Future oncology最新文献

For the past few years, researchers and oncologists have been pushing to find biomarkers that would help predict which treatment option would best work on a patient. Tumor Mutational Burden (TMB) is one of the latest biomarkers that is being studied and considered as a promising agnostic immunotherapy biomarker. However, it still shows controversial results in studies due to the difficulty in finding solid comparable results. This is a consequence of different cutoff definitions among many cancer types, age ranges, and the use of different sequencing assays, in addition to its association with other biomarkers such as PD-L1. Finally, the use of composite biomarkers to assess the genetic signature of a tumor might be the way forward to seriously use TMB as an agnostic biomarker.

Background: The global incidence of prostate cancer (PCa) is rising, necessitating improved diagnostic strategies. This study explores coagulation parameters' predictive value for clinically significant PCa (csPCa) and develops a nomogram.

Research design and methods: This study retrospectively analyzed data from 702 patients who underwent prostate biopsy at Shandong Provincial Hospital (SDPH) and 142 patients at Shandong Cancer Hospital and Institute (SDCHI). SDPH patients were randomly assigned at a 7:3 ratio for internal validation, while SDCHI data served as external validation. LASSO and logistic regression identified the best predictive factors for csPCa, which were used to construct a model. The model's efficacy was tested using AUC, calibration curves, and decision curve analysis.

Results: TPSA, age, D-dimer, prostate volume (PV), and digital rectal examination (DRE) were identified as independent risk factors for csPCa. A predictive model was constructed using a nomogram. The AUC for the training set was 0.841, for internal validation 0.809, and for external validation 0.814. Calibration and decision curves confirmed the model's clinical utility.

Conclusions: The nomogram incorporating D-dimer, TPSA, age, PV, and DRE provides a highly accurate tool for assessing csPCa risk in individuals with PSA levels of 4-20 ng/mL, supporting personalized diagnostics and clinical decision-making.

Background: Though efforts have been made toward standardizing access to quality cancer care in Japan, there are still geographical and institutional disparities in the level of cancer care availability. We investigated the utilization of cyclin-dependent kinase 4/6 inhibitors plus endocrine therapy (CDK4/6i+ET) as first-line (1 L) treatment for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) in Japan.

Research design and methods: This cross-sectional survey included physicians who had treated ≥3 1 L patients with HR+/HER2- ABC in the past year.

Results: Of 41,695 physicians invited, 300 were included in the analysis. The mean percentage share of CDK4/6i+ET and ET monotherapy was 38.3% and 42.2%, respectively. Common challenges facing CDK4/6i+ET prescription were adverse reaction management, prohibitive cost, and a preference for ET monotherapy for treating elderly patients. Key solutions included reducing the burden of adverse reaction management, improving financial support, and preparing educational videos for medical staff.

Conclusions: The study concluded that CDK4/6i+ET is not well established as a 1 L option in Japan as of 2022. More effective ways of creating awareness and supportive tools are needed for CDK4/6i+ET to be adopted as standard of care in Japan.

Trial registration number: UMIN000050760.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, with high rates of postoperative recurrence. Identifying reliable biomarkers for predicting recurrence is critical for improving patient outcomes. This study investigates the predictive value of m6A methylation-related genes, METTL4 and METTL5, on HCC recurrence after surgery.

Research design and methods: We analyzed METTL4 and METTL5 expression in HCC and adjacent non-cancerous tissues using the TCGA database and evaluated their levels in surgical samples from 67 hCC patients. A recurrence risk model was developed and validated in an external cohort of 65 patients.

Results: METTL4 and METTL5 were significantly overexpressed in HCC tissues. High expression correlated with shorter recurrence-free survival (RFS). The model stratified patients into high, medium, and low-risk groups with 3-year RFS rates of 18.75%, 69.70%, and 93.75%, respectively.

Conclusions: METTL4 and METTL5 expression levels are strong predictors of HCC recurrence. The risk model offers a novel approach for postoperative management of HCC.

Background: The co-occurrence of PD-L1 positivity and EGFR mutations in advanced NSCLC often limits EGFR-TKIs effectiveness, with unclear mechanisms.

Methods: We analyzed 103 treatment-naive EGFR-mutant LUAD patients from three centers, assessing PD-L1 expression and performing NGS analysis.

Results: SMO mutations and MET amplification were significantly higher in the PD-L1 ≥ 1% group versus PD-L1 < 1% group (SMO: 8% vs. 0%, p = 0.048; MET: 18% vs. 7%, p = 0.023). The DNA Damage Response and Repair (DDR) pathogenic deficiency mutations, along with biological processes and signaling pathways related to DNA recombination, cell cycle transition and abnormal phosphorylation, were more prevalent in the PD-L1 ≥ 1% group. PIK3CA and RARA clonal alterations were more common in PD-L1 < 1% group, while TP53 clonal mutations predominated in PD-L1 ≥ 1% group. Retrospective analysis showed EGFR-TKIs plus chemotherapy extended median PFS by 9.8 months, potentially overcoming EGFR-TKI monotherapy resistance.

Conclusion: This study elucidates the genomic characteristics of PD-L1-induced resistance to EGFR-TKIs. For patients with concurrent mutations in EGFR and PD-L1 expression, a first-line treatment strategy combining EGFR-TKIs with chemotherapy may offer a more effective alternative.

People living with cancer should have access to clear and comprehensible treatment information to empower informed decision-making. With the increasing adoption of open access publishing and plain-language summaries, clinical trial findings in journals are becoming more accessible. However, this will only help patients if they are equipped with the relevant knowledge and understanding to make sense of these findings. This podcast highlights the need to support this aspect of health literacy by bringing together the perspectives of a patient, a patient advocate and a medical oncologist. It is accompanied by two visual, plain-language guides designed to help general audiences understand the key efficacy end points that are commonly used in trials of solid tumor treatments.

Aim: Perform early economic evaluation comparing active surveillance (AS) to surgery for women with low-risk ductal carcinoma in situ, a precursor of invasive breast cancer.Materials & methods: A 10-year incremental costs (€) and quality-adjusted life years (QALYs) were compared between a simulated cohort of women undergoing breast conserving surgery ± radiotherapy, and a cohort with a low-risk subgroup undergoing AS using a semi-Markov model. Scenario and headroom analyses evaluated a better-performing biomarker to select low-risk women for AS.Results: AS resulted in lower costs and survival, but higher QALYs (±0.40). Scenario analyses maintained survival outcomes and maximized QALYs.Conclusion: AS for low-risk ductal carcinoma in situ is cost-effective, but a better-performing biomarker to select low-risk women can maximize quality-adjusted outcomes.

Background: Following an early-stage cancer diagnosis, recurrences can occur. To quantify financial impacts of a first recurrence, we surveyed patients and caregivers.

Methods: The survey was self-administered online to patients (N = 202) with early-stage bladder, gastric, head and neck, melanoma, non-small cell lung, renal cell, and triple-negative breast cancers that recurred and caregivers (N = 100) of such patients. Work productivity and financial impacts were explored.

Results: Negative impacts on work productivity, employment, finances, and healthcare resource use were identified, with significant differences seen across cancer types, between locoregional and distant/metastatic recurrences, and from pre-recurrence to post-recurrence.

Conclusions: The financial burden to patients, caregivers, healthcare systems, and society following early-stage cancer recurrence is substantial. Treatments that decrease recurrences can reduce this burden.