Search Results (8,893)

Background: Baseline lymphopenia is common among advanced solid tumors and may influence the efficacy/safety of immune checkpoint inhibitors (ICIs), but large real-world evidence is limited. We evaluated the association between baseline absolute lymphocyte count (ALC) and clinical outcomes in adults with solid tumors treated with ICIs in routine practice. Methods: We performed a retrospective cohort study using TriNetX. Adults with solid tumors who received pembrolizumab, nivolumab, or atezolizumab (ICI-Naïve) between January 2015 and June 2026 were included. Baseline ALC was measured within 30 days before first treatment and was classified as lymphopenic (ALC < 1.5 × 10⁹/L) or non-lymphopenic (ALC ≥ 1.5 × 10⁹/L). Propensity score matching (1:1) yielded 5249 patients per group. The index date was the first immunotherapy date, and outcomes were assessed at 6, 12, 24, 36 months, and 5 years. The primary outcome was 24-month overall survival (OS); secondary outcomes were OS at 6 and 12 months and 6-month risks of healthcare utilization, immune-related adverse events (irAEs), and serious infections; and exploratory outcomes included OS at 36 months and 5 years. All outcomes were analyzed using Kaplan–Meier analysis, Cox proportional hazards models, and risk ratios. Subgroup analysis included OS stratified by solid tumor subtypes and prior lines of therapy. Results: After matching, patients with baseline lymphopenia had consistently worse OS. Compared with patients without lymphopenia, the lymphopenia cohort had lower OS at 6 months (HR 1.29, 95% CI 1.22–1.37), 12 months (HR 1.28, 95% CI 1.21–1.35), 24 months (HR 1.26, 95% CI 1.2–1.33), and, in exploratory analyses with substantial right censoring and limited observed follow-up, 36 months (HR 1.26, 95% CI 1.2–1.33) and 5 years (HR 1.26, 95% CI 1.2–1.33), though these estimates should be considered hypothesis-generating only. At 6 months, baseline lymphopenia was associated with a greater healthcare utilization (RR 1.05, 95% CI 1.02–1.09), a higher infection risk (RR 1.08, 95% CI 1.01–1.15), and similar rates of clinically coded irAEs (RR 1.0, 95% CI 0.93–1.09), an observation subject to competing risk from early mortality in the lymphopenic cohort. Subgroup analysis, stratified by tumor subtypes and prior lines of therapy, showed consistently lower OS in the lymphopenia group, consistent with the primary outcome results. Conclusions: In this large propensity-matched real-world analysis of 10,498 patients with diverse solid tumors, baseline lymphopenia at ICI initiation was associated with persistently inferior OS at 6, 12, and 24 months (primary and secondary endpoints), greater early healthcare utilization, and a higher serious infection risk. Critically, lymphopenic patients developed irAEs at an identical rate to non-lymphopenic patients despite worse survival, a dissociation suggesting that baseline ALC stratifies patients along mortality risk and immune activation capacity as partially independent axes. These findings could support the use of baseline ALC as a simple, universally available biomarker that informs not only survival prognosis but also the anticipated toxicity profile of ICI therapy and highlight the need for competing-risk analyses and prospective immune phenotyping to characterize this relationship fully. Full article

