Sean Pitroda, M.D.

1/ Our latest - @JAMAOncology Viewpoint! Ablative radiotherapy has a dual effect on metastatic cancer that changes how we should interpret progression after treatment.

IFN signaling at the nexus of the radiotherapy response in malignant peripheral nerve sheath tumors: doi.org/10.1172/JCI202… Sean P. Pitroda @SeanPitroda, Ralph Weichselbaum @rweichselbaum & team @UChicago provide a Commentary on Iowis Zhu et al.: doi.org/10.1172/JCI195…

@rweichselbaum @UCCancerCenter @LudwigCancer Shocking indeed!

@UCCancerCenter @SeanPitroda @LudwigCancer More to come shocking!

In a viewpoint, Sean Pitroda, MD and Ralph Weichselbaum, MD emphasizes the need to personalize treatment based on tumor biology, immune profiles, and metastatic patterns rather than relying on a single treatment. @SeanPitroda @rweichselbaum @LudwigCancer ow.ly/BGBL50XvWcf

@max_diehn @CELL Congrats!

We’re excited to share our latest study describing a new urine tumor DNA (utDNA) liquid biopsy method for #BladderCancer that accounts for the field effect, a key challenge for urine MRD detection. Out today in @Cell: authors.elsevier.com/c/1mWEl_278y-E… 🧵 (1/14) #LiquidBiopsy

💬 Viewpoint: The badscopal effect following ablative radiotherapy signals not failure but biological reorganization, prompting serial metastasis-directed therapy in selected patients. ja.ma/4k0HzJk

Radiotherapy duality in metastatic disease: inhibiting seeding, unmasking dormancy Viewpoint | jamanetwork.com/journals/jamao… @SeanPitroda @rweichselbaum @JAMAOnc @JAMANetwork Key insights 🟢 Metastasis-directed radiotherapy (MDT) suppresses metastatic seeding from treated lesions 🟢 Ablative RT can unmask dormant distant disease (“badscopal effect”) rather than promote spread 🟢 Post-MDT progression reflects biological reorganization, not treatment failure 🟢 Radiation reshapes systemic immunity (amphiregulin-mediated), enabling dormant clone outgrowth 🟢 Metastatic disease should be viewed as dynamic and iterable, not static Clinical implications 🟢 Strong rationale for serial MDT, not one-time local therapy 🟢 Explains limited benefit in trials restricting MDT to a single round 🟢 Supports treat-all-visible-disease strategies when feasible 🟢 Calls for MDT personalization using immune phenotype, clonality, and metastatic kinetics @seanmcbride @drjefstathiou @SeanPitroda @rweichselbaum @JAMAOnc @JAMANetwork @seanmcbride @drjefstathiou #Radiotherapy #OligometastaticDisease #Metastasis #CancerBiology #MDT #Oncology #JAMAOncology

@xrtGenomics @NatureCancer @nataliesilvermd @GeneCollector Congrats!

🥳🎆 Kicking of 2026 with our work showing intra-tumoral bacteria 🦠 affect outcomes of Radiotherapy + anti-PD-L1 now out in @NatureCancer with sister paper by @nataliesilvermd! Even when trials "fail" – we can learn from them! nature.com/articles/s4301…. -- w/ @GeneCollector, @imrtlee, @TylerAlban1, @DrHaddadRobert, the Pfizer team and more! (1/N)

@ebludmir @ChadTangMD @drdavidpalma @CJTsaiMDPhD Agree - Important to develop additional data in this clinical context to move treatment paradigms forward and test these preclinical predictions.

@ChadTangMD @SeanPitroda @drdavidpalma @CJTsaiMDPhD Candidly this is a theory vs practice issue. CURB, CURB2, EXTEND-OP seek to answer this question clinically, with promising early clinical (not preclinical) data. With respect to my preclinical friends: clinical data will tell us which way to go here.

1/ Our latest - @JAMAOncology Viewpoint! Ablative radiotherapy has a dual effect on metastatic cancer that changes how we should interpret progression after treatment.

@ChadTangMD @ebludmir @drdavidpalma @CJTsaiMDPhD Certain systemic therapies when given with RT might also obviate the need to irradiate all sites

@SeanPitroda @ebludmir @drdavidpalma @CJTsaiMDPhD But cannot in oligoprogression as usually the number of lesions it too may to irradiate. Also each site has its own risk of toxicities.

@ChadTangMD @ebludmir @drdavidpalma @CJTsaiMDPhD Probably better to irradiate all sites and not leave untreated disease.

