Top Clinical Trials from ESTRO

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Gfunk6

Gfunk6

And to think . . . I hesitated
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PLATO ACT 4 - early stage anal cancer, dose de-escalation

T1-T2, <= 4 cm N0

Arm 1: 41.4 Gy in 23 fx
Arm 2: 50.4 in 28 fx

2:1 randomization, concurrent chemo = Capecitabine, MMC x1

3 year local-regional failure free rate:
Arm 1: 87.6%
Arm 2: 83.6%

3 year OS:
Arm 1: 98.1%
Arm 2; 92.6%

Conclusion: Reduced dose radiation should be standard of care in early stage anal cancer
 
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STAR-TREC - Chemoradiation (50 in 25 with capecitabine) vs 5x5 Gy short course RT for early stage rectal cancer

cT1-T3b N0 (70% were T2), < 4 cm

Treating Meaorectum ONLY (50% volume reduction)

With either radiation arm, if cCR then surgery was deferred in favor of surveillance

12 month TME free survival
80%: long course
61%: short course

30-month outcome planned

Conclusion (preliminary): Short course XRT appears less effective that long course for pre op treatment for early-intermediate stage rectal cancer
 
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PRIME-RT - Durvalumab with extended TNT regimens in locally advanced rectal cancer

T1-T4, N1-N2

Arm A: FOLFOX x 6c with IO plus SCRT (at start)
Arm B: FOLFOX x 4c with IO plus LCRT + capecitabine (at start)

cCR @ 18 months
Arm A: 48%
Arm B: 33%

38% grade 3-5 tox on Arm A vs 9% on Arm B

Conclusion: SCRT is superior in this scenario, possibly reflecting divergent immuno-modulatory effects with hypo-fractionated RT
 
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STELLAR - Short course XRT + chemo for locally adjacent rectal cancer

T3/T4 or N+

Arm 1: pre-op SCRT —> surgery —> adjuvant chemo
Arm 2: Neoadjuvant FOLFOX —> surgery

No significant differences in DFS but provides 8.4% improvement in OS at 5 years in Arm 2 which should be the standard of care in LA-CRC
 
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STELLAR 2 - SCRT —> chemotherapy plus IO for LARC

Arm 1: SCRT —> CapeOX —> TME vs WW
Arm 2: SCRT —> CapeOX + IO —> TME vs WW

cCR rate
Arm 1: 25%
Arm 2: 45.5%

Conclusion: Addition of IO to TNT with SCRT appears to be more effective than standard TNT.
 
Gfunk6 said:
PLATO ACT 4 - early stage anal cancer, dose de-escalation

T1-T2, <= 4 cm NO

Arm 1: 41.4 Gy in 23 fx
Arm 2: 50.4 in 28 fx

2:1 randomization, concurrent chemo = Capecitabine, MMC x1

3 year local-regional failure free rate:
Arm 1: 87.6%
Arm 2: 83.6%

3 year OS:
Arm 1: 98.1%
Arm 2; 92.6%

Conclusion: Reduced dose radiation should be standard of care in early stage anal cancer
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One less dose of MMC sounds awesome to me can we get a study cooking in N+ disease too please
 
Gfunk6 said:
PLATO ACT 4 - early stage anal cancer, dose de-escalation

T1-T2, <= 4 cm NO

Arm 1: 41.4 Gy in 23 fx
Arm 2: 50.4 in 28 fx

2:1 randomization, concurrent chemo = Capecitabine, MMC x1

3 year local-regional failure free rate:
Arm 1: 87.6%
Arm 2: 83.6%

3 year OS:
Arm 1: 98.1%
Arm 2; 92.6%

Conclusion: Reduced dose radiation should be standard of care in early stage anal cancer
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I’ve treated these to 45 for years. Not at all surprised.

What I am about to say will surprise some of you since I have traditionally been a SCRT proponent for rectal cancer. I would really like to see late toxicity follow up with concurrent IO. I recently reviewed data that is not published yet, so I can’t share specifics. There certainly appears to be something to the efficacy story (unlike LC + pembro in GI-001) but may come at a non-trivial cost. I’m not poo-pooing the general idea. It’s starting to look like not all IO is the same when you start mixing regimens and there are just some details to work out.
 
STORM- Prostate cancer s/p RP/XRT with biochemical failure and positive disease on PSMA PET

Most of patient had a solitary lymph node

Arm 1: ENRT to regional nodes + 6 mo ADT
Arm 2: SBRT to positive nodes + 6 mo ADT

3 year biochemical relapse free survival:

Arm 1: 69%
Arm 2: 47%

Locoregional repulse free survival

Arm 1: 90%
Arm 2: 70%

In the setting of previous radical therapy for prostate cancer ENRT appears superior to SBRT.
——————————

It should be pointed out that the systemic therapy in this trial is considered inferior by modern day standards. EMBARK used ADT + enzalutamide (median duration 17 mo). In this scenario, SBRT is favored for oligomets and ENRT for locoregional failure (bed +- LNs).
 
