Future oncology最新文献

Vasculogenic mimicry (VM) allows tumor cells to form vessel-like channels, promoting growth, metastasis, and therapy resistance. Persistent infection with high-risk human papillomavirus (HPV), mainly types 16 and 18, is a key factor in various cancers, including anogenital and head and neck cancers. VM has been documented in cervical cancer and oral squamous cell carcinoma (OSCC), but its role in other HPV-associated cancers remains unexplored. This review summarizes literature published between October 2024 and April 2025 in PubMed and Google Scholar, focusing on VM in HPV-related cancers. General mechanisms highlighted include epithelial-mesenchymal transition, hypoxia, and activation of STAT3 and PI3K/AKT pathways. Molecular regulators include TXNDC5, CHI3L1, erythropoietin, and microRNAs miR-124 and miR-29b in cervical cancer; and collagen XVI, LGR5, ALDH1, Beclin 1, VE-cadherin, CD44, HIF-1α, and SOX7 in OSCC. From a translational perspective, elucidating the molecular regulators of VM could reveal therapeutic opportunities through strategies targeting specific signaling pathways in tumor cells.

The unsatisfactory prognosis of patients with early-stage hepatocellular carcinoma (HCC) emphasizes the urgent need for perioperative treatment to reduce recurrence after surgery. The combination of transarterial chemoembolization (TACE), tyrosine kinase inhibitor (TKI), and programmed cell death protein 1 (PD-1) inhibitor has emerged as a promising treatment for unresectable HCC, yet its perioperative application was not explored. PERI-START is a prospective, single arm phase II trial which aims to investigate the efficacy and safety of TACE, tislelizumab (PD-1 inhibitor), and lenvatinib (TKI) in perioperative (neoadjuvant and adjuvant) use for resectable, high-risk HCC. Within 1 week after enrollment, TACE will be administered. Subsequently, intravenous tislelizumab will be given every 3 weeks in combination with daily oral lenvatinib. Unless disease progression occurs, liver resection will then be performed. 4-6 weeks after liver resection, tislelizumab and lenvatinib will be resumed for 6 months. The primary endpoint is the major pathological response (MPR) rate, with secondary endpoints including objective response rate (ORR), R0 resection rate, event-free survival (EFS), overall survival (OS), and adverse events (AEs).Clinical trial registration: ChiCTR2400085067 (www.chictr.org.cn).

Aims: To develop and validate a nomogram for predicting high - grade components in primary lung adenocarcinomas using tumor growth rate and clinical radiological characteristics.

Materials & methods: This retrospective study included 735 patients who underwent surgical resection for lung adenocarcinoma. Tumor segmentation was performed on two preoperative CT scans to calculate the specific growth rate (SGR), defined as the natural logarithm of 2 divided by the volume doubling time (VDT) of the tumor. A nomogram was constructed using multivariable logistic regression analysis with significant predictors.

Results: The nomogram included tumor volume, consolidation - to - tumor ratio (CTR), and SGR. The model showed excellent discrimination in the training cohort (AUC = 0.884), validation cohort (AUC = 0.910), and test cohort (AUC = 0.969). Decision curve analysis indicated a higher net benefit compared to imaging or growth models alone.

Conclusions: The nomogram, incorporating clinical and radiological characteristics with tumor growth metrics, accurately predicted high - grade components in primary lung adenocarcinomas. This tool may aid in preoperative planning and personalized treatment. Future work should focus on prospective multic - center validation and exploring automated segmentation methods.

Aims: This retrospective study aimed to assess the potential of radiomic features extracted from dual-energy computed tomography (DECT) images, combined with machine learning algorithms, for the noninvasive prediction of microvessel density (MVD) in clear cell renal cell carcinoma (ccRCC).

Methods: We manually segmented regions of interest (ROIs) on corticomedullary phase (CMP) images to extract radiomic features. Tumor microvessel parameters were determined by immunohistochemical staining. Prediction models for MVD were developed using both multi-energy and monoenergetic sequence DECT images. Subsequently, a combined model was constructed based on the best-performing radiomics score and statistically significant clinical features, and was visualized as a nomogram. Furthermore, an external validation cohort was recruited from Center II to evaluate the performance of the nomogram.

