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Joe Mehanna,1 Fady GH Haddad,1 Roland Eid,1 Matteo Lambertini,2,3 Hampig Raphael Kourie11Oncology Department, Faculty of Medicine, Saint Joseph University of Beirut, Beirut, Lebanon; 2Department of Medical Oncology, U.O.C. Clinica Di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 3Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, ItalyAbstract: Triple-negative breast cancer (TNBC) is known to have a poor prognosis and limited treatment options, namely chemotherapy. Different molecular studies have recently classified TNBC into different subtypes opening the door to potential new-targeted treatment options. In this review, we discuss the current standard of care in the treatment of TNBC in the neoadjuvant, adjuvant and metastatic settings. In addition, we summarize the ongoing phase III clinical trials evaluating different associations between the 3 pillars of anticancer treatment: chemotherapy, targeted therapy and immunotherapy.Keywords: breast cancer, triple-negative, immunotherapy, PARP inhibitors

Khalil Saleh, Roland Eid, Fady GH Haddad, Nadine Khalife-Saleh, Hampig Raphaël Kourie Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon Abstract: Head and neck squamous cell carcinoma (HNSCC), a heterogeneous group of upper aerodigestive tract malignancies, is the seventh most common cancer worldwide. Tobacco use and alcohol consumption were the most identified risk factors of HNSCC. However, human papilloma virus, a sexually transmitted infection, has been determined as another primary cause of HNSCC. Early-stage disease is treated with surgery or radiotherapy. Recurrent or metastatic HNSCC is associated with poor prognosis with a median overall survival of 10 months. The EXTREME protocol is commonly used in first-line setting. Recently, pembrolizumab, an anti-programmed death-1 agent, has been approved by the US Food and Drug Administration for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after a platinum-based therapy. It demonstrated a durable objective response rate with a good safety profile and quality of life. Many ongoing trials are evaluating the use of pembrolizumab for the treatment of HNSCC in various indications such as adjuvant and neoadjuvant setting, maintenance and recurrent disease, alone or in combination with chemotherapy, radiation and targeted therapy. Finding those biomarkers predictive of response to immune checkpoints inhibitors has been a major concern. However, markers have been identified, such as PD-L1 expression, human papilloma virus infection, interferon-γ signature score, microsatellite instability and neoantigen production. Keywords: epidemiology, HPV, pharmacokinetics, PD-1/PD-L1 inhibitors, immunotherapy, biomarkers

Recent advancements in cancer immunotherapy have spotlighted the PD-1/PD-L1 pathway, crucial for its role in immune checkpoint regulation. Traditional inhibitors, though successful, face challenges like resistance and adverse effects. Bispecific antibodies targeting PD-1 and PD-L1 present a ground-breaking solution by simultaneously engaging multiple immune regulatory molecules. Developments in PD-1/PD-L1 bispecific antibodies up to now have been summarized, and the latest findings from the 2024 ASCO conference are presented, revealing that bispecific antibodies exhibit robust efficacy in treating various types of cancers, marking a significant step forward in cancer treatment., Competing Interests: Declarations Conflicts of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Treatment of non-small-cell lung cancers (NSCLC) has evolved over the last decade. According to studies, the use of targeted therapies has significantly increased the life expectancy of patients. Moreover, ALK-tyrosine kinase inhibitors (ALK-TKIs) have improved clinical outcomes. In Lebanon, translating recommendations into clinical practice remains challenging. A Lebanese expert panel of oncologists was convened to describe the management paradigm and the clinical evidence supporting the optimal use of next-generation TKIs in patients with ALK -rearranged NSCLC and to provide an expert overview of local challenges and recommendations for optimizing the management of advanced NSCLC in Lebanese patients. The experts agreed that these recommendations should be part of a healthcare strategy to be implemented at the national level.

Antibody-drug conjugates (ADCs) have recently emerged as a promising therapeutic option that combine the specificity of monoclonal antibodies and the cytotoxic effect of chemotherapy. With numerous ADCs approved and on the market, a particular concern of ADCs that target HER-2 has been their cardiac side effects, in view of the crucial role of HER-2 in cardiac development and physiology. While rarely toxic and generally safe, numerous publications have outlined the consistent association of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) with the development of cardiac toxicity. Despite not being clinically relevant in most cases, cardiac baseline evaluation, monitoring and early detection of cardiac adverse events remain pivotal with HER-2 targeting ADCs. This review aims to summarize and better characterize the complete cardiac toxicity profile of HER-2 ADCs, with the goal of improving clinical understanding of this adverse event, leading to better recognition, monitoring and management.

