BACKGROUND: Aspirin, a non-steroidal anti-inflammatory drug and platelet inhibitor, has been shown to reduce cancer incidence, lower metastatic rates and improve survival in certain cancer types. However, data on the effect of aspirin on prognosis in pancreatic ductal adenocarcinoma (PDAC) are limited. Therefore, we conducted a retrospective, single-center study to evaluate the impact of aspirin use on disease characteristics and survival in PDAC patients. MATERIALS AND METHODS: The study analyzed data from all consecutively treated PDAC patients over a 6-year period. Operability, Tumor-Node-Metastasis (TNM) stage, and survival endpoints were compared between patients who had used aspirin for 2 or more years prior to their diagnosis (ASA ≥ 2) and those who did not (ASA 0). RESULTS: A total of 182 patients were included. In the ASA ≥ 2 group, significantly fewer patients had metastatic disease at diagnosis, and a significantly larger proportion presented in the operable stages, compared to the ASA 0 group. No significant differences were observed between the two groups in the T or N stages, overall survival, disease-free survival, or time to progression-free survival. CONCLUSIONS: Although long-term aspirin use did not influence survival endpoints, it was associated with a significantly lower probability of demonstrable distant metastases at diagnosis and a higher rate of resectable disease. This finding warrants further research to explore new therapeutic approaches for the treatment of PDAC.

• Klíčová slova
• aspirin, metastasis, operability, pancreatic adenocarcinoma,
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) highlights the urgent need for novel therapeutic strategies. Immune checkpoint inhibitors (ICIs) seem to be ineffective in most PDAC studies. Therefore, we conducted an open-label, multicenter phase 1/2 study (CA209-9KH) to evaluate the safety of stereotactic radiotherapy (SRT) and sequential ICI therapy in PDAC, as well as to validate the efficacy of this regimen as a potential activator of antitumor immunity. METHODS: Patients aged ≥ 18 years with unresectable non-metastatic PDAC following four FOLFIRINOX induction cycles were included. Treatment comprised SRT (4 × 8 Gy) and sequential nivolumab administration until disease progression or unacceptable toxicity. The primary endpoints were safety and toxicity assessment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), biomarker evaluation, and quality of life (QoL) analysis. RESULTS: Twenty-two patients were screened, with 15 enrolled. Eleven (median) nivolumab cycles were administered. SRT demonstrated low and clinically nonsignificant toxicity, whereas nivolumab toxicity aligned with prior safety profiles, without grade 4-5 events observed. Three patients discontinued therapy owing to toxicity. Median PFS and OS were 8.1 and 13.0 months, respectively, with 12-month PFS and OS rates of 0% and 66.7%, respectively, and a 24-month OS rate of 8.9%. Biomarker levels correlated with clinical or radiological disease control. Patient-reported QoL remained acceptable, deteriorating with disease progression. CONCLUSION: SRT and nivolumab therapy exhibited manageable toxicity profiles consistent with previous findings; however, long-term treatment responses were not achieved with this regimen in locally advanced PDAC. Another strategy to trigger antitumor immunity in PDAC needs to be sought. TRIAL REGISTRATION: EudraCT: 2017-003404-52; ClinicalTrials.gov: NCT04098432.

• Klíčová slova
• Nivolumab, Pancreatic ductal adenocarcinoma, Stereotactic radiotherapy,
• Publikační typ
• časopisecké články MeSH

The following main treatment approaches are currently used in locally advanced adenocarcinomas of the oesophagus and gastrooesophageal junction (GOJ): preoperative chemoradiotherapy and surgery, and perioperative chemotherapy and surgery. While preoperative chemoradiotherapy is used primarily in oesophageal tumours, perioperative chemotherapy is the treatment of choice in Western countries for gastric cancer. The optimal treatment strategy for GOJ adenocarcinoma is still not clear. In comparison to other malignancies, biomarkers are used as predictive factors in distal oesophageal and GOJ adenocarcinomas in a very limited way, and moreover, only in metastatic stages (e.g., HER2 status, or microsatellite instability status). The aim of the article is to provide an overview of current treatment options in locally advanced adenocarcinomas of oesophagus and GOJ based on the latest evidence, including the possible potential of predictive biomarkers in optimizing treatment.

• Klíčová slova
• adenocarcinoma, gastro-oesophageal junction, oesophagus, perioperative chemotherapy, preoperative chemoradiotherapy,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH