INTRODUCTION:With the widespread use of human epidermal growth factor receptor 2 (HER2) inhibitors in cancer treatment, cardiovascular diseases induced by these agents have become a significant adverse event. METHODS:We retrieved reports of HER2 inhibitor-induced cardiovascular adverse events (CVAEs) from the FDA Adverse Event Reporting System(FAERS) database, covering the period from the first quarter of 2004 to the fourth quarter of 2024. Disproportionality analyses were conducted using reporting odds ratios and proportional reporting ratios. The signals of HER2 inhibitor-related CVAEs were evaluated at both the standardized MedDRA query and preferred term levels. RESULTS:A total of 12,698 reports associated with CVAEs were identified, with HER2 inhibitors listed as the primary suspected drug, involving 12,398 patients. Most cases were observed in individuals aged 45 years and older, with a notably higher proportion in women. The time to onset of HER2 inhibitor-induced CVAEs showed certain variability. Trastuzumab exhibited higher cardiovascular toxicity compared with other HER2 inhibitors. In general, monoclonal antibodies demonstrated greater cardiovascular toxicity, whereas antibody-drug conjugates and HER2-tyrosine kinase inhibitors displayed comparable and lower effects. CONCLUSION:This pharmacovigilance analysis reveals a strong association between HER2 inhibitors and CVAEs, providing valuable insights for their prevention and clinical management.
INTRODUCTION:The immune landscape of the tumor microenvironment significantly influences the development and prognosis of colorectal cancer (CRC). High intratumoral and stromal expressions of CD3+ and CD8+ T-lymphocytes have been associated with a better prognosis in CRC patients. However, the prognostic role of antigen-presenting cells, such as dendritic cells and macrophages, has less attention. METHODS:In this study, we assessed the impact of CD11c expression and the disease-specific survival (DSS) in CRC patients. Thus, we evaluated the CD11c expression on tissue microarray samples via immunohistochemistry from 516 patients who underwent surgery at Helsinki University Hospital between 2000 and 2005. Samples were categorized as low expression (<5% positive stromal area) and high expression (≥5% positive). Colon and rectal cancer patients were analyzed separately using Cox regression for survival analysis. RESULTS:A lower CD11c expression associated with a worse DSS among rectal cancer patients (p < 0.001) and right-sided colon cancer patients (p = 0.03), but not among left-sided colon cancer patients (p = 0.41). Among rectal cancer patients, results remained consistent regardless of whether the patient received preoperative radiation (p < 0.003 and p = 0.03, respectively). In the multivariable analysis after adjusting for age, sex, stage, grade, and a mismatch repair status, a lower CD11c expression remained an independent prognostic factor among rectal cancer patients (p = 0.009), but not among colon cancer patients (p = 0.15). These results suggest that stromal CD11c expression captures the distinct immunological characteristics of rectal cancer compared to colon cancer. CONCLUSIONS:We conclude that CD11c could serve as a prognostic marker for rectal cancer patients. However, the immunological mechanisms differentiating colon and rectal cancers warrant further research.
INTRODUCTION:We investigated the relationship between neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy-induced neutropenia and histological tumor response or prognosis to support appropriate postoperative treatment selection in patients with esophageal cancer receiving neoadjuvant DCF. METHODS:Patients with esophageal cancer who underwent neoadjuvant DCF followed by surgery at Showa Medical University Hospital, Japan were retrospectively analyzed. A Cox proportional hazards regression analysis including prognostic factors (chemotherapy-induced neutropenia) was performed to determine progression-free survival (PFS). Survival curves for the histological tumor response grades 0-1b and 2-3, stratified by neutropenia severity, were estimated by Kaplan-Meier analysis, and compared using the log-rank test. RESULTS:Among 53 patients (median age, 66 years [range: 48-78]; median PFS, 21 months), 33 (62.2 %) had clinical stage (cStage) IV disease, and 36 (67.9%) had grade 3/4 neutropenia. Multivariate analysis showed that cStage IVb (hazard ratio [HR]: 3.46, P = 0.004) and histological tumor response grade 0-1b (HR: 6.09, P < 0.001) were independent poor prognostic factors for PFS. In the grade 3/4 neutropenia group, a lower histological tumor response was associated with shorter PFS (median PFS: grade 0-1b, 10.1 months vs. grade 2-3, not reached, P < 0.001). CONCLUSIONS:In this study, cStage IVb and histological tumor response grade 0-1b were poor prognostic factors for PFS in patients with esophageal cancer who received neoadjuvant DCF followed by surgery. The histological tumor response was associated with PFS in patients with grade 3/4 neutropenia.
