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  • American Society of Clinical Oncology (ASCO)  (3)
  • Medicine  (3)
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  • American Society of Clinical Oncology (ASCO)  (3)
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  • Medicine  (3)
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  • 1
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 8568-8568
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 8568-8568
    Abstract: 8568 Background: Low dosage computer tomography (LDCT) has been widely adopted as a sensitive method to detect early-stage lung cancer; however, debate regarding its accuracy and overdiagnosis is still ongoing. An accurate non-invasive test is needed to identify malignant nodules and reduce unnecessary invasive procedures. Studies show that plasma proteins and LDCT imaging features may be used to discriminate malignant pulmonary nodules from benign ones. We aimed to develop a combinatorial approach integrating serum protein markers and imaging features to improve the classification of pulmonary nodules. Methods: This study established a prospective research cohort, which enrolled 608 patients of pulmonary nodules. Plasma samples were collected to measure protein levels using Proximity Extension Assay (PEA) technology. The imaging features of the pulmonary nodules were extracted using the python 'radiomics' package. Following feature extraction, a deep learning networks model was built using training cases. The model was then tested in the testing set to evaluate its accuracy and robustness. Results: From the study cohort, 184 benign (BN) and 184 malignant (MT) samples matched for sex and age were chosen to have a representative training set. The rest 240 samples (81 BN and 159 MT) were used as a testing set. Image features were extracted from 448 patients (119 BN and 153 MT in training; 57 BN and 119 MT in testing) with raw LDCT image available. In the testing set, the model trained using only protein levels had an AUC of 0.83 [0.782-0.877] (sensitivity = 71.1% [95% CI 63.6-77.6] ; specificity = 82.7% [73.1-89.4]) when classifying plasma samples of lung cancers from those of benign nodules. In comparison, the imaging features-only model had an AUC of 0.874 [0.821-0.916] (sensitivity = 81.5 [73.6-87.5]; specificity = 73.7 [61.0-83.4] ). The combinatorial model integrating both protein and imaging features had an AUC of 0.878 [0.830-0.921] (sensitivity = 83.2% [75.5-88.8] ; specificity = 77.2% [64.8-86.2]). Notably, the combinatorial model was highly sensitive for early-stage lung cancer, achieving a sensitivity of 93.1% [78.0-98.1] when classifying stage-0 lung cancer cases(n = 29) and 94.8% [85.9-98.2] for stage-I cases (N = 58). Its sensitivity for stage II-IV (n = 7) and clinically diagnosed lung cancers cases (n = 25) were 100% [64.6-100] and 40.0% [23.4-59.3], respectively. Conclusions: This study aimed to construct a model to distinguish malignant pulmonary nodules from benign lung diseases using protein levels and LDCT imaging features. The resulted combinatorial model showed by utilizing both types of features, it was able to accurately differentiate benign and malignant pulmonary nodules, suggesting it may provide guidance for the clinical management of these nodules.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 16 ( 2020-06-01), p. 1797-1806
    Abstract: Platinum-based chemotherapy for first-line treatment of metastatic urothelial cancer is typically administered for a fixed duration followed by observation until progression. “Switch maintenance” therapy with PD-1 blockade at the time of chemotherapy cessation may be attractive for mechanistic and pragmatic reasons. PATIENTS AND METHODS Patients with metastatic urothelial cancer achieving at least stable disease on first-line platinum-based chemotherapy were enrolled. Patients were randomly assigned double-blind 1:1 to switch maintenance pembrolizumab 200 mg intravenously once every 3 weeks versus placebo for up to 24 months. Patients with disease progression on placebo could cross over to pembrolizumab. The primary objective was to determine the progression-free survival. Secondary objectives included determining overall survival as well as treatment outcomes according to PD-L1 combined positive score (CPS). RESULTS Between December 2015 and November 2018, 108 patients were randomly assigned to pembrolizumab (n = 55) or placebo (n = 53). The objective response rate was 23% with pembrolizumab and 10% with placebo. Treatment-emergent grade 3-4 adverse events occurred in 59% receiving pembrolizumab and 38% of patients receiving placebo. Progression-free survival was significantly longer with maintenance pembrolizumab versus placebo (5.4 months [95% CI, 3.1 to 7.3 months] v 3.0 months [95% CI; 2.7 to 5.5 months] ; hazard ratio, 0.65; log-rank P = .04; maximum efficiency robust test P = .039). Median overall survival was 22 months (95% CI, 12.9 months to not reached) with pembrolizumab and 18.7 months (95% CI, 11.4 months to not reached) with placebo. There was no significant interaction between PD-L1 CPS ≥ 10 and treatment arm for progression-free survival or overall survival. CONCLUSION Switch maintenance pembrolizumab leads to additional objective responses in patients achieving at least stable disease with first-line platinum-based chemotherapy and prolongs progression-free survival in patients with metastatic urothelial cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 4504-4504
    Abstract: 4504 Background: Platinum-based chemotherapy for 1st-line treatment of pts with metastatic urothelial cancer (mUC) is typically administered for a fixed duration followed by observation until recurrence. PD-1 blockade with pembro improves survival of pts with mUC progressing despite platinum-based chemotherapy. We explored the potential benefit of earlier use of PD-1 blockade using a "switch maintenance" approach. Methods: Pts with mUC achieving at least stable disease after up to 8 cycles of 1st-line platinum-based chemotherapy were enrolled. Pts were randomized 1:1 to pembro 200 mg IV q3 weeks versus placebo for up to 24 months; pts progressing on placebo could cross over to pembro. Randomization was stratified based on pre-chemotherapy visceral metastases (Y/N) and response to 1 st -line chemotherapy (CR/PR vs. SD). The primary objective was to determine the progression-free survival (PFS) as per irRECIST among pts treated with pembro versus placebo. Results: Between 12/2015 and 11/2018, 107 pts were randomized to placebo (n=52) versus pembro (n=55). The baseline pt characteristics are shown in the Table. Pts randomized to placebo and pembro received a median of 6 and 8 cycles, respectively. Excluding patients with baseline CRs, the objective response rate was 12% (5/42) on placebo and 22% (10/46) on pembro. Grade 3-4 treatment emergent adverse events occurred in 48% of pts on placebo and 56% on pembro. At a median follow-up of 14.7 months, 41 pts have died and 26/52 pts randomized to placebo have crossed over to pembro. PFS was significantly longer in patients randomized to pembro vs. placebo (Maximum Efficiency Robust Test p=0.036; log-rank p = 0.038). The 18-month restricted mean progression-free survival time was 5.6 months with placebo and 8.2 months with pembro (p=0.023). Conclusions: Switch maintenance pembro may “deepen” responses achieved with 1 st -line chemotherapy. Switch maintenance pembro prolongs PFS in pts with mUC completing 1 st -line platinum-based chemotherapy. Clinical trial information: NCT02500121. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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