Yakup Ergun

Background: Reliable biomarkers that predict outcomes with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) remain limited. ABO blood group antigens may influence tumor immunity and response to immunotherapy. Methods: We retrospectively analyzed 239 patients with advanced NSCLC treated with ICI-based therapy between 2019 and 2024. Patients were classified according to ABO blood group, and overall survival (OS), progression-free survival (PFS), and treatment response were evaluated. Results: Patients with blood group O had significantly longer OS (18.6 vs. 11.0 months; p < 0.001) and PFS (9.4 vs. 4.2 months; p = 0.001) than patients with non-O blood groups. In multivariable analyses, blood group O remained independently associated with improved OS and PFS. Conclusions: Blood group O may represent a simple and readily available host-related prognostic marker in patients with advanced NSCLC receiving ICI-based therapy. Prospective multicenter studies are required to validate these findings.

Background: Sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) are TROP2-directed antibody–drug conjugates with topoisomerase I inhibitor payloads but distinct recognized adverse-event profiles. Comparative reporting patterns for these agents remain incompletely characterized. Methods: We analyzed a case-level line listing downloaded from the U.S. Food and Drug Administration (FDA) Adverse Event Monitoring System (AEMS; formerly the FDA Adverse Event Reporting System [FAERS]) Public Dashboard on 7 July 2026. Reports listing SG or Dato-DXd among suspect product names or active ingredients were assigned mutually exclusively. Prespecified toxicity phenotypes and individual MedDRA Preferred Terms (PTs) were compared using reporting proportions, comparative reporting odds ratios (RORs), false-discovery-rate correction, and multivariable logistic regression. A breast cancer-restricted analysis with crude RORs and 95% CIs was also performed. Results: The cohort comprised 6368 distinct Case IDs (SG, 5714; Dato-DXd, 654). Compared with SG, Dato-DXd reports were enriched for mucositis/stomatitis (18.3% vs. 1.3%; ROR, 17.61; adjusted reporting odds ratio [aROR], 20.04) and ocular toxicity (10.9% vs. 0.9%; ROR, 13.26; aROR, 13.98). The aRORs for Dato-DXd versus SG were 0.11 for hematologic cytopenia, 0.12 for neutropenia/febrile neutropenia, 0.11 for diarrhea/colitis, and 0.57 for infection/sepsis. Exact interstitial lung disease/pneumonitis showed reporting enrichment with Dato-DXd in the unadjusted analysis (ROR, 3.12), but the comparative reporting association was attenuated after adjustment (aROR, 1.44; 95% CI, 0.87–2.39). Overall gastrointestinal reporting was similar, and the breast cancer-restricted crude RORs were directionally consistent with the full-cohort comparisons. Conclusions: SG and Dato-DXd showed distinct adverse-event reporting profiles. SG reports were characterized by relative enrichment of hematologic and diarrheal events, whereas Dato-DXd reports were enriched for mucosal and ocular events. These findings are hypothesis-generating reporting comparisons and should not be interpreted as incidence estimates, causal associations, or conventional head-to-head safety estimates.

Background: Reliable biomarkers to predict response to immune checkpoint inhibitors (ICIs) in non–small cell lung cancer (NSCLC) remains limited.ABO blood group antigens may influence tumor immunity and response to immunotherapy. Methods: We retrospectively analyzed patients with advanced NSCLC treated with ICIs between 2019 and 2024. Patients were classified according to ABO blood group. Overall survival (OS), progression-free survival (PFS), and treatment response were evaluated. Results: Patients with blood group O demonstrated significantly longer OS (18.6 vs 11.0 months, p< 0.001) and PFS (9.4 vs 4.2 months, p=0.001). Conclusion: ABO blood group, particularly blood group O, may serve as a clinically relevant host-related prognostic biomarker in NSCLC immunotherapy.

Metastasis is the leading cause of cancer-related death and involves biological processes such as genomic instability and immune evasion. Although metastatic tumors generally retain major alterations present in primary tumors, the extent of additional genomic divergence across cancer types remains insufficiently characterized. A pan-cancer analysis was performed using targeted sequencing data from 2846 patients with matched primary and metastatic tumors (totaling 5692 samples) from the AACR Project GENIE-v18.0 cohort. Comparisons between primary and metastatic samples included mutation count, fraction of genome altered (FGA), gene-level mutation frequencies, copy number alterations (CNA), and structural variants (SV). Metastatic tumors showed modest but statistically significant increases in mutation count (median 6 vs. 5) and FGA (0.186 vs. 0.140), with the largest differences observed in lung, breast, colorectal, pancreatic, and prostate cancers. Eleven genes, including KDM5A, CDKN2A, MYC, ESR1, and AR, were more frequently altered in metastases. Differences in CNA and SV patterns were also observed, particularly in genes involved in cell cycle control and DNA repair. Compared with primary tumors, metastatic tumors demonstrated small but consistent genomic differences. These findings varied across cancer types and may reflect changes associated with the evolutionary transition from primary to metastatic disease.

