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Philip Crosbie
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-43 - PD-RAD: A Translational Study Investigating PD-L1 Expression After Radiotherapy for Non-Small Cell Lung Cancer - Trial in Progress (ID 1811)
09:45 - 18:00 | Author(s): Philip Crosbie
- Abstract
Background
Radiotherapy (RT) is delivered to 30-50% of NSCLC patients. However, over half of patients progress following RT and mechanisms of resistance are poorly understood. RT has immune-modulatory properties such as the ability to upregulate tumour PD-L1 expression and can recalibrate the immune contexture. Blockade of the PD-1/PD-L1 axis has been shown to enhance the efficacy of RT in several pre-clinical models and the recent PACIFIC trial. Exploiting immuno-regulatory effects of RT therefore has the ability to enhance local and distant anti-cancer effects of RT, especially when combining RT with immunotherapies such as anti-PD-1 or costimulatory agonists.
Method
PDRAD is a prospective UK multi-centre feasibility study of paired pre- and post-treatment biopsies in NSCLC patients receiving palliative or radical RT. The study will recruit up to 30 patients with inoperable disease that is accessible to core biopsy by CT or bronchoscopy within the proposed RT field. Patients with archival baseline histology containing sufficient tumour material are eligible. Consented patients undergo a repeat biopsy in the second week of RT (fig.1). Blood samples will be collected at baseline, repeat biopsy, and following RT to assess immune changes that may correlate with the tumour microenvironment (TME). PDRAD opened to recruitment in November 2018 and will continue recruitment over 16 months.
Research aims include investigating:
Feasibility and acceptability of obtaining paired biopsies
Changes in the immune contexture in irradiated tumour and ‘out of field’ sites
Immune changes in the TME and peripheral blood
Interim feasibility results after recruitment of 15 patients will be presented at World Lung.
Result
Section not applicable
Conclusion
We are at a pivotal point in evolving our knowledge of how the TME may influence responses to RT. The PDRAD study will help to influence further clinical trials, including combination studies with immunotherapies and predictive and prognostic biomarker development within the field.
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P1.11 - Screening and Early Detection (ID 177)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.11-36 - A Simple Tool to Prioritize US Ever-Smokers for CT Screening Eligibility Assessment (ID 1233)
09:45 - 18:00 | Author(s): Philip Crosbie
- Abstract
Background
CT lung cancer screening can be more efficient when risk models are used to determine eligibility. However, detailed risk assessment requires time spent by a healthcare provider and may present a barrier to screening when resources are limited. Here, we developed a tool to identify ever-smokers with low probability of risk-based eligibility.
Method
We analyzed ever-smokers aged 50-80 in the representative 2015 US National Health Interview Survey. We defined ever-smokers with 6-year risk ≥1.3% by the 12-question PLCOm2012 model as screening-eligible. We considered that detailed risk assessment may be inefficient when the probability of eligibility is less than 5%. Accordingly, we used cross-tabulations of age, cigarettes-per-day, and quit-years to identify groups in whom risk assessment might be avoided.
Result
There are approximately 44,140,774 U.S. ever-smokers aged 50-80 who could consider detailed risk assessment. However, a simple decision-tree tool identified 22,293,477 ever-smokers (50.5%) who are less than 5% likely to be screening-eligible (Figure). This includes all those who smoke(d) less than 5 cigarettes-per-day. Over 1 year, approximately 103,512 lung cancers were predicted among eligible ever-smokers. If our tool were used, then 1,784 of these eligible cases (1.7%) would not undergo detailed risk assessment or screening.
Conclusion
When resources are limited, a simple decision-tree tool could avoid detailed risk assessment for more than half of U.S. ever smokers aged 50-80, while still identifying 98.3% of eligible cases. Such a tool could be self-administered by patients in the waiting room or applied automatically to electronic health records to optimize use of provider time.
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P2.09 - Pathology (ID 174)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.09-23 - PD-L1 Expression of Paired Primary Resected Non Small Cell Carcinoma and Metastatic Lymph Node Fine Needle Aspirates (Now Available) (ID 2640)
10:15 - 18:15 | Author(s): Philip Crosbie
- Abstract
Background
Small biopsy or cytology samples may present with a different level of PD-L1 expression compared to resected samples (which usually entail scoring of a much greater number of cells) resulting in relatively increased or reduced tumour proportion scores (TPSs). Many PD-L1 results are based on cytology fine needle lymph node aspirates (FNLNAs), encompassing analysis of metastatic disease and the substitution of cytology for histology samples. We compared the PD-L1 TPS of metastatic FNLNAs with that of resected non small cell carcinoma.
Method
The pathology archive at Wythenshawe Hospital was searched for cases with adequate material over a period spanning 2010-2016. The Ventana SP263 PD-L1 clone was used to stain blocks select from 50 resected NSCCs and matched FNLNA cell blocks from each individual, along with a fresh H&E and negative PD-L1 control section.
Result
Four of the cell block sections were inadequate for TPS assessment. The remaining 46 cases comprised 21 adenocarcinomas, 3 large cell carcinomas, 1 large cell neuroendocrine carcinoma, 1 atypical carcinoid tumour, and 20 squamous carcinomas. 34 cell block PD-L1 TPSs (68%) were in broad agreement with the corresponding resection block TPS, based on cut-off levels of 1% and 50%. Of the 12 (32%) cases in which differences occurred, 6 (50%) reflected an increase in TPS from resection to FNA, while 6 reflected a decrease causing a change in therapeutic cut-off. Nine of the FNLNAs were sampled after the resection, favouring the presence of recurrent disease.
TABLE 1. PD-L1 expression of resections versus FNLNAs across TPS categories Resection Tumour Proportion Scores n, (%)
FNLNA Tumour Proportion Scores n, (%)
0 / <1%
1 - 49%
≥ 50%
p
0 / <1% 1 - 49% ≥ 50% p Total n = 46
12 (26)
15 (33)
19 (41)
16 (35)
7 (15)
23 (50)
0.14 Median age at diagnosis (yrs)
63 64 64 62 69 64 Adenocarcinoma
Squamous ca.
Othera
2 (4)
7 (15)
3 (7)
8 (20)
6 (11)
1 (2)
10 (22)
8 (17)
1 (2)
0.132 2 (4)
10 (22)
4 (9)
5 (11)
2 (4)
0 (0)
13 (28)
9 (20)
1 (2)
0.035 Discrepant cases n = 12
1 (8)
9 (75)
2 (17)
4 (33)
2 (17)
6 (50)
a Includes large cell carcinoma, large cell neuroendocrine carcinoma, atypical carcinoid
Conclusion
The majority of metastatic TPS FNLNAs are in broad agreement with a primary resected carcinoma TPS. FNLNAs tended to score less in the 1-49% category, possibly due to limits of cellularity. In addition to heterogeneity of expression, sampling of recurrent rather than residual disease may contribute to discrepancies.
