Thread by @MPishvaian

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📣 51 yoF presents with abdominal pain

FH – Father with lung cancer (🚬)

Imaging 📷 showed a 2.9 x 2.6cm panc head mass encasing the SMA

EUS-FNA 💉 - Well-diff adenocarcinoma

➡️Dx: locally advanced unresectable PDAC

❓How you would Tx this Pt?

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Case Follow Up

Patient treated with FOLFOX + SBRT ⚡️
Then maintenance capecitabine
✅(SDz for 2 years!) 👍

Eventually progression with a right ovarian metastasis

❓Poll: Now how would you treat the patient?

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Additional details - NGS DNA Testing 🧬

Somatic tumor testing – pathogenic ATM mutation❗️

Germline testing – no germline ATM mutation

➡️ Share how this information would change your treatment plans 🤔

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🧑‍🎓Mini-Tweetorial 1

💡Tumor somatic NGS 🧬 ➡️ “Actionable Mutations” in 25% of PDACs
pubmed.ncbi.nlm.nih.gov/32135080/

💡ATM ➡️ most common actionable mutation-6.2%
pubmed.ncbi.nlm.nih.gov/31676541/

💡2% of PDAC pts harbor a germline ATM mutation
pubmed.ncbi.nlm.nih.gov/29922827/

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👨‍🎓Mini-Tweetorial 2

💡ATM plays a critical role in sensing DNA 🧬 damage

💡ATM ➡️ cell cycle arrest

💡ATM ➡️ DNA repair 🛠️ by homologous recombination

💡Pathogenic ATM muts render tumors sensitive to radiation ⚡️

💡And to platinum-based chemo

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👨‍🎓Mini-Tweetorial 3

💡Not all DDR muts are =
➡️ Need to 🔎 how to Tx each mut differently

💡Unclear 🤔 if ATM-mut tumors respond to PARP inh

💡There is synth lethality of DNA damaging chemo + an ATR inh and an ATM mut

pubmed.ncbi.nlm.nih.gov/32568634/

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Case Outcome

➡️Patient retried on FOLFOX 🚫 Ox allergy

➡️Then Phase I trial with a PARP inhibitor
❌No benefit

➡️Treated with gemcitabine plus nab-paclitaxel

➡️Phase I trial of irinotecan + an ATR inhibitor
✅Stable disease through 6 months

@TumorBoardTues CME info & Post-case Test: integrityce.com/posttest1-12

Question #1

65 yo male diagnosed with met pancreatic cancer. He is started on treatment with first-line mFOLFIRINOX. During the course of treatment, additional testing should include:

@TumorBoardTues CME info & Post-case Test: integrityce.com/posttest1-12

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Question #2

The most common potentially “actionable” alteration in pancreatic cancer is a (an):