Search Results (2,181)

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by providing durable responses and a favorable safety profile, ushering in a new era of tumor immunotherapy. However, immune-related adverse events (irAEs) remain a significant clinical challenge. Among these, gastrointestinal irAEs, especially immune-related colitis (ir-colitis), can lead to serious complications if not promptly recognized and managed. Here, we present a case of grade 3 ir-colitis induced by the programmed cell death protein 1 (PD-1) inhibitor sintilimab in a 68-year-old woman with endometrial cancer. The patient developed severe acute diarrhea following ICI administration, which progressed despite initial antidiarrheal and antimicrobial treatments. A multidisciplinary team (MDT) involving gastroenterologists, oncologists, a pathologist, and a clinical pharmacist confirmed the diagnosis and implemented high-dose corticosteroid therapy, yielding significant clinical improvement. Importantly, this report highlights the mechanistic link between PD-1 blockade and ir-colitis pathogenesis, focusing on the dysregulation of the mucosal immune environment and its role in triggering colonic injury. In addition to the case description, we provide a comprehensive review of the literature and clinical guidelines, discussing risk factors, diagnostic approaches, therapeutic strategies, and long-term monitoring. By integrating insights from pharmacology, immunology, and clinical practice, this work emphasizes the importance of early detection, patient education, and MDT collaboration for optimizing therapeutic outcomes and advancing the understanding of ir-colitis in the context of ICI therapy. Full article

Background/Objectives: Acute exacerbation of interstitial lung disease (AE-ILD) is a life-threatening complication in lung cancer patients with pre-existing ILD. Anatomical resection is recognized as a significant risk factor for AE-ILD. We investigated the safety and feasibility of wedge resection in lung cancer patients with ILD. Methods: This retrospective study analyzed clinical stage IA–IIIA primary lung cancer patients with ILD, as recorded in the Shizuoka Registry across eight institutions from January 2019 to May 2023. Patients were categorized into a wedge resection group (WG) and an anatomical resection group (AG), which included segmentectomy, lobectomy, and bilobectomy. Perioperative outcomes were compared between the groups. Results: The WG comprised 36 patients, while the AG included 81. The WG had significantly older patients (77 vs. 72 years, p < 0.01) and smaller tumors (18 vs. 24 mm, p < 0.01). Wedge resection was associated with shorter operative time (100 vs. 205 min, p < 0.01) and less blood loss (5 vs. 30 mL, p = 0.02). The incidence of postoperative complications did not differ significantly (p = 0.84). AE-ILD occurred in three patients (8%) in the WG and four patients (4%) in the AG. Perioperative mortality was 0% in the WG and 2% in the AG; both deaths were due to AE-ILD. Marginal recurrence was observed in four patients (11%) in the WG. Conclusions: Although AE-ILD incidence was higher, no deaths due to IP-AE were observed in the WG. While wedge resection cannot completely prevent postoperative AE-ILD, it may reduce perioperative mortality in lung cancer patients with ILD. Full article

Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with survival outcomes influenced by a range of demographic and pathological factors. While cirrhosis is a well-established risk factor, recent evidence shows that HCC can also develop in patients with only mild to moderate liver fibrosis. However, there is limited understanding of how fibrosis severity interacts with other clinical variables, such as patient age, to affect mortality. This study aims to explore how fibrosis scores relate to both overall and cancer-specific mortality in US HCC patients, with an emphasis on how this relationship may shift across different age groups. Methods: We utilized data from the Surveillance, Epidemiology, and End Results (SEER) database to identify 15,796 adult patients diagnosed with HCC between 2010 and 2021. Baseline demographics, disease characteristics, and treatment variables were examined. Mortality outcomes were evaluated using Cox proportional hazard regression. Variables significant at p < 0.1 in univariate analysis were included in multivariate models to identify independent predictors of mortality (with hazard ratios [HRs] > 1 signifying increased risk). A secondary analysis assessed how age modifies the association between fibrosis score and mortality. Results: The study population was predominantly male (77.2%), with most patients aged 60–79 (59.6%) and presenting with localized disease (61%). A majority had advanced liver fibrosis or cirrhosis (81.7%) and lived in large urban areas (62.9%). Crude comparisons indicated that male sex, older age, single status, advanced tumor stage, lower income, and cirrhosis were linked to worse outcomes. In adjusted models, independent predictors of increased mortality included male sex, older age, unmarried status, and more advanced disease stage. Receipt of surgery or chemotherapy was associated with a lower risk of death. Notably, the influence of fibrosis on mortality was found to be greater in older patients than in their younger counterparts. Conclusions: This analysis identifies key prognostic indicators in HCC and suggests that the relationship between fibrosis and survival is not uniform across age groups. These findings support the need for age-specific clinical management strategies and highlight the potential benefit of early detection and appropriate interventions, even in non-cirrhotic patients. Full article