Background: Response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) varies considerably, and oxidative stress may modulate radiosensitivity. This study evaluated ischemia-modified albumin (IMA) and thiol–disulfide homeostasis as potential biochemical predictors of pathological tumor regression. Methods: A prospective observational cohort study was conducted to assess pre- and post-treatment oxidative stress biomarkers in patients with LARC receiving capecitabine-based long-course CRT. Serum IMA, native thiol, total thiol, and disulfide levels were quantified spectrophotometrically. Pathologic regression was graded according to the Modified Ryan system as good (TRG 0–1) or poor (TRG 2–3). Receiver operating characteristic (ROC) analyses, Firth-penalized logistic regression, and internal validation using cross-validation, calibration, and decision-curve analyses were performed. Results: Of 38 screened patients, 31 met eligibility criteria and completed CRT, alongside 31 matched healthy controls. Compared with controls, patients had higher baseline disulfide (15.7 ± 5.2 vs. 11.9 ± 3.1 µmol/L; p = 0.012) and IMA levels (0.886 ± 0.062 vs. 0.798 ± 0.048 ABSU; p = 0.006). Poor responders exhibited higher pre-treatment IMA (0.927 ± 0.045 vs. 0.842 ± 0.050 ABSU; p = 0.020) and disulfide levels (18.4 ± 5.2 vs. 13.0 ± 3.8 µmol/L; p = 0.012). Pre-treatment IMA demonstrated the highest predictive accuracy for poor tumor regression (AUC = 0.872; 95% CI 0.751–0.993). In multivariable Firth-penalized logistic regression, elevated baseline IMA was independently associated with poor pathological response (OR = 3.63; 95% CI 1.22–16.20; p = 0.043), whereas negative circumferential resection margin (CRM) status was independently associated with favorable regression (OR = 0.21; 95% CI 0.02–0.71; p = 0.003). The internally validated model demonstrated excellent discrimination (AUC = 0.948; 95% CI 0.866–0.966) and good calibration. Conclusions: Baseline IMA and CRM status were independently associated with pathological response after CRT in LARC. These findings suggest that oxidative-stress biomarkers may have potential value for response stratification; however, the results should be considered exploratory and require external validation in larger independent cohorts before clinical application. Full article

Hashimoto thyroiditis (HT) coexists with differentiated thyroid carcinoma (DTC), particularly papillary thyroid carcinoma, in approximately 25% of cases. However, the impact of this association on DTC outcomes remains controversial. The aim of this study was to analyze the influence of Hashimoto thyroiditis on disease-specific survival (DSS) and recurrence-free survival (RFS) in DTC patients. Methods: A retrospective study conducted at our institution between 2007 and 2020 analyzed 707 DTC patients treated with surgery and/or I-131 therapy. Cox proportional hazards regression was used to identify independent predictors, including sex, age, tumor histology, HT status, and initial TNM stage. Results: Among 707 DTC patients, 628 (88.8%) had papillary cancer, 582 (82.3%) were female, 395 (55.9%) were <55 years old; HT coexisted in 137 (19.4%) patients. During follow-up, 23 (3.25%) developed recurrent disease; at last follow-up, 638 (90.2%) were alive. Initial distant metastases (p < 0.001) and higher T stage (p = 0.002) independently predicted worse DSS. For RFS, male sex (p = 0.015), higher T stage (p = 0.018), and lymph node involvement (p = 0.023) independently predicted an increased risk of recurrence. HT was not an independent predictor of DSS (HR 0.97, 95% CI 0.21–4.52; p = 0.964) or recurrence (HR 0.36, 95% CI 0.05–2.73; p = 0.322). Conclusions: Although Hashimoto thyroiditis was associated with favorable clinicopathological features, it was not independently associated with disease-specific or recurrence-free survival. Conventional staging parameters, particularly tumor stage, remain the principal determinants of prognosis in differentiated thyroid cancer. Full article

