Clinical Medicine Insights-Oncology最新文献

Background: Colorectal cancer (CRC) remains a global health issue with high morbidity and mortality. According to molecular profiling, genetic mutations such as KRAS, NRAS, and BRAF play a significant role in tumor biology, treatment effectiveness, and patient prognosis. The exact effect of these alterations on overall survival (OS) is, however, unclear. This systematic review and meta-analysis estimated the combined effect of KRAS, NRAS, and BRAF mutations on CRC survival relative to wild-type tumors.

Methods: This study focused on research conducted in the last decade and was registered on PROSPERO (Reg No: CRD420251003000). Search was done using PubMed, EMBASE, MEDLINE, and Google Scholar. Cohort, case control, and randomized controlled trials reporting Overall Survival Hazard Ratios (HRs) for CRC patients with and without KRAS, NRAS, or BRAF mutations were considered. Multiple reviewers independently extracted and assessed data quality using the Newcastle-Ottawa Scale. For heterogeneity, pooled HRs were computed using a random-effects model. Publication bias was determined by funnel plot asymmetry.

Results: Nine trials with 3096 participants qualified. Compared to wild-type CRC, KRAS, NRAS, and BRAF mutations were substantially linked with lower overall survival (pooled HR > 1, P < .05). KRAS mutations were most common and consistently associated with poor survival, while BRAF mutations had the largest impact. Mild funnel plot asymmetry suggested publication bias, but risk-of-bias assessment showed moderate to high methodological quality across trials.

Conclusions: This meta-analysis shows that KRAS, NRAS, and BRAF mutations are important for adverse prognostic markers in colorectal cancer, linked to reduced overall survival. Routine molecular testing for these mutations is vital to enable personalized treatment, improve patient stratification, and enhance clinical outcomes in colorectal cancer management.

Background: The goal of this comprehensive meta-analysis was to evaluate the efficacy and safety of combining Epidermal Growth Factor Receptor (EGFR)-tyrosine kinase inhibitors (TKIs) with bevacizumab vs EGFR-TKI monotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR-sensitizing mutations.

Methods: From inception until October 2023, we retrieved eligible studies comparing EGFR-TKIs combined with bevacizumab to EGFR-TKI monotherapy for the treatment of NSCLC with EGFR-sensitizing mutations. These studies were obtained from databases including CNKI, Wanfang, CBM, VIP, PubMed, Embase, Cochrane Library, and Web of Science. The International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) registration number is 2023120059.

Results: This meta-analysis of 14 randomized controlled trials demonstrated that the combination significantly improved key efficacy outcomes compared to monotherapy. Superior partial response (odds ratio [OR] = 1.33, P = .05), objective response rate (OR = 1.52, P = .005), and reduced disease progression (OR = 0.31, P = .009) were observed. Furthermore, it significantly enhanced 1-year PFS (OR = 2.04, P < .00001), 2-year PFS (OR = 1.38, P = .02), and 1-year overall survival (OR = 1.41, P = .04). The safety profile was manageable, with no significant increase in rash (P = .72) or pneumonitis (P = .16). Expected increases in diarrhea, hypertension, and proteinuria were observed.

Conclusions: The combination of bevacizumab and EGFR-TKIs provides substantial short-to-medium-term survival benefits with an acceptable safety profile for patients with advanced EGFR-mutant NSCLC. These findings support its use as a valuable first-line treatment option for this population.

Background: Atezolizumab combined with bevacizumab (Atezo + Bev) has received regulatory approval as a first-line systemic therapy for unresectable hepatocellular carcinoma. This study aimed to evaluate the effectiveness and safety of atezolizumab combined with bevacizumab (Atezo + Bev) in treating unresectable hepatocellular carcinoma (uHCC) in a real-world Chinese population, focusing on both first-line and second-line treatment settings.

Methods: In this multicenter, retrospective study, patients with uHCC treated with Atezo + Bev were included at 5 centers in China from Jan. 2021 to Jan. 2023. Treatment efficacy was assessed using RECIST 1.1 and mRECIST criteria. Overall response (ORR), disease control rates (DCRs), time to disease progression (TPP), progression-free survival (PFS), and overall survival (OS) were calculated.

