Search Results (51,165)

Objectives: The objectives of this study were as follows: (1) statistical investigation of the association between systemic diseases and dental pulp condition; and (2) utilization of locally running large language models (LLMs) to handle a large number of dental charts written in natural languages, while protecting patients’ information. Methods: A total of 5820 endodontic charts, including healthy controls and patients with a history of cancer, HIV, type 1 diabetes mellitus (DM), and type 2 DM, were selected from 15,147 samples. Using a local LLM environment, the dental charts from each group were classified into six categories: normal pulp (NP); reversible pulpitis (RP); asymptomatic irreversible pulpitis (AIP); symptomatic irreversible pulpitis (SIP); pulp necrosis (PN); and “others”, including unclear diagnoses. The distributions of these diagnoses across groups were statistically analyzed. Results: The prompt for the local LLM was repeatedly refined by classifying 400 test cases, resulting in 97.0% agreement with the judgments of three human dentists. The refined prompt was then applied to classify 5820 charts, followed by statistical analyses. Using a generalized linear mixed-effects model (GLMM), the cancer-history group showed a significantly higher NP and a lower AIP proportion, whereas the type 2 DM group showed a significantly lower AIP and a higher SIP proportion. Conclusions: The findings in the cancer-history group could be attributable to a worsened oral environment in the patients and difficulties in diagnosing AIP. Meanwhile, the lower proportion of AIP and higher proportion of SIP in type 2 DM group may reflect pulpal inflammation associated with the disease. Additional attention may be warranted for caries’ prevention and treatment in patients with type 2 DM. Full article

Background/Objectives: In metastatic breast cancer (MBC) treated with CDK4/6 inhibitors, baseline neutrophil-to-lymphocyte ratio (NLR) is an established prognostic marker. On-treatment NLR dynamics have shown inconsistent associations with survival, and no prior study has applied a dominant-driver decomposition to classify patients by whether NLR change is neutrophil- or lymphocyte-driven. Methods: We retrospectively analyzed 352 patients with HR+/HER2− MBC treated with ribociclib. Using paired neutrophil and lymphocyte counts at baseline and at approximately 12 weeks (before cycle 4), a log-linear decomposition classified patients into four NLR-trajectory phenotypes by the dominant driver of change. Associations with progression-free survival (PFS) and overall survival (OS) were assessed using a 4-month landmark approach with multivariable Cox models, with consistency evaluated across four thresholds, tertiles, and a continuous model. Secondarily, NLR change was compared across five response-trajectory groups. Results: NLR trajectory was not associated with PFS in any specification (multivariable hazard ratio [HR] 1.15 per standard deviation [SD], 95% CI 0.97–1.37, p = 0.12) but was independently associated with OS (HR 1.40 per SD, 95% CI 1.18–1.67, p < 0.001), confirmed on bootstrap resampling. Adding NLR trajectory improved discrimination (C-index +0.04) and fit (likelihood-ratio p < 0.001). The OS effect was time-varying, attenuating beyond 24 months. NLR trajectory was unrelated to dose-limiting neutropenia (p = 0.58) or dose reduction (p = 0.69). Primary refractory patients showed blunted NLR decline versus responding or stable patients (p = 0.005), independent of baseline NLR. Conclusions: On-treatment NLR trajectory is a correlate of OS, independent of PFS, dose-limiting neutropenia, and dose reduction, in ribociclib-treated MBC, distinct from direct tumor control. Prospective validation is warranted. Full article

