Aim of work Reporting the incidence and the variants of BRCA1 /2 mutations in ovarian cancer patients exploring their effects on the treatment outcomes. Patients and methods In total, 104 patients with epithelial ovarian cancer were prospectively recruited to the study. Analysis consisted of the sequencing of all the translated exons and immediately adjacent intronic regions of the BRCA1/2 genes. Responses to multiple lines of chemotherapy were assessed, as well as the effect of BRCA gene mutations on progression-free survival (PFS) and overall survival (OS). Results Pathogenic BRCA1 / 2 mutations were found in 21.15% of the patients. BRCA1 mutations represented 68.2% of the total mutations. Two novel BRCA1 mutations were identified. Age at diagnosis was a strong predictor of the presence of a pathogenic BRCA1/2 mutation. Patients with a family history of cancer had a higher incidence of BRCA mutations ( P =0.005). As high as 72% of the patients with BRCA mutations were diagnosed at advanced stage. High-grade serous tumors have a higher incidence of pathogenic mutation ( P =0.07). Response to neoadjuvant chemotherapy was high (93.9%). All patients underwent surgery which was optimal in 73.1% of the patients. As high as 85.6% of the patients received adjuvant chemotherapy. Relapse rate was 45.2%. Visceral metastasis was more often in BRCA carriers ( P =0.01). Patients carrying pathogenic BRCA1/2 mutations had a longer median PFS of 42.43 months (95% CI 32.04–52.83) compared to 22.24 months (95% CI 14.83–29.58) for non-carriers ( P =0.08). OS was 64.32 months (95% CI 38.09–90.06) for BRCA mutation patients versus 56.63 months (95% CI 50.05–63.21) ( P =0.04) for non-carriers. In multivariate analysis, early stage at diagnosis and optimal debulking were the only independent predictors of better PFS and OS. Conclusion We documented a number of pathogenic BRCA1 and 2 mutations in this patients cohort; two novel mutations were detected. BRCA status seemed to affect survival in ovarian cancer patients.

IntroductionLung cancer is the leading cause of cancer mortality worldwide, despite advances in management, especially with targeted agents and immunotherapy. Numerous oncogenes have been identified that control the growth of these malignancies. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase that develops distorted functioning as a result of chromosomal rearrangement. Crizotinib, a tyrosine kinase inhibitor (TKI), was approved by the Food and Drug Administration (FDA) in 2011 for the treatment of advanced ALK-positive non-small-cell lung cancer (NSCLC).Patients and methodsIn this chart review, we compiled data from two cancer hospitals in Kuwait and Saudi Arabia which were collected from patients with advanced NSCLC treated between January 2013 and September 2017 with crizotinib after diagnosed with ALK-positive disease. Crizotinib 250 mg BID was given orally with/without food intake. We assessed overall survival (OS), objective response rate (ORR), progression-free survival (PFS), duration of the response, and dose reduction/cessation.ResultsDe-identified data from 38 subjects were compiled. Their median age was 53 years, 65.8% were male, the 1-year OS was 88%, and the PFS was 16.5 months. Two cases (5.3%) had a complete response (CR), while 17 (44.7%) had a partial response (PR). Side effects of grade III/IV occurred, including elevated transaminase levels, diarrhea, and prolonged QT intervals, in 8% patients, with dose reduction in six patients (15.8%).ConclusionIn NSCLC, crizotinib is a viable treatment option with good response and tolerable toxicity for patients with ALK-positive advanced disease.

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.

Microbiological bioassay, utilizing sensitive microbial indicator, commonly applied in quality control to determine the potency of antimicrobial agents. This method depends on the biological inhibitory activity of the tested antimicrobial agent on the growth of suitable microbial indicator in comparison to reference standard. The current study aimed to follow up the potency of three of the most prescribed antimicrobial agents namely, amikacin, ceftriaxone, and ciprofloxacin, in various commercial pharmaceutical preparations. The 5 X 1 microbiological bioassay in presence of Staphylococcus aureus ATCC 6538P strain, as a sensitive indicator, was used to evaluate the potency of the tested antimicrobial agents. It was observed that the products decomposition rates varied throughout test intervals; however, the potency of all products remained within the range established by the US Pharmacopeia (USP) by the end of the study. In conclusion, microbiological bioassay using Staphylococcus aureus ATCC 6538P standard strain is appropriate for the assessment of amikacin, ceftriaxone, and ciprofloxacin, in different commercial antimicrobial products, and can be routinely applied in their quality control.