Future oncology最新文献

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.

What is this summary about?: This is a summary of a phase 2 clinical study called DeLLphi-301. The study looked at how effective and safe a medicine called tarlatamab was in participants with small cell lung cancer (SCLC). Participants previously received at least two other treatments for their SCLC. Tarlatamab is a new medicine that locates a protein called DLL3 on the cancer, which allows T cells to attack the cancer. T cells belong to the body's natural defense system known as the immune system. The DeLLphi-301 study separated participants into two groups to receive tarlatamab 10 mg or 100 mg to determine which dose best shrank SCLC with minimal side effects. All participants received a small first dose (1 mg tarlatamab) to decrease the risk of an immune system reaction called cytokine release syndrome (CRS). Tarlatamab was given through the participant's vein once every 2 weeks. This method of administration is known as intravenous (IV) infusion.

What were the results of the dellphi-301 study?: In the group given 10 mg tarlatamab, 40% of participants responded to treatment (cancer shrank). In the group given 100 mg tarlatamab, 32% of participants responded to treatment (cancer shrank). After taking tarlatamab at either dose, 59% of participants lived for at least 6 months without their cancer growing or getting worse.The most common side effect was CRS, which occurred in 51% of participants in the group given 10 mg tarlatamab and 61% of participants in the group given 100 mg tarlatamab. Other common side effects were decreased appetite, fever, constipation, and anemia. Some participants had a type of immune reaction called immune effector cell-associated neurotoxicity syndrome (ICANS). A small number of participants (3%) stopped taking tarlatamab because of side effects related to tarlatamab.

What do the results from the dellphi-301 study mean?: The study found that tarlatamab given every 2 weeks shrank SCLC in participants with SCLC who received previous treatments. Participants given the 10 mg tarlatamab dose had fewer side effects than those given the 100 mg tarlatamab dose.Clinical Trial Registration: NCT05740566 (DeLLphi-304) (ClinicalTrials.gov).

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.

While suppressing testosterone to castration levels is the aim of androgen deprivation therapy for the treatment of advanced prostate cancer, studies have shown that prolonged low testosterone levels can have negative effects on patients' overall health and quality of life. This podcast covers two recently published papers that examined testosterone recovery in different ways. One real-world study assessed the impact of delayed testosterone recovery on clinical outcomes in patients with prostate cancer. A second subgroup analysis of the HERO trial assessed rates of testosterone recovery in patients receiving the long-acting, injectable gonadotropin-releasing hormone receptor agonist, leuprolide or the oral, once-daily gonadotropin-releasing hormone receptor antagonist, relugolix.

Aim: The Ovarian Cancer Retrospective European (O'CaRE) study assessed the cumulative impact of high-risk factors on progression-free survival (PFS) and overall survival (OS) following first-line treatment in patients diagnosed with advanced ovarian cancer.Patients & methods: Medical records were collected from five European countries (2014 and 2015). Patients were grouped by number of high-risk factors: stage IV diagnosis, no known BRCA mutation, interval debulking surgery or no surgery, or visible residual disease.Results: Our analysis included 405 patients grouped based on having one (20.4%); two (32.3%); three (33.7%) or four (11.9%) high-risk factors. Increasing cumulative numbers of high-risk factors were associated with numerically shorter PFS and OS.Conclusion: Risk profiles should be carefully considered when planning clinical care.

What is this summary about?: This article presents a patient-friendly summary of the MOTION phase 3 clinical trial results, which were published in The Lancet in June 2024.The primary goal of the MOTION trial was to understand if treatment with a drug called vimseltinib shrank tumors more than a placebo in participants with symptomatic tenosynovial giant cell tumor, also known as TGCT, for which surgery was unlikely to provide benefit. A placebo is something that looks like the treatment being studied but does not contain any medicine.The MOTION trial compared the effects of vimseltinib versus a placebo using several different outcomes associated with TGCT. These outcomes included tumor size, active range of motion of the affected joint, and several patient-reported quality-of-life measures including physical function, stiffness, overall health, and pain.

What were the main conclusions reported by the researchers?: The trial showed that more participants treated with vimseltinib experienced significant tumor shrinkage, as defined by a 30% or greater reduction in tumor size, compared with those receiving a placebo. Participants receiving vimseltinib had improved active range of motion, and they reported improved physical function, stiffness, overall health, and pain, regardless of the amount of tumor shrinkage, compared with participants receiving a placebo. Most side effects in participants treated with vimseltinib were not severe and were manageable.

