Outcomes of Patients with Metastatic Colorectal Cancer Treated with Trifluridine/Tipiracil beyond the Second Line: A Multicenter Retrospective Study from Saudi Arabia.

Background: The outcome of patients with refractory metastatic colorectal cancer (mCRC) treated with trifluridine/tipiracil (FTD/TPI) beyond the second-line has not been studied in Saudi Arabia. Therefore, this multicenter retrospective analysis was conducted to evaluate the efficacy of FTD/TPI. Methods: This multicenter retrospective analysis included five centers in Saudi Arabia. FTD/TPI was administered to all the patients beyond the oxaliplatin- and irinotecan-based chemotherapy regimens. The electronic medical records were reviewed, and progression-free survival (PFS) and overall survival (OS) were determined. Results: The study included 100 patients with a mean age of 55.4 ± 11.8 years. The overall response to FTD/TPI was 4%. The median PFS was 4 months (95% confidence interval (CI) 3.487-4.513), and the median OS was 11 months (95% CI, 9.226-12.771). In a Cox regression analysis of the independent predictors for PFS, advanced stage of the disease (P = 0.037; HR, 2.614; and CI, 1.102-7.524), presence of lymph node metastasis (P = 0.018; HR, 3.664; and 95% CI, 1.187-8.650), and >2 metastatic sites (P = 0.020; HR, 1.723; and 95% CI, 1.089-2.727) were independent factors predicting disease progression. The Cox regression analysis confirmed that age ≥ 55 years (P = 0.046; HR, 1.667; and 95%, 1.097-3.100), advanced disease stage (P = 0.044; HR, 1.283; and 95% CI, 1.035-2.940), prior use of adjuvant chemotherapy (P = 0.037; HR, 0.892; and 95% CI, 0.481-0.994), liver metastasis (P = 0.025; HR, 2.015; and 95% CI, 1.091-3.720), >2 metastatic sites (P = 0.038; HR, 1.248; and 95% CI, 1.036-1.846), development of neutropenia after receiving first cycle of FTD/TPI (P = 0.042; HR, 1.505; and 95% CI, 1.064-2.167), and increased number of FTD/TPI cycles (P = 0.002; HR, 0.769; and 95% CI, 0.664-0.891) were independent variables for OS. Conclusion: Treatment with FTD/TPI is feasible and effective in daily clinical practice in Saudi Arabian patients. The risk of progression increased with advanced disease stage, lymph node metastasis, bone metastasis, and metastasis to >2 sites. Age ≥ 55 years, advanced disease stage, liver metastasis, metastasis to >2 sites, neutropenia after the first cycle of FTD/TPI, and increased number of FTD/TPI cycles were independent factors predicting mortality.

Assessment of IL-1ß, IL-6, TNF-α, IL-8, and CCL 5 levels in newly diagnosed Saudi patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which mainly affects small joints, occurs most commonly in middle-aged adults, and can be fatal in severe cases. The exact etiology of RA remains unknown. However, uncontrolled expression of pro-inflammatory cytokines and chemokines can contribute to the pathogenesis of RA. AIM: In the current study, we assessed the potential of serum concentrations of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, IL-8, and C-C motif chemokine ligand (CCL)5 as early predictive markers for RA. METHODS: In addition to clinical examination, blood samples were collected from 100 Saudi patients recently diagnosed with early RA for basic and serological tests, including rheumatoid factor (RF), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Sera of 32 healthy individuals were used as controls. Specific enzyme-linked immunosorbent assay was used to quantify the serum IL-1ß, IL-6, TNF-α, IL-8, and CCL5 levels in the samples. RESULTS: Our results indicated that RF, CRP, and ESR levels were higher in RA patients compared to controls. Furthermore, serum levels of IL-1ß, IL-6, IL-8, and CCL5, but not TNF-α, significantly increased in RA patients compared to controls. CONCLUSION: Overall, the findings suggested that IL-1ß, IL-6, IL-8, and CCL5 can be used as biomarkers in the early diagnosis of RA.

Concurrent use of nivolumab and radiotherapy for patients with metastatic non-small cell lung cancer and renal cell carcinoma with oligometastatic disease progression on nivolumab.

Checkpoint inhibitors (CPIs), such as nivolumab, have transformed the treatment paradigm for patients with metastatic non-small cell lung cancer (mNSCLC) and metastatic renal cell carcinoma (mRCC). The combination of CPIs and radiotherapy (RT) constitutes a multimodal treatment approach that may work synergistically and facilitate augmented systemic responses. The aim of the present retrospective study was to assess the efficacy and safety of continuation of nivolumab treatment with the addition of RT in patients with mNSCLC and mRCC who develop oligometastatic disease progression on single-agent nivolumab. All patients with mNSCLC and mRCC who received nivolumab at the Department of Oncology, Prince Sultan Military Medical City (Riyadh, Saudi Arabia) between November 2016 and April 2018 were identified. The records of patients who developed oligometastatic disease progression during nivolumab treatment and were subsequently treated with RT, with nivolumab continued beyond disease progression, were retrospectively reviewed. Details of RT, clinical outcomes and toxicity data were collected. Of the 96 patients who received nivolumab, 22 received multiple courses of RT. A total of 39 sites were irradiated: Bone (n=15), lung (n=9), brain (n=8), adrenal gland (n=2), renal bed (n=2), skin (n=1), ethmoid sinus (n=1) and scalp (n=1). Partial response and complete response were noted at 25 (64%) and 3 (8%) sites, respectively. Stable disease was noted at 6 sites (15%) and disease progression was noted at 5 sites (13%). The median time on nivolumab from the date of the first fraction of RT was 4.5 months (range, 1.5-29 months) for patients with mNSCLC and 5 months (range, 1-38.5 months) for patients with mRCC. No patients developed grade 3-4 toxicities. Grade 2 pneumonitis was noted in 3 patients receiving lung RT. The addition of RT appeared to initiate a response and prolong the duration of nivolumab treatment. Therefore, the combination of nivolumab and RT was found to be well tolerated, with response rates exceeding those in published studies of nivolumab monotherapy.

