Managing the Adverse Events Associated with Pembrolizumab and Lenvatinib Therapy in Endometrial Cancer.

Endometrial cancer (EC) is the most common gynaecological cancer. The combination of lenvatinib and pembrolizumab has exhibited efficacy as the second line treatment for advanced EC, with a significant benefit in terms of progression free survival (PFS) and overall survival, but the adverse events (AE) profile is complex. AEs associated with the treatment may represent a limitation to this combination. Here, we report the case of a 38-year-old female patient diagnosed with stage IV EC elsewhere, whose disease progressed after the first line of treatment and was referred to a specialised cacncer centre in Muscat, Oman, in 2021. We treated her with the combination of lenvatinib and pembrolizumab. During the course of the treatment, she developed hand-foot syndrome grade III and hypothyroidism grade II. The AEs were managed with supportive medications, dose interruptions, dose reductions and multidisciplinary care, which allowed the continuation of the treatment. The patient achieved a good partial response and an ongoing PFS of more than 12 months.

Clinicopathological Features and Outcomes of Endometrial Cancer: A single institution experience.

Objectives: This study aimed to report the demographic features, clinical presentation, pathological types and long-term outcomes of patients diagnosed with endometrial cancer (EC) in Oman. EC is the sixth most common cancer in women worldwide and the fifth most common cancer in women in Oman. Survival outcomes of EC have not been reported previously from Oman. Methods: This retrospective study was carried out on consecutive patients treated at the Sultan Qaboos University Hospital, Muscat, Oman, between 2008 and 2020. Survival was estimated using the Kaplan and Meier method. Results: A total of 50 patients with EC were included. The median age was 61 years (range: 31-86 years), and 72% of the patients had type I histology. Most patients were diagnosed with stage IA and IB EC (49% and 20%, respectively), and the majority had grade 1 or 2 tumours (40% and 34%, respectively). Overall, the 5-year survival and 10-year survival rates were estimated to be 70% and 56%, respectively. Weight (>75 kg) and body mass index (>30 kg/m2) were significantly associated with better survival. Tumour histology (type I versus type II or carcinosarcoma), grade (1 versus 2 versus 3) and stage (IA or IB versus II-IV) were associated with better overall survival (P = 0.007, P <0.0001 and P <0.0003, respectively). Patients diagnosed with EC with co-morbidities, other than obesity, had inferior survival compared to those without co-morbidities. Conclusion: Median age at presentation, histological sub-type, clinical stage and outcomes are comparable to the published literature. Almost two-thirds of the patients were obese. These data could be used as a benchmark for outcomes of EC in the region.

An Unusual Presentation of Choriocarcinoma in a Postmenopausal Woman: A case report.

Choriocarcinoma (CC) is a malignant neoplasm of the trophoblastic tissue, with a potential to metastasise to distant organs. Limited case of gestational CC develops after a long latent period. We report a 52-year-old postmenopausal woman who developed metastatic choriocarcinoma presumably of gestational origin, 8 years after the last pregnancy and 2 years after the last menstrual period. The patient was brought to the emergency room of a tertiary care centre in Muscat, Oman, in 2022 and was diagnosed with CC metastatic to the brain, spleen, lung and the kidney. The ß-human chorionic gonadotrophin level was found to be raised (1,292,867 mIU/mL). The International Federation of Gynecologic Oncology risk score was calculated to be 14 (very high risk). The patient was initially treated with whole-brain radiotherapy and splenic artery embolisation because of a hemoperitoneum. Afterwards the patient received systemic treatment using the standard EMA/CO regimen till complete serological remission.

Successful Treatment of a Case of Crescentic Glomerulonephritis in a Patient with Primary Peritoneal Carcinoma: A case report.