Background: Biliary drainage is a key component of palliative management in patients with malignant biliary obstruction. In cases where endoscopic approaches are unsuccessful or cannot be performed, percutaneous transhepatic biliary drainage (PTBD) represents an established alternative for achieving biliary decompression. The C-reactive protein–albumin–lymphocyte (CALLY) index combines inflammatory, nutritional, and immune-related parameters into a single marker, while the modified Glasgow Prognostic Score (mGPS), based on C-reactive protein and albumin concentrations, reflects the systemic inflammatory status of the patient. This study aimed to evaluate the prognostic value of the preprocedural CALLY index and mGPS in predicting 30-day mortality among patients with advanced malignant biliary obstruction undergoing palliative PTBD. Methods: This single-center retrospective study was conducted in a total of 179 patients who underwent palliative PTBD for malignant biliary obstruction at Ankara Etlik City Hospital between December 2022 and June 2025. Results: The 30-day mortality rate was 25.1%. The cut-off value for CALLY was determined as 67 based on receiver operating characteristic (ROC) curve analysis, and mGPS was categorized as 0–1 versus 2. In univariable Cox regression analyses, pancreaticobiliary tumor type, mGPS = 2, and CALLY < 67 were associated with early mortality. In multivariable Cox analysis, CALLY ≥ 67 was independently associated with a reduced risk of 30-day mortality, whereas pancreaticobiliary tumor type was independently associated with an increased risk. In the CALLY–mGPS risk stratification, 30-day mortality rates were 8.0%, 13.5%, and 44.1% in the low-, intermediate-, and high-risk groups, respectively. Conclusions: In this retrospective cohort, preprocedural inflammation- and nutrition-based markers were found to be associated with early mortality in patients with malignant biliary obstruction undergoing PTBD. Accordingly, risk stratification using readily available parameters such as CALLY and mGPS appears feasible in the preprocedural setting. The CALLY–mGPS-based approach may provide a practical framework for clinical risk assessment; however, prospective multicenter validation, including tumor-specific subgroup analyses, is warranted. Full article

Background: Age at diagnosis and histologic differentiation are clinically relevant in early gastric cancer (GC), as poorly differentiated tumors and those diagnosed in younger patients often demonstrate more aggressive characteristics. Serum microRNAs (miRNAs) may provide insights into the molecular basis of these features. Methods: We compared expression profiles between undifferentiated and differentiated early GC cases to identify differentially expressed miRNAs (DEmiRNAs) and associated enriched pathways. Using Lasso regression, we developed and cross-validated a histologic differentiation classifier based on miRNA profiles from 1399 early GC serum samples. Finally, cancer-specific miRNA differences between adolescent and young adult (AYA) and non-AYA patients were evaluated using samples from cancer cases and normal controls. Results: We identified 75 differentiation-associated DEmiRNAs targeting genes enriched in cancer hallmark pathways such as TP53 and PI3K/AKT/mTOR signaling. In the validation set, the combined Lasso model predicted differentiation status with a sensitivity of 69.2%, specificity of 75.3%, positive predictive value (PPV) of 66.9%, negative predictive value (NPV) of 77.2%, an overall accuracy of 73.1%, and an area under the curve (AUC) of 79.7%. Comparison of AYA and non-AYA groups identified 52 cancer-specific and age-related miRNAs. Notably, three components of a previously reported four-miRNA GC diagnostic signature were significantly associated with age. Conclusions: Age-related variation in miRNA expression suggests that patient age may influence the performance of the existing four-miRNA diagnostic signature in early GC. Overall, our findings demonstrate the utility of miRNA profiling for predicting differentiation status in early GC and reveal age-associated variation in cancer-specific miRNAs. Full article

Mitochondrial reactive oxygen species (mtROS) are central regulators of cellular function, yet their biological roles are often reduced to an oxidative-stress/antioxidant dichotomy. This review reframes mtROS through the concept of mitohormesis, in which outcomes are neither inherently harmful nor beneficial but are determined by a defined set of contextual variables. We present a mechanistic framework in which mtROS effects depend on chemical species identity, sub-mitochondrial site of production, temporal dynamics, redox-buffering capacity, and metabolic state; together, these variables determine whether mtROS promote adaptive eustress or pathological distress. We then show that, across polyphenols, isothiocyanates, terpenoids, alkaloids, and quinones, the biologically relevant effects of natural redox-modulating compounds are mediated less by direct radical scavenging than by pro-hormetic mechanisms, including mild electron transport chain perturbation, nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (NRF2/KEAP1) activation, modulation of mitochondrial membrane potential, mitochondrial quality control, and NAD⁺/NADPH regulation. Applying this framework to disease reveals strong tissue and state dependence: neurodegeneration favors buffering expansion and mitophagy; metabolic disease may benefit from exercise-mimetic and NRF2-activating strategies; cardiovascular disease illustrates mitohormesis through ischemic preconditioning and CoQ10 supplementation; and cancer requires distinction between prevention and therapy because redox buffering can either protect normal tissue or support tumor survival. Finally, we argue that the failure of non-specific antioxidant supplementation is mechanistically predictable and propose context-aware, biomarker-guided, temporally optimized, and compartment-targeted redox interventions as a more rational translational path. Full article

