Nicholas Hornstein

GI Med Oncologist @NorthwellHealth via Fellow @MDAndersonNews + IM @UCLAHealth
| CUMC ‘18 | Interests: ML/AI, Clinical Trials, CRC | COI:

[Nicholas Hornstein @GIMedOnc]

@MrBeast 5126603 pennies

[Nicholas Hornstein @GIMedOnc]

@polytroponpd @p_ciracimd @OncoAlert I sure hope providers aren’t treating KRAS + patients with anti-EGFR in the first line SOC setting…

[Nicholas Hornstein @GIMedOnc]

@Erman_Akkus @OncoAlert Practice changing?
Risk benefit of celecoxib seems pretty favorable… could also wuss out and use aspirin…

[Nicholas Hornstein @GIMedOnc]

Great newsletter from @OncoAlert highlighting last weeks major advances in oncology (not included is ongoing coverage of #ASCOGI26 which you can find on their feed)

[OncoAlert @OncoAlert]

The OncoAlert Newsletter June 25- July 1, ,2026
REGISTER TO GET IT👉 https://t.co/mrihkMKWad or https://t.co/R13F8zzj1Y

🔥 Highlights include:
🔹 Industry Update:
🇪🇺 EU approval of trastuzumab deruxtecan as the first tumour-agnostic HER2-directed ADC for previously treated HER2-positive solid tumors — expanding the impact of biomarker-driven oncology.
#ADC #PrecisionOncology #HER2

🔹 Lung Cancer:
🫁 TP53 gain-of-function mutations linked to early osimertinib resistance in EGFR-mutant NSCLC
🫁 Identifying patients at risk for early failure with dual immunotherapy in metastatic NSCLC

🔹 GU Cancers:
🧬 9+ year follow-up confirms durable survival benefit of nivolumab + ipilimumab in advanced RCC
🧬 PSMA PET/CT-guided MDT associated with improved outcomes in oligometastatic CRPC

🔹 Breast Cancer:
🎗️ iSBRT + immunotherapy strategies in ER+/HER2− disease
🎗️ Pregnancy-associated breast cancer outcomes and the role of tumor biology

🔹 GI Cancers:
🎯 New ESTRO recommendations for rectal cancer reirradiation
🎯 Real-world data on adjuvant chemotherapy in biliary tract cancers

🔹 Cancer & Innovation:
🤖 AI decision support in hematologic malignancies
🤖 Machine learning models for cervical cancer risk stratification
🧬 The evolving role of intratumoral therapies in melanoma
📚 Stay updated with the latest evidence shaping clinical practice.

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[Nicholas Hornstein @GIMedOnc]

#ESMOGI26
An interesting exploratory analysis from ATOMIC asks an important question:
How much chemotherapy do patients receiving adjuvant FOLFOX + atezolizumab actually need?

(Remember, this is our only adjuvant prospective study in MSI-H CRC and is with FOLFOX + Atezolizumab vs FOLFOX. If you can catch these patients before surgery, almost certainly better to treat neoadjuvantly).

Quick takeaways:

• Patients receiving >6 cycles of FOLFOX appeared to derive the greatest DFS benefit from the addition of atezolizumab (adjusted HR 0.45).

• That benefit was not apparent among patients receiving ≤6 cycles (HR 0.84), although this subgroup was relatively small.

• Receiving ≥12 cycles of atezolizumab was associated with numerically better DFS than shorter treatment, but this analysis is difficult to interpret given treatment discontinuation for toxicity and other confounders.

My interpretation:

This actually makes biological sense. Atezolizumab has consistently appeared less active than PD-1 inhibitors in MSI-H CRC. If that's true, then maintaining adequate chemotherapy intensity may be particularly important in this regimen.

I don't think these exploratory data answer whether 3 months of CAPOX is sufficient in dMMR disease. If anything, they reinforce that ATOMIC should probably be viewed as the regimen that was studied, than the exact regimen used in clinical practice.

Slides nabbed from @GillSharlene

@TheGutOncLab @OncoAlert @Onco_Nexus @ESMO

[Nicholas Hornstein @GIMedOnc]

#ESMOGI2026
Surprising news for mCRC out of ESMOGI.
KRYSTAL-10: Adagrasib + cetuximab misses its primary endpoint in 2L KRAS G12C mCRC.

After the accelerated approval and encouraging activity from KRYSTAL-1, many expected dual KRAS/EGFR inhibition to outperform chemotherapy in the second line. That didn't happen.