Crescentic glomerulonephritis has been associated with several solid tumour malignancies. Only a few cases of nephropathy have been reported in association with tubo-ovarian/peritoneal malignancies. We report a 55-year-old female patient who presented to a tertiary care centre, Muscat, Oman, in 2022. She developed combined immune complex-mediated glomerulonephritis and pauci-immune necrotising crescentic vasculitis simultaneously with the diagnosis of tubo-ovarian/peritoneal cancer. The baseline estimated glomerular filtration rate (eGFR) was 13 mL/min. The patient received two doses of rituximab and three doses of pulse corticosteroids, leading to significant improvement in renal function and the disappearance of her proteinuria. The eGFR improved to >60mL/min; her proteinuria gradually resolved after 10 weeks of treatment. She was then given a combination chemotherapy treatment for tubo-ovarian/peritoneal cancer leading to a normalisation of her CA-125 after three months of therapy.

Direct and Moderating Effects of Work Environment and Structural Empowerment on Job Stress and Job Satisfaction Among Nurses in Oman.

Objectives: This study aimed to explore the relationships between nurses' work environment, job stress and job satisfaction, along with the moderating effects of work environment and empowerment on the relationship between job stress and job satisfaction. Methods: A descriptive correlational design was utilised for this study. The study encompassed a convenience sample of 1,796 hospital nurses from the 11 governorates in Oman. Moreover, a self-report questionnaire that included a set of instruments was used to collect the data. Results: Nurses who perceived higher levels of job stress reported lower levels of satisfaction and empowerment and perceived their work environment as less favourable and supportive. The findings only confirmed the direct effects of work environment and empowerment on satisfaction, whereas no support was found for indirect or moderating effects. Furthermore, the hierarchical regression model showed that 46.5% of the variation in the level of job satisfaction was explained by the study variables. Conclusion: The results of this study demonstrate the importance of implementing strategies that empower staff, provide a supportive and positive work environment and tackle job stress to enhance levels of job satisfaction.

Evolution of the Management of Brain Metastases: A Bibliometric Analysis.

A systematic review of the published literature was conducted to analyze the management evolution of brain metastases from different cancers. Using the keywords "brain metastasis", "brain metastases", "CNS metastasis", "CNS metastases", "phase III" AND/OR "Randomized Controlled Trial" (RCT), relevant articles were searched for on the SCOPUS database. A total of 1986 articles were retrieved, published over a 45-year period (1977-2022). Relevant articles were defined as clinical studies describing the treatment or prevention of brain metastases from any cancer. Articles on imaging, quality of life, cognitive impairment after treatment, or primary brain tumors were excluded. After a secondary analysis, reviewing the abstracts and/or full texts, 724 articles were found to be relevant. Publications significantly increased in the last 10 years. A total of 252 articles (34.8%) were published in 12 core journals, receiving 50% of the citations. The number of publications in Frontiers in Oncology, BMC Cancer, and Radiotherapy and Oncology have increased considerably over the last few years. There were 111 randomized controlled trials, 128 review articles, and 63 meta-analyses. Most randomized trials reported on brain metastases management from unselected tumors (49), lung cancer (47), or breast cancer (11). In the last 5 years (2017 to 2022), management of brain metastasis has moved on from WBRT, the use of chemotherapy, and radio-sensitization to three directions. First, Radiosurgery or Radiotherapy (SRS/SRT), or hippocampal-sparing WBRT is employed to reduce radiation toxicity. Second, it has moved to the use of novel agents, such as tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) and third, to the use of molecularly directed therapy such as TKIs, in asymptomatic low volume metastasis, obviating the need for WBRT.

The Prevalence and Patterns of Toxicity With Immune Checkpoint Inhibitors in Solid Tumors: A Real-World Experience From a Tertiary Care Center in Oman.

Introduction Immune checkpoint inhibitors (ICIs) have revolutionized the management of multiple cancers over the last decade. They work by employing the immune system and exhibiting activity over T cells resulting in immune upregulation. Despite their widespread use, they produce side effects that can limit their use. The immune-related adverse events (irAEs) can be sometimes significant. The irAEs caused by ICIs may occur at any time during the treatment and can vary in grade (G). We sought to study the prevalence and toxicity patterns of ICIs in Oman. Methods One hundred forty-one adult patients (≥18 years) who received at least one dose of nivolumab, pembrolizumab, atezolizumab, or durvalumab between 2016 and 2022 were included. The data were analyzed retrospectively using univariable and multiple-variable logistic regressions. The Wilcoxon rank-sum test and Cochran-Armitage trend test were also used to summarize the continuous and ordinal data. Results Out of the 141 patients, 80 patients (56.7%) received pembrolizumab, and 48 (34%) received nivolumab. Common irAEs included endocrine abnormalities, pneumonitis, and colitis. Thirty patients (21.3%) experienced varying irAE grade toxicity. Out of the 30, 23 patients (82%) developed grade 2 and 3 irAEs. Discussion Predictive analysis showed that male sex and lower hemoglobin (Hb) and bilirubin levels were all significant predictors (p < 0.05) when associated with irAE occurrence. The prevalence of irAEs was similar compared to other reports, literature reviews, or meta-analyses. Female sex has been mentioned previously also to be a predictive factor for endocrine-related toxicities.

