Expert Review of Anticancer Therapy最新文献

Introduction: Tenosynovial giant cell tumors (TGCTs) are locally aggressive mesenchymal neoplasms that often occur in younger patients and cause long-term disability. Surgical management remains the standard of care, but with high risks of surgical morbidity, systemic treatment options are important to consider, particularly in diffuse disease. Improved understanding of the molecular pathogenesis of TGCTs has led to exciting developments in this arena.

Areas covered: This review aims to provide historical context for systemic treatments for patients with TGCTs with a focus on the diffuse subtype (DT-TGCT) while exploring the more recently available treatments in depth. Current literature on TGCTs and therapy was reviewed and summarized by a comprehensive search of MEDLINE (1/1/1989-11/30/2024). We also suggest directions for future investigation in the systemic treatment space for TGCT with a goal to alleviate symptoms and improve quality of life while minimizing treatment-related toxicity.

Expert opinion: Advances in the understanding of the molecular pathogenesis of TGCT has led to systemic therapies targeting the CSF1 receptor (CSF1R), including the first FDA approval in this space of pexidartinib. These developments provide the foundation for further investigation into additional treatments, optimal sequencing, and duration of therapies for patients with symptoms and reduced functionality secondary to TGCT.

Introduction: The rise of recent novel therapies teclistamab, elranatamab, and talquetamab for the treatment of relapsed/refractory multiple myeloma (RRMM) is a rapidly evolving area with significant clinical implications that require exploration and evaluation.

Areas covered: The current review highlights the clinical trial data, safety endpoints, and practical administration considerations for the bispecific therapies currently used in multiple myeloma. This article reviewed the efficacy and safety results between the three different bispecifics, and the differences in dosing and monitoring requirements. Adverse event management for the bispecific antibodies will be explored including the need for antimicrobial prophylaxis, premedication, and IVIG replacement. Future considerations for widespread bispecific administration and ongoing clinical trials are discussed.

Expert opinion: Practical considerations for bispecific administration such as hospitalization requirements, monitoring of adverse events, and medication considerations are emphasized. Future directions and clinical implications regarding the pivotal role of these agents will be discussed.

Background: The role of 21-gene recurrence score (RS) testing on chemotherapy decision-making and survival outcomes for T3N0 luminal breast cancer (BC) remains unclear. This study aimed to investigate the effect of RS testing in chemotherapy selection and prognosis in these patients.

Research design and methods: Patients diagnosed with T3N0 luminal BC were included from the Surveillance, Epidemiology, and End Results Oncotype database. The likelihood of undergoing chemotherapy was analyzed using the chi-square test and binomial logistic regression. Survival analysis used Kaplan-Meier method and multivariate Cox proportional hazards models.

Results: Of the 3186 patients, 852 (26.7%) underwent RS testing. Those who had RS testing demonstrated a lower probability of chemotherapy receipt than those without RS testing (27.0% vs. 47.5%, p < 0.001). Higher RS correlated with increased the probabilities of chemotherapy receipt. The probabilities of chemotherapy for low-risk, intermediate-risk, and high-risk were 9.8%, 26.7%, and 60.6%, respectively (p < 0.001). RS testing independently improved breast cancer-specific survival (p < 0.001) and overall survival (p < 0.001). In the high-risk cohort, chemotherapy administration was associated with improved overall survival than those who did not (p = 0.038).

Conclusions: Our study highlights the significant role of RS testing in guiding treatment decisions and improving survival outcomes for patients with T3N0 luminal BC.

Background: To identify the diagnosis and treatment strategies by analyzing the clinical characteristics and treatment methods of RNNCLR.

Methods: A total of 210 patients pathologically diagnosed with RNNCLR were retrospectively included. Clinical characteristics, MRI features, treatment methods, and survival outcomes were analyzed. Propensity score matching (PSM) analysis was performed to adjust the surgical benefit.

Results: Ninety-one patients (43.3%) took a single biopsy, 67 patients (31.9%) underwent repeated biopsies and 52 patients (24.8%) received endoscopic surgery to obtain pathological positive tissues. RNNCLR had characteristic imaging features distinguished from pure radiation necrosis. The interval from the previous radiotherapy was 13.2 (7.0, 23.3) months. The 1-year, 3-year, and 5-year overall survival rates were 59.6%, 32.3%, and 14.6%. Patients with reirradiation, detectable EBV-DNA level, or ICA exposure had a worse prognosis. Overall survival was significantly higher in the endoscopic surgery group than in nonsurgery group after PSM (3-year OS rates, 44.5% vs. 23.9%, p = 0.011).

Conclusions: Histopathological diagnosis of RNNCLR needs repeated biopsies or even surgery. Careful analysis of MRI images, correlation with interval time from last radiation, and short-term follow-up may solve the diagnostic dilemmas. Endoscopic surgery results in a survival benefit by completely resecting lesions or removing necrotic tissue to reduce necrosis-related complications.