Background/objectives: Melanoma is one of the deadliest forms of malignant cancers; ultraviolet radiation exposure together with genetic mutations, such as BRAF, represent the main risk factors and are involved in metastatic dissemination. Previous studies demonstrated the anti-emetic and anti-proliferative effects of the flavonoid genistein and the turmeric curcumin in cancers. This study aimed at investigating the anticancer effects of curcumin, genistein and their association in melanoma cells. Methods: Human A375 and CHL-1 cell lines were cultured and treated with different concentrations of curcumin or genistein or curcumin + genistein for 24 h according to IC50. Results: Genistein and curcumin induced cell death, as demonstrated by MTT assay and FDA/PI staining. The anti-apoptotic protein Bcl-2 was significantly reduced after curcumin and curcumin + genistein treatment, but unexpectedly not with genistein alone. Curcumin and genistein significantly increased DNA fragmentation, thus indicating apoptosis induction. Moreover, comet assay confirmed that curcumin and genistein stimulated cell death, as quantified by measuring the displacement between the ‘comet head’ and the resulting ‘tail’. FAK protein expression was significantly reduced by genistein and curcumin in CHL-1 cells and after the treatment with genistein + curcumin in the most aggressive A375 cells. These anti-proliferative effects were confirmed by scratch assay and phospho-p38 reduction. Moreover, both curcumin and genistein alone and in association inhibited cell adhesion, thus indicating that these nutraceuticals could reduce invasion and metastasis. Conclusion: The obtained results provided new insights for the anticancer effects of genistein and curcumin, which could be used to improve therapeutic adherence and drug response. Full article

This was a single-centre retrospective cohort study of patients diagnosed with glioblastoma (GB) at the Juravinski Cancer Centre (JCC). The charts of 528 patients diagnosed with GB at the JCC from an 8-year period from 1 January 2013, to 31 December 2020, were reviewed. The primary objective was to assess the incidence of venous thromboembolism (VTE) in newly diagnosed GB. The secondary objective was to identify patients at higher risk of developing VTE to understand who might benefit from prophylactic anticoagulation. Data on the following factors were collected: date of diagnosis, time to death or last follow-up, location and size of tumour, degree of resection, presence and location of weakness, performance status, body mass index, comorbidities (hypertension, diabetes, dyslipidemia, smoking history), baseline blood counts, and treatments administered. A total of 111 of the 528 patients (21%) were diagnosed with VTE. Most VTE (87%) occurred within 12 months of diagnosis. A previous cancer diagnosis and recurrence or disease progression were the only factors identified as predictive of a higher risk for developing thrombosis. Newly diagnosed patients with GB have been shown to have a significant risk of developing VTE. Consideration should be given for prophylactic anticoagulation at the time of diagnosis. Full article

Background: This study evaluated the prognostic significance of quantitatively assessed interstitial lung abnormalities (ILAs) after lung cancer surgery. Methods: We included patients with pathologic stage I non-small-cell lung cancer (NSCLC) who underwent segmentectomy or lobectomy. ILAs were quantified using deep learning texture analysis software. Five-year overall survival (OS) was compared before and after propensity score matching. Competing risks for lung cancer and non-cancer mortality were also analyzed. Results: Among the 1711 patients, 263 (15.4%) comprised the ILA group. The ILA group was older and had a higher proportion of smokers and pathologic stage IB cases (all p < 0.001). The median follow-up period was 48.0 months. Before matching, 5-year OS was significantly worse in the ILA group than in the non-ILA group (82.5% vs. 93.4%, p < 0.001). After 2:1 matching (N = 697), 5-year OS remained lower in the ILA group (85.8% vs. 91.1%, p = 0.025). Multivariable Cox regression analysis showed that the presence of ILAs was associated with increased risk of all-cause mortality (HR 1.52, 95% CI 1.05–2.18, p = 0.025). Restricted cubic spline analysis revealed a nonlinear increase in mortality risk with greater fibrotic ILA burden. In competing risk analysis, death from lung cancer was similar between groups (2.9% vs. 4.2%, p = 0.3), whereas death from other causes was significantly higher in the ILA group (13.0% vs. 3.7%, p < 0.001). Conclusions: Quantitative assessment of ILAs may provide prognostic value in resected stage I NSCLC, particularly in patients with fibrotic changes. Full article

