THE BENEFITS OF BIG DATA

Transcription

1 THE BENEFITS OF BIG DATA

2 Disclosures I am a named inventor on a number of patents and patent applications relating to the evaluation of pulmonary nodules on CT scans of the chest which are owned by Cornell Research Foundation (CRF). As of April 2009, I signed away any financial benefit including royalties and any other proceeds related to the patents or patent applications owned by CRF. I am the President of the Early Diagnosis and Treatment Research Foundation

3 Axillary LNs Vascular CAC Breast density Lung Cancer IELCAP Database 1992-present COPD Chronic bronchitis Bronchiecta sis Focal pneumonia Interstitial disease CAC Atherosclerosis Hypertension Stenosis Aorta Peripheral /vascular

4 Cohort of People Undergoing CT screening for lung cancer 1992-ongoing Long-term outcome Robust data on less frequent findings 75,000 + people enrolled Single slice imaging to the latest state of the art

5 mm Size 7mm Size 10mm , 10mm non-solid nodule , non-solid nodule, slow growth 2013, suspicious to become part-solid nodule 2014, definitely to become part-solid nodule 2015, increase in allover size and its solid component Now she is 85 yo What should we do next step?

6 The regimen for screening Baseline round 1000 people screened cancers 80% Stage I Type of nodules, most < 6mm Solid: 250 people Part-solid: 40 people Nonsolid: 30 people Some nodules resolve All annual repeat rounds 1000 people screened??? cancers??? Stage I Type of nodules Solid:?? people Part-solid:? people Nonsolid:? people A higher % resolve than on baseline

7 What is the difference between the baseline and the subsequent annual rounds of screening?

8 The regimen for screening Baseline round 1000 people screened cancers 80% Stage I Type of nodules, most < 6mm Solid: 250 people Part-solid: 40 people Nonsolid: 30 people Some nodules resolve All annual repeat rounds 1000 people screened 5-9 cancers 80% Stage I Type of nodules Solid: 30 people Part-solid: 2 people Nonsolid: 2 people A higher % resolve than on baseline

9 Baseline vs. Annual Repeat: Distribution by cell type 100% 80% Baseline Column1 60% 48% 40% 20% 0% 28% 11% 4% Adeno-solid Adeno-subsolid Squamous Small-cell

10 Baseline vs. Annual Repeat: Distribution by cell type 100% 80% Baseline Annual Repeat 60% 40% 20% 0% 48% 39% 28% 22% 12% 11% 16% 4% Adeno-solid Adeno-subsolid Squamous Small-cell Tumor aggressiveness is indicated by the change from baseline to annual repeat

11 Threshold for Workup of Nodules Developed in I-ELCAP focused on imaging since 2006 slice thickness of 1.25 mm or less Validated in the NLST images collected slice thickness mm

12 Threshold in Baseline Round NLST use 4 mm in greatest length I-ELCAP no threshold; but thick section used 5.0 mm threshold 2014-pesent 6.0 mm

13 I-ELCAP Results ,396 36% 56% Positive Result Cancers 2, ,498 68% 1, % 0 0% 5% 6% 7% mm 6.0 mm 7.0 mm 8.0 mm 9.0 mm Henschke CI, Yip R, Yankelevitz DF et al. Definition of a positive test result in computed tomography screening for lung cancer: a cohort study. Ann Intern Med. 2013;158(4):

14 NLST Positive results 5,000 Positive result 4,000 4,080 34% Cancers 55% 3,000 2,700 67% 2,000 1,847 74% 1,362 1, mm 6.0 mm 7.0 mm 8.0 mm 9.0 mm 1,067 1% 3% 6% 10% Yip R, Henschke CI, Yankelevitz DF, Smith JP. CT Screening for Lung Cancer: Alternative Definitions of Positive Test Result Based on the National Lung Screening Trial and International Early Lung Cancer Action Program Databases. Radiology Jun 19:

15 Cancers manifesting in nonsolid, part-solid, and solid nodules: demonstration of length bias Baseline Annual Repeat Nonsolid 10% Part-solid 8% Nonsolid 15% Partsolid 21% Solid 66% Solid 85% Increasing percentage of cancers in solid nodules on annual repeat screening. Thus, cancers in solid nodules are more aggressive than those in part-solid and nonsolid nodules

16 The Approach Large databases with long-term followup I-ELCAP database has latest approaches Follow-up since 1992 NLST database- stopped in 2006 Follow-up for 5-7 years Meta-analyses of the world literature

