Background Although osimertinib is widely used and is the most recommended drug worldwide for epidermal growth factor receptor (EGFR) -mutated lung cancer, treatment strategies post-osimertinib failure remain unclear. A previous report showed that if administered to patients previously treated with EGFR-tyrosine kinase inhibitors (TKIs), erlotinib or gefitinib plus bevacizumab resulted in an objective response rate (ORR) of 13%, disease control rate (DCR) of 88%, median progression-free survival (PFS) of 4.1 months, and median overall survival (OS) of 13.5 months. However, the efficacy of erlotinib plus ramucirumab therapy in patients previously treated with EGFR-TKIs has not been reported. Methods This retrospective study was designed to exploratorily evaluate the efficacy and safety of erlotinib plus ramucirumab therapy after osimertinib treatment in clinical practice. Forty-three patients with EGFR -mutated lung cancer were enrolled from 14 centers. The primary endpoint was PFS of erlotinib plus ramucirumab therapy. The secondary endpoints were time to treatment failure (TTF), OS, ORR, DCR, and safety of erlotinib plus ramucirumab therapy. Results The median PFS for erlotinib plus ramucirumab therapy was 7.1 months, median TTF 4.8 months, median OS 14.4 months, ORR 31.7%, and DCR 87.8%. In the group in which osimertinib was discontinued because of disease progression, the median PFS was 3.8 months and one-year PFS rate was 19.0%. In the group in which osimertinib was discontinued owing to adverse events, the median PFS was 11.1 months and one-year PFS rate was 48.3%, and treatment was continued without serious adverse events. Conclusions Erlotinib plus ramucirumab therapy may be a promising treatment option for patients with EGFR -mutated lung cancer who received initial treatment with osimertinib, especially in cases in which osimertinib was discontinued owing to adverse events.
Objective This systematic review and network meta-analysis aimed to evaluate the incidence and safety ranking of hematological toxicities associated with targeted therapies for malignant solid tumors in RCTs. Methods PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to June 2026 for RCTs in adults with malignant solid tumors receiving at least one targeted agent and reporting anemia. Anemia was the main result, while other secondary outcomes included thrombocytopenia, neutropenia, leukopenia, etc. Subgroup analyses were carried out according to research phase, tumor type, country category, etc. ROB was assessed using the Cochrane tool. Consistency was evaluated by node-splitting and loop-specific approaches. Sensitivity analyses were performed by sequentially removing individual trials. Publication bias was assessed using funnel plots. Treatment safety was ranked using the SUCRA. Results 27 phase II/III RCTs (n = 8985) were included. The incidence of grades 1-5 anemia was 25.79%, and grades 3-5 anemia was 6.53%. Among single targeted agents, erlotinib had the highest all-grade anemia incidence, while alectinib had the lowest severe-grade anemia incidence. Targeted therapy combined with chemotherapy generally showed higher hematological toxicity than single-agent or doublet targeted therapy. Tepotinib plus gefitinib ranked highest in safety for both all-grade and severe-grade anemia, whereas afatinib plus chemotherapy ranked lowest for severe-grade anemia. For secondary outcomes, erlotinib monotherapy carried the highest risk of all-grade and severe-grade neutropenia, FN, and WBC count decrease among single agents. Overall, 136 treatment-related deaths were recorded, of which only 2 were attributed to hematological toxicity. Subgroup analysis revealed that, apart from the type of tumor, it was the key factor contributing to the heterogeneity. Sensitivity analyses confirmed the robustness of the primary findings. Conclusions Each targeted therapeutic regimen has a unique safety profile. In clinical practice, early detection and treatment of hematological toxicities linked to targeted medications are crucial.
Background Preoperative treatment is central to rectal cancer, but its benefit in elderly patients remains unclear. This study evaluated its impact on clinical outcomes in elderly patients undergoing surgery. Methods This cohort included 5,533 patients aged ≥65 years with newly diagnosed locally advanced rectal cancer (LARC) who underwent surgical resection between January 1, 2008, and December 31, 2017. Patients were stratified into the neoadjuvant chemoradiotherapy (nCRT) group (n = 1,086) and the upfront surgery group (n = 4,447). Cox proportional hazards models were used to estimate the overall survival (OS) and disease-free survival (DFS) between groups. Stratified analyses were further performed according to relevant prognostic factors. Results Elderly LARC patients who received nCRT were more likely to be male, younger (65–75 years), have stage III disease (clinically node-positive), and have no comorbidities (CCI = 0). These patients were also more likely to achieve significant tumor downstaging (p < 0.05), as reflected by higher rates of ypT0 and ypN0 status, along with a lower lymph node yield. nCRT was associated with improved OS in univariable analysis (p=0.0002), but this association was no longer significant after multivariable adjustment (p=0.5645). No significant associations were observed for DFS. Consistent with the adjusted analysis, stratified analyses across relevant prognostic factors showed no significant associations between nCRT and either OS or DFS. Conclusions The use of nCRT was associated with increased pathological tumor downstaging but not improved survival outcomes in elderly patients with locally advanced rectal cancer. Individualized treatment decisions are therefore warranted.
