Krishnan: Shows linearity of signal to DNA concentration; showing mCRC progression; correlation w/clin status, CEA #Tricon
1:15pm February 23rd 2017 via Hootsuite
Krishnan: To the FDA, cfDNA >300bp. Smear can ID a signal there, showed trace from a prostate cancer pt #Tricon
1:14pm February 23rd 2017 via Hootsuite
Krishnan: Trtmt resp std of care via imaging or limited tumor markers; emerging is liquid biopsies and molecular imaging #Tricon
1:13pm February 23rd 2017 via Hootsuite
Krishnan: Cost of side-effects to immunotherapies add 16-18% to the treatment cost (per Moffitt study) #Tricon
1:11pm February 23rd 2017 via Hootsuite
Krishnan: Treatment response monitoring application: most cancer pts are Stg III-IV, and feel this can help #Tricon
1:09pm February 23rd 2017 via Hootsuite
Krishnan:Shows Biological Dynamics video of how it works https://t.co/K6TNTLSdoO #Tricon
1:08pm February 23rd 2017 via Hootsuite
Krishnan:Currently going through FDA, clin appl for treatment resp monitoring (Class II) #Tricon
1:06pm February 23rd 2017 via Hootsuite
rishnan:Size ranges in blood: <0.01um HSA, Ig, fibrinogen. To 1um: exosomes, large protein aggregates, HMW cfDNA (>300bp), debris #Tri
1:05pm February 23rd 2017 via Hootsuite
Krishnan: 150uL of sample (blood, serum, plasma as native), nanoparticles captures on electrodes; fluidic wash and imaging #Tricon
1:03pm February 23rd 2017 via Hootsuite
Krishnan: Dielectrophoresis (DEP); AC electrothermal flow; AC electro-osmotic flow. Non-uniform electric fields to move particles #Tricon
1:02pm February 23rd 2017 via Hootsuite
Raj Krishnan (Biological Dynamics) Noval AC electrokinetic platform for isolating cfDNA and exosome biomarkers for clinical app's #Tricon
1:01pm February 23rd 2017 via Hootsuite
Bettegowda: Concluded with BRAF detection in CSF, monitoring over 5mos. Ancillary fluids can be a rich source of tumor-spec DNA #Tricon
12:57pm February 23rd 2017 via Hootsuite
Bettegowda: A few lower-grade tumors didn't detect. Recent work on ctDNA in CSF ref https://t.co/JtgQwlHwFH #Tricon
12:54pm February 23rd 2017 via Hootsuite
Bettegowda: Concluded that CNS shed little ctDNA into the blood. For CSF: ctDNA is there. '15 PNAS https://t.co/MX7UzS9pju #Tricon
12:52pm February 23rd 2017 via Hootsuite
Bettegowda: Showed work on pap-smear in '13 Isaac Kinde's work https://t.co/Olp18BwE2H #Tricon
12:51pm February 23rd 2017 via Hootsuite
Bettegowda: Points out Kinde et al '11 PNAS https://t.co/kmU86RoYK4 and description of SafeSeqS. 410 cases https://t.co/hCoiKP1RPe #Tricon
12:43pm February 23rd 2017 via Hootsuite
Bettegowda: Points to this '15 ref https://t.co/H5CSPR4Vzd that describes branched evolution of brain mets, potential targets #Tricon
12:38pm February 23rd 2017 via Hootsuite
Bettegowda: Shows MRI of a glioblasmoma, after Tx what do you say with suboptimal resp. via imaging afterwards? #Tricon
12:36pm February 23rd 2017 via Hootsuite
Bettegowda: As a neurosurgeon, looks at neuro-oncology. PET and CAT scans - shows a lesion, what to say to the pt? #Tricon
12:35pm February 23rd 2017 via Hootsuite
Bettegowda: Shows data of non-synon mutations per tumor from '13 ref https://t.co/gHcnTPu63d #Tricon
12:34pm February 23rd 2017 via Hootsuite
Chetan Bettegowda (Johns Hopkins MD) Tumor derived cell free DNA as a diagnostic tool for human malignancies #Tricon
12:32pm February 23rd 2017 via Hootsuite
Q:Absolute conc helpful? Diehn:Yes, better, they can back into it; they always look at both internally #Tricon
12:26pm February 23rd 2017 via Hootsuite
Q: Early det/localization require imaging? Diehn:Pattern, protein markers, clinical knowledge also helpful about pts #Tricon
12:25pm February 23rd 2017 via Hootsuite
Diehn: Clinical trial results needed for screening. Future effort: further improvements; other markers; other fluids. #Tricon
12:22pm February 23rd 2017 via Hootsuite
Diehn: How to localize a tumor ID'd via ctDNA? May be able to det tissue of origin: pattern of muts, methylation, exosomes, protein #Tricon