@SeanPitroda @ebludmir @drdavidpalma @CJTsaiMDPhD In oligoprogression there are dormant and active lesions. We irradiate the active ones only.

@ChadTangMD @ebludmir @drdavidpalma @CJTsaiMDPhD Thanks Chad. Sorry I don't understand. Can you clarify?

@SeanPitroda Wonderful writing as always. Correct me I am misunderstanding but if this mechanism is correct the real test should be oligoprogression, which in large part shouldn’t work. @ebludmir @drdavidpalma @CJTsaiMDPhD

I think Sean's thinking here has been clear from the get go. There's no claim of accelerated progression of non-irradiated mets in the SBRT arm compared to the non-SBRT arm. The claim is simply that one biological driver of out-of-field progression, when it occurs post-SBRT, acknowledging it occurs LESS FREQUENTLY in the SBRT arms of the trials mentioned, may be amphiregulin driven immune suppression. His work has identified a druggable target that may make the SBRT arms of oligomet trials even more successful than they've already been. Kudos to him! #radonc

@CJTsaiMDPhD @drdavidpalma @NiuSanford @piet_ost @rweichselbaum We don't know the source of post-RT mets. Easy to assume pre-existing lesions destined to grow, but may be more complex. RT controls treated lesions and reduces seeding, yet progression occurs. Why not study mechanisms rather than assume we understand them?

@SeanPitroda @drdavidpalma @NiuSanford @piet_ost @rweichselbaum We need a RCT - not single arm trials. Results from RCTs have not shown evidence suggesting this. For SBRT arms, post-SBRT progression (delayed compared to no-SBRT) had to be from new growth because SBRT controlled irradiated lesions. There is no other way of disease progression.

Nice viewpoint & biologically interesting hypothesis, but how would one actually distinguish b/w new tumors from “badscopal” effect vs. normal metastatic progression in humans? & are there any RCTs that demonstrate accelerated progression post ablative RT (I can't think of one)?

@DrewMoghanaki @5_utr @drdavidpalma @NiuSanford @piet_ost @CJTsaiMDPhD @rweichselbaum @sueyom @NehaVapiwala @IyengarPuneeth Agree—no data show radiation increases metastatic rate. That's not our claim. It's the NATURE of post-RT metastases that remains unclear (dormancy reactivation vs. pre-destined growth) and requires investigation. Understanding mechanism matters for therapeutic strategy.

@SeanPitroda @5_utr @drdavidpalma @NiuSanford @piet_ost @CJTsaiMDPhD @rweichselbaum SABR does not increase the rate of metastasic growth in people who already have metastases. The title is merely click bait to bring attention to mouse studies that warrants the authors spend some time in the penalty box. @sueyom @NehaVapiwala

@5_utr @drdavidpalma @NiuSanford @piet_ost @CJTsaiMDPhD @rweichselbaum Primary endpoints for the trials have been published but secondary analysis pertaining to AREG will be soon.

@SeanPitroda @drdavidpalma @NiuSanford @piet_ost @CJTsaiMDPhD @rweichselbaum Can you link these 3 trials please?

@DrSpratticus @Nature @ASCO @myESMO @TylerSbrt @DrewMoghanaki Thanks Dan. Excellent summary and appreciate your support.

1/n X-torial: It seems the biomedical field needs some help in understanding the @Nature paper on RT induced amphiregulin effects in cancer recently published. #Sec49" target="_blank" rel="nofollow noopener">nature.com/articles/s4158… @ASCO @myESMO #misinformation #fakenews @TylerSbrt @DrewMoghanaki

@5_utr Several recent pubs demonstrating inflammation-induced dormancy unmasking, the established role of ERBB/EGFR signaling across cancers, and AREG validation in two additional randomized trials establish this as reproducible biology, not statistical artifact.

While I’m not a fan of DAGs in general, they can be helpful at times to simply visibly map out pathways; focus on the indigo pathway here, with correlated other unmeasured genes. This is the challenge with high-dimensional genomics work which seeks to “name names” like AREG

@DrJashDatta Thanks Jash! Great seeing you recently!

Surgery can unmask dormant metastatic cancer cells by immune reprogramming also. Another 🔑 to understand is why this is hyperactive in some pts and not others 🤔

@xrtcell 🤣

@SeanPitroda thanks Sean! can't wait to accidentally run into you in another country again.

What if nature already has the optimal cytokine solution for T cell therapy, but we just haven’t found it yet? Check out our paper out today in Immunity on IL-9 as a naturally orthogonal cytokine ideally tuned for T cell therapy authors.elsevier.com/sd/article/S10… 1/9