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.

Breast Cancer in the Arabian Gulf Countries.

Breast cancer stands as the prevailing malignancy across all six Gulf Cooperation Council (GCC) nations. In this literature review, we highlighted the incidence and trend of breast cancer in the GCC. Most of the studies reported a consistent increase in breast cancer incidence over the past decades, which was particularly attributed to the adoption of a Westernized lifestyle in the region and the implications of emerging risk factors and other environmental and societal factors, the increase in screening uptake, as well as the improvement in data collection and reporting in the GCC. The data on breast cancer risk factors in the GCC were limited. In this geographic region, breast cancer frequently manifests with distinctive characteristics, including an early onset, typically occurring before the age of 50; an advanced stage at presentation; and a higher pathological grade. Additionally, it often exhibits more aggressive features such as human epidermal growth factor receptor 2 (HER2) positivity or the presence of triple-negative (TN) attributes, particularly among younger patients. Despite the growing body of literature on breast cancer in the GCC, data pertaining to survival rates are, regrettably, meager. Reports on breast cancer survival rates emanating from the GCC region are largely confined to Saudi Arabia and the United Arab Emirates (UAE). In the UAE, predictive modeling reveals 2-year and 5-year survival rates of 97% and 89%, respectively, for the same period under scrutiny. These rates, when compared to Western counterparts such as Australia (89.5%) and Canada (88.2%), fall within the expected range. Conversely, Saudi Arabia reports a notably lower 5-year survival rate, standing at 72%. This disparity in survival rates underscores the need for further research directed toward elucidating risk factors and barriers that hinder early detection and screening. Additionally, there is a pressing need for expanded data reporting on survival outcomes within the GCC. In sum, a more comprehensive and nuanced understanding of breast cancer dynamics in this region is imperative to inform effective strategies for prevention, early detection, and improved patient outcomes.

The first Middle East and North Africa expert consensus recommendations for the management of advanced colorectal cancer.

Colorectal cancer (CRC) is ranked as the third most prevalent and the second deadliest cancer worldwide. In the Middle East and North Africa (MENA) region, the number of CRC cases increased over the past decades and will nearly double by 2030. The lack of clear MENA guidelines for the management of patients with CRC represents a step backwards in the fight against this burden. Therefore a panel of 24 MENA experts in the field of gastrointestinal oncology developed, using a Delphi process, the first consensus recommendations for the management of patients with advanced CRC. Forty-seven different statements were formulated in the areas of epidemiology, screening, biomarkers and treatment. These recommendations will guide, standardize and unify the management of this cancer in the MENA region.

Real-World Data on the Prevalence of Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer in the Middle East and North Africa.

PURPOSE: Anaplastic lymphoma kinase (ALK) gene alterations are potent oncogenic drivers in non-small-cell lung cancer (NSCLC). Tyrosine kinase inhibitors targeting the ALK pathway are effective in treating ALK-positive NSCLC. Around 5% of Asian and White patients with NSCLC have ALK-positive tumors, but ALK rearrangement prevalence data in the Middle East and North Africa (MENA) region are limited. METHODS: In this noninterventional epidemiology study, histologically confirmed nonsquamous NSCLC samples retained for < 5 years in tissue banks at six centers in MENA were retrospectively analyzed for ALK rearrangement using the VENTANA immunohistochemistry (IHC) method. Patient characteristics obtained were analyzed for association with ALK rearrangement. Concordance between IHC and Vysis fluorescence in situ hybridization (FISH) ALK detection methods was assessed in a subset of samples. RESULTS: Four hundred forty-eight tissue samples were analyzed using IHC: 137 (30.6%) in Lebanon, 104 (23.2%) in Saudi Arabia, 97 (21.7%) in Egypt, 80 (17.9%) in the United Arab Emirates, and 30 (6.7%) in Morocco. On the basis of IHC, the prevalence was 8.7% (95% CI, 6.3 to 11.7) for ALK-positivity and 91.3% (95% CI, 88.3 to 93.7) for ALK-negativity. On the basis of FISH (n = 148), the prevalence was 5.4% positivity and 81.8% negativity (12.8% nonevaluable). Concordance between IHC and FISH (n = 129) was 98.4% (95% CI, 94.2 to 99.8) for negative agreement and 98.5% (95% CI, 94.5 to 99.8) for overall agreement. Univariate analysis showed that ALK rearrangement was significantly associated with epidermal growth factor receptor wild-type status (P = .03) but was not significantly associated with sex, race, smoking history, or histologic subtype. CONCLUSION: Our findings suggest that ALK rearrangements are more prevalent in MENA than other geographic regions. High concordance was found between FISH and IHC. Except for epidermal growth factor receptor wild-type status, no clinicopathologic characteristics were associated with ALK-positive NSCLC.

