This study aimed to characterize pharmacogenomic variation in genes involved in the metabolism and transport of drugs used in Berlin–Frankfurt–Münster-based therapy in Amazonian Indigenous individuals and to compare allele frequencies with major continental populations. Whole-exome sequencing data previously generated from 64 healthy Indigenous individuals from 12 Amazonian ethnic groups were analyzed. A total of 120 genes associated with drugs used in Berlin–Frankfurt–Münster protocols were selected. Variants were annotated and filtered using bioinformatic quality-control criteria, and allele frequencies were compared with African, Admixed American, East Asian, European, and South Asian populations from the 1000 Genomes Project. Multidimensional scaling was used to assess population-level genetic similarity. After quality control, 648 variants were identified. Twenty-eight variants were observed exclusively in the Indigenous study population, including four nonsynonymous coding variants with moderate predicted impact. Significant allele-frequency differences were observed for ADA rs11555566, CBR3 rs881711, and CYP2B6 rs3745274; rs881711 and rs3745274 differed from all five reference populations. Multidimensional scaling showed a distinct Indigenous pharmacogenomic profile, with greater similarity to the Admixed American population. Amazonian Indigenous populations exhibit substantial pharmacogenomic diversity in genes relevant to Berlin–Frankfurt–Münster-based therapy. These findings identify candidate variants for functional and clinical validation and reinforce the importance of including underrepresented populations in pharmacogenomic research.
Chronic inflammation is a significant driver of carcinogenesis, particularly in the context of obesity; yet its role and the predictive value of common inflammatory biomarkers in overweight people (BMI 25–29.9) remain unclear and controversial. This study evaluated six hematologic inflammatory indices (BLR, NLR, MLR, SII, SIRI, PLR) for predicting cancer incidence and mortality among overweight adults. Cross-sectional observational data from NHANES involving 11,348 overweight subjects and 9,181 normal-weight controls were analyzed; 823 overweight cancer patients were included for mortality assessment. Cancer status was self-reported, and cancer-specific death was defined by ICD-10 C00-C97 codes. Six inflammatory markers were derived from routine blood tests. Covariates were selected using LASSO and VIF, while nonlinearity was assessed through RCS. Predictive performance was evaluated using logistic regression, Cox proportional hazards models, and XGBoost with five-fold cross-validation. All six markers presented U-shaped correlations with cancer risk and mortality. Fully adjusted models showed BLR independently predicted cancer risk (OR = 1.343, 95
To develop and internally validate the PANTHEIA-SIRI prognostic model, which integrates log-transformed systemic inflammation response index (SIRI) with clinical predictors, to estimate overall survival (OS) in metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with first-line chemotherapy. We used data from the multicenter PANTHEIA-SEOM registry. OS was defined from chemotherapy start. The model was fitted as a Weibull accelerated failure time model in the survival-analysis population with multiple imputation. Predictors were log-transformed baseline SIRI, modeled with restricted cubic splines, ECOG, tumor burden, chemotherapy regimen, and anorexia-cachexia syndrome. Internal validation used a separate, non-overlapping cohort from the same registry; the centers contributing to each cohort are listed in a supplementary annex. TRIPOD was followed. Discrimination was assessed with Harrell´s C-index and calibration with IPCW Brier scores and IPA. The derivation cohort comprised 672 patients with SIRI data (593 analyzed for survival) across 22 Spanish hospitals (2015–2025); 80.1 https://pantheia-siri.shinyapps.io/calc/ ) may support prognostic communication, treatment-intensity selection, and supportive-care planning. Routine clinical implementation will require further validation in larger, fully independent cohorts.
Humanization in cancer care is increasingly recognized as a core component of healthcare quality, yet its implementation in clinical practice remains uneven. To address this gap, the Spanish Society of Medical Oncology (SEOM) developed a humanization protocol to guide its integration into routine oncology care. Based on a review of scientific literature, including clinical guidelines and documents from scientific societies, together with a SEOM survey of medical oncologists, the recommendations are organized around four domains: people, processes, spaces, and society. For each domain, practical and adaptable measures are proposed, ranging from communication and shared decision-making to care coordination, the design of healthcare environments, professional well-being, and community engagement. A cross-cutting person-centered approach, combined with regular evaluation using patient-experience and professional well-being indicators, may support the integration of humanization into routine cancer care.