Background: Young women with breast cancer (BC) have an increased chance of carrying germline BRCA pathogenic variants (PVs). Limited data exist on the prognostic impact of tumor histology (i.e. ductal versus lobular) in hereditary breast cancer., Methods: This multicenter retrospective cohort study included women aged ≤40 years with early-stage breast cancer diagnosed between January 2000 and December 2020 and known to carry germline PVs in BRCA1/2. Histology was locally assessed in each center. The Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival and overall survival., Results: Of 4628 patients included from 78 centers worldwide, 3969 (86%) had pure ductal, 135 (3%) pure lobular, and 524 (11%) other histologies. Compared with ductal tumors, lobular tumors were more often grade 1/2 (57.7% versus 22.1%), stage III (29.6% versus 18.5%), and luminal A-like (42.2% versus 12.2%). Lobular tumors were more often associated with BRCA2 PVs (71.1% BRCA2), while ductal tumors were more often associated with BRCA1 PVs (65.7% BRCA1). Patients with lobular tumors more often had mastectomy (68.9% versus 58.3%), and less often received chemotherapy (83.7% versus 92.9%). With a median follow-up of 7.8 years, no significant differences were observed in disease-free survival (adjusted hazard ratio 1.01, 95% confidence interval 0.74-1.37) or overall survival (hazard ratio 0.96, 95% confidence interval 0.62-1.50) between patients with ductal versus lobular tumors. No significant survival differences were observed according to specific BRCA gene, breast cancer subtype, or body mass index., Conclusions: In this large global cohort of young BRCA carriers with breast cancer, the incidence of pure lobular histology was low and associated with higher disease stage at diagnosis, luminal-like disease and BRCA2 PVs. Histology did not appear to impact prognosis., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The absence of KRAS and NRAS gene mutations (RAS wild type) in metastatic colorectal cancer (mCRC), is associated with a good response to targeted therapy with anti-EGFR receptor antibodies. The current gold standard for RAS mutational status identification is genetic testing on tissue biopsy samples., Objective: This study aimed to assess the relevance of liquid biopsy as a less invasive alternative to tissue biopsy for detecting KRAS/NRAS and BRAF mutations in patients with metastatic colorectal cancer (mCRC). The study also aimed to determine the concordance between liquid biopsy and tissue biopsy., Methods: This is a phase IV, observational, uncontrolled, non-comparative, non-randomized, open label study. RAS/BRAF status will be tested at baseline using tissue and liquid biopsy using the Idylla/Biocartis PCR-based device. The primary endpoint is the comparison of the RAS status based on liquid biopsy with the RAS status based on tissue biopsy., Results: 100 patients with mCRC were included in the study. 75 % of patients showed concordant results between liquid biopsy and tissue biopsy, while 25 % had discordant results. Liquid biopsy demonstrated a sensitivity of 62 % and a specificity of 93 %. The accuracy of liquid biopsy was 75 %, with a moderate agreement between the two tests. The most frequent mutations in concordant cases were in KRAS (41 %), followed by NRAS (4 %) and BRAF (3 %). Mutations were not detected in 42 % of tissue biopsy samples and 60 % of liquid biopsy samples. The presence of hepatic metastases did not significantly affect the concordance between the biopsy methods., Conclusion: Liquid biopsy using the Idylla™ system showed a relatively low sensitivity but high specificity for detecting KRAS/NRAS and BRAF mutations in mCRC patients. Despite some discordant cases, liquid biopsy remains a promising alternative to tissue biopsy due to its non-invasiveness, ability to provide multiple samples, and better representation of tumor heterogeneity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hampig Raphael Kourie reports financial support was provided by Merck KGaA, Darmstadt, Germany. Hampig Raphael Kourie reports financial support was provided by Biocartis. Hampig Raphael Kourie reports financial support was provided by Saint-Joseph University of Beirut Research Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

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., (Copyright © 2023 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

