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Objective: Bladder cancer (BC) is a significant public health concern in the Middle East and North Africa, but the epidemiology and clinicopathology of the disease and contributors to high mortality in this region remain poorly understood. The aim of this systematic review was to investigate the epidemiological features of BC in the Arab world and compare them to those in Western countries in order to improve the management of this disease. Methods: An extensive electronic search of the PubMed/PMC and Cochrane Library databases was conducted to identify all articles published until May 2022, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. A total of 95 articles were included in the final analysis after title, abstract, and full-text screening, with additional data obtained from the GLOBOCAN and WHO 2020 databases. Results: Most of the included articles were case-control studies examining the risk factors and molecular mechanisms of BC. These studies originated from 10 different countries, with Egypt being the most active contributor. While BC in the Arab world shares some common risk factors with Western countries, such as smoking and occupational exposure, it also exhibits unique features related to schistosomiasis. The high mortality rates in this region are alarming and can be attributed to various factors, including the prevalence of smoking, the impact of schistosomiasis, a combination of genetic and socioeconomic factors, treatment shortages, and limited access to care or inadequate assessment of the quality of care. Conclusion: Despite the relatively low incidence of BC in Arab countries, the mortality rates are among the highest worldwide. BC tends to be more aggressive in the Arab world, making it essential to implement strategies to address this burden.

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Cholangiocarcinoma (CCA) is a rare malignancy with a very poor prognosis. Considering that most cases of CCA are diagnosed at a locally advanced stage and the standard of care for advanced CCA remains suboptimal, new prognostic and predictive biomarkers must be developed to improve the management and survival of patients diagnosed with CCA regardless of disease stage. According to recent studies, 20% of biliary tract cancers exhibit the BRCAness phenotype, meaning that these tumors do not have germline mutations in BRCA but share phenotypic traits with tumors that possess hereditary BRCA mutations. Therefore, screening for these mutations in CCA patients is beneficial to predict tumor sensitivity and response to DNA-damaging chemotherapy such as platinum agents.

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Gallbladder cancer (GBC) is a relatively infrequent but highly lethal cancer with a poor prognosis. Management remains challenging and controversial, and most patients are diagnosed at an advanced stage. However, with the progressive advances in the use of immunotherapies, new treatment modalities are being implemented. In September 2022, the US FDA approved durvalumab (a PD-L1 inhibitor) in combination with chemotherapy for adult patients with locally advanced or metastatic GBC. This groundbreaking news is the first FDA approval for the use of immunotherapy in biliary tract cancers. This article reviews the newest advances and trials regarding immunotherapy for GBC.

Gallbladder cancer (GBC) is a malignant tumor that affects the cells of the gallbladder. Management of this condition is challenging and continuously evolving. Surgery, radiotherapy and chemotherapy are the current standards of care. However, recently, immunotherapy, a treatment that stimulates the host's immune system to target cancerous cells, has proven to be effective as a line of treatment. Promising results are continuously published. This article reviews the major advances in immunotherapy regarding the management of GBC.

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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.

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Esophageal cancer (EC) is relatively frequent and highly lethal cancer, being the sixth most common cause of cancer death worldwide. The progressive approvals of immunotherapy as first-line and second-line treatment options have paved the way for an evolving new approach to the treatment of this disease. Management of esophageal cancer is challenging and requires a multimodality approach. Treatment options include surgery, chemoradiotherapy and, recently, immunotherapy. The newest guidelines and FDA approvals regarding immunotherapy for esophageal cancer are reviewed here.

Esophageal cancer is a malignant tumor that affects the cells in the esophagus. To treat this condition, doctors may use surgery, radiation therapy, chemotherapy and immunotherapy. Depending on the characteristics of the tumor and the medical history of the patient, these treatments may be used alone or in combination to optimize their effects. Immunotherapy is a treatment that aims to stimulate the immune defenses of the body against cancerous cells. Recently, it has proven to be very effective in the management of esophageal cancer, with very favorable results. It is now becoming the standard of care in the management of this disease.

