Development of a prognostic and predictive tool for chemotherapy response in patients with locally advanced and metastatic pancreatic adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most formidable challenges in modern oncology, marked by its asymptomatic progression, late diagnosis, limited therapeutic options, and dismal prognosis. In Spain, PDAC ranks as the eighth leading cause of cancer-related mortality, with the majority of patients diagnosed at an advanced or metastatic stage—well beyond the window for curative surgical intervention. For these individuals, systemic chemotherapy remains the cornerstone of treatment. However, the absence of validated prognostic biomarkers, a lack of consensus on optimal treatment sequencing, and the limited availability of reliable survival prediction tools continue to hinder the implementation of truly personalized care. This doctoral thesis aimed to address several of these critical gaps by analyzing a real-world cohort of patients treated for PDAC at the San Pedro University Hospital in Spain. Beyond confirming well-established observations—such as the survival benefit of surgical and chemotherapeutic interventions over best supportive care—the study contributed novel insights into the optimization of treatment strategies. Notably, it identified a potentially superior sequential regimen: initiating treatment with gemcitabine plus nab-paclitaxel (GEM-NABP), followed by a gemcitabine-based regimen in the second line. This sequence was associated with significantly improved survival outcomes compared to conventional 5-FU-based approaches. Parallel to the therapeutic analysis, the study explored the prognostic potential of commonly available blood biomarkers. A predictive model based on gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), and monocyte count demonstrated notable accuracy in estimating one-year survival using logistic regression. Furthermore, a novel biomarker—the monocyte-to-hemoglobin ratio (MHR)—emerged as a robust, accessible, and cost-effective prognostic indicator, showing predictive capacity even in high-risk patient subgroups. Although other markers, such as the Systemic Inflammation Response Index (SIRI), did not consistently achieve statistical significance, their differential associations with treatment response suggest avenues for refining therapeutic strategies in selected patients. Importantly, the analysis also included patients who did not undergo chemotherapy. In this subgroup, specific blood biomarkers continued to exhibit prognostic value, underscoring their potential role in risk stratification and patient counseling, even in the absence of active treatment. In conclusion, this thesis offers meaningful contributions toward a more personalized and evidence-based management of advanced PDAC. Through the proposal of a new treatment sequence and the development of pragmatic prognostic tools based on routine clinical data, it lays a solid foundation for future research and clinical translation. While prospective validation is necessary, the findings represent a promising step toward improving therapeutic decision-making and ultimately enhancing the care and quality of life for patients facing this aggressive malignancy.

Grantor dc:publisher

Universidad de La Rioja (España)

Year dc:date

2025

Author dc:creator

• Campo Pedrosa, Rocío del

Contributors dc:contributor

• González Marcos, Ana (Universidad de La Rioja)
• Arnedo Piqueras, León (Universidad de La Rioja)

Statement dc:rights

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Language dc:language

eng

Repository record dc:identifier

https://dialnet.unirioja.es/servlet/oaites?codigo=396429

OAI identifier oai:identifier

oai:dialnet.unirioja.es:TES0000023208