Happy to share our recent publication on the use of quantum technology for machine learning to differentiate between brain metastases and high-grade gliomas on MRI. 1/3 doi.org/10.1007/s10278-023-0…

Thank you Sean for this stellar comment!! Can't agree more! As @TylerSbrt mentioned, PSMA-PET remains the elephant in the room, and I totally agree that DASL-HiCaP sheds some light on this, as ~55% had a baseline PET. Eagerly waiting for the full manuscript! While CI-M0 / miM1 were eligible, I think the vast majority of physicians wouldn't offer it to these patients. This is particularly important because many people believed that intensification benefit was perhaps driven by occult M1 on CI. The absence of HTE by PSMA-PET in DASL-HiCaP makes this very unlikely. On another note as we're discussing the PSMA-PET dilemma, patients with small pelvic PET+ nodes that otherwise don't meet the criteria for STAMPEDE / DASL-HiCaP weren't included in either trials. Are you intensifying with ARPI for these patients? If yes, are you using 2 years of intensification? I personally think these patients may benefit from some sort of intensification, but I believe the total duration could be lowered. Eager to know what do you and other colleagues think about this. @DrSpratticus @Soum_Roy_RadOnc @seanmmcbride @TylerSbrt @alison_tree @PCaParker @ChrisSweens1 @Prof_Nick_James @Prof_IanD @5_utr @adib_elio @jryckman3 @GrattonMatthieu @dr_coops @ChapinMD @brookmans76 @VedangMurthy @docpriyamvada @cpeedell @dr_alimuhammad @WallisCJD @piet_ost @PaulSargos @GiuliaMarvaso84 @alongi_filippo

Very much agree with you, Tony. For DASL Very High Risk N0 patients, the MFS-CI benefit is substantial and very robust (and a surrogate for OS). In addition to a group more enriched in Gleason 9-10 than Enzarad, our patients were enrolled in era replete with PSMA PET. How does that impact the enrolled group (even though it was not formally included in eligibility)? There are two putatively localized settings where pts may not experience a significant MFS benefit from fixed duration ARPI intensification: 1) localized lower risk disease where metastatic potential is constrained and 2) localized by conventional imaging disease where PSMA PET reveals already extant mets. In the former, the metastatic cat may never get out of the bag; in the latter, it already is. In the DASL era, a patient with CI neg/PSMA PET pos disease probably wasn’t enrolled. Investigators might not have viewed the arms in equipoise in that setting. They may have thought such patients needed ARPI intensification as SOC for OS purposes. We thus removed a patient population unlikely to realize an MFS benefit, since they already had Mets. This, in combination with enrolling higher grade gleasons, really enriched for the N0 population most likely to benefit. That’s why I would argue that in our PSMA PET era, DASL should have controlling weight in decision making regarding adding an ARPI in the N0 setting. And for the RadOncs out there, with its favorable side effect profile, you might feel more comfortable take the initiative on prescribing Daro. #radonc

I think the data generates hypotheses: Hyp#1: Unmeasured factors (e.g. PSMA+,cN0) Hyp#2: RT draining VHR PCa dampens down pro-cancer immune infiltration to allow ARi to be more effective &/or ARi augment an anti-cance RT abscopal effect Meta-analyses & biological assays planned

@TonyFelefly the outcomes of the groups in #ENZARAD with and without pelvic RT are in Fig 4 of #JCO manuscript (thx to G8 collab with Assoc Editor @AndreaNecchi). Proofs reviewed-full pub soon @ANZUPtrials @Prof_IanD @DrPaulNguyen @Uromigos @brookmans76 @Silke_Gillessen

🧵 2/3 I’d read the EFS gap cautiously 👇 PSMA PET was scheduled differently by arm: 📅 RP alone: scans at 3/9/15 mo regardless of PSA 📅 Apalutamide: first routine scan only ~3 mo after treatment, then at PSA failure Where did the events come from? (apa vs RP) ⚠️ Local/regional recurrence by PSMA PET w/o BCF: 4 vs 48 ⚠️ Distant mets by PSMA PET w/o BCF: 2 vs 23 ⚖️Most control-arm events were caught only by early scheduled scans the apalutamide arm never got 👉 potential ascertainment bias ⭐️Of course this is not the only limitation, but an important to highlight