Background: Classical Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and myelofibrosis, frequently occur in patients with renal, hepatic, cardiovascular, or hematologic comorbidities. These vulnerabilities complicate treatment selection, dose adjustment, and toxicity monitoring. However, patients with advanced kidney disease, dialysis dependence, decompensated cirrhosis, severe cytopenias, or overlapping organ impairment are often underrepresented in prospective trials. Summary: This narrative review presents a practical, organ-adapted framework for selecting MPN therapy in clinically complex patients. We define renal and hepatic impairment, compare commonly used cytoreductive and targeted therapies, including hydroxyurea, busulfan, anagrelide, ruxolitinib, fedratinib, momelotinib, pacritinib, ropeginterferon alfa-2b, and pegylated interferon alfa-2a, and discuss their use in dialysis, decompensated liver disease, cytopenic myelofibrosis, anemia-dominant myelofibrosis, and combined organ vulnerability. The proposed approach prioritizes label-based dose modification when available, cautious dose initiation when evidence is extrapolated, structured early monitoring, and multidisciplinary review for high-risk patients. Key Messages: Management of Philadelphia-negative MPNs in organ dysfunction should be individualized according to disease phenotype, treatment goal, organ reserve, hematologic tolerance, frailty, and label-specific safety restrictions. In renal impairment, hydroxyurea and ruxolitinib may remain feasible in selected patients when dose-adjusted and monitored closely, whereas dialysis and severe renal impairment require conservative initiation and multidisciplinary review because direct evidence remains limited. In myelofibrosis, JAK inhibitor choice should be phenotype-adapted; ruxolitinib remains a common standard when blood counts and organ function permit, momelotinib is attractive in anemia-dominant disease, pacritinib is particularly relevant in severe thrombocytopenia, and fedratinib is useful in selected settings but requires thiamine-focused safety management. In hepatic dysfunction or overlapping organ vulnerability, therapy should prioritize safety, reversible contributors, conservative starting strategies, explicit stopping rules, and early reassessment.
Aim The lymphocyte-to-monocyte ratio (LMR) has emerged as a potential immune-related biomarker; however, its prognostic significance in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atezo/Bev) remains unclear. To investigate the prognostic significance of the LMR in patients with unresectable HCC treated with Atezo/Bev. Methods This multicentre study included 941 patients with unresectable HCC treated with Atezo/Bev therapy at 30 institutions in Japan. The optimal LMR cutoff value was determined using time-dependent receiver operating characteristic (ROC) analysis. Multivariate survival analyses were performed for progression-free survival (PFS) and overall survival (OS). The prognostic utility of the LMR was compared with that of the neutrophil-to-lymphocyte ratio (NLR) using integrated discrimination improvement and net reclassification improvement. Results Time-dependent ROC analysis identified an optimal LMR cutoff value of 3.6 based on median OS. The median PFS was 5.6 months in patients with an LMR < 3.6 and 8.9 months in those with an LMR ≥ 3.6 (P<0.01). The disease control rate was significantly higher in the high LMR group (P<0.01). Multivariate analysis identified the LMR as an independent factor associated with prolonged PFS (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.90-0.98; P<0.01) and OS (HR, 0.90; 95% CI, 0.85-0.96; P<0.01). Compared with NLR, LMR demonstrated a significantly greater improvement in prognostic predictive performance for both PFS and OS (P<0.01). Conclusions The LMR is a simple and clinically useful prognostic biomarker for predicting both PFS and OS in patients with unresectable HCC treated with Atezo/Bev therapy.