Background/Objectives: Tarin exhibits immunomodulatory and antiproliferative properties against several tumor cell lines. Nano-encapsulation in liposomes enhances its therapeutic potential by improving protein stability, bioavailability, and sustained release. Previous studies demonstrated that nano-encapsulated tarin induces cell cycle arrest, migration inhibition, apoptosis, and autophagy in triple-negative breast cancer cells; however, the molecular mechanisms underlying these effects remain poorly understood. To investigate the proteomic response elicited by nano-encapsulated tarin, MDA-MB-231 cells were treated for 24 and 48 h. Methods: Intracellular proteins were extracted, digested with trypsin, and analyzed by label-free LC-2D-MS/MS using HDMSE acquisition. Differentially expressed proteins were identified and quantified using the Progenesis QI platform, and then functional classification and pathway enrichment analyses were performed. Results: A total of 2818 proteins were identified, of which 2150 displayed time-dependent modulation following treatment. After 24 h, cells exhibited an adaptive stress response profile characterized by increased DNA repair proteins (CHEK1, CDK12), migration/remodeling factors (LAMA4, CTTN, A2M), and immune/cell cycle regulators (PER2, HLA-B), while antioxidant proteins (SOD1, GPX1) and BRCA1 were reduced, indicating oxidative stress and DNA damage. After 48 h, the proteomic profile shifted toward cell death, with increased PARK7, OPA1, ATL3, and CASP8 expression, disruption of DNA repair and cell cycle regulators (CHEK1, CDK12, MSH6, KIF2C), and decreased migration-related proteins (LAMA4, CTTN, ITGB3, A2M). Conclusions: Nano-encapsulated tarin promotes a time-dependent transition from early adaptive stress responses to apoptosis, autophagy, cell cycle disruption, and loss of migratory capacity. These findings provide novel insights into the molecular mechanisms underlying tarin antitumoral activity and support its potential as a promising therapeutic strategy against triple-negative breast cancer. Full article

Background: Although POLD1 exhibits oncogenic properties in multiple malignancies, its precise role and regulatory mechanisms in cisplatin resistance of bladder cancer (BC) remain elusive. This study aims to elucidate the functional involvement and upstream regulatory axis of POLD1 in BC chemoresistance. Methods: We evaluated the impact of POLD1 on chemoresistance and DNA damage repair (DDR) using public clinical databases and cisplatin-resistant cell lines, employing CCK-8, colony formation, flow cytometry, immunofluorescence, and comet assays. Protein interactions were examined via Co-IP, molecular docking, and truncation mutant analysis. ChIP-PCR and dual-luciferase reporter assays were utilized to identify the upstream transcription factor. In vivo functionality was further validated in a nude mouse xenograft model. Results: POLD1 was markedly upregulated in BC tissues and cisplatin-resistant BC cells, and its elevated expression was tightly associated with advanced tumor stage, high pathological grade, and poor patient prognosis. Functional experiments verified that POLD1 knockdown aggravated cisplatin-induced DNA damage and drastically sensitized BC cells to cisplatin in vitro, and attenuated tumor growth under cisplatin treatment in vivo, indicating that POLD1 is a key driver of cisplatin resistance. Mechanistically, POLD1 physically interacted with and activated ATM, thereby initiating homologous recombination (HR) repair signaling. Moreover, transcription factor MAZ directly bound the promoter region of POLD1 to transcriptionally upregulate its expression. Rescue experiments in vitro further validated that the MAZ-POLD1 axis facilitates cisplatin resistance by modulating the DDR pathway in BC. Conclusions: Therapeutic targeting of the POLD1-regulated DDR pathway holds great promise as an effective strategy to reverse acquired cisplatin resistance in BC. Full article

Background: Precision oncology has significantly transformed the management of non-small cell lung cancer (NSCLC) through the integration of molecular diagnostics, targeted therapies, and biomarker-driven treatment selection. Advances in next-generation sequencing (NGS) and liquid biopsy have improved the identification of actionable molecular alterations and enabled dynamic monitoring of tumor evolution. Objective: To provide a structured narrative review of current evidence regarding actionable molecular biomarkers, diagnostic methodologies, targeted therapies, and future directions in NSCLC precision oncology, with a specific focus on conceptualizing acquired resistance mechanisms. Methods: A structured narrative literature review was conducted by searching PubMed and Google Scholar for English-language studies published between 2015 and 2026. Eligible publications included clinical trials, cohort studies, translational research, reviews, and clinical guidelines addressing molecular profiling, targeted treatments, diagnostic approaches, and resistance mechanisms in NSCLC. Results: A total of 99 foundational studies and clinical documents were analyzed. Key actionable biomarkers included EGFR (Epidermal Growth Factor Receptor), ALK (Anaplastic Lymphoma Kinase), ROS1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase), KRAS (Kirsten Rat Sarcoma Viral Oncogene Homolog), RET (Rearranged during Transfection), MET (Mesenchymal–Epithelial Transition Factor), HER2 (Human Epidermal Growth Factor Receptor 2) and NTRK (Neurotrophic Tyrosine Receptor Kinase) alterations, along with emerging targets such as NRG1 (Neuregulin 1) fusions. NGS emerged as the cornerstone of comprehensive molecular profiling, while liquid biopsy enabled longitudinal monitoring of tumor dynamics and resistance development. To organize the biological complexity of treatment failure, acquired resistance mechanisms were categorized into a three-tiered conceptual framework: target-centric genetic evolution (Tier 1), cellular plasticity and intratumoral heterogeneity (Tier 2), and non-genetic/microenvironmental adaptation (Tier 3). Targeted therapies significantly improved clinical outcomes compared with conventional chemotherapy; however, acquired resistance remained a major challenge across all tiers. Conclusions: Precision oncology in NSCLC is evolving from a biomarker-focused approach toward a dynamic framework integrating molecular diagnostics, targeted therapies, and continuous resistance monitoring. The proposed three-tiered resistance framework provides a structured basis for understanding treatment failure, guiding molecular reassessment at progression, and informing future adaptive therapeutic strategies to improve long-term patient outcomes. Full article

