Critical reviews in oncology/hematology最新文献

Background: Primary central nervous system lymphoma (CNSL) is a rare, aggressive non-Hodgkin lymphoma confined to the CNS. Although radiation and chemotherapy, particularly high-dose methotrexate (HD-MTX), are effective treatments, the relapse rates remain high, prompting the exploration of novel therapeutic options. Ibrutinib, an irreversible Bruton tyrosine kinase (BTK) inhibitor, has shown promise in various B-cell malignancies, including CNSL.

Objectives: This systematic review and meta-analysis aimed to evaluate the safety and efficacy of ibrutinib in the treatment of CNSL, focusing on overall response (OR), complete response (CR), partial response (PR), progression-free survival (PFS), overall survival (OS), and adverse events.

Methods: A comprehensive search of the PubMed, Google Scholar, and Scopus databases was conducted. The included studies were prospective and retrospective studies focusing on ibrutinib as monotherapy or in combination with CNSL. Data extraction and quality assessment were independently performed by two reviewers, and statistical analyses were conducted using R version 4.4.0.

Results: Fourteen studies (eight cohort studies and six clinical trials) involving 784 patients were included. The median age was 61 years, with nearly equal sex distribution. The meta-analysis for CNSL, the partial response rate was 29.52 %, complete response rate was 49.19 %, and overall response rate was 72.11 %. For PCNSL, the partial response rate was 20.85 %, complete response rate was 48.13 %, and overall response rate was 66.92 %. For SCNSL, the partial response rate was 29.42 %, complete response rate was 44.64 %, and overall response rate was 66.82 %. Significant heterogeneity was observed in some comparisons. There were no significant differences in the efficacy of ibrutinib between CNSL subtypes.

Conclusions: Ibrutinib shows promising efficacy in improving partial and complete response rates in CNSL. The substantial heterogeneity observed underscores the need for further well-designed studies to confirm these findings and explore the optimal use of ibrutinib in CNSL treatment protocols. Future trials should consider comparing ibrutinib to standard therapies and investigate its long-term efficacy and safety profile.

Background: High-grade gliomas are devastating cancers that remain incurable with standard surgical resection and radiochemotherapy. Although beneficial against neoplasms, radiation lowers lymphocyte counts, weakens immune activation, and recruits suppressive myeloid cells impairing immune responses. Tumor environments treated with radiation experience long-term immunosuppression, reducing immunotherapy effectiveness and contributing to recurrence. Investigating pre-radiation treatments in newly diagnosed patients could identify active agents, assess immunotherapy impact, and enable multiomic analyses without radiation-induced confounding factors. This literature review was conducted to describe the feasibility, safety, and outcomes of postsurgical, pre-radiation clinical trials for adults with newly diagnosed high-grade glioma.

Methods: A systematic review was performed of the English-language literature reporting results of clinical trials for adults with newly diagnosed high-grade glioma administered postsurgical treatment prior to radiation therapy. A search was conducted in PubMed and references cited in research and review articles were also considered.

Results: From 1991 to 2024, 52 clinical trials were identified: 3 phase I, 38 phase II, 4 phase III, and 7 of unknown phase. Nine trials were randomized, 24 were multicenter trials, 21 investigated temozolomide-containing regimens, and 12 focused on inoperable tumors, involving a total of 2737 patients.

Conclusion: Pre-radiation neoadjuvant studies are feasible and may identify active drugs. This is particularly relevant in the era of personalized medicine with brain-penetrant drugs, targeted therapy, and immuno-oncology advancements. Investigating pre-radiation treatments in newly diagnosed high-grade glioma is a viable approach to rapidly identify active and inactive regimens while the immune system and tumor microenvironment remain intact.

