Low baseline vitamin D levels increase the risk of bone metastases among females with breast cancer - Hospital based cohort study.

BACKGROUND: Serum vitamin D (Vit-D) has been linked to the development of breast cancer (BC); however, their effect on pathological features and outcomes is undetermined. The purpose of this study was to examine the prognostic significance of baseline Vit-D levels and their effect on clinical outcomes. METHODS: We evaluated baseline serum Vit-D levels and baseline clinic-pathological features of female patients with non-metastatic BC between October 2018 and December 2019. A low Vit-D level was described as less than 30 nanogram per liter (ng/l). Patients were observed for a median of 24 months. To evaluate relationships between qualitative variables, the chi-square test was used. The Kaplan-Meier technique was used for survival analysis, and the log-rank test was used to compare the two survival curves. Correlation analysis was also used to examine the link between Vit-D levels and clinical outcomes. RESULTS: The eligibility criteria were fulfilled by 221 patients. The median age of onset was (50.7). The median Vit-D level was (23.1 ng/l) with a range of (4-46 ng/l). Approximately half of the patients (56.5%) had Vit-D levels < 30 ng/l, with HER2 positive and triple negative (TNBC) patients having a greater proportion of low Vit-D levels (p = <0.001). Patients with low baseline Vit-D levels had a larger tumor size, more positive lymph nodes, and were diagnosed at a later stage. Following follow-up, Vit-D deficiency was associated with a significantly increased risk of bone metastases (HR 3.37, 95% CI 1.32-8.59, p = 0.006), and Vit-D levels were significantly correlated with disease-free survival (DFS) and overall survival (OS) (r = 0.850, r = 0.573, p < 0.00, p < 0.001, respectively). CONCLUSIONS: Low serum Vit-D is associated with advanced stage and adverse characteristics. It is more prevalent in HER-2 positive and TNBC patients; it increases the chance of bone metastases, and has a significant correlation with DFS and OS.

Is Survival with Conservative Breast Therapy Becoming Superior to That with Modified Radical Mastectomy Alone for the Treatment of Early Breast Cancer in This Era?

This study aims to assess survival rates in early breast cancer patients treated by conservative breast therapy (CBT), including radiotherapy, compared with those treated by modified radical mastectomy (MRM) alone. The South Egypt Cancer Institute and the Assiut University Oncology Department patients' records, from January 2010 to December 2017, were searched for T1-2N0-1M0 breast cancer patients treated by CBT or MRM. Patients who did not receive chemotherapy were excluded to reduce the treatment variation. The 5-year locoregional disease-free survival (LRDFS) was 97.3% for the CBT patients was and 98.0% for the MRM patients (P = .675). The 5-year distant disease-free survival (DDFS) was 93.6% for CBS and 85.7% for MRM (P = 0.033). The DFS was 91.9% for the BCT patients and 85.3% for the MRM patients (P = 0.045). The 5-year OS was 98.2% for the CBT patients and 94.3% for the MRM patients, (P = 0.02). By Cox regression analysis, the CBT resulted in significantly better OS, (P = 0.018) and the HR = 0.350, 95% CI 0.146-0.837. The adjusted OS, estimated by the propensity score-based weights, remained superior in CBT than in MRM patients (P < 0.001). CBT resulted in better DDFS, DFS, and OS than MRM. Future randomized trials are needed to confirm these findings and determine the cause.

Diagnostic Value of Claudin-4 and EZH2 Immunohistochemistry in Effusion Cytology.

BACKGROUND: Metastatic adenocarcinoma (MAC) accounts for most cases of malignant effusions. Sometimes, it can be difficult to distinguish MAC from reactive mesothelial cells (RMC) in cytologic specimens. Our aim was to assess the diagnostic performance of a novel immunohistochemical panel composed of claudin-4 and EZH2 in differentiating MAC from RMC in effusion cytology. METHODS: A total of 80 cases of serous effusions (48 MAC and 32 RMC) were included. Immunohistochemistry using claudin-4 and EZH2 was performed on cell block sections of these cases. Assessment of staining patterns, intensity and percentage of target cells stained was done. RESULTS: Claudin-4 showed membranous staining in 46/48 of MAC and 1/32 of RMC. High EZH2 (≥ 50% of target cells) was detected in 42/48 MAC and 2/32 RMC. For the discrimination between MAC and RMC, claudin-4 exhibited 95.8% sensitivity and 96.9% specificity, high-EZH2 exhibited 87.5% sensitivity and 93.8% specificity, while the combination of both claudin-4 and high EZH2 showed 100% sensitivity and 90.6% specificity. CONCLUSION: Claudin-4 shows high sensitivity and specificity in differentiation between MAC and RMC in effusion cytology, and might be useful as a solitary marker for MAC. Adding EZH2 to claudin-4 increases the sensitivity to 100%. However, the interpretation of EZH2 results can be challenging due to its focal expression in RMC and inflammatory cells.