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.

Patterns of diagnostic procedures for lung cancer pathology in the Middle East and North Africa.

BACKGROUND: Accurate pathological diagnosis is the first critical step in the management of lung cancer. This step is important to determine the histological subtype of the cancer and to identify any actionable targets. Our study aimed at evaluating the patterns of procedures used to obtain pathological diagnosis of lung cancer in the Middle East and North Africa (MENA) Region. METHODS: Data of consecutive patients with the diagnosis of non-small cell lung cancer (NSCLC) were collected from participating centers from different countries in the MENA Region. Methods of obtaining tissue diagnosis and workup were analyzed to determine the practice patterns of obtaining tissue diagnosis of lung cancer. RESULTS: A total of 566 patients were recruited from 10 centers in 5 countries including Saudi Arabia, United Arab Emirates (UAE), Qatar, Lebanon and Algeria. Majority of patients were males (78.1%) with a median age of 61 years (range, 22-89 years). Obtaining tissue diagnosis was successful in the first attempt in 72.3% of patients, while 16.4% and 6.3% of patients required 2nd and 3rd attempt, respectively. The success in first attempt was as follows: image guided biopsy (91%), surgical biopsy (88%), endobronchial biopsy (79%) and cytology (30%). The success in the second attempt was as follows; surgical biopsy (100%), image guided biopsy (95%), endobronchial biopsy (65%), cytology (25%). CONCLUSIONS: More than quarter of the patients required repeated biopsy in the MENA Region. Image guided biopsy has the highest initial yield. Implementing clear process and multidisciplinary guidelines about the selection of diagnostic procedures is needed.

Supportive care needs of multicultural patients with cancer in the United Arab Emirates.

Despite the high prevalence of cancer in the Middle East, there is limited published data reporting the needs of cancer patients in this region of the world. The purpose of this study is to assess the unmet supportive care needs of oncology patients in the United Arab Emirates (UAE). From December 2014 to December 2016, a cross-sectional survey of cancer patients was conducted at a large tertiary care hospital and an oncology referral centre in the UAE, using a validated Arabic translation of the supportive care needs survey--short form (SCNS-SF34-A), assessing cancer-specific perceived needs across five domains: psychological, health system information, patient care and support, physical and daily living and sexuality. Chi-square test and Pearson's correlation coefficient were used to assess the association between variables. Participant responses were tabulated as mean ± standard error of the mean (SEM). The response rate was 78% (210/268). Five of the 10 items from the psychological domain constituted the 10 most prevalent unmet moderate or high needs, followed by physical and daily living needs (3.04 ± 0.029, p < 0.001), health system information (3.03 ± 0.02, p < 0.001), patient care and support (2.95 ± 0.24, p < 0.001), with low sexuality needs (1.79 ± 0.08, p < 0.001). Women had significantly higher psychological unmet needs. Cultural differences were noted only in the health system information domain. Improvements in mental health services, development of multidisciplinary cancer care teams, introduction of cancer support groups and fully engaging women in all treatment decisions are feasible and easy to implement interventions that can significantly improve the care and wellbeing of oncology patients in the UAE.

A multicenter prospective phase II trial of neoadjuvant epirubicin, cyclophosphamide, and 5-fluorouracil (FEC100) followed by cisplatin-docetaxel with or without trastuzumab in locally advanced breast cancer.

PURPOSE: To evaluate the efficacy and safety profile of the (FEC100) followed by cisplatin/docetaxel with and without trastuzumab as primary chemotherapy for patients with locally advanced breast cancer (LABC). METHODS: Eighty patients with LABC (T2-T4, N0-N2, M0) were enrolled to receive 24 weeks of neoadjuvant chemotherapy using epirubicin, cyclophosphamide, and 5-fluorouracil (FEC100) followed by cisplatin and docetaxel, plus trastuzumab if HER2 positive. The primary endpoint was pathologic complete response (pCR) in breast and axilla in separate HER2-negative and HER2-positive cohort. RESULTS: Eighty patients were evaluable for analysis of which 51 were HER2 negative and 29 HER2 positive: median age: 43 years, premenopausal: 82%, median tumor size: 7.0 cm (4-10), stage IIB: 25% and IIIA/IIIB: 75%, both ER/PR positive: 56%, HER2 positive (3+) by IHC staining: 36%. Clinical complete response was seen in 48%, and clinical partial response was seen in 52%. Overall the pathologic complete response (pCR) was 36% in breast, 64 % in axilla, and 32% in both breast and axilla. Analysis of pCR in breast and axilla, as a function of the hormonal receptor (HR) and HER2, was as follows: HR(+)/HER2(-): 11%; HR(+)/HER(+): 56 %; HR(-)/HER2(-): 36%; HR(-)/HER2(+): 62%. CONCLUSION: In this series of locally advanced breast cancer, the combination of (FEC100) followed by cisplatin/docetaxel with and without trastuzumab was very active obtaining an impressive rate of pCR, particularly in HER2-positive and triple negative disease, which merits further investigation.

