Prevalence of BRCA1 and BRCA2 pathogenic sequence variants in ovarian cancer patients in the Gulf region: the PREDICT study.

BACKGROUND: Patients with pathogenic sequence variants (PSVs) in BRCA1/BRCA2 are at high risk of developing ovarian cancer (OC). However, genetic testing for BRCA1/BRCA2 PSVs is still not a routine practice in the Middle East. With the lack of epidemiological studies in the region, we aim to describe the prevalence of BRCA1/BRCA2 PSVs in patients with OC across different countries in the Gulf region. METHODS: The PREDICT study was an observational, prospective, epidemiological study, which consecutively recruited women with ovarian, primary peritoneal, and fallopian tube cancers from the following Gulf countries over the period from July 2017 to July 2019; United Arab Emirates (UAE), Kuwait, and Oman. The study was approved by the local ethics committee of participating centers. The BRCA1/BRCA2 PSVs were assessed by tissue genetic testing using next-generation sequencing (NGS). RESULTS: A total of 105 women were included with a median age at diagnosis of 52 years (IQR 44.5 - 61.0). Nearly 11.4% of patients reported a family history of ovarian or breast cancer, while 4.7% of patients reported a family history of other cancers. Most of the patients (70.3%) had advanced disease (FIGO stage III/IV) at presentation. Eighty-eight patients (84%) were successfully tested for somatic BRCA1/BRCA2 PSVs. Fifteen patients (17%) were found to have PSVs in either BRCA1, BRCA2, or both genes; of them, 10 patients (11.2%) had BRCA1 somatic PSVs alone, eight patients (9.1%) had BRCA2 somatic PSVs, while three patients (2.9%) had both PSVs. Five patients with BRCA1/BRCA2 somatic PSVs had germline PSVs tests, and three of them tested positive. Concerning treatment, 87.6% of patients received perioperative chemotherapy and 6.6% as first-line palliative chemotherapy. Eighty-seven (82.9%) patients underwent debulking surgery, with no residual disease in 42.5% of patients. CONCLUSION: Our study showed that the prevalence of BRCA1/BRCA2 somatic PSVs in patients with OC is higher than the reported global figures (2-8%). However, more studies are warranted to further elucidate the prevalence of BRCA1/BRCA2 somatic and germline PSVs, as well as other relevant genetic alterations, to better understand their impact on OC patient outcomes in Gulf countries. TRIAL REGISTRATION: NCT03082976 .

Oncotype DX in Breast Cancer Management: Insights and Outcomes From the United Arab Emirates.

Introduction Breast cancer remains the most significant cancer affecting women worldwide, with an increasing incidence, especially in developing regions. The introduction of genomic tests like Oncotype DX has revolutionized personalized treatment, allowing for more tailored approaches to therapy. This study focuses on the United Arab Emirates (UAE), where breast cancer is the leading cause of cancer-related deaths among women, aiming to assess the predictive accuracy of the Oncotype DX test in categorizing patients based on recurrence risk. Materials and methods A retrospective cohort study was conducted on 95 breast cancer patients diagnosed at Tawam Hospital between 2013 and 2017 who underwent Oncotype DX testing. Data on patient demographics, tumor characteristics, treatment details, and Oncotype DX scores were collected. Survival analysis was performed using the Kaplan-Meier method, with the chi-square goodness of fit test assessing the model's adequacy. Results The cohort's age range was 27-71 years, with a mean age of 50, indicating a significant concentration of cases in the early post-menopausal period. The Oncotype DX analysis classified 55 patients (57.9%) as low risk, 29 (30.5%) as medium risk, and 11 (11.6%) as high risk of recurrence. The majority, 73 patients (76.8%), did not receive chemotherapy, highlighting the test's impact on treatment decisions. The survival analysis revealed no statistically significant difference in recurrence rates across the Oncotype DX risk categories (p = 0.268231). Conclusion The Oncotype DX test provides a valuable genomic approach to categorizing breast cancer patients by recurrence risk in the UAE. While the test influences treatment decisions, particularly the use of chemotherapy, this study did not find a significant correlation between Oncotype DX risk categories and actual recurrence events. These findings underscore the need for further research to optimize the use of genomic testing in the UAE's diverse patient population and enhance personalized treatment strategies in breast cancer management.