Resource Oriented Decision Making for Treatment of Metastatic Colorectal Cancer (mCRC) in a Lower-Middle Income Country: Egyptian Foundation of Medical Sciences (EFMS) Consensus Recommendations 2020.

PURPOSE: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second cause of cancer related mortality. Treatment options for patients with metastatic CRC (mCRC) expanded during the last two decades, with introduction of new chemotherapeutic and targeted agents. Egypt is a lower middle-income country; Egyptian health care system is fragmented with wide diversity in drug availability and reimbursement policies across different health care providing facilities. We report the results of consensus recommendations for treatment of patients with metastatic colorectal cancer developed by Egyptian Foundation of Medical Sciences (EFMS), aiming to harmonize clinical practice through structured expert consensus-based recommendations consistent with the national status. EFMS recommendations could be utilized in other countries with similar economic status. METHODS: EFMS recommendations were developed using a modified Delphi process, with three rounds of voting till the final recommendations were approved. A non-systematic review of literature was conducted before generating the provisional statements. Content experts were asked to vote on some recommendations in two different resource groups (restricted resources and non-restricted resources). External review board of experts from a low income and lower-middle countries voted on the applicability of EFMS recommendations in their countries. RESULTS: The current recommendations highlighted the discrepancy in health care between restricted and non-restricted resources with expected survival loss and quality of life deterioration. Access to targeted agents in first line is very limited in governmental institutions, and no access to agents approved for third line in patients who failed oxaliplatin and irinotecan containing regimens for patients treated in restricted resource settings. CONCLUSION: Management of mCRC in developing countries is a challenge. The currently available resource-stratified guidelines developed by international cancer societies represent a valuable decision-making tool, adaptation to national status in each country based on healthcare system status is required.

Role of post-therapy 99mTc-MIBI single-photon emission computed tomography/computed tomography scan in predicting survival in patients with high-grade glioma.

OBJECTIVE: High-grade gliomas (HGGs) carry dismal prognosis with survival typically reported as less than a year. We explored the predictive value of qualitative and quantitative evaluations of post-treatment 99m-technetium-labelled methoxyisobutylisonitrile (99mmTc-MIBI) brain single-photon emission computed tomography-computed tomography (SPECT/CT) tumor uptake in relation to overall survival (OS) in patients with HGG. METHODS: Thirty patients with pathologically or radiologically documented high-grade glioma (HGG) were prospectively recruited for this study (24 male, 6 female; mean age 43 ± 14 years). All patients had a clinical or radiological suspicion of residual/recurrent tumor after initial therapy. 99mTc-MIBI brain SPECT/CT scanning was performed, and the scans were evaluated qualitatively on a five-point probability score (1-5, scores ≥3 considered positive for residual/recurrent tumor); and quantitively via drawing volumes of interest (VOI) on the suspected lesions and normal contralateral brain tissue. All patients were followed up for 1 year or till death. RESULTS: Positive visual MIBI results were associated with poor survival. Among 10 patients with negative MIBI scores, only two patients died (OS = 75%), while 11/20 patients reported positive on MIBI died, with a median survival of 9 months (OS = 14.5%; P = 0.03). All patients with active isocontour volume ≤1.96 cm3 were alive at the end of the study, compared to a median survival of 9 months and OS of 12% for patients with an isocontour volume of >1.97% (P = 0.003). CONCLUSION: In patients with HGG, post-therapy brain SPECT/CT with 99mTc-MIBI can provide useful prognostic information.

Molecular targets of gemcitabine action: rationale for development of novel drugs and drug combinations.

Gemcitabine is one of the most widely used pyrimidine analogues, with a well-established role as a first- and second-line treatment of several types of tumors. Several preclinical and clinical studies have been done to obtain information on molecular determinants of gemcitabine activity and metabolism, in order to predict whether this drug will be effective and safe for the individual patient. Among these molecular determinants, the mRNA and protein expression of equilibrative transporter-1 (ENT1) and ribonucleotide reductase (RR) emerged as possible predictors of drug activity in studies on pancreatic and non-small cell lung cancer. However, cytidine deaminase polymorphisms and activity were correlated with clinical outcome and severe toxicities, whereas further studies should evaluate both P53 dependent and independent pathways involved in gemcitabine induced apoptosis. Improved knowledge on these determinants is critical for the optimal development of combination of gemcitabine with other conventional or biological therapies, as well as to exploit the radiosensitizing potential of gemcitabine. Emerging technologies such as massive parallel sequencing, gene expression arrays and proteomics may identify novel biomarkers in tumor material, while polymorphisms and phenotyping analysis should unravel factors involved in drug toxicity. Validation of these markers in preclinical models should be used for the appropriate patient enrolment into subsequent prospective studies. Hopefully, novel pharmacogenetic biomarkers will be validated in these prospective studies and used to select cancer patients to be treated with gemcitabine-based regimens in the near future or to enroll them in studies with prodrugs in order to bypass resistance mechanisms.