Dimitrios Alexandrou

In breast cancer, current knowledge of the associations between clinicopathologic characteristics, genetic changes, and subtype-specific patterns remain unclear. This research investigated how pathological and clinical variables affect the actionability of NGS-based tumor molecular data. Materials and methods: 227 breast cancer patients referred to Genekor’s laboratory for tumor molecular profile analysis were included in the study. Pathology records, available in all cases, were used to assess critical clinicopathological features including HER2, ER, PR, Ki67, grade, metastatic site, and age. A 1021 gene NGS-based multigene panel was utilized to assess tumors’ biology alongside tumor mutational burden (TMB) and microsatellite instability (MSI) Results: Comprehensive genomic profiling revealed that 95.6% of the patients harbored at least one oncogenic or likely oncogenic alteration, highlighting the high diagnostic yield of NGS-based testing. Distinct subtype-specific patterns were observed: HR+/HER2-tumors were enriched for PIK3CA and ESR1 gene alterations, while Triple Negative Breast Cancer (TNBC) was dominated by TP53 alterations. Clinically actionable alterations were most common in HR+/HER2-tumors (~60% on-label), whereas TNBC more often harbored off-label or trial-associated targets. The inclusion of tumor-agnostic biomarkers (TMB/MSI) increased on-label actionability up to 64.5% in ER−/PR+ tumors. primarily driven by TMB-high cases. Median TMB values were low, and age was the only independent predictor. Furthermore, the presence of actionable alterations was significantly higher in metastatic tumors, and TP53 alterations were associated with aggressive tumor characteristics.Conclusions: Comprehensive NGS-based genomic profiling identifies clinically actionable alterations in over half of breast cancer patients, with substantial variability across molecular subtypes. The HR+/HER2-subtype demonstrates the highest prevalence of on-label actionable biomarkers. These findings support the routine implementation of comprehensive genomic profiling, especially in metastatic HER2-negative breast cancer, to guide precision oncology strategies and enable enrollment in biomarker-driven clinical trials.

Background/Objectives: Ki-67 is widely used as an immunohistochemical marker of tumor proliferation in hormone receptor-positive (HR-positive), HER2-negative breast cancer, but its interpretation is limited by variability and uncertain concordance with genomic assays. The Oncotype DX^® Recurrence Score (RS) is a validated multigene assay with established prognostic and predictive utility. This study evaluated the relationship between Ki-67 and RS in clinical practice. Methods: We retrospectively analyzed women in Greece with early-stage estrogen receptor-positive, HER2-negative breast cancer without distant metastasis (pM0) who underwent Oncotype DX testing between 2020 and 2023. Eligible patients were node-negative or postmenopausal with node-positive disease. RS was categorized as low (0–25) or high (>25). Ki-67 was assessed using binary (5–p < 0.001). After stratification, associations with RS were observed only in tumors with high Ki-67 expression, whereas no correlation was detected in low or intermediate groups. RS distributions differed significantly across Ki-67 strata. Overall concordance between Ki-67-based proliferation categories and RS-based genomic risk was 56.2%, with discordant cases in both directions. Conclusions: Ki-67 shows a modest association with Oncotype DX RS, but substantial discordance indicates Ki-67 should not substitute genomic testing in HR-positive/HER2-negative early breast cancer.

Background: Colorectal cancer (CRC) represents a major global health burden, accounting for roughly 10% of all newly diagnosed cancers and cancer-related deaths worldwide. According to the World Health Organization, it is the third most diagnosed malignancy and the second leading cause of cancer mortality. Postoperative complications remain a significant concern after CRC resection, occurring in up to 50% of patients and contributing to increased morbidity, mortality, prolonged hospitalization, and substantial healthcare expenditure. Artificial intelligence (AI) has emerged as a transformative tool in modern healthcare, offering advanced capabilities in predictive analytics, clinical decision support, and personalized perioperative management. Methods: This review systematically evaluates the application of AI, specifically machine learning (ML) and deep learning (DL) algorithms, in the prediction of anastomotic leak (AL) and other major postoperative complications. In this context, AI models are generally used to refine risk stratification and enhance surgical decision-making. Results: A total of 13 studies were included, encompassing 15,105 patients. Across these studies, ML and DL algorithms consistently outperformed conventional statistical models in forecasting postoperative outcomes. Conclussions: Current evidence suggests that AI has substantial potential to improve perioperative risk prediction, support intraoperative decision-making, and personalize postoperative surveillance in patients undergoing CRC surgery. Methodological limitations, including a high risk of bias, limited external validation, heterogeneous outcome definitions, and inconsistent reporting, necessitate more robust, prospective, multicenter research before widespread clinical adoption can be realized.