Background Given the widespread prevalence of epithelial ovarian cancer as a global malignant tumor, there is an urgent need to deeply explore its risk determinants. This study used cluster analysis to summarize the association patterns of different histological subtypes of epithelial ovarian cancer, and employed the two-sample Mendelian randomization method to evaluate the potential causal association between genetic prediction of IgA nephropathy susceptibility and the risk of epithelial ovarian cancer. This method, under the condition of satisfying the correlation, independence, and exclusion of restrictive assumptions of instrumental variables, helps to reduce the influence of traditional confounding and reverse causation. Methods Genome-wide association data from 15,587 European IgA nephropathy patients served as the primary exposure, with GWAS data from epithelial ovarian cancer subtypes. Three Mendelian randomization(MR) methods including inverse variance weighting MR-Egger regression and weighted median were adopted for causal inference. Sensitivity analyses included Cochran’s Q test, MR-Egger intercept, MR-PRESSO, and Leave-one-out analysis. Six subtype-specific UVMR analyses were conducted, and the results were reported separately. Because the subtype outcome datasets were overlapping or nested, no formal meta-analysis or pooled estimate was performed. Results In the subtype-specific UVMR analyses, the effect estimates were generally below the null value, suggesting a directionally concordant pattern towards a lower risk of epithelial ovarian cancer. The association was statistically significant for high-grade serous ovarian cancer (OR =0.81, 95% CI: 0.75- 0.87, P <0.05). The estimates for clear cell ovarian cancer and the remaining evaluated histological subtypes were not statistically significant, although some showed similar inverse directions. Because the subtype-specific outcome datasets were overlapping or nested and shared the same IgA nephropathy exposure GWAS, no formal pooled estimate was calculated. Sensitivity analyses [including MR-Egger intercept, MR-PRESSO, leave-one-out analysis, and Steiger directionality testing] yielded results consistent with the primary subtype-specific analyses. Conclusion Genetically predicted liability to IgA nephropathy may be associated with a lower risk of epithelial ovarian cancer, particularly high-grade serous ovarian cancer, although this finding requires validation in independent and sex-matched datasets.
Objective To investigate the predictive value of gastric fluid levels of Regulator of G-protein Signaling 1 (RGS1) and Collagen Type IV Alpha 1 Chain (COL4A1) for prognosis in patients with gastric cancer. Methods From January 2021 to May 2022, 240 patients who underwent radical gastrectomy for gastric cancer were prospectively enrolled in this single-center prospective observational study and followed up for 3 years. Patients were categorized into a poor-prognosis group (n=68) and a good-prognosis group (n=172) based on follow-up outcomes. Gastric fluid RGS1 and COL4A1 levels were measured by enzyme-linked immunosorbent assay. Spearman correlation, receiver operating characteristic (ROC) curve, Kaplan–Meier, and multivariable Cox proportional hazards regression analyses were performed. Results The poor-prognosis group exhibited a higher TNM stage, greater depth of invasion, and a higher rate of lymph node metastasis (all P < 0.05). RGS1 and COL4A1 levels were elevated in the poor-prognosis group; the two markers were positively correlated (r = 0.319, P < 0.05). ROC curve analysis showed areas under the curve of 0.852 and 0.838 for RGS1 and COL4A1 alone, respectively, with a combined area under the curve of 0.878. Kaplan–Meier analysis indicated significantly shorter mean survival time in the high-expression groups (log-rank χ 2 = 119.98 and 69.73, respectively; both P < 0.001). Multivariable Cox regression identified higher TNM stage, depth of invasion, lymph node metastasis, elevated RGS1 (hazard ratio [HR] = 1.064, 95% confidence interval [CI]: 1.040–1.088, per 100 pg/mL), and elevated COL4A1 (HR = 1.492, 95% CI: 1.221–1.822, per 100 pg/mL) as independent risk factors for poor prognosis (all P < 0.05). Conclusions Elevated gastric fluid RGS1 and COL4A1 levels are closely associated with poor prognosis in gastric cancer, suggesting their potential exploratory value as adjunctive indicators for prognostic stratification; however, their clinical applicability remains to be validated.
