Future oncology最新文献

Aim: The aim of our study was to investigate a methylation-associated predictor for prognosis in patients with stage I-III lung adenocarcinoma (LUAD). Methods: A DNA methylation-based signature was developed via univariate, least absolute shrinkage and selection operator and multivariate Cox regression models. Results: We identified a 14-site methylation signature that was correlated with recurrence-free survival of stage I-III lung adenocarcinoma patients. By receiver operating characteristic analysis, we showed the high ability of the 14-site methylation signature for predicting recurrence-free survival. In addition, the nomogram result showed a satisfactory predictive value. Conclusion: We successfully identified a DNA methylation-associated nomogram which can predict recurrence-free survival in patients with stage I-III lung adenocarcinoma.

Background: This study aims to investigate biomarkers for predicting non-SLN metastasis and tumor metastatic burden in patients with 1-2 positive sentinel lymph nodes (SLNs).

Research design and methods: 581 patients with SLN metastasis were enrolled, and their blood biochemical indices and clinical information were tested and analyzed.

Results: Among patients with 1-2 positive SLNs, the SLN positivity rate was higher in the non-SLN metastasis group than in the non-metastasis group. Additionally, thrombin time (TT) and fibrinogen (Fbg) levels were lower in the non-SLN metastasis group compared with the non-metastasis group, with ROC AUC = 0.712. Regarding tumor burden, among patients with 1-2 positive SLNs, the SLN positivity rate was significantly higher in those with metastasis lymph nodes (mLNs) ≥ 4 than in those with <4 mLNs, with ROC AUC = 0.727.

Conclusions: The SLN positivity rate, TT, and Fbg may serve as potential biomarkers for non-SLN metastasis in patients with 1-2 positive SLNs. Additionally, the SLN positivity rate may serve as a potential biomarker for mLNs ≥ 4 in cases with 1-2 positive SLNs and in those with only 1 positive SLN.

Background: Approvals of Bruton's tyrosine kinase inhibitors (BTKis) and other novel agents have changed the Mantle Cell Lymphoma (MCL) treatment paradigm, necessitating assessment of contemporaneous, real-world (rw) treatment and outcomes by line of therapy (LOT).

Methods: Patients diagnosed with MCL on or after 1 January 2012 who initiated first-line (1 L) treatment in the COTA database were eligible, excluding those with concurrent primaries, history of hematologic malignancies, clinical trial participation, or missing/imprecise key dates. Rw time to next treatment (rwTTNT) and overall survival (rwOS) were evaluated using the Kaplan-Meier method from LOT start (index).

Results: Of 499 patients, most were ≥ 50 years (94.8%), male (71.5%), treated in the community (58.7%), and diagnosed with stage III/IV disease (91.2%). The most common 1 L regimen was bendamustine+rituximab (BR)±R maintenance (12.6%/23.0%, respectively). Fifty (10.0%) patients received 1 L autologous stem cell transplant. One hundred and seventy-three patients (34.7%) received 2 L, of which 72 (41.6% of 2 L) received 3 L, of which 29 (40.3% of 3 L) received 4 L +. BTKi monotherapy was the most frequently administered therapy in 2 L (26.0%).Median rwTTNT and rwOS from 1 L to 4 L were 36.8-3.2 and 86.2-8.7 months, respectively.

Conclusions: Outcomes of patients who received 2 L+ for MCL remain poor, highlighting unmet need in the contemporary treatment paradigm.

Background: Avoiding unnecessary dose reductions is important for patients with advanced breast cancer (ABC) receiving trastuzumab deruxtecan (T-DXd). Nausea and vomiting, the most common adverse events of T-DXd, frequently necessitate dose reductions, which may impact treatment benefit.

Methods: This retrospective exploratory study investigated the impact of triple antiemetic regimen (TAR) prophylaxis on T-DXd dose preservation over time. Data from 143 human epidermal growth factor receptor 2 (HER2)-positive or HER2-low ABC patients who received ≥2 T-DXd cycles were stratified based on TAR use in the first cycle. TAR included an NK₁ receptor antagonist, a 5-HT₃ receptor antagonist (or fixed netupitant/palonosetron combination), and dexamethasone.

Results: Patients receiving TAR in the first cycle were significantly less likely to require T-DXd dose reductions in subsequent cycles than the non-TAR group (31.3% vs. 66.7%, P = 0.033). The lowest T-DXd dose relative to initial dose for each patient was significantly higher in the TAR group than in the non-TAR group (100% vs. 80.6%, P = 0.001). There was a trend toward a longer median time to T-DXd dose reduction in the TAR group (15.7 vs. 3.9 months; P = 0.183).

Conclusion: These findings suggest that upfront TAR may help maintain the dosing of T-DXd in patients with HER2-positive or HER2-low ABC.

