Individual Prediction
Michael W. Kattan, Ph.D.
Professor of Medicine, Epidemiology and Biostatistics,
Cleveland Clinic Lerner College of Medicine of Case
Western Reserve University
Chairman, Department of Quantitative Health Sciences,
Cleveland Clinic
Disclosures
Hodgkin’s Disease Prognosis
Time 0 1 Su rvi va l I II IIIIV
Many clinical counseling tools are not designed to predict accurately
Problems with my prediction:
•
Didn’t feel very tailored!
–
Not adjusted for age, comorbidities–
Categories (e.g., extent of disease) were very broad•
Was this staging system really optimized for
prediction?
When The Patient Wants A Prediction, What Options Does The Clinician Have?
• Quote an overall average to all patients
• Assign the patient to a risk group, i.e. high, intermediate, or low
• Apply a model • Predict based on
Biopsy Gleason Grade ≤ 2+ ≤ 2 3+3 ≤ 3+≥ 4
≤ 2+3 ≥ 4+ ?
Total Points 0 20 40 60 80 100 120 140 160 180 200
60 Month Rec. Free Prob. .96 .93 .9 .85 .8 .7 .6 .5 .4 .3 .2 .1 .05 3+ ≤ 2
Clinical Stage T1c T1ab
T2a T2c T3a
T2b
Points 0 10 20 30 40 50 60 70 80 90 100
PSA 0.1 1 2 3 4 6 7 8 9 10 12 16 20 30 45 70 110
Preoperative Nomogram for Prostate Cancer Recurrence
Instructions for Physician: Locate the patient’s PSA on the PSA axis. Draw a line straight upwards to the Points axis to determine how many
points towards recurrence the patient receives for his PSA. Repeat this process for the Clinical Stage and Biopsy Gleason Sum axes, each time drawing straight upward to the Points axis. Sum the points achieved for each predictor and locate this sum on the Total Points axis. Draw a line straight down to find the patient’s probability of remaining recurrence free for 60 months assuming he does not die of another cause first.
Instruction to Patient: “Mr. X, if we had 100 men just like you, we would expect <predicted percentage from nomogram> to remain free of their
disease at 5 years following radical prostatectomy, and recurrence after 5 years is very rare.”
1997 Michael W. Kattan and Peter T. Scardino
CaPSURE
Heterogeneity within Risk GroupsRisk Group
Nomogram Values by Prostate Cancer Risk Group
Pr eo p er ativ e No m o g ra m Pr ed icted Pr o b ab ility
Low Intermediate High
1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 J Urol. 2005 Apr;173(4):1126-31
The consequence of risk stratification relative to a statistical model
•
Mr. X, from the Cleveland Clinic:
–
PSA=6, clinical stage = T2c, biopsy Gleason sum=9, planned dose of 66.6 Gy without neoadjuvant hormones•
Radiation risk stratification: 81% @ 5 yr.
•
Surgery nomogram: 68% @ 5yr.
•
Radiation therapy nomogram: 24% @ 5yr.
Heterogeneity within stages for gastric cancer
0 10 20 30 0.0 0.2 0.4 0.6 0.8 1.0 0 5 10 15 20 0 2 4 6 8 0 2 4 6 8 0 5 10 15 20 0 5 10 20Nomogram Predicted Probability of 5-Year Disease-Specific Survival
P er ce nt o f P at ient s w ithi n A JC C S tage AJCC IV (32) II (117) IA (102) IB (115) IIIA (69) IIIB (24)
Continuous Models vs. Staging/Grouping Systems
Model Comparator CI (M vs C)
Preop L/I/H Risk Groups 0.67 vs. 0.64
Preop + IL6/TGFβ1 L/H Risk Groups 0.84 vs. 0.73
Pre XRT L/I/H Risk Groups 0.76 vs. 0.69
Melanoma SLN+ AJCC Stage 0.69 vs. 0.66
Pancreatic Ca AJCC Stage 0.64 vs. 0.56
Gastric Ca AJCC Stage 0.77 vs. 0.75
Breast Ca NPI Groups 0.69 vs. 0.64
When The Patient Wants A Prediction, What Options Does The Clinician Have?
• Quote an overall average to all patients
• Assign the patient to a risk group, i.e. high, intermediate, or low
• Apply a model • Predict based on
Urologists vs. Preoperative Nomogram
•
10 case descriptions from 1994 MSKCC patients presented to 17 urologists– In addition to PSA, biopsy Gleason grades, and clinical stage, urologists were provided with patient age, systematic biopsy details, previous biopsy results, and PSA history.
•
Preoperative nomogram was provided.•
Urologists were asked to make their own predictions of 5 yearprogression-free probabilities with or without use of the preoperative nomogram.
•
Concordance indices: – Nomogram = 0.67– Urologists = 0.55, p<0.05
Nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node biopsy
Breast Cancer Prediction: 17 Clinicians vs. Nomogram on 33 Patients Nomogram AUC 0.72 Clinician AUC 0.54 Areas 0.75 0.72 Nomogram 0.68 0.65 0.65 0.63 0.59 0.58 0.55 0.55 0.53 0.52 0.50 0.49 0.47 0.43 0.42 0.40
Dendreon: Proprietary and Confidential
Dendreon: Proprietary and Confidential
Survey Results
nomo doc2 doc8 doc11 doc18 doc14 doc24 doc13 doc22 doc5 doc1 doc7 doc9 doc17 doc12 doc15 doc16 doc4 doc21 doc20 doc23 doc10 doc3 doc19 doc6 C onc or danc e i ndex 0 .0 0 .2 0 .4 0 .6 0 .8 1 .0Comparative Effectiveness
Treatment options
Benefits
T1
T2
B1
B2
Harms
H1
H2
Must tailor the probabilities to the individual patient.