The Role of Direct Oral Anticoagulants in the Treatment of Cancer-Associated Venous Thromboembolism: Review by Middle East and North African Experts.

Venous thromboembolism is a leading cause of morbidity and mortality in patients with active cancer who require anticoagulation treatment. Choice of anticoagulant is based on careful balancing of the risks and benefits of available classes of treatment: vitamin K antagonists, low-molecular-weight heparin (LMWH), and direct oral anticoagulants (DOACs). Results from randomized controlled trials have shown the consistent efficacy of DOACs versus LMWH in the treatment of cancer-associated venous thromboembolism (VTE). However, increased major gastrointestinal bleeding was observed for edoxaban and rivaroxaban, but not apixaban, compared with LMWH dalteparin. Most guidelines recommend DOACs for the treatment of cancer-associated VTE in patients without gastrointestinal or genitourinary cancer, and with considerations for renal impairment and drug-drug interactions. These updates represent a major paradigm shift for clinicians in the Middle East and North Africa. The decision to prescribe a DOAC for a patient with cancer is not always straightforward, particularly in challenging subgroups of patients with an increased risk of bleeding. In patients with gastrointestinal malignancies who are at high risk of major gastrointestinal bleeds, apixaban may be the preferred DOAC; however, caution should be exercised if patients have upper or unresected lower gastrointestinal tumors. In patients with gastrointestinal malignancies and upper or unresected lower gastrointestinal tumors, LMWH may be preferred. Vitamin K antagonists should be used only when DOACs and LMWH are unavailable or unsuitable. In this review, we discuss the overall evidence for DOACs in the treatment of cancer-associated VTE and provide treatment suggestions for challenging subgroups of patients with cancer associated VTE.

Patients with cancer are at risk of blood clots forming in their veins, which can cause illness and death. To prevent such blood clots, most patients with cancer need anticoagulant therapy. There are three types of anticoagulants available for the treatment of cancer-associated blood clots in a vein, namely, vitamin K antagonists, low-molecular-weight heparin (LMWH), and direct oral anticoagulants (DOACs). Drug trials have shown that DOACs are more effective than LMWH; however, DOACs can have a greater risk of causing major gastrointestinal bleeding. Among DOACs, edoxaban and rivaroxaban are drugs associated with higher rates of gastrointestinal bleeding. Recently updated guidelines for doctors recommend that DOACs be used as the first treatment for patients with cancer at risk of blood clot formation in a vein. For doctors in the Middle East and North Africa, this new approach differs from existing practices. Notably, choosing a treatment also depends on the type of cancer, because gastrointestinal cancers and cancers of the genitals and urinary system have an especially high risk of gastrointestinal bleeding. The choice also depends on the presence of kidney problems, drug­drug interactions, and access to the drugs. Apixaban may be the preferred DOAC in patients with gastrointestinal cancer, but this drug should be used with care in patients with upper or unresected lower gastrointestinal tumors. For patients with upper or unresected lower gastrointestinal tumors, treatment with LMWH may be preferred. Vitamin K antagonists should be used only when DOACs and LMWH are unavailable or unsuitable.

Unilateral Axillary Lymphadenopathy in Cancer Patients Post-COVID-19 Vaccination: Review and Case Series.