Determinants of Physicians' Job Satisfaction: A national multi-centre study from the Sultanate of Oman.

Objectives: This study aimed to examine and assess job satisfaction of physicians across several factors, such as quality of care, ease of practice, relationship with leadership and inter-professional collaboration. Methods: The data for this descriptive cross-sectional study were collected between July 2019 and January 2020. Participants provided demographic information and completed surveys related to physician job satisfaction and inter-professional collaboration. Multiple linear regressions were used to determine the relationship between overall job satisfaction and demographic features and inter-professional collaboration. Results: Out of the 396 physicians contacted, 354 responded (response rate: 89.4%). Results showed that out of the 354 physicians, 4.3% were not satisfied with their jobs, 36.5% expressed a moderate level of satisfaction and 59.2% were highly satisfied. There was no difference in the mean job satisfaction score among different groups of study participants, except for gender and the working grade (P <0.05). The overall job satisfaction rates were higher for the quality of care (mean = 3.93 ± 0.61) and ease of practice (mean = 3.89 ± 0.55) and lower for relationship with leadership (mean = 3.67 ± 0.86). Having a clinical postgraduate degree together with a PhD, a senior level of responsibility and good inter-professional relationship were associated with higher job satisfaction rates (P = 0.003 and 0.007, respectively). Conclusion: Overall, the job satisfaction rate was high. There was no difference among different groups of study participants, except for the working grade. Having a clinical postgraduate degree, a senior level of responsibility and good inter-professional relationship were associated with higher job satisfaction rates. The overall job satisfaction rates were higher for the quality of care and for ease of practice and lower for relationship with the leadership. Relationship with leadership is a modifiable factor and efforts at enhancing the physician-leadership relationship may lead to even higher satisfaction rates.

Predictors of Hypersensitivity Reactions to Platinum-Based Chemotherapy in a Tertiary Care Hospital in Oman: A case control study.

Objectives: This study aimed to estimate the prevalence and evaluate risk factors of hypersensitivity reactions (HSRs) to platinum-based compounds (PBCs) in cancer patients. PBCs play an important role in cancer therapy. However, one of the drawbacks of PBCs is the occasional occurrence of HSRs, which can lead to serious consequences. Methods: This retrospective case control study was conducted from January 2013 to December 2020 at Sultan Qaboos University Hospital, Muscat, Oman and included patients who received any PBC for the management of non-haematological cancers. Data regarding demographic characteristics and diseases and treatment details were collected from the hospital's electronic database. The data were quantitatively described and Student's t-test and Wilcoxon Mann-Whitney tests were used to detect significant differences. Results: A total of 38 cases and 148 matched controls were studied. The prevalence of HSRs to PBCs in the cohort of this study was 4.7% (95% confidence interval: 3.33-6.37%), higher with carboplatin compared with cisplatin and oxaliplatin. The female gender (P = 0.032), concomitant taxanes (P = 0.002) and concurrent radiation (P <0.001) were significant predictors of HSRs to PBCs. The majority of the reactions were of mild to moderate severity, and the rechallenge rate after HSR development was 13%. Conclusion: HSRs to PBCs impact therapy decisions and understanding the risk factors is important to improve treatment outcomes in cancer patients.

Durable Response to Pazopanib in a Patient with Fumarate Hydratase-Mutant Tubulocystic Renal Cell Carcinoma.

