Predictive Role of Computed Tomography Texture Analysis in Patients with Metastatic Urothelial Cancer Treated with Programmed Death-1 and Programmed Death-ligand 1 Inhibitors

2020 ◽  
Vol 3 (5) ◽  
pp. 680-686 ◽  
Author(s):  
Francesco Alessandrino ◽  
Rahul Gujrathi ◽  
Amin H. Nassar ◽  
Arwa Alzaghal ◽  
Arvind Ravi ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Texture Analysis ◽  
Urothelial Cancer ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Metastatic Urothelial Cancer ◽  
Programmed Death 1 ◽  
Predictive Role

Tumor, immune, and stromal characteristics associated with clinical outcomes with atezolizumab (atezo) + platinum-based chemotherapy (PBC) or atezo monotherapy (mono) versus PBC in metastatic urothelial cancer (mUC) from the phase III IMvigor130 study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5011-5011 ◽  
Author(s):  
Matt D. Galsky ◽  
Romain Banchereau ◽  
Habib Rahman Hamidi ◽  
Ning Leng ◽  
Will Harris ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Urothelial Cancer ◽  
Phase Iii ◽  
Rna Seq ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Tumor Mutational Burden ◽  
Predictive Role ◽  
Clinical Trial Information

5011 Background: Tumor mutational burden (TMB), PD-L1 expression, T-effector gene expression (GE) and a fibroblast TGF-β–response signature (F-TBRS) are associated with clinical outcomes with atezo mono in mUC (Mariathasan, Nature, 2018). Here we explore the potential predictive role of these biomarkers and APOBEC mutagenesis in IMvigor130. Methods: Pts receiving first-line (1L) mUC treatment (tx) were randomized 1:1:1 to atezo + PBC, atezo mono, or placebo + PBC. Coprimary efficacy endpoints were PFS and OS. Planned exploratory biomarker analyses included PD-L1 expression, TMB (FoundationOne), and T-effector GE (RNA-seq). Results: The 851 biomarker-evaluable pts (BEP) were representative of the 1200 ITT pts. Biomarker results are shown in Table. PD-L1 IC2/3 was associated with significantly longer OS for atezo mono vs placebo + PBC and a combination of PD-L1 IC2/3, and high TMB (> 10 muts/Mb) identified a pt subset (≈ 14% of BEP) with particularly favorable outcomes with atezo mono vs placebo + PBC; similar results for PD-L1 and TMB were not seen with atezo + PBC vs placebo + PBC. APOBEC mutagenesis was associated with improved OS with atezo-containing regimens whereas high F-TBRS was associated with inferior OS with atezo mono. Conclusions: These results reinforce the potential predictive nature of biomarkers associated with response/resistance to atezo and highlight potentially distinct biology driving benefit with atezo and atezo + PBC. These findings suggest a possible biomarker-directed approach to 1L mUC tx that warrants mechanistic interrogation and prospective validation. Clinical trial information: NCT02807636 . [Table: see text]

Predictive role of CT texture analysis in patients with metastatic urothelial cancer treated with PD-1/PD-L1 inhibitors.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 424-424
Author(s):  
Francesco Alessandrino ◽  
Rahul Gujrathi ◽  
Amin Nassar ◽  
Arwa Alzaghal ◽  
Arvind Ravi ◽  
...  
Keyword(s):  
Texture Analysis ◽  
Urothelial Cancer ◽  
Stepwise Logistic Regression ◽  
Stepwise Logistic Regression Analysis ◽  
Contrast Enhanced Ct ◽  
Specificity And Sensitivity ◽  
Metastatic Urothelial Cancer ◽  
Ct Texture Analysis

424 Background: Reliable biomarkers to predict response of urothelial cancer to PD-1/PD-L1 inhibitors are still being investigated. Texture analysis represents underlying tumor heterogeneity and may serve as a predictor of response in urothelial cancer. The purpose of this study was to assess predictive ability of CT texture analysis for disease progression in patients with metastatic urothelial cancer treated with PD-1/PD-L1 inhibitor. Methods: In this IRB-approved HIPAA-compliant retrospective study, from total 93 consecutive patients with metastatic urothelial cancer treated with PD-1/PD-L1 inhibitors from 2013-2018, 43 patients with measurable disease per RECIST 1.1 criteria who had contrast-enhanced CT performed within three months after starting treatment were included. Progression-free survival was calculated based on serial follow-up CTs, and 11 patients without progression who did not reach 1 year follow-up were excluded. Texture features of measurable lesions on first follow-up CT were extracted (TexRAD Ltd, Feedback Plc, Cambridge, UK). Stepwise logistic regression analysis to identify patients who had progressive disease (PD) at 12 months was performed and performance assessed using receiver operator curves. Results: Of 32 included patients (24 men, 8 women; median age: 65 years) who had total 80 measurable lesions, 22 progressed by 12 months. On first follow-up CT, the entropy and mean of the lesions were higher (p = 0.04, p = 0.02) for patients with PD by 12 months. Calculated specificity and sensitivity of entropy (AUC = 0.79) were 90%, and 63%; of mean (AUC = 0.81) were 90%, and 50%. A predictive model including mean and entropy yielded 95% sensitivity, 80% specificity, 91% PPV, 89% NPV and 91% accuracy (AUC = 0.863) to identify patients with PD at 12 months. Conclusions: Texture analysis of CT performed within three months after starting PD-1/PD-L1 can help predict patients who progress by 12 months with high accuracy. Further studies investigating the correlation of texture analysis with survival endpoints may help validate the role of texture analysis as a biomarker to predict response to PD1/PD-L1 inhibitors.

