Thread by @pashtoonkasi

#GI21 time for another #Tweetorial🧵 on

#LiquidBiopsies
#CirculatingTumorDNA
#ctDNA

in a very 🎯 “Target-rich” disease
#Cholangiocarcinoma
#HPBCSM

~3️⃣0️⃣% actionable findings

Interestingly we found more #FGFR🧬 fusions on liquid🩸than tissue 🔬. #OncoAlert
@TempusLabs

🧵2️⃣ #GI21
#Cholangiocarcinoma is the poster child of actionable aberrations & truly a 🎯“Target-rich” disease.

We focused on %numbers for aberrations for which there’s either an ✅approved drug, guideline endorsement, #clinicaltrials or even off-label reports/cases.👇🏾

🧵3️⃣ #GI21
We often don’t think of #ctDNA based platforms to be as sensitive for detecting fusions; when present it is real & an actionable finding.

Interestingly we found #FGFR🧬fusions
🩸LIQUID>>TISSUE🔬
💭 maybe because of selection bias. #ctDNA filling the void. #OncoAlert

🧵4️⃣ #GI21
Focusing #FGFR 🧬 fusions & fusions in general, you have to know your testing platform. Whether it’s tissue🔬or🩸liquid, fusions can be detected.

🩸is not meant to replace🔬but for some pts may be the only option. Tissue often not sufficient in #cholangiocarcinoma.

🧵5️⃣ #GI21
All of us who treat #cholangiocarcinoma & doing #clinicaltrials using #FGFR🧬⛔️ know challenging it is to find these patients who would derive immense benefit from these new drugs. 🔐

#ctDNA can help aid & find the additional cohort of pts where 🔬wasn’t feasible.

🧵6️⃣ #GI21
With increasing number of 🎯targeted⛔️therapies now being approved or available through trials or off-label, acquired mechanisms of resistance can be non-invasively be captured on #ctDNA based platforms.

👇🏾pt ē ERRFI1 on Erlotinib.
Exquisite response📉.
Later MET📈.

🧵7️⃣ #GI21
We have a real opportunity to make an impact on the lives of our pts ē #cholangiocarcinoma. We may not have drugs or options/trials for all the aberrations👇🏾.
However, in about ~ 3️⃣0️⃣% of these➡️ #PrecisionMedicine.
#ctDNA can fill the void. #HPBCSM #OncoAlert @ASCO

8️⃣🧵
#GI21 #HappeningNow @ASCO
Glad that
IDH1⛔️
Is now @NCCN guidelines.
>1️⃣5️⃣% of intrahepatic #cholangiocarcinoma #HPBCSM.

Again cannot overemphasize the “Target-rich” nature of disease. #ctDNA NGS platforms upfront & potentially at progression. New trials open too. PARP⛔️.

9️⃣🧵
#GI21 #HappeningNow
Moving from one targeted therapy for again intrahepatic #cholangiocarcinoma to another.

#FGFR⛔️
We already have pemigatinib approved. This is Infigratinib BGJ398 QED.

~1️⃣5️⃣% IHCC.

Note 👆🏾liquid can fill the void for some pts ➡️ ⬇️tissue. #OncoAlert

🔟🧵
One under recognized utility of 🧬 testing results here is for pts ē #CUP #CancerofUNKNOWNprimary presenting as a liver mass. While advances in pathology help guess which 🪣 to classify, it’s not always diagnostic.
If you find 🧬FGFR or IDH; likely #cholangiocarcinoma. #GI21

#GI21 interesting discussion on value of NGS 🔬as well as #liquidbiopsies #ctDNA which is theme of 👆🏾#Tweetorial.

Post IDH1⛔️➡️ISOTYPE SWITCHING 1️⃣➡️2️⃣❗️; maybe role for other therapies; needs to be studied.
Post FGFR⛔️➡️FGFR mutations; ❌fusions. Role for ?sequencing.

#GI21 on post-FGFR⛔️resistance.

Please do 👀/🖍 💭 on my📝on #FGFR-fusion➕ #cholangiocarcinoma.
🆓 Available now👉🏾 karger.com/Article/Fullte…
Acquired 📈🔴🟠⚪️ #FGFR mutations ➡️ FGFR⛔️ #ctDNA 🩸🧬;📉chemo💡♻️.
HETEROGENEITY:
1️⃣Intra-tumoral
2️⃣Temporal ⏳

#HPBCSM
#LiquidBiopsies