American Journal of Clinical Oncology-Cancer Clinical Trials最新文献

Background: Currently, cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors combined with hormone therapy are the standard treatment for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer. It remains unclear which patients benefit most from CDK4/6 inhibitors and whether predictive biomarkers exist to guide treatment decisions. Therefore, we evaluate the association between phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation status and treatment response to CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer.

Methods: We extensively searched PubMed, Web of Science, Cochrane Library, and Google Scholar databases for articles published until December 2024. The primary outcome of our study was progression-free survival (PFS), and the secondary outcomes included overall survival (OS) and objective response rate (ORR).

Results: Seven studies-involving 2221 women with HR+/HER2 metastatic breast cancer-were systematically analyzed. The pooled results showed that patients with PIK3CA mutation had significantly poorer PFS than those with PIK3CA wild-type (hazard ratio [HR]: 1.47; 95% CI: 1.22-1.77; P<0.0001). Similarly, PIK3CA mutation was associated with significantly poorer OS than PIK3CA wild-type (HR: 1.42; 95% CI: 1.06-1.89; P=0.02). ORR was only reported in one study, with the results showing that the ORR was higher in patients with wild-type PIK3CA than in patients with PIK3CA alteration (53/180 (29%) versus 13/85 (15%).

Conclusions: PIK3CA mutation correlates with poor PFS and OS in patients with HR+/HER2- metastatic breast cancer receiving CDK4/6 inhibitors. Therefore, PIK3CA mutation status should be considered a potential predictive biomarker of resistance to CDK4/6 inhibitors.

Objectives: Care guidelines recommend specific treatment pathways for early-stage breast cancer, but real-world adherence may vary due to institutional workflow and system-level limitations. This study examined rates of guideline-concordant care (GCC) at a single academic medical center over 5 years and evaluated differences by stage, patient demographics and time frame involving the COVID-19 pandemic.

Methods: A retrospective review was performed of all women diagnosed with American Joint Committee on Cancer (AJCC) Stage 0-III breast cancer at a National Cancer Institute-designated cancer center between September 1, 2019, and September 1, 2024. GCC was defined according to National Comprehensive Cancer Network (NCCN) guidelines as mastectomy alone, lumpectomy with radiation, or lumpectomy alone in patients ≥70. Demographic and clinical data were extracted, and rates of GCC were assessed by stage, race, insurance type, and for variance during the COVID-19 pandemic.

Results: Among 1455 patients diagnosed with stage 0-III breast cancer, 981 (67.4%) received some form of treatment, and 515 (35.4%) received GCC. Stage II patients had the lowest rate of GCC (28.7%). Rates of GCC remained stable before and after April 2020, though total diagnoses declined. Black patients had the highest rate of GCC (52.1%), while Asian/Pacific Islander patients had the lowest (21.9%). No clear relationship was observed between insurance type or ZIP code-based income and GCC receipt.

Conclusions: Most patients diagnosed with breast cancer received treatment, but fewer than half met criteria for GCC. Differences in GCC rate by stage and race suggest both institutional and patient-level barriers to standard care. System improvements aimed at strengthening coordination between diagnosis and treatment may help increase adherence to guideline-based breast cancer care.

The combination in patients with HER2-positive and HER2-low metastatic breast cancer (MBC) of Concurrent Trastuzumab Deruxtecan (T-DXd) and Radiation Therapy (RT) is not enough studied. We conducted a retrospective study including patients treated between 11/2020 and 01/2024. Patients with HER2-positive and HER2-low MBC who received concurrent T-DXd and RT were identified. Data on patient demographics, treatment regimens, radiation doses, toxicity profiles, efficacy, and treatment discontinuations were collected. The toxicities were graded using CTCAE V5.0. Population of 33 patients with HER2-positive and HER2-low MBC who underwent concurrent T-DXd&RT, were studied. The median follow-up (FU) was 14 months. There were 39.4 partial remissions and 9.4 attained complete remission. In addition, 39.4% experienced stable disease, and 12.1% faced disease progression necessitating a change in therapy. Safety assessment revealed that acute toxicities were mainly associated with systemic treatment. Survival analysis showed 11 deaths (33.3%) during the FU period, with a median overall survival of 26 months and median progression-free survival of 12 months. The combination of T-DXd with RT in demonstrates promising efficacy with a manageable safety profile. Further studies are warranted to fully elucidate the potential synergistic effects of this treatment regimen and its impact on patient outcome.

Objectives: To determine if chemotherapy contributes to the development of overactive bladder (OAB) in female cancer patients.