I think it depends on the risk in N0. In STAMPEDE and DASL-HiCaP, nodal status was a stratification factor, and prespecified subgroup analysis didn't show any sign of HTE (photos below). So N0 clearly benefited from intensification. In ENZARAD, they included more favorable high-risk patients. Those who got pelvic nodal RT derived a benefit as per their subgroup analysis. Although the characteristics of these patients weren't reported, most of them were N0, and my guess is that they were on the higher-risk end, as physicians felt they would benefit from pelvic ENI. I'm not aware of any interaction between nodal RT and hormonal therapy that would explain the results. Curious to know how others interpret these results, and if they would intensify with ARPI for some N0 patients. @DrSpratticus @Soum_Roy_RadOnc @seanmmcbride @TylerSbrt @alison_tree @PCaParker @ChrisSweens1 @Prof_Nick_James @Prof_IanD @5_utr @adib_elio @jryckman3 @GrattonMatthieu @dr_coops @ChapinMD @brookmans76 @VedangMurthy @docpriyamvada @cpeedell @dr_alimuhammad @WallisCJD

Thanks Adam. Alternative interpretation: #ENZARAD showed that systemic intensification is not needed except for very high risk #ProstateCancer (as shown by #STAMPEDE and #DASLHiCAP). Top quality RT + 2yr ADT gave excellent outcomes for high risk in both arms.

There is some free text that was collected and we are trying to figure out how these pieces of information could be presented/shared in subsequent disclosures. As you can imagine, it is very difficult to extract these features in ways that are easily communicable in data form. But the work is ongoing. I do believe there are ways to achieve this.

I’m curious how many medoncs in the current immunotherapy era would support a study of CRT for medically fit operable stage III NSCLC to challenge the primacy of surgery so we can finally get a real signal on how well it works and appreciate whether surgical resection matters as much as it’s said it does. As we see in the slide below by @SalmaJabbour1: Surgery Has Never Been Proven Superior

And median RFS for SBRT not reached at ~10 year follow-up for operable patients on STARS! @JoeChangMD @5_utr

Not sure we can compare EFS for inoperable patients here with operable (more fit, less comorbid) patients in the neoadjuvant CT-IO trials, particularly when we look at DSS curves below. @SalmaJabbour1 EFS here is mostly driven by deaths unrelated to the disease or AEs. VALOR will ultimately settle this question @drewmoghanaki

When we presented data from all the neoadjuvant/periop IO studies people were understandably concerned about what happened to those who didn’t get operated. People were also confused by the stage overlap between PACIFIC and the surgical trials. So the goal of MDT-BRIDGE was to better understand these gaps and evaluate whether an early MDT reassessment after 2 cycles could allow most patients to achieve definitive locoregional control, which they did in 95% of cases. MDT reassessment also enabled very high R0 rates. Complication profile for the CRT group seemed reasonable as well which was another gap in knowledge. The goal wasn’t AT ALL to compare the survival outcomes between the two forms of locoregional therapy. Our intent was to bring data to areas of uncertainty after multiple phase 3 trials. We also wished to understand why MDTs might interpret resectability differently and this work is still ongoing. The data are also not meant to be used to justify a trial. Before such an RCT could be done, I think the Rad Onc community would have to prove that neoadj chemoIO followed by CRT is superior or at least equivalent to PACIFIC. Once this is done, we can talk about the RCT… still much work to be done.

How does lymphatic leak occur after PLND for prostate cancer? Cloquet's node: rarely metastatic, almost always the site of leak. Diligent lymphostasis particularly at the Cloquet site @UrologyMSK @JUrology
#UroSoMe #ProstateCancer #PLND #Lymphocele auajournals.org/doi/10.1097/…

2/ LU002: ~90% IO-based 1L (more contemporary sys tx), control 1-yr PFS 48%. SARON: mixed SACT with longer accrual. Need: patterns of failure, SBRT-to-all-sites subgroup, crossover/salvage RT, ctDNA/biology selection.

