How to find a needle in a haystack: a systematic review on targeting KRAS wild-type pancreatic cancer.

Aim: Pancreatic adenocarcinoma is a very aggressive type of cancer, in which targeted therapies have not yet been fully utilized. KRAS wild-type pancreatic adenocarcinoma tumors are associated with different genomic alterations in comparison to KRAS mutated pancreatic adenocarcinoma. Objective: This systematic review aims to provide a one-stop summary of all these alterations, their proposed targeted treatment and their effect on disease progression. Methods: An electronic search strategy was elaborated in the PubMed database between 2020 and January 2024. Results: 21 studies were included, and we found that the most frequent targetable genomic alterations in KRAS wild-type pancreatic adenocarcinoma were BRAF, EGFR, FGFR, MSI-H/dMMR, Her2/ERBB2 amplification, BRCA1/2 and other HRDs, and gene fusions like ALK, NTRK and NRG1.

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Supplement use and its impact on daily life of cancer patients: a cross-sectional study.

PURPOSE: This cross-sectional study aimed to investigate the prevalence and characteristics of supplement usage among cancer patients and explore its potential associations with anxiety, excessive daytime sleepiness, and overall quality of life. METHODS: Cancer patients receiving specific care at Hôtel Dieu de France University Hospital, Beirut, were enrolled between April and June 2023. In face-to-face interviews, participants were asked to complete a questionnaire consisting of sociodemographic information, supplement usage details, and cancer-related variables. Three validated surveys (Epworth Sleepiness Scale, GAD-7, and EORTC-QLQ-C15-PAL) were employed to assess excessive daytime sleepiness, anxiety, and overall quality of life. Statistical analyses, including chi-square tests, t-tests, and multiple regression models, were conducted to examine associations between supplement use and other variables. RESULTS: A total of 202 participants were interviewed. Fifty-two percent reported regular use of supplements following their cancer diagnosis, with vitamin D being the most commonly used supplement. Using multivariate logistic regression, supplement use was associated with being female, having lower educational levels, having a longer duration since cancer diagnosis, and having a poor overall quality of life. The multivariate logistic regression showed no significant correlation between supplement use and excessive daytime sleepiness and anxiety. CONCLUSION: This study highlights a high prevalence of supplement usage among cancer patients in Lebanon, indicating a rising interest in alternative therapies aimed at enhancing quality of life. Larger prospective studies are needed to assess the relation between supplement intake and excessive daytime sleepiness and anxiety and establish clear guidelines pertaining to supplement use in cancer patients.

Landscape of HER2-low breast cancer: Insights from a six-year study on prevalence and clinicopathological characteristics.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer has emerged as a subtype of breast cancer, defined by HER2 1+/2+ in immunohistochemistry (IHC) and absence of ERBB2 gene amplification on fluorescence in situ hybridization (FISH). Recent trials showed marked response of HER2-low breast cancer to novel anti-HER2 antibody-drug-conjugates. Data on characteristics of HER2-low breast cancer subtype is limited. Real-world data from the Anatomic Pathology Department of Hotel-Dieu de France, spanning 2017-2023, was retrospectively collected. HER2-positive patients were excluded to compare HER2-low to HER2-zero breast cancer subtypes. Clinicopathological characteristics between the groups were compared using a Chi-Squared test. Out of 1195 patients, we observed 341 (28.5 %) HER2-low breast cancers cases. HER2-positive breast cancer cases (n = 178; 14.9 %) were excluded. There was no significant difference in age and sex between HER2-low and HER2-zero group (p = 0.33 and 0.79, respectively). HER2-low breast cancer was associated with positive estrogen receptor status and positive progesterone receptor status (p < 0.001 and p = 0.01, respectively). Ductal adenocarcinomas were more commonly observed in HER2-low group (p < 0.001). When stratified by hormone (HR) status, 87.4 % of patients had HR-positive status and 12.6 % were HR-negative. Among the HR-negative group, HER2-low tumors tended to show lower proliferation index compared to HER2-zero tumors (25%vs.10 %, p = 0.04). This study showed that HER2-low is distinct from HER2-zero and is common among patients with breast cancer. Clinicopathological features such as histological type differ between HER2-zero and HER2-low breast cancer. Within HR-negative breast cancer, those with low HER2 expression exhibit a less aggressive profile compared to HER2-zero tumors.