Efficacy of Nivolumab in a Patient with Metastatic Renal Cell Carcinoma and End-Stage Renal Disease on Dialysis: Case Report and Literature Review.

Treatment of patients with metastatic renal cell carcinoma (mRCC) and end-stage renal disease (ESRD) on dialysis poses a therapeutic challenge, particularly as this patient group was excluded from the pivotal clinical trials. In addition, there is uncertainty regarding drug dosing/pharmacokinetics, lack of safety and efficacy data, and potential for increased toxicity when using targeted therapy or immunotherapy for the management of patients with mRCC on dialysis. Nivolumab, an anti-programmed death-1 immune checkpoint inhibitor antibody, is indicated for the treatment of patients with mRCC who have received prior antiangiogenic therapy. Given the above-mentioned uncertainties, clinicians may be reluctant to use nivolumab for this patient population, leading to potential denial of life-prolonging medications. We report the case of a 72-year-old gentleman with mRCC and ESRD on dialysis who received second-line nivolumab therapy and achieved an excellent symptomatic and radiological response, remaining progression-free for over 22 months. In addition, we have reviewed the pharmacokinetic data and published retrospective case studies to review the management options for patients with mRCC and ESRD on dialysis.

Rare Case of Intracardiac Renal Cell Carcinoma Metastasis with Response to Nivolumab: Case Report and Literature Review.

Intracardiac metastases in the absence of inferior vena cava involvement is a rare occurrence in patients with metastatic renal cell carcinoma (mRCC). There is limited evidence regarding the efficacy and safety of standard treatment modalities for mRCC patients with intracardiac metastases. Presence of intracardiac metastases is known to indicate poor prognosis and may potentially increase risk of treatment-related complications. Recent advances in RCC management have integrated nivolumab, a programmed death-1 (PD-1) receptor inhibitor, as a preferred treatment option in the second-line setting after failure of prior anti-angiogenic therapy; or in combination with ipilimumab, an anti-Cytotoxic T-lymphocyte antigen-4 antibody as first-line therapy for intermediate to poor risk patients with mRCC. The efficacy and toxicity of nivolumab in patients with mRCC and intracardiac metastases has never been reported previously. We herein present the first reported case of mRCC with intracardiac metastasis and a resultant excellent response to nivolumab treatment and discuss the imaging techniques and treatment options for this rare presentation.

To what extent are Arab pilgrims to Makkah aware of the middle east respiratory syndrome coronavirus and the precautions against it?

BACKGROUND: Approximately, 80% of the many cases of the Middle East respiratory syndrome coronavirus (MERS-CoV) confirmed worldwide were diagnosed in the Kingdom of Saudi Arabia (KSA). The risk of the disease spreading internationally is especially worrying given the role of KSA as the home of the most important Islamic pilgrimage sites. This means the need to assess Arab pilgrims' awareness of MERS-CoV is of paramount importance. MATERIALS AND METHODS: A cross-sectional study was carried out during Ramadan 2015 in the Holy Mosque in Makkah, Saudi Arabia. Self-administered questionnaires were distributed to 417 Arab participants at King Fahad Extension, King Abdullah Prayer Extension and, King Abdullah Piazza Extension after Taraweeh and Fajr prayers. RESULTS: The mean MERS-CoV knowledge score was 52.56. Majority of the respondents (91.3%) were familiar with MERS-CoV. Saudis had significantly higher knowledge of MERS-CoV than non-Saudis (56.92 ± 18.55 vs. 44.91 ± 25.46, p = 0.001). Females had significantly more knowledge about consanguineous MERS-CoV than males (55.82 ± 19.35 vs. 49.93 ± 23.66, p = 0.006). The average knowledge was significantly higher in respondents who had received health advice on MERS-CoV (56.08 ± 20.86 vs. 50.65 ± 22.51, p = 0.024). With respect to stepwise linear regression, knowledge of MERS-CoV tended to increase by 14.23 (B = 14.23%, p = 0.001) in participants who were familiar with MERS-CoV, and by 8.50 (B = 8.50, p = 0.001) in those who perceived MERS-CoV as a very serious disease. CONCLUSION: There is a great need for educational programs to increase awareness about MERS-CoV.