Objectives: This meta-analysis aimed to evaluate the prognostic significance of circulating long non-coding RNAs (lncRNAs) in colorectal cancer (CRC).

Methods: A comprehensive literature search was conducted in databases (Embase, Web of Science, PubMed, and Cochrane Library) up to July 2022. The quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). Statistical analysis was performed with Review Manager 5.4 and Stata 17.0. Publication bias was assessed using Begg's test, and sensitivity analysis was conducted to validate the meta-analysis results.

Results: Ten articles, comprising 1,473 CRC patients and 18 different circulating lncRNAs, were included. Thirteen circulating lncRNAs were found to be up-regulated in CRC patients, while five were down-regulated. High expression of circulating lncRNAs up-regulated in CRC patients was associated with shorter CRC OS (HR = 2.91, 95% CI: 1.17, 7.22; P = 0.02, I2 = 86%). Conversely, high expression of circulating lncRNAs down-regulated in CRC patients was linked to longer CRC OS (HR = 0.16, 95% CI: 0.07, 0.40; P < 0.0001, I2 = 0%) and improved DFS (HR = 0.52, 95% CI: 0.37, 0.74; P = 0.0002, I2 = 0%). Additionally, circulating lncRNA levels correlated with TNM staging, tumor location, and lymph node metastasis.

Conclusion: Circulating lncRNAs show promise as prognostic markers for CRC patients, but further studies are warranted to validate these findings.

Objective: This meta-analysis aims to examine the effectiveness of veliparib, a poly ADP-ribose polymerase inhibitor, in combination with chemotherapy in treating bronchogenic carcinoma.

Methods: PubMed, Cochrane, Scopus, and Web of Science were searched for eligible randomized controlled trials comparing veliparib plus chemotherapy to standard chemotherapy in adult lung cancer patients, until July 2023. The main outcomes were overall survival (OS) and progression-free survival (PFS).

Results: This meta-analysis included six studies encompassing 2,136 patients. Veliparib has a slight OS improvement over placebo, HR = 0.91, 95% CI [0.83 to 1.0], p = 0.05. Veliparib offers more OS benefit in the subpopulation of non-small cell lung cancer (NSCLC) than small-cell lung cancer (SCLC), HR = 0.89, 95% CI [0.81,0.99], p = 0.03 and HR = 1.00, 95% CI [0.79, 1.28], p = 0.97, respectively. There was no significant PFS benefit between the two groups, HR = 0.92, 95% CI [0.81-1.01], p = 0.08).

Conclusion: Veliparib has a marginal inclination for overall survival improvement, more so in NSCLC, with an acceptable safety profile. Our results merit the pursuit of better-powered trials to support further the extent of veliparib's effectiveness in lung cancer patients.

Registration: PROSPERO (CRD42023453705).

Background: The research on the associations between tissue inhibitors of metalloproteinase-1 (TIMP1) expression and the clinicopathological characteristics and prognosis of patients with gastric cancer (GC) have resulted in contradictory findings. Exploring the associations between TIMP1 and clinicopathological parameters and the prognosis of GC patients is essential.

Methods: We searched the literature in the databases according to the inclusion and exclusion criteria. Hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to evaluate the relationships between TIMP1 expression and the clinicopathological parameters and prognosis of GC patients.

Results: Nine studies with 1,200 GC patients were included. Our results indicated that TIMP1 expression was not related to sex, age, TNM stage, depth of invasion, lymph node metastasis, or tumor size in GC patients. However, TIMP1 expression was associated with the differentiation of GC. Furthermore, TIMP1 expression was associated with poor prognosis in GC patients.

Conclusion: TIMP1 expression was related to tumor differentiation and poor prognosis but not sex, age, TNM stage, depth of invasion, lymph node metastasis or tumor size.

Introduction: Childhood cancers as a group affect around 1 in 500 children but each individual diagnosis is a rare disease. While research largely focuses on improving cure rates, the management of side effects of treatment are high priority for clinicians, families and children and young people.

Areas covered: The prevention and efficient management of infectious complications, oral mucositis, nausea and vomiting and graft-vs-host disease illustrated with examples of implementation research, translation of engineering to care, advances in statistical methodologies, and traditional bench-to-patient development. The reviews draw from existing systematic reviews and well conducted clinical practice guidelines.

Expert opinion: The four areas are driven from patient and family priorities. Some of the problems outlined are ready for proven interventions, others require us to develop new technologies. Advancement needs us to make the best use of new methods of applied health research and clinical trial methodologies. Some of the greatest challenges may be those we're not fully aware of, as new therapies move from their use in adult oncological practice into children. This will need us to continue our collaborative, multi-professional, multi-disciplinary and eclectic approach.