Poll: using GRID or Lattice radiation?

[IonsAreOurFuture]

I've noticed a recent uptick in publications on Spatially Fractionated RT (SFRT) and wanted to see who's using it from the forum?

https://www.practicalradonc.org/article/S1879-8500(22)00083-2/fulltext

https://www.ctro.science/article/S2405-6308(23)00002-2/fulltext

I've noticed some impressive complete responses in bulky tumors >10 cm size but wanted to see if anyone else has had a similar experience.

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[RickyScott]

Yes, several times a year. What dose/fractionation have you tried?

 

[evilbooyaa]

Good thread topic - I have a case I'm considering on it when pt's symptoms progress (again) to require intervention. Some discussion on dose/fractionation as well as whether you treat just the stereo part vs give a low dose to the entire GTV would be of value, especially from people that have utilized it clinically.

 

[RickyScott]

spraker needs to offer tap podcast on this

 

[madchemist89]

I have done it once so far. I think it was 18 gy x 1 to the spheres then 30 in 10. It was a large melanoma met. Seemed to work ok.

 

[NotMattSpraker]

Good thread topic - I have a case I'm considering on it when pt's symptoms progress (again) to require intervention. Some discussion on dose/fractionation as well as whether you treat just the stereo part vs give a low dose to the entire GTV would be of value, especially from people that have utilized it clinically.

The off the books advice that I've learned from Mayo is that you have to come back and "consolidate" the rest of the tumor with conventional radiation, ie don't just treat the GRID fraction. People will progress if you don't.

This would be one advantage of the Lattice SBRT (SIB) approach.

Dose/fractionation and technique are intense areas of discussion but I am not convinced these matter very much. If they do, I am not convinced we will ever have the studies to really know the answer.

I have given an "intro" lecture a few times. I hope to record it and get this posted up soon. Other possible spatial fractionation content in development

 

[IonsAreOurFuture]

There was this interesting study out of the Univ of Chicago 5 years ago showing that partial tumor irradiation for masses over 65 cc was just as effective as total tumor irradiation for masses < 65 cc. The patients received at least one cycle of pembrolizumab. Not all lesions were irradiated, some were monitored for non-target (abscopal) responses.

There weren't abscopal responses per se, but there were a lot of what they called ADscopal (local bystander) responses in tumors that were only partially irradiated.

The local control rates were statistically the same for partially (88%) and fully (95%) irradiated tumors, even though the partially-treated tumor mean volume was 116.6 mL, vs only 7.2 mL for fully irradiated:

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2017.76.2229

The take home for me was that maybe partial tumor irradiation could work in the immunotherapy era, or at least some form of margin reduction - maybe negative margins? Maybe we need to get out of our own way a little bit, I know I'm always messing up my intended results, sometimes from trying too hard to "fix it real good"

 

[NotMattSpraker]

There was this interesting study out of the Univ of Chicago 5 years ago showing that partial tumor irradiation for masses over 65 cc was just as effective as total tumor irradiation for masses < 65 cc. The patients received at least one cycle of pembrolizumab. Not all lesions were irradiation, some were monitored for non-target (abscopal) responses.

There weren't abscopal responses per se, but there were a lot of what they called ADscopal (local bystander responses) in tumors that were only partially irradiated.

The local control rates were statistically the same for partially (88%) and fully (95%) irradiated tumors, even though the partially-treated tumor mean volume was 116.6 mL, vs only 7.2 mL for fully irradiated:

https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2017.76.2229

The take home for me was that maybe partial tumor irradiation could work in the immunotherapy era, or at least some form of margin reduction - maybe negative margins are the way to go. Maybe we need to get out of our own way a little bit, I know I'm always messing up my intended results, sometimes from trying too hard to "fix it real good"

Great study. If you wanna get in to some weird and wild partial tumor irradiation stuff, SBRT-Pathy. Love this work. I heard it is still ongoing, looking forward to future papers.

Novel stereotactic body radiation therapy (SBRT)-based partial tumor irradiation targeting hypoxic segment of bulky tumors (SBRT-PATHY): improvement of the radiotherapy outcome by exploiting the bystander and abscopal effects

Despite the advances in oncology, patients with bulky tumors have worse prognosis and often receive only palliative treatments. Bulky disease represents an important challenging obstacle for all currently available radical treatment options including ...

www.ncbi.nlm.nih.gov

https://www.redjournal.org/article/S0360-3016(20)32653-5/fulltext

 

[IonsAreOurFuture]

Great study. If you wanna get in to some weird and wild partial tumor irradiation stuff, SBRT-Pathy. Love this work. I heard it is still ongoing, looking forward to future papers.