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FLAME - Standard prostate fractionation +- SIB boost to gross disease

Int-High risk (84% high risk)
Lymph nodes NOT treated

Arm 1- 77 Gy in 35
Arm 2 - as above but up to 95 Gy via SIB to lesions (median 84.7 Gy)

ADT given at the discretion of the investigator
1/3 did not get ADT

10 year bPFS
Arm 1 - 71%
Arm 2 - 86%

10 year DFS
Arm 1 - 67%
Arm 2 - 81%

10 year regional LN DFS
Arm 1 - 84%
Arm 2 - 95%

No difference in toxicity in both arms.

SIB shows unequivocal long term clinical advantages compared to more homogenous conventional dosing.

Multiple trials using hypofrac and SBRT trials underway based on the above.
 
Phase II - Nivolumab + CRT In muscle invasive bladder cancer

cT2-T4aN0M0

All patients had vigorous TURBT but were otherwise surgically ineligble

Arm 1: 60 Gy to bladder + 10 Gy boost + CDDP
Arm 2: As above + nivolumab

2 year OS
Arm 1: 60.5%
Arm 2: 86.8%

No differences in Gr3+ tox in either arm

These results warrant a followup Phase III trial
 
Gfunk6 said:
EMBRACE used ADT + enzalutamide (median duration 17 mo).
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I presume, you mean EMBARK?

EMBARK on the other hand did not include patients with oligometastasis on PSMA-PET-CT staging, but only patients with BCR and "seemless" cN0 cM0, based on CT-staging. I am saying "seemless", because if you have a look at the protocol of EMBARK, patients could go on trial with what we would define as "pathologic" nodes on CT, as long as those did not surpass a certain threshold.
From the protocol
Patients with softtissue pelvic disease may be eligible if the short axis of the largest lymph node is< 20 mm for lymph nodes below aortic bifurcation.

I strongly believe, that the study populations of STORM and EMBARK are not the same.
 
Gfunk6 said:
PRIME-RT - Durvalumab with extended TNT regimens in locally advanced rectal cancer

T1-T4, N1-N2

Arm A: FOLFOX x 6c with IO plus SCRT (at start)
Arm B: FOLFOX x 4c with IO plus LCRT + capecitabine (at start)

cCR @ 18 months
Arm A: 48%
Arm B: 33%

38% grade 3-5 tox on Arm A vs 9% on Arm B

Conclusion: SCRT is superior in this scenario, possibly reflecting divergent immuno-modulatory effects with hypo-fractionated RT
Click to expand...

What I do not understand about this trial, as well as other trials in rectal cancer giving IO on top of RT/CRT, is the following thing:

Do we think that all patients would benefit, or is the benefit observed with IO guided by a subgroup of patients in the trials with a specific biomarker.
We know that in colorectal cancer IO works the best in patients with MMR-deficiency. Those trials did not select patients based on biomarkers (and they all started recruting before the MSKCC-data with IO-monotherapy came out - "the-19-patients-NEJM-paper").

So, is IO reasonable on top of any neoadjuvant treatment (or organ preservation strategy) for rectal cancer in molecularly unselected patients?
 
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Vienna is fantastic. Beautiful city, just a unique fusion of modern and Hapsburg architecture. Paid for a 7 day mass transit pass ~ $30. I can get anywhere in the city within 30-40 min tops without having to pay for an Uber.

The things that you can do outside the conference, culturally, so far exceeds the typical US city, it is almost laughable.

I find the content of the meeting far superior to ASTRO. Better organized, higher yield, real science and interesting discussions.

For my purposes, ESTRO is superior to ASTRO in every way.
 
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Gfunk6 said:
FLAME - Standard prostate fractionation +- SIB boost to gross disease

Int-High risk (84% high risk)
Lymph nodes NOT treated

Arm 1- 77 Gy in 35
Arm 2 - as above but up to 95 Gy via SIB to lesions (median 84.7 Gy)

ADT given at the discretion of the investigator
1/3 did not get ADT

10 year bPFS
Arm 1 - 71%
Arm 2 - 86%

10 year DFS
Arm 1 - 67%
Arm 2 - 81%

10 year regional LN DFS
Arm 1 - 84%
Arm 2 - 95%

No difference in toxicity in both arms.

SIB shows unequivocal long term clinical advantages compared to more homogenous conventional dosing.

Multiple trials using hypofrac and SBRT trials underway based on the above.
Click to expand...

Do you have a link for this?
 
I like FLAME, but it goes against the trend toward hypofractionation. I have seen people use hypofrac and do SIB, but this would have been off trial as far as I know. Can we do FLAME in US with insurers the way they are or is it dead here unless you incorporate that into a hypofrac plan? Do we have safety data on that approach?
 
madchemist89 said:
I like FLAME, but it goes against the trend toward hypofractionation. I have seen people use hypofrac and do SIB, but this would have been off trial as far as I know. Can we do FLAME in US with insurers the way they are or is it dead here unless you incorporate that into a hypofrac plan? Do we have safety data on that approach?
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I haven't had any pushback from US insurers whatsoever when it comes to FLAME. It's my go to for high risk patients.
 
OTN said:
I haven't had any pushback from US insurers whatsoever when it comes to FLAME. It's my go to for high risk patients.
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The funny thing is that FLAME did not include nodal radiation. However to get conventional frac approved by payors, you have to explicitly state that you are treating lymph nodes.
 