Explore modern metastatic breast cancer care: longer survival, smarter symptom control, caregiver support, and steps to close racial treatment gaps.
This cross-sectional study evaluated the genetic landscape of a cohort of patients with metastatic prostate cancer who were treated at a referral center in Mexico City, Mexico.
We describe a unique clinical case of primary melanoma of the ascending colon presenting with intussusception and profuse hemorrhage. A 72-year-old man on anticoagulant therapy was admitted with massive rectal bleeding and hypotension. Colonoscopy revealed an 8-cm obstructing exophytic tumor. CT scan confirmed enteroenteric intussusception via the pathognomonic pseudokidney sign. Diagnosis was established by immunohistochemical analysis, demonstrating positive expression of S100 protein and melanoma-associated antigens, while negative for melanocyte antigen A and BRAF mutations. The patient underwent emergency right-sided hemicolectomy with lymphadenectomy. Pathomorphological evaluation confirmed stage T4aN0M0 (R0 resection). Following an accelerated recovery protocol, the patient started adjuvant immunotherapy with PD-1 inhibitors. This case underscores the need for a multidisciplinary approach and extended immunohistochemical profiling to diagnose rare mucosal pathologies. It highlights the effectiveness of radical surgery combined with modern systemic immunotherapy in emergency settings. Given the aggressive nature of mucosal melanoma, adhering to oncological guidelines and considering early immunotherapy are crucial for optimizing clinical outcomes.
A primary driver of skyrocketing health care budgets has been the cost of prescription medications, which is particularly true for oncology, as personalized medicine is the standard of care.
In this retrospective cohort study, it was shown that acute pancreatitis hospitalizations occurred more frequently in patients with multiple myeloma who were older and more medically complex.
INTRODUCTION:Immune checkpoint inhibitors (ICIs) are widely prescribed as the first-line treatment for metastatic renal clear-cell carcinoma because of their overall survival (OS) benefits. However, ICIs are associated with unreliable efficacy and sometimes severe and unpredictable toxicities. There is a lack of biomarkers for efficacy or toxicity beyond the IMDC score. Body composition (fat and muscle mass) may also be a biomarker of interest. The aim of this retrospective study was to analyze the association between body composition, OS, and toxicities in patients with RCC treated with ICI as a first-line metastatic treatment. METHODS:Body composition parameters - subcutaneous fat index (SFI), visceral fat index (VFI), total fat index (TFI), and skeletal muscle index (SMI) - were measured on computed tomography scans using semiautomated software. RESULTS:In 71 patients, no significant association was found between TFI and OS (adjusted HR, 0.71 [0.35; 1.45]) or toxicities. The TFI was strongly correlated with BMI (r = 0.81), whereas the SFI and VFI were weakly correlated. CONCLUSION:Larger studies would be valuable to better define the thresholds of different parameters (SFI, VFI, TFI, and SMI) and their association with the efficacy and toxicity of ICI.
INTRODUCTION:Identifying pathological markers to differentiate between high- and low-grade pancreatic intraepithelial neoplasia (PanIN) remains an unmet clinical need. Recent studies suggest that the tumor microenvironment undergoes dynamic changes during PanIN progression. To establish objective pathological markers, this study investigated histological, immunohistochemical, and molecular alterations in PanIN-associated stroma across different grades. METHODS:Fibroblastic cluster (FC) was defined and characterized using immunohistochemistry (IHC) for SMA, CD31, and CD34, and their frequency was assessed according to PanIN grade in 202 PanIN lesions and 58 normal ducts. To identify molecular differences among PanIN types, multiple gene expression analysis (MGEA) was performed for six normal ducts and for three PanIN1, three PanIN2, and six PanIN3 lesions. IHC and fluorescent dual IHC for CD31 and CD36 were performed to quantify CD36-positive stromal vessels. RNA scope for PPARγ and IHC for thrombospondin-1 (TSP-1) and forkhead box O1 (FOXO-1) were performed to explore the molecular basis of CD36 downregulation. RESULTS:FCs were identified in 86.6% of PanIN3 stroma and were significantly more frequent than in lower-grade PanINs. MGEA revealed downregulation of CD36 in PanIN2-3 compared with PanIN1, and CD36-positive vessels were significantly fewer in higher-grade PanIN stroma. PPARγ signals were present in low-grade but absent in high-grade PanIN stroma. TSP-1 expression paralleled CD36 expression. These findings suggest that the possible relationship between the repression of CD36 in the stromal vasculature of high-grade PanIN and reduced PPARγ and TSP-1 signaling. CONCLUSIONS:Higher-grade PanINs harbor a unique stroma characterized by FC formation and an increased proportion of CD36-negative vessels.
