VanderWalde: #ampeurope2018 As a medical oncologist: muts/MB, acquired not germline. Accuml. over time, '13 Lawrence https://t.co/b8tS2QX0fj

5:58am May 1st 2018 via Twitter Web Client

VanderWalde: #ampeurope2018 But cutoff seemed to be a bit of hand-waving; ajuv+ Nivo response corr w/TMB '18 NEJM https://t.co/unOxrlmQEv

5:56am May 1st 2018 via Twitter Web Client

VanderWalde: #ampeurope2018 PD-L1 is impt; however there are different tests. Bladder ca: https://t.co/uGlQID3A6g S… https://t.co/3xlBqVhAn2

5:54am May 1st 2018 via Twitter Web Client

VanderWalde: #ampeurope2018 '18 NEJM https://t.co/SPxi9K6Bsf Pembro + chemo in metastatic NSCLC OS for chemo + PD-1… https://t.co/WVq5hex7X2

5:52am May 1st 2018 via Twitter Web Client

Ari VanderWalde (TN USA): #ampeurope2018 Microsatellite Instability in Relation to PDL1 Expression and Tumor Mutati… https://t.co/l6nxiph64D

5:49am May 1st 2018 via Twitter Web Client

Q: A centralized approache to TMB? Stenzinger: #ampeurope2018 In DE, 15K to 20K pts to screen, TMB is so complex, n… https://t.co/feu8dOTXQl

5:16am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 'Real life clinical utility of TMB: CURRENTLY UNKNOWN' (his quote). Critical pt: bioinformatics. C to T from FFPE

5:11am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 'WES sounds robust but it is not'. A platform-dependent measurement, poster used FOne data.

5:10am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 "0.5MB will not work; think of 1MB or above for TMB" #AACR18 poster 5528 https://t.co/FhAG3M2iep

5:09am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 Also CRC, simulated TCGA data, 1.4MB panel, panel cutoff 10/MB. 'Size and composition of panels matter'

5:08am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 Clonality, sub-clonality: include a 10% VAF? Shows unpubl data w/cutoff of only 3 mut/MB… https://t.co/VrcIzu9zuE

5:08am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 Also size, composition of panels, effect of germline events. Not via subtracting blood, not standardized

5:04am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 So many variables: prenanalytical tumor cellularity, DNA quality; sequence enrichment panel (need >>0.5MB)

5:03am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 BMS quotes from Sci Am Feb 18 https://t.co/WtaRueyqTI 'no std way to measure or report TMB'

5:02am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 Det TMB cutoff? CheckMate 568 shows ROC curves, TMB at 9-10 muts/MB w/AUC 0.73

4:58am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 Hi mut load group PD-L1 nice response. #AACR18 Checkmate 227: NSCLC https://t.co/NtAeEy4jKb

4:57am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 Showing utility in clin trial: CheckMate 26 prosp. chemo vs Nivo failed completely. Retrospective, learned

4:55am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 Plot of TMB vs ORR, where Merkel-cell is outlier, and CRC MMR-def another one. 'But be c… https://t.co/9Us9KJ44zn

4:54am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 Showing data from Rizvi '15, '14 CTLA-4 https://t.co/8RGyIWR0GC TMB and resp rates https://t.co/dhqMA0ts8n

4:54am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 DNA repair def beyond MSI: fig from https://t.co/TdqJaJ5lox Several hundred genes involved with DNA repair.

4:50am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 EGFR del 19: you still want to know if its a lung adenocarcinoma. For MSI-H, you don't care, Pembro Rx

4:49am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 Points to FDA approval for MSI-H, first histology-agnostic biomarker. US FDA 'a game-changer'.

4:49am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 The MSI-H predicts response to PD-1 across major cancer types, endometrial at the top. B… https://t.co/OVjMSY3DYJ

4:48am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 Targeting PD-1 in MSI-driven tumors, sporadic accumulating TMB later in life '15 https://t.co/aWXuwqo4hy

4:47am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 And Rizvi '15 https://t.co/2HHXLoc6zK Drivign mutational load w/PD-1 in NSCLC

4:46am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 Connecting TMB to neoantigens is not 'that new'. Vogelstein's '13 paper, https://t.co/VJtwNJoaSD

4:46am May 1st 2018 via Twitter Web Client

Stenzinger: #ampeurope2018 Reviews genetic heterogeneity, why do some pts take different paths down the 'mountain topology' landscape?

4:44am May 1st 2018 via Twitter Web Client

Albrecht Stenzinger: #ampeurope2018 The evolution of Tumour mutational Burden (TMB) into clinical research

4:43am May 1st 2018 via Twitter Web Client

Q: Anything unusual about 2 samples failed? Heydt: #ampeurope2018 One was control, another high quality DNA, just sample handling.