Moving away from chemotherapy in newly diagnosed Philadelphia chromosome-positive B-cell acute lymphoblastic leukaemia.

Chemotherapy-free regimens are reshaping the treatment landscape of Philadelphia chromosome-positive acute lymphoblastic leukaemia. The report by Xie et al. suggests that the combination of dasatinib and prednisone is effective as induction and early consolidation. Survival was improved in patients who subsequently underwent allogeneic stem cell transplantation. Commentary on: Xie et al. Dasatinib plus prednisone as induction and consolidation for adults with Ph-positive acute lymphoblastic leukaemia: A single-arm, multicentre, phase 2 trial. Br J Haematol 2023;202:1119-1126.

Mesenchymal stem cells: a trojan horse to treat glioblastoma.

Glioblastoma multiforme (GBM) is the most common and lethal primary tumor of the central nervous system. What makes it so dreadful is the very low survival rate, despite the existence of a standard treatment plan. An innovative and more effective way to treat glioblastoma based on Mesenchymal Stem Cells (MSCs) has been explored recently. MSCs are a group of endogenous multipotent stem cells that could mainly be harvested from adipose tissue, bone marrow, and umbilical cord. Having the ability to migrate toward the tumor using multiple types of binding receptors, they could be used either as a direct treatment (whether they are enhanced or not) or as a delivery vehicle carrying various anti-tumoral agents. Some of these agents are: chemotherapy drugs, prodrug activating therapy, oncolytic viruses, nanoparticles, human artificial chromosome… Promising results have started to surface; however, more evidence is needed to perfect their use as a glioblastoma multiforme treatment option. Alternative treatment, using unloaded or loaded MSCs, leading to a better outcome.

Beyond the Horizon: A Cutting-Edge Review of the Latest Checkpoint Inhibitors in Cancer Treatment.

Immune checkpoint inhibitors (ICIs) have emerged as a revolutionary paradigm in oncology, offering a potent arsenal against various malignancies by harnessing the body's own immunological prowess. In a whirlwind of advancement, an abundance of new ICIs have come to light, rendering it a Herculean task for physicians to remain au courant with the rapidly evolving landscape. This comprehensive review meticulously explores the crescendo of clinical investigations and FDA approvals that have come to light during 2022 and 2023, showcasing the metamorphic impact of ICIs in cancer therapeutics. Delving into the pith of pivotal Phase 3 trials across diverse cancer types - including lung, renal, melanoma, and more - the review illuminates the significant strides made in enhancing patient outcomes, alongside the unveiling of novel ICIs that have garnered attention in the oncological community. The analysis extends to the notable presentations at the esteemed ESMO and ASCO conventions, providing a panoramic view of the contemporary advancements in ICI technology. Furthermore, the review underscores the imperative of continuous exploration in overcoming the extant challenges, such as the quest for reliable predictive biomarkers and the optimization of combinatorial strategies to surmount resistance and augment therapeutic efficacy. Through a holistic lens, this article elucidates the monumental impact of ICIs, marking a significant epoch in the odyssey towards rendering cancer a conquerable adversary.

Immune checkpoint inhibitors in BRAF-mutated advanced colorectal cancer.

Colorectal cancer has been around for a long time, but is still a challenge nonetheless. However, the heterogeneity of the disease opens new potential therapeutic doors. BRAF-mutated advanced colorectal cancer is a demanding entity that does not respond to standard chemotherapy regimens (FOLFOX, capecitabine) and the presence of the mutation significantly weakens the prognosis, but the rise of immunotherapy could reverse the trend. Indeed, pembrolizumab and nivolumab have boasted promising outcomes and increased survival rates among this subset of patients. This article is a collection of these results which could potentially bring immunotherapy to the front line.