Major depressive disorder (MDD) is a complex and heterogeneous psychiatric disorder with a high prevalence. Neuroinflammation may define biologically distinct patient subgroups with different mechanisms, clinical phenotypes, and treatment responses. This narrative review integrates current evidence around three linked questions: how neuroinflammatory processes contribute to depression, how biomarkers can identify clinically relevant inflammatory phenotypes, and how these findings can inform anti-inflammatory treatment strategies. The major mechanisms discussed include microglial activation and neuroimmune signaling, hypothalamic–pituitary–adrenal axis dysregulation and glucocorticoid receptor resistance, kynurenine pathway alterations, and cytokine-driven impairment of neurogenesis and synaptic plasticity. These pathways interact with stress responses, neurotransmitter systems, and neuronal function, while their expression may vary according to sex, age, hormonal status, disease stage, and treatment exposure. These interconnected pathways may contribute to depressive symptoms by disrupting neurotransmitter systems and impairing neural plasticity. In addition, this review discusses several candidate biomarkers, including C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF) and transforming growth factor-β1 (TGF-β), which may support patient stratification, treatment prediction, and assessment of target engagement. Clinical trials of anti-inflammatory agents have shown inconsistent and generally modest effects in unselected MDD populations. By integrating mechanistic evidence with biomarker-guided therapeutic implications, this review aims to clarify how neuroinflammatory research may inform more precise and individualized treatment strategies for depression. Full article

Melanoma treatment has been transformed by immune checkpoint blockade, yet many patients still experience primary resistance, limited durability of response, or acquired resistance. These limitations underscore the need for additional targets that reflect melanoma biology while enabling new therapeutic strategies, particularly in biologically defined settings of immune escape such as checkpoint-resistant, HLA-low, dedifferentiated, or stress-adapted melanoma. The B7-H6/NKp30 axis has gained attention as a link between tumor cell stress, immune recognition, and therapy-related adaptation. B7-H6 (NCR3LG1), an inducible ligand for NKp30, has been detected in melanoma cell lines and tumor specimens, and soluble B7-H6 has been identified in a subset of patients. Membrane-bound B7-H6 may support NK-cell activation, whereas ligand shedding and accumulation of soluble B7-H6 may reduce effective antitumor recognition and promote immune evasion. Emerging evidence further suggests that B7-H6 expression may be linked to tumor-intrinsic programs relevant to melanoma cell survival, migration, and adaptation to therapeutic stress. However, B7-H6 is not yet a validated predictive biomarker or an established therapeutic target in melanoma, and current evidence remains limited by small melanoma-specific datasets, incomplete information on spatial and temporal heterogeneity, and the absence of melanoma-focused clinical validation. In this review, we examine the role of the B7-H6/NKp30 axis in immune surveillance, tumor escape, biomarker development, and therapeutic targeting, and discuss its translational potential in melanoma as an emerging but incompletely validated pathway that warrants focused investigation in melanoma states where conventional immune control is limited. Full article