Background: Breast cancer and gynecological malignancies, including cervical, ovarian, and endometrial cancers, remain leading causes of cancer incidence and mortality among women worldwide. This study investigated hereditary predisposition rates in women diagnosed with breast or gynecological cancer, focusing on the effect of age on germline pathogenic/likely pathogenic (P/LP) variant detection. We sought to determine whether younger age at diagnosis should be used as a criterion for patient selection for genetic testing. Methods: A total of 9084 consecutive females with breast cancer or gynecological tumors underwent germline NGS-based genetic testing (52 cancer-relevant genes) at Genekor laboratory from 2020–2026. Multivariable logistic regression evaluated factors associated with P/LP variant detection, adjusting for tumor type and family history. Results: Overall P/LP prevalence was approximately 20% (one in five patients), with tumor-specific rates of 19.24% in breast cancer, 27.59% in ovarian cancer, and 26.67% in endometrial cancer. P/LP prevalence declined significantly with age from 24.37% in patients p < 0.001), driven predominantly by high-risk genes (13.87% in BRCA1 showed stronger age enrichment than BRCA2 (8.14% vs. 3.16% in <40 y; median diagnosis 43 vs. 45 years). Age remained independently associated with P/LP detection in multivariable analysis, with an 18% reduction in odds per 10-year increase for any P/LP (OR 0.82, 95% CI 0.78–0.86) and a stronger 28% reduction for high-risk variants (OR 0.72, 95% CI 0.67–0.78). Family history also independently predicted P/LP detection (OR 1.40, 95% CI 1.19–1.66). Conclusions: Although derived from a referral-based (and thus selected) population, these findings show that while younger patients have a higher prevalence of high-risk P/LP variants, clinically actionable findings are present across all age groups, including those ≥70 years. These results suggest that reliance on age alone to determine eligibility for genetic testing may be insufficient. Broadening access to testing beyond strict age-based criteria could improve the identification of hereditary cancer risk and inform patient management, although further evaluation in less selected populations is warranted.

Background: Breast cancer and gynecological malignancies, including cervical, ovarian, and endometrial cancers, remain leading causes of cancer incidence and mortality among women worldwide. This study investigated hereditary predisposition rates in women diagnosed with breast or gynecological cancer, focusing on the effect of age on pathogenic/likely pathogenic (P/LP) variant detection. We sought to determine whether younger age at diagnosis should be used as a criterion for patient selection for genetic testing. Methods: A total of 9084 consecutive females with breast cancer or gynecological tumors underwent NGS-based genetic testing (53 cancer-relevant genes) at Genekor laboratory from 2020-2026. Multivariable logistic regression evaluated factors associated with P/LP variant detection, adjusting for tumor type and family history. Results: Overall P/LP prevalence was approximately 20% (one in five patients), with tumor-specific rates of 19.24% in breast cancer, 27.59% in ovarian cancer, and 26.67% in endometrial cancer. P/LP prevalence declined significantly with age from 24.37% in patients <40 years to 15.90% in those ≥70 years, while VUS remained stable (40-43%). P/LP patients had earlier diagnosis (median 45 vs 46 years, p<0.001), driven predominantly by high-risk genes (13.87% in <40y vs 7.11% in ≥70y). BRCA1 showed stronger age enrichment than BRCA2 (8.14% vs 3.16% in <40y; median diagnosis 43 vs 45 years). Age remained independently associated with P/LP detection in multivariable analysis, with an 18% reduction in odds per 10-year increase for any P/LP (OR 0.82, 95% CI 0.78-0.86) and a stronger 28% reduction for high-risk variants (OR 0.72, 95% CI 0.67-0.78). Family history also independently predicted P/LP detection (OR 1.40, 95% CI 1.19-1.66). Conclusions: While younger patients have a higher prevalence of high-risk variants, clinically actionable findings were identified across all age groups, including patients ≥70 years These findings indicate that focusing on age to determine eligibility for genetic testing is insufficient. Expanding testing accessibility to individuals regardless of their age at diagnosis may enhance the identification of genetic cancer risk and optimize patient management.

Background/Objectives Ki‑67 is widely used as an immunohistochemical marker of tumor proliferation in hormone receptor–positive (HR‑positive), HER2‑negative breast cancer, but its inter-pretation is limited by variability and uncertain concordance with genomic assays. The Oncotype DX® Recurrence Score (RS) is a validated multigene assay with established prognostic and predictive utility. This study evaluated the relationship between Ki‑67 and RS in clinical practice. Methods We retrospectively analyzed women in Greece with early‑stage estrogen receptor–positive, HER2‑negative breast cancer without distant metastasis (pM0) who under-went Oncotype DX testing between 2020 and 2023. Eligible patients were node nega-tive or postmenopausal with node positive disease. RS was categorized as low (0–25) or high (>25). Ki‑67 was assessed using binary (< 20% vs ≥20%) and three‑tier (≤5%, >5%–< 30%, ≥30%) classifications. Associations were analyzed using correlation, con-cordance, and nonparametric methods. Results Among 2,967 patients, the median RS was 16, with similar distributions across nodal subgroups. Ki‑67 and RS demonstrated a moderate positive correlation as continuous variables (r = 0.42, p < 0.001). After stratification, associations with RS were observed only in tumors with high Ki‑67 expression, whereas no correlation was detected in low or intermediate groups. RS distributions differed significantly across Ki‑67 strata. Overall concordance between Ki‑67‑based proliferation categories and RS‑based ge-nomic risk was 56.2%, with discordant cases in both directions. Conclusions Ki‑67 shows a moderate association with Oncotype DX RS, but substantial discordance indicates it should not substitute genomic testing in HR‑positive/HER2‑negative early breast cancer.