Genetic markers of chronic lymphocytic leukemia: a retrospective study of 312 patients from a reference center in Lebanon.

Aim: Chronic lymphocytic leukemia (CLL) is a highly heterogenous hemopathy. Genetic stratification of CLL patients has important prognostic and therapeutic values - mainly immunoglobulin heavy chain variable region gene (IGHV) mutational status and the presence of cytogenetic abnormalities. The genetics of CLL in Lebanon is scarcely described in the literature. Patients & methods: In this work, we studied the genetic biomarkers of 312 Lebanese CLL patients. Results: Prominent IGHV genes were IGHV4-34, IGHV1-69 and IGHV3-30; and CLL #1 and #5 presented major subsets. Some similarities as well as major differences were highlighted when comparing our data with previously published data. Conclusion: The distribution of IGHV alleles in our series differed from previously described distributions, suggesting involvement of antigenic selection and regional variables in CLL pathogenesis.

The first Middle East and North Africa expert consensus recommendations for management of advanced gastric cancer.

Gastric cancer (GC) ranks as the fifth most prevalent cancer and the fourth deadliest cancer worldwide. In the Middle East and North Africa (MENA) region, GC represents about 4.8% of cancer cases with more than 35,000 new cases in 2020. To strengthen and improve the management of this cancer in the region, a group of MENA experts in the field of GC developed the first MENA consensus recommendations for the management of advanced GC. A total of 28 statements were drafted, discussed and voted on, using a modified Delphi process, during a virtual consensus meeting. The statements addressed the areas of epidemiology, biomarkers and treatment.

A prospective, real-world, multinational study of febrile neutropenia (FN) occurrence in oncology patients receiving chemotherapy with intermediate risk of FN: a MASCC Neutropenia, Infection, and Myelosuppression Study Group initiative.

PURPOSE: Limited knowledge is available on the incidence of febrile neutropenia (FN) in intermediate-risk patients and the rationale for use of granulocyte colony-stimulating factor (G-CSF) in these patients. We aimed to estimate the rate at which patients associated with intermediate risk (10-20%) of FN would develop ≥ 1 episode of FN with a commonly used chemotherapy regimen in clinical practice. METHODS: This prospective, real-world, observational, multinational, multicenter study (December 2016-October 2019) recruited patients with solid tumors or Hodgkin's/non-Hodgkin's lymphoma. Patients receiving chemotherapy with intermediate risk of FN, but not G-CSF as primary prophylaxis were included and observed for the duration of the chemotherapy (≤ 6 cycles and ≤ 30 days after the last chemotherapy administration). RESULTS: In total, 364 patients (median age, 56 years) with 1601 cycles of chemotherapy were included in the analysis. The incidence of FN was 5% in cycle 1, 3% in cycles 2-3, and 1% in cycles 4-6. The rate of patients with ≥ 1 episode of FN was 9%, and 59% of FN events were reported during cycle 1. The rate of grade 4 neutropenia in cycle 1 was 11%, and 15% of patients experienced ≥ 1 episode of grade 4 neutropenia. CONCLUSIONS: Overall, the incidence of FN was low, with a high incidence in cycle 1 and a decrease in the subsequent cycles. These results provide the real FN risk for common chemotherapy regimens in patients generally excluded from clinical trials. Prophylactic G-CSF in intermediate-risk patients could be considered as per clinician's judgement.

Cognitive functions of patients treated with chemotherapy: A comparative study.

