Is there a radiation dose-response relationship for rectal cancer managed non-surgically?

Short answer: Yes - at least based on published patient series

Longer answer: See our #ESTRO2020 Poster Highlight - or thread below

#radonc… ImageImage
Non-operative management of rectal cancer is becoming increasingly important - more and more patients are offered observation instead of surgery if they have a complete response after (chemo-)radiotherapy #radonc #ESTRO2020 Image
Most published series are only reporting on that select group of patients - the ones who got a complete response. That's great if we want to understand if observation is a safe strategy for those patients #ESTRO2020…
But it doesn't tell us how large a proportion of *all treated* patients can get long term control without surgery. Or really give us any robust information as to whether we can increase that number by altering our treatment up front #ESTRO2020 #radonc
We are particularly interested in whether dose escalation has a role to play!

I've previously explained why dose escalation to the primary tumour probably doesn't help much in the neoadjuvant setting:

But how about for organ preservation? #ESTRO2020
We systematically searched the literature for studies of non-operative management of rectal cancer; which:
1) Included the total patient cohort treated, not just those managed with observation
2) Reported the dose to tumour
3) Reported total proportion without surgery at 2 years Image
Now, out of the 15 papers that we found, 6 of them didn't systematically screen patients for complete response. So we couldn't trust that they actually allowed everybody to avoid surgery who could do so - i.e. their estimate of 'proportion managed without surgery' will be biased
One more tricky part: Some of the patient cohorts were treated with brachy or Papillon boosts - so estimating the tumour dose wasn't super easy ...
#ESTRO2020 #medphys
For one cohort, I actually had MRI-based dose plans, so getting exact EQD2 doses was possible. And for another (Papillon) cohort, I got information on tumour thickness and individual prescriptions + applicators - so I could estimate the average tumour EQD2
#ESTRO2020 #medphys ImageImage
For others, I did a lot of approximations, based on average cohort tumour size and application information ...
(Side note: We're improving on this! People have kindly shared individual patient dose data with me, so we'll do better for the final publication!)
But altogether, we were able to estimate a dose response for local control (without surgery) as a function of tumour EQD2, using a weighted and bounded logistic regression. Our best estimate:
D50 = 71Gy
gamma50 = 1.1
#ESTRO2020 #radonc Image
One more important thing:
We know that smaller / early stage rectal cancers are more likely to respond to RT. There is an obvious risk that the observed dose-response relationship is purely due to cohorts with early cancers also receiving higher doses
#ESTRO2020 #radonc
So we controlled for this! We used a IPD meta analysis based measure of relative response probability, adjusted the data points accordingly, and allowed for different upper bounds for T1-2 and T3-4 cancers…
#ESTRO2020 #radonc
Even when doing this, we still saw clear dose-response
- and we found different upper bounds for the maximum local control we can expect to achieve for early (~80%) and advanced (~65%) cancers.
D50 = 66Gy for T1-2 and 85Gy for T3-4
#ESTRO2020 #radonc Image
Does this provide definite evidence of a dose-response relationship? Obviously not. We still need randomized trials ... but that's why we are currently doing them! 😉

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More from @cancerphysicist

21 Nov 20
For the first question: No trials showing higher pCR w/ higher dose. Trials are actually remarkably consistent (no difference):
#jc questions #radonc
❗️*However* ❗️
pCR doesn't matter to the patient! Only OS or QoL does! And pCR / tumour regression is not a surrogate for radiotherapy effects on OS, so why should we care about it? #radonc #jc
If you think about it, we are actually unlikely to see a dose-response relationship for rectal cancer in the (neo-)adjuvant setting: Even if there exists a dose-response relationship, it must be very shallow
Read 11 tweets
18 Dec 19
After reviewing 'predictive modelling & radiomics' abstracts for #ESTRO202, I had quite a few thoughts. I've finally found time to organise them in a semi-coherent manner

To follow: Some common pitfalls in modelling & radiomics abstracts for clinical conferences #radonc #medphys
First of all, the basic stuff:
Get somebody who’s never seen your study before to read through the abstract - to ensure fundamental information isn't missing.
(And no, you won't notice yourself, because you’re too concerned with whether you can squeeze in another AUC value ...)
If you are submitting to a radiotherapy conference, maybe make clear what the relevance is for radiotherapy? Several image analysis / radiomics / AI abstracts were probably technically excellent, but I scored them low due to lack of radiotherapy relevance
Read 11 tweets
20 May 19
Part II of today’s tweetorial for International clinical trials day: #CTD2019 #ICTD2019

Why do you want to give physicists a central role in your radiotherapy trials?

#medphys #radonc
@ipemnews @EFOMP_org @aapmHQ @EORTC @CTRad_CChan
First, what characterises medical physicists?
- We're quantitative, systematic & analytical
- We're trained in modelling, data visualisation, & interpretation of evidence

(And sometimes we - by which I mean me - go exploring in caves, which is almost like running a trial 😅)
But importantly, we understand the opportunities and limitations in current technology & are uniquely placed to understand current gaps in knowledge.

We can ask

“How can we best utilise technology to improve outcomes?”
“Will this be achievable in daily practice?”
Read 22 tweets
20 May 19
Today is International Clinical Trials Day! #CTD2019

In the spirit of #CTD2019, I thought I’d take a bit of time to talk about medical physicists and radiotherapy trials #medphys #radonc
@ipemnews @EFOMP_org @aapmHQ
Why should radiotherapy trialists care about medical physicists? And why should physicists involve themselves in trials?
The short answer: It makes trials a whole lot better!

The slightly longer answer: It ensures maximum value from data that we are entrusted by patients

And the properly detailed answer will take a couple of tweetorials ☺️
Read 14 tweets

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