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Paul Mitchell
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MA11 - Biomarkers of IO Response (ID 912)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 10:30 - 12:00, Room 203 BD
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MA11.05 - Indoleamine 2,3-Dioxygenase Expression in Non-Small-Cell Lung Cancer: Analyses of Prevalence, Clinical Correlations and Prognostic Impact (ID 13309)
11:00 - 11:05 | Author(s): Paul Mitchell
- Abstract
- Presentation
Background
Indoleamine 2,3-dioxygenase-1 (IDO-1) is a cytosolic enzyme involved in the catabolism of tryptophan; IDO-1-related immune suppression is due to decreased tryptophan availability and to the generation of tryptophan metabolites, culminating in substantial suppression of T-lymphocytes. Here we investigate IDO-1 expression in a cohort of non-small-cell lung cancer (NSCLC) specimens, both in tumor cells and in immune infiltrate, with correlation of IDO-1 to PD-L1 expression, clinical patient demographics and outcomes.
a9ded1e5ce5d75814730bb4caaf49419 Method
A cohort of 1.200 NSCLC samples were obtained from 437 patients who underwent surgical lung resections at Austin Health, Melbourne, Australia. IDO-1 expression was evaluated by immunohistochemistry. Correlations were assessed using Spearman and Kendall tests. A Cox proportional hazards (PH) model was used to assess if overall survival (OS) was associated with IDO-1 positivity in univariate and multivariable settings.
4c3880bb027f159e801041b1021e88e8 Result
Samples from 437 patients were analyzed for IDO-1 expression, with 111 (25.4%) determined as positive (H-Score ≥ 1) and 326 patients (74.6%) as negative (H-Score: 0). IDO-1 expression was determined to be greater in tumor immune infiltrate, with 406 patients (93.8%) determined as positive, while just 27 (6.2%) were IDO-1 negative. There was a significant positive correlation between IDO-1 positive tumor cells and immune cells (0.2167, p < 0.001). Both continuous and binary versions of tumor H-Score showed a significant positive correlation with the amount of tumor immune infiltrate (0.1806 and 0.1698, p < 0.0001, respectively). None of the analyzed variables (age, sex, histology, stage, EGFR, KRAS and PD-L1 status) were found to display a significant correlation with IDO-1 positivity in tumor and immune cells. IDO-1 positivity in tumor cells was found to be significantly associated with OS in the univariate setting and in the multivariable model where variables age, sex, histology, stage, EGFR, KRAS and PD-L1 status were included [P-value = 0.009 and 0.021, respectively; HR: 0.72 (95% CI: 0.55-0.95)]. IDO-1 positivity in immune cells was found to be significantly associated with OS in the univariate setting and was borderline significant in the multivariable model [P-value = 0.006 and 0.053, respectively; HR: 0.798 (95% CI: 0.635-1.003)].
8eea62084ca7e541d918e823422bd82e Conclusion
To our knowledge, this is the most extensive analysis of IDO-1 expression in NSCLC patients reported in the literature. Our results suggest the possible prognostic role of IDO-1 expression in tumor and immune cells, highlighting the relevance of IDO-1 detection in tumor tissue. Since new compounds targeting IDO-1 are actually under investigation, the identification of potential prognostic and predictive biomarkers will be needed.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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MS12 - Immunotherapy and RT (ID 791)
- Event: WCLC 2018
- Type: Mini Symposium
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 15:15 - 16:45, Room 105
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MS12.04 - Implications for Routine Practice (ID 11452)
16:15 - 16:35 | Presenting Author(s): Paul Mitchell
- Abstract
- Presentation
Abstract not provided
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.16-58 - Hospital Lung Surgery Volume and Patient Outcomes in Victoria (ID 12674)
16:45 - 18:00 | Author(s): Paul Mitchell
- Abstract
Background
Surgical resection remains the primary curative option for early stage non-small cell lung cancer (NSCLC) with lobectomies considered the gold standard due to a reduction in local recurrence and improved overall survival. There has been growing evidence of an association between patient outcomes and the number of cancer surgeries performed at a hospital since the seminal paper by Luft et al in 1979.