OBJECTIVES: Chemobrain is a well-established clinical syndrome that has become an increasing concern because of the growing number of long-term cancer survivors. It refers to the post-chemotherapy related cognitive dysfunction. The aim of this study was to objectively assess the impact of cancer treatment on the cognition of cancer patients. METHODS: This was a convenience sample comparative study conducted at the Hematology and Oncology Department of Hôtel Dieu de France University Hospital in Beirut, Lebanon. It included cancer patients (G1) aged under 65 years who had already been treated for cancer compared to two control groups. The first control group (G2) consisted of treatment-naïve cancer patients aged under 65, and the second group (G3) was recruited from a pool of healthy controls aged between 40 and 65 years. All participants were asked to complete the part B of the trail making test (TMT) and the digital symbolic substitution test (DSST). RESULTS: In the bivariate analysis, patients in G1 had significantly higher scores than patients in G2 (P=0.017) and G3 (P<0.001) on the TMT-B. However, patients in G1 only had lower scores on DSST when compared with G3 (P=0.017). In the logistic regression taking different groups two-by-two as the dependent variable, the only significant difference was found in the comparison between G2 and G3 with higher TMT-B scores more in favor of belonging to G2 (OR=0.946; P=0.003). CONCLUSIONS: Our results suggest that, after controlling for anxiety and depression symptoms, patients treated with chemotherapy have significantly poorer outcomes on the DSST and TMT-B than treatment-naïve cancer patients and healthy controls. However, when taking confounding factors into account, the difference only persisted between patients undergoing chemotherapy and healthy controls. These findings are in favor of a multifactor cognitive impairment in patients with cancer partially related to chemotherapeutic treatment.

First advanced course on biomarkers in molecular and immuno-oncology in the Middle East.

The first 'advanced course on biomarkers in molecular and immuno-oncology' in the Middle East took place in Beirut, Lebanon, as a hybrid meeting on 11 December 2020. The aim of this seminar was to discuss biomarker development, implications and detection modalities and to highlight advances in molecular technologies as well as the clinical applicability of biomarkers in oncology. The seminar consisted of five sessions, each discussing a special topic in the biomarker field. It also included a competition in the form of a quiz following each session. This was followed by a plenary session presented by well-known national and international speakers, highlighting various aspects of biomarkers in immuno-oncology.

YouTube as a source of information on breast cancer in the Arab world.

BACKGROUND: The general population is increasingly using YouTube as a source of information on breast cancer, the most frequent cancer among women. Arabs are the most interested population in breast cancer on YouTube. The transmission of accurate information is important to reduce mortality rates. This cross-sectional study aims to evaluate breast cancer videos on YouTube in the Arab world. METHODS: A YouTube search for "breast cancer" in Arabic was performed. The most viewed 60 videos included were evaluated for global quality (GQS score), reliability (modified DISCERN score), content (content score), and misleading claims. Recorded and calculated data included views, duration, videos power index, and viewers' interaction. Sources from legal persons (governments, universities, TV channels, physicians' groups), and blogs (online health channels, individuals) were categorized. RESULTS: The median global quality (3/5), reliability (2/5), and content scores (4/11) were overall low. Misleading information was found in 42% of the videos. Although videos uploaded by legal persons were less popular (163,454 vs 327,488 views), they hosted more physicians (52% vs 15%), were less misleading (15% vs 64%), covered more content, and were of higher global quality and reliability than videos uploaded by blogs [p < 0.05]. While the topic of symptoms (55%) was discussed the most, genetic counseling (13%) and prevention (20%) were the least mentioned. CONCLUSIONS: YouTube is poorly informational and inaccurate on breast cancer in the Arab World where it is highly used. Although videos uploaded by legal persons tend to be more adequate, they are of lower popularity. Governments and physicians are encouraged to upload more intelligibly informational videos, guide the population to reliable sources, and support regulations.

Acute myeloid leukemia transformed to a targetable disease.

Acute myeloid leukemia (AML) is a heterogeneous neoplasm characterized by the monoclonal proliferation of immature progenitors. It is the most common acute leukemia in adults and its incidence increases with age. The standard traditional treatment in fit patients was the '3 + 7' regimen and cytarabine consolidation followed or not with allogeneic stem cell transplantation. Recently, several targeted therapies such as gemtuzumab ozogamicin targeting the CD33+ AML, midostaurin, gilteritinib and crenolanib inhibiting FLT3-positive AML and ivosidenib and enasidenib blocking IDH-mutated AML have been approved. These new drugs led to the change of the landscape of the treatment of AML and transforming this disease to a targetable one. We aimed in this paper to review the implications of each new target, the mechanisms of action of these new drugs and we discuss all the studies leading to the approval of these new drugs in their indications according to each target.

