Pathogenic BRAF mutations drive constitutive MAPK pathway activation in melanoma, and targeted therapies with dabrafenib plus trametinib have improved outcomes in the adjuvant setting. However, the optimal duration of adjuvant therapy remains unclear. This retrospective study examined whether extending dabrafenib plus trametinib beyond 1 year offers additional clinical benefit in Chinese patients with resected Stage III melanoma. Medical records from six centers were reviewed for adults with BRAF V600E/K-positive, completely resected Stage III melanoma who received at least 12 months of adjuvant dabrafenib plus trametinib. Patients were divided into a 1-year therapy group and a more-than-1-year therapy group. Relapse-free survival (RFS) was the primary end point; adverse events were also assessed. Of the 122 patients included, 77 received more than 1 year of adjuvant therapy. The more-than-1-year group experienced significantly better RFS (log-rank p = 0.04), and longer therapy independently reduced recurrence risk in multivariate analysis (HR, 2.42; p = 0.035). Adverse event profiles did not differ between groups, and toxicity-related treatment modifications occurred primarily within the first year. Extending dabrafenib plus trametinib beyond 1 year may provide improved RFS without increasing toxicity. Further prospective trials are warranted to confirm the impact on overall survival and identify optimal patient subsets for prolonged therapy.

Abstract Sanren Decoction (SRD) has emerged as a promising therapeutic agent for ulcerative colitis (UC) due to its multifaceted mechanisms of action. This study employed an integrative methodology, including network pharmacology, molecular docking, and in vivo experimentation, to elucidate the underlying pharmacological mechanisms of SRD in UC management. The findings identified 87 genes targeted by SRD that are associated with UC, highlighting PTGS2 (Prostaglandin-Endoperoxide Synthase 2) as a crucial target involved in inflammatory processes. Molecular docking analysis confirmed significant interactions between the active compounds of SRD and PTGS2, suggesting a potential anti-inflammatory pathway. In vivo experiments utilizing a DSS-induced colitis mouse model demonstrated that SRD effectively ameliorates clinical symptoms and histopathological damage, enhances intestinal barrier integrity, and modulates macrophage polarization from a pro-inflammatory M1 state to an anti-inflammatory M2 phenotype. Furthermore, SRD was found to alter gut microbiota composition by increasing the abundance of beneficial bacteria and influencing metabolic pathways. These findings establish a strong scientific foundation for the potential of SRD as a comprehensive therapeutic approach for UC, offering promising prospects for its integration into clinical practice.

This case report examines the challenges associated with removing a totally implantable venous access port (TIVAP) used for long-term chemotherapy in a patient with breast cancer. Prolonged use of TIVAPs can result in complications such as catheter kinking, thrombosis, and adhesions between the catheter and surrounding tissues, potentially complicating their removal. A breast cancer patient with bone metastasis presented with difficulty aspirating blood from a TIVAP that had been placed in the right internal jugular vein for 3 years. Initial removal attempts at the Department of Venous Access Center were unsuccessful, likely due to adhesions, necessitating a subsequent successful catheter extraction in a hybrid operating room. Imaging revealed no abnormalities, and the catheter was removed using a mosquito clamp to detach it from surrounding tissues. This case highlights the challenges of removing TIVAPs inserted via the internal jugular vein, particularly when the catheter traverses the sternocleidomastoid muscle. Repeated neck movements might lead to significant adhesions around the catheter, complicating its removal. Careful consideration should be given during catheter placement to avoid muscle-related adhesions and facilitate smoother extraction in long-term use.

Pyrido[2,3-d]pyrimidine and its derivatives have garnered significant attention due to their potential biological and pharmacological activities. Research has demonstrated their significant potential for antitumor and antibacterial applications. Over the years, pyrido[2,3-d]pyrimidine derivatives have remained a research focus for scientists, with numerous synthetic methods and reaction conditions reported. This review comprehensively summarizes the fast, facile, and economical synthetic methods for pyrido[2,3- d]pyrimidine derivatives over the past years, which are categorized based on different synthetic precursors, and evaluates their antitumor and antibacterial activities, aiming to make them better serve the cause of human health.

