Laudy Chehade

Opinion Statement Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by enabling the immune system to effectively target and destroy cancer cells. While ICIs offer significant survival benefits across various malignancies, their use is associated with a unique profile of immune-related adverse events, including potentially fatal cardiovascular toxicities. Recent studies have highlighted various cardiac complications associated with ICIs, such as myocarditis, arrhythmias, heart failure, pericarditis, atherosclerosis, and hypertension. These complications arise from mechanisms involving T-cell activation and cytokine release. Patient-related factors such as pre-existing cardiovascular disease, diabetes mellitus, age, gender, and genetic predisposition, along with treatment-related factors like specific ICI regimens, contribute to these toxicities. To manage these complications effectively, comprehensive cardiovascular risk assessment and monitoring before, during, and after ICI therapy are crucial. Adhering to guidelines from the European Society of Cardiology (ESC) and other international organizations allows for early recognition of cardiovascular toxicities and tailored interventions. This review emphasizes the importance of cardioprotective measures, regular monitoring, and multidisciplinary collaboration between oncologists and cardiologists to mitigate cardiovascular risk and optimize patient outcomes. Ongoing research is essential to better understand the mechanisms of ICI-induced cardiovascular toxicities and to develop effective management strategies for affected patients. As we continue to expand the use of ICIs in oncology, balancing oncologic efficacy with cardiovascular safety remains critical.

Background/Objectives: Predictive tools are needed to assess the response to treatment and guide treatment decisions for locally advanced rectal cancer (LARC). This study explores the value of combining the immunoscore (IS) and magnetic resonance imaging tumor regression grade (mrTRG) with pathologic and radiologic neoadjuvant rectal (NAR) scores in predicting pathologic complete response (pCRs). Methods: The scores were assessed for patients with LARC enrolled in the Averectal study (NCT03503630), who received five fractions of short-course radiotherapy, followed by six cycles of mFOLFOX-6 plus avelumab, and total mesorectal excision. The IS was calculated using the mean density percentiles of CD3- and CD8-positive T-cells on baseline biopsy samples. Baseline and post-treatment MRIs were reviewed to measure the mrTRG. NAR scores were calculated using the pre-treatment T stage and post-treatment pathologic and radiologic N and T stages. Results: Fifteen out of thirty-five patients whose data were available achieved pCR (42.8%), and seven out of fourteen patients with mrTRG = 1 (complete response) attained pCR. In patients with both a mrTRG = 1 and high IS, the pCR rate was 66.7% (6/9). All of the patients who achieved pCR had a low or intermediate pathologic NAR score with a significant correlation between pCR and pathologic NAR scores (p < 0.0001). Both pathologic and radiologic NAR scores were correlated with overall survival and disease-free survival. Conclusions: The IS can supplement the mrTRG to better predict TNT outcomes, along with the use of the NAR score. This combination could potentially help with patient selection for non-operative management and guide treatment strategies for those with different recurrence risks.

Colorectal cancer (CRC) is a significant public health concern, ranking third in incidence and second in mortality worldwide. Despite rising CRC incidence rates in the Arab world, understanding of trends and patterns in CRC screening research remains limited. This study addresses this gap through a bibliometric analysis of CRC screening research in the Arab world from 2007 to 2023. We conducted an extensive literature search in Web of Science and Scopus databases, analyzing 124 articles using the Bibliometrix Package in R. Our findings revealed a 16.5% annual growth in research output, with significant increases from 2014 onwards. Saudi Arabia led in scientific production, followed by Lebanon, Jordan, and Egypt, while Qatar had the highest country production when adjusted for population size. Disparities in research output relative to the CRC burden were evident, especially in lower-resource countries. Three regional clusters were identified: Saudi Arabia, with strong collaborations with Canada and Egypt; a second cluster including Lebanon, UAE, Jordan, Qatar, Iraq, and Oman; and a third cluster featuring Morocco, with significant collaboration with France. Thematic analysis showed a focus on CRC screening awareness, barriers, and adherence but a lack of studies on implementation strategies and cost-effectiveness. This analysis highlights significant trends and gaps in CRC screening research in the Arab world, underscoring the need for increased investment in CRC research and screening initiatives to improve outcomes in the region.

