operating entirely without a graphical processing unit. This study highlights that digital histopathology paired with rigorous image harmonization provides a powerful solution for pediatric sarcoma classification. SIGNIFICANCE: An approach pairing a multi-institutional dataset with a published pipeline extends imaging-based diagnostic capabilities and creates the potential for accurate, rapid cancer diagnoses across resource-limited and remote settings. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI .
5 Apr 2026
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