Quick hits:
• Primary endpoint (PFS): Negative
• mPFS 7.5 vs 8.1 months
• HR 0.89 (95% CI 0.71-1.13)
• Response rate dramatically improved
• ORR 47% vs 16%
• CR 7% vs <1%
• No improvement in OS at the final analysis despite the higher response rate.

So what happened?
This is a reminder that response rate ≠ durable disease control. Nearly half of patients responded, but those responses did not translate into longer PFS or OS compared with modern chemotherapy. Targeted therapy works, but mCRC can overcome via resistance mechanisms (such as via massive KRAS upregulation). Will be interesting to see how novel degraders come into the mix here... Remember, this is a first gen KRASi, the future is still bright here.

What does this mean for clinic tomorrow? Honestly, I still love a chemo-free option that is at least on par with chemotherapy.

This isn't the end of KRAS G12C in CRC. Far from it.

The focus now shifts to moving targeted therapy earlier, where combinations with chemotherapy may produce deeper, more durable responses before resistant clones emerge. Multiple frontline studies are already underway.
@TheGutOncLab @OncoAlert @Onco_Nexus @myESMO

[Nicholas Hornstein @GIMedOnc]

@Aiims1742 @BrunoBockorny @RevMedicines MTAP deleted tumors about to see enormous improvements in outcomes.

[Nicholas Hornstein @GIMedOnc]

Proud to know and grateful to have the opportunity to work with @UGrewalMD I’ve never seen someone with such passion and deep caring as Udhay has with NET and his patients. Now I can say he literally wrote the book on it.
Now if only I can convince him to start sleeping more than four hours a night…

[Udhayvir Grewal @UGrewalMD]

Elated to share our latest in @ASCO Educational Book on the evolving role of personalized therapies in Neuroendocrine Neoplasms.
🔗 https://t.co/lKginm8Sjx

Grateful to Drs Simron Singh, Jen Chan and @OncoThor for the opportunity to be a part of this tour de force. The book chapter discusses biomarker-driven advances in radioligand therapy, targeted therapies, and emerging novel agents across NEN spectrum. @SShaheenMD

[Nicholas Hornstein @GIMedOnc]

New episode of @TheMoonlightShift where I discuss AI in medicine, next generation sequencing and colorectal cancer, and also disclose that medicine was Plan B after chef. Still not sure I made the right call, but the patient outcomes are arguably better than my plating. 👇 https://t.co/upbOhdQAsW

@Onco_Nexus @TheGutOncLab

[Gina Mauro @ginacolumbusonc]

The Moonlight Shift is live &amp; with a new set! 🎙️

Dr. @GIMedOnc on #ctDNA, CRC, and taking @NorthwellHealth's GI oncology program to the next level.

Also: he almost became a chef first. Watch here — https://t.co/fv7Miei5Ns

#TheMoonlightShift #CRCsm #GIOncology

[Nicholas Hornstein @GIMedOnc]

@ginacolumbusonc @NorthwellHealth Definitely not built from scratch (and more focused on Colorectal cancer)! Huge group of people bringing amazing trial opportunities and research to the GI portfolio including
@DrDanielKing and @sepideh_gholami among many others!

[Nicholas Hornstein @GIMedOnc]

@allisonoconn If you see anything anywhere near the pancreas, consider it pancreas cancer. Pancreas cancer is lame and likes to hide.

[Nicholas Hornstein @GIMedOnc]

New @TheGutOncLab publication on early onset NET

Say it from the back:
Early-onset cancers are different from their average onset counterparts.

https://t.co/zAqpYVVcSH

@OncoAlert @Onco_Nexus

[Udhayvir Grewal @UGrewalMD]

Kudos to @SuriyaBaskarMD for leading this paper in @MASCC_JSCC on symptom burden and outcomes in patients with early-onset neuroendocrine neoplasms.
🔗 https://t.co/TarI8F8UMz

Young people with NENs appear to have higher symptom burden (similar to our data from the NET-PRO study) and may potentially harbor a distinct disease biology compared to average-onset NENs (more to come on this).

@TheGutOncLab @TimothyJBrownMD @GIMedOnc @Deebacca @RPatel20166 @sawyer_bawek @BRoseMDMPH @michael_ororke

[Nicholas Hornstein @GIMedOnc]

@DavidHongMD Absolutely; had a follow-up post on that as well.

