Thread by @jessrzanotti

@TumorBoardTues 1/15 #TumorBoardTuesday #PanCan #OncTwitter
46yo 👩🏻 asymptomatic
no comorb
🌀Screening abd US: liver nodules + pancreatic mass (body/tail)
🔬Liver bx + NET G2 Ki67 12%
🩻PET-Ga + uptake in pancreas & liver (SUVs>20)
💉1L: Lanreotide SC - DP liver after 1y (⬆️volume)
🤨What 2L tx?

@TumorBoardTues 2/15 #TumorBoardTuesday

👩🏻 starts 2L CAPTEM: major partial response🙏🏼
🔪Pancreatectomy + R0 liver resections
🔬Path: NET G3 Ki67 90%

🗓️2 mo later
back pain + weight loss: large retroperitoneal LN
💉3L: rechallenge CAPTEM ➡️ poor clinical control 🔀 Cisplatin + Etoposide

@TumorBoardTues 3/15 #TumorBoardTuesday #NETCancer @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD

👩🏻 DP mediastinal LN after 6 mo
💉4L: FOLFIRINOX with partial response/severe toxicity
📑NGS (Foundation One): very high TMB 97 MSS

🧐What 5L tx would you pick?

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD 4/15 #TumorBoardTuesday #NETCancer
Due to findings👆🏽

💉 Systemic therapy modified to Pembrolizumab

See image for full biomarker assay

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc 5/15 #TumorBoardTuesday
👩🏻‍🏫Mini tweetorial 1 👩🏻‍🏫

📌Pancreatic G3 #NETCancer
🔹may evolve from a G1/2 NET
🔹molecularly distinct from neuroendocrine carcinomas
🔹resemble G2 tumors
🔹Molecular profiling mutations often in ATRX, DAXX, MENIN, PI3K and typically low TMB (3-5)

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc 6/15 #TumorBoardTuesday
👩🏻‍🏫Mini tweetorial 2👩🏻‍🏫

📌MSI biomarker
📍≤ 10% of neuroendocrine carcinoma
📍MSI & TMB-h rare in G3 (<1%)
📍Hypermutation may be induced by temozolamide in #gliomas and #NETCancer
📍Molecular profiling upon DP on alkylating agents may find TMB-h

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc @pedrojfreire @MadisonConces @AGangiMD @gi_campiolo @ClaudioVladmir @PoHienEar @ArndtVogel @drallysonocean @aparna1024 @anup_kasi @HannahAlison20 @SebLange @Mvgs1706 @rachaelguenter @Ja_Capdevila @AmanChauhanMD @PatrickMcGarrah @sonbol_bassam @NirajGusani @cives_mauro @altoubaht

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc @pedrojfreire @MadisonConces @AGangiMD @gi_campiolo @ClaudioVladmir @PoHienEar @ArndtVogel @drallysonocean @aparna1024 @anup_kasi @HannahAlison20 @SebLange @Mvgs1706 @rachaelguenter @Ja_Capdevila @AmanChauhanMD @PatrickMcGarrah @sonbol_bassam @NirajGusani @cives_mauro @altoubaht 7/15 #TumorBoardTuesday
👩🏻‍🏫Mini tweetorial 3👩🏻‍🏫

Mechanism of hypermutation post temozolamide in #gliomas likely similar in #NETCancer: loss of function mutations of mismatch repair genes
📚 frontiersin.org/articles/10.33…

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc @pedrojfreire @MadisonConces @AGangiMD @gi_campiolo @ClaudioVladmir @PoHienEar @ArndtVogel @drallysonocean @aparna1024 @anup_kasi @HannahAlison20 @SebLange @Mvgs1706 @rachaelguenter @Ja_Capdevila @AmanChauhanMD @PatrickMcGarrah @sonbol_bassam @NirajGusani @cives_mauro @altoubaht 8/15 #TumorBoardTuesday
👩🏻‍🏫Mini tweetorial 4👩🏻‍🏫