Little is known about the manifestation of cardiovascular diseases (CVD) among individuals with ocular cancer (OC), a population for whom reports on sex-based differences in survival remain inconsistent. We evaluated the occurrence of CVD mortality after the diagnosis of OC in the United States. We used data from 11,460 adults diagnosed with OC from 2000 to 2021 who were ≥18 years and were enrolled in the Surveillance, Epidemiology, and End Results program. We used competing risk models to estimate hazard ratios (HR) and 95% confidence intervals (CI). About 55% of adults were male, with uveal melanoma being the most common OC (72.1%). During a median follow-up of 5.4 years, 4561 deaths occurred, with 15% attributable to CVD. In models adjusted for sociodemographic and clinico-pathophysiological factors, male adults had elevated risk for CVD mortality (HR: 1.54, 95%CI: 1.31–1.81). The sex difference in CVD mortality was more prominent for adults diagnosed with OC before 65 years of age (HR: 2.15; 95%CI: 1.48–3.11). These associations remained largely unchanged in propensity score analysis. In this study of adults with OC, CVD deaths were higher among young and middle-aged males. Implementation of optimal cardiovascular health interventions after diagnosis of OC, especially among men, holds promise in enhancing survival in this population. Full article

Background: Epidermal growth factor receptor (EGFR) mutations are presented in approximately 50% of East Asian populations with advanced non-small cell lung cancer (NSCLC). While EGFR-tyrosine kinase inhibitors (TKIs) are the standard treatment, patient outcomes are also influenced by host-related factors. This study aimed to investigate clinical and radiological factors associated with early mortality and develop a prognostic prediction model in advanced EGFR-mutated NSCLC. Methods: A retrospective cohort was conducted in patients with EGFR-mutated NSCLC treated with first line EGFR-TKIs from January 2012 to October 2022 at Chiang Mai University Hospital. Clinical data and radiologic findings at the initiation of treatment were analyzed. A multivariable flexible parametric survival model was used to determine the predictors of death at 18 months. The predicted survival probabilities at 6, 12, and 18 months were estimated, and the model performance was evaluated. Results: Among 189 patients, 84 (44.4%) died within 18 months. Significant predictors of mortality included body mass index <18.5 or ≥23, bone metastasis, neutrophil-to-lymphocyte ratio ≥ 5, albumin-to-globulin ratio < 1, and mean pulmonary artery diameter ≥ 29 mm. The model demonstrated good performance (Harrell’s C-statistic = 0.72; 95% CI: 0.66–0.78). Based on bootstrap internal validation, the optimism-corrected Harrell’s C-statistic was 0.71 (95% CI: 0.71–0.71), derived from an apparent C-statistic of 0.75 (95% CI: 0.74–0.75) and an estimated optimism of 0.04 (95% CI: 0.03–0.04). Estimated 18-month survival ranged from 87.1% in those without risk factors to 2.1% in those with all predictors. A web-based tool was developed for clinical use. Conclusions: The prognostic model developed from fundamental clinical and radiologic parameters demonstrated promising utility in predicting 18-month mortality in patients with advanced EGFR-mutated NSCLC receiving first-line EGFR-TKI therapy. Full article

Background: The development of brain metastases (BM) is a relatively uncommon but significantly adverse event in the spread of colorectal cancer (CRC). Although management of CRC BM has improved with advances in imaging and systemic therapies, clinical outcomes remain poor. Methods: This retrospective cohort study used the U.S. National Cancer Database to evaluate survival outcomes, treatment patterns, and prognostic factors in CRC patients diagnosed with BM between 2010 and 2020. Patients with isolated brain-only metastases formed the primary analytic cohort, while those with additional extracranial metastases were included for descriptive comparison. Multivariable Cox proportional hazards and logistic regression models were used to assess factors associated with of survival. Proportional hazards assumptions were tested using Schoenfeld residuals. Accelerated failure time models were also employed. Results: From a cohort of 1,040,877 individuals with CRC, 795 had metastatic disease present along with relevant data, of which 296 had isolated BM. Median overall survival (mOS) in BM-only metastatic disease group was 7.82 months (95% CI: 5.82–9.66). The longest survival was observed among patients treated with stereotactic radiosurgery combined with systemic therapy (SRS+Sys), with a median OS of 23.26 months (95% CI: 17.51–41.95) and a 3-year survival rate of 35.8%. In adjusted Cox models, SRS, systemic therapy, and definitive surgery of the primary site were each independently associated with reduced hazard of death. Rectal cancer patients had longer survival than those with colon primaries (mOS: 10.35 vs. 6.08 months). Age, comorbidity burden, and insurance status were not associated with survival in adjusted analyses. Conclusions: SRS+Sys was associated with longer survival compared to other treatment strategies. However, treatment selection is highly dependent on individual clinical factors such as performance status, comorbidities, and disease extent; therefore, these findings must be interpreted with caution Future prospective studies incorporating molecular and biomarker data are warranted to better guide care in this rare and high-risk group. Full article