Melanoma is the most aggressive type of skin cancer, driven by early invasion, phenotypic plasticity, and frequent resistance to targeted therapies. Although genomic profiling informs treatment selection, genotype alone often fails to predict therapeutic response, underscoring the need for rapid and physiologically relevant functional testing platforms. Here, we present a three-dimensional melanoma–skin organoid (mSO) model that integrates primary skin cells with melanoma cell lines in a self-assembling, high-throughput format. The spherical mSOs recapitulate native human skin architecture, including a stratified epidermis and a dermal–hypodermal core, while supporting melanoma growth within an appropriate tissue microenvironment. In this niche, melanoma cells display epidermal spreading in radial growth-like patterns, outward invasion, and transcriptional shifts toward a pro-invasive phenotype. Using live confocal imaging coupled with a custom automated image analysis pipeline, we quantitatively measured tumor growth, migration beyond the organoid boundary, and interactions between melanoma cells and normal melanocytes. The mSOs also captured genotype-specific drug responses: BRAF-mutant melanoma cells were sensitive to BRAF and MEK inhibition, whereas NRAS-mutant, BRAF–wild-type cells were resistant to BRAF inhibition but remained responsive to MEK inhibition. Altogether, our mSO platform combines architectural and functional complexity with experimental scalability, providing a robust framework for modeling melanoma progression and evaluating targeted therapeutic responses within a relevant skin microenvironment. In the future, adaptation of this system to include patient-derived tumor cells could support personalized therapeutic decision-making in melanoma. Full article

Precision medicine in prostate cancer (PCa) is increasingly best understood as a continuum linking risk-adapted detection, multimodal diagnosis and phenotyping, and implementation-ready decision pathways. Contemporary clinical guidelines emphasize structured diagnostic strategies, appropriate use of advanced imaging, and selective deployment of biomarkers when results can alter management. Upstream risk enrichment using polygenic risk scores and multivariable prediction models may improve the yield of clinically significant disease while mitigating harms related to overdiagnosis. At the point of suspicion, magnetic resonance imaging-first pathways and reflex biomarker testing provide practical tools to reduce unnecessary biopsy while maintaining safeguards for the detection of clinically important disease. Beyond diagnosis, prostate-specific membrane antigen positron emission tomography refines disease-state phenotyping in initial staging, biochemical recurrence, and limited-burden presentations, while standardized acquisition and reporting improve reproducibility and multidisciplinary communication. Germline and tumor-based molecular profiling should be operationalized as a longitudinal care process with clear consent, turnaround targets, and test-to-action rules that define what each result enables at specific decision nodes. Finally, longitudinal monitoring approaches, including liquid biopsy and artificial intelligence-enabled pathology, are evolving rapidly and require transparent reporting and rigorous risk-of-bias appraisal before broad clinical adoption. This narrative review synthesizes key evidence across the precision continuum and outlines a decision-node-based, test-to-action framework for maximizing clinical benefit, maintaining quality, and ensuring equitable access. Full article

Background/Objectives: Robotic gastrectomy (RG) for gastric cancer requires structured implementation to ensure oncological safety, particularly in Western centers with lower case volumes. Indocyanine green (ICG)-guided near-infrared lymphography may facilitate adequate lymphadenectomy and reliable tumor localization. We report our stepwise institutional introduction of RG and evaluate the perioperative outcomes and diagnostic accuracy of ICG-guided lymphography. Methods: All consecutive patients who underwent curative-intent RG at the University Medical Center Ljubljana between June 2022 and September 2025 were retrospectively analyzed. The implementation followed a structured stepwise approach, beginning with subtotal gastrectomy and progressing to total gastrectomy after formal training at Severance Hospital, Yonsei University Health System, under the mentorship of Prof. Woo Jin Hyung. ICG was administered endoscopically the day before surgery for tumor localization and intraoperative lymphatic mapping. The operative learning curve was assessed by CUSUM analysis, segmented regression, and bootstrapped plateau estimation. Results: Thirty-eight patients underwent RG (17 subtotal and 21 total). R0 resection was achieved in 100% of cases. The conversion rate was 2.6%. Major complications (Clavien–Dindo ≥ IIIb) occurred in six patients (15.8%). The 30-day mortality rate was 0%, and the 90-day mortality rate was 2.6%. Bootstrapped plateau operative times were 321.2 min (95% Bias-corrected and accelerated confidence interval (BCa CI): 278.4–344.1) for subtotal and 413.5 min (95% BCa CI: 378.1–476.1) for total gastrectomy, with the steepest learning phase confined to the first 2–4 cases. ICG was used in 23 patients. In a validation subset of five patients (259 lymph node stations), the sensitivity and negative predictive value were both 100%, with zero false negatives in 57 ICG-negative stations. Conclusions: RG can be safely introduced using a structured, stepwise strategy supported by training at a high-volume expert center. ICG-guided lymphography demonstrated 100% sensitivity for tumor-draining nodal basins in a small validation cohort (n = 5), supporting the feasibility of the technique during program introduction and warranting prospective evaluation in larger series. Full article

