Impact of the number of therapy lines on survival in advanced gastric and esophagogastric adenocarcinoma - a real-world retrospective analysis from Croatia

Background: The EXTREME regimen (cetuximab with cisplatin/carboplatin and 5-fluorouracil) has long been a standard first-line treatment for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC), particularly in patients ineligible for immunotherapy. However, real-world evidence remains limited, especially in regions with delayed access to novel therapies. Methods: We conducted a retrospective, multicenter study of 217 patients with R/M HNSCC treated with cetuximab-based chemotherapy at six Croatian oncology centers between 2016 and 2022, prior to reimbursement of pembrolizumab. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), response rates, and safety. Results: The majority (91%) received the EXTREME regimen. Median OS was 14 months (95% CI, 12–17), and median PFS was 6.2 months (95% CI, 6.0–7.2). Objective response rate was 21%, and disease control rate was 63%. Cetuximab-induced rash correlated with longer PFS. Grade ≥ 3 toxicity occurred in 18.9% of patients. No treatment-related deaths were observed. Conclusion: In routine clinical practice, cetuximab combined with platinum-based chemotherapy remains an effective and well-tolerated first-line treatment for R/M HNSCC, particularly in patients who are ineligible for immunotherapy or with PD-L1–negative tumors. These findings support its continued use in appropriately selected patients.

Some sources report a connection of cellular senescence with chronic pathological conditions; however, the association between particular cellular processes and general health is rarely examined. This study aims to test the relationship of general health with DNA damage pathways that play a crucial role in senescence. The association of ten selected SNPs with subjective and objective general health and functional ability indicators has been tested in 314 oldest-old people from Croatia. Multivariate logistic regression was employed to simultaneously test the impact of variables potentially influencing targeted health and functional ability variables. The best model, explaining 37.1% of the variance, has six independent significant predictors of functional ability scores: rs16847897 in TERC, rs533984 in MRE11A, and rs4977756 in CDKN2B, chronic disease count, Mini-Mental State Examination scores, and age at surveying. In conclusion, the examined ten loci involved in DNA damage repair pathways showed a more significant association with self-rated health and functional ability than with the number of disease or prescribed medicaments. The more frequent, longevity-related homozygote (GG) in rs16847897 was associated with all three aspects of self-assessments—health, mobility, and independence—indicating that this TERC locus might have a true impact on the overall vitality of the oldest-old persons.

A response to: Artificial immortalization, number of therapy lines, and survival of patients with advanced gastric and esophagogastric adenocarcinoma

The prevalence of relapses in advanced squamous cell head and neck cancer (SCHNC) is significant, and so is treatment morbidity. There is persistent need for reliable biomarkers in order to better personalize treatment. The purpose of the present s...

Head and neck squamous cell carcinoma (HNSCC) remains a major global health challenge, with limited long-term survival in the recurrent/metastatic (R/M) setting. Here, we present a rare case of a patient with metastatic laryngeal squamous cell carcinoma who survived eight years after diagnosis of metastatic disease, treated only with standard chemotherapy, metastasectomy, and palliative radiotherapy. To explore potential genomic underpinnings of this unusually favorable outcome, we performed next-generation sequencing of tumor (lymph node and lung metastases) and germline DNA. Mutations were analyzed across ten key oncogenic signaling pathways and compared with the COSMIC and OncoKB databases. Somatic mutations were found in all ten pathways, with multiple 3′ UTR variants in EIF4EBP1 and CTBP2 , genes implicated in translational regulation and transcriptional repression, respectively. Germline analysis revealed 21 high-impact mutations, three of which were rare and potentially deleterious. Our findings suggest that subtle regulatory variants may contribute to favorable clinical outcomes in rare long-term survivors of R/M HNSCC. Further studies are needed to identify predictive biomarkers in this unique subgroup of patients.