The ever-increasing use of immune checkpoint inhibitors (ICIs) has significantly improved cancer management, but at the cost of frequent immunologic side effects. Among them, neurologic immune-related adverse events (nirAEs) are less common but pose a challenge to clinicians due to their severity, heterogeneous nature and nonspecific clinical presentation, making diagnosis complex. The prognosis of these nirAEs, especially those related to the central nervous system (CNS), correlates with their rapid recognition and therapeutic management. Indeed, the therapeutic options are sometimes unfamiliar and may be further complicated by the lack of recommendations in the event of failure of a well-managed first-line treatment. Finally, the attribution of ICIs to certain CNS disorders is controversial and may lead to an incorrect decision to discontinue or contraindicate treatment, resulting in an irremediable loss of opportunity for the patient. Therefore, the aim of this review is to present known/suspected CNS nirAEs induced by ICI, their diagnostic approach and management through therapeutic advices for optimal treatment and rechallenge opportunities.

A major advance in cancer treatment has been the development and refinement of cancer immunotherapy. The discovery of immunotherapies for a wide range of cancers has revolutionized cancer treatment paradigms. Despite relapse or refractory disease, immunotherapy approaches can prolong the life expectancy of metastatic cancer patients. Multiple therapeutic approaches and agents are currently being developed to manipulate various aspects of the immune system. Oncolytic viruses, cancer vaccines, adoptive cell therapies, monoclonal antibodies, cytokine therapies, and inhibitors of immune checkpoints have all proven successful in clinical trials. There are several types of immunotherapeutic approaches available for treating cancer, and others are being tested in preclinical and clinical settings. Immunotherapy has proven successful, and many agents and strategies have been developed to improve its effectiveness. The purpose of this article is to present a comprehensive overview of current immunotherapy approaches used to treat cancer. Cancer immunotherapy advancements, emerging patterns, constraints, and potential future breakthroughs are also discussed.

Background and aims: The aim of this systematic review was to assess the risk of cardiac toxicity in patients undergoing approved PD-1 (nivolumab, pembrolizumab, cemiplimab, dostarlimab), PD-L1 (atezolizumab, avelumab, durvalumab), and CTLA-4 (ipilimumab) inhibitors.

Results: Among a total of 2272 articles, 11 phase II and III clinical trials included: 5463 patients and 175 cardiac adverse events. The most common cardiac disorder was atrial fibrillation (12 %), while cardiac arrest and cardiac failure (6 %) led to death in three cases. Overall, ICI treatment increased the risk of cardiotoxicity compared with control groups (RR=1.62, 95 %-CI= 1.18-2.24, p-value=0.0033; OR=1.71, 95 %-CI= 1.20-2.42, p-value=0.0027).

Conclusions: This study proved that the recognition of frequency and severity of all grade cardiotoxicity associated with ICIs is still underestimated. Thus, a systematic cardiological screening becomes necessary, in order to intercept the potential cardiological complications beforehand and optimize the outcomes of the respective treatment with PD-1, PD-L1 and CTLA-4 inhibitors.

Clonal hematopoiesis (CH) typically refers to the clonal expansion of hematopoietic stem cells (HSCs) due to genetic mutations, serving as the pathogenic basis for various diseases. Clonal hematopoiesis of indeterminate potential (CHIP) is a subtype of CH, emerging as a significant risk factor for myeloid malignancies and cardiovascular diseases, which has attracted increasing attention. However, recent research has unveiled previously overlooked links between CHIP and lymphoma. This paper reviews the relationship between CHIP and lymphoma, focusing on the role and mechanism of TET2 and DNMT3A-mediated CHIP in lymphoma from the perspective of laboratory research and clinical observation. Additionally, we explore the therapeutic implications of targeting CHIP genes and inflammatory pathways in lymphoma. Our findings underscore the multifaceted influence of CHIP on lymphoma development and provide a promising avenue for therapeutic interventions in CHIP mediated lymphoma.