Outcome of 3 pregnancies in a patient with chronic myeloid leukemia who received 3 types of tyrosine kinase inhibitors each in different pregnancy: follow-up of the case with a review of published reports.

The management of patients with chronic myeloid leukemia (CML) during pregnancy remains a matter of continuous debate. Tyrosine kinase inhibitors (TKIs) have become the standard of care in managing patients with CML. These drugs have a good safety profile, but animal studies have shown that they are potentially teratogenic. Therefore, these drugs are not recommended for use during pregnancy or if a female patient plans to conceive. Despite the extensive clinical experience with TKIs, the available information about the effects of TKIs on fertility, pregnancy, and outcome of babies who were exposed to TKIs during pregnancy and lactation is limited. We reported on 1 female CML patient who conceived 3 times while being on different types of TKIs in each pregnancy. All 3 pregnancies were uneventful, and only 1 of the babies was diagnosed with a minor cardiac malformation at the age of 30 months, which was corrected surgically.

Impact of Oncotype†DX testing on adjuvant treatment decisions in patients with early breast cancer: a single-center study in the United Arab Emirates.

AIM: To evaluate the distribution of the Oncotype DX Recurrence Score (a validated prognostic/predictive tool in early-stage estrogen-receptor positive [ER+] breast cancer) and its impact on adjuvant treatment decisions in the United Arab Emirates. METHODS: A retrospective analysis of a single-center cohort. RESULTS: The analysis included 47 node-negative ER+ breast cancer patients with low-to-intermediate risk according to the St. Gallen criteria. The mean (SD) Recurrence Score result was 17.7 (8.0); 25 (53.2%), 19 (40.4%) and 3 (6.4%) patients had low, intermediate and high Recurrence Score results, respectively. Recurrence Score risk categories were concordant with risk groups according to the St. Gallen criteria in 23 patients (48.9%). Before testing, 24 patients (51.1%) were recommended endocrine therapy alone and 23 patients (48.9%) were recommended chemoendocrine therapy. After testing, 13 patients (27.7%; 95% confidence interval 16.3-42.4%) had a treatment change (from pretesting recommendation to posttesting actual treatment), and chemotherapy use decreased overall (from 48.9 to 25.5%; P = 0.0023, McNemar's test), and particularly in the low Recurrence Score category (from 56.0 to 8.0%; P = 0.0005, McNemar's test). After testing, the proportions of patients with chemoendocrine therapy recommendations differed significantly across the Recurrence Score categories (8.0, 36.8 and 100% in the low, intermediate and high Recurrence Score categories, respectively; P = 0.0012, Fisher's exact test). With an average follow-up of 31.2 months (range: 17-51), no locoregional/systemic relapses were observed. CONCLUSION: This first decision impact study in a Middle Eastern country showed the significant effect of Oncotype DX testing on clinical practice, further demonstrating the consistent impact of such testing worldwide.

Metastatic castration resistant prostate cancer: current strategies of management in the Middle East.

Although most patients with prostate cancer respond to initial androgen-deprivation therapy, progression to castration-resistant prostate cancer (CRPC) is almost inevitable. In 2004, the docetaxel/prednisone regimen was approved for the management of patients with metastatic CRPC, becoming the standard first-line therapy. Recent advances have also led to an unprecedented number of approved new drugs; thus, providing several treatment options for patients with metastatic CRPC. Five new drugs have received US Food and Drug Administration-approval between 2010 and 2012: sipuleucel-T, an immunotherapeutic agent; cabazitaxel, a novel microtubule inhibitor; abiraterone acetate, a new androgen biosynthesis inhibitor; enzalutamide, a novel androgen receptor inhibitor; and denosumab, a bone-targeting agent. Such drugs are either already marketed or about to be marketed in the Middle East. Data supporting the approval of each of these agents are described in this review, as are recent approaches to the treatment of metastatic CRPC.

Strongyloides hyper-infection causing life-threatening gastrointestinal bleeding.