Gfunk6 said:
It should be pointed out that the systemic therapy in this trial is considered inferior by modern day standards. EMBARK used ADT + enzalutamide (median duration 17 mo). In this scenario, SBRT is favored for oligomets and ENRT for locoregional failure (bed +- LNs).
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I personally don't think its that simple. If someone has a single positive node on PYL-PET-imaging with multiple high risk features (say negative surgical margins and failure within 12 months of primary therapy), they almost certainly don't really have oligomets, and I would be more comprehensive. I was way more gunho about SBRT early on but it quickly became pretty clear that traditional clinical predictors (duration of control, PSA velocity, margin status, etc) can help you figure out when SBRT has a reasonable chance of delaying progression or not. Good thing is, if you guess wrong, you can usually still try the other approach.

OTN said:
I haven't had any pushback from US insurers whatsoever when it comes to FLAME. It's my go to for high risk patients.
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Fortunately, Im in the same boat you are. I use it for UFIR patients with a DIL on either MRI or PYL imaging without treating nodes and so far, I have not had a single denial for fraction number. I've had to defend using IMRT and or IGRT, but always gotten it. I can't help but feel like im living on borrowed time before they start pushing back on 35 fractions...
 
Palex80 said:
What I do not understand about this trial, as well as other trials in rectal cancer giving IO on top of RT/CRT, is the following thing:

Do we think that all patients would benefit, or is the benefit observed with IO guided by a subgroup of patients in the trials with a specific biomarker.
We know that in colorectal cancer IO works the best in patients with MMR-deficiency. Those trials did not select patients based on biomarkers (and they all started recruting before the MSKCC-data with IO-monotherapy came out - "the-19-patients-NEJM-paper").

So, is IO reasonable on top of any neoadjuvant treatment (or organ preservation strategy) for rectal cancer in molecularly unselected patients?
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This is completely undefined right now. This was only initiated as an exploratory phase 2 (feasibility). There are non-PD1/PDL1-dependent factors (as one example) but not in a way that has been sorted out yet. This trial is the right idea but it is too early even begin discussing a phase 3 imo. I would wait until IO is approved in MMR proficient subsets in metastatic and use that as inclusion for ph3.
 
StIGMA said:
This is completely undefined right now. This was only initiated as an exploratory phase 2 (feasibility). There are non-PD1/PDL1-dependent factors (as one example) but not in a way that has been sorted out yet. This trial is the right idea but it is too early even begin discussing a phase 3 imo. I would wait until IO is approved in MMR proficient subsets in metastatic and use that as inclusion for ph3.
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Very unclear. I'll be honest, some of the cervial/endometrial trials are getting good results in a more tumor agnostic manner than I would have expected with different systemic combinations (example, MSS subgroup in the RUBY trial). Some rectal trials are also looking like its not just the MMRd patients who may benefit but there are many caveats. Just giving them IO does nothing. Just giving it with LC CRT doesn't seem to do anything. And when it does work, the effect isn't even close to what you see in MMRd patients. More like what you see above with a meaningful improvement in local responses, but not a magical cure.

Its a very long way of saying there probably is a role for IO in MMRp patients. At least more than I would have assumed previously. Hopefully there are better biomarkers eventually. And clearly, we are far from knowing how to best put it all together. I do think there is something to the SCRT. Plenty of studies have shown that MHC tumor antigen presentation after RT is highly dose dependent. So there is a reason to think hypofrac "could" (and I stress could) at least hypothetically make it easier for the immune system to recognize tumors with a lower antigenic burden.

If someone wanted to take one of the above studies to phase 3, fine. I just hope they would do good correlatives to help us know where to look in future studies to address some of these issues. Still lots to figure out and really get this right.
 
Gfunk6 said:
Phase II - Nivolumab + CRT In muscle invasive bladder cancer

cT2-T4aN0M0

All patients had vigorous TURBT but were otherwise surgically ineligble

Arm 1: 60 Gy to bladder + 10 Gy boost + CDDP
Arm 2: As above + nivolumab

2 year OS
Arm 1: 60.5%
Arm 2: 86.8%

No differences in Gr3+ tox in either arm

These results warrant a followup Phase III trial
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Very interesting, few questions for you guys.

1. Is CRT usually done with cisplatin as here? Usually seen with 5-FU or other agents if i recall correctly.
2. Any data on xrt + antibody/conjugate drugs like enfortumab vedotin? Given EV-Pembro is now SOC in metastatic TCC, and have a suspicion will become so in the neoadjuvant setting based on ongoing trials, wonder if any trials looking at EV-Pembro + XRT are in the works.
 
madchemist89 said:
I like FLAME, but it goes against the trend toward hypofractionation. I have seen people use hypofrac and do SIB, but this would have been off trial as far as I know. Can we do FLAME in US with insurers the way they are or is it dead here unless you incorporate that into a hypofrac plan? Do we have safety data on that approach?
Click to expand...

I wouldn’t hypofrac in a flame-boost scenario but the trend does seems to be swinging back towards more fractions. As much as many want to control to narrative and push for a certain approach (likely to attract more out of towners), the data is becoming clear that a more standard fractionation is safer and more effective and it’s especially easy to justify in a flame-boost type scenario. How you are compensated will entirely depend on your contracts.
 