Background: Organized cervical cancer screening aims to reduce the burden of advanced disease through earlier detection. However, a substantial proportion of women continue to present with locally advanced cervical cancer (LACC) requiring definitive chemoradiation. This study evaluated temporal changes in the demographic and clinicopathological characteristics of women with LACC treated with definitive chemoradiation before and after implementation of the organized cervical cancer screening program in Serbia. Methods: This retrospective single-center cohort study included 200 consecutive women with histologically confirmed LACC treated with definitive chemoradiation at the Institute of Oncology and Radiology of Serbia. Two cohorts were analyzed: a pre-screening cohort (2010–2011, n = 100) and a post-screening cohort (2022–2023, n = 100). Demographic and clinicopathological characteristics, including age, histopathology, FIGO stage, lymph node involvement, and geographic distribution, were compared. For study purposes, all patients were retrospectively restaged according to the FIGO 2018 classification using the best available clinical, radiological, and pathological data. Results: Women in the post-screening cohort were significantly older at diagnosis than those in the pre-screening cohort (mean age 54.9 vs. 49.7 years, p = 0.0046), with a substantially higher proportion of patients older than 64 years (28% vs. 2%, p < 0.0001). Although the overall distribution of FIGO stages II–IV did not differ significantly, a marked redistribution of FIGO 2018 substages was observed (p < 0.0001), characterized by an increased proportion of stage IIIC disease and significantly more frequent lymph node involvement (63% vs. 41%, p = 0.0018). Geographic distribution remained stable, with most patients referred from the Belgrade administrative district. Conclusions: This study demonstrated clinically relevant temporal changes in the demographic and clinicopathological characteristics of women requiring definitive chemoradiation for LACC in Serbia. More than a decade after implementation of organized cervical cancer screening, tertiary referral centers continue to manage a substantial burden of patients with locally advanced disease requiring complex, resource-intensive treatment. These findings should not be interpreted as a direct evaluation of the national screening program but may provide valuable insights for healthcare planning in Serbia and other countries with similarly resource-constrained healthcare systems. Strengthening participation in organized screening, ensuring timely diagnostic evaluation, and improving HPV vaccination uptake remain essential to reduce the burden of advanced cervical cancer. Full article

Focused ultrasound (FUS) is an emerging and evolving minimally invasive therapeutic platform that is helping to redefine the management of malignant diseases. Clinical translation is advancing rapidly, with several completed and ongoing clinical trials demonstrating the safety, feasibility, and early efficacy of FUS in the treatment of cancer. This manuscript provides a synthesis of some of the available clinical data and device platforms being used and evaluates the results from completed and active clinical trials for cancers involving four different solid organs. To stay within the editorial parameters of the invited article, this review will not provide a meta-analysis of clinical trials data and/or the literature but rather highlight some of the currently available clinical evidence and FUS technologies that have been used in the treatment of cancers of the brain, liver, prostate gland, and breast. Full article