Tubulocystic carcinoma of the kidney (TC-RCC) is a rare renal tumor and has been recently included as a distinct entity in WHO classification of renal neoplasms. We report the case of a patient with metastatic tubulocystic RCC whose disease progressed through standard of care treatment for nonclear RCC. However, genetic analysis revealed a germline pathogenic variant of fumarate hydratase (FH) gene, and the patient had a sustained and durable response to pazopanib.

Identification and validation of a novel long non-coding RNA (LINC01465) in ovarian cancer.

Epithelial Ovarian Cancer (EOC) is a heterogeneous disease usually diagnosed at advanced stages. Therefore, early detection is crucial for better survival. Despite the advances in ovarian research, mechanisms underlying EOC carcinogenesis are not elucidated. We performed chromatin immunoprecipitation sequencing to identify genes regulated by E2F5, a transcription factor involved in ovarian carcinogenesis. Results revealed several putative candidate genes (115 protein-coding genes, 20 lncRNAs, 6 pseudogenes, and 4 miRNAs). A literature review and bioinformatics analysis of these genes revealed a novel lncRNA candidate (LINC01465) in EOC. We validated LINC01465 by quantifying its expression in EOC cell lines and selected OVSAHO and SKOV3 as a model with high LINC01465 levels. We silenced LINC01465 and performed proliferation, wound healing, invasion, and drug resistance assays. Knocking-down LINC01465 resulted in reduced migration, suggesting potential involvement in EOC. Furthermore, to identify the significance of LINC01465 in chemoresistance, we assessed the LINC01465 levels in A2780 S cells treated with malformin, which revealed higher LINC01465 expression as compared to untreated A2780S cells implying the involvement of LINC01465 in cell death. Thus, this study unraveled the repertoire of E2F5 regulated candidate genes and suggested a putative role of LINC01465 in malformin-induced cell death in EOC.

Addition of Gallic Acid Overcomes Resistance to Cisplatin in Ovarian Cancer Cell Lines.

OBJECTIVE: Ovarian cancer is one of the leading causes of cancer-related mortality in women, and is often associated with drug resistance. Therefore, finding effective drugs, including naturally derived compounds, is urgently needed. Herein, we aimed to test the anti-cancer potential of gallic acid monohydrate (GA) and its congeners on cisplatin-sensitive (A2780S), and resistant (A2780CP) ovarian cancer and normal ovarian (HOSE6-3) cell lines. METHODS: Cytotoxicity was assessed by AlamarBlue and CCK08 assays by exposing cells to different concentrations of cisplatin (0-21µg/mL), GA and its congeners (0-100µg/mL), and a combination of GA and cisplatin. Apoptosis was estimated by Hoechst stain and monitoring the relative RNA expression of the apoptotic effector caspase-3 using qRT-PCR. RESULTS: GA decreased cell viability in a concentration-dependent manner in all cell lines, with an IC50 of 19.39µg/mL (A2780S), 35.59 µg/mL (A2780CP), and 49.32µg/mL (HOSE6-3). GA displayed higher cytotoxicity than its congeners. An apoptotic rate estimation of approximately 20% and 30% was obtained in A2780S and A2780CP. While the cytotoxicity observed with cisplatin and GA was comparable, combining the two enhanced the cytotoxicity significantly, especially in the A2780CP cell line (p<0.05). CONCLUSION: These data suggest that GA may help overcome the resistance. Hence, the cytotoxic effects of GA, especially on chemo-resistant ovarian cancer cells merit further investigation.
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A Comparison of Two Scales to Determine Prevalence of Mood Disorders in Omani Patients Recently Diagnosed with Cancer.

