Early-Onset Colorectal Cancer in Egypt: Pathological Characters, Patterns of Care, and Survival Compared to Average-Age Onset Colorectal Cancer: A Retrospective Multicenter Study.

PURPOSE: Early-onset colorectal cancer (EOCRC) is a rising health problem. The incidence of EOCRC has increased over the past 2 decades all over the world. Reports from Egypt since the 1990s have reported a higher incidence among young populations with no identifiable risk factors. The aim of this study was to assess EOCRC in Egypt regarding incidence, characteristics, treatment pattern, and survival compared with average age onset and elderly patients. MATERIALS AND METHODS: This was a retrospective, record-based, cohort study combining data from four different cancer centers in Egypt. We grouped patients according to age into three categories: the EOCRC group for patients age ≤45 years and the average age onset and elderly cancer group (for patients age ≥65 years). RESULTS: The study included 1,310 patients with histopathologically proven colorectal cancer, representing four different geographical areas in Egypt. Patients with EOCRC represented 42.4% of the study population. Female patients were 50.6% among the EOCRC group and 52.5% among the average age group. Rectal tumors were significantly higher in EOCRC (54.7% v 40.6%; P < .001). There was no significant difference between both groups regarding the tumor stage at presentation, obstruction, or presence of metastases at presentation. Patients with EOCRC had a significantly higher rate of peritoneum/adnexa metastases than the average age ones (12.3% in EOCRC v 6.9% in the average age group; P < .001). No statistically significant differences between EOCRC and average age groups in both disease-free survival and overall survival were reported. CONCLUSION: A comprehensive framework for the study of EOCRC is required in Egypt as well as a genomic analysis to identify possible underlying genetic alterations responsible for the high incidence of EOCRC.

A Panel of Circulating Non-Coding RNAs in the Diagnosis and Monitoring of Therapy in Egyptian Patients with Breast Cancer.

Background: Non-coding RNAs (ncRNAs) have recently been identified to have a pivotal role in many diseases, including breast cancer (BC). This study aims to investigate the relative quantification of long non-coding RNA (lncRNA) H19, microRNA (miR) 675-5p, 675-3p, and miR-let 7 in breast cancer patients. Methods: The study was performed on three groups: Group 1: 30 non-intervened BC female patients about to undergo breast surgery; group 2: 30 postoperative female BC patients about to receive adjuvant anthracycline chemotherapy; and group 3: 30 apparently healthy female volunteers as the control group. Plasma samples were drawn before and after the intervention in groups 1 and 2, with a single sample drawn from group 3. The relative quantification levels were compared with healthy control subjects and were related with the clinicopathological statuses of these patients. Results: There was a statistically significant increase in H19, miR-675-5p, miR-675-3p, and miR-let 7 in the non-intervened BC patients when compared to the control group. Surgery resulted in a significant reduction in all four ncRNAs under investigation. Chemotherapy brought about a significant increase in the level of miR-let 7, with no significant effect on the remaining parameters measured. The assay discriminated normal from BC where a receiver operating characteristic for the area under the curve (ROCAUC) of miR-675-3p showed the maximal AUC of 1.000. The diagnostic sensitivity and specificity were also 100% when CA 15-3 and H19 were combined. Conclusion: The results strongly indicate that the panel of ncRNAs in this study can all potentially act as novel biomarkers whether alone or combined in the diagnosis of BC.

Factors associated with Late-Stage Diagnosis of Breast Cancer among Egyptian Women.

Background: Detecting Breast Cancer (BC) at earlier stages comes with a better prognosis, while diagnosis at late stages has poor outcomes and escalating mortality rates from the disease. The study aims to understand the factors associated with the late-stage diagnosis of BC in Egypt. Design and Methods: A sample of 400 women with a pathologically confirmed BC were enrolled from one of the main tertiary cancer hospitals in Egypt. A cross-sectional study design was conducted. The collected data included: clinical characteristics of the tumor, socio-demographic characteristics of the studied women, reproductive and medical history, screening practices, and the time from symptom onset to definite diagnosis as suspected predictors to the stage of BC at diagnosis. Data was analyzed by crude odds ratios (95% confidence interval) and multivariate logistic regression analysis. Results: The study revealed that 47.5% were diagnosed at late stages (40% at stage III/ 7.5% at stage IV), while (52.5%) were diagnosed at early stages (6.5% at stage I/46% at stage II). A binary logistic regression model showed that unmarried females (p=0.012), had non-luminal molecular subtype of BC including HER2 enriched and triple-negative tumors (p<0.001), presentation with breast changes and a non-palpable lump (p=0.024) or non-breast symptoms (P=0.002), a delay longer than 3 months to the first presentation by patients (p<0.001), and a delay to definite diagnosis longer than 1 month by providers (p<0.001) were significant risk factors of late-stage diagnosis of BC. Conclusions: Late-stage diagnosis of BC in Egypt is associated with the aggressiveness of some molecular subtypes and other important modifiable factors that should be addressed.

The Prognostic Significance of Metabolic Response Heterogeneity in Metastatic Colorectal Cancer.

BACKGROUND: Tumoral heterogeneity is a major determinant of resistance in solid tumors. FDG-PET/CT can identify early during chemotherapy non-responsive lesions within the whole body tumor load. This prospective multicentric proof-of-concept study explores intra-individual metabolic response (mR) heterogeneity as a treatment efficacy biomarker in chemorefractory metastatic colorectal cancer (mCRC). METHODS: Standardized FDG-PET/CT was performed at baseline and after the first cycle of combined sorafenib (600mg/day for 21 days, then 800mg/day) and capecitabine (1700 mg/m²/day administered D1-14 every 21 days). MR assessment was categorized according to the proportion of metabolically non-responding (non-mR) lesions (stable FDG uptake with SUVmax decrease <15%) among all measurable lesions. RESULTS: Ninety-two patients were included. The median overall survival (OS) and progression-free survival (PFS) were 8.2 months (95% CI: 6.8-10.5) and 4.2 months (95% CI: 3.4-4.8) respectively. In the 79 assessable patients, early PET-CT showed no metabolically refractory lesion in 47%, a heterogeneous mR with at least one non-mR lesion in 32%, and a consistent non-mR or early disease progression in 21%. On exploratory analysis, patients without any non-mR lesion showed a significantly longer PFS (HR 0.34; 95% CI: 0.21-0.56, P-value <0.001) and OS (HR 0.58; 95% CI: 0.36-0.92, P-value 0.02) compared to the other patients. The proportion of non-mR lesions within the tumor load did not impact PFS/OS. CONCLUSION: The presence of at least one metabolically refractory lesion is associated with a poorer outcome in advanced mCRC patients treated with combined sorafenib-capecitabine. Early detection of treatment-induced mR heterogeneity may represent an important predictive efficacy biomarker in mCRC. TRIAL REGISTRATION: ClinicalTrials.gov NCT01290926.