Introduction: Acute promyelocytic leukemia (APL) is among the most curable acute leukemias, but real-world early mortality continues to undermine population-level cure. This study evaluated long-term outcomes and prognostic factors among adults with APL treated in a single tertiary center in Qatar. Methods: We conducted a retrospective cohort study of consecutive adult patients diagnosed with APL between 2012 and 2024. Baseline demographic, clinical, and laboratory data, treatment regimens, and response outcomes were extracted from electronic medical records. Patients were stratified according to Sanz risk criteria. Overall survival (OS) was estimated using the Kaplan-Meier method, and prognostic factors were assessed using log-rank tests and Cox proportional hazards regression. Results: A total of 87 patients were included (median age: 36 years; 47.1% high-risk groups by Sanz criteria). Early mortality within 30 days occurred in 26.4% (n = 23), predominantly due to intracranial hemorrhage (47.8% of early deaths). Among 71 patients who received treatment, the complete remission (CR) rate was 84.1%, with the highest CR observed in those treated with all-trans retinoic acid (ATRA)-arsenic trioxide (90.9%). Treatment-related complications occurred in 73.2% of patients, most commonly infections (66.2%) and differentiation syndrome (21.1%). Three-year OS was 93% in low-risk groups, 88% in intermediate-risk groups, and 56% in high-risk groups (log-rank p = 0.001). In multivariable analysis, ICU admission (hazard ratio [HR]: 5.42) and lack of treatment initiation (HR: 8.06) were independent predictors of mortality. Excluding patients presenting with intracranial hemorrhage, early mortality decreased to 14.7%, and 5-year OS improved to 87.6%. Conclusion: Despite the effectiveness of contemporary APL therapies, early mortality, primarily driven by hemorrhagic complications, remains a significant challenge. Strategies to improve outcomes should focus on rapid diagnosis, immediate initiation of empiric ATRA, and aggressive correction of coagulopathy. Integration of APL-specific emergency care pathways may represent a key opportunity to reduce preventable deaths.
BACKGROUND:Bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CAR) T-cell therapies have transformed the management of hematologic malignancies, including relapsed/refractory multiple myeloma (RRMM), lymphomas, and leukemias. These approaches enable targeted cytotoxicity through T-cell redirection and engineered cellular activity, achieving high response rates in heavily pretreated populations. Data presented at the 2025 Immune Cell Effector Therapies (ICE-T) Symposium highlighted expansion beyond B-cell maturation antigen (BCMA) to additional targets such as GPRC5D and FcRH5, alongside emerging multitarget and next-generation constructs aimed at improving durability and overcoming resistance. METHODS:This narrative review summarizes key findings from the 2025 ICE-T Symposium, integrating data from clinical trials, real-world studies, and contemporary guideline-based management, with a focus on efficacy, safety, sequencing, and emerging therapeutic platforms. RESULTS:Across hematologic malignancies, immune-based therapies demonstrated substantial and clinically meaningful activity, with outcomes varying by disease subtype, target antigen, and therapeutic platform. In multiple myeloma, BCMA-directed bispecific antibodies, including teclistamab and elranatamab, achieved overall response rates (ORRs) of approximately 63% and 61%, respectively, in heavily pretreated populations, with median progression-free survival (PFS) of approximately 11 to 17 months across pivotal studies. Talquetamab demonstrated ORR of approximately 73% to 74% in the MonumenTAL-1 study (NCT03399799), supporting efficacy in post-BCMA settings. Cevostamab has shown promising early-phase activity, with response rates of approximately 55% to 60% at higher dose levels, reflecting the expansion of therapeutic targets beyond BCMA. In B-cell lymphomas, CD19-directed CAR T-cell