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A.A. Vaporciyan
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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.01-054 - Lung Cancer PD-L1 mRNA Expression Profile and Clinical Outcomes - An Analysis From The Cancer Genome Atlas and Cancer Cell Line Encyclopedia (ID 5048)
14:30 - 14:30 | Author(s): A.A. Vaporciyan
- Abstract
Background:
Programmed death ligand 1 (PD-L1) has become one of the most studied biomarkers in early, and advanced non-small cell lung cancers (NSCLC). Conflicting results have been reported in the literature on the value of PD-L1 in predicting survival in surgically resected lung cancers. Our aim was to evaluate mRNA PD-L1 expression and survival based on the data available from the Cancer Genome Atlas (TCGA), and Cancer Cell Line Encyclopedia (CCLE).
Methods:
To determine the expression profile and clinical correlations of PD-L1 in lung cancers we used publicly available lung adenocarcinoma and squamous cell carcinoma (SCC) data from TCGA, and small cell and NSCLC line data from the CCLE. We performed Kaplan-Meier and correlation analyses to show how PD-L1 expression correlates with overall survival and other clinical variables. Lung cancer and normal tissue expression comparisons were also performed using normal tissue expressions from the Genotype-Tissue Expression (GTEx) project.
Results:
Results: PD-L1 mRNA expression from RNA sequencing was available for 517 lung adenocarcinoma and 501 lung SCC samples in the TCGA. The CCLE database contained PD-L1 expression for 12 small cell and 75 NSCLC cell lines. Lung cancers demonstrated a higher PD-L1 expression than most other cancers and normal tissues, and we found that PD-L1 expression was significantly higher in SCC than in adenocarcinoma (p<0.001). Furthermore, PD-L1 showed a significantly higher expression level in pathologic stage II SCC compared to stages I, III, and IV (p<0.05, p<0.05, p<0.001, respectively). Interestingly, stage IV was associated with a lower PD-L1 expression compared to stages I, II, and III (p<0.001). We did not identify similar expression associations with pathologic stage in adenocarcinoma. However, we found that current and also reformed smokers for less than 15 years had a higher PD-L1 expression in adenocarcinoma (p<0.05), but not in SCC. PD-L1 expression was not significantly associated with a survival difference in any stage or histology subgroups. Using the CCLE data we found that NSCLC cell lines show various expression of PD-L1 that is significantly higher compared to lung small cell carcinoma (p<0.001).
Conclusion:
The value of PD-L1 expression based on mRNA sequencing in predicting survival in anti PD-1 naïve patients appears to be limited. However, the levels of PD-L1 expression in various disease stages and subgroups of lung cancer patients provide rational for neoadjuvant or window-of-opportunity immunotherapy trials, which would enable us to sort out the mechanisms and to identify patients best suited for immunotherapy.
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P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.02-014 - Perioperative Outcomes and Downstaging Following Neoadjuvant Therapy For Lung Cancer – Analysis of the National Cancer Database (ID 4929)
14:30 - 14:30 | Author(s): A.A. Vaporciyan
- Abstract
Background:
Administration of chemotherapy prior to surgical resection is one of the strategies for the treatment of locally advanced non-small cell lung cancer (NSCLC). Potential benefits of this approach include improved treatment tolerance, tumor downstaging, and the evaluation of tumor response. Utilizing the National Cancer Database (NCDB), we sought to compare short-term perioperative outcomes and treatment response of neoadjuvant chemotherapy followed by surgery with surgery alone.
Methods:
We queried the NCDB Participant User File (PUF) for patients with clinical stage IB-IIIA NSCLC who underwent definitive surgical resection for NSCLC between 2006-2013. We identified 83,274 patients with complete datasets who met the inclusion criteria. Patients were grouped by stage and perioperative outcomes were assessed, comparing those who underwent neoadjuvant therapy to surgery alone. Neoadjuvant therapy response was assessed by downstaging on final pathology in both unmatched and matched cohorts.