📌Treatment sequencing of G3 #NETCancer
📍similar to G2 cases
📍Aggressive #NETCancer are managed by chemo
📍CAPTEM is preferred chemo, but FOLFIRINOX also effective in #PancreaticCancer

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc @pedrojfreire @MadisonConces @AGangiMD @gi_campiolo @ClaudioVladmir @PoHienEar @ArndtVogel @drallysonocean @aparna1024 @anup_kasi @HannahAlison20 @SebLange @Mvgs1706 @rachaelguenter @Ja_Capdevila @AmanChauhanMD @PatrickMcGarrah @sonbol_bassam @NirajGusani @cives_mauro @altoubaht 9/15 #TumorBoardTuesday
👩🏻‍🏫Mini tweetorial 5👩🏻‍🏫

📌Treatment sequencing of G3 #NETCancer

CAPTEM for metastatic, well-differentiated G3 NET cancers: multicenter retrospective study
📚@OncoThor ncbi.nlm.nih.gov/pmc/articles/P…
💥ORR 41%
💥Time to Tx failure 5.7 months
💥Median OS 31.7 months

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc @pedrojfreire @MadisonConces @AGangiMD @gi_campiolo @ClaudioVladmir @PoHienEar @ArndtVogel @drallysonocean @aparna1024 @anup_kasi @HannahAlison20 @SebLange @Mvgs1706 @rachaelguenter @Ja_Capdevila @AmanChauhanMD @PatrickMcGarrah @sonbol_bassam @NirajGusani @cives_mauro @altoubaht 10/15 #TumorBoardTuesday
👩🏻‍🏫Mini tweetorial 6👩🏻‍🏫

There’s limited evidence for immunotherapy in molecularly unselected #NETCancer
Hypermutated G3 #NETCancer cases have a response to immunotherapy

📚pubmed.ncbi.nlm.nih.gov/33230973/
📚pubmed.ncbi.nlm.nih.gov/35737914/

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc @pedrojfreire @MadisonConces @AGangiMD @gi_campiolo @ClaudioVladmir @PoHienEar @ArndtVogel @drallysonocean @aparna1024 @anup_kasi @HannahAlison20 @SebLange @Mvgs1706 @rachaelguenter @Ja_Capdevila @AmanChauhanMD @PatrickMcGarrah @sonbol_bassam @NirajGusani @cives_mauro @altoubaht 11/15 #TumorBoardTuesday #NETCancer
Back to our case🔎

👩🏻 DP after 7mo of Pembrolizumab with mediastinal LN

🤨 Now what would you do for your patient?

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc @pedrojfreire @MadisonConces @AGangiMD @gi_campiolo @ClaudioVladmir @PoHienEar @ArndtVogel @drallysonocean @aparna1024 @anup_kasi @HannahAlison20 @SebLange @Mvgs1706 @rachaelguenter @Ja_Capdevila @AmanChauhanMD @PatrickMcGarrah @sonbol_bassam @NirajGusani @cives_mauro @altoubaht 12/15 #TumorBoardTuesday #NETCancer
Back to our case🔎

🔀 Treatment changed
💉Current treatment: Nivolumab3 + Ipilimumab1
🙏🏼 C3 completed, no toxicities reported to date
📆 Will see 👩🏻 for regular follow-up every 3 weeks

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc @pedrojfreire @MadisonConces @AGangiMD @gi_campiolo @ClaudioVladmir @PoHienEar @ArndtVogel @drallysonocean @aparna1024 @anup_kasi @HannahAlison20 @SebLange @Mvgs1706 @rachaelguenter @Ja_Capdevila @AmanChauhanMD @PatrickMcGarrah @sonbol_bassam @NirajGusani @cives_mauro @altoubaht 13/15 #TumorBoardTuesday
📌Ipilimumab + Nivolumab
✨DART trial