Methods: A prospective, longitudinal study was conducted from 2017 to 2023 at Mount Auburn Hospital to assess the effects of chemotherapy on the development of OAB. Sixty-five female patients diagnosed with nonmetastatic breast cancer, lung cancer, or lymphoma were asked to complete 5 validated questionnaires regarding bladder symptoms just before starting chemotherapy and again at 6 weeks, 3 months, 6 months, and 12 months.

Results: Fifty-eight patients completed the study. Overall, we detected no significant increase in OAB symptoms at any time point relative to baseline. However, an analysis of the data according to different chemotherapy regimens revealed that patients being treated with human epidermal growth factor receptor-2 (HER2) monoclonal antibodies, either trastuzumab alone or in combination with pertuzumab, had significantly higher scores on the questionnaires after the start of chemotherapy. When the HER2-treatment group was further subdivided, we found that patients receiving both monoclonal antibodies, trastuzumab, and pertuzumab, reported more significant urinary tract discomfort and changes in quality of life, particularly at the 6-month and 12-month time points.

Conclusions: We conclude from our study that women receiving both trastuzumab and pertuzumab for HER2-positive breast cancer may experience an increase in OAB symptoms during the course of their treatment.

To systematically evaluate the risk factors for postoperative complications of venous thromboembolism in patients with gynecologic malignancies. Cohort studies and case-control studies on the risk factors of postoperative venous thromboembolism in gynecologic malignancy patients were included in the search of China Knowledge, Wanfang, Wipro, China Biomedical Literature Database, PubMed, Cochrane Library, Embase, and Web of Science databases from inception to March 2025, and were analyzed. Studies. Data were statistically analyzed using RevMan 5.2 software. A total of 19 studies involving 123,329 patients with gynecologic malignancies were included. The analysis showed that advanced age (OR=3.08, 95% CI=2.85-3.32, P <0.00001), open surgery (OR=9.18, 95% CI=2.38-35.34, P =0.001), high surgical complexity (OR=9.97, 95% CI=5.80-17.15, P <0.00001), and surgical duration (OR=3.33, 95% CI=2.97-3.73, P <0.00001), high BMI (OR=4.77, 95% CI=3.47-6.57, P <0.00001), comorbidities (OR=21.02, 95% CI=8.72-50.70, P <0.00001), and prolonged bed rest in the postoperative period ( OR=25.16, 95% CI=10.32-61.32, P <0.00001), high intraoperative bleeding (OR=107.53, 95% CI=17.71-652.85, P <0.00001), and high D-dimer level (OR=5.55, 95% CI=3.27-9.43, P <0.00001), advanced tumor stage (OR=7.58, 95% CI=2.22-25.90, P =0.001), high tumor grade (OR=27.67, 95% CI=8.39-91.18, P <0.00001), and occurrence of lymph node metastasis (OR=31.21, 95% CI=9.54-102.15, P <0.00001) were all were risk factors for postoperative venous thrombosis in patients with gynecologic malignancies. Clinical staff should take into account the 12 risk factors identified in this study to actively identify gynecologic malignant tumor patients at high risk for venous thromboembolism after surgery and provide targeted measures to prevent or reduce the risk of postoperative DVT.

Objectives: This practice parameter was revised collaboratively by the American College of Radiology (ACR) and American Radium Society (ARS). Stereotactic body radiation therapy (SBRT) precisely delivers higher dose(s) of radiation in 5 of fewer fractions, compared with conventional radiation. Given the complexity and technical nature of this treatment technique, practice parameters are needed to provide guidance to physicians and physicists.

Methods: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website ( https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards ) by the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ARS.

Results: Workflow, qualifications/responsibilities of personnel, quality control, and treatment delivery/verification are reviewed. Notable elements of SBRT include image guidance, immobilization, and motion management, with the treatment planning goal of minimizing the volume of normal tissue exposed to medium and high dose levels and maximizing dose safely to the target. Specialized training is encouraged, as some technologies are not used in standard treatments.

Conclusions: This practice parameter provides direction on key components recommended for SBRT and may be used as a guide to physicians and physicists wanting to provide this treatment to their patients.

Objectives: The practice parameter was revised collaboratively by the American College of Radiology (ACR), the American Brachytherapy Society (ABS), the American College of Nuclear Medicine (ACNM), the American Radium Society (ARS), the Society of Interventional Radiology (SIR), and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). This document summarizes current evidence-based guidelines for the administration of Yttrium radioembolic therapy to the liver, including training requirements, evidence-based guidelines for administration, and safe practice for administration.