Glioblastoma is the most aggressive and common malignant primary brain tumor among adults. Due to its aggressiveness, GBM entails a short median overall survival and fatal outcomes. Incidence notably increases with age, 50
We conducted the first multicentre Spanish real-world study assessing the efficacy and safety of stereotactic body radiotherapy (SBRT) in oligometastatic patients treated in routine clinical practice. This retrospective, multicentre observational study included oligometastatic patients with primary solid tumours treated with SBRT between 2020 and 2024 across 12 Spanish radiotherapy centres. The primary endpoint was 1-year progression-free survival (PFS). The secondary endpoints included overall survival (OS), local control (LC), and acute and late adverse events by CTCAE v.5.0. 300 patients with 451 treated lesions were included. Median age was 69 years. After a median follow-up of 22 months, 1- and 2-year PFS were 45.1
Electronic brachytherapy (eBT) is an emerging alternative to conventional Ir-192 HDR brachytherapy for adjuvant vaginal cuff irradiation. We evaluated long-term clinical outcomes, dosimetric parameters, and treatment-related toxicity in patients with early-stage endometrial cancer treated with adjuvant eBT. This single-center retrospective study included 98 patients with early-stage endometrial cancer selected for adjuvant vaginal eBT between 2015 and 2019. Standard fractionation schedules were used. Dosimetric parameters, and acute and late toxicity graded according to CTCAE v5.0 were analyzed. Survival outcomes were assessed using Kaplan–Meier methodology. The median follow-up was 82.5 months. Adequate target coverage was achieved with a median D90 of 92.5
Prostate cancer (PCa) remains a leading cause of cancer-associated morbidity among men globally. Although enzalutamide (ENZ), a second-generation androgen receptor (AR) antagonist, serves as a mainstay therapy for castration-resistant prostate cancer (CRPC), therapeutic resistance inevitably emerges. This underscores an urgent demand for innovative treatment strategies. CCK-8, colony formation, EdU staining, flow cytometry, Hoechst 33,258 staining, western blotting, proteomics analysis, and senescence-associated β-galactosidase (SA-β-gal) staining were performed to reveal the role and underlying mechanisms of S.C in ENZ-resistant prostate cancer. Target prediction, molecular docking, and cellular thermal shift assay (CETSA) were used to identify the target of S.C. Finally, the impact of S.C in vivo was evaluated using ENZ-resistant xenograft models. Our results showed that S.C effectively suppresses cell viability in ENZ-resistant models through the dual induction of apoptosis and cellular senescence. Database mining, molecular docking, and CETSA identified AR as a putative target of S.C, which was subsequently validated in vivo. S.C treatment significantly inhibited the AR signaling pathway and suppressed tumor growth in ENZ-resistant xenograft models. To our knowledge, this study demonstrates that S.C could be a promising multi-mechanistic agent which can overcome ENZ resistance by targeting AR and inducing two distinct cell death pathways, offering a potential novel therapeutic strategy for CRPC.