Results: The study included 48 patients, with a median age of 58 years, among which 35 and 13 patients received Atezo + Bev as first- and second-line treatment, respectively. The ORR and DCR were 39.6% and 70.8% according to RECIST 1.1, and 60.4% and 75.0% according to mRECIST, respectively. With a median follow-up of 14.5 months, the median PFS was 8.5 months (95% CI [4.4, 11.2]) in the first-line treatment group, while in the second-line group it was 5.1 months (95% CI [2.1, 7.9]). The median OS was not reached. Adverse events of any grade were observed in 75% of patients (n = 36), most commonly being thrombocytopenia (27.1%), lymphopenia (25%), and abnormal liver function (14.6%).

Conclusion: This study confirmed the practical efficacy and safety of Atezo + Bev in real-world Chinese patients with uHCC, both as a first-line and second-line treatment. Further studies are warranted to validate these findings and optimize treatment strategies.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized advanced lung cancer treatment, but immune-related adverse events (irAEs) remain a significant challenge. This study aimed to identify peripheral blood indicators associated with Immune-Related Adverse Events (irAEs) to improve early prediction and management.

Methods: A retrospective analysis of 1910 advanced lung cancer cases treated with ICIs (2015-2024) was conducted. Patients were categorized into 2 groups: irAEs (n = 323) and control (n = 323). Peripheral blood indicators were analyzed at baseline and during treatment. Statistical analyses included t-tests, Mann-Whitney U tests, logistic regression, and Cox proportional hazards models.

Results: Age (odds ratio [OR] = 0.96, P < .001) and radiotherapy history (OR = 2.35, P = .004) were significant irAE risk factors. Hemoglobin, red blood cells, and lymphocyte ratios decreased, while neutrophil ratios, neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and systemic inflammation markers increased in irAE patients. The NLR and LDH were independent predictors of irAEs and overall survival (P < .05).

Conclusion: Peripheral blood indicators are valuable for irAE prediction. Specifically, elevated NLR (hazard ratio [HR] = 1.14, P = .002) and LDH (HR = 1.00, P = .03) were identified as independent risk factors for irAEs and were also significantly associated with poorer overall survival.

Background: Computed tomography (CT) features and clinical characteristics have been shown in recent studies to be effective predictive indicators for risk stratification of thymic epithelial tumors. High-risk thymoma and thymic carcinoma (HRT-TC) are highly aggressive and are associated with poor prognoses. The aim of this study is to evaluate the predictive value of CT features and clinical characteristics to assess postoperative progression in patients with HRT-TC.

Methods: Clinical and enhanced CT data were retrospectively collected from patients who underwent HRT-TC surgery between June 1, 2012, and June 1, 2022. A univariate Cox regression analysis was conducted to identify the risk factors associated with postoperative progression. A multivariate Cox regression analysis was then used to determine the independent risk factors. Three-year and 5-year single-factor models as well as multifactorial combined models were then constructed based on the results of these analyses to assess their efficacy, accuracy, and net benefit. The best-performing model was selected to create a nomogram for a consistency assessment.

Results: A total of 215 patients were included in the study. The multivariate Cox regression analysis revealed that independent prognostic factors that influenced postoperative progression were the tumor length (hazard ratio [HR] = 1.027; 95% confidence interval [CI] = 1.004-1.049, P = .018), tumor resection (HR = 4.122; 95% CI = 2.054-8.274, P < .001), and the mediastinal vascular invasion (MVI; HR = 2.779; 95% CI = 1.140-6.775, P = .025). The 3-year and 5-year combined models demonstrated superior predictive efficacy, accuracy, and net benefits. The nomogram and calibration curves showed that the predicted risk probabilities from the nomogram aligned well with actual observations.

Conclusions: A nomogram based on clinical and CT features provided effective predictions of progression following HRT-TC. This prognostic tool holds significant value for clinicians to guide therapeutic decisions and personalize survival assessments.

Background: With advances in cancer treatment, the number of cancer survivors has increased, bringing attention to long-term complications such as alterations in bone mineral density (BMD). Although survivors are at elevated risk for low BMD, prior studies have focused on specific cancer types and relied on traditional regression models, which are limited in capturing complex inter-variable relationships. This study aimed to examine the causal relationships among factors affecting BMD in cancer survivors and age-matched controls using causal Bayesian network (CBN) modeling.

Methods: Data from the 2010-2011 Korea National Health and Nutrition Examination Survey (KNHANES) V were analyzed. We included 227 cancer survivors and 681 age- and sex-matched controls. Associations between BMD and variables such as age, sex, body composition, smoking, fracture history, and vitamin D were assessed using linear regression. A CBN model was then applied to evaluate probabilistic dependencies and potential causal relationships between variables and femoral neck BMD.