Background: Prostate cancer is a significant global health concern, with rising incidence and disease burden in the Middle East (ME). This review aims to explore the current state of prostate cancer epidemiology in the ME, particularly in low- to middle-income settings, investigating trends in incidence and mortality, assessing challenges related to de novo metastatic prostate cancer, and evaluating the need for region-specific screening guidelines. Methods: We conducted a comprehensive narrative review of epidemiological data on prostate cancer in the ME, examining trends in incidence and mortality, de novo metastatic cases, and current screening practices. Additionally, we assessed the applicability of international guidelines for prostate cancer screening to the ME context. Results: The ME exhibits a rising trend in prostate cancer incidence, with a mortality-to-incidence ratio of 0.3–0.4, compared to 0.1 in the United States, reflecting significant differences in healthcare access and quality that contribute to poorer outcomes. The incidence rates are particularly high in Lebanon, reaching 37.2 per 100,000 in 2012. De novo metastatic prostate cancer is also more prevalent in the ME, often exceeding 20–30%, with a value of 23% reported in Lebanon and reaching 54% in a study including six Middle Eastern countries, compared to 4–14% in the United States. Our review identified a critical need for enhanced screening and early detection efforts tailored to the ME’s unique epidemiological and socio-cultural factors. Conclusions: The substantial burden of de novo metastatic prostate cancer in the ME underscores the need for region-specific screening guidelines. Tailored approaches, including increased awareness, early detection, and resource-stratified strategies, are essential to address the unique epidemiological and socio-cultural factors of the ME and improve patient outcomes.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths. Classically, liver transplantation (LT) can be curative for HCC tumors within the Milan criteria. Bridging strategies to reduce the dropouts from LT waiting lists and/or to downstage patients who are beyond the Milan criteria are widely utilized. We conducted a literature-based review to evaluate the role of systemic therapies as a bridging treatment to liver transplantation (LT) in HCC patients. Tyrosine kinase inhibitors (TKIs) can be used as a systemic bridging therapy to LT in patients with contraindications for locoregional liver-directed therapies. Immune checkpoint inhibitor (ICI) treatment can be utilized either as a monotherapy or as a combination therapy with bevacizumab or TKIs prior to LT. Acute rejection after liver transplantation is a concern in the context of ICI treatment. Thus, a safe ICI washout period before LT and cautious post-LT immunosuppression strategies are required to reduce post-LT rejections and to optimize clinical outcomes. Nevertheless, prospective clinical trials are needed to establish definitive conclusions about the utility of systemic therapy as a bridging modality prior to LT in HCC patients.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths. Classically, liver transplantation (LT) can be curable for HCC tumors within the Milan criteria. Bridging strategies to reduce the dropouts from LT waiting lists or/and to downstage patients who are beyond Milan criteria are widely utilized. We conducted a literature-based review to evaluate the role of systemic therapies as a bridging treatment to liver transplantation (LT) in HCC patients. Tyrosine Kinase Inhibitors (TKIs) can be used as a bridging systemic therapy to LT in patients with contraindication to locoregional liver-directed therapies. Immune Checkpoint Inhibitors (ICIs) treatment can be utilized either as a monotherapy or as a combination therapy with Bevacizumab or TKIs prior to LT. Acute rejection post liver transplantation is a concern in the context of ICIs treatment. Thus, a safe ICI washout period before LT and cautious post-LT immunosuppression strategies are required to reduce post-LT rejections and to optimize clinical outcomes. Nevertheless, prospective clinical trials are needed to establish definitive conclusions about the utility of systemic therapy as a bridging modality prior to LT in HCC patients.

Bladder cancer (BC) poses a significant health challenge, particularly in metastatic cases, where the prognosis is unfavorable and therapeutic options are limited. Poly ADP-ribose polymerase (PARP) inhibitors have gained approval for use in various cancer types, but their application in BC remains controversial, despite the notable prevalence of DNA damage response alterations in advanced or metastatic urothelial carcinomas. In this report, we describe a 66-year-old heavy-smoking female diagnosed with muscle-invasive BC. She underwent multiple rounds of chemotherapy and radiation, yet her disease remained poorly controlled, leading to metastasis in the left obturator internus muscle. Comprehensive genomic profiling through FoundationOne^® Liquid CDx, examining a 324-gene panel using circulating tumor DNA from blood samples, revealed a pathogenic ATM gene alteration (p.Q654fs*10, c.1960delC), suggesting potential eligibility for PARP inhibitor therapy. Remarkably, the patient achieved a complete response to talazoparib, prompting an optimal investigation into BC candidates for this promising therapy.

Targeted monoclonal antibody therapy against Epidermal Growth Factor Receptor (EGFR) is a leading treatment modality against metastatic colorectal cancer (mCRC). However, with the emergence of KRAS and BRAF mutations, resistance was inevitable. Cells harboring these mutations overexpress Glucose Transporter 1 (GLUT1) and sodium-dependent vitamin C transporter 2 (SVCT2), which enables intracellular vitamin C transport, leading to reactive oxygen species generation and finally cell death. Therefore, high dose vitamin C is proposed to overcome this resistance. A comprehensive search strategy was adopted using Pubmed and MEDLINE databases (up to 11 August 2022). There are not enough randomized clinical trials to support its use in the clinical management of mCRC, except for a subgroup analysis from a phase III study. High dose vitamin C shows a promising role in overcoming EGFR resistance in mCRC with wild KRAS mutation with resistance to anti-epidermal growth factor inhibitors and in patients with KRAS and BRAF mutations.