Following lung cancer, prostate cancer is the leading cause of cancer death in men. High-risk localized tumor burden or metastatic disease often progresses, refractory to initial treatment regimens. There is ongoing development of technology to appropriately identify high-risk patients, stage them correctly, and offer appropriate treatments to obtain the best clinical outcomes. Prostate cancer-specific membrane antigen (PSMA) is a transmembrane glutamate carboxypeptidase, which helps regulate folate absorption, and its overexpression is pathologically directly proportional and associated with prostate cancer. Increased PSMA expression is a known independent risk factor for poorer survival, and most metastatic lesions in CRPC are PSMA positive. Over the last decade, several PSMA-based PET radiopharmaceuticals have demonstrated superior sensitivities and specificities compared to traditional imaging methods. These outcomes have been demonstrated by several large clinical trials. As the data emerges, these diagnostics are being integrated into standard of care protocol to facilitate nuanced identification of malignant lesions. PSMA is also being targeted through several therapeutics, including radioligands and immunotherapies such as CAR-T, BiTEs, and ADCs. This review will discuss the landscape of PSMA-based theranostics in the context of prostate cancer. Full article

Background: Programmed cell death-related genes (PCDRGs) have been reported to play an important role in diagnosis, treatment and immunity regarding cancer, but their prognostic value and therapeutic potential in acute myeloid leukemia (AML) patients still need to be fully explored. Methods: Cox regression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) analysis were used to identify PCDRGs significantly associated with the prognosis of AML patients. Furthermore, a prognostic risk model for AML patients was constructed based on the selected PCDRGs, and their immune microenvironment and biological pathways were analyzed. Cell experiments ultimately confirmed the potential role of PCDRGs in AML. Results: The results yielded four PCDRGs that were used to develop a prognostic risk model, and the prognostic significance of this model was confirmed using an independent external AML patient cohort. This prognostic risk model provides an independent prognostic risk factor for AML patients. This prognostic feature is related to immune cell infiltration in AML patients. The inhibition of solute carrier family 39 member 14 (SLC39A14) expression enhanced apoptosis and inhibited cell cycle progression in AML cells. Conclusions: This study integrates bioinformatics analysis and cellular experiments to reveal potential gene therapy targets and prognostic gene markers in AML. Full article

Prostate Cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death among men. In Louisiana (LA), Black men are disproportionately diagnosed at later stages compared to White men. This study explores environmental risk factors as potential intermediate variables linking race to cancer diagnosis stage. The Louisiana Tumor Registry data included 24,647 male patients diagnosed with PCa in LA between 2010 and 2018. Among them, 15,875 (64.40%) were Caucasian American (CA) and 8772 (35.59%) African American (AA). Mediation analysis using multiple additive regression trees (MART) identified possible intermediate variables that potentially explain the observed disparity. The study found that individual characteristics and environmental factors jointly explained 84% (95% CI: 44.1%, 94.6%) and 18.6% (95% CI: 7.3%, 53.7%) of the observed racial disparity in PCa stage at diagnosis, respectively. Individual factors included BMI (35.9%), marital status (28.5%), CDI (8.2%), female-headed households (2.3%), comorbidity (3.9%), and insurance status (6.3%). Environmental contributors included cancer risk due to air toxicity exposure (7.2%), asthma prevalence (6.6%), acetaldehyde levels (2.1%), railroad proximity (2.1%), walkability (0.3%), and ozone level (−0.1%). Environmental factors jointly played a significant role in the observed racial disparity. The factors such as air toxicity, acetaldehyde levels, and asthma prevalence highlight the need to address industrial pollutants to reduce the differences. Full article