Early-onset colorectal cancer (EOCRC), defined as diagnosis before the age of 50 years, is increasing globally and is frequently characterized by aggressive biology and a disproportionate burden of liver metastases. This review synthesizes emerging evidence on the distinct molecular, immunologic and clinical features that differentiate EOCRC liver metastases from those arising in older adults. Genomic studies revealed increased chromosomal instability, increased copy number variation burden and unique amplification patterns involving MYC, RAD21, GNAS and MAPK1, alongside altered frequencies of classical driver mutations and increased germline predisposition. EOCRC liver metastases also exhibit a progenitor-like transcriptional state and an immune-cold microenvironment marked by reduced myeloid infiltration, impaired antigen presentation and profound resistance to immunotherapy, particularly in microsatellite-stable disease. Mechanistic insights into ferroptosis highlight therapeutic vulnerabilities, especially in PIK3CA-mutant tumors, where aspirin and ferroptosis inducers show synergistic potential. Clinically, high-risk EOCRC patients often present with left-sided primary tumors, synchronous metastases, adverse histology, elevated CEA levels and a hereditary predisposition, with prognostic models incorporating these variables outperforming traditional staging. Collectively, accumulating evidence suggests that EOCRC liver metastases may represent a biologically and clinically distinct entity, although ongoing debates regarding the extent of this distinction underscore the need for age-specific molecular profiling and prospectively validated therapeutic strategies.

Colorectal cancer (CRC) represents a major global health burden, accounting for roughly 10% of all newly diagnosed cancers and cancer-related deaths worldwide. It is the third most diagnosed malignancy and the second leading cause of cancer mortality according to the World Health Organization. Postoperative complications remain a significant concern after CRC resection, occurring in up to 50% of patients and contributing to increased morbidity, mortality, prolonged hospitalization, and substantial healthcare expenditure. Artificial intelligence (AI) has emerged as a transformative tool in modern healthcare, offering advanced capabilities in predictive analytics, clinical decision support, and personalized perioperative management. The present review systematically evaluates the application of AI, specifically machine learning (ML) and deep learning (DL) algorithms, in predicting anastomotic leak (AL) and other major postoperative complications. AI models aim to refine risk stratification and enhance surgical decision-making. A total of 13 studies were included, encompassing 15,105 patients. Across these studies, ML and DL algorithms consistently outperformed conventional statistical models in forecasting postoperative outcomes. Current evidence suggests that AI has substantial potential to improve perioperative risk prediction, support intraoperative decision-making, and personalize postoperative surveillance in CRC surgery. Methodological limitations including high risk of bias, limited external validation, heterogeneous outcome definitions, and inconsistent reporting necessitate more robust, prospective, multicenter research before widespread clinical adoption can be realized.

Background/Objectives: Colorectal cancer (CRC) is among the most commonly reported malignancies globally, taking the third place in incidence among males as well as the second among females, with over 1.9 million new cases and 935,000 deaths estimated worldwide in 2020. One of the most common and clinically significant comorbidities in patients undergoing CRC surgery is preoperative anemia, with reported prevalence ranging from 23% to over 60% depending on the population and diagnostic criteria used. The objective of the current study is to systematically evaluate the current body of evidence on preoperative anemia management in adults undergoing surgery for non-metastatic CRC. This review aims to assess the clinical impact of different iron supplementation strategies, particularly IV versus oral iron in pre-operative hematologic optimization, transfusion requirements, postoperative complications, and recovery outcomes. Methods: The current systematic review was conducted based on the PRISMA for Systematic Reviews and Meta-analysis checklist. The study has been registered to PROSPERO with the ID CRD420251113455. Results: Across all studies, IV iron and erythropoiesis-stimulating agents emerged as safe and more efficient alternatives to iron per os, especially when initiated at least two weeks before surgery. Thus, highlighting the clinical value of proactive anemia management as a cornerstone of surgical prehabilitation, potentially reducing transfusion burden and improving recovery outcomes for CRC patients. Conclusions: It is observed that IV iron therapy offers a more effective strategy than per os supplementation for correcting preoperative anemia in non-metastatic colorectal cancer patients. Their hematologic benefits enhance surgical readiness and reduce postoperative intervention needs. Thus, supporting the integration of IV iron into preoperative optimization protocols.