12:21pm February 23rd 2017 via Hootsuite
Diehn: Problem of hematopoeisis - majority of ccfDNA is from blood cells. #Tricon
12:20pm February 23rd 2017 via Hootsuite
Diehn: Benign conditions w/somatic mutations are nevi, leiomyomas (esp uterine fibroids), clonal hematopoiesis #Tricon
12:18pm February 23rd 2017 via Hootsuite
Diehn: Unclear what fraction of pre-invasive lesions release much ctdDNA. 1/11 colonic adenomas w/det ctDNA #Tricon
12:16pm February 23rd 2017 via Hootsuite
Diehn: From NIPT, incidental detection of ctDNA from 125K tests, 0.008% was occult cancer. But rel late stg. #Tricon https://t.co/V940xolHSS
12:15pm February 23rd 2017 via Hootsuite
Diehn: Showed results from SafeSeqS pub '14; Stg I sens at 42%; median was 1 fragment per 5mL #Tricon
12:13pm February 23rd 2017 via Hootsuite
Diehn: Showed cases from '14 ref - progression, amount of mutant cfDNA cp to tumor volume. #Tricon
12:12pm February 23rd 2017 via Hootsuite
Diehn: Showed ROC curve from Newman '14 comparing Stg I 50% sens to Stg II-IV 100% sens even when mutations were known. #Tricon
12:11pm February 23rd 2017 via Hootsuite
Diehn: For colorectal and lung, early-detection has improved survival. ctDNA may be an ideal biomarker. #Tricon
12:10pm February 23rd 2017 via Hootsuite
Diehn: Tumors at early stg assoc'd with better 5-y OS; 95% for CR Stg I vs 10% at Stg IV; for NSCLC, 60% at Stg I, 5% at Stg IV. #Tricon
12:09pm February 23rd 2017 via Hootsuite
Diehn: Also went into xenografts with MET ampl and dose-response; showed pathway inh restores sens to rociletinib #Tricon
12:07pm February 23rd 2017 via Hootsuite
Diehn: Also found MET ampl mediates innate and acquired resistance; showed progress over time. Also 5 other muts in same pt #Tricon
12:05pm February 23rd 2017 via Hootsuite
Diehn: Mutation via structure analysis, showed binding pocket affected, showed in-vitro dose-response in Ba/F3 cells #Tricon
12:04pm February 23rd 2017 via Hootsuite
Diehn: Difference was a different third-gen TKI. Found a novel EGFR L798I, showed progression over time. #Tricon
12:03pm February 23rd 2017 via Hootsuite
Diehn: Showed emergence of EGFR C797S in a single pt, and how it progressed over time. Found in 2%; other report 32% #Tricon
Diehn: For Rociletinib, found significant intra- and inter-pt heterogeniety. Weakness of PM - selection of multiple resistance #Tricon
12:02pm February 23rd 2017 via Hootsuite
Diehn: All pts have EGFR activating, T780M; 46% had more than 1 mechanism '16 ref https://t.co/huMro79E4v #Tricon
12:00pm February 23rd 2017 via Hootsuite
Diehn: Looking at resistance heterogeneity; is first-line Rx lead to intra-pt heterogeneity in resistance? #Tricon
11:59am February 23rd 2017 via Hootsuite
Diehn: 10% had more than one mechanism of resist; 49% T790M; 30% unk '11 ref https://t.co/GFseY5snQ3 #Tricon
11:58am February 23rd 2017 via Hootsuite
Diehn: T790M resistance is most frequent - 50-60%; Third-gen TKI is osimertinib, rociletinib, others #Tricon
11:56am February 23rd 2017 via Hootsuite
Diehn: Applied to NSCLC, EGFR mutants. 15-50% of lung ca; sens to EGFR TKI's. First line Rx 9-12 mos resistance #Tricon
Diehn: Looking at clinical samples, 50 advanced NSCLC pts, showed Sens 93%, Spec 100%, PPV 100%, NPV 95% #Tricon
11:55am February 23rd 2017 via Hootsuite
Diehn: Observed and expected AF% based on ddPCR, linear R=0.93 down to well below 0.5% #Tricon
11:54am February 23rd 2017 via Hootsuite
Diehn: iDES=integrated Digital Error Correction. Other methods require a lot more input DNA. Chart stochastic and stereotype errors #Tricon
11:53am February 23rd 2017 via Hootsuite
Diehn: Looked at background errors from healthy individuals, then developed both barcoding and polishing they call iDES #Tricon
11:52am February 23rd 2017 via Hootsuite
Diehn: Looked at distribution of errors for all types G>T etc. https://t.co/X1KajWfFTp went to published data at 0.03%, saw same #Tricon
11:51am February 23rd 2017 via Hootsuite