What are the key takeaways?: Vimseltinib was better at shrinking tumors and improving active range of motion, stiffness, pain, and other health measures than the placebo for participants with TGCT. Vimseltinib has the potential to become a new treatment option for patients with TGCT for whom surgery may not provide benefit.

Aim: Studies on immune checkpoint inhibitor (ICI)-related potential neurological adverse events (pNAEs) in Korean lung cancer (LC) patients are scarce. We aimed to examine ICI prescription trends from 2018 to 2022, patient characteristics and factors associated with ICI prescription or concurrent pNAEs in LC.Research design & methods: This observational, cross-sectional study of Korean LC patients investigated four ICIs (pembrolizumab, nivolumab, atezolizumab and durvalumab). The annual ICI prescription rate was calculated by dividing the number of LC patients prescribed ICIs with the total annual number of LC patients. Factors associated with ICI prescriptions or concurrent pNAEs were assessed.Results: The annual ICI prescription rate increased from 3.29% to 9.74% (average: 6.20%). Higher Charlson Comorbidity Index (CCI) scores were associated with more ICI prescriptions (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.07-1.08). Targeted therapy was associated with fewer prescriptions (OR: 0.45; 95% CI: 0.41-0.49). The anti-programmed cell death protein 1 (anti-PD-1) prescription rate was higher in patients with concurrent pNAEs than those without pNAEs (53.09% vs. 50.84%), and this was associated with higher pNAEs prevalence (OR: 1.10; 95% CI: 1.03-1.18).Conclusion: ICI prescription for LC has increased in Korea, CCI and anti-PD-1 increased pNAEs prevalence.

Aim: To understand physicians' attitudes and behaviors regarding EGFR testing and retesting strategies in newly diagnosed metastatic non-small cell lung cancer patients.Materials & methods: Oncologists and pathologists completed an online, cross-sectional survey.Results: Most oncologists (73.3%) and pathologists (53.4%) agreed that concurrent testing increases sensitivity for detecting EGFR mutations. Upon tissue insufficiency, oncologists and pathologists reported using liquid biopsy 77.0% and 39.0% of the time, respectively. Tumor accessibility, smoking status, patient willingness and age were key drivers of tissue re-biopsy. Most oncologists reported high confidence in proceeding to first-line therapy based solely on liquid biopsy (60.7-80.0%); fewer pathologists (37.9%) were comfortable with this decision.Conclusion: Variation in physicians' perceptions of testing and retesting highlights the need for greater stakeholder consensus.

Drug resistance remains a major obstacle in cancer treatment, leading to treatment failures and high mortality rates. Despite advancements in therapies, overcoming resistance requires a deeper understanding of its mechanisms. This review highlights CDK2's pivotal role in both intrinsic and acquired resistance, and its potential as a therapeutic target. Cyclin E upregulation, which partners with CDK2, is linked to poor prognosis and resistance across various cancers. Specifically, amplifications of CCNE1/CCNE2 are associated with resistance to targeted therapies, immunotherapy, endocrine therapies and chemo/radiotherapy. Given CDK2's involvement in resistance mechanisms, investigating its role presents promising opportunities for developing novel strategies to combat resistance and improve treatment outcomes.

Aim: To investigate the prognostic value of pre-ablation stimulated thyroglobulin (ps-Tg) in children and adolescents with persistent differentiated thyroid cancer (DTC) following initial radioiodine therapy (RAI).

Materials & methods: Patients were classified into "no clinical evidence of disease" (NED), "biochemical persistent disease" (BPD), and "structural/functional persistent disease" (S/FPD) groups, based on their therapeutic response to initial RAI. BPD patients were further categorized as incomplete response (IR) or Non-IR; S/FPD patients were categorized as remission or Non-remission. Receiver operating characteristic (ROC) curves were used to assess the predictive value of ps-Tg for long-term prognosis. Univariate and multivariate regression analyses were performed to identify risk factors for IR in BPD group and Non-remission in S/FPD group.

Results: In total, 130 patients were included, with NED (32), BPD (61), and S/FPD (37) patients. Multivariate analysis identified therapeutic response to initial RAI as the only independent predictor of IR in the BPD group. ROC analysis determined an optimal ps-Tg threshold of 112.40 ng/mL for predicting Non-remission in S/FPD patients. Multivariate analysis further confirmed that ps-Tg > 112.4 ng/mL was significantly associated with Non-remission.

Conclusions: Findings indicate ps-Tg as a valuable predictor of long-term prognosis in children and adolescents with persistent DTC post initial RAI.