Noninvasive detection of isocitrate dehydrogenase (IDH) mutations is crucial for preoperative decision-making in patients with glioma. While radiomics has been applied, data imbalance-specifically between IDH wild-type and mutated genes-remains underexplored. We developed a one-class classification-empowered radiomics (OCCR) model, trained exclusively on IDH wild-type patients, to distinguish them from IDH mutation cases. This study included 495 patients from the UCSF Preoperative Diffuse Glioma MRI dataset. T1, T1ce, and FLAIR sequences were registered to T2 and resampled to a 1-mm isotropic resolution. The coregistered data were skull-stripped, and the tumor region was segmented using an ensemble model, followed by manual refinement. We extracted 386 radiomics features from the four MRI sequences and input them into an auto-encoder with 7 hidden layers for reconstruction. The OCCR model was trained on wild-type IDH patients, using the mean square error between the original and reconstructed features as guidance. During validation, reconstruction error was used to differentiate IDH mutations from the wild type. The hold-out validation demonstrated that OCCR performance improved as the number of training samples increased, achieving a peak area under the receiver operating characteristic curve of 0.8018. Visualization of reconstruction errors highlighted first-order and gray-level co-occurrence matrix features in the T1ce sequence. This study demonstrates the feasibility of integrating one-class classification into radiomics for the determination of preoperative IDH mutation status in patients with glioma using multiparametric MRI. This versatile model holds potential for other diseases with substantial data imbalance.

Abstract Background: In the China cohort of the FLAURA study (NCT02296125), first-line (1L) osi demonstrated clinically meaningful progression-free survival (PFS) and overall survival benefits vs comparator EGFR-TKI in Chinese patients (pts) with EGFR-mutated (EGFRm) advanced NSCLC. This exploratory longitudinal ctDNA analysis from the FLAURA China cohort assessed if EGFRm alone vs 168-gene panel (including EGFRm) ctDNA testing identified PD before RECIST PD, the correlation of baseline (BL) plasma EGFRm detection and its clearance with PFS and investigated acquired resistance mechanisms to osi. Methods: Pts ≥18 yrs with untreated, EGFRm (Ex19del or L858R) locally advanced or metastatic NSCLC were randomized 1:1 to osi 80 mg once daily (QD; n=71) or comparator EGFR-TKI (gefitinib or erlotinib; all sites selected gefitinib 250 mg QD, n=65). ctDNA samples were collected at BL, throughout the osi treatment period, and after investigator-assessed RECIST PD and were sequenced by a capture-based 168-gene panel (Burning Rock OncoCompassTM). ctDNA profiling was assessed for acquired resistance and vs PFS for molecular response and ctDNA PD. Results: Overall, 2426 ctDNA samples from 127 pts in China were analyzed. At BL, pts with undetected plasma EGFRm (n=17, 13%) had longer median PFS (mPFS) vs pts with detected EGFRm (n=110); 20.6 mo vs 13.8 mo, respectively (HR 0.68; 95% CI 0.33, 1.25). At Week 3, 64% (38/59) and 72% (36/50) of pts in the osi and comparator arms, respectively, had EGFRm clearance. In both arms, pts with EGFRm clearance had longer mPFS than pts with non-clearance (osi: HR 0.38; 95% CI 0.19, 0.77; comparator: HR 0.23; 95% CI 0.12, 0.48); a positive association with mPFS was also seen at Week 6. When analyzing all mutations (mut) in the 168-gene panel at Week 3, the results were consistent; those pts with EGFRm clearance also had clearance of other BL detected mut. For pts with samples at Week 3 and RECIST PD, 52/81 (64%) had EGFRm ctDNA PD (by predefined criteria) that was equivalent (within 1 week) or earlier than RECIST PD, with median lead times of 2.4 and 2.1 mo for the osi and comparator arms, respectively. Similarly, using the entire 168-gene panel, 56/81 pts (69%) had total ctDNA PD equivalent/earlier than RECIST PD, with median lead times of 2.7 and 2.8 mo for the osi and comparator arms, respectively. In 35 pts in the osi arm with detected EGFRm at BL and PFS events, the most common acquired mut in the last 3 samples up to RECIST PD were MET amplification (6%), EGFR L718Q (6%), PIK3CA mut (6%) and CDKN1B/CDKN2A (6%). Conclusions: BL undetected or early clearance of EGFRm ctDNA were associated with longer mPFS. Longitudinal ctDNA analysis could detect molecular PD before RECIST PD. Analysis of EGFRm was as informative as a 168-gene panel in its association with PFS and detection of molecular PD lead time. Acquired resistance mut profiles to 1L osi were consistent with prior reports. Citation Format: Ying Cheng, Dan Wang, Jacqulyne Robichaux, Yong He, Wei Li, He-long Zhang, Qing Zhou, Buhai Wang, Chunling Liu, Yao Wang, Xiangning Huang, Zhanjian Dong, Rui Mao, Tianyuan Zhou, Ryan Hartmaier. Longitudinal circulating tumor DNA (ctDNA) analysis and acquired mechanisms of resistance to osimertinib (osi) in the China cohort of the FLAURA study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1944.