📚@mdmanishshah aacrjournals.org/clincancerres/…

📍For non pancreatic #NETCancer:
✨Basket trial🧺
💥40% response for high-grade tumors but no distinction btwn neuroendocrine carcinomas vs G3 tumors
💥50% G3-5 adverse events

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc @pedrojfreire @MadisonConces @AGangiMD @gi_campiolo @ClaudioVladmir @PoHienEar @ArndtVogel @drallysonocean @aparna1024 @anup_kasi @HannahAlison20 @SebLange @Mvgs1706 @rachaelguenter @Ja_Capdevila @AmanChauhanMD @PatrickMcGarrah @sonbol_bassam @NirajGusani @cives_mauro @altoubaht @mdmanishshah 14/15 #TumorBoardTuesday
🔥BONUS🔥

One step further - comment and let us know about your practice
🧐 Do you use MGMT status to select treatment with CAPTEM?

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc @pedrojfreire @MadisonConces @AGangiMD @gi_campiolo @ClaudioVladmir @PoHienEar @ArndtVogel @drallysonocean @aparna1024 @anup_kasi @HannahAlison20 @SebLange @Mvgs1706 @rachaelguenter @Ja_Capdevila @AmanChauhanMD @PatrickMcGarrah @sonbol_bassam @NirajGusani @cives_mauro @altoubaht @mdmanishshah 15/15 #TumorBoardTuesday
🔥BONUS🔥

📌MGMT

💥Deficiency associated with response
💥Routine testing NOT recommended - considered to select pts needing objective response
💥Both arms +TEM - study not designed to test as predictive biomarker

📚@PamelaKunzMD pubmed.ncbi.nlm.nih.gov/36260828/

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc @pedrojfreire @MadisonConces @AGangiMD @gi_campiolo @ClaudioVladmir @PoHienEar @ArndtVogel @drallysonocean @aparna1024 @anup_kasi @HannahAlison20 @SebLange @Mvgs1706 @rachaelguenter @Ja_Capdevila @AmanChauhanMD @PatrickMcGarrah @sonbol_bassam @NirajGusani @cives_mauro @altoubaht @mdmanishshah #PostTest Q1️⃣ #TumorBoardTuesday
#CME Eval: integrityce.com/TBTeval23

🤔@RachelRiechelm2 @jessrzanotti taught us #NETCancer, test your 🧠

🧐What 2L Tx?
46yo 👩🏽‍🦱
Asx G2 (Ki6712% & body/tail panc mass)
🩻uptake in panc & liver (SUVs >20) high-vol progress on liver ➡️1y of lanreotide

@TumorBoardTues @RachelRiechelm2 @MPishvaian @JohnEbbenMDPhD @PamelaKunzMD @marklewismd @DianeReidyLagun @timpawlik @CanHealeu @duiliorocha_onc @RenataDAlpino @DBulzico @Juanmaoconnor @Nanodioca @OncoThor @helops79 @rcarvalhoonco @donadio_ds @leogilsan @ManikAmin4 @chirayumohin @carlacav @realbowtiedoc @jaypsv @viniciu_antonio @letswinpc @pedrojfreire @MadisonConces @AGangiMD @gi_campiolo @ClaudioVladmir @PoHienEar @ArndtVogel @drallysonocean @aparna1024 @anup_kasi @HannahAlison20 @SebLange @Mvgs1706 @rachaelguenter @Ja_Capdevila @AmanChauhanMD @PatrickMcGarrah @sonbol_bassam @NirajGusani @cives_mauro @altoubaht @mdmanishshah #PostTest Q2️⃣ #TumorBoardTuesday
👉🏽 Free CME 🔗 integrityce.com/TBT2023

🧐What 5L would you pick for 👆🏽46yo who developed:
G3 NET (Ki67 90%)
LN involvement
very high TMB (97 muts/Mb) following tx with 2L CAPTEM (pancreatectomy & R0 liver ✂️)
3L cis + etoposide
4L FOLFIRINOX