therapies, including axicabtagene ciloleucel and lisocabtagene maraleucel, produced high response rates with durable remissions in relapsed/refractory large B-cell lymphoma, with long-term follow-up demonstrating sustained survival in a subset of patients. Among bispecific antibodies, epcoritamab achieved an ORR of approximately 60% to 65%, whereas glofitamab demonstrated an ORR of approximately 45% to 50% in heavily pretreated populations, supporting their role as effective off-the-shelf therapeutic options. In acute lymphoblastic leukemia, CD19-directed CAR T-cell therapies, including tisagenlecleucel and brexucabtagene autoleucel, achieved high rates of remission with deep measurable residual disease negativity, supporting their role as definitive or bridging strategies in relapsed disease. Beyond hematologic malignancies, early-phase data highlighted the expansion of T cell-redirecting therapies into solid tumors. The DLL3-directed bispecific antibody tarlatamab demonstrated clinically meaningful activity in relapsed small cell lung cancer and has received accelerated regulatory approval based on response rate and durability. Safety profiles were broadly consistent across platforms. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were frequent but predominantly low grade and manageable with IL-6 blockade and corticosteroids. Infections and prolonged cytopenias represented the principal drivers of morbidity, emphasizing the need for structured supportive care. Contemporary recommendations from the NCCN and International Myeloma Working Group support proactive toxicity mitigation, antimicrobial prophylaxis, and multidisciplinary management. Emerging strategies, including trispecific antibodies, dual-target CAR T-cell constructs, and allogeneic "off-the-shelf" cellular therapies, demonstrated promising early efficacy and represent key approaches to improving durability, overcoming resistance, and expanding access across hematologic malignancies. CONCLUSIONS:T cell-redirecting therapies represent a central pillar in modern oncology, delivering high response rates across hematologic malignancies with expanding roles in earlier treatment settings. Future progress will depend on improving durability, optimizing sequencing, mitigating toxicity, and enhancing real-world deliverability through next-generation and multitarget platforms.
INTRODUCTION:Splicing factor 3a subunit 3 (SF3A3) is a core component of the SF3A complex essential for pre-mRNA splicing. However, its role and prognostic significance in liver hepatocellular carcinoma (LIHC) remain poorly characterized. METHODS:We systematically investigated the role of SF3A3 in LIHC using RNA sequencing data, promoter methylation profiles, and proteomic data from The Cancer Genome Atlas and Genotype-Tissue Expression datasets. Associations between SF3A3 expression and clinical or pathological features were analyzed, and the prognostic value of SF3A3 was assessed using survival analysis. RESULTS:SF3A3 mRNA and protein levels were elevated in LIHC tumors, whereas promoter methylation was reduced compared with matched normal liver tissues. High SF3A3 expression was positively associated with advanced tumor stage and grade, as well as TP53 mutation status. Elevated SF3A3 expression was linked to significantly poorer overall survival in patients with LIHC. SF3A3 expression showed a positive correlation with tumor-associated fibroblast infiltration. Survival analyses indicated that SF3A3 expression level and tumor stage are key factors associated with LIHC overall survival. Gene set enrichment analysis revealed that tumors with high SF3A3 expression were significantly enriched for pathways related to the GABA-A receptor complex and FGFR3 mutant receptor activity. CONCLUSION:The expression of SF3A3 in LIHC tumors is correlated with adverse pathological features and poor prognosis, and potential biological mechanisms underlying the role of SF3A3 in LIHC were elucidated. This study highlights SF3A3 as a promising biomarker for prognosis and disease severity in LIHC.