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Aim: This paper presents the reported dermatological adverse events (AEs) associated with approved combinations of immunotherapy with drugs of the same class, or in combination with targeted therapy or chemotherapy. Materials & methods: PubMed was used as an electronic database, and a total of 29 articles were reviewed which reported dermatological AEs following combination therapies with nivolumab, ipilimumab, axitinib, pembrolizumab, lenvatinib, avelumab, atezolizumab, carboplatin, etoposide, paclitaxel, bevacizumab, pemetrexed, cisplatin and durvalumab. Results: The dermatological AEs reported were mutually inclusive and the highest incidence of specific AEs was seen in the following combinations: rash in the nivolumab/ipilimumab and lenvatinib/pembrolizumab combinations, pruritus in the atezolizumab/nab-paclitaxel combination, dry skin and palmar-plantar erythrodysesthesia in the axitinib/pembrolizumab combination, and alopecia and severe skin reactions in the pembrolizumab/carboplatin/paclitaxel combination. Conclusion: Knowledge of such side effects is of benefit when choosing an optimal treatment regimen and should be integrated into the monitoring and follow-up phases of treatment.

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As a developing country, Lebanon lacks adequate awareness about Human papillomavirus (HPV) among its population, whether working in the medical field or not. Lebanon is traditionally considered conservative with a low incidence of sexually transmitted infections in general, but recently the incidence of HPV infections has significantly increased. The present cross-sectional study aims to evaluate the level of awareness on HPV and the attitude toward HPV vaccine among Lebanese medical students in a self-administered questionnaire-based survey. A total of 1009 answers were collected and analyzed from a population of about 3000 Lebanese medical students. Our study revealed a significant lack of knowledge and awareness on HPV among medical students in Lebanon, with a strikingly low vaccination rate (16.4%) due to many barriers. Education initiatives in medical schools remain crucial to raise awareness on HPV and promote HPV vaccination, especially among medical students, who represent the country's future healthcare providers and policymakers.

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Lung cancer is the second most common cancer worldwide and the leading cause of death among cancers. The progressive approvals of immunotherapy as first-line treatment options have helped improve cancer prognosis. However, longer follow-up has confirmed the possibility of acquired resistance to immune checkpoint inhibitors (ICIs) which can lead to late relapses. Chemotherapy can act as a priming therapy to increase a tumor's response to immunotherapy. We aim through this review to explain the mechanism behind ICI resistance and the value of chemotherapy in escaping this resistance. Finally, all US FDA approvals regarding the management of metastatic non-small-cell lung cancer using a combination of ICIs and chemotherapy are summarized.

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Metastatic colorectal cancer is the second most common cause of cancer death. Standard chemotherapy in combination with targeted therapies represent the backbone for the treatment of advanced disease. However, options are limited for patients progressing on these regimens. Genetic testing can offer patients the opportunity to benefit from novel therapies, namely immune checkpoint inhibitors in microsatellite instability-positive tumors. HER2 overexpression has recently emerged as a potentially targetable tumor marker in colorectal cancer (CRC). Despite the absence of approvals for anti-HER2 therapies in CRC, many agents such as trastuzumab and pertuzumab were tested and demonstrated significant antitumor activity, even in heavily pretreated patients. Early trials are also evaluating lapatinib, T-DM1, tucatinib and other anti-HER2 agents in patients with metastatic CRC, with promising results.

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Driving molecular mutations such as rearrangement of ALK and EGFR mutation is present in 5-10% of non-small-cell lung cancer. Tyrosine kinase inhibitors have shown good efficacy and thus become the standard of care. However, tumors have developed several resistance mechanisms against tyrosine kinase inhibitors, including transformation to small-cell lung carcinoma (SCLC). Transformation to SCLC after administration of anti-EGFR in EGFR-mutated adenocarcinoma has been well documented. Similarly, it appears that the same transformation happens in ALK-rearranged adenocarcinoma after the use of anti-ALK. In fact, to date eight cases have been reported in the literature. We aimed in this paper to focus on the characteristics, prognosis and treatment of these transformed SCLC.

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OBJECTIVE: By 2020, 70% of all cancers will occur in patients aged 65years and older, causing an increase in related morbidity, mortality, and cost. This study projects cancer trends in the elderly population in Lebanon, a country experiencing accelerating aging trends. Findings will guide future policy decisions regarding geriatric oncology in Lebanon and the surrounding Arab world. MATERIALS AND METHODS: Cancer incidence rates were derived for men and women 65years and above, divided into three age groups: 65-69years, 70-74years, and 75years and above. Raw data were obtained from the National Cancer Registry reports 2003-2010. The eight consecutive year data were used to project the incidence until 2025 using a logarithmic model. The Average Annual Percent Change in incidence rates was calculated to determine whether it would significantly increase, decrease, or remain stable over time. RESULTS: Incidence rates are projected to increase significantly in all age groups of both genders until 2025. In men, the fastest rise is expected in prostate cancer, followed by bladder, lung, colorectal, and NHL. In women, the rise will be fastest in breast, followed by colorectal, lung, NHL, and ovary. Projected rates increase faster in the "younger" age group 65-69 compared to the "oldest" ≥75, both in men and women. Only kidney and liver cancers continue to rise significantly after 75. CONCLUSIONS: Cancer incidence is projected to increase in individuals between 65 and 74years of age. Lebanese and Middle Eastern physicians must implement adapted therapeutic strategies in the management of the increasing caseload among frail, elderly patients.