Lorlatinib is a third-generation tyrosine kinase inhibitor approved for first- and second-line treatment of ALK-positive advanced non-small cell lung cancer. The CROWN study demonstrated that first-line lorlatinib significantly improves progression-free survival and intracranial control compared to crizotinib, with sustained benefits observed over a follow-up period of up to 5 years. As lorlatinib is associated with a distinct adverse event (AE) profile, we aim to analyze lorlatinib's safety profile, focusing on AEs incidence, severity, timing and management. A comprehensive safety management framework is also outlined to address lorlatinib-associated toxicity, drawing on evidence from the literature and the clinical expertise of an Italian expert panel. The most frequent AEs associated with lorlatinib are hypercholesterolemia and hypertriglyceridemia, which emerge early after treatment initiation. The 5-year analysis of the CROWN study revealed minimal changes in most AE rates over time. Pharmacological and non-pharmacological approaches effectively resolved most AEs; lorlatinib dose reduction did not affect its efficacy. The proposed safety management framework emphasizes patient preparation and regular monitoring to predict AE occurrence, indicating AE-specific interventions, mitigation strategies and multidisciplinary collaboration to optimize outcomes. Lorlatinib's toxicity appears generally predictable and manageable; the safety framework offers pragmatic guidance to clinicians for appropriate management in clinical practice.

Breast cancer is one of the leading cause of mortality among females worldwide. Regarding the side effects of current therapeutics, the development of novel target-specific treatments is a priority. Probiotic bacteria, as nutraceuticals, have shown anti-cancer potential, supported by cell culture-based and animal model studies. There are studies indicating differences in gut and breast microbiota between healthy individuals and cancerous patients. Given the immunomodulatory and regulatory effects of probiotics on hormone-mediated pathways, the consumption of probiotics can be considered a safe approach in breast cancer management. This review summarizes the recent research on the potential therapeutic roles of Lactobacillus strains in breast cancer.

Background: Barriers preventing oncologists from engaging patients as research partners remain. This study aimed to understand oncologists' barriers to patient engagement and involvement (PEI) in research and identify solutions to overcome barriers.

Research design and methods: The study consisted of three phases: I, insights research (n = 6); II, qualitative research (n = 30); III, a Working Group of PEI experts providing recommendations (n = 10). Five hypotheses representing oncologists' barriers to PEI identified in phase I were tested in phase II: A) preference for physician-led approach to medicine; B) limited PEI value in research processes; C) misconceptions about approaching PEI; D) practical barriers to PEI; E) traditional research dynamics preventing PEI.

Results: Hypotheses C, D, and E were identified as the most critical and ranked in descending order of difficulty to overcome (D, E, and C). Solutions were ranked according to importance (whether oncologists perceived barriers as prominent within their communities) and feasibility (for stakeholders to find solutions). Solutions included leveraging institutional PEI teams, allocating funding for PEI, practical/logistical support for patient research partners, incentivising PEI, facilitating training, creating a patient research partner directory, and PEI guidelines.

Conclusions: Enhanced support for oncologists and institutional incentives to encourage PEI in all aspects of research are required.

Aim: Programmed death (ligand) 1 inhibitors (e.g., avelumab, pembrolizumab, and retifanlimab) are first-line treatment options for patients with locally advanced or metastatic Merkel cell carcinoma (MCC). In the absence of comparative and randomized trials, we aimed to systematically identify and synthesize real-world evidence (RWE) on the effectiveness and safety of immunotherapies in patients with advanced MCC.

Methods & materials: MEDLINE and Embase searches were conducted for observational RWE studies in locally advanced or metastatic MCC from January 2017 to December 2023. Avelumab was the only immunotherapy with sufficient data for analysis. Landmark 12-month overall survival (OS) and progression-free survival (PFS) were assessed by meta-analysis.

Results: Screening of 1731 records identified 37 publications eligible for inclusion (16 unique studies), of which eight were included in the meta-analysis. In line with results from the JAVELIN Merkel 200 trial, pooled 12-month OS rates of 77.7% in stage III and 63.0% in stage IV MCC and 12-month PFS rates of 53.3% and 39.3%, respectively, were estimated. Although safety data were insufficient for meta-analysis, two retrospective studies reported lower adverse event rates than JAVELIN Merkel 200.

Conclusions: The results of this study support broader use of avelumab in advanced MCC.

Aims: The study team investigated the relative efficacy of brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) versus positron emission tomography (PET)-guided doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) among previously untreated adults with advanced Hodgkin lymphoma via matching-adjusted indirect comparison (MAIC).

Materials & methods: A systematic literature review identified ECHELON-1 (A+AVD), RATHL, and SWOG S0816 as feasible trials referencing a targeted comparator (PET-guided ABVD). Effect modifiers/prognostic variables were identified by clinical expert opinion and Cox regression using long-term ECHELON-1 individual patient-level data. Weighted Cox regressions generated hazard ratios (HR) and 95% confidence intervals (CI) representing A+AVD versus PET-guided ABVD relative treatment effect on overall survival (OS) and progression-free survival (PFS).

Results: OS improved significantly with A+AVD versus PET-guided ABVD (HR [95% CI] 0.48 [0.32, 0.73], p < 0.001 [RATHL]; 0.49 [0.26, 0.92], p = 0.043 [SWOG S0816]). PFS significantly favored A+AVD over PET-guided ABVD in both trial comparisons. While the proportional hazards assumption did not hold for these comparisons, 8-year restricted mean survival time and piecewise Cox regression results aligned with the main results.

Conclusion: MAIC results indicated durable A+AVD treatment benefits in adults with newly diagnosed advanced Hodgkin lymphoma versus PET-guided regimens evaluated in RATHL and SWOG S0816.