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., Competing Interests: Declaration of competing interest No conflict of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In recent years, kidney cancer has shown an increased worldwide incidence of more than 400 000 novel cases annually. Although more than half of patients are diagnosed at a localised stage, this disease presents a high-risk of relapse after surgery. Thus, there is a need for adjuvant therapy post-resection to reduce cancer recurrence and prolong disease-free and overall survival. Thorough investigation of adjuvant drugs for renal cell carcinoma (RCC) has shown little promise in the last fifty years, with no recorded overall survival benefits. This was the case until pembrolizumab, an immune checkpoint inhibitor, was introduced into the adjuvant RCC space through the KEYNOTE-564 trial. The adjuvant administration of this novel anti-PD-1 drug demonstrated a significant overall survival benefit which has led to an update in the current treatment guidelines of RCC. This substantial change in the standard of care also caused an investigation of possible treatment combinations and an adoption of innovative predictive biomarkers. In this review, we will present the evolution of past adjuvant ICI trials for the treatment of RCC, the implications of pembrolizumab's overall survival benefits and a discussion of future directions concerning new RCC drug trials and liquid biopsy-based biomarkers., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) targeting HER2-positive malignancies across various tumor types. Through its unique composition, T-DXd achieves selective payload delivery, inducing cell death and halting tumor progression. Clinical trials initially investigated T-DXd's efficacy in HER2-positive advanced or metastatic breast, gastric, lung, and colorectal cancers; however, recent results from the DESTINY-PanTumor02 trial further underscore T-DXd's versatility, prompting T-DXd's US FDA approval for HER2-positive (immunohistochemistry [IHC] 3+) solid tumors. Moreover, in addition to T-DXd's efficacy against brain metastasis, T-DXd is showing promising results in HER2-low and HER2-ultra-low metastatic breast cancer, indicating a broader population of patients who may benefit., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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., Competing Interests: The authors declare no conflict of interest., (© 2024 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.)

Human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC) is a subtype of BC that has been recently recognized as a separate clinical entity with distinct clinical and molecular characteristics. It is defined by a low level of HER2 protein expression, which distinguishes it from other more aggressive BC subtypes. Early studies suggest that it may have a more favorable prognosis than HER2-positive BC, as it is less likely to spread to other parts of the body and may be more responsive to standard BC treatments such as chemotherapy, radiation therapy, and hormone therapy. Given the relative new emergence of HER2-low BC, there is still much to be learned about this subtype; ongoing research is focused on identifying the underlying genetic mutations that contribute to HER2-low BC as well as developing targeted therapies that can improve outcomes for patients with this disease. This review is aimed at summarizing the current clinical knowledge on HER2-low BC, with the aim of creating a better understanding of this entity and paving the way for potential interventions and a new standard of care., Competing Interests: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript., (Copyright © 2024 Georges El Haddad et al.)

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 .

Purpose: This systematic review summarizes evidence of VEGFR gene mutations and VEGF/VEGFR protein expression in glioblastoma multiforme (GBM) patients, alongside the efficacy and safety of anti-VEGFR tyrosine kinase inhibitors (TKIs) for GBM treatment., Methods: A comprehensive literature review was conducted using PubMed up to August 2023. Boolean operators and MeSH term "glioma," along with specific VEGFR-related keywords, were utilized following thorough examination of existing literature., Results: VEGFR correlates with glioma grade and GBM progression, presenting a viable therapeutic target. Regorafenib and axitinib show promise among studied TKIs. Other multi-targeted TKIs (MTKI) and combination therapies exhibit potential, albeit limited by blood-brain barrier penetration and toxicity. Combining treatments like radiotherapy and enhancing BBB penetration may benefit patients. Further research is warranted in patient quality of life and biomarker-guided selection., Conclusion: While certain therapies hold promise for GBM, future research should prioritize personalized medicine and innovative strategies for improved treatment outcomes., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: As a consequence of the economic crisis, the sociopolitical instability and the advent of the coronavirus disease-19 pandemic, nested challenges faced the Lebanese healthcare system. These have resulted in critical shortages of essential resources, including medications vital for oncologic patients., Aim: To assess the ramifications of the ongoing economic crisis on oncology patient care focusing on our outpatient oncology department., Methods: A questionnaire was distributed during the month of February 2022 to oncology patients in Hôtel Dieu de France University Hospital in Beirut during their outpatient therapy. The primary objective was to assess the far-reaching impact of the economic crisis on patient care and the resulting psychological implications., Results: Among 182 interviewed patients, 31.87% experienced treatment interruption mainly due to acute drug shortages. Despite 87.91% of the patients benefiting from third-party coverage, 69.60% had to self-pay for their medications leading to 69.78% of patients perceiving that healthcare was more difficult to access after 2020. Psychologically, one-third of the patients exhibited symptoms of anxiety and/or depression, with 7 patients reporting suicidal ideations. Notably, 37.93% of patients who interrupted cancer treatment reported a history of comorbidities, and 89.66% who altered their treatment cited financial difficulties., Conclusion: Lebanese cancer patients face complex challenges spanning economic, healthcare, and psychological realms. Income inequalities exacerbated by the economic crisis hindered healthcare access., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