DoctwoB said:
1. Is CRT usually done with cisplatin as here? Usually seen with 5-FU or other agents if i recall correctly.
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This is likely country-specific in Europe. In the UK lot's of MMC, in mainland Europe, esp. Germany, cisplatin/carboplatin
DoctwoB said:
2. Any data on xrt + antibody/conjugate drugs like enfortumab vedotin? Given EV-Pembro is now SOC in metastatic TCC, and have a suspicion will become so in the neoadjuvant setting based on ongoing trials, wonder if any trials looking at EV-Pembro + XRT are in the works.
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Trials are running, for example
clinicaltrials.ucsf.edu

UCSF Bladder Cancer Trial: Enfortumab Vedotin and Pembrolizumab Combined With Radiotherapy in Muscle Invasive Bladder Cancer

This Bladder Cancer and Urinary Bladder Tumor study at UCSF is now recruiting people ages 18 years and up.
clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu
 
DoctwoB said:
Very interesting, few questions for you guys.

1. Is CRT usually done with cisplatin as here? Usually seen with 5-FU or other agents if i recall correctly.
2. Any data on xrt + antibody/conjugate drugs like enfortumab vedotin? Given EV-Pembro is now SOC in metastatic TCC, and have a suspicion will become so in the neoadjuvant setting based on ongoing trials, wonder if any trials looking at EV-Pembro + XRT are in the works.
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Usually the folks w/ bladder Ca I treat are generally pretty poor performance status and are getting the twice weekly low dose Gem regimen. Really good folks can consider 5-FU/Cis. Occasionally Cis alone. It's more dependent on potential tolerability of treatment than anything else. I have not seen 5-FU/MMC, as was done in BC2001, in my pt population.

ADCs need to be studied w/ RT especially to definitive doses - not nearly as 'free' as most ICIs in terms of combining with RT.

Really interesting series of studies presented. I'm confused as to the obsession with ICI in rectal cancer. All studies need to report some form of analysis, even if post-hoc, between MMRd and MMRp when talking about sprinkling IO into rectal cancer...
 
evilbooyaa said:
Really interesting series of studies presented. I'm confused as to the obsession with ICI in rectal cancer. All studies need to report some form of analysis, even if post-hoc, between MMRd and MMRp when talking about sprinkling IO into rectal cancer...
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Not sure we are seeing any of the MMRd patients these days though? I thought the study was looking specifically at the proficient population
 
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Any highlights this year? Won’t get a chance to peruse the abstract book until next week so curious what’s caught folks attention. Looks like long term outcomes from RAPCHEM and DOREMY but nothing too crazy from a quick search.
 
taserlaser said:
Any highlights this year? Won’t get a chance to peruse the abstract book until next week so curious what’s caught folks attention. Looks like long term outcomes from RAPCHEM and DOREMY but nothing too crazy from a quick search.
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Will post tomorrow after session. Shorter list this year:

FASTRACK II - SBRT for primary kidney cancer

INTRAGO-II - Dose escalation with IORT for GBM

RADiatE cohort analysis - subsets receiving local control benefit associated with local control after SBRT

20 year follow up of EORTC 22922

DBCG RT trial “when less is not enough”
 
New IASLC consensus paper on definitive RT to the primary tumor in stage IV NSCLC (published 2 weeks ago)

My take-home:

This is not a license to blast every stage IV lung primary. It is a permission slip to stop pretending the primary tumor magically becomes irrelevant once M1 appears.

The strongest data are in EGFR/driver-positive oligometastatic disease. In those patients, early thoracic RT/consolidation after systemic response is no longer a fringe idea. It is a reasonable life-prolonging strategy and should be discussed.

For non-driver metastatic NSCLC, the evidence is weaker but the concept is still very real. If the patient has good PS, low-volume disease, good systemic response, and a persistent lung primary that is likely to be the first site of failure, RO should be involved early — not six months later when the patient is bleeding, obstructed, or drowning in post-obstructive pneumonia.

Also: dose matters. If the goal is durable control, do not reflexively give “stage IV dose.” Treat with intent appropriate to anatomy: SBRT for safe peripheral primaries, more fractionated regimens for central/ultracentral or nodal disease.

The unresolved issue is target volume. Primary only? Primary plus involved nodes? Elective nodes? The paper basically says: we do not know. There is biologic rationale to spare draining lymph nodes during immunotherapy, but that is not yet validated. Translation: use judgment, not dogma.

For MOs, the workflow should be simple:

At the first response scan, ask:
“Is the primary still a major residual site of disease, and can local RT improve durability without interrupting systemic therapy?”

If yes, send to RO then. Not after it becomes a mess.

Final point: toxicity is additive. Thoracic RT + IO/TKI/chemo is not magic, and pneumonitis is still pneumonitis. Coordinate sequencing, drug holds when needed, and fields carefully.

Bottom line: stage IV NSCLC is no longer one disease state. In selected patients, definitive RT to the primary is not palliation. It is part of disease control.
 

Attachments

FASTRACK II final results for primary RCC SABR.

This should end the “RCC is radioresistant” nonsense.

No, RCC is not radioresistant to 26 Gy x1 or 42 Gy in 3 fractions delivered properly.

Trial population was exactly the group where this matters clinically: biopsy-proven solitary primary RCC, medically inoperable/high-risk for surgery, not appropriate for surveillance, eGFR >30, tumor ≤10 cm, and importantly not abutting bowel.