Methods: This practice parameter was revised according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website ( https://www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards ) by the Committee on Practice Parameters-Interventional and Cardiovascular Radiology of the ACR Commission on Interventional and Cardiovascular, Committee on Practice Parameters and Technical Standards-Nuclear Medicine and Molecular Imaging of the ACR Commission on Nuclear Medicine and Molecular Imaging and the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the ABS, the ACNM, the ARS, the SIR, and the SNMMI.

Results: This review seeks not to be a comprehensive discussion of radiotherapy to the liver, but rather, seeks to provide a parameter for safe and effective therapy. We discuss the qualifications of physicians involved in this therapy, basic indications, contraindications, procedural work-up, safe-handling, and regulatory requirement for the administration of selective internal radiation therapy to patients that are likely to benefit. The goal of this document is not to define which patients are best treated by these therapies, as this is best determined for individual patients after multidisciplinary review. A consistent and evidence-based approach to therapy, however, would benefit all patients who are offered this therapy. This document seeks to provide a framework for current best practices for the administration of the 2 currently available radioembolization devices.

Conclusions: As Yttrium-90 radiotherapy to the liver occupies a growing role in the treatment of primary and metastatic liver cancer, this review seeks to assist clinicians of all involved specialties to optimize the efficacy and safety of these procedures.

Objectives: The vascular endothelial growth factor (VEGF) pathway plays a crucial part in tumor angiogenesis by enhancing the creation of new blood vessels that supply oxygen. Breast cancer cells with overexpressed human epidermal growth factor receptor 2 (HER2) usually produce high levels of VEGF, because HER2 signaling upregulates VEGF expression. We aim to investigate the clinical benefit of VEGF and HER2 inhibitors in the treatment of breast cancer.

Methods: A systematic search for records from inception until January 2025 was conducted in PubMed, Web of Science, MEDLINE, Scopus, and Google Scholar. The primary endpoint of the present review was the overall response rate (ORR), and the secondary endpoints were complete response (CR) and partial response (PR).

Results: Five distinct clinical trials enrolling 307 women with HER2-positive breast cancer were included in the present meta-analysis. The pooled analysis revealed that the ORR of breast cancer patients treated with anti-HER2 combined with anti-VEGF was 31.9% (95% CI: 21.6%-44.2%). Moreover, 4.9% of patients treated with anti-HER2 combined with anti-VEGF achieved CR, and 32.6% achieved PR. Data from 2 included trials also showed that patients treated with lapatinib and pazopanib had significantly higher response rates than patients receiving lapatinib alone (OR: 2.21; 95% CI: 1.15-4.22; P = 0.017).

Conclusions: Dual inhibition of HER2 and VEGF demonstrated promising responses, with 31.9% of patients achieving ORR. Furthermore, the combined targeting of HER2 and VEGF, with lapatinib and pazopanib results in better responses than monotherapy targeting of HER2 with lapatinib.

Objectives: Chemotherapy-induced cardiotoxicity is still a major clinical problem, usually appearing subclinically before structural or symptomatic cardiac dysfunction appears. Standard surveillance methods use imaging and biomarkers, which are time-intensive and money-intensive and can only identify damage at more advanced levels. Electrocardiography (ECG) provides a low-cost, non-invasive method that can detect early electrophysiological changes but is not fully utilized in cardio-oncology. The present work was designed to build an explainable machine learning model for predicting chemo-like cardiotoxicity patterns at an early stage from single-lead ECG signals.

Methods: A public ECG data set (n=4997 segments) underwent preprocessing and was converted to 18 temporal, morphologic, and spectral features. Two ensemble learning algorithms-Random Forest and XGBoost-were trained and validated with stratified splits. Model performance was assessed with ROC-AUC, PR-AUC, and F1-score with 1000 bootstrap resampling. Feature interpretability was evaluated through permutation importance and SHAP analysis.

Results: Both models scored near-perfect classification (ROC-AUC and PR-AUC>0.99, F1-score ≈ 0.986). Spectral entropy, band3 (high-energy frequency), QT surrogate, and peak count were the top features ranking alongside early cardiotoxicity indicators like repolarization instability and autonomic imbalance.

Conclusions: The feature-driven, interpretable ML architecture suggested here shows that single-lead ECG has the potential to be an affordable and clinically relevant tool for the early detection of chemotherapy-induced cardiotoxicity. The method provides a feasible route toward implementation in precision cardio-oncology, particularly in resource-poor or ambulatory environments.