Background: The comparative prognostic value of the Endothelial Activation and Stress Index (EASIX) and the Inflammatory Prognostic Index (IPI) in extensive-stage small-cell lung cancer remains unclear. This study aimed to compare the prognostic value of EASIX and IPI and assess their contribution beyond established clinical factors. Methods: This retrospective single-center study included 129 patients with de novo extensive-stage small-cell lung cancer who initiated first-line systemic therapy between December 2022 and October 2025. Pretreatment EASIX and IPI values were analyzed as log₂-transformed continuous variables in multivariable Cox models. Overall survival was the primary outcome, and first-line progression-free survival was the secondary outcome. Results: During a median follow-up of 26.91 months, 116 deaths and 123 progression-or-death events occurred. Each doubling of the EASIX value was independently associated with a higher hazard of death (adjusted hazard ratio, 1.14; 95% confidence interval, 1.01–1.28; p = 0.019), whereas IPI was not independently associated with overall survival. Neither index was independently associated with first-line progression-free survival. Adding EASIX to the clinical model improved model fit and increased the C-index from 0.619 to 0.650, whereas IPI provided no additional prognostic contribution. Conclusions: EASIX may provide prognostic information beyond established clinical factors for overall survival in extensive-stage small-cell lung cancer. These findings warrant validation in larger multicenter cohorts. Full article

Cancer cachexia is a multifactorial metabolic syndrome characterized by progressive skeletal muscle loss, affecting 30–60% of patients with advanced renal cell carcinoma (RCC). It significantly impacts treatment tolerance, quality of life, and prognosis, yet its diagnosis and management remain challenging due to fragmented RCC-specific evidence, particularly in the era of immune checkpoint inhibitor (ICI)-based therapy. The pathogenesis involves persistent systemic inflammation, metabolic reprogramming, and tumor–host interactions. The IL-6/STAT3 and TNF-α/NF-κB pathways are central to muscle catabolism, while tumor-derived mediators such as GDF15 and PTHrP, along with mitochondrial dysfunction, further drive cachexia progression. For prognostic assessment, CT-derived skeletal muscle mass evaluation combined with systemic inflammatory and nutritional biomarkers—including neutrophil-to-lymphocyte ratio (NLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), and cachexia index (CXI)—has improved risk stratification in advanced RCC. Preclinical and emerging clinical data suggest that targeted therapies may partially attenuate cachexia by modulating inflammatory signaling, while multimodal interventions integrating nutritional support and exercise rehabilitation remain the cornerstone of management. Novel strategies, such as inhibition of the GDF15/GFRAL axis, are under active investigation. Future research should prioritize identification of early biomarkers, standardization of cachexia assessment, and prospective evaluation of cachexia-directed interventions in the immunotherapy era. Integrating cachexia assessment into routine practice may ultimately enable personalized treatment and improve long-term outcomes for patients with advanced RCC. Full article

Colorectal cancer (CRC) has shown significant heterogeneity regarding its response to immunotherapy. Long-lasting, beneficial effects have been observed in mismatch repair-deficient, microsatellite instability-high (dMMR/MSI-H) tumours, while mismatch repair-proficient, microsatellite stable (pMMR/MSS) tumours have remained resistant. Such differences in results have been studied in this review through the “hot” and “cold” tumour concept. It explains how various biological and microenvironmental factors play a role in immune resistance and T-cell priming and infiltration. Key factors include a low neoantigen load and defects in antigen presentation, which reduce the overall immune recognition of tumour cells. The review also studies certain processes such as Wnt/β-catenin and mitogen-activated protein kinase (MAPK) signalling and what input they have in the prevention of effective antitumour immune responses. Conventional treatments like chemotherapy and radiotherapy have been considered alongside more targeted treatments such as the inhibition of vascular endothelial growth factor (VEGF) signalling and the suppression of myeloid-mediated immune evasion, to convert “cold” MSS tumours into immune-responsive lesions. Methods which aim to modify the tumour microenvironment such as metabolic reprogramming and microbiome modulation have also been covered in this review. Artificial intelligence and nanomedicine are new technologies that could provide improved patient stratification and therapeutic precision, although their clinical application in pMMR/MSS CRC remains under investigation. A systematic literature search of PubMed and PubMed Central (PMC) was conducted from 10 June 2026 to 19 August 2026 using predefined eligibility criteria, with study selection reported according to PRISMA 2020. Because of substantial heterogeneity in study design, therapeutic approach and reported outcomes, the included evidence was synthesized narratively rather than by meta-analysis. A total of 158 studies were included. Full article

