De Bono #AACR19 Looked at 10-15 CTCs per pt. Benefit to pt: can transform clinical pt care: freq testing feasible,… https://t.co/LI7gWbSDl7
7:40am April 1st 2019 via Twitter Web Client
De Bono #AACR19 From 200 CTCs: copy number data from 200 scCTCs cp with mCRPC exomes very similar. Shows sig intra-pt heterogeneity.
7:38am April 1st 2019 via Twitter Web Client
De Bono #AACR19 In cancer pts: n>50, tolerated well. '18 CCR https://t.co/3ijvDKjxbb Shows increase of yield in PrCa. 1000x yield.
7:36am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Major limitation: low cell count. Diagnostic apheresis: mean of >10K CTCs in 50mL apheresis product… https://t.co/kq1aXkU
7:35am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Serial single CTC low-pass WGS: manuscript in prep. Neves AACR 2018: changes of subclones over time… https://t.co/CtAvA5hj8F
7:34am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Before Rx, Wk 4, Wk 14: 8q gain (MYC) lost by week 4. Pt did not respond, but the Rx did affect the… https://t.co/VoOJ7s79TT
7:33am April 1st 2019 via Twitter Web Client
De Bono #AACR19 TOPARP-A, TO-PARP-B will be ASCO2019. Single CTC isolation and genomic analysis: subclonal changes during PARPi Rx
7:32am April 1st 2019 via Twitter Web Client
De Bono #AACR19 But in early-stage in PrCa: Very few CTCs, struggling 'with this for over a decade'. CTC counts are used as co-primary endpt
7:31am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Changes in CTC w/Rx in PhIII: pt-level surrogacy demonstrated in PrCa. Counts embedded in multiple trials.
7:30am April 1st 2019 via Twitter Web Client
De Bono #AACR19 CTC counts 'highly prognostic' (br, pros, CRC, SCLC). No doubt - changes in CTC counts post-Rx assoc'd w/resp.
7:29am April 1st 2019 via Twitter Web Client
De Bono #AACR19 CTCs "are making a comeback". Where we are now: assays 'highly reproducible', regulatory clearance obtained.
De Bono #AACR19 Shows fig from '18 Cell https://t.co/kig8IjorbL
7:28am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Shows during Rx response (flat copy number); at progression copy number looks very similar. aCGH da… https://t.co/BneQgxwFKU
7:27am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Different sites have different mutations. Shows unpubl data, low-pass WGS of mCRPC: defining CNV. A… https://t.co/CGgk4T6R7H
7:26am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Other markers - miRNA and mRNA are 'attracting attention but need further validation'. Mehra '18 Go… https://t.co/VikHj6lohf
7:25am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Whole-blood apheresis: CTC counts do not fall - continuously produced. Methods - targeted NGS, ddPCR, WES, low-pass WGS.
7:22am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Lack of proof for clin utility. Onto circulating biomarkers: cfDNA conc. can be prognostic; cfDNA c… https://t.co/Kbb7Lh18BI
7:21am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Plenty of reasons of failure for validation and qualification; reproducibility crises of 11%. Insuf… https://t.co/Ql8iqwvTTm
De Bono #AACR19 Clinical qualification: for many biomarkers 'we have not done that' - like w/AR-V7 we have not done… https://t.co/EiD115MC8S
7:20am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Repro: intra-lab, inter-lab, biological variability across time. Diurnal rhythm, fasting/fed, exercise.
