Circulating Tumor DNA Analysis During Radiotherapy for Localized … · 2017-09-24 · Circulating...
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Circulating Tumor DNA Analysis During Radiotherapy for Localized Lung Cancer Predicts Treatment Outcome A. A. Chaudhuri 1 , A. F. Lovejoy 1 , J. J. Chabon 1 , A. Newman 1 , H. Stehr 1 , D. J. Merriott 2 , J. N. Carter 1 , T. D. Azad 1 , S. Padda 1 , M. F. Gensheimer 1 , H. A. Wakelee 1 , J. W. Neal 1 , B. W. Loo Jr 1 , A. A. Alizadeh 1 , and M. Diehn 1 1 Stanford Cancer Institute, Stanford, CA, 2 Stanford University School of Medicine, Stanford, CA
Transcript of Circulating Tumor DNA Analysis During Radiotherapy for Localized … · 2017-09-24 · Circulating...
Circulating Tumor DNA Analysis During Radiotherapy for Localized Lung Cancer Predicts
Treatment Outcome
A. A. Chaudhuri1, A. F. Lovejoy1, J. J. Chabon1, A. Newman1, H. Stehr1, D. J. Merriott2, J. N. Carter1, T. D. Azad1, S. Padda1, M. F. Gensheimer1, H. A. Wakelee1, J. W. Neal1, B. W. Loo
Jr1, A. A. Alizadeh1, and M. Diehn1
1Stanford Cancer Institute, Stanford, CA, 2Stanford University School of Medicine, Stanford, CA
Background• Circulating tumor DNA (ctDNA)
• Typically <1% of total cell-free DNA in cancer patients
• We recently developed an ultrasensitive method to quantitate ctDNA called Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq)1,2
• MRD = Minimal Residual Disease or Molecular Residual Disease• Prognostic biomarker important in the management of leukemia
• Currently no role in lung cancer management
• Hypotheses: • ctDNA analysis can detect MRD after definitive intent treatment of lung
cancer
• ctDNA MRD detection is prognostic for progression and survival
1Newman & Bratman et al, Nature Medicine, 2014
2Newman, Lovejoy & Klass et al, Nature Biotech, 2016
Study Design
Patient CohortParameter n = 41
Follow-up time (mo) 35.1 (6.9-56)
Age (y) 66.8 (47-91)
Gender
Male 28 (68%)
Female 13 (32%)
Smoking history
Yes 36 (88%)
No 5 (12%)
Pack-years 30 (0-150)
Stage
IA 1 (2%)
IB 7 (17%)
IIA 3 (7%)
IIB 4 (10%)
IIIA 15 (37%)
IIIB 11 (27%)
Histology
Adenocarcinoma 20 (49%)
Squamous carcinoma 15 (37%)
Small Cell 3 (7%)
NOS 3 (7%)
Local therapy
Radiotherapy 36 (88%)
Radiotherapy + Surgery 3 (7%)
Surgery 2 (5%)
Chemotherapy
Yes 28 (68%)
No 13 (32%)
Circulating DNA
ctDNA detected pre-tx 39 (95%)
Results: Patients with detectable ctDNA MRD have significantly worse outcomes
Patient Example: EGFR activating mutation detected by ctDNA MRD
Stage IB Adeno No recurrence Brain metRadiologyinterpretation
0 1 2 3 4 5 6 7
1
10
Time (Months)
EG
FR
L858R
(hG
E/m
L)
ND
Scan 2 Scan 3Scan 1
SA
BR
0.51 hGE/mL
Potential adjuvant treatment based on ctDNA MRD
0 6 12 18 240
20
40
60
80
100
Time from landmark (mo)
Fre
edom
fro
m
Pro
gre
ssio
n (
%)
Survival of Mid-tx (<28d from chemoRT start): FFP
> 0.1% ctDNA (n = 8)
< 0.1% ctDNA (n = 5)
P = 0.037
HR = 4.4
Cox Regression
P = 0.006
HR = 2.7
13 patients with ctDNA measured within 4 weeks of chemoRT start
Exploratory Analysis: Mid-treatment ctDNA levels correlate with future lung cancer progression
Conclusions and Future Directions
ctDNA detects MRD after definitive intent treatment for localized lung
cancer
ctDNA MRD detection after treatment correlated with significantly
worse progression and survival
ctDNA MRD may be useful for selecting patients for early
administration of targeted therapies
ctDNA levels may be prognostic at the mid-treatment time point
Potential for future studies that offer early therapeutic intervention
based on ctDNA quantitation