To our knowledge, there are no Australian data on hospital cancer surgery volumes and patient outcomes by procedure, and few data worldwide on specific lung surgery procedures and outcomes. We evaluated the relationship between hospital NSCLC surgery volume and patient outcomes in Victoria.
a9ded1e5ce5d75814730bb4caaf49419 Method
Victorians with a primary diagnosis of NSCLC between 2008 and 2014 were identified in the Victorian Cancer Registry (n=15,469), 3,420 (22%) of whom had surgery. Primary outcome was death within 90 days of surgery and secondary outcomes were overall survival, use of postoperative ventilation, ≥24hours spent in ICU and length of stay >17days. Hospital volume was measured as the average number of lung surgeries performed per year, with quartiles Q1: 1-17, Q2: 18-34, Q3: 35-58 and Q4: 59+.
4c3880bb027f159e801041b1021e88e8 Result
57% (1,941/3,420) lung cancer patients underwent lobectomy, 38% (1,299/3,420) sub-lobar resection and 5% (180/3,420) pneumonectomy. The overall 90-day mortality after lung surgery was 3.5%, and was 2.6% for patients undergoing lobectomy compared with 4.5% for those undergoing sub-lobar resection. There was no difference in 90-day mortality between low- and high-volume centres regardless of procedure. Patients operated in lower volume centres had more admissions to ICU ≥24hours (Q1. 55% vs. Q4. 11%, p-trend <0.001). Median overall survival was 6.2 years, 5.4 years and 5.8 years for lobectomy, sub-lobar resection and pneumonectomy, respectively. The distribution of ASA scores differed between patients attending public and private hospitals. A higher proportion of patients attending private hospitals (19%) had an ASA score of 4 compared with patients attending a public hospital (9%).
8eea62084ca7e541d918e823422bd82e Conclusion
We observed no evidence of survival differences between lung cancer patients attending low- and high-volume hospitals for surgery, regardless of surgical procedure. Median overall survival in Victorian is substantially better compared to interstate and international data. Of interest, a higher proportion of patients had an ICU admission ≥24hours in lower volume centres. We also observed a higher proportion of patients with an ASA score of 4 in private hospitals compared to public hospitals; the reasons for this are unclear and warrant further investigation.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.04-13 - The Immune Checkpoint, HVEM Contribute to Immune Escape in Non Small Cell Lung Cancer of Lacking PDL1 Expression (ID 13116)
16:45 - 18:00 | Author(s): Paul Mitchell
- Abstract
Background
Herpes Virus Entry Mediator (HVEM) is an important immune checkpoint in cancer recognition. HVEM expressed on tumor cell membranes activates immune cell signaling pathways leading to either inhibition of activity (BTLA) or activation of immune activity (LIGHT). The aim of this study is to investigate the prevalence of HVEM expression and its association with PDL1 expression in NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
A TMA of 527 resected NSCLC samples and 53 NSCLC cell lines were evaluated for HVEM and PD-L1 expression. The IHC assay for HVEM was optimized on the Dako Link48 autostainer using a polyclonal antibody from R&D Systems（AF356). PD-L1 IHC was performed on the Dako Link48 autostainer using the PD-L1 22C3 pharmDx kit. Scoring HVEM employed the H-score system while for PD-L1 the tumor proportion score (TPS) was used.
4c3880bb027f159e801041b1021e88e8 Result
HVEM expression in the NSCLC resected samples and cell lines revealed a positive H-score more than 1 was18.6%(77/415) and 45.3%(24/53) respectively. HVEM expression was significantly higher in patients with lymph node N2 metastasis (25.5% vs 7.9% vs 17.5%, P=0.046) when comparing with N1 or no lymph node metastasis, and was marginally significantly higher in patients with stage III/IV disease (24.5% vs 16.4%, P=0.059). Subgroup analysis showed that HVEM (median 45 vs 36 months, p=0.706) and PD-L1 expression (median 45 vs 48 months, p=0.178) status was not predictive of overall survival. HVEM was found to have a significant negative correlation with PD-L1 expression (r=-0.232, p=0.002, Figure 1A) in patients with NSCLC and also have a negative correlation in NSCLC cell lines(r=-0.055, p=0.764,Figure 1B).
8eea62084ca7e541d918e823422bd82e Conclusion
HVEM was found to be overexpressed in patients of NSCLC with advanced disease or lymph node metastasis and has a negative co-relationship with PD-L1 expression, while, it did not have a prognostic role in patients with NSCLC.
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