The latest clinical trails of pancreatic cancer

Introduction: Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), is a leading cause of cancer-related deaths globally and is projected to become the second-leading cause by ۲۰۳۰. Annually, it affects over ۴۵۰,۰۰۰ people, with more than ۶۴,۰۰۰ cases in the United States alone. The poor survival rates of PDAC are attributed to its biological complexity and clinical challenges, including genetic diversity, early metastasis, and a protective stroma that significantly impacts patients' quality of life. Most patients are older, with an average diagnosis age of around ۷۰ years. Although genomic testing has enhanced understanding and the potential for targeted therapies, the best chance for five-year survival remains surgical resection combined with chemotherapy. Recent advancements have improved outcomes and altered clinical practices. This review summarizes current treatment strategies and milestones shaping our understanding of pancreatic cancer. Methods: A stepped-wedge cluster randomized trial conducted in the Netherlands in ۲۰۲۳ analyzed five practices: optimal use of perioperative chemotherapy, palliative chemotherapy, pancreatic enzyme replacement therapy (PERT), referral to a dietitian, and the use of metal stents in patients with biliary obstruction. The study included ۵,۸۸۷ patients with pathologically or clinically diagnosed PDAC. Additionally, several phase II trials in countries such as France, the United States, Spain, and Canada investigated preferred chemotherapy regimens, including GnP alternating with FFX or FOLFIRINOX and Gemcitabine. A molecular navigation strategy utilizing whole genome and RNA sequencing identified GATA۶ expression in tumors as a robust surrogate biomarker for distinguishing classical from basal PDAC subtypes. Irreversible electroporation (IRE) is a non-thermal ablative technique for unresectable locally advanced PDAC, inducing apoptosis without damaging adjacent structures. A pilot study involving ۲۷ patients with unresectable locally advanced pancreatic cancer evaluated either resection of the primary tumor with IRE. Results: The Netherlands study found similar one-year survival rates: ۲۴?fore vs. ۲۳?ter implementing best practices (hazard ratio ۰.۹۸). Treatment changes included increased palliative chemotherapy (۲۴% to ۳۰%, OR ۱.۳۸), pancreatic enzyme replacement therapy (۳۴% to ۴۵%, OR ۱.۶۴), and metal biliary stents (۷۴% to ۸۳%, OR ۱.۷۸). No significant changes were noted for neoadjuvant/adjuvant chemotherapy or dietitian referrals. Regarding regimen choice, patients with classical phenotypes responded better to FFX, while those with basal expression fared better with GnP. Furthermore, FOLFIRINOX demonstrated improved median overall survival compared to Gemcitabine. Despite the introduction of new chemotherapy regimens, overall survival rates for FOLFIRINOX and Gemcitabine slightly improved. IRE resulted in complete tumor destruction in all patients without local recurrence; however, one patient (۳.۷%) died, and ۳۳% morbidity was reported. Conclusion: In summary, The treatment landscape for pancreatic cancer is evolving, with significant advancements in therapeutic strategies and patient management, leading to some improvements and the emergence of new treatment options. However, outcomes remain poor. Achieving optimal care for pancreatic ductal adenocarcinoma (PDAC) requires multidisciplinary collaboration and ongoing research to address the challenges of this formidable disease and improve patient outcomes.

کلیدواژه ها:

Pancreatic cancer ، Chemotherapy ، Irreversible electroporation