A colorectalis daganatos páciensek ellátását, túlélését előrejelző tényezők: az egészségügyben eltöltött várakozási idők és új biomarkerek szerepe

Abstract

Introduction Hungary has one of the leading colorectal cancer incidence and mortality rates in Europe. Patient-related and healthcare-related factors may all play a role. Rectal cancer constitutes nearly one-third of all colorectal cancer diagnoses and certain clinical and molecular markers have been studied as potential prognosticators of patient survival. Objectives I. Our objective was to investigate the characteristics related to the treatment of colorectal cancer patients by analysing their initial symptoms, disease stage, referral characteristics and Total Treatment Intervals (TTI). II. The main objective of our study was to investigate the relationship between the expression intensities of certain proteins: Growth hormone-releasing hormone receptor (GHRH-R), Hsp90, Hsp16.2, p-Akt and SOUL in specimens of locally advanced rectal cancer patients and time to metastasis as well as 10-year overall survival (OS). We also investigated whether these outcome measures were associated with the presence of other clinical parameters. Methods I. A retrospective study was conducted based on data from colorectal patients (n=212) from the databases of 26 General Physician (GP) practices and the University of Pécs Clinical Center. The Total Treatment Interval (TTI) was determined as the number of days from the first patient- physician consultation with symptoms until the first day of treatment. Descriptive analysis and analysis of variance were performed. II. 109 patients were investigated retrospectively. Samples of pretreatment tumors were stained for proteins GHRH-R, Hsp90, Hsp16.2, p-Akt and SOUL using immunhistochemistry methods. Kaplan-Meier curves were used to show the relationship between intensity of expression of biomarkers, clinical parameters, time-to metastasis and 10-year OS. Results I. Patients’ most common symptom was abdominal/rectal pain when presenting at the Emergency Department while bloody stool was the most common among patients visiting their GP. The proportion of patients with advanced stage (III.-IV.) cancer was significantly higher at the Emergency Department (ED), than among patients visiting their GP (61% and 42.7%, respectively). The TTI was shorter when patients presented at the ED (TTI median: 15 days for advanced stage, 34.5 days for early (I-II.) stage cancer), than when they initially visited their GP (TTI median: 83 days for early stage, 86 days for advanced stage cancers). II. High levels of p-Akt, GHRH-R and Hsp90 were associated with significantly decreased 10- year OS (p=0.001; p=0.000; p=0.004;) and high expression levels of p-Akt and GHRH-R were correlated with significantly shorter time to metastasis. Tumors localized in the lower third of the rectum were linked to both significantly longer time to metastasis and improved 10-year OS. Conclusions I. The TTIs for patients visiting the ED or their GPs were similar to those found in Western European countries. The high mortality rates in Hungary are more probably due to patient- related delays, which highlight the importance of primary and secondary prevention. II. Hsp 90, pAkt and GHRH-R as well as the lower-third localization of the tumor were predictive of 10-year OS in locally advanced rectal cancer patients. GHRH-R and Hsp90 expression were independent prognosticators of OS. Our results imply that GHRH-R could play a particularly important role both as a molecular biomarker and as a target for anticancer treatment of advanced rectal cancer.