OBJECTIVES: Studies on the prevalence rate of mood disorders in patients recently diagnosed with cancer from Middle East are scare in the literature. Therefore, this study assesses the prevalence rates of anxiety and depression, and their associations with socio-demographic factors, in recently diagnosed patients with cancer living in the Sultanate of Oman. METHODS: In this prospective study, adult patients were interviewed within the first three months of diagnosis of cancer using the Hospital Anxiety and Depression Scale (HADS), and the Centre for Epidemiological Studies Depression (CES-D) Scale. Associations were studied among symptoms of anxiety and depression, and the socio-demographic factors, along with levels of agreement between the two scales. RESULTS: Eighty-nine patients were interviewed, and 65% were females. Using the HADS tool, 41.6% of patients had anxiety, 28% had depression, whereas 5.6% displayed severe depression. Using the CES-D tool, 41.6% of patients had depression, and 11.2% had severe depression. A fair correlation between the CES-D and HADS tools was evidenced with a Cohen's Kappa coefficient value of 0.37 (P<0.001). The socio-demographic factors were not significantly associated with the presence of anxiety and depression (P >0.05). CONCLUSION: Collectively, these findings indicate high prevalence rates of anxiety and depression in Omani patients recently diagnosed with cancer along with a significant correlation between the two scales. These results support the implementation of screening tools early in the trajectory of cancer illness to improve the overall healthcare of these patients.

Clinicopathological Features, Treatment, and Outcome of Omani Patients with Metastatic Prostate Cancer.

OBJECTIVES: Prostate cancer (PCa) is the third most common cancer worldwide, with its incidence rising in the Middle East. There is a paucity of data about the clinicopathological features and outcomes of metastatic prostate cancer (mPCa) from the Middle East. We report the outcomes of mPCa from Oman. METHODS: We recruited consecutive men diagnosed with mPCa and treated at Sultan Qaboos University Hospital in Oman between January 2006 and December 2017. Information about demographics, clinical, laboratory, pathological, and radiological features at presentation, treatment, and survival outcomes was collected. Data were gathered until April 2019 or until the patient's death for progression-free survival (PFS) and overall survival (OS), whichever came first. Survival rates were estimated using the Kaplan-Meier method. Univariate and multivariate analysis and Cox regression analyses were performed to study factors affecting the PFS and the OS. RESULTS: Of the 239 men diagnosed with PCa over the study period, 62 were diagnosed with mPCa. The median age was 71 (range = 57-92) years. The majority of patients (61.3%) had a Gleason score ≥ 8. Median prostate-specific antigen (PSA) level was 100.0. Bone was the most common site of metastatic disease (90.3%). The majority of patients with the hormone-sensitive disease were treated with testosterone suppression only, while abiraterone, enzalutamide, and docetaxel were added for treating metastatic castration-resistant mPCa (mCRPC). After a median follow-up of 34.5 months, the median PFS was 17 months, while the median OS was 43 months. Median survival post mCRPC was 17 months. CONCLUSIONS: Omani patients with mPCa present with high PSA and Gleason score and with widespread metastatic disease burden. Treatments offered are according to internationally accepted standards and have comparable PFS and OS as reported elsewhere.

Relationship between interprofessional teamwork and nurses' intent to leave work: The mediating role of job satisfaction and burnout.

BACKGROUND: Reducing nurse turnover is a top priority for nursing management globally. While evidence has demonstrated that working in a favorable environment with greater interprofessional teamwork is essential in increasing nurse retention, few studies have explored the mechanism underlying this relationship. AIM: To examine the direct and indirect effects of interprofessional teamwork on nurses' intentions to leave their jobs via the intermediary roles of job satisfaction and burnout. METHODS: A cross-sectional study was conducted to collect data from 2113 nurses working in 21 hospitals in Oman. Data were collected using a survey questionnaire measuring teamwork, job satisfaction, burnout, and intention to leave. Logistic regression was used to investigate the direct effect of teamwork on intent to leave. A sequential mediation model was conducted to examine the mediating role of job satisfaction and burnout. RESULTS: Interprofessional teamwork was directly associated with nurses' intentions to leave. The influence of teamwork on intention to leave was indirectly mediated by both job satisfaction and job burnout. CONCLUSION: Findings illustrate the potential benefits of enhancing interprofessional teamwork in reducing nurses' intentions to leave. Interventions intended to foster teamwork could create satisfying workplaces, reduce perceived burnout, and ultimately contribute to organizational strategy for reducing nursing shortages.

Beliefs and Perceptions About Cancer Diagnosis and Treatment-Seeking and Decision-Making Behaviors Among Omani Patients with Cancer: A Single-Center Study.

