Thread by @DAielloMD

1/26 #TumorBoardTuesday #LungCancer #OncTwitter @DrSteveMartin
⛹🏻‍♀️Case 1⛹️‍♂️
80 yo 👵🏼 never 🚬
🩻 Imaging shows R lung mass
🦴 New hip pain found to have R femoral lytic lesion
⚒️Undergoes ORIF R femur
🔬R femur path: metastatic squamous cell carcinoma, TPS 1%
🤔What next?

2/26 #TumorBoardTuesday #LCSM

🩸🧬Surprise, surprise - you send ctDNA!
➡️Results show MET Exon 14 skipping mutation (VAF 0.5%)
👵🏼started on MET TKI capmatinib 400mg BID
👍CTCAP 2 months later shows impressive response 🙌🏽

3/26 #TumorBoardTuesday #LCSM
👨🏻‍🏫Mini tweetorial 1👩🏻‍🏫

⭐️~10.5% of pts w SCC have actionable alterations
🕵🏻‍♀️Consider NGS in nonadeno #NSCLC pts who
1⃣🚭or light 🚬hx (1-10 pack yrs)
2⃣young age (dx age <50)
bc potentially ⬆️ prevalence driver muts
📚@IASLC jto.org/article/S1556-…

4/26 #TumorBoardTuesday
👨🏻‍🏫Mini tweetorial 2👩🏻‍🏫

⭐️ctDNA 🧬 useful complement to tissue-based molecular testing
👍Pros:
⬆️TAT
⬆️concordance rate
minimally invasive
better captures tumor heterogeneity 🎯
👎Cons
Protein biomarkers such as PD-L1 not evaluable
potential false➕or ➖

5/26 #TumorBoardTuesday
👨🏻‍🏫Mini tweetorial 3👩🏻‍🏫
⭐️MET Exon 14 skipping mutation➡️protein lacking CBL binding site ➡️🔻MET degradation ➡️🔺MET activity (See image)

⭐️Pts w MET exon 14 skipping mutations more likely to be
✅elderly
✅female
✅nonsmokers
📚pubmed.ncbi.nlm.nih.gov/30089599/

6/26 #TumorBoardTuesday #LCSM
⛹️‍♀️Case 2⛹️‍♂️

👱🏼45 yo with advanced ALK fusion positive #NSCLC on
💊1L alectinib x 3 yr
🫁s/p prior SBRT to isolated lesion
☣️ CTCAP suggests limited POD in

@BrunaPellini @SpaceJacky @ShrutiPatelMD @SA_Rosenberg @ADesaiMD @drshieldsmd @MktgSalesMom @christine_lovly @s_j_kearney @aadel_chaudhuri @btfoundation @pradeep198212 @WashURadOnc @almdavenport @NaglaAKarimMD @cwspeers @GutmannLab @EarlandNoah @JMHerndone

7/26 #TumorBoardTuesday #LungCancer

🧪ctDNA results show
1⃣ALK-EMLA4 fusion (VAF 0.8%) and
2⃣new ALK L1196M alteration (VAF 0.7%)

🤨 What do you do next?

8/26 #TumorBoardTuesday
👨🏻‍🏫Mini tweetorial 4👩🏻‍🏫

🧬ctDNA
👍detects acq resist mechanisms
👎canNOT confirm SC transformation
❌#NSCLC coexpressing EML4-ALK fusion + L1196M mut resistant to 1st & 2nd gen ALKi
✅L1196M mut: 3rd gen ALKi lorlatinib sensitive
📚aacrjournals.org/cancerdiscover…

9/26 #TumorBoardTuesday #LCSM

⛹️‍♀️Case 3⛹️‍♂️

60yo 👩 never 🚬
p/w cough
🫁R mass with mediastinal LN
✅Bronch/EBUS confirms lung adeno (Stage IIIC)
🔬Tissue mol testing: EGFR Exon 19 del
⏳Patient tx with definitive chemoRT
😱Post-tx scans: nodules suspicious for POD
🧪Send ctDNA

10/26 #TumorBoardTuesday #LCSM @DrStevenMartin @MPishvaian
👀 Results show EGFR Exon 19 deletion with VAF 0.07%

⛹️‍♀️⛹️‍♂️ Team huddle! 🏀

🧠💭How do you interpret this result?

11/26 #TumorBoardTuesday
👨🏻‍🏫Mini tweetorial 5👩🏻‍🏫
📢Detection of ctDNA minimal residual disease (MRD) following CRT🔮 in local #NSCLC

🧐FFP at 36 mo after MRD
0% in pt w detectable ctDNA
93% in pt w undetectable ctDNA
(P < 0.001, HR 43.4; 95% CI, 5.7–341)
📚pubmed.ncbi.nlm.nih.gov/28899864/

12/26 #TumorBoardTuesday
👨🏻‍🏫Mini tweetorial 6👩🏻‍🏫
📝posthoc✨PACIFIC (consolidation durvalumab after chemoRT) - EGFRm #NSCLC show🙅🏻‍♂️OS or PFS diff with IO vs placebo
🍛Food for thought 💭
🤔EGFR TKI preferable to durva?
🤔ctDNA MRD help select appropriate pts for TKI?
TBD✨LAURA

@emmacfields @abulusmani @StevenLin_MDPhD @PatelOncology @SprakerMDPhD @TylerSbrt @BenjaminSchrank @YWangPhD @binayshah @WashU_ctDNA @DrRiyazShah @JackWestMD @AndresFCardonaZ @TommyJohn00

13/26 #TumorBoardTuesday
🔎Back to Case 3

👩 started on osimertinib💊
🧬 Repeat ctDNA sent 2 months later
👍 Shows clearance of ctDNA

14/26 #TumorBoardTuesday #LCSM

⛹️‍♀️Case 4⛹️‍♂️

58 yo 👩🚭
multiple comorbs
Hx: Stage IB EGFR Exon 19 deletion s/p definitive XRT
😬F/u imaging with R 🫁 mass in postRT field
👩‍🦼🏥Patient poor bronch/EBUS candidate due to other medical issues

15/26 #TumorBoardTuesday #LungCancer #LCSM @TumorBoardTues @ChristianRolfo

😉🩸🧬In usual fashion, you send ctDNA!
🧪 Results show only an ATM G1016R mutation (VAF 0.1%)

🧐 What is the next best step in management?