BRAF gliomas have garnered significant attention in research due to the lack of effective treatments and their notable incidence, constituting 3% of all gliomas. This underlines the importance of investigating this area and the impact that targeted therapies could hold. This review discusses the development of targeted therapies for these tumors, examining the effectiveness of first-generation BRAF inhibitors such as Vemurafenib, Dabrafenib and Encorafenib, while addressing the challenges posed by paradoxical ERK activation. The advent of pan-RAF inhibitors, notably Tovorafenib, offers a promising advance, demonstrating enhanced efficacy and better penetration of the blood-brain barrier, without the issue of paradoxical activation. Nevertheless, continued research is essential to refine therapeutic strategies for BRAF-mutated gliomas, given the evolving nature of targeted therapy development.

Background: Prostate cancer (PC) is the second most common cancer in men worldwide. It's the second leading cause cancer men in death. Prognostic tests based on molecular and biomarker analysis of tumor tissue may improve risk stratification of prostate cancer 2., Materials and Methods: After a search on Pubmed for PC biomarkers, 72 papers responded to the objectives and will be included in the review., Results: A plethora of biomarkers are predictive for the prognosis of PC and its response to certain therapies, while others, once thought to be indicative of prognosis in PC, were not., Conclusions: This study can help in the development of diagnostic and prognostic tests of PC and contribute to the ongoing research into already existing tests.

Primary mediastinal B cell lymphoma (PMBCL) is considered a distinct pathology according to the WHO classification of lymphoid malignancies. Patients have a better prognosis after the addition of Rituximab to anthracycline-based chemotherapy. The role of consolidative radiotherapy is controversial after the approval of dose-adjusted R-EPOCH and the selection of patients to undergo radiotherapy is based on end-of-therapy PET CT. In the relapsed/refractory setting, new approved drugs and other under investigation have improved patient outcomes. This review summarizes the different treatment modalities in (PMBCL) in the frontline and the relapsed/refractory settings., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bladder cancer (BC) has been associated with genetic susceptibility. Single peptide polymorphisms (SNPs) can modulate BC susceptibility. A literature search was performed covering the period between January 2000 and October 2020. Overall, 334 articles were selected, reporting 455 SNPs located in 244 genes. The selected 455 SNPs were further investigated. All SNPs that were associated with smoking and environmental exposure were excluded from this study. A total of 197 genes and 343 SNPs were found to be associated with BC, among which 177 genes and 291 SNPs had congruent results across all available studies. These genes and SNPs were classified into eight different categories according to their function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kourie, Zouein, Succar, Mardirossian, Ahmadieh, Chouery, Mehawej, Jalkh, kattan and Nemr.)

Osteosarcoma (OS) is an aggressive primary bone malignancy that metastasizes rapidly. The standard of care has changed little over the previous four decades, and survival rates have plateaued. In this context, tyrosine kinase inhibitors (TKIs) emerge as potential treatments. A literature search was conducted to collect data related to receptor tyrosine kinase genetic alterations and expression in OS specimens. Gene amplification and protein expression of these receptors were linked to prognosis and tumor behavior. Relevant TKIs were evaluated as monotherapies and as parts of combination therapies. Certain TKIs, such as apatinib, regorafenib, and cabozantinib, present a potential therapeutic avenue for OS patients, especially when combined with chemotherapy. Producing long-lasting responses and enhancing quality of life remain key goals in OS treatment. To this effect, optimizing the use of TKIs by identifying biomarkers predictive of response and assessing promising TKIs in larger-scale trials to validate the efficacy and safety outcomes relative to these drugs reported in phase II clinical trials. To this effect, it is necessary to identify biomarkers predictive of response to TKIs in larger-scale trials and to validate the efficacy and safety of these drugs reported in phase II clinical trials., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

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.

Lung cancer is the most common cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) represents the majority of lung cancer cases, and its standard treatment is primarily surgery. Nonetheless, this type of cancer exhibits an important rate of tumor recurrence. Immune checkpoint inhibitors (ICIs) have demonstrated significant survival benefits in many cancers, especially in early-stage NSCLC. This review considers the latest CheckMate816, IMpower010 and KEYNOTE-091 trials that led to US FDA approvals. The new wave of resectable NSCLC trial results are also summarized. Finally, the latest challenges for these treatment modalities, such as the choice between neoadjuvant and adjuvant use, the accurate identification of biomarkers and the presence of driver mutations such as EGFR, are discussed.

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., (© 2023. The Author(s).)

