Future oncology最新文献

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.

Aim: Immunomodulatory drugs (IMiDs), proteasome inhibitors, and monoclonal antibodies (MAbs) alone or in combination form the backbone of multiple myeloma (MM) treatment, yet MM remains incurable requiring further lines of therapy (LOT). This study investigated real-world treatment patterns, clinical outcomes, and healthcare utilization among triple-class exposed (TCE) patients initiating subsequent LOTs.

Methods: TCE patients receiving additional LOTs (January 2012-December 2022) in the Alberta Health System databases were included.

Results: Median age among 221 TCE patients requiring subsequent LOT was 70 years. MAbs (42%) and IMiDs (51%) were the most common drug classes incorporated as first and second LOT, respectively. After first LOT, attrition rate was 32%. From first LOT, median time to next treatment or death (TTNT-D) was 10.1 (95% confidence interval: 8.4-13.3) months, median TTNT was 18.1 (15.6-22.4) months and overall survival was 18.7 (16.0-24.3) months. Within first year of subsequent LOT, patients had a median of 1 emergency department visit, 1 hospitalization, 33 clinic visits, 4 infusion appointments, 37 unique healthcare encounters, and a mean of 32 days spent on laboratory tests.

Conclusion: Treatment for TCE patients has limited effectiveness and a high healthcare system burden, emphasizing the unmet need for therapies with novel mechanisms of action.

Breast cancer is a complex disease due to its heterogeneity. While there have been impressive advancements in the treatment of the different breast cancer subtypes, challenges persist when the tumor develops acquired treatment resistance and finally progresses on a given therapy. Since human epidermal growth factor receptor 3 (HER3) plays a key role in developing resistance to several anticancer therapies, many efforts have been performed over the last decades to effectively target HER3. However, most of these attempts have been unsuccessful due to their limited efficacy or severe toxicity. Numerous antibody-drug conjugates (ADCs) targeting HER3 are now being explored. Patritumab deruxtecan (U3-1402; HER3-DXd), the most advanced ADC targeting HER3 in clinical development, has demonstrated significant antitumor activity and a manageable safety profile in patients with breast cancer. This efficacy has been observed across diverse tumor subtypes and varying levels of HER3 expression. In this review, we will analyze the results of clinical trials investigating HER3-DXd in breast cancer and explore its potential role in future clinical applications and treatment algorithms.

Aims: The ALIDHE study aims to supplement previous clinical trial data by evaluating the safety and tolerability of ivosidenib + azacitidine in adult patients with newly diagnosed mutant isocitrate dehydrogenase acute myeloid leukemia (AML).

Methods: Notably, this study has been designed in collaboration with patient representatives from the Acute Leukemia Advocates Network (ALAN) at all stages. Patient representatives from ALAN completed a survey and attended workshops to share feedback on the study design to reduce the burden of participation for patients. Using feedback from ALAN, the study protocol was adjusted to minimize clinical visits and optimize study duration. Quality of life and mental health were included as endpoints in ALIDHE as these outcomes have been recognized as important to capture the lived experiences of patients with AML. Efforts were made to ensure patient comprehension through accessible study documents such as a plain language video and one-page summary.

Conclusions: ALIDHE represents, to our knowledge, the first AML clinical trial that involves patient representatives from development of the study concept to follow-up. ALAN will continue to be involved in ALIDHE as part of the patient steering committee, to ensure that patient perspectives and needs continue to be considered throughout the study duration.