Novel stereotactic body radiation therapy (SBRT)-based partial tumor irradiation targeting hypoxic segment of bulky tumors (SBRT-PATHY): improvement of the radiotherapy outcome by exploiting the bystander and abscopal effects

Despite the advances in oncology, patients with bulky tumors have worse prognosis and often receive only palliative treatments. Bulky disease represents an important challenging obstacle for all currently available radical treatment options including ...

www.ncbi.nlm.nih.gov

https://www.redjournal.org/article/S0360-3016(20)32653-5/fulltext

Yes, that Pathy stuff is pretty cool. Basically 15 Gy x 3, but only to the hypoxic core of the tumor, and deliberately try not to kill cells in the tumor periphery where immune infiltration is occurring.

This paper is interesting too, albeit in mice. Irradiate 50% of a tumor, get the same response as 100% coverage:

An Antitumor Immune Response Is Evoked by Partial-Volume Single-Dose Radiation in 2 Murine Models - PubMed

In these models, radiation controls tumor growth both directly through cell killing and indirectly through immune activation. This outcome raises the possibility that this effect could be induced in the clinic.

pubmed.ncbi.nlm.nih.gov

The response was abrogated if they gave CD8 T-cell inhibitors. The really interesting thing to me is that the lymphocytes that killed the un-irradiated half of the tumor didn't come from the lymph nodes or circulation, but were already in the tumor or surrounding microenvironment.

 

[NotMattSpraker]

Yes, that Pathy stuff is pretty cool. Basically 15 Gy x 3, but only to the hypoxic core of the tumor, and deliberately try not to kill cells in the tumor periphery where immune infiltration is occurring.

This paper is interesting too, albeit in mice. Irradiate 50% of a tumor, get the same response as 100% coverage:

An Antitumor Immune Response Is Evoked by Partial-Volume Single-Dose Radiation in 2 Murine Models - PubMed

In these models, radiation controls tumor growth both directly through cell killing and indirectly through immune activation. This outcome raises the possibility that this effect could be induced in the clinic.

pubmed.ncbi.nlm.nih.gov

The response was abrogated if they gave CD8 T-cell inhibitors. The really interesting thing to me is that the lymphocytes that killed the un-irradiated half of the tumor didn't come from the lymph nodes or circulation, but were already in the tumor or surrounding microenvironment.

I treated about 100 patients with Lattice SBRT. Im a believer there is some unique radiobiology going on. It made me feel like numeric dose-escalation is actually one of the more boring things we can do with our modality.

I look forward to future research playing with spacial fractionation, temporal feathering, and stuff like pulsar.

Tubins work is criminally unknown given the early results.

 

[RickyScott]

I treated about 100 patients with Lattice SBRT. Im a believer there is some unique radiobiology going on. It made me feel like numeric dose-escalation is actually one of the more boring things we can do with our modality.

I look forward to future research playing with spacial fractionation, temporal feathering, and stuff like pulsar.

Tubins work is criminally unknown given the early results.

Same for pulsed low dose external radiation.

 

[IonsAreOurFuture]

I treated about 100 patients with Lattice SBRT. Im a believer there is some unique radiobiology going on. It made me feel like numeric dose-escalation is actually one of the more boring things we can do with our modality.

I look forward to future research playing with spacial fractionation, temporal feathering, and stuff like pulsar.

Tubins work is criminally unknown given the early results.

What is temporal feathering? Is that like junction feathering in the spinal cord, but over days?

 

[NotMattSpraker]

What is temporal feathering? Is that like junction feathering in the spinal cord, but over days?

Technical Note: A step-by-step guide to Temporally Feathered Radiation Therapy planning for head and neck cancer - PubMed

Temporally Feathered Radiation Therapy planning is possible with modern treatment planning systems. Modest dosimetric changes are observed with TFRT planning compared with non-TFRT IMRT planning. We await the results of the current prospective trial to seeking to demonstrate the feasibility of...

pubmed.ncbi.nlm.nih.gov

 

[IonsAreOurFuture]

Thanks for that note on Temporally Feathered RT!

I missed this result when it first came out in 2020: the PEMBRO-RT trial and MDACC trial of SBRT + Pembro each had some interesting results but were too small for definitive signals. The PEMBRO RT trial only reached statistical significance in the PD-L1 negative lung cancers. This is now a meta-analysis combining the 2 trials.

Median progression-free survival was 4·4 months (IQR 2·9–5·9) with pembrolizumab alone versus 9·0 months (6·8–11·2) with pembrolizumab plus radiotherapy (hazard ratio

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0·67, 95% CI 0·45–0·99; p=0·045), and median overall survival was 8·7 months (6·4–11·0) with pembrolizumab versus 19·2 months (14·6–23·8) with pembrolizumab plus radiotherapy (0·67, 0·54–0·84; p=0·0004). No new safety concerns were noted in the pooled analysis.

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30391-X/fulltext

The PEMBRO-RT trial is the one that didn't treat whole tumor volumes over 5 cm size, instead giving partial XRT. They found what they call the "ADscopal" effect, in the partially treated tumor but not the observed tumor.