Congrats to Reck, Spicer, Filippi and team on the full MDT-BRIDGE paper in Nature Medicine! Really appreciate seeing the RT protocol and full denominators alongside the ASTRO results. 👏 This single-arm ph2 enrolled 142 pts with resectable or borderline-resectable stage IIB-selected IIIB, EGFR/ALK-wt NSCLC. Durvalumab + platinum chemo x2c→ MDT reassessment→ additional chemoimmunotherapy and surgery, or CRT, followed by durvalumab. Resection was 74.6% (95CI 66.7-81.6), with R0 in 96.2% of those who started surgery. pCR was 27.3% in the resectable analysis cohort. The 12-mo EFS estimates are 88.5% overall and 90.1% in that resectable cohort. Different denominators, same readout. The RT protocol details are useful: nominal 60/30 (60 Gy ±10% in 2 Gy fx), 5 fx/wk for ~6 wk, concurrent or sequential platinum chemo. SBRT was not allowed. IMRT with daily CBCT was preferred, then consolidation durvalumab q4w up to 12c. All 25 pts who started CRT completed it: 21 concurrent, 4 sequential. 23 received consolidation durvalumab. The post hoc CRT-treated analysis estimated 12-mo PFS at 85% (95CI 59.8-95.0), measured from the FIRST study-treatment dose, including induction. CRT-period G3/4 AEs were 28%; pneumonitis 8% (2 pts, both G2). During consolidation, G3/4 AEs were 17.4%, AE discontinuation 13%, and pneumonitis 8.7% (G1/2). One cardiac-failure AE death occurred during consolidation; the paper reports no treatment-related AE deaths in that period. The safety windows extend beyond treatment delivery and can overlap. The ESMO ctDNA analysis adds an interesting association. Pre-Sx/CRT clearance occurred in 33/90 evaluable pts (36.7%). C2D1 clearance had an 83.3% PPV for pCR (95CI 43.6-99.1). Among resected pts, no EFS events occurred with pre-Sx clearance (n=28); 12-mo EFS without clearance was 88.9% (n=40). In CRT-treated pts, 12-mo PFS was 100% with pre-CRT clearance vs 77.5% without. The paper now supplies those subgroup sizes: just 4 vs 16 pts, with 2 vs 6 at risk at 12 mo. One later event occurred in the clearance group, so 100% is a timepoint estimate, not no events throughout follow-up. Useful prospective evidence that patients can reach definitive CRT after starting on a surgical pathway. The unanswered question remains who benefits from that sequence versus going directly to CRT or selecting for NAC-ICO with intent for organ preservation. Selected cohorts, immature EFS/PFS and no reported OS cannot settle that, and ctDNA does not yet tell us which local therapy to choose or omit. doi.org/10.1038/s41591-026-0… cslide.ctimeetingtech.com/es… #radonc #ESMO26 #LCSM

Yes I like RMSD as well. No perfect metric unfortunately!

CRC has been a fascinating space for many years, but in 2026, wow... Just wow! For example, switching gears from dMMR colon in NICHE-2 and going below the peritoneal reflection for pMMR rectal cancer, UNION, STELLAR II, and TORCH-iTNT have shown eye-popping response rates with a short-course RT backbone (?!) plus immunotherapy. @NiuSanford @DrEmmaHolliday @nbn426 @KrishanJethwa @GIMedOnc @adapthyun @TimothyJBrownMD @manjuggm @OncoAlert @OncBrothers #ASTRO26 #ESMO26 #OncTwitter #CRCSM

Presenting the UK’s SARON study Dr @fifimcdrmh to a full hall at #ESMO26 In patients with de novo oligometastatic mutation driver negative #NSCLC , consolidation radiotherapy to the primary and metastases improved PFS but no OS No significant difference in QOL or AEs Huge thanks to all the patients and trialists involved

Of note, the Surrogate Threshold Effect for MFS in ICECaP-2 was 0.81. So basically even if we buy into the PSMA-PET MFS in PROTEUS, HR was 0.8 (95%CI 0.67-0.96). Consequently, this MFS HR does not predict an OS benefit by surrogacy, as the CI upper limit is way above the surrogate threshold. Actual OS data are needed in this context.

🚨 Two major ARPI trials in high-risk localized prostate cancer, each adding a drug to standard local therapy 🧵 #ProstateCancer #RadOnc #pcsm