Results: Among all participants, age, sex, smoking, fracture history, body fat percentage, muscle mass, and cancer history were significantly associated with femoral neck BMD. In cancer survivors, age (β = -0.032, P < .001) and sex (β = -0.680, P < .001) showed negative associations with BMD, whereas higher muscle mass (β = 0.073, P < .001) was a strong positive predictor. Smoking (β = -0.779, P = .005) and previous fractures (β = -0.507, P = .003) were also linked to lower BMD. The CBN model identified direct effects of age and muscle mass on BMD, with indirect effects from sex, smoking, and fracture history. Among women aged >60 years, greater muscle mass appeared particularly protective.

Conclusion: Causal Bayesian network modeling identified muscle mass as a key modifiable factor influencing BMD among cancer survivors. These findings highlight the importance of muscle-preserving lifestyle interventions, including resistance exercise and adequate protein intake, in survivorship care. The CBN approach provides a framework for identifying individualized risk pathways and can support personalized bone-health management strategies in clinical practice.

Background: Pancreatic cancers (PCs)-especially pancreatic ductal adenocarcinoma (PDAC)-are among the deadliest digestive system cancers, with a 5 year survival of approximately 13%. Beta blockers (BBs), which inhibit beta-adrenergic receptor-mediated angiogenesis and immunosuppression, are potential candidates for oncological drug repurposing. However, the clinical evidence is inconsistent, and robust subgroup analyses are lacking. This study systematically evaluated the association between BB use and survival in PC patients. Furthermore, subgroup analyses were conducted to clarify differential clinical effects.

Methods: This study was conducted in accordance with PRISMA guidelines and registered with PROSPERO (CRD420251106076). The PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify observational studies on all-cause mortality (ACM) and cancer-specific mortality (CSM). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using RevMan 5.3 and R, and the results were presented in forest plots.

Results: This analysis included nine retrospective cohort studies involving over 30 000 patients. There were no significant associations between BB use and ACM (HR = 1.07; 95% CI [0.95-1.20]) or CSM (HR = 0.89; 95% CI [0.70-1.14]). However, subgroup analysis revealed that BB use was significantly associated with increased ACM risk in surgical patients (HR = 1.18; 95% CI [1.05-1.31]). Moreover, non-selective BB (NSBB) use significantly reduced CSM risk (HR = 0.81; 95% CI [0.68-0.97]). Both sensitivity and trim-and-fill analyses confirmed the robustness and consistency of these results.

Conclusions: This meta-analysis presents the first systematic evidence regarding the potential role of NSBBs in mitigating CSM, thus providing support for their potential repurposing. In addition, these findings indicate that perioperative BB use may be associated with increased ACM risk, highlighting the need for careful perioperative risk assessment. To further substantiate these findings, future prospective studies should explore combined approaches, particularly those integrating immune or anti-angiogenic therapies.

Background: Recent trials of ribociclib, a cyclin-dependent kinase inhibitor, have shown promising results in patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) breast cancer. This meta-analysis evaluates the efficacy and safety of combining ribociclib with endocrine therapy (ET) versus ET alone in this patient population.

Methodology: A comprehensive search of PubMed, Embase, CENTRAL, Scopus, and Web of Science (up to July 2024, no language restrictions) identified randomized controlled trials (RCTs) comparing endocrine therapy (ET) with and without ribociclib for HR+/HER2- breast cancer. Bias was assessed using Cochrane's Risk of Bias tool. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and odds ratios (ORs) for Grade III + adverse effects (neutropenia, hepatobiliary toxicity, QT prolongation, and interstitial pneumonitis) were calculated with 95% confidence intervals (CI). A random-effects model accounted for heterogeneity (I² statistic). The protocol was registered in PROSPERO (CRD42024558512).

Results: The meta-analysis of 5 RCTs (7286 participants) showed ribociclib plus ET significantly improved OS (HR 0.76, 95% CI 0.68-0.85, P < .001) and PFS (HR 0.57, 95% CI 0.51-0.64, P < .001) compared with ET alone. Grade III + adverse effects of special interest that were more common with ribociclib plus ET include neutropenia (OR 75.76, 95% CI 35.23-162.93, P < .001), hepatobiliary toxicity (OR 2.54, 95% CI 1.32-4.90, P = .005), and QT prolongation (OR 2.95, 95% CI 1.69-5.16, P < .001). The rare grade III + interstitial pneumonitis events (OR 3.36, 95% CI 0.56-20.07, P = .18) also warrant ongoing vigilance.