Targeted therapies in urothelial bladder cancer: a disappointing past preceding a bright future?

Bladder cancer (BC) is the most frequent cancer affecting the urinary tract. With the growing era of targeted therapies around the 2000s, many trials evaluated the efficacy of targeted therapy in advanced BC. However, no approval was given yet to any form of targeted therapy when it comes to BC. The aim of this paper was to report the most pivotal trials that evaluated different families of targeted therapy in the treatment of BC, according to their biomarkers (FGFR3, EGFR, HER2, VEGF and PI3K/AKT/mTOR). The ongoing trials testing targeted therapies in advanced BC were then summarized. Finally, the different immunotherapies approved for this disease and their potential combination with targeted therapy were addressed.

Skin adverse events in recently approved targeted therapies in solid malignancies.

Targeted anticancer therapies are an important weapon in the fight against cancer. Targeted therapies interfere with specific molecules necessary for tumor growth and cancer progression. They are divided mainly to either monoclonal antibodies or small molecules inhibitors. Their primary objective is to target directly and precisely the cancer cells leading to a minimal side-effects profile. The dermatologic adverse reactions of these targeted therapies is different from those seen with classical cytotoxic chemotherapy. Rashes, xerosis, hand-foot-skin reaction and mucositis are the most frequent side effects. In this paper, we aim to present a comprehensive review of the dermatologic side effects of targeted therapies including, specific side effects related to recently, approved targeted therapies.

Immunotherapy: last bullet in platinum refractory germ cell testicular cancer.

Testicular germ cell tumors are chemosensitive with very high cure-rates even in the metastatic setting. However, patients with platinum-refractory and relapsing tumors after autologous stem cell transplant have very poor outcomes despite salvage treatments, and with no effective alternative therapies. Immunotherapy, notably with PD-1 inhibitors, has proven to be very effective in treating various solid tumors. This review summarizes the experience with anti-PD-1 agents (pembrolizumab, nivolumab) in the treatment of testicular germ cell tumor relapsing after multiple lines of treatment, and exposes future trials evaluating newer checkpoint inhibitors in this setting.

Ocular and orbital side effects of ALK inhibitors: a review article.

ALK inhibitors are a new group of tyrosine kinase inhibitors, highly efficient in the treatment of non-small-cell lung carcinoma. However, these targeted therapies can induce various adverse effects, including ocular toxicity. To date, few articles reporting ophthalmological side effects of ALK inhibitors have been published. In this review, we aim to describe the different side effects and to collect information regarding the causes behind the discrepancy between the reported rates of visual disorders. Frequent ocular side effects of ALK inhibitors included flashes, post-flashbulb effect, stripes, photopsia, accommodation disorder, presbyopia, reduced visual acuity and blurred vision. Optic neuropathy, vitreous floaters, diplopia, cataract and macular edema were also reported.

The merit of tyrosine kinase inhibitors in the adjuvant setting of high-risk renal cell carcinoma: a meta-analysis.

AIM: As no meta-analyses have evaluated tyrosine kinase inhibitors in the adjuvant setting of high-risk renal cell carcinoma (RCC), the aim was to evaluate the benefit of sunitinib and pazopanib in the adjuvant setting. METHODS: This meta-analysis included all Phase III randomized controlled trials evaluating adjuvant sunitinib and pazopanib in high-risk RCC. Primary outcome was the comparison of disease-free survival (DFS) between tyrosine kinase inhibitors and placebo. RESULTS: There was a tendency for significant overall effect of both sunitinib and pazopanib on DFS (hazard ratio: 0.85; 95% confidence interval: 0.72-1.01; p = 0.06). There was no significant difference between the effect of sunitinib and pazopanib on DFS (p = 0.51;  I2 = 0%). CONCLUSION: Pazopanib and sunitinib could prolong DFS in the adjuvant treatment of high-risk RCC and seem equally effective in this setting.