7:18am April 1st 2019 via Twitter Web Client
De Bono #AACR19 The devil in the details with analytical validation: LoD, FNs, continuous variables are preferred o… https://t.co/ZxdTeRE1Fn
De Bono #AACR19 If good prognosis: you have a problem; you'll need large randomized trials... The process of obtain… https://t.co/EzjgrXAvsN
7:16am April 1st 2019 via Twitter Web Client
De Bono #AACR19 PTEN loss: studying a PhIII Roche drug: AKT-blockade. Both prognostic and predictive: if prog of po… https://t.co/cy2BXO4lgV
7:14am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Pre-Rx: can be difficult to dissect the prognostic from the prognostic AND predictive. AR7 splice v… https://t.co/MMxBMJjjiZ
7:13am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Pre-cancer Dx: risk markers (BRCA); Dx (BCR-ABL); pre-Rx: prognostic (Ki67) or predict (guide Rx);… https://t.co/M0sTjeZa0d
7:11am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Ex of markers: blood press; HIV viral load; HER2 and ER in Br cancer. Shows slide #3 from this FDA… https://t.co/jXPuc6QobX
7:09am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Whole blood GEX (WBC), looking at myeloid cell's involvement with PrCa. Assuming: people knowing le… https://t.co/DjPhXf9SHh
7:07am April 1st 2019 via Twitter Web Client
De Bono #AACR19 PrCa: after Rx, 2-3 mo the drug doesn't work, you don't learn anything. Spent a lot of time w/CTC.… https://t.co/AM9qiz8cZD
7:06am April 1st 2019 via Twitter Web Client
De Bono #AACR19 Has been working on circulating biomarkers since '07; early trials 'were not really interpretable' - needed more info.
7:05am April 1st 2019 via Twitter Web Client
Johann De Bono (Royal Marsden UK) #AACR19 Impacting cancer research and patient care through circulating biomarkers
7:03am April 1st 2019 via Twitter Web Client
#AACR19 Q:Antigen retrieval? Akoya Kennedy-Darling: Analysis and retrieval on the coverslip isn't standard, current… https://t.co/Qm7d3d0Xqm
2:33pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: Aqua analysis invented '99. Patented '07, owned by Novartis in '13 (Navigate biopharma, limited dist.)
2:31pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: QIF: how deep the stain goes? Est only 1-1.5um. Depth may not be important, rather diffusion.
#AACR19 Akoya Q: How thick can CODEX go? Rimm: Up to 10um. Higher - can the Ab get to the tissue. Need to also optimize fluidics protocol.
2:30pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Q: One objection is archiving Rimm: Pretty soon we won't have glass at all for archiving (only digital).
2:29pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Q: Calibration - do you normalize across specimens? Rimm: Can't normalize out pre-analytical var's.
2:28pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: Hypothesis - talking on Monday, MOA is on macrophages binding PD-L1; when inhibited, macrophage… https://t.co/axCwVIXxMQ
2:26pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: Points to this https://t.co/LQ1dUZE83d and https://t.co/6bg3cC9kRu showing high correlation bet… https://t.co/2ZCbaqLsen
2:23pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: Concl "Counting and measuring are related but not equal'. Counting more accurate with rare events.
2:21pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: PFS and OS of RECIST categories - retrospective analysis looking at the charts, validating their criteria.
2:17pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: The problem w/% cells pos: you still need a threshold. Points to this recent CCR piece… https://t.co/qm88PQI5tD
2:16pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: Measuring cells with chromagens: percent positive cells, and count via phenotypes. QIF: what's… https://t.co/2fcud6T1Jk
2:14pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: "15y ago when we started everyone thought we were nuts, now everyone is doing (QIF)"
2:13pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: Inter-site PD-L1 R2 = 0.81. Taking human judgement out - MITRE w/ QIF represents the first pros… https://t.co/a4aEOZgQvu
#AACR19 Akoya Rimm: Tonsil CD20 slides: new LEDs reduces unmixing issues. Inter- and intra-site. MITRE initial resu… https://t.co/vewOqKOb1y
2:12pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: Measuring stain intensity; started with lymph, and cell line TMA ('control pellets') with neg,… https://t.co/ZPZpqeuxo7
2:10pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: Standards for quantitative fluorescence - a standardization TMA. Their mIF panel: PD-L1, Cd8, F… https://t.co/elJHCecAdo
#AACR19 Akoya Rimm: A 6-plex panel: PDL1, PD1, CD8, CD68, Foxp3, tumor (CK/lung, Sox10%S100/mel).
2:08pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: Results under embargo and will be published 'soon'. MITRE: have a drug, "a validation of the QI… https://t.co/oo9Lkw22hC
2:07pm March 31st 2019 via Twitter Web Client
#AACR19 Akoya Rimm: Interesting - combinations of modes - get to 0.802 (multiplex IF + IHC). QIF of 0.8 has a low n… https://t.co/L0bjNlLGbK
2:06pm March 31st 2019 via Twitter Web Client