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Granulosa cell tumors of the ovaries (GCTO), the most common sex cord tumors of the female genitalia, are characterized by a remarkably favorable prognosis but tend to recur even after several years of follow-up. Standard approach to manage these relapsing tumors is almost inexistent and physicians' choice is most commonly based on his/her personal expertise. Recently, the use of hormone therapy in GCTO has induced prolonged response and survival. In this case report, we report the first successful use of everolimus in the combination of exemestane to reverse the resistance to hormonal therapy with letrozole in a 53-year-old woman with GCTO.

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PURPOSE OF REVIEW: The concept of mutually exclusive oncogenic driver alterations has prevailed over the past decade, but recent reports have stressed the possible occurrence of dual-positive non-small-cell lung cancer (NSCLC) and even triple-positive disease for these oncogenes. This entity presents novel prognostic and therapeutic challenges. The present review highlights the available data in an effort to clarify the clinical and pathological significance of coexisting mutations as well as the subsequent therapeutic consequences. RECENT FINDINGS: Patients with a known driver oncogene can be successfully treated with the appropriate tyrosine kinase inhibitor, which will provide them with significant responses and lesser toxicities compared with cytotoxic therapy. Unfortunately, most patients will eventually progress. Although some resistance mechanisms have been identified, others remain to be determined but the emergence of secondary oncogenes could be part of the answer. SUMMARY: Approximately 20-25% of NSCLC harbor treatable driver mutations/rearrangements; epidermal growth factor receptor mutation, anaplastic lymphoma kinase and ROS-1 gene rearrangements are the main alterations for which a Food and Drug Administration-approved tyrosine kinase inhibitor can be used.Because of recent technological advances, high sensitivity assays with a broad range of genomic targets have become more easily accessible in clinical practice, which has led to an increased detection of coexisting driver alterations in patients with advanced NSCLC. The prognostic/predictive and therapeutic implications of this novel entity are still unsettled for the time being. Randomized trials specifically designed to address this subset of patients will soon be necessary to help determine the optimal therapeutic agent to administer.

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The choice of immunotherapy in the treatment of cancer has improved the prognosis of many patients affected by various malignancies. The high expectations foreseen with immunotherapy have led to fast approvals despite the incomplete understanding of the toxicity profiles in the different organs, including the kidneys. The high prevalence of chronic kidney disease in cancer patients complicates the issue further and requires a better knowledge of the renal safety profile to ensure an optimal safe treatment. This review summarizes the present knowledge of renal adverse events secondary to immune checkpoint inhibitors and discusses their pathophysiology, clinical presentation and adequate management. We also advocate the need for a multidisciplinary approach in patients with immune-related toxic adverse events.

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Immune checkpoint inhibitors (ICI) represent a new revolutionary weapon in the armamentarium of anti-cancer therapies. The side effects of these new agents represent a new challenge for oncologists; they are usually unpredictable and sometimes life threatening, if not managed rapidly and adequately. The most frequent side effects are the dermatologic, but they are usually low grade side effects and consequently easily manageable. Rash, pruritus and vitiligo are the most frequent dermatologic side effects. We aimed in this review to describe first all the dermatologic side effects of ICI according to the subtype of ICI and combination therapies in the clinical trials, then to report all the rare case reports dermatologic side effects, and finally to present the management algorithm of these side effects.

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PURPOSE OF REVIEW: The aim of this review is to draw the attention of the physicians and oncologists on the rare side-effects of checkpoint inhibitors not usually reported in clinical trials to treat them quickly and render their prognosis better. RECENT FINDINGS: Rare side-effects of checkpoint inhibitors are mainly neurologic, haematologic, rheumatologic, renal, and cardiac. The majority of reported side-effects are consequent of the treatment by ipilimumab in patients diagnosed with melanomas. Neurologic side-effects have poorer prognosis compared with other rare side-effects. There is no relationship between developing rare side-effects and the outcome of the disease. SUMMARY: It is important to be aware, when treating patients with checkpoint inhibitors, to detect as early as possible the unpredictable and uncontrollable rare side-effects of these agents. The large spectrum of these rare side-effects should be well documented and reported to assure to the physicians a road map for the diagnosis and the management of these toxicities.

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