Background/Objectives: Evidence on longitudinal changes in nutrition, inflammation, and body composition during adjuvant chemotherapy for Stage II/III colorectal cancer (CRC) remains limited. We therefore evaluated these changes and explored preoperative factors associated with treatment discontinuation and prognosis. Methods: This single-center retrospective study included patients with Stage II/III CRC who underwent curative surgery and adjuvant chemotherapy. Body mass index (BMI), computed tomography (CT)-derived psoas muscle index (PMI), psoas muscle density (PMD), modified intramuscular adipose tissue content (mIMAC), Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), hemoglobin–albumin–lymphocyte–platelet (HALP) score, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were assessed preoperatively and 6 months after chemotherapy initiation. Analyses were stratified into oxaliplatin-based doublet therapy (CAPOX/FOLFOX) and fluoropyrimidine monotherapy. Results: Among 142 patients, GNRI, PNI, and HALP score increased, whereas BMI, NLR, and PLR decreased from preoperative assessment to follow-up. Adjuvant therapy was discontinued in 45 patients (31.7%). In the doublet therapy group, discontinuation was associated with lower preoperative GNRI, PNI, and HALP scores and higher NLR and PLR. In the monotherapy group, only older age was associated with discontinuation. Lower preoperative PMD and mIMAC, but not PMI, were associated with poorer overall survival. No other nutritional or inflammatory markers were associated with overall survival. Conclusions: Several nutritional and inflammatory markers improved from preoperative assessment to follow-up. Preoperative nutritional and inflammatory markers were associated with treatment discontinuation, particularly in the doublet therapy group. CT-derived muscle quality markers were associated with overall survival, suggesting prognostic relevance of muscle quality in this setting. Full article

Background/Objectives: Women undergoing endocrine therapy after breast cancer often experience sexual-health concerns, but opportunities for individualized nursing support are limited. This case series implemented and preliminarily evaluated a novel sexual health-care model for women undergoing endocrine therapy after breast-cancer treatment. Methods: A care model was developed from Comfort Theory, a literature review, and clinical experience and underwent content-validity review by experts, including one nurse with lived experience of breast cancer. It was implemented individually for 6 months in five premenopausal women receiving endocrine therapy after breast-conserving surgery or total mastectomy. Data included baseline characteristics, care records, final interviews, and Self-affirmation Scale scores. Nursing goal attainment and final interviews were evaluated qualitatively. Results: All nursing goals appeared to have been achieved based on provider assessment and participants’ narratives. Participants gradually expressed distress, questions, and sexual health needs related to bodily and sexual changes, developed greater understanding of treatment-related changes, identified individualized coping strategies, and showed greater self-worth and self-care. Self-affirmation scores were descriptively higher after care. Phenomenological analysis identified four constituents: having a place to discuss a body marked by breast and fertility loss; sharing with a midwife who accepted them as they were; reconnecting with their changed bodies; and discovering new meaning in life with altered fertility and bodily integrity. Conclusions: The care model may provide a safe, individualized space for women undergoing endocrine therapy after breast cancer to express concerns, understand bodily changes, and reconstruct meaning. The findings are preliminary and represent provider-assessed observations rather than evidence of effectiveness. Full article

Background: Sarcomatoid renal cell carcinoma (sRCC) is an aggressive RCC subtype with a poor prognosis. Although racial disparities in RCC outcomes are reported, survival patterns across racial and ethnic groups in metastatic sRCC (msRCC) remain unclear. Methods: We conducted a retrospective analysis of 2122 patients with msRCC diagnosed between 2010 and 2020 using the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized by race and ethnicity as non-Hispanic White, non-Hispanic Black, Hispanic, Asian/Pacific Islander, or American Indian/Alaska Native. Three-year cancer-specific survival (CSS) and overall survival (OS) were estimated using Kaplan–Meier methods. Multivariable Cox proportional hazards regression models were used to evaluate racial disparities in survival. Results: Non-Hispanic Black patients experienced the poorest outcomes, with 3-year CSS and OS of 9.3% and 8.6%, compared with 23.3% and 20.9% in non-Hispanic White, 22.1% and 19.0% in Hispanic, 21.2% and 19.4% in Asian/Pacific Islander, and 23.4% and 20.7% in American Indian/Alaska Native patients. Non-Hispanic Black patients were associated with higher estimated hazards of cancer-specific mortality (HR = 1.5, p < 0.0001) and overall mortality (HR = 1.5, p < 0.0001) versus non-Hispanic White. From 2010–2015 to 2016–2020, survival improved across most racial groups with the introduction of immune checkpoint inhibitors. However, non-Hispanic Black patients remained the only group with persistently inferior survival. Subgroup analysis further demonstrated worse survival for non-Hispanic Black patients in both clear cell msRCC and non-clear cell msRCC subgroups. Conclusions: Although survival was higher during the later diagnosis period, non-Hispanic Black patients with msRCC continued to have the poorest observed survival. These differences may be associated with unmeasured social, structural, socioeconomic, healthcare access, treatment, or clinical factors, but their causes cannot be determined from this observational study. Further research is needed to identify the factors underlying these survival differences. Full article