Conclusion: Ribociclib combined with ET improves OS and PFS but is associated with higher rates of adverse effects, compared with ET alone, highlighting the need for careful monitoring and management.

Funding: None.

Background: Colonic gastrointestinal stromal tumors (cGISTs) represent an exceptionally rare subtype of gastrointestinal stromal tumors (GISTs) and exhibit distinct clinicopathological features. Nonetheless, limited research has systematically assessed the prognostic differences between cGISTs and GISTs originating from other anatomical sites under comparable baseline and oncological conditions. Current prognostic stratification systems for GISTs have significant limitations in evaluating colonic subtypes.

Methods: A retrospective case-control study. Surgical cGIST cases (2012-2024) from 4 tertiary hospitals were analyzed, along with 676 contemporaneous gastric GISTs (gGISTs) controls. Additional individual patient data were extracted from published articles, reviews, letters, and comments identified through a systematic literature search. Propensity score matching (1:4) was performed to balance baseline variables before comparing survival outcomes.

Results: Compared with gGISTs, cGISTs exhibited distinct clinicopathological characteristics, including older average age (P = .001), larger tumor diameter (P = .003), higher mitotic index (P = .007), and lower positive expression rates of CD117 (79.25% vs 98.81%, P < .001), CD34 (80.43% vs 98.81%, P < .001), and DOG-1 (76.67% vs 98.35%, P < .001). After propensity score matching successfully eliminated baseline differences, gGIST patients demonstrated superior survival outcomes, with higher 1-, 3-, and 5-year recurrence-free survival (RFS) rates of 100.0%, 98.76%, and 94.13%, compared with 95.50%, 86.69%, and 86.69% in matched cGIST cases. Similarly, gGIST patients showed higher 1-, 3-, and 5-year overall survival (OS) rates of 100.0%, 99.39%, and 97.06%, compared with 95.50%, 86.58%, and 82.45% in matched cGIST cases. Of note, the difference in OS was statistically significant (P = .04), whereas the difference in RFS did not reach significance (P = .31).

Conclusions: The cGISTs exhibit distinct clinicopathological characteristics and are associated with a significantly poorer prognosis compared with gGISTs. Therefore, diagnostic and therapeutic strategies for cGISTs warrant further exploration and refinement.

Background: Patient-derived tumor cell cluster (PTC)-based drug sensitivity assays show promise for enabling precision drug selection; however, their predictive value in advanced non-small cell lung cancer (NSCLC) requires further elucidation.

Methods: To assess the concordance between PTC-based drug sensitivity and clinical outcomes, we conducted a single-center prospective cohort study at Peking University Third Hospital from August 2021 to August 2024. We enrolled 38 consecutive patients, from whom 44 fresh tumor specimens were obtained for PTC-based drug sensitivity assays and compared with paired clinical outcomes of chemotherapy and targeted therapy regimens. Concordance was assessed using the Kappa statistic and receiver operating characteristic curve analysis. A Cox proportional-hazard model was used to identify prognostic factors for progression-free survival (PFS).

Results: We observed an 81.8% (36/44) concordance between the PTC killing rate (>0% vs 0%) and the best overall clinical response (disease controlled vs disease progression per RECIST v1.1) (Kappa = 0.484, area under the curve (AUC) = 0.740). The concordance with the local response of the biopsied lesions was even higher, at 87.5% (35/40) (Kappa = 0.593, AUC = 0.841). A PTC killing rate >0% was correlated with significantly longer PFS (8.6 vs 2.0 months, P < .001) and emerged as an independent predictor of PFS in multivariate analysis (hazard ratio (HR) 3.507, 95% confidence interval (CI) 1.289-9.536). Exploratory subgroup analysis revealed concordance rates of 73.7% (14/19) for malignant effusion-derived PTCs and 88.0% (22/25) for tumor tissue-derived PTCs; 95.2% (20/21) for first-line therapy and 69.6% (16/23) for later-line therapies; and 80.0% (12/15) for targeted therapy and 85.2% (23/27) for chemotherapy. Notably, the concordance rate reached 100% (14/14) in patients receiving chemotherapy plus immune checkpoint inhibitors.

Conclusions: These findings validate the predictive value of the PTC-based drug sensitivity assay in guiding personalized treatment for patients with advanced NSCLC and support its clinical translation.

Registration: Chinese Clinical Trial Registry, Registration No.: ChiCTR2100048791, https://www.chictr.org.cn/showproj.html?proj=129885.