Novel coronavirus-19 (COVID-19) variants continue to spread worldwide with the development of highly transmissible strains. Several guidelines addressing management of cancer patients during the COVID-19 pandemic have been published, primarily based upon expert opinion. The COVID-19 pandemic has affected all aspects of breast cancer care including screening, diagnosis, treatment, and long-term follow-up. Recent reports indicate that mRNA COVID-19 vaccines can provoke lymphadenopathy in both cancer patients and healthy individuals. Unilateral axillary lymphadenopathy (UAL) post-COVID-19 vaccination is a challenging presentation for cancer patients because of the potential for misinterpretation as malignancy. The World Health Organization's target to vaccinate 70% of the world's population by mid-2023 is likely to increase the incidence of post-COVID-19 vaccination UAL. In this article, we review the published evidence regarding UAL post-COVID-19 vaccination and present diverse cases of breast cancer patients where false-positive UAL post-COVID-19 vaccination proved to be a therapeutic challenge. The United Arab Emirates (UAE) vaccination program is well ahead of other countries in the world, having accomplished the target of 100% vaccination of the population with at least one dose. Therefore, an increasing number of recently vaccinated patients are likely to present with UAL, detected by surveillance imaging, post-vaccination. We have therefore made recommendations regarding the management of cancer patients with UAL post-COVID-19 vaccination in order to avoid misdiagnosis and unnecessary imaging or invasive biopsy procedures.

Endometrial Carcinoma: A Comprehensive Analysis of Clinical Parameters, Treatment Modalities, and Prognostic Outcomes at a Tertiary Oncology Center in the UAE.

Background Endometrial carcinoma (EC) remains a pressing global health issue, with a discernible upsurge in incidence, especially in developed countries. Notably, the United Arab Emirates (UAE) has witnessed a surge in EC cases, demanding an in-depth, region-specific exploration into the disease's clinical, treatment, and prognostic facets against the backdrop of its unique socio-genetic and environmental contours. Aim This study aimed to profess a comprehensive understanding of EC by examining clinical parameters, treatment modalities, and prognostic outcomes in the UAE context, thereby seeking to delineate potential correlations between varied therapeutic combinations, patient demographics, and tumor characteristics in affecting prognostic outcomes. Materials and methods A retrospective cohort study involving 93 patients diagnosed with EC from January 2011 to March 2023 at a leading oncology center in the UAE was conducted. Data, including demographic information, clinical presentation, treatment modalities, and prognostic outcomes, were meticulously extracted and analyzed. The R software (version 4.2.2) facilitated exhaustive statistical analyses, involving descriptive statistics, correlation analyses with the polycor package, and survival analyses utilizing the Kaplan-Meier method and Cox regression analysis via the survival and survminer packages, respectively. Results Although the correlation matrix revealed a noticeable relationship between "Family history" and "Age," most parameters displayed independence, offering a robust platform for ensuing multivariate analyses. Kaplan-Meier survival curves, stratified by therapeutic modalities, exhibited no statistically significant survival differences across therapeutic cohorts (p-values: 0.44, 0.86, and 0.83). Conversely, the composite Cox regression model underscored "non-national" demographic, Diabetes Mellitus II, and stromal invasion as pivotal prognostic factors, indicating the multifactorial nature of survival in EC patients and emphasizing demographic and tumor characteristics over therapeutic modalities as influential prognostic determinants. Conclusion In conclusion, while therapy types were not directly correlated with survival, demographic and tumor traits prominently impacted prognostic outcomes, advocating for an intricate, multidimensional approach to managing EC in the UAE. This study hopes to sow seeds for subsequent research, shaping clinically and culturally apt practices and policies in the region's healthcare landscape.

Rare case of chemotherapy-refractory metastatic vaginal squamous cell carcinoma with complete response to concurrent pembrolizumab and radiotherapy- case report and literature review.

Primary vaginal cancer is a rare malignancy with a lack of international guidelines and supporting clinical trial evidence to guide decision making. Historical results have shown poor outcomes with chemotherapy for stage IVB vaginal squamous cell carcinoma (SCC). The evolving role of checkpoint inhibitors in rare gynaecological cancers prompted us to investigate the role of pembrolizumab in this setting. The efficacy of pembrolizumab in vaginal SCC has never been investigated in any clinical trial. There is established data to support the use of concurrent chemoradiotherapy in gynaecological cancers, however, the data for concurrent use of immunotherapy and radiotherapy is still lacking but is the subject of several clinical trials. We herein present the first reported case of chemotherapy refractory vaginal SCC with complete response to pembrolizumab and concurrent pelvic radiotherapy. We also present wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) as a rare but new immune related adverse event.