70 patients. Median age 77. Median tumor size 4.6 cm. Charlson comorbidity index 7. Mostly T1b disease. In other words, not just tiny renal masses in perfect surgical candidates.

Dose:
- 26 Gy x1 for tumors ≤4 cm
- 42 Gy / 3 fx for tumors >4 cm

Outcomes:
- Local control: 100%
- Cancer-specific survival: 100%
- Freedom from distant failure: 97% at 3 years, 88% at 5 years, 78% at 7 years
- Renal function dropped early, then largely plateaued
- One patient required dialysis: central 59 mm tumor with baseline eGFR 34
- 7 patients had at least one grade 3 adverse event
- No grade 4 or 5 adverse events

The RO takeaway is simple: primary renal SABR is no longer some boutique Australian hobby. It is now guideline-recognized — NCCN category 2A in 2026 and EAU-recommended for medically inoperable patients.

This does not mean we replace partial nephrectomy in a healthy 55-year-old. It does mean that when urology says “too frail,” IR says “not ideal,” and the patient is not a surveillance candidate, RO should not be sitting quietly in the corner anymore.

Caveats still matter: bowel proximity, baseline eGFR, centrality, and motion management are not trivial. This is not “throw 5 fractions at the kidney and call it innovation.”

But for selected patients, the data are now strong enough to say it plainly:

Primary RCC SABR is ready for prime time.
 
INTRAGO-II: IORT dose escalation for newly diagnosed GBM.

This is the kind of trial GBM needed because it answers a question we all quietly wonder about:

If GBM mostly fails locally, can we just hammer the cavity harder?

Answer: apparently no.

Design:
Resectable, newly diagnosed supratentorial GBM, age <80, KPS ≥60, tumor felt amenable to GTR. Randomized after surgery to:

- SOC: 60 Gy EBRT + concurrent/adjuvant TMZ
- IORT arm: intraoperative RT 20–30 Gy boost + same 60 Gy EBRT/TMZ

Full analysis set: 298 patients. Reasonably balanced arms. Mostly IDH-wildtype, median age early 60s, MGMT methylated ~40%.

Results:
- Median PFS: 11.0 mo with IORT vs 11.4 mo SOC
- p = 0.47
- Median OS: 17.7 mo with IORT vs 18.7 mo SOC
- p = 0.20
- Local recurrence remained the dominant failure pattern in both arms, about 70%
- No subgroup clearly benefited
- Neurologic toxicity numerically worse with IORT:
- radiation necrosis 6.8% vs 2.2%
- seizures 10.6% vs 5.8%
- not statistically significant, but not exactly confidence-inspiring either

RO takeaway:

This is a very clean negative trial.

The seductive logic was obvious: GBM fails locally, so escalate dose immediately at surgery before repopulation, then give standard chemoradiation.

But biology beat geometry again.

Local relapse remaining dominant despite IORT is the important point. This does not prove local therapy is irrelevant. It does prove that simply throwing a big single intraoperative dose into the cavity does not meaningfully alter the natural history of resectable GBM.

Also worth noting: this is another warning shot against single-arm GBM studies with historical controls. They can look exciting. Randomization is where enthusiasm goes to die.

Bottom line:

For newly diagnosed resectable GBM, IORT boost up to 20–30 Gy followed by standard Stupp does not improve PFS or OS.

More local dose is not the answer by itself.

GBM remains a systemic-brain, infiltrative biology problem masquerading as a local failure problem.
 
OligoCare interim analysis: real-world SBRT for oligometastatic disease.

This is not a randomized trial and nobody should pretend it is. It is a large prospective observational registry, which is exactly the kind of dataset that tells us what actually happens when SBRT leaves the clean world of single-institution phase II papers.

Dataset:
- 57 institutions
- 2447 eligible patients
- 3533 treated lesions
- Median follow-up 31 months
- Primary sites: prostate 42%, NSCLC 22%, CRC 21%, breast 15%
- Most common treated sites: non-vertebral bone, lung, nodes, spine, liver, brain

Overall result:
- Local in-field progression: 5.0% at 1 year
- Local in-field progression: 11.4% at 3 years
- Translation: 88.6% 3-year local control in real-world oligometastatic SBRT.

That is a very good number.

The interesting part is not just “SBRT works.” We already knew that. The interesting part is what predicted local control.

On multivariable analysis, the key technical factor was:

minimum PTV dose.

Not age. Not sex. Not PS. Not lesion site. Not CTV volume. Not concomitant systemic therapy. Minimum PTV dose.

In other words: coverage still matters. Fancy systemic therapy does not rescue a cold PTV.

Also notable:
- De novo OMD had better local control than repeat OMD, likely because higher dose was delivered.
- CRC had worse local control despite receiving the highest median dose per fraction.
- CRC 3-year local progression: 19.6%
- Prostate: 8.1%
- NSCLC: 9.8%
- Breast: 11.3%

So yes, histology still matters. CRC remains CRC. It is relatively radioresistant and may need dose escalation, better selection, or smarter combinations.

RO takeaway:

This is a very practical paper. The main message is not “SBRT everything.” The main message is:

If you are going to offer oligometastatic SBRT, do not underdose the target and then congratulate yourself for being conformal.