17 SUBSOLID NODULES nonsolid and part-solid I-ELCAP Yankelevitz DF, Yip R, Smith JP et al. Radiology 2015; 2015; 277:

18 Prevalence of Lung Cancer: Nonsolid and Part-solid Nodules Baseline Round Annual Repeat Rounds 30.0% 29% 30.0% 20.0% Nonsolid Part-solid 20.0% Nonsolid Part-solid 10.0% 0.0% 9% 3% 0.1% < % 0.0% 3% 3% 5% 0.3% < Annual Repeat Rounds: No cancer in nonsolid nodules 15+ or in part-solid nodules 31+

19 Prevalence of Lung Cancer: Nonsolid, Part-solid, and Solid Nodules 60.0% 40.0% 20.0% 0.0% Baseline Round Nonsolid 50% Part-solid Solid 18% 0.3% 4% < Annual Repeat Rounds 60.0% Nonsolid Part-solid 40.0% Solid 26% 21% 20.0% 10% 2.0% 0.0% < Annual Repeat Rounds: No cancer in nonsolid nodules 15+ or in part-solid nodules 31+

20 Frequency and Resolution on Follow-up CT

21 Nonsolid, Part-solid, and Solid Nodules: Baseline round N = 57,496 < Frequency Annual Repeat Rounds N = 64,677 < Much higher frequency of solid nodules on baseline, particularly for those < 10 mm in diameter (7 times higher)

22 Nonsolid, Part-solid, and Solid Nodules: Baseline round N = 57,496 Follow-up Annual Repeat Rounds N = 64, %; 19% 12% % %; 70% Res/Decr 0 Res/Decr Like, nonsolid nodules, a higher proportion of part-solid nodules resolved or decreased in annual repeat: 70% vs. 19%

23 I-ELCAP Subsolid Nodule Summary No lymph node metastases when solid component < 10 mm in diameter Solid component may be due to inflammation, mucus, scar, granuloma, etc. Follow-up important High rate of resolution on annual CT scans Growth assessment is helpful in distinguishing between lung cancer and non-malignant processes

24 NONSOLID NODULES NLST Dataset Yip R, Li K, Xu DM, et al. Radiology In press

25 Conclusion on NSNs in NLST Unlikely that cases with lung cancer as COD occurred in solitary or dominant NSN as long as annual follow-up was done to assess change Lung cancers manifesting as NSN have an indolent course and can be managed with annual follow-up Yip R, Li K, Xu DM, et al. Radiology In press

26 NONSOLID NODULES Meta-analysis Yip R, Wolf A, Tam K, et al. Lung Cancer In press

27 Meta-analysis of NSNs Comprehensive review and re-analysis of literature on outcome of lung cancer manifesting as NSN 24 articles from 5 countries 704 people diagnosed with lung cancer manifesting as NSN All Stage I adenocarcinoma 5-year lung cancer-specific survival: 100% Yip R, Wolf A, Tam K, et al. Lung Cancer In press

28 PART-SOLID NODULES NLST Dataset Yip R, Xu DM, Li K, et al. Submitted

29 Mixed Nodule in NLST

30 Mixed Nodule in NLST

31 Mixed Nodule in NLST

32 Mixed Nodule in NLST

33 Mixed Nodule in NLST Thick section CT

34 NLST: Part-solid Nodules 20 cases with part-solid nodule 1 death

35 Single Death in a Part-solid Nodule in NLST Multi-lobar part-solid nodules, some of them > 30 mm in length at baseline This person underwent baseline and 2 annual repeat rounds of screening prior to diagnosis and died some 72 months (6 years) after randomization Yip R, Xu DM, Li K, et al. Submitted

36 Importance of the Definition of Part-solid Nodules

37 Definition of Part-solid Nodules CT slice thickness of 1.25 mm or less If there is only one scan and the diameter of the solid component is more than 80% of the diameter of the nodule, consider it to be solid and workup accordinly.

38 A New Cohort Study

39 Initiative on Early Lung Cancer Research on Treament IELCART

40 Stage I Lung Cancer 1. How much lung tissue should be resected? 1. Lobectomy vs. limited resection 2. How many mediastinal lymph nodes need to be resected 1. Full resection vs. sampling vs. targeted vs. none 3. Which cases can be followed by watchful waiting? 4. Quality of life issues

41 IELCART Goal to enroll 3,000 patients in the next 3 years to address these questions Why? CALGB trial: started in 2005 with goal to enroll 1,100 patients, but in 2016 have not reached the reduced goal. Difficult to enroll in an RCT for early stage lung cancer