Critical reviews in oncology/hematology最新文献

Hepatocellular carcinoma (HCC) is a severe neoplastic disease associated with high morbidity and mortality rates. HCC is often detected at advanced stages leading to ineffective curative treatments. Recently, liquid biopsy has emerged as a non-invasive method to identify highly specific HCC biomarkers in bodily fluids such as blood, serum, urine, and saliva. Circulating cell-free nucleic acids (cfNAs), particularly cell-free DNA (cfDNA) and cell-free RNA (cfRNA), have become promising candidates for biomarkers in liquid biopsy applications. While cfDNA presented significant challenges, researchers have turned their attention to cfRNA, which can be efficiently identified through various methods and is considered a potential biomarker for cancer diagnosis and prognosis. This review primarily focuses on studies related to detecting various cfRNA in body fluids as biomarkers. The aim is to provide a summary of available information to assist researchers in their investigations and the development of new diagnostic and prognostic tools.

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment approach for patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL). However, the long-term prognosis has been discouraging. Moreover, the urgent resolution of two critical issues is necessary: minimize tumor burden before CAR-T infusion and control fatal toxicities post CAR-T therapy. By combining radiotherapy (RT), the safety and efficacy of CAR-T can be improved. RT can serve as bridging therapy, reducing the tumor burden before CAR-T infusion, thus enabling safe and successful CAR-T infusion, and as salvage therapy in cases of CAR-T therapy failure. This review aims to discuss the current evidence supporting the use of RT in CAR-T therapy for patients with R/R NHL. Although most studies have shown a positive role of RT in combined modality treatments for patients undergoing CAR-T therapy, the synergy gained from these remains uncertain. Furthermore, the optimal dose/fraction and radiation response require further investigation.

A multitude of TKI has been developed and approved targeting various oncogenetic alterations. While these have provided improvements in efficacy compared with conventional chemotherapies, resistance to targeted therapies occurs. Mutations in the kinase domain result in the inability of TKI to inactivate the protein kinase. Also, gene amplification, increased protein expression and downstream activation or bypassing of signalling pathways are commonly reported mechanisms of resistance. Improved understanding of mechanisms involved in TKI resistance has resulted in the development of new generations of targeted agents. In a race against time, the search for new, more potent and efficient drugs, and/or combinations of drugs, remains necessary as new resistance mechanisms to the latest generation of TKI emerge. This review examines the various generations of TKI approved to date and their common mechanisms of resistance, focusing on TKI targeting BCR-ABL, epidermal growth factor receptor, anaplastic lymphoma kinase and BRAF/MEK tyrosine kinases.

In the last decade, targeted therapies have shown rapid advancement in biliary tract cancer (BTC). Today, many targeted agents are available and under investigation for patients with BTC. More recently, immune checkpoint inhibitors (ICI) such as durvalumab and pembrolizumab in combination with gemcitabine plus cisplatin (gem/cis) have resulted in improved overall survival and progression-free survival in the first-line setting. However, the efficacy benefit of these novel therapeutics is often short-lived, with literature outlining concerns about both primary and secondary resistance to these agents. Investigators also need to consider toxicity profiles that can emerge using this strategy. There have been efforts to reduce evolving resistance through combinatory approaches, both pre-clinically and in early clinical settings. This review summarizes the emerging targeted therapies in BTC, evolving biomarkers of resistance, strategies to overcome them, and an analysis of ongoing clinical trials of patients with advanced BTC.

Introduction

Cancer cachexia is a clinical condition characterized by recognizable “sickness behaviors” accompanied by loss of lean body tissue. The Global Leadership on Malnutrition (GLIM) has proposed phenotypic (unintentional weight loss, low body mass index and low muscle mass) and aetiologic (reduced food intake and inflammation or disease burden) diagnostic criteria. Recent work has suggested serum lactate dehydrogenase (LDH) might represent a 3rd aetiologic criteria. Little is known of its relationship with GLIM. A systematic review and meta-analysis of their comparative prognostic value and association was performed.

Methods

A search of electronic databases (PubMed, Medline, Ovid, Cochrane) up to February 2023 was used to identify studies that compared the prognostic value of LDH and components of the GLIM criteria in cancer. An analysis of the relationship between LDH and the components of GLIM was undertaken where this data was available. RevMan 5.4.1 was used to perform a meta-analysis for each diagnostic criteria that had 3 or more studies which reported hazard ratios with a 95 per cent confidence interval for overall survival (OS).

Results

A total of 119 studies were reviewed. Advanced lung cancer was the most studied population. Included in the meta-analysis were 6 studies (n=2165) on LDH and weight loss, 17 studies (n=7540) on LDH and low BMI, 5 studies (n=758) on LDH and low muscle mass, 0 studies on LDH and food intake and 93 studies (n=32,190) on LDH and inflammation. There was a significant association between elevated serum LDH and each of low BMI (OR 1.39, 1.09 – 1.77; p=0.008), elevated NLR (OR 2.04, 1.57 – 2.65; p<0.00001) and elevated CRP (OR 2.58, 1.81 – 3.67; p<0.00001). There was no association between elevated serum LDH and low muscle mass. Only one study presented data on the association between LDH and unintentional weight loss. Elevated LDH showed a comparative OS (HR 1.86, 1.57 – 2.07; p<0.00001) to unintentional weight loss (HR 1.57, 1.23 – 1.99; p=0.0002) and had a similar OS (HR 2.00, 1.70 – 2.34; p<0.00001) to low BMI (HR 1.57, 1.29–2.90; p<0.0001). LDH also showed an OS (HR 2.25, 1.76 – 2.87; p<0.00001) congruous with low muscle mass (HR 1.93, 1.14 – 3.27; p=0.01) and again, LDH conferred as poor an OS (HR 1.77, 1.64–1.90; p<0.00001) as elevated NLR (HR 1.61, 1.48 – 1.77; p<0.00001) or CRP (HR 1.55, 1.43 – 1.69; p<0.00001).

Conclusion

Current literature suggests elevated serum LDH is associated with inflammation in cancer (an aetiologic GLIM criterion), however more work is required to establish the relationship between LDH and the phenotypic components of GLIM. Additionally, elevated serum LDH appears to be a comparative prognosticator of overall survival in cancer when compared to the GLIM criteria.

Introduction and purpose

With a significant global impact, treatment of gastrointestinal (GI) cancers still presents with challenges, despite current multimodality approaches in advanced stages. Clinical trials are expanding for checkpoint inhibition (ICI) combined with radiation therapy (RT). This review intends to offer a comprehensive image of the current data regarding the effectiveness of this association, and to reflect on possible directions to further optimize the results.

Results

Several early phase studies demonstrated encouraging potential. However, translating preclinical outcomes to clinical settings proves challenging, especially in immunologically "cold" environments. GI cancers exhibit heterogeneity, requiring tailored approaches based on disease stage and patient characteristics. Current results, though promising, lack the power of evidence to influence the general practice.

Conclusions

Finding biomarkers for identifying or converting resistant cancers is essential for maximizing responses, moreover in this context strategic RT parameters need to be carefully considered. Our review emphasizes the significance of having a thorough grasp of how immunology, tumour biology, and treatment settings interact in order to propose novel research avenues and efficient GI cancer therapy.

DNA mismatch repair (MMR) deficiency and the associated microsatellite instability (MSI) phenotype has become a subject of enormous interest in recent years due to the demonstrated efficacy of immune checkpoint inhibitors (ICI) in advanced tumours. Assessing MSI in patients with gastrointestinal tract (GI) cancers is useful to exclude Lynch syndrome, but also to predict benefit for ICI. Following review of the relevant literature, this review article aims to outline the clinicopathologic spectrum of MSI and mismatch repair deficiency (dMMR) in the GI tract, hepatobiliary system and pancreas and discuss the therapeutic consideration in this disease.

Breast cancer (BC) is currently the most common malignant tumour in women and one of the leading causes of their death around the world. New and increasingly personalised diagnostic and therapeutic tools have been introduced over the last few decades, along with significant advances regarding the study and knowledge related to BC. The tumour microenvironment (TME) refers to the tumour cell-associated cellular and molecular environment which can influence conditions affecting tumour development and progression. The TME is composed of immune cells, stromal cells, extracellular matrix (ECM) and signalling molecules secreted by these different cell types. Ever deeper understanding of TME composition changes during tumour development and progression will enable new and more innovative therapeutic strategies to become developed for targeting tumours during specific stages of its evolution. This review summarises the role of BC-related TME components and their influence on tumour progression and the development of resistance to therapy. In addition, an account on the modifications in BC-related TME components associated with therapy is given, and the completed or ongoing clinical trials related to this topic are presented.

Introduction

Nanoliposomal irinotecan (nal-IRI) is a novel regimen for pancreatic cancer, featuring a longer half-life and an increased area under the concentration-time curve. This study aims to assess the safety and efficacy of nal-IRI as a second-line treatment for advanced pancreatic cancer.

Methods

A systemic literature search was conducted based on articles published before September 26th, 2023 in databases, including PubMed, Cochrane Library, EMBASE and Web of Science. The fixed effects model was used to calculate the pooled mean difference for overall survival (OS) and progression-free survival (PFS), as well as the pooled odds ratio for the overall response rate (ORR) and the risk of adverse events.

Results

A total of 21 studies, including 3044 patients with locally advanced unresectable or metastatic pancreatic cancers, were considered eligible. The use of nal-IRI, combined with 5-fluorouracil and leucovorin, resulted in significantly improved PFS (pooled mean difference=1.01 months, 95 % confidence interval [CI]=0.97–1.05, p<0.01) and OS (pooled mean difference=0.29 months, 95 %CI=0.18–0.39, p<0.01), as well as significantly better ORR (pooled odds ratio=2.06, 95 %CI=1.30–3.27, p=0.002) compared to other second-line regimens. Nonetheless, an increased risk of grade 3 or greater neutropenia, anemia, hypokalemia, diarrhea, and vomiting was also noted.

Conclusion

Second-line treatments based on nal-IRI exhibited significantly improved PFS, OS, and ORR compared to other available treatments in advanced pancreatic cancer. Further research is necessary to corroborate these findings and define the role of nal-IRI in both first and later lines of therapy.