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.

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.

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., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Aim: Bone tumors are rare and have an uneven geographic distribution., Methods: 730 patients diagnosed with bone tumors were included in this retrospective analysis., Results: With a 64% rate of malignancy, the most common tumors were metastasis (40%) mostly in the axial skeleton, Osteosarcoma (9%) mostly in the femur, Osteochondroma (8%) mostly in the femur, giant cell tumors (7%) mostly in the knee, and Ewing's sarcoma (6%) mostly in the axial skeleton., Conclusion: Even though a some of the tumors have a predilection for certain localizations in the human body, they may differ in the middle-eastern population. One must also pay attention to the higher rates of malignancies as compared with other cohorts., Competing Interests: Competing interests disclosure The authors declare that there are no conflicts of interest present., (© 2023 The Authors.)

Background: ALK rearrangements account for around 5% of non-small-cell lung cancers. Aim: This study surveys physicians on the potential efficacy of a mobile application in improving the management of ALK-rearranged non-small-cell lung cancer, through knowledge, treatment adherence and real-time adverse events reporting. Materials & methods: A total of 118 physicians from 11 countries in the Middle East participated. Results & conclusion: Results indicate 94% support for enhancing team communication via an application, and 93% believe real-time adverse events reporting improves the quality of care. Participants found an ALK-rearrangement patient-physicians forum valuable for communication improvement. Motivations for application use included treatment planning (73%), care enhancement (60%) and contributing to publications (40%).

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.

Immunotherapy has improved the prognosis of many cancers, yet a large number of patients have demonstrated resistance to current immune checkpoint inhibitors. LAG-3 is an immune checkpoint expressed on tumor-infiltrating lymphocytes CD4 + and CD8 + , Tregs and other immune cells. Coexpression of PD-1 and LAG-3 in solid or hematological cancers is generally associated with a poor prognosis and may be responsible for immunotherapy resistance. Dual inhibition therapy in the RELATIVITY-047 trial significantly improved progression-free survival in metastatic melanoma. This article discusses the presence of a possible synergistic interaction between LAG-3 and PD-1 in the tumor microenvironment and the utility of targeting both immune checkpoint inhibitors as an effective way to bypass resistance and increase treatment efficacy.

Background: Bladder cancer is a common urogenital malignancy characterized by frequent genetic alterations. Histone demethylase gene KDM6A is commonly mutated in bladder cancer. Aim: To review the characteristics of KDM6A and its mutation consequences, and to introduce a potential KDM6A-targeted treatment. Methods: We conducted a comprehensive literature search using two electronic databases, MEDLINE and Cochrane Library, to retrieve topic-related articles from July 2013 to July 2022 using keywords 'KDM6A', 'bladder cancer', 'UTX', 'treatment' and 'mutation'. Five reviewers independently screened literature search results and abstracted data from included studies. Descriptive analysis was conducted and 30 articles were retained. Main Results: A total of 30 articles were retrieved. Experimental and clinical data were collected and grouped by theme. Therapeutic strategies are depicted and organized by tables for a better understanding. Conclusion: This review demonstrates that KDM6A has crucial implications in bladder cancer pathogenesis and treatment.

With an annual incidence of less than 1%, Ewing sarcoma mainly occurs in children and young adults. It is not a frequent tumor but is the second most common bone malignancy in children. It has a 5-year survival rate of 65-75%; however, it has a poor prognosis when it relapses in patients. A genomic profile of this tumor can potentially help identify poor prognosis patients earlier and guide their treatment. A systematic review of the articles concerning genetic biomarkers in Ewing sarcoma was conducted using the Google Scholar, Cochrane, and PubMed database. There were 71 articles discovered. Numerous diagnostic, prognostic, and predictive biomarkers were found. However, more research is necessary to confirm the role of some of the mentioned biomarkers. ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Locoregional, as well as metastatic renal cell carcinoma, tends to relapse after nephrectomy or metastasectomy. Adjuvant therapy seems to be an effective strategy to reduce the risk of recurrence. All anti-VEGF tyrosine kinase inhibitors except sunitinib have failed to show any benefit in the adjuvant setting in patients with locally advanced disease and an intermediate-to-high chance of recurrence. On the other hand, immune checkpoint inhibitors, which are now used in the first-line in the metastatic setting, are being tested in the adjuvant setting. Pembrolizumab has shown benefit in the adjuvant setting in patients with a high risk of recurrence or with resected metastatic disease with no evidence of disease. Results for other checkpoint inhibitors are still awaited.

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.

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.