Results: The support vector machine (SVM) classifier achieved the best performance for the multi-energy sequence MVD prediction model, with an AUC of 0.914 in the validation set. The MVD prediction model based on iodine-based material decomposition images (IMDI), constructed using the SVM classifier, achieved an AUC of 0.889 in the validation set. The nomogram showed good calibration, achieving an AUC of 0.757 in the external validation cohort.

Conclusions: DECT-based radiomic features show potential for noninvasive predicting microangiogenesis in patients with ccRCC.

Introduction: Ivosidenib is an inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1) that is approved alone or in combination with azacitidine in patients with mIDH1 acute myeloid leukemia (AML) that are ineligible to receive intensive chemotherapy.

Aims: Here we describe the design of ALIDHE, an international, multicenter, single-arm, open-label Phase 3b study of ivosidenib + azacitidine for treatment of newly diagnosed mIDH1 AML in usual clinical practice.

Methods: The primary endpoints are adverse events (AEs), clinical laboratory anomalies assessed as AEs, patients requiring transfusion and number of units transfused, and infection rate. The impact of ivosidenib + azacitidine treatment on health-related quality of life, healthcare resource utilization and measurable residual disease will also be assessed.

Clinical trial registration number: NCT05907057 (ClinicalTrials.gov).

Perioperative chemoimmunotherapy improves pathological complete response (pCR), EFS, and OS in patients with resectable NSCLC versus chemotherapy, as shown in several phase-III-trials. However, approximately 17-22% of patients did not proceed to surgery, partly due to toxicity, highlighting the need for more efficacious and tolerable regimens. NeoTRACE is a phase II, multicenter, single-arm study to evaluate neoadjuvant sacituzumab govitecan (SG) and the PD-1 inhibitor zimberelimab (ZIM) in resectable stage II to IIIB (N2) NSCLC with no known EGFR/ALK alterations. The trial plans to enroll 50 participants, with neoadjuvant treatment administered for four cycles before resection, followed by adjuvant ZIM with/without SG at the physicians' discretion. The primary endpoint is the rate of pCR in tumor and lymph nodes. Secondary endpoints include major pathological response, surgical resection rate, disease-free survival, OS, safety, and quality of life. The study also explores circulating tumor DNA (ctDNA) dynamics, TROP2 expression, and spatial transcriptomics to identify biomarkers. NeoTRACE assesses a platinum-sparing approach in resectable NSCLC. Previous studies showed ADC and immunotherapy combinations are effective in advanced NSCLC, suggesting potential perioperative benefit. This study aims to improve pCR rate, reduce toxicity, enhance surgical eligibility, and personalize adjuvant treatment to improve long-term outcomes.Clinical Trial Registration: EudraCT: 2024-517561-16.

Aim: Gene fusions involving Neurotrophic Receptor Tyrosine Kinase (NTRK) genes lead to Tropomyosin Receptor Kinases (TRK) overexpression. Detecting NTRK1-3 fusions through advanced molecular techniques has revolutionized cancer care through personalized medicine, such as TRK inhibitors.

Methods: We conducted a comprehensive search of databases (PubMed/MEDLINE, SCOPUS, Web of Science) and extracted data on study characteristics, molecular characteristics, and clinical outcomes. Data synthesis involved narrative and thematic analysis and study quality assessment using the Methodological Standard for Epidemiological Research (MASTER) scale.

Results: We included 136 studies with 18,077 patients. The most common tumor categories were unclassified soft tissue sarcomas (11.09%), gynecological sarcomas (5.64%), and liposarcomas (3.37%). Most tumors were gynecologic (5.64%), followed by the limbs (1.45%). Genomic sequencing was the predominant diagnostic method used in 110 studies. Overall, 551 patients with sarcoma tested positive for NTRK1-3 gene fusions, primarily involving NTRK1 and NTRK3 (~93%), with ETV6-NTRK3 fusion being the most frequently reported fusion. Larotrectinib was used in 142 patients, demonstrating an 83.80% response rate, with low mortality (2.82%) and recurrence (2.11%) rates. Entrectinib had a lower response rate of 63.64%.

Conclusions: We confirm the rarity of NTRK1-3 fusions in sarcomas. TRK inhibitors show high efficacy in sarcomas, emphasizing the necessity of genomic testing in all cases.Protocol registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024563594.