[Nicholas Hornstein @GIMedOnc]

A historic day for solid tumor oncology.

China has approved satri-cel (CLDN18.2 CAR-T) for advanced gastric/GEJ cancer, making it the first CAR-T therapy ever approved for a solid tumor. For years, CAR-T has transformed hematologic malignancies while solid tumors remained left in the dust.

📊 CT041-ST-01 (3L+ CLDN18.2+ gastric/GEJ cancer) in the Lancet

• Median PFS: 3.25 vs 1.77 months (HR 0.37)
• Median OS: 7.9 vs 5.5 months (HR 0.69)
• 18-month OS: 20% vs 10%
• Demonstrated superiority over physician’s choice therapy in a heavily pretreated population.

The absolute numbers are not dramatic, but that isn’t the point.

This is the first regulatory approval of a CAR-T for a solid tumor.

Also notable: this happened in China, not the United States.

As China continues to accelerate development of cell therapies, ADCs, and other oncology platforms, it is increasingly becoming the site of first-in-class innovation.

Satri-cel may ultimately be remembered less for the 2.4-month OS gain and more for what it represents:

The beginning of the solid tumor CAR-T era.

@Onco_Nexus @OncoAlert @TheGutOncLab

https://t.co/gon4I3udIR

[Nicholas Hornstein @GIMedOnc]

New episode of the @TheGutOncLab is out!
Had the pleasure of having a world leader in colorectal cancer on; Arvind Dasari! We talk about what is here now, and what will be in the future for colorectal cancer, including new technology and targeted therapy.

Available on Apple/Spotify below.

Great conversation.

Watch now on OncoNexus: https://t.co/xKcH5ApLc7

Spotify: https://t.co/Sft2mEriPf

Apple: https://t.co/Ij2FbbUQMX

@OncoAlert @Onco_Nexus

[OncoNexus @Onco_Nexus]

CRC treatment is getting more precise...

In this ASCO 2026 episode of The Gut Onc Lab, Dr. Nicholas Hornstein (@GIMedOnc), Dr. Udhay Grewal (@UGrewalMD), Dr. Tim Brown (@TimothyJBrownMD) & featured guest Dr. Arvind Dasari (@adasarimd) break down the evolving role of biomarkers, ctDNA, molecular profiling, and emerging treatment strategies in colorectal cancer.

The discussion covers what is changing, what is ready for clinic, and how these advances may impact treatment decisions for patients with CRC.

Watch now on OncoNexus: https://t.co/iGxEHZxKtj

Spotify: https://t.co/aRdnRKo8oN

Apple:
https://t.co/7xC7T4HtGO

@NorthwellHealth
@UTMDAnderson
@UTSWMedCenter
@WinshipAtEmory

[Nicholas Hornstein @GIMedOnc]

@DrPaulyDeSantis Why take a risk when you can just acquire?

[Nicholas Hornstein @GIMedOnc]

China approves the world’s first CAR-T therapy for a solid tumor.

Hours later, the FDA responds with full approval of afami-cel and expansion into pediatric synovial sarcoma.

A remarkable day for cellular therapy.

🇨🇳 Satri-cel (CLDN18.2 CAR-T)
CT041-ST-01, refractory gastric/GEJ cancer

• PFS: 3.25 vs 1.77 months (HR 0.37)
• OS: 7.9 vs 5.5 months (HR 0.69)
• 18-month OS: 20.1% vs 8.6%
• First CAR-T ever approved for a solid tumor

🇺🇸 Afami-cel (MAGE-A4 TCR-T)
SPEARHEAD-1, advanced synovial sarcoma

• ORR: 43%
• CR: 4.5%
• Median DoR: 6.0 months
• Median OS: 15.4 months
• First FDA-approved engineered cellular therapy for a solid tumor

For decades, solid tumors were where cellular therapies went to fail.

Now, on the same day, regulators in China and the United States have approved two different engineered T-cell platforms for two different solid tumors.

A brave new world for solid tumor oncology.

Any cancer center not providing cellular therapies is going to be left in the dust.

@OncoAlert @TheGutOncLab @Onco_Nexus

[Nicholas Hornstein @GIMedOnc]

@OncLive @FDAOncology

[Nicholas Hornstein @GIMedOnc]

Aaaand the FDA just approved afami-cel… Interesting timing.

[Nicholas Hornstein @GIMedOnc]

@kyleconcannonMD @PTarantinoMD My thoughts as a US Investigator: