Critical reviews in oncology/hematology最新文献

Leptomeningeal carcinomatosis (LC) is a metastatic complication of breast cancer that imparts a very poor prognosis and distressing neurologic symptoms in affected patients. While the incidence of LC has risen with improving survival rates for cancer patients, there remains no established treatment protocol for LC and clinical trial data comparing available therapies is limited. Here, a comprehensive literature search of the pubmed and Cochrane databases was performed. Current treatment modalities and their safety/ efficacy profiles are summarized for LC in breast cancer. Roles for emerging therapies in LC are discussed, including targeted agents, CAR-T, immune checkpoint inhibitors, CDK inhibitors and novel antibody conjugates. A treatment pathway for LC is also proposed to guide clinicians through management of this severe metastatic complication of breast cancer.

Background

Early detection of fatigue is crucial for cancer patients. Although single-item scales are convenient, their diagnostic accuracy remain unclear, and the variability across studies may affect generalizability. This systematic review and meta-analysis evaluates the diagnostic value of single-item fatigue detection scales.

Methods

We systematically searched CINAHL, Cochrane Library, Embase, and PubMed. Meta-analyses were conducted to calculate pooled sensitivity, specificity, likelihood ratios, predictive values, and diagnostic odds ratios (DOR). We also calculated the area under a hierarchical summary receiver operating characteristic curve. Subgroup analyses were performed to address heterogeneity. All analyses were done R (version 4.3.1). The study registered in PROSPERO (CRD42023457658).

Results

Eleven studies involving 3509 participants were included. Pooled results revealed a sensitivity of 0.89 (95 % CI: 0.82–0.93), specificity of 0.72 (95 % CI: 0.63–0.80), DOR of 19.95 (95 % CI: 10.47–38.04), and an AUC of 0.90 (95 % CI: 0.89–0.91). Moderate to high heterogeneity was observed, influenced by variations in cancer types, study designs, and gold standard references.

Conclusion

Single-item fatigue scales demonstrate commendable diagnostic accuracy, comparable to multidimensional scales. Despite study variability, they are effective for routine clinical use to detect and manage fatigue in cancer patients. Future research should focus on standardizing assessment criteria and optimizing the balance between simplicity and diagnostic precision.

Biliary tract cancers (BTCs) are aggressive malignancies with a dismal prognosis that require intensive targeted therapy. Approximately 10 % of BTCs have PBRM1 mutations, which impede DNA damage repair pathways and make cancer cells more susceptible to DNA-damaging chemicals. This review focus on development of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeting delivery system to selectively deliver chemotherapy into PBRM1-deficient BTC cells. These nanoparticles improve therapy efficacy by increasing medication targeting and retention at tumour locations. In preclinical studies, pharmacokinetic profile of this nanoparticle was encouraging and supported its ability to achieve extended circulation time with high drug accumulation in tumor. The review also highlights potential of Pou3F3:I54N to expedite bioassays for patient selection in BTC targeted therapies.

Colorectal cancer (CRC) with BRAF V600E mutation presents a formidable scientific and clinical challenge due to its aggressive nature and poor response to standard therapeutic approaches. BRAF V600E mutation-induced conspicuous activation of the MAPK pathway contributes to the relentless tumor progression. Nevertheless, the efficacy of multi-targeted MAPK pathway inhibition remains suboptimal in clinical practice. Patients with high microsatellite instability (MSI-H) have shown favorable results with immune checkpoint inhibitors (ICIs). The combination of the MAPK pathway inhibition with ICIs has recently emerged as a promising regimen to improve clinical outcomes in the microsatellite stable (MSS) subgroup of BRAF V600E-mutant metastatic CRC patients. In this review, we elucidate the unique tumor biology of BRAF V600E-mutant CRC, with a particular focus on the immune features underlying the rationale for ICI treatments in the MSI-H and MSS subpopulations, then highlight the trends in clinical trials of the ICI therapy for BRAF V600E-mutant metastatic CRC.

Background

We conducted a systematic review to evaluate outcomes and toxicities associated with proton therapy in the treatment of adult-type diffuse glioma.

Methods

Following PRISMA guidelines, we searched PubMed for both prospective and retrospective studies on proton therapy for adult diffuse gliomas, including IDH-mutated gliomas WHO grade 2-3 and glioblastomas. Survival and toxicity outcomes were reported separately for these glioma types.

Results

Twelve studies from 2013 to 2023 were selected, comprising 3 prospective and 9 retrospective studies. The analysis covered 570 patients with WHO grade 2-3 gliomas and 240 patients with glioblastoma or WHO grade 4 gliomas. Proton therapy was found to be comparable to conventional radiotherapy in terms of survival outcomes. Its main advantage is the ability to minimize radiation exposure to healthy tissues.

Discussion

Proton therapy offers comparable survival outcomes to conventional radiotherapy for adult diffuse gliomas and may enhance treatment tolerance, especially regarding neurocognitive function. A major limitation of this review is the predominance of retrospective studies. Future research should ensure rigorous patient selection and adhere to the latest WHO 2021 classification

Early detection of malignancies, through regular cancer screening, has already proven to have potential to increase survival rates. Yet current screening methods rely on invasive, expensive tissue sampling that has hampered widespread use. Liquid biopsy is noninvasive and represents a potential approach to precision oncology, based on molecular profiling of body fluids. Among these, circulating cell-free RNA (cfRNA) has gained attention due to its diverse composition and potential as a sensitive biomarker. This review provides an overview of the processes of cfRNA delivery into the bloodstream and the role of cfRNA detection in the diagnosis of central nervous system (CNS) tumors. Different types of cfRNAs such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been recognized as potential biomarkers in CNS tumors. These molecules exhibit differential expression patterns in the plasma, cerebrospinalfluid (CSF) and urine of patients with CNS tumors, providing information for diagnosing the disease, predicting outcomes, and assessing treatment effectiveness. Few clinical trials are currently exploring the use of liquid biopsy for detecting and monitoring CNS tumors. Despite obstacles like sample standardization and data analysis, cfRNA shows promise as a tool in the diagnosis and management of CNS tumors, offering opportunities for early detection, personalized therapy, and improved patient outcomes.

Hematologic malignancies are lethal diseases arising from accumulated leukemic cells with substantial genetic or epigenetic defects in their natural development. Epigenetic modifications, including DNA methylation and histone modifications, are critical in hematologic malignancy formation, propagation, and treatment response. Both mutations and aberrant recruitment of epigenetic modifiers are reported in different hematologic malignancies, which regarding the reversible nature of epigenetic regulations, make them a potential target for cancer treatment. Here, we have first outlined a comprehensive overview of current knowledge related to epigenetic regulation’s impact on the development and prognosis of hematologic malignancies. Furthermore, we have presented an updated overview regarding the current status of epigenetic-based drugs in hematologic malignancies treatment. And finally, discuss current challenges and ongoing clinical trials based on the manipulation of epigenetic modifies in hematologic malignancies.