Testicular germ cell cancer (TGCC) is a rare malignancy whose incidence is increasing in many European countries. This study aimed to describe the trends in the incidence, mortality, and survival of TGCC and its morphological types (seminoma and non-seminoma) in the province of Tarragona (Spain) over the last four decades, using population-based data from the Tarragona Cancer Registry. The study included all incident cases of TGCC diagnosed between 1980 and 2018 in the province of Tarragona. Descriptive and bivariate analyses were performed to examine the association between disease stage and the following variables: period of diagnosis, age, morphology, lactate dehydrogenase (LDH), beta–human chorionic gonadotropin (β-hCG), and alpha-fetoprotein (AFP). Incidence and mortality were assessed by calculating the mean annual number of cases, crude and age-adjusted rates, and the annual percentage change (APC) over the study period. Five- and 10 year survival rates were estimated for all tumors as a whole and stratified by stage, period of diagnosis, age, and morphology. A total of 458 cases of TGCC were identified, 55
Aberrant activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway, particularly STAT3, contributes to tumour progression, metastasis, immune evasion, and therapeutic resistance, making it an attractive target for cancer prevention and therapy. Numerous natural compounds have been reported to modulate this pathway in preclinical studies; however, their clinical translation remains constrained by limited mechanistic validation and poor pharmacokinetic properties. Retinoids, well established as regulators of cellular differentiation and proliferation, have recently emerged as potential modulators of JAK/STAT signalling, although the molecular basis of this interaction remains poorly understood. This review critically evaluates current evidence linking natural compounds with JAK/STAT inhibition, with particular emphasis on the emerging retinoidJAK/STAT interface. By distinguishing established findings from hypothesis-generating observations, identifying key mechanistic gaps, and outlining future experimental priorities, this review provides a framework for evaluating the therapeutic potential of retinoid-mediated JAK/STAT modulation in cancer.
Chronic inflammation is an important contributor to the development of oral cancer, particularly in Oral Potentially Malignant Disorders (OPMDs) progressing to Oral Squamous Cell Carcinoma (OSCC). PELP1 is an inflammation-responsive nuclear coregulator identified in multiple cancers; however, its role in oral cancer remains unclear. This study evaluates the expression of PELP1 and determines its clinical significance in inflammation-associated oral tumorigenesis. PELP1 transcript levels were examined in the TCGA-HNSC dataset using different online tools. Immune infiltration analysis using TIMER and Kaplan–Meier survival analysis plots was also performed. Protein expression was validated by immunohistochemistry (IHC) in human normal oral mucosa, OPMDs, and OSCC tissues and in chemically induced murine OSMF models. Functional validation was performed by shRNA-mediated PELP1 knockdown in SCC131 cells, followed by western blot analysis of Cyclin B1 and NF-κB signaling. PELP1 expression was significantly upregulated in TCGA-HNSC tumors compared to normal tissues (p < 0.05) and was associated with advanced stage, higher grade, and nodal metastasis (p < 0.05). A positive correlation and a significant association between PELP1 expression and the abundance of immune cell infiltrates were observed (p < 0.05). In addition, high PELP1 expression was associated with markers of oral epithelial transformation (p < 0.05). Survival analysis showed a trend toward reduced overall survival (p = 0.24). IHC analysis showed a stepwise increase in nuclear PELP1 expression from normal mucosa to OPMDs; and OSCC (p < 0.05); along with elevated expression in fibrotic murine models (p < 0.05) compared to saline-treated control models. Functional validation demonstrated that PELP1 knockdown reduced Cyclin B1 expression, reduced total NF-κB p65 protein levels, and suppressed NF-κB signalling in SCC131 cells. PELP1 is significantly upregulated during oral cancer development and correlates with adverse clinicopathological features, supporting its potential role as a biomarker associated with inflammation-driven oral cancer progression.
Gastric cancer remains a major cause of cancer mortality in Vietnam and illustrates how social conditions shape cancer trajectories. This narrative review synthesizes Vietnam-relevant evidence across infection, diet, tobacco and alcohol exposure, early detection, treatment, financial protection, survivorship, and palliative care. Helicobacter pylori acquisition is socially patterned by household and hygiene conditions; salt intake remains above recommended levels; and early gastric cancer represents about 4
Immunotherapy holds promise for gastric cancer, but its efficacy is constrained by primary and acquired resistance. Resistance mechanisms are complex, stemming from tumor features—such as the tumor microenvironment (TME). The TME is a dynamic ecosystem where tumor–immune–stromal interactions shape antitumor responses. Existing prognostic markers have clinical value, yet their insufficiency reflects the multidimensional nature of tumor–immune crosstalk. Emerging evidence indicates that immunotherapy response is a systems-level phenomenon. This review synthesizes current data on cellular, molecular, and systemic predictors, focusing on immune cell phenotypes, protein biomarkers, gene signatures, and metabolic factors. Integrative models capturing the functional state of the TME consistently outperform single biomarkers. Nevertheless, significant challenges remain, including a lack of standardization, limited prospective validation, and TME temporal plasticity, which complicates static biomarker assessments. Ultimately, predicting response requires understanding the tumor–immune ecosystem as an integrated, dynamic system to improve patient stratification and outcomes.
