Download BME 1300 Problem 1 Newstetter Group

BME 1300 Problem 1
NewstetterGroup
Haval Amedi
Mollie Bryan
Eric Flynn
Peymaun Ghafouri-Kia
Ryan Gleber
Walter Kim
Chelsea Proffitt
Laini Whitton
Problem
Currently, non-small cell lung cancer is being detected at
stages III and IV, causing a five year mortality rate of 86%.
This is due to a lack of widespread lung cancer screening
methods that have sensitivity and specificity greater than
60%.
Evaluation of Current Methods
• Data suggests no current implementation of screening
• High mortality rate
• Caught after symptoms develop—stages III and IV
• X-rays and sputum cytology - have been proven ineffective in
lowering mortality rate
• Physical exam - ineffective for screening in early stages due to lack
in symptoms
• CT Scan – has only been proven effective for high risk patients
• Bronchoscopy and biopsy – overly invasive and used primarily for
detection
Humphrey et al., Annals of Internal Medicine, 2004
Evaluation of Screening Procedure
• Practically no screening done
• Patients assessed for risk
•
•
•
•
•
•
Smoker (10 pack years), occupation, family history
If patient is high risk, some will screen, others will wait for symptoms
X-rays followed by CT scans if abnormalities present
CT followed by biopsy/treatment
Sputum occasionally used
Doctors very negative about screening situation
Cayelli, et al., Phone Interview, 2011.
Recommendations for Current
Methods
• Annual CT for high risk age 55-74 with 30 pack years
• Biannual CT for other high risk patients not in 55-74/30 pack year
category
•
Mathematical modeling available soon for other risk groups1
• Eliminate X-rays for high risk groups
• Add PET to CT scan when available2
• Cell block and smear with sputum cytology3
1. Peres, Journal of the National Cancer Institute, 2010
2. Pastorino, British Journal of Cancer, 2010
3. Erkiliç et al., Acta Cytol, 2003
Evaluation Numbers For Future
Methods
• Grading Scale for Future Methods
• 2 x Sensitivity
• 2 x Specificity
• 1 x Invasiveness
• 1 x Risk of Injury from Test Complications
• 1 x Practicality (Ease of Analyzing and Collecting Data)
• 1 x Implementation (Ease of Achieving Widespread Usage)
• Each Ranked 1-5 with 5 being the highest rating
Evaluation Numbers For Future
Methods
Sputum Biomarkers – 21/40
• Methylation of tumor suppression
genes
• 64% sensitivity and specificity4
• PPV = 11.72%
Criteria
Rating
Serum Based miRNA – 28/40
• Both miR-1254 and miR-547-5p
significantly increased in early stage
NSCLC
• 78% sensitivity/75% specificity5
Criteria
Rating
Sensitivity (x2)
4
Sensitivity (x2)
6
Specificity (x2)
4
Specificity (x2)
4
Invasiveness
4
Invasiveness
4
Risk
4
Risk
5
Practicality
5
Practicality
5
Implementation
4
Implementation
4
Total Score
21
Total Score
28
4. 5. Keller et al., BMC Cancer, 2009
Evaluation Numbers For Future
Methods
Circulating Tumor Cells – 29/40
• Blood test
• 71% sensitivity/83% Specificity6
Criteria
Rating
Breath Biomarkers – 31/40
• Analyzes biomarkers in exhaled breath
• 84% sensitivity/92% specificity7
Criteria
Rating
Sensitivity (x2)
4
Sensitivity (x2)
6
Specificity (x2)
6
Specificity (x2)
8
Invasiveness
4
Invasiveness
5
Practicality
5
Risk
5
Risk
5
Practicality
5
Implementation
5
Implementation
3
Total Score
29
Total Score
31
6. 7. Tanaka et al., Clin Cancer Res, 2009
Evaluation Numbers For Future
Methods
Protein Blood Biomarkers – 33/40
• Uses aptamers
• 91% sensitivity/84% specificity6
Criteria
Rating
Bronchoscopy (Epithelial Cells) – 34/40
• Genetic testing of epithelial cells
from endobronchial brushings
• 95% sensitivity and specificity7
Criteria
Rating
Sensitivity (x2)
8
Sensitivity (x2)
10
Specificity (x2)
6
Specificity (x2)
10
Invasiveness
4
Invasiveness
3
Practicality
5
Practicality
4
Risk
5
Risk
3
Implementation
5
Implementation
4
Total Score
31
Total Score
34
Proof of Concept
• Given a random population of 100,000 people, 6,9509 will be
diagnosed with lung cancer. 6,04610 of these people will die.
With our proposed future method of genetic testing in
epithelial cells from endobronchial brushings, our new
mortality rate is 53.07%7,10,11, saving 2,357 lives.
7. 9. 10. Problem Statement 11. Minna, Harrison’s Prin of Int Med, 2005
Final Recommendations
• Screening methods in distant future
•
•
•
•
Partial Wave Spectroscopy12
Urine Test
Proteomics
Spirometry
12. Backman, et al., Cancer Research, 2010