Minimum PTV dose is not a planning footnote. It is the technical variable most associated with local control.

Also, stop treating all oligometastases as biologically equivalent. Prostate oligomets are not CRC oligomets. De novo OMD is not repeat OMD. Lung is not liver. Histology and disease state still matter.

Limitations are obvious:
- registry data
- no randomization
- RECIST/institutional follow-up
- no central response review
- heterogeneous dose/fractionation
- heterogeneous systemic therapy

But for a real-world SBRT dataset, this is useful.

Bottom line:

SBRT provides durable local control in oligometastatic disease, about 89% at 3 years, but the result is not magic. It depends on dose, coverage, histology, and patient selection.

The machine matters less than the plan.

And the plan still has to cover the damn target.
 
EORTC IM-MS trial, 20-year update.

Internal mammary + medial supraclavicular nodal irradiation in stage I–III breast cancer.

This is the kind of trial that makes everyone unhappy because both sides get ammunition.

4004 patients. Enrolled 1996–2004. Median follow-up 22.2 years. About 44% pN0, 43% pN1, with a mix of BCS/mastectomy and systemic therapy that obviously reflects the era.

At 20 years:

- Overall survival: 61.0% vs 61.8%
- HR 1.00
- p = 0.967

So no OS benefit. None. Flat.

DFS:
- 48.2% vs 49.0%
- p = 0.515

DMFS:
- 58.9% vs 59.8%
- p = 0.578

Also basically nothing.

But breast cancer mortality was lower:

- BCM: 18.6% vs 22.4%
- HR 0.82
- p = 0.006

So nodal RT did reduce breast cancer death by about 3.8% absolute at 20 years.

The problem: non-breast cancer mortality went the wrong way.

- non-BC mortality: 20.4% vs 15.8%
- HR 1.26
- p = 0.002

Late separation after about 15 years. Exactly the kind of finding that keeps breast RO honest.

Reported RT-related late effects were numerically higher:
- Lung fibrosis: 6.3% vs 3.2%
- Cardiac fibrosis: 2.7% vs 1.7%
- Cardiac diseases: 15.2% vs 11.7%

No statistical difference in second cancers / second breast cancers, at least per the slide.

My take:

Regional nodal irradiation is not free. It buys breast cancer control, but if you pay for it with heart/lung dose, the OS benefit can vanish into late competing mortality.

This does not mean “never treat IMNs.” That would be idiotic.

It means stop pretending IMN coverage is a religion. It is a risk/benefit decision.

High-risk medial/central tumors? Multiple positive nodes? Gross IMN involvement? Young patient with modern DIBH/IMRT/protons and low heart dose? Different discussion.

Low-risk lateral pN0 or marginal pN1 disease where the IMN benefit is theoretical and the heart/lung dose is real? Be careful.

Also, this was 1996–2004 radiation. Modern planning should reduce cardiac dose substantially. But the biological lesson survives the technology change:

You can lower breast cancer mortality and still fail to improve survival if your normal tissue price is too high.

RO takeaway:

Treat nodes when the recurrence/mortality risk justifies it.

But contouring IMNs because “that’s what comprehensive RNI means” is not medicine. It is autopilot.
 
DBCG RT Natural trial.

Title basically says it all: when less is not enough.

This was a phase III trial in the modern “low-risk older breast cancer” space:

Women ≥60, breast conservation, pT1N0, unifocal, non-lobular, ER ≥10%, HER2 negative, grade 1–2, margins ≥2 mm.

Randomized to:

- PBI 40 Gy / 15 fx
- No PBI

Plus a self-selecting no-RT cohort.

Accrual: 802 patients. Trial stopped early after interim review.

This is exactly the patient population where everyone loves to say, “Just omit radiation, endocrine therapy will handle it.”

Except endocrine therapy adherence was only mediocre. Only 55.6% started ET, and among those who started, 5-year adherence was only about 60–64%.

Primary endpoint was local recurrence.

Median follow-up: 4 years.

Results:

- PBI arm: 5-year local recurrence 1.5%
- Randomized no RT: 9.8%
- Self-selected no RT: 8.2%

41 local recurrences total. 39 of 41 occurred in patients who had no PBI.

The most useful slide was local recurrence by PBI and endocrine therapy:

- PBI + ET: 0%
- PBI without ET: 3.0%
- No PBI + ET: 3.7%
- No PBI + no ET: 12.2%

That is the whole trial.

Either PBI or endocrine therapy gives reasonable local control. Both together are best. Neither is a problem.

IDFS favored PBI numerically:
- 90.9% with RT
- 78.1% randomized no RT
- 77.6% self-selected no RT

Overall survival was obviously unchanged at this early follow-up:
- 94.5% vs 96.0% vs 94.8%

Side effects were mild. Dyspigmentation was higher with PBI, around 7.4% vs 1%, but otherwise this looked well tolerated.

RO takeaway:

This is a direct hit against lazy RT omission in “low-risk” older ER+ breast cancer.

The key problem is not the biology on paper. The key problem is the actual human being.

Endocrine therapy adherence is not a theoretical checkbox. Patients stop it. They hate it. They forget it. They get arthralgias, fatigue, hot flashes, mood changes, and then the “safe omission” strategy quietly becomes no RT and no effective systemic therapy.

