Thread by @cancerphysicist, For the first question: No trials showing higher pCR w/ higher dose. [...]

For the first question: No trials showing higher pCR w/ higher dose. Trials are actually remarkably consistent (no difference):
INTERACT https://pubmed.ncbi.nlm.nih.gov/31005204/
RECTAL-BOOST https://pubmed.ncbi.nlm.nih.gov/32565319/
Dose-Effect https://pubmed.ncbi.nlm.nih.gov/22592048/
#jc questions #radonc https://twitter.com/CarmeloT2681/status/1330177386592301057

*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
https://pubmed.ncbi.nlm.nih.gov/25611452/ https://pubmed.ncbi.nlm.nih.gov/26723110/

Pathologic Response, When Increased by Longer Interval, Is a Marker but Not the Cause of Good...

The radiation-induced sterilization rate of the preoperative cancer specimen was a marker of good prognosis. The interval duration (the treatment being the same) although it is modifying the steril...

https://pubmed.ncbi.nlm.nih.gov/25611452/

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 https://twitter.com/cancerphysicist/status/1268839637889490945?s=20

https://twitter.com/cancerphysicist/status/1268839637889490945?s=20

(Side note: pCR / tumour regression / neoadjuvant rectal score *might* be a surrogate for chemotherapy effects on OS or PFS, but not validated on trial level:
https://pubmed.ncbi.nlm.nih.gov/29206996/
https://pubmed.ncbi.nlm.nih.gov/29718095/
And data are inconsistent
https://pubmed.ncbi.nlm.nih.gov/19759186/
#radonc #jc)

Surrogate end points for overall survival and local control in neoadjuvant rectal cancer trials:...

In the FFCD 9203 trial, pathological parameters were not surrogate for OS or LC.

https://pubmed.ncbi.nlm.nih.gov/29206996/

So what matters to patients? Organ preservation (NOM) would - but that depends on
1) clinical complete response (cCR), and
2) long term local control without surgery
#radonc #jc

Can we get more cCR with higher RT dose? pCR is different from cCR, so we can't rely just on the trials examining pCR. We only have the (old) data from Lyon R 96-02:
https://pubmed.ncbi.nlm.nih.gov/22579379/ #radonc #jc

Correlation in rectal cancer between clinical tumor response after neoadjuvant radiotherapy and...

In cancer of the lower rectum, CXRT increases the complete CR, turning in a significantly higher rate of long-term permanent sphincter and organ preservation.

https://pubmed.ncbi.nlm.nih.gov/22579379/

On the other hand, the trials quoted above (INTERACT, RECTAL-BOOST, Dose-Effect) are consistent in showing an effect of dose escalation on tumour regression (TRG1-2). OR=1.6, OR=2.7, OR=1.9. This is still path endpoint, though, so still doesn't matter to patients #radonc #jc

There are ongoing trials testing radiation dose escalation for organ preservation / NOM:
APHRODITE https://ctru.leeds.ac.uk/aphrodite/
WW3 https://clinicaltrials.gov/ct2/show/NCT04095299
So we have to wait for the outcome of these

#radonc #jc

Standard Dose Versus High Dose of Radiotherapy in Rectal Preservation With Chemo-radiotherapy in...

Standard Dose Versus High Dose of Radiotherapy in Rectal Preservation With Chemo-radiotherapy in Rectal Cancer Patients - Full Text View.

https://ctru.leeds.ac.uk/aphrodite/

In the meantime, here are some data based on a literature-based meta-analyses #radonc #jc
https://www.estro.org/Congresses/ESTRO-2020/413/posterhighlights5cl-gi/543/istherearadiationdose-responserelationshipfornon-o

This doesn't address the question of dose escalation for patients w/ risk of incomplete surgical resection: T4 tumours, pelvic side wall nodes, etc. To the best of my knowledge, we don't have firm evidence in this setting either - and I'm unsure if any ongoing trials? #radonc #jc

And here ends my tweetorial on rectal cancer dose escalation. That was probably far more than you wanted to know

#radonc #jc

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