16/26 #TumorBoardTuesday #LCSM

🏥Patient admitted for inpatient bronch/EBUS
🔬pathology confirms recurrence
🧪Tissue molecular testing shows an EGFR Exon 19 deletion

😢You shed a single tear because the ctDNA test let you down
🤨 What happened?

17/26 #TumorBoardTuesday
👨🏻‍🏫Mini tweetorial 7👩🏻‍🏫

🚩Some reasons for negative ctDNA🚩

📍low tumor burden potential
📍ctDNA concentration correlates with tumor stage + volume
📍Negative ctDNA doesn’t r/o active disease & tissue-bx should be done

📚@Nature pubmed.ncbi.nlm.nih.gov/28445469/

18/26 #TumorBoardTuesday #LungCancer
⛹️‍♀️Case 5⛹️‍♂️

60yo 👨🚭
L sided 🫁 mass - extensive mets
🔬Tissue path - adenocarcinoma
👎Bx insufficient for molecular testing

🧬ctDNA testing shows
1️⃣ RET fusion (VAF 1.4%)
2️⃣ BRCA mutation (48.4%)

🤨 How do you interpret the results?

19/26 #TumorBoardTuesday #LungCancer #LCSM

🏥Patient presents to clinic for f/u
🗨️👨asks, "What is next step for therapy, doc?"

🤔 What do you say?

20/26 #TumorBoardTuesday #LCSM
👨🏻‍🏫Mini tweetorial 8👩🏻‍🏫

🚩Nontumor sources of +ctDNA🚩

📍VAF ≈50% suspect germline variant
📍VAF <1% consider clonal hematopoiesis of indeterminate potential (CHIP) 🍪
📍Common 🍪variants: TP53, DNMT3A, ASXL1
🧬Confirmatory testing required

21/26 #TumorBoardTuesday
👨🏻‍🏫Mini tweetorial 9👩🏻‍🏫

⭐️RET fusions⭐️
👉Identified in 1%-2% of patient with #NSCLC
👉Selpercatinib and pralsetinib = selective RETi approved for RET fusion➕NSCLC

🎼LIBRETTO-001: pubmed.ncbi.nlm.nih.gov/36122315/
🏹ARROW: pubmed.ncbi.nlm.nih.gov/35973665/

22/26 #TumorBoardTuesday
🏀Final 4 - Q1️⃣🏀

72 👵 former heavy 🚬
New R 🫁 mass + multi liver lesions
😣Rapid sx progression
🔬Liver bx: TTF+ lung adeno TPS 60%
🧪ctDNA: no actionable alterations, but STK11 mutation (VAF 0.3%)

🧐What did you learn from the ctDNA?

23/26 #TumorBoardTuesday
🏀Final 4 - Q 2⃣ 🏀

75 👵active 🚬 p/w SOB
Large R sided 🫁 effusion, cytology negative x 2 💉💉
🩻PET/CT with lung/nodal/bone/liver involvement
📅Liver bx planned
🧬ctDNA - EGFR R836C (VAF 18.0%) and PTEN N3IT (VAF 15.4%)

🤨Next best step in mgmt?

24/26 #TumorBoardTuesday
🏀Final 4 - Q3⃣🏀

58M former 🚬 with CP
L 🫁mass, nodal involvement, 🧠 mets
FNA LN 🔬c/w met lung adeno, TPS >50%
🧬ctDNA sent
🚨Results show BRAF V600E (VAF 0.2%)

🤨What is front-line tx for BRAF V600E+, PD-L1 TPS >50% adv #NSCLC?

25/26 #TumorBoardTuesday
🏀Final 4 - Q 4⃣🏀

👉So how did you do?

26/26 #TumorBoardTuesday #LCSM
🧬Recap🧬
1⃣ctDNA Validated for expediting/completing mol testing 🎯
2⃣ctDNA dynamics for response/resistance to TKI
3⃣MRD for tx response/early recurrence
4️⃣Potential for "false"➕(germline or CHIP🍪mut)
5️⃣Potential for "false"➖(low tumor burden)

#PostTest Q1️⃣ #TumorBoardTuesday
👉🏽#CME Eval integrityce.com/tbtEval
👉🏽ALL CME integrityce.com/tbt

🤔@DrSteveMartin @DAielloMD taught us ctDNA🧬utility in #NSCLC test your🧠with CME❓

🧐What would U do
80yo🚭
path-confirmed mSCC
TPS 1%
R🫁 mass
R fem lytic lesion - RORIF?

#PostTest Q2️⃣ #TumorBoardTuesday
👉🏽Free CME (AMA & MOC)
🔗 integrityce.com/tbt
🧐What’s cause of discordant 🧬findings btwn ctDNA & tissue molecular 🧪 in pt with recur #NSCLC post definitive ☢️ w ➕ EGFR exon 19 del on 🔬 bx but ctDNA shows ATM G1016R mutation (VAF 0.1%)?

@PTarantinoMD has asked a similar Q before...

Nay it is-
Pts w STK11 mut may not respond to single agent IO

🔬Tissue is the issue
😮LN Bx revealed an unexpected dx
🚨 Lymphoma

⭐️ctDNA not always diagnostic, and can be misleading