Background: Mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal tumors constitute 5% of metastatic colorectal cancer(mCRC). Immunotherapy is a new standard, but it is difficult to provide for all patients. 5-Flurouracil-based treatment with anti-EGFRs (cetuximab and panitumumab) in RAS/BRAF-wild or anti-VEGF (bevacizumab) is used in mCRC. Data is limited for the efficacy of anti-VEGF or anti-EGFRs in dMMR/MSI-H mCRC due to the small number of cases in the colorectal cancer population in trials. Aims: To evaluate prognostic factors in dMMR/MSI-H mCRC and compare progression-free survival time of patients receiving anti-VEGF and anti-EGFR combined with first-line 5FU-based therapy. Methods: Patients with metastatic dMMR/MSI-H colorectal cancer diagnosed between January 2015 and January 2023 were included in this cohort study. Progression-free survival times of patients treated with first-line therapy were compared. Prognostic factors associated with overall survival were investigated. Results: A total of 132 patients were included. Mutation rates were 35.6% (n:47) for RAS and 12.1% (n: 16) for BRAF (. Median progression-free survival (PFS) was 10.9 (95% CI: 9.2–12.6) months. Median overall survival (OS) was 44 months (95% CI: 26.23–63.03). 82 (62.1%) patients had primary tumor resection (PTR), 26 (19.7%) had PTR and metastasectomy. A total of 17 (12.8%) de novo mCRC patients had maximal cytoreductive surgery (MCS). A total of 14 (10.6%) patients had subsequent immunotherapy (IO). In multivariate analysis, RAS/BRAF mutation status, MCS, and subsequent IO are defined as prognostic factors for OS (p < 0.01, p: 0.022, and p: 0.005, respectively). No statistically significant difference (PFS, OS) was found in patients receiving first-line anti-VEGF or anti-EGFR therapy. Conclusions: dMMR/MSI-H mCRC is an entity with different tumor biology. We consider that dMMR/MSI-H mCRC patients with BRAF wild, MCS and subsequent IO have better outcomes with 1st line 5FU-based treatment with anti-VEGF/anti-EGFRs.

Introduction: Metastasis represents the leading cause of cancer-related mortality and is characterized by complex biological processes such as genomic instability, immune evasion, and therapy resistance. While metastatic tumors often retain the truncal drivers of their primary counterparts, the extent and nature of additional somatic alterations acquired during progression remain incompletely defined across cancer types. Methods: A comprehensive pan-cancer analysis was conducted using targeted sequencing data from 2,846 patients with matched primary and metastatic tumors (totaling 5,692 samples) obtained from the AACR Project GENIE v18.0 cohort. Harmonized variant calls were used to compare mutation burden, fraction of genome altered (FGA), gene-level mutation frequencies, copy number alterations (CNA), and structural variants (SV) between compartments. Statistical comparisons were adjusted for multiple testing using the Benjamini-Hochberg method. Results: Metastatic tumors exhibited a significantly higher median mutation count (6 vs. 5; p < 0.001) and FGA (0.186 vs. 0.140; p < 0.001) compared to matched primary tumors. This increase was most prominent in non-small cell lung, breast, colorectal, pancreatic, and prostate cancers. Eleven genes, including KDM5A, CDKN2A, MYC, ESR1, and AR, were significantly enriched in metastases, suggesting mechanisms such as cell cycle deregulation, therapy-induced selection, and chromatin remodeling. Notably, ESR1 alterations were enriched in breast cancer metastases, consistent with endocrine therapy resistance, while AR alterations were markedly more frequent in metastatic prostate cancer. CNA analysis revealed recurrent amplifications (MYC, ERBB2, CCND1) and deletions (CDKN2A, PTEN, RB1) in metastatic tumors. Structural variants involving genes linked to DNA damage response and epigenetic regulation were also more prevalent in the metastatic setting. Conclusions: In this large-scale matched cohort of 2,846 patients and 5,692 tumor samples, metastatic tumors exhibited increased mutation burden and widespread genomic instability. Although treatment data were not available to directly associate resistance-related alterations with specific therapies, the observed patterns suggest that these acquired changes reflect context-dependent selection for survival and proliferative advantage in advanced disease, rather than the emergence of novel metastasis-specific driver events.