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David F. Yankelevitz
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EP1.04 - Immuno-oncology (ID 194)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.04-15 - NSCLC Response Determinants to Chemoimmunotherapy: Deep Profiling of Tumors Following Neoadjuvant Cemiplimab and Chemotherapy (Now Available) (ID 1021)
08:00 - 18:00 | Author(s): David F. Yankelevitz
- Abstract
Background
Clinical trials have demonstrated synergistic effects of combination chemoimmunotherapy in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC), however, our understanding is limited as to why and for whom PD-1 blockade with or without chemotherapy is effective, as is our understanding of the mechanism of synergy between these therapies.
While most patients with resectable NSCLC receive neoadjuvant or adjuvant chemotherapy, this intervention only changes the natural course of disease for ~5% of patients. Early studies have demonstrated major pathologic responses to neoadjuvant immunotherapy ± chemotherapy.
Method
To investigate the immunodynamic effect of PD-1 blockade and chemotherapy, and identify potentially more effective immune modifying targets or combinations, we will use novel immunophenotyping platforms to characterize the effect of this combination on the tumor. This trial will enroll 52 patients with Stage Ib-IIIa NSCLC into three cohorts receiving 2 cycles of 1) platinum-doublet chemotherapy, 2) the PD-1 antibody cemiplimab, or 3) combination chemoimmunotherapy. Following surgery, patients will receive additional adjuvant chemoimmunotherapy; in total all patients will receive 4 cycles of standard platinum-doublet chemotherapy and 8 cycles of cemiplimab. All patients will undergo pre-treatment biopsies of their tumor, and blood will be collected at 6 time-points before and after surgery.
The primary endpoint for this clinical trial is major pathologic response, defined as ≤10% viable tumor within resection. Secondary endpoints include: delay of surgery, disease-free survival, overall response rate, overall survival, measurement of adverse events, and change in CD8 T-cell infiltration.
Exploratory endpoints include in-depth analysis of the pre-treatment tumor biopsies and post-treatment surgical specimens, and paired blood. We will characterize proteomic and transcriptomic changes in the stromal and immune compartment of tumors at the histologic level using a multiplexed ion-beam imaging (MIBI)—a novel multiplex immunohistochemistry platform capable of analyzing >50 markers on a single section of tissue—and at the single-cell level using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITEseq), a novel platform combining the proteomic data-potential of mass cytometry (CyTOF) and the transcriptomic data-potential of single cell RNA sequencing including TCR sequencing. Feasibility of this multi-pronged approach has been demonstrated on untreated NSCLC (unpublished data, submitted as abstract to WCLC by our group).
To probe for biomarkers correlating with response or resistance to therapy, we will perform unbiased analysis of peripheral blood lymphoid and myeloid populations by CyTOF, and measure nearly 100 soluble factors in serum using Olink.
Result
This trial opened to accrual April 2019.
Conclusion
Section not applicable.
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OA06 - Refining Lung Cancer Screening (ID 131)
- Event: WCLC 2019
- Type: Oral Session
- Track: Screening and Early Detection
- Presentations: 1
- Now Available
- Moderators:Tomasz Grodzki, Lluis Esteban Tejero
- Coordinates: 9/09/2019, 11:00 - 12:30, Hilton Head (1978)
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OA06.03 - An Open Source Lung Screening Management System (Now Available) (ID 1467)
11:00 - 12:30 | Author(s): David F. Yankelevitz
- Abstract
- Presentation
Background
Starting in 1992, the Early Lung Cancer Screening Project (ELCAP) investigators developed the ELCAP Management System (MS) to ensure high quality care and follow-up of the first 1,000 ELCAP participants. The resulting Lancet publication in 1999 created worldwide interest in screening and an updated web-based ELCAP MS was updated to be web-based and provided free of charge to participating institutions, together with the I-ELCAP protocol.
Method
The ELCAP MS was designed to be comprehensive and rapidly capture information on each participant to be used by coordinators, navigators, nurses, radiologists, and other medical professionals to ensure appropriate follow-up and care. It provides rapid documentation of telephone or other inquiries, registering, scheduling screening appointments, reporting results, diagnosis of lung cancer, and treatment, and archives all CT images for integrated access of image and patient information. It has been iteratively updated through user feedback, and supports medical reimbursement requirements and continuous quality improvement to minimize harms of lung screening across International ELCAP (I-ELCAP) sites.
Result
More than 81,000 participants in 80 institutions worldwide have contributed their LDCT findings and images. The MS has provided efficient data collection for rigorous assessment of screening outcomes which has resulted in some 300 publications and abstracts for protocol updating, comparisons, and continuous quality improvement.
Having anticipated “open science”, the ELCAP MS has been translated into an open source MS that offers a reference standard for data elements (1,500 data fields, 267 required) for robust and efficient management of lung screening programs. This first open source translation has been adopted by the United States Veterans Administration (VA) and integrated into its VistA Electronic Healthcare System for deployment at 10 VA medical centers through a grant for VA Partnership to increase Access to Lung Screening (VA-PALS). The software is being certified by the Open Source Electronic Health Record Alliance (OSEHRA); source code is available on GitHub.
Automated quantitative tools have been developed for identification and characterization of nodules, emphysema, major airways, calcification scoring of coronary arteries, aortic valve, thoracic aorta, breast tissue, liver, bone, and image quality. These tools are integrated into the ELCAP MS, and in the future will provide automatically-generated quantitative LDCT reports.
Conclusion
The ELCAP MS and I-ELCAP protocol have helped define current global standards for lung screening. Its developers have now made the ELCAP MS publicly available through OSEHRA for support of lung screening programs of any scale throughout the world.
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