PBI is local insurance.

This does not mean every 75-year-old with a 6 mm grade 1 ER+ tumor needs RT. But it does mean we should stop pretending omission is automatically benign just because the tumor board spreadsheet says “favorable biology.”

Modern imaging and pathology do not repeal breast cancer biology.

My practical counseling from this trial:

If she is genuinely going to take endocrine therapy, omission can still be discussed.

If she is ambivalent about endocrine therapy, already hates medications, or is likely to stop after six months, PBI starts looking very attractive.

And if she wants neither RT nor endocrine therapy, she needs to understand that the 5-year local recurrence risk in this trial was about 12%, not 1–2%.

Bottom line:

For low-risk older ER+ breast cancer, less can be enough — but not nothing.
 
PEACE 2 — pelvic RT in very high-risk localized prostate cancer

Very high-risk localized prostate cancer: Gleason ≥8, T3–4, PSA ≥20, with ≥2 risk factors. All got long-term ADT and prostate RT; randomized to prostate-only vs pelvic RT, with/without cabazitaxel.

Cabazitaxel did nothing. No improvement in cPFS, bPFS, MFS, PCSS, or OS.

Pelvic RT showed a numerical but not statistically significant benefit:
- 7-yr cPFS: 67.1% pelvic RT vs 62.9% prostate-only
- HR 0.81, p=0.088
- 7-yr bPFS: 65.8% vs 61.0%
- HR 0.84, p=0.17

Toxicity was not meaningfully worse with pelvic RT, at least globally.

RO takeaway: pelvic RT in very high-risk N0 prostate cancer remains biologically reasonable, but PEACE 2 does not give a clean positive randomized win. It is a trend, not a mandate.

Caveat: staging was mostly conventional/choline PET, not modern PSMA PET, and the pelvic field was slightly smaller than current NRG-style fields.

My practical takeaway: I would still strongly consider pelvis for very high-risk patients with high nodal risk, but I would not pretend PEACE 2 proves it. It supports selective use, not automatic dogma.
 
PACE-NODES — 5-fraction pelvic nodal SBRT

High-risk localized prostate cancer randomized to:

- Prostate-only SBRT: 36.25 Gy / 5 fx
- Prostate + pelvic nodal SBRT: 36.25 Gy / 5 fx prostate + 25 Gy / 5 fx nodes

Planned ADT: 12–36 months. Accrual was excellent: 1166 patients in under 3 years.

Acute safety result:

Pelvic nodal SBRT increased short-term GI toxicity:
- CTCAE grade ≥2 GI: 28.0% vs 21.3%
- RTOG grade ≥2 GI: 23.9% vs 14.8%

But grade ≥3 GI events were low:
- 2.2% vs 1.6%

GI symptoms peaked around 2 weeks and largely resolved by 12 weeks.

GU toxicity: no meaningful difference.

Patient-reported outcomes: more bowel deterioration at 4 weeks with pelvic nodal SBRT, but no difference in urinary, hormonal, sexual, or global health measures.

RO takeaway:

5-fraction prostate + pelvic nodal SBRT is feasible in a multicenter setting.

The price is a transient acute bowel hit, not a major early GU signal.

Cancer control and late toxicity are still pending, so this is not yet a “treat every high-risk pelvis in 5 fractions” result.

But technically, the approach is clearly doable.
 
PCS-XI — pelvic ultra-hypofractionation + HDR boost

Different question than PACE-NODES.

PACE-NODES asked: can we add pelvis to 5-fraction prostate SBRT?

PCS-XI asks: if you are already doing HDR boost + pelvic RT + ADT, can the pelvic RT be compressed?

Design:

- CF: HDR 15 Gy x1 + pelvic IMRT 43–46 Gy / 20–23 fx
- UHF: HDR 15 Gy x1 + pelvic IMRT 25 Gy / 5 fx QOD
- ADT 4–36 months
- 500 patients
- >80% high-risk or very high-risk
- Median follow-up only 8.5 months

Early toxicity looked very reasonable.

Grade 2 GU at 3 months was actually lower with UHF:

- CF: 15.4%
- UHF: 9.4%
- p = 0.038

GI toxicity: no significant difference.

PROs: IPSS, SHIM, EPIC bowel, irritative, and incontinence domains were essentially parallel. No between-arm difference reached MCID.

No grade 4–5 toxicity.

RO takeaway:

Pelvic 25 Gy / 5 fx after HDR boost appears feasible and well tolerated early.

But this is still early toxicity only. The real test is late GU/GI toxicity and disease control.

For now: encouraging, not practice-ending.
 
DART phase II — SBRT ± 6 months darolutamide for PSMA PET oligorecurrent prostate cancer

Randomized PSMA PET-detected oligorecurrent HSPC to SBRT alone vs SBRT + 24 weeks darolutamide.

Small trial: ~124 pts. Mostly bone mets, mostly 1–2 lesions. PSA DT <12 months.

Signal:

- Better biochemical control with darolutamide
- cRFS: 18 vs 13 months, HR 0.71, p=0.11
- MFS: 18 vs 15 months, HR 0.84, p=0.4

So: daro delays progression while patients are taking it, but no convincing durable MFS/cRFS win here.