Background: Homologous recombination deficiency (HRD) is emerging as a clinically relevant biomarker across diverse tumor types, in addition to ovarian cancer. In this study, we evaluated the genomic instability score (GIS) across multiple tumor types using the TruSight Oncology 500 HRD assay, which incorporates the Myriad Genetics GIS algorithm, a widely used reference standard for HRD assessment. Methods: A total of 162 tumor samples (17 ovarian cancers and 145 non-ovarian tumors) underwent next-generation sequencing using the TruSight Oncology 500 HRD assay. Results: A total of 14 tumors were classified as GIS-High, defined as a GIS score ≥42, representing 8.6% of all cases. Among ovarian cancers, 7 out of 17 cases (41.2%) met the GIS-High threshold. Among non-ovarian tumors, seven GIS-High tumors were identified, accounting for 4.8% of cases (7/145). GIS-High cases occurred in breast (n = 4), lung (n = 2), and hepatobiliary tract (n = 1) cancers. GIS scores showed significant associations with BRCA1/2 and TP53 mutational status. In contrast, alterations in HRD-related genes other than BRCA1/2 did not show significant associations with GIS score. Conclusions: GIS-High tumors were identified in a small subset of non-ovarian cancers. These findings support further investigation of GIS as an exploratory biomarker of HRD-like genomic scarring beyond ovarian cancer, but its predictive and therapeutic relevance in non-ovarian tumors requires additional validation. Full article

HER2DX is a 27-gene genomic assay generating three complementary scores: a pCR score predicting the likelihood of achieving pathological complete response (pCR, defined as absence of residual invasive disease after neoadjuvant therapy), a Risk score estimating long-term recurrence risk, and an ERBB2 mRNA score quantifying HER2 transcriptional activation. Together, these scores may guide treatment escalation or de-escalation strategies in routine practice. We performed a single-center observational study at 12 de Octubre University Hospital (Madrid, Spain), including patients with early-stage HER2-positive breast cancer who underwent HER2DX testing (2023–2025), and analyzed clinicopathologic features, treatment decisions, and pathological outcomes. Forty-five patients were included (median age 57 years). Stage II accounted for 71.1% of cases; 66.7% were hormone receptor-positive, and 31.3% were node-positive. HER2DX modified clinical management in 51.1% of patients. The pCR score changed the initial strategy (neoadjuvant therapy versus upfront surgery) in 17.8% of cases and, independently, favored de-escalation to taxane plus dual HER2 blockade, with 90% of high-score tumors achieving a pathological complete response. The Risk score informed chemotherapy backbone selection within stage II disease. The ERBB2 score correlated with HER2 immunohistochemical intensity. In this exploratory real-world cohort, HER2DX provided biologically distinct information beyond traditional immunohistochemistry and was associated with modifications in multidisciplinary treatment decision-making in early-stage HER2-positive breast cancer, warranting prospective validation in larger cohorts. Full article