A 55-year old male patient was diagnosed with strongy-loides hyper-infection with stool analysis and intestinal biopsy shortly after his chemotherapy for myeloma. He was commenced on albendazole anthelmintic therapy. After initiation of the treatment he suffered life-threatening gastrointestinal (GI) bleeding. Repeated endoscopies showed diffuse multi-focal intestinal bleeding. The patient required huge amounts of red blood cells and plasma transfusions and correction of haemostasis with recombinant activated factor VII. Abdominal aorto-angiography showed numerous micro-aneurysms ('berry aneurysms') in the superior and inferior mesenteric arteries' territories. While the biopsy taken prior to the treatment with albendazole did not show evidence of vasculitis, the biopsy taken after initiation of therapy revealed leukoclastic aggregations around the vessels. These findings suggest that, in addition to direct destruction of the mucosa, vasculitis could be an important additive factor causing the massive GI bleeding during the anthelmintic treatment. This might result from substances released by the worms that have been killed with anthelmintic therapy. Current guidelines advise steroids to be tapered and stopped in case of systematic parasitic infections as they might reduce immunity and precipitate parasitic hyper-infection. In our opinion, steroid therapy might be of value in the management of strongyloides hyper-infection related vasculitis, in addition to the anthelmintic treatment. Indeed, steroid therapy of vasculitis with other means of supportive care resulted in cessation of the bleeding and recovery of the patient.

[Life-threatening gastrointestinal bleeding related to the treatment of strongyloidiasis hyperinfection in an immunocompromised patient]. / Eletet veszélyeztetó gastrointestinalis vérzés strongyloides hiperinfekció kezelése kapcsán immunszupprimált betegben.

The clinical course and sequel of the life-threatening gastrointestinal (GI) bleeding during the treatment of strongyloides helmintic hyperinfection induced by immunosuppression in a patient with multiple myeloma is presented. A 55-year old male patient was diagnosed with strongyloides infection with stool analysis and intestinal biopsy shortly after his combined chemotherapy for myeloma. He was commenced on albendazole anthelmintic therapy. However, after initiation of the treatment he suffered life-threatening GI bleeding. Repeated endoscopies, including intraoperative enteroscopy, concluded to diffuse multifocal intestinal bleeding. The patient required huge amounts of red blood cells and plasma transfusions and correction of haemostasis with recombinant activated factor VII. Abdominal aorto-angiography showed numerous microaneurysms ("berry aneurysms") in the superior and inferior mesenteric arteries' territories. While the biopsy taken prior to the treatment with albendazole did not show evidence of vasculitis, the biopsy taken after initiation of therapy revealed leukoclastic aggregations around the vessels which was also consistent with vasculitis. These findings suggest that--in addition to direct destruction of the mucosa-vasculitis could be an important additive factor to the massive GI bleeding during the anthelmintic treatment. This might result from substances released by the worms that have been killed with anthelmintic drugs. Current guidelines advise steroids to be tapered and stopped in case of systematic parasitic infections as they reduce immunity and precipitate parasitic hyperinfection. In our pinion, steroid therapy might be of value in the management of strongyloides hyperinfection related vasculitis--in addition to the specific anthelmintic treatment. Indeed, steroid therapy of vasculitis with other means of supportive care yielded in sequel of the bleeding and in recovery of the patient.

Serum Flt3 ligand variation as a predictive indicator of hematopoietic stem cell mobilization.

Flt3 ligand (FL) is a good indicator of bone marrow (BM) cellularity, having a reciprocal relationship with white blood cell (WBC) count in aplastic anemia and chemotherapy-induced neutropenia. In this report, serum FL level was measured by enzyme-linked immunosorbent assay (ELISA), in 16 consecutive patients undergoing autologous peripheral stem cell transplantation, with an average of 12 selected levels for each patient based on major changes of WBC counts at different procedure stations. We found a significant increase of serum FL level at the WBC nadir after mobilization chemotherapy and a more dramatic increase at the WBC nadir post transplantation, consistent with a more profound BM aplasia after myeloablative chemotherapy as compared to high-dose cyclophosphamide used for mobilization. Hence, we reproduced the reciprocal relationship between serum FL and BM cellularity. A direct correlation between the increase of FL level after mobilization chemotherapy and the length of mobilization was also established, which may help physicians, at the individual patient level, to predict the time of stem cell collection. Finally, we showed a direct correlation between the peripheral CD34+ count at the time of stem cell collection and the peak FL level after transplantation, which can reflect BM stromal cell function. Our results suggest that variation of serum FL level may be used as predictive indicator of hematopoietic stem cell (HSC) mobilization.