Turning the tide: pembrolizumab's triumph in adjuvant RCC therapy.

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.

Liquid biopsy as a tool for KRAS/NRAS/BRAF baseline testing in metastatic colorectal cancer.

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.

Insights Into the Emerging Entity of HER2-Low Breast Cancer.

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.

Trastuzumab-Deruxtecan: Redefining HER2 as a Tumor Agnostic Biomarker.

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.

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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Impact of the economic crisis and drug shortage on Lebanese cancer patients' care.

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.

A critical review of RAF inhibitors in BRAF-mutated glioma treatment.

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.

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.

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 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.

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.

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.