To characterize sustainability practices and identify implementation barriers among radiation oncology (RO) professionals in Spain. A 38-item survey was distributed to members of the Spanish Society of Radiation Oncology (SEOR) in October 2025. Responses from 122 specialists (out of 1355 invited, 9.0
Total body irradiation is widely used in conditioning regimens before allogeneic hematopoietic stem-cell transplantation (allo-HSCT), most often in high-risk acute lymphoblastic leukemia. This study assessed survival outcomes and treatment-related toxicity in patients who underwent TBI-based myeloablative conditioning. We conducted a retrospective single-center study of patients who underwent allo-HSCT after TBI-based conditioning at a reference TBI-unit serving transplant across the Community of Madrid. Between 2011 and 2020, most patients (n = 52) received 10 Gy in 2 Gy fractions twice daily. Primary endpoints were overall survival (OS), disease-free survival (DFS), and relapse; secondary endpoints included non-relapse mortality (NRM), disease-related mortality (DRM), and toxicity. 58 patients underwent TBI-based conditioning using peripheral blood stem cells (PBSC; n = 37), umbilical cord blood (UCB; n = 19), or bone marrow (BM; n = 1); one patient died before graft infusion. Diagnoses were B-ALL (79.3
Oligometastatic disease (OMD) and oligoprogression are clinically actionable states in which local treatment of limited tumour burden can prolong disease control for selected patients. Randomised phase II trials support metastasis-directed therapy (MDT), usually stereotactic body radiotherapy (SBRT/SABR), in several settings, but the effect is not uniform across tumour types. SABR-COMET and two non-small-cell lung cancer (NSCLC) trials showed progression-free or overall-survival gains, whereas NRG-BR002 did not improve progression-free or overall survival in newly oligometastatic breast cancer. In oligoprogression, CURB improved progression-free survival in NSCLC but not breast cancer. These divergent results make biological and treatment-context selection more important than lesion count alone. Biologically adaptive radiation oncology extends adaptation beyond setup correction by linking anatomy-of-the-day, molecular imaging, tumour phenotype, and response to target definition, dose, fractionation, and timing. This narrative review critically compares conventional image-guided SBRT, cone-beam CT (CBCT)-guided online adaptive radiotherapy, MR-guided online adaptive radiotherapy, PET/PSMA-guided planning, biology-guided radiotherapy, dose painting, and radiomics/AI. CBCT-guided adaptation is positioned as an increasingly available bridge between conventional image guidance and MR-guided adaptation. The practical value of MR guidance is greatest when soft-tissue visibility, motion, or daily organ-at-risk proximity would otherwise prevent safe ablative dosing; biology-guided delivery, biomarker-triggered adaptation, predictive AI, and radioligand–MDT combinations remain investigational. A clinical decision framework is proposed to separate approaches ready for routine use from selectively useful and research-only strategies.
MutL homolog 1 (MLH1) is a key component of the mismatch repair (MMR) pathway, and promoter methylation-mediated silencing is a well-established oncogenic mechanism in several tumor types. However, its prevalence and prognostic relevance in pancreatic ductal adenocarcinoma (PDAC) remain unclear. We retrospectively analyzed 55 patients with PDAC diagnosed between 2012 and 2021 at a tertiary center. MLH1 promoter methylation (
The bilirubin-to-albumin (BA) ratio may reflect the balance between circulating bilirubin and albumin-related binding capacity, but its association with lung cancer risk remains unclear. We analyzed data from the Korean Cancer Prevention Study-II, a nationwide prospective cohort. After excluding participants with baseline cancer or missing key variables, 81,746 men and 49,421 women were included. Total, indirect, and direct BA ratios were calculated and standardized per 1-standard deviation increase. Sex-specific associations with lung cancer risk were assessed using Cox proportional hazards models, quartile analyses, restricted cubic splines, and causal survival forest models. In Cox models, higher total and direct BA ratios were inversely associated with lung cancer risk in men, whereas higher total and indirect BA ratios were positively associated with risk in women. Restricted cubic spline analyses supported inverse dose–response patterns for total and direct BA ratios in men. Causal survival forest analyses showed statistically significant positive average treatment effects for lung cancer-free survival probability only in men across 5-, 10-, and 13-year horizons. BA ratio showed sex-specific associations with lung cancer risk, with more consistent inverse associations among men.
