Periostin in ovarian carcinoma: from heterogeneity to prognostic value

Introduction. Periostin (POSTN), an extracellular matrix protein, is involved in tumor-associated extracellular matrix (ECM) remodeling. However, its potential value as a prognostic and/or predictive factor has not yet been confirmed. The present study aims to assess POSTN expression separately in tumor cells and stroma of different ovarian carcinoma (OC) histological types, and its relationship with clinicopathological features. Material and methods. 102 cases of different histological OC subtypes were immunohistochemically investigated, for POSTN expression assessment in both epithelial tumor cells and tumor stroma. Statistical analysis was performed to correlate POSTN profile with clinicopathological characteristics, therapeutic response, and survival. Results.  POSTN expression in epithelial tumor cells was significantly correlated with POSTN expression in tumor stroma. The expression of POSTN in tumor cells was associated with histological type, tumor type (type I and II), tumor recurrence, progression-free survival (PFS), and overall survival (OS), whereas stromal POSTN expression was significantly correlated with age, histological type, tumor type, grade, and stage, residual disease, tumor recurrence, response to chemotherapy, and OS. Survival analysis revealed significant differences of PFS and OS in patients with high POSTN expression in tumor cells and negative stromal POSTN expression compared to patients with low POSTN expression in tumor cells and positive stromal POSTN expression (PFS: hazard ratio (HR) = 2.11, 95% confidence interval (CI): 1.33–3.37, P = 0.002; OS: HR = 1.78, 95% CI: 1.09–2.89, P = 0.019). Conclusions. The comparative assessment of POSTN immunoexpression in two tumor compartments: in tumor cells and stroma, by use of different scoring systems revealed that higher stromal POSTN levels are evidently correlated with unfavorable clinical features and poorer prognosis, while POSTN expression in tumor cells seems to be associated with a better patient outcome

Can Extended Chemotherapy Improve Glioblastoma Outcomes? A Retrospective Analysis of Survival in Real-World Patients

Standard treatment for glioblastoma multiforme (GBM) is surgery followed by radiotherapy plus concurrent chemotherapy with daily temozolomide (TMZ), and six subsequent TMZ 5/28-day cycles. Research has focused on identifying more effective alternatives to the current protocol, including extension of the number of adjuvant TMZ cycles. We performed a retrospective analysis of all GBM patients treated in our hospital (160 patients, 2011–2020). Median follow-up was 16.0 months. Analysis of prognostic factors was performed with a particular focus on the benefit of extending TMZ chemotherapy. Improved survival correlated with younger age, female gender, good performance status, absence of cognitive dysfunctions, no steroid use, and total tumor resection. Median progression-free survival (PFS) was 12 months and median overall survival (OS) was 20.0 months for the entire cohort. Median OS by adjuvant TMZ was 10.0 months if no adjuvant chemotherapy given (group 0), 15.0 months for patients that did not complete six TMZ cycles (group A), 24.0 months for those that did (group B), and 29.0 months for patients having received more than six cycles (group C) (p < 0.0001). At the three-year mark, 15.9% patients were alive in group A, 24.4% in group B and 38.1% in group C. Carefully selected GBM patients may derive benefit from extending the standard adjuvant chemotherapy beyond six TMZ cycles, but more data is required

KRAS, NRAS, BRAF, HER2 and microsatellite instability in metastatic colorectal cancer – practical implications for the clinician

Colorectal cancer is a successful model of genetic biomarker development in oncology. Currently, several predictive or prognostic genetic alterations have been identified and are used in clinical practice. The RAS gene family, which includes KRAS and NRAS act as predictors for anti-epithelial growth factor receptor treatment (anti-EGFR), and it has been suggested that NRAS mutations also play a role in prognosis: patients harboring NRAS alterations have a significantly shorter survival compared to those with wild type tumours. BRAF V600E mutations are rare and occur mostly in tumors located in the ascending colon in elderly female patients. BRAF is instrumental in establishing prognosis: survival is shorter by 10–16 months in BRAF-mutant patients, and BRAF may be a negative prognostic factor for patients who undergo hepatic or pulmonary metastasectomy. Moreover, this mutation is used as a negative predictive factor for anti-EGFR therapies. Two new biomarkers have recently been added to the metastatic colorectal cancer panel: HER2 and microsatellite instability. While HER2 is still being investigated in different prospective studies in order to validate its prognostic role, microsatellite instability already guides clinical decisions in substituted with advanced colorectal cancer