Immunotherapy has emerged as a powerful tool in cancer treatment, achieving remarkable success in combating various cancers. However, it also raises concerns due to its potential adverse effects, with immune-associated pneumonia being one of the most significant. The clinical symptoms of this condition primarily include dyspnea, persistent cough, and fever. Diagnosis requires knowledge of the patient's medication history and diagnostic tools like chest CT and bronchoalveolar lavage bronchoscopy to differentiate immune-associated pneumonia from other lung diseases. Studies suggest that the pathogenesis of CIP involves an immune response characterized by overexpression of T-lymphocyte subsets and elevated levels of inflammatory factors. The prevalence of CIP generally ranges between 2 % and 6 %, though it can vary depending on factors like the patient's individual characteristics, tumor type, and treatment strategy. Corticosteroids are the first-line treatment for CIP, with dosage adjustments based on clinical response. Additionally, traditional Chinese medicine is being explored as an adjuvant therapy to potentially enhance therapeutic outcomes.

Targeted therapy, the milestone in the development of human medicine, originated in 2004 when the FDA approved the first targeted agent bevacizumab for colorectal cancer treatment. This new development has resulted from drug developers moving beyond traditional chemotherapy, and several trials have popped up in the last two decades with an unprecedented speed. Specifically, EGF/EGFR, VEGF/VEGFR, HGF/c-MET, and Claudin 18.2 therapeutic targets have been developed in recent years. Some targets previously thought to be undruggable are now being newly explored, such as the RAS site. However, the efficacy of targeted therapy is extremely variable, especially with the emergence of new drugs and the innovative use of traditional targets for other tumors in recent years. Accordingly, this review provides an overview of the major signaling pathway mechanisms and recent advances in targeted therapy for gastrointestinal cancers, as well as future perspectives.

Current therapeutic strategies for benign prostatic hyperplasia (BPH) and prostate cancer focus mainly on androgen receptors (AR) and 5-alpha reductase inhibition to suppress androgen-driven prostate growth. However, these methods often result in side effects and resistance. Recent research identifies novel targets like integrin and cadherin inhibitors, gene regulation, microRNAs, cellular senescence, and metabolomics pathways to overcome these limitations. These innovations offer more personalized approaches with potentially fewer adverse effects and reduced resistance compared to traditional androgen-focused therapies. Novel target sites and pathways, either suppressed or overexpressed, offer control points for modulating signaling in prostate diseases, suggesting future potential for treatment through innovative exogenous substances. Data was compiled from Google Scholar, PubMed, and Google to highlight the comparative potential of these emerging methods in enhancing treatment efficacy for prostate health.

The application of circulating tumor cells (CTCs) as diagnostic and prognostic markers in oncology is gaining increasing importance in clinical practice. Currently, various methods exist for detecting CTCs in patients' biological fluids. This systematic review aimed to compare the efficacy of different techniques for isolating and detecting CTCs from blood, against the FDA-cleared CellSearch® technology, in breast cancer patients. We performed a systematic literature search using two databases (PubMed and the Cochrane Library) with the following terms: ("Circulating tumor cells" OR CTC) AND "breast cancer", covering the period from 2004 to April 2023. The primary outcome measured was the sensitivity, specificity, and overall accuracy of various CTC enrichment methods in comparison with the CellSearch® System. Secondary outcomes included the prognostic value of CTCs in evaluating response to treatment based on survival rates. Generally, a high level of agreement between CellSearch and other methods was observed in isolating CTCs from patients' blood with both metastatic and early-stage disease. Studies asserting the superiority of new methods over CellSearch frequently used clinically unvalidated cut-off thresholds for their patient cohorts. Additionally, these studies sometimes included different nonoverlapping patient cohorts and lacked a standardized chemotherapy treatment protocol, which could affect the quantitative changes in CTC. It is evident that methods simultaneously composed of physical and immunomagnetic approaches for CTC isolation significantly surpass CellSearch, which relies solely on the expression of specific markers on the CTCs' surface. The count of CTCs has been established as a predictive marker in terms of clinically important parameters namely progression-free survival (PFS) and overall survival (OS). The CTC-count value was significantly correlated with PFS and OS rates.