Objectives: Thoracic sarcomas are a heterogeneous group of rare mesenchymal tumors. This study aimed to identify prognostic factors for overall survival (OS) and progression-free survival (PFS) in patients undergoing resection of primary thoracic soft tissue and bone sarcomas. Methods: We retrospectively reviewed patients with primary intrathoracic or chest wall sarcomas who underwent surgical resection between 2005 and 2020. Eighty-four patients were included: 60 with soft tissue sarcoma and 24 with bone sarcoma. Univariate and multivariate Cox regression analyses were performed to identify prognostic factors for PFS and OS. Results: The most common histological subtypes were chondrosarcoma (19%) and undifferentiated pleomorphic sarcoma (17.8%). Overall, 54.8% of patients were female, and the mean age was 55.7 years (SD 17.9). Neoadjuvant and adjuvant therapies were primarily administered in intermediate- (G2) and high-grade (G3) tumors. Median OS was 28.4 months. On multivariate analysis, high tumor grade (G3 vs. G1–2) independently predicted worse PFS (HR 3.21, 95% CI 1.34–7.68; p = 0.01) and OS (HR 4.40, 95% CI 1.56–12.41; p = 0.01). Larger tumor size (HR 1.09, 95% CI 1.03–1.15; p = 0.001) and incomplete resection (HR 12.21, 95% CI 2.56–58.34; p = 0.002) were independently associated with worse OS, while lung metastases at diagnosis independently predicted worse PFS (HR 4.89, 95% CI 1.21–19.69; p = 0.03). Conclusions: Histological grade is the strongest independent predictor of survival in resected thoracic sarcoma. Surgery alone appears adequate for low-grade sarcomas, whereas multimodal treatment strategies seem particularly relevant for patients with higher-grade sarcomas. Full article

Background: Accurate prognostication in terminal cancer patients receiving best supportive care (BSC) is essential for guiding end-of-life decision-making and avoiding non-beneficial interventions. Several prognostic models have been developed for advanced cancer, including the Palliative Prognostic Index (PPI) and the Objective Prognostic Score (OPS). However, prospective data evaluating their performance specifically in patients managed with BSC are limited. This study evaluated the prognostic performance of PPI and OPS in terminal cancer patients receiving BSC. It also examined whether their combined use provides additional value for short-term mortality risk stratification. Methods: This prospective observational cohort study included hospitalized adult patients with terminal-stage cancer and a documented BSC decision. Terminal-stage cancer was operationally defined as stage IV malignancy with poor performance status and no remaining feasible disease-directed oncological treatment option due to severe clinical deterioration and/or major organ dysfunction. Patients were prospectively enrolled from 12 April 2024 to 13 December 2024 and followed until death. Eligible patients had poor Eastern Cooperative Oncology Group performance status (ECOG 3–4) and had not received oncologic treatment within the preceding month. PPI and OPS were calculated at baseline using predefined criteria. Survival time was defined as the interval between baseline assessment and death. The prognostic performance of the scores for 3-, 4-, and 6-week mortality was evaluated, and survival outcomes were analyzed using standard survival analysis methods. Results: A total of 112 patients were included in the final analysis. The mean age was 62.3 ± 12.3 years; 66 patients (58.9%) were male and 46 (41.1%) were female. The most common primary tumor sites were colon cancer (20.5%), non-small cell lung cancer (17.0%), and gastric cancer (15.2%). Both PPI > 6 and OPS ≥ 3 were associated with higher short-term mortality, although their individual discriminatory performance was modest. The combined OPS–PPI approach showed statistically significant but still modest discrimination at all time points. Although this difference was limited, the combined approach supported the stratification of a clinically relevant subgroup at particularly high risk of imminent death. Patients with both OPS ≥ 3 and PPI > 6 had the poorest survival, with a median overall survival (OS) of 11 days. In multivariable Cox regression analysis, the combined high-risk group remained independently associated with poorer OS (HR 1.53, 95% CI 1.01–2.31; p = 0.046). Conclusions: Although the individual discriminatory performance of PPI and OPS was modest, their combined use may provide additional risk stratification value and may help identify patients at particularly high risk of short-term mortality among terminal cancer patients receiving BSC. These findings should be interpreted as supporting bedside risk stratification rather than indicating a definitive individual-level prediction model. Full article