BACKGROUND:The standard induction regimen for newly diagnosed acute myeloid leukemia (AML) in eligible patients remains cytarabine-daunorubicin (7+3), although FLAG-based regimens are increasingly used in high-risk disease. METHODS:We performed a PRISMA 2020-compliant systematic review and meta-analysis comparing FLAG-based induction with standard 7+3 in adults with newly diagnosed AML. Five retrospective cohort studies, including 534 patients, were analyzed. RESULTS:FLAG-based induction was associated with a significantly higher overall response rate than 7+3 (OR: 1.83, 95% CI: 1.03-3.22), without a significant difference in 30-day mortality (OR 0.56, 95% CI: 0.12-2.69) or 60-day mortality (OR: 0.79, 95% CI: 0.29-2.14). Survival outcomes were heterogeneous and could not be pooled: median overall survival (OS) was similar in 1 cohort, whereas 2 studies reported improved OS with FLAG-based induction; disease-free survival/relapse-free survival outcomes were inconsistently reported. FLAG-based induction was associated with higher receipt of consolidation therapy, while bridging to allogeneic transplantation did not differ significantly. Cytogenetic and molecular risk data were variably defined and incompletely reported, precluding reliable pooled subgroup analyses. CONCLUSIONS:Overall, FLAG-based induction improves response rates without a clear increase in early mortality or selected reported safety outcomes; however, its impact on survival remains uncertain and appears influenced by post-remission strategies. Prospective randomized trials are needed to better define its role in frontline AML therapy.
INTRODUCTION:Tyrosine kinase inhibitors (TKIs) have transformed chronic-phase chronic myeloid leukemia (CML) into a chronic condition with excellent long-term survival. As outcomes improve, attention has shifted toward treatment-related metabolic effects and survivorship issues. Body weight and body mass index (BMI) are important indicators of metabolic health; however, the long-term effects of TKIs on these parameters remain incompletely characterized, particularly in real-world settings. This study evaluated longitudinal changes in body weight and BMI in adults with chronic-phase CML treated with TKIs. METHODS:We conducted a retrospective longitudinal observational study at a tertiary care center between January 2016 and December 2023. Adult patients with chronic-phase CML who initiated TKI therapy and had baseline and follow-up weight measurements were included. Patients with major preexisting metabolic conditions or factors likely to confound weight were excluded. Body weight and BMI were assessed at predefined time points up to 7 years. Paired analyses evaluated within-patient changes over time, and stratified analyses were performed according to initial TKI and cumulative exposure patterns. RESULTS:A total of 175 patients were included in the analytic cohort (82.9% male; mean age 39.2 ± 11.7 years). The marked male predominance and younger age reflect the demographic context of CML care in Qatar. Mean baseline weight was 68.2 ± 14.4 kg, and baseline BMI was 24.6 ± 3.9 kg/m2. Weight increased significantly from baseline at 6 months (+4.27 kg), 12 months (+6.00 kg), 18 months (+6.63 kg), and 24 months (+6.41 kg) (all p < 0.001). At the last follow-up, the mean weight gain was 6.12 kg (p < 0.001), with 56.9% of patients achieving ≥5% weight gain. The temporal pattern showed rapid weight gain during the first 6-12 months, followed by stabilization through 2-3 years with persistent elevation thereafter. Weight and BMI increases were observed across all first-line TKIs and cumulative exposure groups, without statistically significant differences between agents. CONCLUSION:In this real-world cohort of adults with chronic-phase CML, TKI therapy was associated with early and sustained increases in body weight and BMI, largely occurring within the first year of treatment. These changes likely reflect a combination of treatment-related metabolic effects and reversal of cancer-associated catabolism. Given the long life expectancy of patients with CML, routine metabolic surveillance, early lifestyle interventions, and prospective studies incorporating metabolic biomarkers, body composition, edema assessment, treatment response, and toxicity outcomes should be incorporated into long-term CML survivorship research and care.
