5 / 17
Allied Journal of Medical Research
|
Volume 2
Page 23
allied
academies
CANCER THERAPY AND ONCOLOGY
NEUROLOGY AND BRAIN DISORDERS
&
International Conference on
International Conference on
J u n e 2 1 - 2 2 , 2 0 1 8 | O s a k a , J a p a n
Joint Event on
PROGNOSTIC ASSOCIATION OF PLASMA
CELL FREE DNA BASED ANDROGEN RECEPTOR
AMPLIFICATION AND CIRCULATING TUMOR
CELLS IN PRE-CHEMOTHERAPY METASTATIC
CASTRATION RESISTANT PROSTATE CANCER
PATIENTS TREATED WITH ABIRATERONE
ACETATE
Manish Kohli
Mayo Clinic, USA
Background:
The prognostic significance of plasma cell-free DNA (cfDNA)
androgen receptor amplification (ARamp) in metastatic castration
resistant prostate cancer (mCRPC) stage is not known.
Methods:
As part of a prospective study in mCRPC stage, concurrent
collection of plasma and circulating tumor cell (CTC) counts was
evaluated for determining prognostic value of plasma cfDNA ARamp.
Specimen collection was performed twice, after progression on androgen
deprivation therapy (baseline) and then repeated after 12 weeks.
QuantStudio3D digital PCR. system (dPCR) was used to determine
plasma cfDNA AR copy number variations (CNVs) and Cell search assay
for enumerating CTC counts. Association of baseline cfDNA ARamp
status/CTC counts with overall survival (primary goal) was evaluated
using Kaplan–Meier method and log-rank test (p ≤ 0.05 for significance)
and Receiver Operator Curves (ROC) for ARamp status and CTCs ≥ 5. A
multivariate analysis was also performed using Cox regression models
that included ARamp, CTC counts, volume of metastatic disease, cfDNA
amount, Gleason score and PSA levels.
Results:
ARamp was detected in 19/70 patients of baseline plasma
specimens. At the time of analysis, 28/70 patients had died (median
study follow-up 806 days (IQR: 535-966)). ARamp was associated with
poor overall survival (2 year OS of 35% vs. 71% in non-ARamp; log-rank
p-value= <0.0001). Baseline CTC count ≥ 5 (vs < 5) was also associated
with poor survival (2 year OS of 44% vs 74%); log-rank p=0.001). ROC
analysis demonstrated area under the curve (AUC) of 0.66 for ARamp and
0.68 for CTC counts based prognosis (p=0.84 for difference). The best
two variables included for multivariable analysis were ARamp and CTC
≥ 5, however the two factor model was not significantly better than using
ARamp alone for predicting survival (HR=5.25; p=0.0002).
Conclusions:
Plasma cfDNA ARamp has clinical utility as an independent
prognostic factor in mCRPC stage.
Manish Kohli holds an academic rank of Profes-
sor and Consultant in Oncology at Mayo Clinic.
He has participated extensively in cancer clini-
cal research for the past 15 years. During this
time, he has initiated therapeutic trials, recruited
several hundred patients for intervention and
non-intervention cancer biomarker-based clini-
cal trials andpublished resultsof several of these
studies. During the course of this research ef-
fort, he interacted with multi-disciplinary teams
which involved working with geneticists, labora-
tory scientists, bio-statistical and bio-informatic
colleagues, study personnel among others. His
early publications were focused on clinical re-
search, mainly in prostate cancer therapeutics.
These publications helped advanced therapeu-
tic science in particular with the establishment
of docetaxel chemotherapy in castrate resistant
prostate cancer in 2004. Subsequently, he built
upon these research experiences in developing
genomic-based biomarker profiling in advanced
prostate/kidney cancer therapeutics as a tool
towards developing a precision medicine that
is based on cancer’s genetic landscape. In this
regard, he initiated the building of prospective
clinically annotated bio-repositories, which have
uniform processing protocols for obtaining
quality research specimens.
Kohli.Manish@mayo.eduBIOGRAPHY
Manish Kohli, Allied J Med Res 2018, Volume 2