Patient selection and risk factors in the changing treatment landscape of metastatic renal cell carcinoma.

INTRODUCTION: The approval of combination treatments for metastatic renal cell carcinoma (mRCC) represents a major change in the clinical management of this malignancy. Updated treatment guidelines differentiate first-line mRCC treatment by patient risk group as defined by prognostic models and the number of risk factors. AREAS COVERED: Current prognostic models, with a focus on the International Metastatic RCC Database Consortium and the Memorial Sloan Kettering Cancer Center models, the heterogeneity of the intermediate risk group, and first- and second-line mRCC treatment outcomes according to patient risk group are discussed. Consideration is given to the future direction of treatment selection strategies including refinement of prognostic factors, genetic biomarkers and gene signatures. EXPERT OPINION: Current prognostic models require updating, but initial data suggests they are effective in stratifying patients treated with immune checkpoint inhibitors or combination therapy. Treatment selection for patients with 1-2 risk factors may require further consideration due to the heterogeneous nature of the intermediate risk group. Future prognostic models may benefit from inclusion of gene signatures and stratification by molecular subtype. Prognostic risk factors are not the only consideration in treatment selection; tumor burden, location of metastases, and comorbidities, among other factors, should also be considered.

The State of Cancer Care in the United Arab Emirates in 2020: Challenges and Recommendations, A report by the United Arab Emirates Oncology Task Force.

With cancer being the third leading cause of mortality in the United Arab Emirates (UAE), there has been significant investment from the government and private health care providers to enhance the quality of cancer care in the UAE. The UAE is a developing country with solid economic resources that can be utilized to improve cancer care across the country. There is limited data regarding the incidence, survival, and potential risk factors for cancer in the UAE. The UAE Oncology Task Force was established in 2019 by cancer care providers from across the UAE under the auspices of Emirates Oncology Society. In this paper we summarize the history of cancer care in the UAE, report the national cancer incidence, and outline current challenges and opportunities to enhance and standardize cancer care. We provide recommendations for policymakers and the UAE Oncology community for the delivery of high-quality cancer care. These recommendations are aligned with the UAE government's vision to reduce cancer mortality and provide high quality healthcare for its citizens.

Studying the Impact of Golgi Protein 73 Serving as a Candidate Biomarker in Early Diagnosis for Hepatocellular Carcinoma among Saudi Patients

Background: Due to the prevalence of Hepatocellular carcinoma (HCC) in Saudi Arabia, using new markers to give best diagnostic performance than alpha-feto protein (AFP) are important in early diagnosis. The aim of this work was to compare the significance between serum and mRNA Golgi glypican73 (GP-73) as newly identified diagnostic and prognostic markers for HCC among Saudi patients. Materials and Methods: A total of 300 subjects were divided into: 250 blood samples where 145 samples from HCC, 105 samples from chronic liver cirrhosis (CLC) and 50 normal controls were investigated for serum GP73 (sGP73) by ELISA. GP-73 mRNA from peripheral blood mononuclear cells was amplified by RT-PCR. The sensitivity and specificity of both techniques was compared. Results: Serum Golgi glypican 73 was significantly higher in HCC group compared to cirrhotic and normal controls (p<0.001). Sensitivity and specificity were 95% for sGP-73, 100% and 90% for Golgi glypican 73 mRNA. The combination of sensitivity between AFP and sGP73 was 80% and 95% respectively. Conclusion: Both serum Golgi glypican-73 and GP-73Mrna are good diagnostic biomarkers for early detection of HCC in Saudi patients. RT-PCR is more accurate and sensitive (100%) than ELISA (95%) in detecting Golgi glypican 73.