Results:
Neoadjuvant chemotherapy was administered to 11.9% (9,961/83,274) of potentially eligible patients. The incidence of neoadjuvant therapy increased with clinical stage; rates of 2.7% (995/37,453) for IB, 5.4% (724/13,435) for IIA, 15% (2,048/13,619) for IIB, and 33% (6,194/18,767) for IIIA. All cause 30-, and 90-day mortality was 3.1% and 6.3% vs. 3.1% and 6.0% for neoadjuvant vs. surgery alone across all stages, (p=0.159, p<0.001). The unplanned 30-day re-admission rates were 3.8% vs. 4.3% for neoadjuvant vs. surgery alone (p<0.001). Median length of hospital stay was similar between the groups, 7.6 vs. 7.2 days for neoadjuvant vs. surgery alone (p=0.015); stage specific analysis revealed similar results. Overall downstaging was seen in 29.5% in the neoadjuvant group compared to 17% in the surgery group (p<0.001). Primary tumor downstaging occurred in 31.5% vs 9.5% (p<0.001) and nodal downstaging in 23% vs 14.4% (p<0.001) for neoadjuvant and surgery groups respectively. Additionally, significantly improved R0 resection rate was achieved for stages IIIA and IIB in the neoadjuvant group 88.1% and 86.1% vs. 82.0% and 84.5% in the surgery alone group respectively (p<0.001 for IIIA and IIB).
Conclusion:
In this largest review of perioperative outcomes and downstaging effect of neoadjuvant chemotherapy prior to definitive surgical resection for NSCLC, we demonstrate that the treatment strategy of neoadjuvant chemotherapy followed by surgery is safe and effective. Tumor downstaging and increased R0 resection rate in locally advanced lung cancer stages support the utilization of this treatment paradigm.
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SC30 - Novel Approaches and Regulation in Surgical Education (ID 354)
- Event: WCLC 2016
- Type: Science Session
- Track: Surgery
- Presentations: 1
- Moderators:D. Grunenwald, Y.T. Kim
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall C8
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SC30.04 - Impact of Working Time Directives on Thoracic Surgical Training: The North-American Experience (ID 6730)
15:30 - 15:45 | Author(s): A.A. Vaporciyan
- Abstract
- Presentation
Abstract:
The following is in part the STS, TSDA and AATS combined response to ACGME (collated and written up by Dr. Ara Vaporciyan) regarding the effect of Duty hour regulations on resident education in Thoracic Surgery in North America. A greater reliance on midlevel providers and physician extenders. This has impacted the profession in terms of additional cost from their much higher salaries, which are anywhere from 50% to 100% higher, but also a subtle but steady transfer of bedside teaching previously focused on the trainee to bedside teaching focused on the mid-level provider. Limited exposure to our field. Our profession still fills the bulk of its training position from general surgery graduates. Duty hour restrictions have contracted the ability of those programs to provide elective rotations in thoracic and cardiac. Limited exposure translates into limited interest and diminished applications. Quality of Surgical and postoperative teaching. This is where we have felt the greatest impact. We, like all surgical professions, have developed an increasing variety of procedures necessitating expansion of our case log requirements. This puts pressure on trainees to participate in every available case. Appropriate cases are harder to find due to increasing case complexity and outcome reporting. Therefore, the inability to scrub on just one or two of these cases can be significant. While some large surgery programs have implemented float pools to ensure that all cases provide someone a learning experience most CT training programs are small and cannot implement that solution Even more difficult to overcome is when a trainee misses a rare postoperative event. As a high acuity specialty our patients will frequently develop rapid changes in their condition which, if not recognized, can quickly become catastrophic. Most occur in the immediate postoperative period at night. The use of mid-level providers and other services to cover call in an effort to preserve a trainee’s ability to do cases the next day prevents them from taking part in the bedside assessment and management of these rare events. One solution is to lengthen training to allow more opportunities but there is concurrent pressure to reduce what is already one of the longest training paradigms (up to 9 years for congenital surgeons without considering any time for research). Alternatively simulation has been used but these are expensive and are not easily implemented at all programs.. Finally, issues of patient safety and outcomes. While there is no clear study demonstrating documented impact on patient safety there are many surveys of resident and faculty perceptions of patient safety. The majority of these, especially in surgery, have shown that the perception is that safety is compromised. The increased number of handoffs, especially of high acuity cases, is frequently the target of that perception. The subtle aspects of the intraoperative findings cannot always be accurately communicated in a handoff. While patient safety data is not conclusive there is data on worse outcomes in spinal and meningioma surgery post implementation of duty hour regulations. These data may serve to corroborate the perceived concerns.
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