The Vesical Imaging Reporting and Data System (VI-RADS) is used to detect muscle-invasive bladder cancer, with emerging prognostic implications. Integrating imaging parameters with molecular biomarkers may improve risk stratification in bladder cancer. This study evaluated whether combining VI-RADS scores with serum cytokeratin fragment 19 (CYFRA 21-1) levels—a clinically relevant biomarker for bladder cancer—could improve overall survival (OS) prediction. We retrospectively analyzed 134 patients who underwent transurethral resection of bladder tumors, magnetic resonance imaging, and postoperative serum CYFRA 21-1 measurements. In total, 15 cancer-specific deaths were observed during follow-up. Receiver operating characteristic curve analysis identified optimal prognostic cut-off values: VI-RADS score ≥ 4 and CYFRA 21-1 level ≥ 1.8 ng/mL. The 1-, 2-, and 3-year OS in patients with both high VI-RADS scores and CYFRA 21-1 levels were 42.9%, 16.7%, and 8.3%, respectively, significantly lower than those in other groups (p < 0.001, 0.002, and 0.003, respectively). Multivariate Cox proportional hazards analysis demonstrated that such patients had the poorest OS (hazard ratio: 7.51; p = 0.002). This suggests that combining VI-RADS and CYFRA 21-1 improves prognostic accuracy in bladder cancer, demonstrating potential clinical utility by informing individualized treatment strategies; however, limitations include the retrospective study design and absence of external validation. Full article

Background/Objective: People living with human immunodeficiency virus (PHIV) are at increased risk for malignancies, yet their access to immunotherapy remains limited due to concerns about safety and efficacy. This systematic scoping review evaluates the use of immune checkpoint inhibitors (ICIs) in HIV-associated cancers, analyzing patient outcomes, safety profiles, and the impact on HIV status. Methods: A comprehensive literature search was conducted in databases including PubMed, Scopus, Web of Science (WoS), and Medline, up to January 2025. Studies included assessing the efficacy of ICIs in cancer patients with HIV. The primary outcomes were (a) the efficacy of immune ICIs on prognosis, progression-free survival (PFS), and overall survival (OS). Secondary outcomes were the immune-related adverse events (irAEs) and the survival rate of cancer patients receiving ICIs. Results: A total of 107 cases from 19 studies published between 2011 and 2024 were reviewed. Responses to programmed death 1 (PD-1) inhibitors varied, with 27.1% achieving partial response, 23.36% experiencing stable disease, and 6.54% achieving complete response, while 34.57% had disease progression. Adverse events, including hematologic and endocrine toxicities, were common but mostly manageable. HIV viral loads remained stable in most cases. Conclusions: PD-1 inhibitors demonstrated potential efficacy in HIV-associated malignancies with a safety profile comparable to the general population. However, disease progression remained a concern, highlighting the need for optimized patient selection. Further well-controlled trials are essential to establish treatment guidelines and ensure equitable access to immunotherapy for PHIV. Full article

Background/Objectives: Colorectal cancer is a leading cause of cancer-related death worldwide, with rising incidence in younger adults. Unhealthy diets high in red and processed meat and low in fiber are key modifiable risk factors, highlighting the need for preventive nutritional strategies targeting CRC through dietary interventions. Methods: A one-day sample diet for colorectal cancer prevention, consisting of fiber-rich meals excluding red meat and incorporating whole grains, legumes, vegetables, fruits, nuts, and lean protein alternatives (such as fish and poultry), was developed. Its acceptability was assessed in a cross-sectional study using an online questionnaire among healthy Romanian adults aged 18–50, with a total of 395 included participants. Results: Of the 395 respondents meeting the inclusion criteria (aged 18–50, no cancer or chronic gastrointestinal disorders), 63.5% were females, predominantly urban (90.1%), and highly educated. Mean age was 32.4 years; mean BMI was 25.07 kg/m². The proposed colorectal cancer-preventive diet was rated as “quite attractive” and “very attractive” by 74.9% of participants. All meals received high ratings, with dinner and the first snack being most favored. Most respondents (77.2%) found the diet satisfying and the satiety level and energy adequate, and 90.4% were willing to adopt it at least a few times per week. Financial accessibility was affirmed by 77.2% of the respondents. However, 61.8% reported difficulty eliminating red meat consumption. Female participants rated the diet significantly more attractive than males did (p = 0.041). Willingness to adopt the diet strongly correlated with higher acceptability (p < 0.0001), while BMI and education level showed no significant effect. Conclusions: The proposed colorectal cancer-preventive diet was well accepted by Romanian adults aged 18–50, with higher receptivity among women and those with higher education; willingness to adopt the diet at least a few days per week was high, especially among those psychologically ready for dietary change, while key barriers included red meat reduction and perceived cost, underscoring the need for gender-sensitive, culturally adapted interventions and further research on long-term adherence and clinical impact. Full article