To identify real-world prognostic indicators affecting patients with non-small cell lung cancer brain metastasis (NSCLC BM) and to develop a pragmatic nomogram for individualized survival prediction. We collected clinical data from 590 patients with NSCLC BM treated in the department of oncology at our hospital from January 2020 to December 2023, and randomly divided them into a training set (n = 413) and a validation set (n = 177) at a 7:3 ratio. Cox regression analysis was used to screen independent risk factors, and a nomogram prediction model was constructed. Model performance was evaluated using receiver operating characteristic(ROC) curves, C-index, calibration curves, decision curve analysis (DCA) and Kaplan–Meier (KM) survival analysis. Multivariate Cox analysis revealed that Karnofsky Performance Score (KPS) score < 70(HR = 1.95, p < 0.001), number of BMs ≥ 3(HR = 1.40, p = 0.021),and the utilization of whole-brain radiotherapy (WBRT) as a real-world surrogate indicator for high disease burden (HR = 1.65, p = 0.001) were independent predictors of poor overall survival (OS). EGFR mutation status, though with borderline significance in the multivariate analysis (p = 0.052), was retained in the final nomogram due to its established prognostic role. The AUCs for the training set at 6, 12, 18, and 24 months were 0.805, 0.805, 0.846, and 0.836, respectively; the corresponding AUCs for the validation set were 0.745, 0.796, 0.816, and 0.809. Calibration curves showed good consistency between predicted and observed outcomes. DCA demonstrated that our model yields superior net benefit in clinical application. Patients were divided into low-, medium-, and high-risk groups based on nomogram scores. KM analysis showed significant survival differences among the three groups (p < 0.001). The nomogram incorporating KPS score, number of BMs, radiotherapy modality, and epidermal growth factor receptor (EGFR) mutation status demonstrated good discrimination, calibration and clinical utility. Our model distinctively integrates real-world treatment triage (WBRT versus SRS/SRT) as a comprehensive prognostic dimension. This tool enables individualized risk stratification and may aid in early identification of high-risk patients, thereby guiding precise clinical treatment.
Apoptosis plays a pivotal role in the biological process that responds to cellular oxidative stress and significantly contributes to cancer pathogenesis, thereby altering the efficacy of modern cytotoxic treatments. The B-cell lymphoma 2 (BCL-2) protein family exhibits both pro-apoptotic and anti-apoptotic activities that regulate the intrinsic apoptotic pathway. BCL-2 family members, including pro-apoptotic and pro-survival proteins, are highly expressed or dysregulated in cancer cells, thereby promoting tumor progression and therapeutic resistance. This review systematically summarizes the structural organization, molecular functions, and therapeutic significance of the BCL-2 family in cancer. Furthermore, we critically discuss the active role of the BCL-2 family in modulating apoptosis and evaluate recent advances in the development of BH3 mimetics (Venetoclax (ABT-199), Navitoclax (ABT-263), Obatoclax (GX15-070)) and other BCL-2-targeted therapies. The review also highlights emerging mechanisms of drug resistance, including compensatory MCL-1 overexpression, and discusses current combination therapeutic strategies to overcome resistance. The available preclinical and clinical evidence denotes the therapeutic potential of the BCL-2 family as a promising target for cancer treatment. The single- and combined therapy with Venetoclax, a selective BCL-2 BH3 mimetic, has demonstrated higher efficacy and improved safety compared with conventional therapies and has been successfully applied across distinct cancer types. Finally, we discuss current challenges, including resistance mechanisms and treatment-related toxicities, and outline future directions focusing on biomarker-guided patient stratification and next-generation BCL-2-targeted therapeutics.
