Ganguly, Arup

e22007 Background: Long-term neurocognitive impairment is a major source of disability in survivors of pediatric CNS tumors. Proton radiotherapy may reduce dose to developing brain structures, potentially preserving cognition compared with conventional photon therapy. Methods: We performed a systematic review and meta-analysis of MEDLINE, Embase, PsycINFO, and CENTRAL. Eligible studies included pediatric CNS tumor patients treated with proton or photon radiotherapy reporting neurocognitive outcomes (full-scale IQ, attention, processing speed, executive function) over time. Standardized mean differences (SMD) were pooled using random-effects models, and slope analyses assessed longitudinal IQ change. Subgroups included age at radiotherapy, craniospinal vs focal fields, tumor type, chemotherapy exposure, and follow-up duration. Certainty of evidence was graded using GRADE. Results: Eleven studies encompassing 624 patients were included. Proton therapy was associated with significantly less decline in full-scale IQ compared with photon therapy (SMD 0.43, 95% CI 0.21–0.65, p < 0.001). Domain-specific analyses showed preservation of attention (SMD 0.36, 95% CI 0.10–0.61) and processing speed (SMD 0.41, 95% CI 0.18–0.64). Longitudinal slope analysis indicated an average IQ decline of 0.7 points/year after proton therapy versus 2.4 points/year after photon therapy. Benefits were greatest in younger children (<8 years) and those receiving craniospinal irradiation. Attrition and missing data were similar across groups. Conclusions: Proton radiotherapy in pediatric CNS tumors is associated with clinically meaningful preservation of neurocognitive function compared with photon therapy, particularly in younger patients and those receiving extensive fields. Clinical Takeaway: When available, proton therapy should be considered for children at high risk of cognitive decline to optimize long-term functional outcomes.

e19116 Background: PET/CT is the primary end-of-treatment (EOT) evaluation for diffuse large B-cell lymphoma (DLBCL); yet, false positives and insufficient prognostic clarity continue to be significant problems. Circulating tumor DNA (ctDNA)-based minimum residual disease (MRD) provides a tumor-informed, noninvasive way to assess recurrence risk. Methods: We used the MEDLINE, Embase, CENTRAL, and Web of Science databases to perform a systematic review and meta-analysis in accordance with PRISMA 2020 guidelines. DLBCL cohorts with end-of-treatment ctDNA-MRD status and survival outcomes were considered eligible research. The key outcome measures were progression-free survival (PFS) and overall survival (OS). Random-effects models calculated hazard ratios (HRs) and measured heterogeneity using I². Results: Eleven trials with 1,247 participants were included. Individuals with ctDNA-MRD had significantly worse progression-free survival (PFS) (pooled HR 5.48, 95% CI 3.96-7.58; I² = 42%) and overall survival (OS) (pooled HR 4.21, 95% CI 2.71-6.54; I² = 36%) compared to those without MRD. In MRD-positive patients, the 24-month recurrence rate was 68% compared to 14% in MRD-negative patients (absolute difference 54%, p < 0.001), with ctDNA indicating return 4.2 months before clinical advancement. In studies reporting combined PET/CT, ctDNA-MRD showed superior predictive performance, with a higher positive predictive value (79% vs 41%) and negative predictive value (92% vs 78%) compared to PET positivity. Conclusions: End-of-treatment ctDNA-MRD is a strong predictor of DLBCL recurrence and survival, outperforming PET/CT for risk classification. Integrating ctDNA-MRD into post-therapy assessments may allow for early intervention and reduce the number of unnecessary biopsies. Clinical Takeaway: ctDNA-MRD at EOT identifies high-risk DLBCL patients missed by imaging and supports precision-guided post-remission management.

e19090 Background: PET/CT remains crucial for end-of-treatment (EOT) evaluation in large B-cell lymphoma (LBCL), but low specificity results in unnecessary biopsies and patient discomfort. Circulating tumor DNA (ctDNA)-based minimum residual illness (MRD) may aid in the identification of actual residual sickness. Methods: We conducted a systematic review and meta-analysis of diagnostic accuracy using MEDLINE, Embase, CENTRAL, and Scopus. Eligible studies compared EOT ctDNA-MRD to PET/CT with verified recurrence or long-term remission. The outcomes were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The study's quality was rated using the QUADAS-2 scale. A bivariate random-effects model combined sensitivity and specificity, yielding hierarchical summary receiver operating characteristic (HSROC) curves. Results: Nine studies with a total of 932 participants were included. ctDNA-MRD showed higher specificity (92%, 95% CI 88-95%) and PPV (81%, 95% CI 73-88%) than PET/CT (specificity 68%, 95% CI 60-75%; PPV 46%, 95% CI 38-55%), while maintaining similar sensitivity. The negative predictive value for ctDNA was higher (91%, 95% CI 86-95%) than for PET (79%, 95% CI 72-85%). Combined PET+ctDNA techniques had the highest diagnostic odds ratio and fewer false positives. The results were similar across Deauville criteria and testing systems. Conclusions: ctDNA-MRD has higher specificity and predictive value than PET/CT at EOT in LBCL and significantly improves risk categorization whether used alone or in conjunction with imaging. Clinical Takeaway: Incorporating ctDNA-MRD into EOT assessment can reduce unnecessary biopsies and enable more accurate, confidence-based post-treatment decision-making.