BackgroundEffective physician-patient communication is essential in clinical practice, especially in oncology, where radiology reports play a crucial role. These reports are often filled with technical jargon, making them challenging for patients to understand and affecting their engagement and decision-making. Large language models, such as GPT-4, offer a novel approach to simplifying these reports and potentially enhancing communication and patient outcomes.ObjectiveWe aimed to assess the feasibility and effectiveness of using GPT-4 to simplify oncological radiology reports to improve physician-patient communication.MethodsIn a retrospective study approved by the ethics review committees of multiple hospitals, 698 radiology reports for malignant tumors produced between October 2023 and December 2023 were analyzed. In total, 70 (10%) reports were selected to develop templates and scoring scales for GPT-4 to create simplified interpretative radiology reports (IRRs). Radiologists checked the consistency between the original radiology reports and the IRRs, while volunteer family members of patients, all of whom had at least a junior high school education and no medical background, assessed readability. Doctors evaluated communication efficiency through simulated consultations.ResultsTransforming original radiology reports into IRRs resulted in clearer reports, with word count increasing from 818.74 to 1025.82 (P<.001), volunteers’ reading time decreasing from 674.86 seconds to 589.92 seconds (P<.001), and reading rate increasing from 72.15 words per minute to 104.70 words per minute (P<.001). Physician-patient communication time significantly decreased, from 1116.11 seconds to 745.30 seconds (P<.001), and patient comprehension scores improved from 5.51 to 7.83 (P<.001).ConclusionsThis study demonstrates the significant potential of large language models, specifically GPT-4, to facilitate medical communication by simplifying oncological radiology reports. Simplified reports enhance patient understanding and the efficiency of doctor-patient interactions, suggesting a valuable application of artificial intelligence in clinical practice to improve patient outcomes and health care communication.

Abstract Purpose: Developing a novel overlap volumes-basedRapidPlan model for cervical cancer radiotherapy, aiming to spare organs at risk (OARs). Methods: A retrospective analysis was conducted on 110 cases of cervical cancer patients. We utilized the planning target volume (PTV) and two organs at risk (OARs): bladder and bowelbag, as the primary protocol standards for planning. Original and unclassified dose-volume histogram (DVH) estimation models (Model-O) were trained using 80 initial plans, there are 40 cases in RMS and RML respectively. The classification criteria used the ratio of bladder volume overlapping with PTV to total bladder volume, and the ratio of bowelbag volume overlapping with PTV to total bowelbag volume. Based on the sum of these volume ratios (SVR), with thresholds of ≤0.4 and &gt;0.4, new training sets and DVH estimation models were generated, named Model-S and Model-L respectively. The plans created using Model-O were named UMO, those configured with Model-S were referred to as RMS, and the plans configured with Model-L were called RML. An analysis of dosimetric parameters for the PTV and OARs was conducted for the three automated plans. Results: For 15 patients with SVR ≤ 0.40, UMO, RMS, and RML automatically produced clinically acceptable plans. Comparing UMO and RML, RMS reduced the high-dose region V47.25 (V105%) for the PTV and provided greater dose sparing in the Bladder and Bowelbag. In cases where SVR exceeded 0.40, the mean PTV coverage with RMS only 94.9%. Comparing to UMO, RML showed greater dose sparing for the Bladder, Bowelbag, Bladder overlap, and Bowelbag overlap, as well as improved V100% of the PTV. Conclusions: The results indicate that employing overlap volumes-based IMRT Rapidplan enhances sparing of OARs when dealing with significant overlap between PTV and OARs.