Toxicity/QOL as expected: more hot flashes, fatigue, gynecomastia, etc. with daro; SBRT itself looked well tolerated.

RO takeaway: MDT remains useful, but short-course ARSI here looks more like temporary disease suppression than a clear game-changer.
 
Royal Marsden/ICR 2-fraction MR-guided adaptive prostate SBRT

Single-centre randomized phase II trial on Elekta Unity: intermediate/lower high-risk prostate cancer, n=46, 6 months ADT.

Compared:

- 2 fx: 24 Gy/2 fx with 27 Gy MRI-defined tumor boost
- 5 fx: 36.25 Gy/5 fx, 40 Gy to CTV

Primary endpoint: acute grade 2+ GU toxicity.

Results were very similar:

- 5 fx: 7/24, 29.2%
- 2 fx: 6/22, 27.3%

At 24 months, GU/GI toxicity remained low and QoL was maintained. GI grade 2+ was ~4–5% in both arms.

Takeaway: 2-fraction MR-guided adaptive SBRT appears feasible and safe at 2 years, but this is small, single-centre, and toxicity/QoL-focused—not yet a broad efficacy-changing dataset.
 
Gfunk6 said:
PEACE 2 — pelvic RT in very high-risk localized prostate cancer

Very high-risk localized prostate cancer: Gleason ≥8, T3–4, PSA ≥20, with ≥2 risk factors. All got long-term ADT and prostate RT; randomized to prostate-only vs pelvic RT, with/without cabazitaxel.

Cabazitaxel did nothing. No improvement in cPFS, bPFS, MFS, PCSS, or OS.

Pelvic RT showed a numerical but not statistically significant benefit:
- 7-yr cPFS: 67.1% pelvic RT vs 62.9% prostate-only
- HR 0.81, p=0.088
- 7-yr bPFS: 65.8% vs 61.0%
- HR 0.84, p=0.17

Toxicity was not meaningfully worse with pelvic RT, at least globally.

RO takeaway: pelvic RT in very high-risk N0 prostate cancer remains biologically reasonable, but PEACE 2 does not give a clean positive randomized win. It is a trend, not a mandate.

Caveat: staging was mostly conventional/choline PET, not modern PSMA PET, and the pelvic field was slightly smaller than current NRG-style fields.

My practical takeaway: I would still strongly consider pelvis for very high-risk patients with high nodal risk, but I would not pretend PEACE 2 proves it. It supports selective use, not automatic dogma.
Click to expand...


the takeaway IMO should be to STOP using pelvic RT. it doesn't do anything, shown over and over again.
 
Gfunk6 said:
FLAME - Standard prostate fractionation +- SIB boost to gross disease

Int-High risk (84% high risk)
Lymph nodes NOT treated

Arm 1- 77 Gy in 35
Arm 2 - as above but up to 95 Gy via SIB to lesions (median 84.7 Gy)

ADT given at the discretion of the investigator
1/3 did not get ADT

10 year bPFS
Arm 1 - 71%
Arm 2 - 86%

10 year DFS
Arm 1 - 67%
Arm 2 - 81%

10 year regional LN DFS
Arm 1 - 84%
Arm 2 - 95%

No difference in toxicity in both arms.

SIB shows unequivocal long term clinical advantages compared to more homogenous conventional dosing.

Multiple trials using hypofrac and SBRT trials underway based on the above.
Click to expand...
SV's not treated either. In Int-High risk. If I believe in FLAME do I ignore LN and SV RT. 🤔
 
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APHRODITE: rectal organ preservation dose escalation — useful signal, not practice-ending gospel

Randomized UK phase II trial in MRI-defined early rectal cancer, T1–3b N0–1b M0, non-threatened margin, either unfit for TME or strongly preferring organ preservation.

Compared:

Standard RT: 50.4 Gy / 28 fx

vs

Escalated RT: same mesorectal-only approach with 62 Gy SIB to primary tumor

IMRT and daily CBCT mandated. Capecitabine allowed, but decided pre-randomization.

Primary endpoint was 6-month cCR by MRI/sigmoidoscopy/DRE.

Result:

cCR 33.3% with standard dose vs 49.4% with 62 Gy boost

Absolute difference about 16%.

Sensitivity analyses looked similar:
41.7% vs 59.7% when including cCRs outside the narrow assessment window, and 36.1% vs 57.1% with a modified cCR definition allowing superficial ulceration.

Toxicity: overall acute grade ≥3 events 12%, with somewhat more bowel/anorectal toxicity in the escalated arm, but no obvious acute train wreck.

My take:

This is a meaningful signal for rectal organ preservation. If a patient is genuinely pursuing nonoperative management, a 62 Gy primary boost appears to improve early cCR versus 50.4 Gy without an immediate toxicity disaster.

But this is still phase II, with a very generous one-sided 20% alpha, so let’s not pretend this is a definitive phase III standard-of-care answer.

The real question is not “did the rectum look good at 6 months?”

The real question is durable organ preservation, local regrowth, salvageability, late bowel function, and whether patients actually avoid TME without paying for it later.

Pithy version:
APHRODITE makes 62 Gy boost for early rectal organ preservation look reasonable. It changes the tumor board conversation. It does not end the conversation.
 
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