4:39am May 1st 2018 via Twitter Web Client

Heydt: #ampeurope2018 Local data analysis version needed 'esp in DE'. TST170 too small for TMB. Need for total workflow validation.

4:38am May 1st 2018 via Twitter Web Client

Heydt: #ampeurope2018 Concl: works 'well with even very low DNA, RNA conc in cp with other methods'. Usable but - a… https://t.co/Pq4lWljj0q

4:37am May 1st 2018 via Twitter Web Client

Heydt: #ampeurope2018 ROS1 xloc, positive by FISH, IHC, Archer, Agilent, Nanostring. Also seen in TST.

4:36am May 1st 2018 via Twitter Web Client

Heydt: #ampeurope2018 2 ROS1 fusions not det by FISH, orthog. confirmed. 1 ROS1 fusion not det by FISH, not confirmed 'thus prob FP'

4:36am May 1st 2018 via Twitter Web Client

Heydt: #ampeurope2018 MET ampl in case 3: by FISH GCN=10, also be seq. 24/24 for RNA, as low as 1ng. 76-91% on-targ… https://t.co/kippXsLepv

4:35am May 1st 2018 via Twitter Web Client

Heydt: #ampeurope2018 One case of EGFR dupl, reported at E762fs (frameshift) but not correct. nd case w/KRAS, TP53… https://t.co/ZfwK3jEhcf

4:34am May 1st 2018 via Twitter Web Client

Heydt: #ampeurope2018 From 24 samples - 22/24 as low as 9 ng. 2 failed; 1 high level MET amp; low- int-level undetected

4:32am May 1st 2018 via Twitter Web Client

Heydt: #ampeurope2018 Shows biomarkers, Rx options, and MH Guide Reporting. (GenomeWeb https://t.co/U5Fjij5kzu )

4:30am May 1st 2018 via Twitter Web Client

Carina Heydt (Univ Cologee DE) Illumina workshop #ampeurope2018 Shows TST 170 to Variant Interpeter app. They use Molecular Health guide

4:29am May 1st 2018 via Twitter Web Client

Q: Type of sample? Bernards: #ampeurope2018 FFPE, even FNAs.

3:32am May 1st 2018 via Twitter Web Client

A3 Bernards: #ampeurope2018 The catch-22 of reimbursement and standard of care.

3:31am May 1st 2018 via Twitter Web Client

A2: Bernards: #ampeurope2018 Hard to validate all 70 genes; time and $. 'The US FDA has figured it out... EU has no consensus...'

3:31am May 1st 2018 via Twitter Web Client

Q: WT w/DNA is simple. How to std-ize RNA in the lab? Bernards: #ampeurope2018 Now have RNA-seq version of MammaPrint on MiSeq.

3:29am May 1st 2018 via Twitter Web Client

Bernards: #ampeurope2018 Hartwick foundation effort w/6K WGS by end of year, also including RNA-seq. Predict: will… https://t.co/7MWqY52M59

3:21am May 1st 2018 via Twitter Web Client

Bernards: #ampeurope2018 Concludes - examples of DNA-based therapies, but prognosis by GEx, subtypes by GEx, and pathways for classification

3:20am May 1st 2018 via Twitter Web Client

Bernards: #ampeurope2018 A case where the luminal signal is higher than the HER2, even though FISH indicates HER2+/ER+. NBRST study...

3:17am May 1st 2018 via Twitter Web Client

Bernards: #ampeurope2018 But 23% of pt classified into different subgroup cp to IHC/FISH. 1/2 FISH+ for HER2+/ER+ are BP luminal.

3:16am May 1st 2018 via Twitter Web Client

Bernards: #ampeurope2018 He founded Agendia, with Blueprint, dividing to luminal, HER-2 type, Basal-type. Luminal goes onto MammaPrint

3:15am May 1st 2018 via Twitter Web Client

Bernards: #ampeurope2018 Pharma has the fear/greed factor; sound rational for TNBC. 9 mos at Genentech: "The marketing people always win."

3:14am May 1st 2018 via Twitter Web Client

Bernards: #ampeurope2018 i-SPY2 trial: veliparib/carboplatin, shows prelim results Ph 3 trial. Expanding eligable p… https://t.co/RXHQOHrxJa

3:12am May 1st 2018 via Twitter Web Client

Bernards: #ampeurope2018 Shows K-M w/BRCA1-like tumors that clearly benefit. Shows BRCA1-like tumors w/77 gene signature

3:11am May 1st 2018 via Twitter Web Client