Venous thromboembolism (VTE) was once considered rare in the young, but it has become an increasingly important complication of contemporary pediatric care, driven by the improved survival of children with complex chronic illness and by the expanding use of central venous catheters. This narrative review synthesizes current evidence on VTE across the entire pediatric age range, from the critically ill neonate to the injured adolescent. We first examine noncerebral VTE in children beyond the newborn period, describing an incidence that is far lower than in adults yet rising among hospitalized patients, the multifactorial risk factors dominated by central venous catheters, and the age-dependent protection conferred by developmental hemostasis. We outline a diagnostic approach centered on compression ultrasonography and computed tomography pulmonary angiography, and a treatment paradigm that increasingly favors direct oral anticoagulants and shorter, six-week courses for low-risk provoked events. Dedicated sections address the distinct biology, presentation, and management of neonatal thrombosis, including renal vein thrombosis, portal vein thrombosis, and purpura fulminans, for which low-molecular-weight heparin is preferred and warfarin is generally avoided. We review the heightened, malignancy-specific risk of cancer-associated thrombosis, the difficulty of anticoagulating the thrombocytopenic child, and the consistent evidence against routine primary thromboprophylaxis. Cerebral sinovenous thrombosis is considered in depth, emphasizing its age-dependent triggers, the central role of magnetic resonance venography, and the safety of anticoagulation. Finally, we summarize the comparatively low but age-graded risk of VTE after major pediatric trauma and the puberty-based approach to prophylaxis. Throughout, we highlight the continued reliance on extrapolated adult data, the emergence of pediatric randomized trials and multicenter registries, and the unmet need for prospectively validated risk-prediction tools. The review offers clinicians an integrated, contemporary framework for recognizing, diagnosing, treating, and preventing thrombosis from the neonate to the adolescent. Full article

Background/Objectives: While perioperative chemotherapy is standard for locally advanced gastric cancer, no baseline blood marker reliably identifies which patients will respond to treatment. In this retrospective study, we compared eleven inflammatory and nutritional indices against pathological response and survival using data collected between 2020 and 2025. Methods: We analyzed 130 patients with gastric adenocarcinoma receiving perioperative systemic therapy at two centers. Eleven indices—the neutrophil-to-lymphocyte ratio (NLR), systemic immune–inflammation index (SII), Prognostic Nutritional Index (PNI), and eight further indices defined—were assessed against the Mandard tumor regression grade (TRG), overall survival (OS), and disease-free survival (DFS). Results: The median age was 63 years, and the median follow-up was 22.1 months from diagnosis. A Mandard TRG was assigned in 123 patients, 32 of whom achieved a major pathological response (TRG 1–2). The PNI had the highest point estimate of discrimination for major pathological response (AUC 0.618, 95% CI 0.490–0.746; p = 0.070), but its area under the curve did not differ significantly from that of any other index (all p ≥ 0.18), and bootstrap validation incorporating index selection and threshold derivation yielded an optimism-corrected AUC of 0.567. While PNI ≥ 53 was nominally associated with TRG 1–2 (OR 3.823, 95% CI 1.503–9.722; p = 0.005), no association survived correction for multiple comparisons, and the PNI was selected as the best-performing index in only 49% of bootstrap resamples. No index showed a statistically significant association with overall survival, and the event count is insufficient to establish the presence or absence of an association. Conclusions: None of the eleven baseline blood-based indices demonstrated statistically robust or clinically useful discrimination for major pathological response, and none were associated with survival. Although the PNI represented the most promising exploratory signal, its apparent advantage was not statistically distinguishable from the other indices and did not survive internal validation. The threshold of approximately 53 should be regarded as hypothesis-generating only. Full article