A cancer diagnosis is associated with anxiety and psychological distress. Cultural and societal factors greatly affect the complex process of coping mechanisms and decision making. Omani patients receiving cancer treatment at Sultan Qaboos University Hospital in Oman were interviewed about their perceptions regarding cancer, treatment, outcome, and decision making. Out of a total of 360 approached, 216 patients consented. The median age was 42 years. The results showed that 60.6% of patients considered cancer diagnosis as a test from God, 13.9% considered it as a result of an evil eye, 40% believed prayers treat cancer. Fifty-six percent of participants wanted to make treatment decisions themselves, while 2.3% preferred their family to make decisions. Our findings suggest that perceptions about cancer in Oman are specific and are associated with religion and sociocultural background.

Hymenialdisine is Cytotoxic Against Cisplatin-Sensitive but Not Against Cisplatin-Resistant Cell Lines.

OBJECTIVES: New compounds are needed to overcome the resistance to commonly used cytotoxic chemotherapy for epithelial ovarian cancer. Marine sponges are a rich source of diverse chemical compounds and hymenialdisine has been found to have antiproliferative effects. This study aimed to investigate the cytotoxic effect of hymenialdisine in cisplatin-sensitive and cisplatin resistant ovarian cancer cell lines. METHODS: This study took place at Sultan Qaboos University, Muscat, Oman between August and November, 2019. The anti-cancer effects of hymenialdisine or cisplatin were assessed using treating cells with different concentrations of hymenialdisine and cisplatin. Cell viability was determined using the AlamarBlue® Assay. RESULTS: The half-maximal inhibitory concentration (IC50) of cisplatin was estimated at 31.4 µM for A2780S and 76.9 µM for A2780CP, whereas the IC50 of hymenialdisine was evaluated at 146.8 µM for A2780S cells. Despite the higher concentrations of hymenialdisine (up to 300 µM), IC50 could not be determined for the A2780CP cell line. CONCLUSION: When compared to cisplatin, hymenialdisine was less toxic against both A2780S and A2780CP ovarian cancer cell lines.

COVID-19 and the Clinical Phase of the Medical Doctorate Curriculum in Oman: Challenges and the way forward.

COVID-19 has gripped the world with lightning speed. Since the onset of the pandemic, activity throughout the world came to a grinding halt. However, business had to continue and people have to learn to live with the virus while the pandemic continues to rage. Medical education is no exception and may even deserve special mention, as it prepares frontline workers against the endemics of tomorrow. We discuss here the journey of medical education at the College of Medicine and Health Sciences at Sultan Qaboos University, Muscat, Oman, as the pandemic struck the world and Oman. This work suggests a roadmap for changes, discusses challenges and proposes measures to mitigate the effects of COVID-19 on medical schools.

Clinicopathological Features and Outcomes of Gastrointestinal Stromal Tumours in Oman: A multi-centre study.

OBJECTIVES: This study aimed to report the clinicopathological features, management and long-term outcomes of patients with gastrointestinal stromal tumours (GISTs) in Oman. METHODS: This retrospective study was conducted on patients treated for GIST between January 2003 and December 2017 at three tertiary referral centres in Muscat, Oman. All patients with confirmed histopathological diagnoses of GIST and followed-up at the centres during this period were included. Relevant information was retrieved from hospital records until April 2019. RESULTS: A total of 44 patients were included in the study. The median age was 55.5 years and 56.8% were female. The most common primary site of disease was the stomach (63.6%) followed by the jejunum/ileum (18.2%). Two patients (4.5%) had c-Kit-negative, discovered on GIST-1-positive disease. A total of 24 patients (54.5%) presented with localised disease and eight (33.3%) were classified as being at high risk of relapse. Patients with metastatic disease received imatinib in a palliative setting, whereas those with completely resected disease in the intermediate and high-risk groups were treated with adjuvant imatinib. Of the six patients (13.6%) with progressive metastatic disease, of which four had mutations on exon 11 and one on exon 9, while one had wild-type disease. Overall, rates of progression-free survival and overall survival (OS) at 100 months were 77.4% and 80.4%, respectively. Rates of OS for patients with localised and metastatic disease were 89.9% and 80.2%, respectively. CONCLUSION: The presenting features and outcomes of patients with GISTs in Oman were comparable to those reported in the regional and international literature.