INTRODUCTION:We quantified trends and heterogeneity in lung cancer burden attributable to high fasting plasma glucose (HFPG) among women aged ≥50 years (used as a population-level proxy for postmenopausal status) globally and across BRICS countries from 1990 to 2021. METHODS:HFPG-attributable lung cancer deaths and disability-adjusted life years (DALYs) for women aged ≥50 years were obtained from Global Burden of Disease 1990-2021. Burden was summarized as numbers and age-standardized rates (ASR) per 100,000, stratified by age, Socio-demographic Index (SDI) quintile, and country. Trends were assessed using estimated annual percentage change (EAPC) from log-linear regression. RESULTS:Global HFPG-attributable deaths and DALYs increased markedly from 1990 to 2021, with rising ASR (global EAPC 1.21; 95% CI, 1.11-1.31). A strong age gradient was observed; EAPC increased from 0.53% (50-54 years) to 3.65% (≥95 years). In 2021, the DALYs ASR peaked in the 75-79 years group (59.38 per 100,000). High-SDI settings consistently had the highest ASR and increasing burden. In BRICS, the ASR of DALYs increased in all five countries with substantial heterogeneity; India showed the fastest increase (EAPC 3.05; 95% CI, 2.91-3.19), followed by South Africa (2.82; 2.64-3.00), and Brazil (2.36; 2.31-2.42), while China showed the smallest increase (0.87; 0.70-1.03). CONCLUSION:HFPG-attributable lung cancer burden in women aged ≥50 years rose substantially from 1990 to 2021, with disproportionate growth in older ages and clear SDI/BRICS differences, supporting integrated metabolic prevention within cancer control and healthy aging strategies.
Introduction: Real-world evidence is limited for patients with unresectable hepatocellular carcinoma (HCC) who are ineligible for locoregional therapy (LRT) at initial diagnosis. We examined diagnostic pathways and outcomes of first-line atezolizumab plus bevacizumab (Atz+Bev), with a focus on de novo LRT-ineligible HCC. Methods: We retrospectively analyzed 107 systemic therapy-naïve patients with unresectable HCC who received Atz+Bev as first-line systemic therapy. Patients were categorized into LRT-naïve (n = 55) and LRT-experienced (n = 52) groups. Diagnostic pathways, baseline characteristics, and treatment outcomes were evaluated. Results: Among LRT-naïve patients, 34.5% presented with HCC-related symptoms, whereas the majority were diagnosed incidentally during outpatient care for metabolic comorbidities, often triggered by mild liver enzyme abnormalities. In this group, clinically meaningful disease control was observed despite a high intrahepatic tumor burden at presentation, with an objective response rate of 41.8% and a disease control rate of 87.3%. Median progression-free survival was 11.7 months. Clinical outcomes were generally comparable between the LRT-naïve and LRT-experienced groups. Conclusion: Atz+Bev provides clinically meaningful disease control in patients presenting with de novo LRT-ineligible unresectable HCC. The frequent incidental mode of diagnosis highlights opportunities to strengthen risk stratification and surveillance in high-risk metabolic liver disease.
INTRODUCTION:Rectal cancer requires multidisciplinary management, including chemotherapy treatment, for successful clinical outcomes. Splenic characteristics on computed tomography (CT) imaging have been proposed to reflect immune function. This study explores whether splenic size and density on pretreatment CT scans predicts chemotherapy dose-limiting toxicities (DLTs) and cancer outcomes in rectal cancer patients. METHODS:A retrospective study of rectal cancer patients who received chemotherapy treatment with curative intent from February 2013 to March 2023 was conducted. Pretreatment CT scans were collected for measurement of splenic volume and density. Receiver operating characteristics analyses of splenic density and volume was performed to calculate the area under the curve (AUC). The AUC was used to determine association with overall survival (OS), disease-free survival (DFS), and DLT. RESULTS:A total of 234 patients were included, and 98 (41.8%) patients were classified as having diffuse reduction of spleen density (DROSD). The DROSD group experienced significantly reduced DLTs (13.3% vs. 24.3%, p = 0.045). There was no significant association between OS or DFS with splenic volume or density. CONCLUSION:This study has shown that DROSD is an independent predictive factor for reduced DLT in rectal cancer patients undergoing chemotherapy treatment. Further research is needed to validate findings and elucidate underlying mechanisms.