Integration of Ultrasound in Image-Guided Adaptive Brachytherapy in Cancer of the Uterine Cervix

Cervical cancer continues to be a public health concern, as it remains the second most common cancer despite screening programs. It is the third most common cause of cancer-related death for women, and the majority of cases happen in developing nations. The standard treatment for locally advanced cervical cancer involves the use of external beam radiation therapy, along with concurrent chemotherapy, followed by an image-guided adaptive brachytherapy (IGABT) boost. The five-year relative survival rate for European women diagnosed with cervical cancer was 62% between 2000 and 2007. Updated cervical cancer treatment guidelines based on IGABT have been developed by the Gynecological working group, which is composed of the Group Européen de Curiethérapie–European Society for Therapeutic Radiology and Oncology. The therapeutic strategy makes use of three-dimensional imaging, which can be tailored to the target volume and at-risk organs through the use of computed tomography or magnetic resonance imaging. Under anaesthesia, the brachytherapy implantation is carried out. Ultrasonography is utilised to assess the depth of the uterine cavity and to facilitate the dilation of the uterine canal during the application insertion. In this study, we examine data from the international literature regarding the application of ultrasound in cervical cancer brachytherapy

Real Check RIO: A Real-World Analysis of Nivolumab in First Line Metastatic Melanoma Assessing Efficacy, Safety and Predictive Factors

We performed a retrospective study on 51 metastatic melanoma patients treated with Nivolumab in first line, at the Regional Institute of Oncology (RIO) Iasi, Romania between April 2017 and December 2019. We studied the efficacy and safety of anti-PD-1 immune checkpoint inhibitor therapy on a treatment-naive population. After a median follow-up of 36 months, the median progression free survival (PFS) was 26 months (95% CI, 15–36) and the median overall survival (OS) was 31 months (95% CI, 20.1–41.8). At 12 months after the initiation of immunotherapy, the percentage of patients alive was 70%, and at 24 months 62.5%. The most common adverse events observed were dermatological (23.5%) and grade ≥3 was identified in 4 (6.8%) patients. Multivariate analysis indicated that the presence of liver metastases (HR 4.42; 95% CI: 1.88–10.4, p = 0.001) and a neutrophils/lymphocytes ratio (NLR) were associated with poor survival (HR 3.21; 95% CI: 1.04–9.87, p = 0.04). Although retrospective data on a small group of patients were analyzed, we can conclude that our results in RIO are similar to those described in clinical trials and other real-world studies. Our study highlights the potential usefulness of liver metastases and NLR as novel predictive factors in clinical decision-making

Clinical, Pathological and Molecular Insights on KRAS, NRAS, BRAF, PIK3CA and TP53 Mutations in Metastatic Colorectal Cancer Patients from Northeastern Romania

Mutations in RAS, BRAF, PIK3CA, and TP53 are well-established genetic abnormalities in metastatic colorectal cancer (mCRC). However, limited information is available for patients from Eastern Europe, including Romania. In this retrospective analysis, we investigated 104 mCRC patients from the Northeastern region of Romania to determine the frequency, distribution, coexistence, and clinicopathological and molecular correlations of these mutations. TP53 was the most frequently mutated gene (73.1%), followed by KRAS (45.2%) and PIK3CA (6.7%). Patients with KRAS mutant tumors and wild-type TP53 genotype were found to have no personal history of gastrointestinal cancer (p = 0.02, p = 0.007). KRAS mutations in exon 3 were associated with the female gender (p = 0.02) and the absence of lymph node invasion (p = 0.02). PIK3CA mutations were linked to the absence of lymph node invasion (p = 0.006). TP53 mutations were associated with KRAS mutations in exon 2 (p = 0.006), ulcerated histopathologic type (p = 0.04), and G2 differentiation (p = 0.01). It provides novel insights into genetic variations specific to the population from Northeastern Romania, which has been underrepresented in previous studies within Eastern Europe. Furthermore, our findings enable the development of genetic profiles in a developing country with limited access to specialized genetic tests and facilitate comparisons with other populations