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.

Unlocking Hope: Anti-VEGFR inhibitors and their potential in glioblastoma treatment.

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.

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.

Biomarkers in Prostate Cancer: A Review.

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.

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.

Tyrosine kinase inhibitors in osteosarcoma: Adapting treatment strategiesa.

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.

Genetic Polymorphisms Involved in Bladder Cancer: A Global Review.

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.

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.

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.

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.

Epidemiology of bone tumors in Lebanon: a retrospective study from 2000 to 2022 at a tertiary center.

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.

With significant morbidity and mortality, bone tumors incidence is low and varies geographically. In our Lebanese population, Seven-hundred-thirty patients with bone tumors were identified with a 64% rate of malignancy with osteosarcoma being the most common primary bone cancer and metastasis being the overall most prevalent bone malignancy. This higher rate of malignancy compared with other populations should be taken into consideration when evaluating Lebanese or Middle eastern patients.

Improving the management of ALK-rearranged non-small-cell lung cancer through a mobile application: a physicians-based survey.

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%).

Updates in the Management of Primary Mediastinal B Cell Lymphoma.

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.

Tackling the immunotherapy conundrum: advances and challenges for operable non-small-cell lung cancer treatment.

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.

This article explains new results from cancer trials. In fact, the US FDA approved new treatments because of these findings. We sum up how cancer drugs help immune cells kill lung tumors. Moreover, the most common type of these tumors is non-small-cell lung cancer, a group that responds well to these drugs. The article provides a brief review of 2023 results to help both patients and doctors. Finally, some significant debates are presented. Among these questions are the following: Is treatment better before or after surgery? Will mutations reduce drug benefit? How can we tell whether the drug will work? Who can take these medicines? Will new tech help doctors?

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.

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.

Implication of KDM6A in bladder cancer.

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.