scholarly journals The role of Programmed Death-Ligand 1 expression in nasopharyngeal carcinoma

2021 ◽  
Vol 50 (2) ◽  
pp. 174
Author(s):  
Nadya Dwi Karsa
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cancer Cells ◽  
Growth And Development ◽  
Cell Mediated Immunity ◽  
Significant Prognostic Factor ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Immunotherapy Target

ABSTRACTBackground: Nasopharyngeal carcinoma (NPC) is a malignant tumor that arises from the epithelial cell that cover surface of the nasopharynx, which has the highest incidence of all types of head and neck cancer. Cell-mediated immunity plays an important role in the growth and development of NPC. The expressions of Programmed Death-Ligand 1 (PD-L1) of NPC is still being debated and researched. Objective: To find out and understand the role of PD-L1 expression in NPC. Literature review: PD-L1 is a ligand from Programmed Death-1 (PD-1) receptors that could be expressed by cancer cells. When the PD-1/PD-L1 pathway is active, it promotes survival of cancer cells via anti apoptotic signals and inhibits the activation of signaling pathways, which are critical for survival of T cells. Conclusion: Various studies had found an increase of the PD-L1 expression in NPC cancer cells. PD-L1 is also a potentially important tumor immunotherapy target and can be a significant prognostic factor in NPC. ABSTRAKLatar belakang: Karsinoma nasofaring (KNF) merupakan suatu tumor ganas epitelial nasofaring yang mempunyai insiden tertinggi di antara kanker kepala dan leher. Imunitas selular mempunyai peran penting terhadap pertumbuhan dan perkembangan KNF. Ekspresi Programmed Death-Ligand  1 (PD-L1) pada KNF masih diperdebatkan dan diteliti. Tujuan: Mengetahui dan memahami peran PD-L1 terhadap kejadian KNF. Tinjauan Pustaka: PD-L1 merupakan ligan dari reseptor Programmed Death-1 (PD-1) yang dapat diekpresikan oleh sel kanker. Jalur PD-1 / PD-L1 yang teraktivasi akan melindungi sel kanker melalui sinyal anti apoptosis dan menghambat aktivasi jalur-jalur pengiriman sinyal lain yang sangat penting untuk kelangsungan hidup sel T. Kesimpulan: Berbagai penelitian menemukan adanya peningkatan ekspresi PD-L1 pada sel kanker KNF. PD-L1 menjadi suatu target imunoterapi yang sangat penting dalam meningkatkan respon imun terhadap sel kanker dan dapat dijadikan suatu faktor prognosis pada KNF.

scholarly journals The Role of Yes-Associated Protein (YAP) in Regulating Programmed Death-Ligand 1 (PD-L1) in Thoracic Cancer

Biomedicines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 114 ◽  
Author(s):  
Ping-Chih Hsu ◽  
Cheng-Ta Yang ◽  
David Jablons ◽  
Liang You
Keyword(s):  
Immune Responses ◽  
Immune Checkpoint ◽  
T Cell Tolerance ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Anti Cancer ◽  
Thoracic Cancer ◽  
Future Work ◽  
Human Nsclc

The programmed death-ligand 1(PD-L1)/PD-1 pathway is an immunological checkpoint in cancer cells. The binding of PD-L1 and PD-1 promotes T-cell tolerance and helps tumor cells escape from host immunity. Immunotherapy targeting the PD-L1/PD-1 axis has been developed as an anti-cancer therapy and used in treating advanced human non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Yes-associated protein (YAP) is a key mediator of the Hippo/YAP signaling pathway, and plays important roles in promoting cancer development, drug resistance and metastasis in human NSCLC and MPM. YAP has been suggested as a new therapeutic target in NSCLC and MPM. The role of YAP in regulating tumor immunity such as PD-L1 expression has just begun to be explored, and the correlation between YAP-induced tumorigenesis and host anti-tumor immune responses is not well known. Here, we review recent studies investigating the correlation between YAP and PD-L1 and demonstrating the mechanism by which YAP regulates PD-L1 expression in human NSCLC and MPM. Future work should focus on the interactions between Hippo/YAP signaling pathways and the immune checkpoint PD-L1/PD-1 pathway. The development of new synergistic drugs for immune checkpoint PD-L1/PD-1 blockade in NSCLC and MPM is warranted.

scholarly journals Protective Role of Programmed Death 1 Ligand 1 (PD-L1)in Nonobese Diabetic Mice: The Paradox in Transgenic Models

Diabetes ◽  
2008 ◽  
Vol 57 (7) ◽  
pp. 1861-1869 ◽  
Author(s):  
C.-J. Wang ◽  
F.-C. Chou ◽  
C.-H. Chu ◽  
J.-C. Wu ◽  
S.-H. Lin ◽  
...  
Keyword(s):  
Protective Role ◽  
Diabetic Mice ◽  
Transgenic Models ◽  
Nonobese Diabetic ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Nonobese Diabetic Mice
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