Nhi from NY - Dx June 2016

[arojussi]

Second option might not be less aggressive, than first one. If they radiate larger area smaller radiation dose might actually do more damage than little higher dose for smaller area. It is most likely impossoble to kill all cancer cells in bones with radiation alone, so getting immunesystem to regonice and kill cancer is vital. Even before immunotherapies asps-patients sometimes had radical and long lasting responses most likely caused by abscopal effect.

Targeting bone mets one by one is definitely safer, than radiating larger area at once. Sorry if I am missing something important as this case is getting quite complicated.

[ntran727]

Thank you all for your responses. I initially wanted SBRT to a single bone met thinking that it would be similar of a dose to what Ivan had done and still be able to achieve an abscopal effect. Dr. Choi’s explanation is that she feels that we would be able to achieve an abscopal effect either way for options 1 or 2, but option 2 is less toxic because it will be less greys in total (20 vs 27). She also felt that because I have multiple Mets in the same small location that she can encompass them all instead of choosing only 1 area to do SBRT on while leaving the others untreated. She mentioned that option 2 is very low risk but we didn’t speak about specifics pertaining to the gut. Debbie, my pain in the area started way before the pregnancy and gradually got worse as I stopped the Sutent and began the keytruda. The methotrexate and cytotec has no effects on me besides the few hours of cramping that’s supposed to happen after taking cytotec and of course worsened the back pain at the time but much more generalized. Interestingly, since I’ve restarted the Sutent about a week ago, my main has slightly improved, therefore confirming even more that the pain is cancer related.

My question is why can’t I eventually treat them all one by one with either SBRT or perhaps cryoablation? Would we be able to achieve an abscopal effect with cryoablation alone? Do you think this would be feaseable? If so, I would rather start with the SBRT or cryo to the right iliac met or one of the spinal Mets to both attempt to treat it and to achieve an abscopal effect at the same time. Then, if it kicks keytruda into gear, we won’t have to perform more RT to the remaining Mets. If it doesn’t work, I would have to make sure that they would be willing to treat the other Mets or consult with MSK. What do you think? Should I seek a second opinion with MSK either way? My next infusion is scheduled for 6/21 so I do have some time. Dr. Choi said that she is only leaning towards option 2 but is willing to change it to option 1 or whatever I felt more comfortable with.

[arojussi]

There was member here, who had amazing success with cryoablation continued with keytruda. I think it was George from China. So cryoablation is good option for abscopal effect.

[Olga]

Many types of the local ablative treatments for the single met are shown to produce the abscopal effect - although infrequently. There ever were cases when after the biopsy of the non-responding met they would regress abruptly under continued ICI. There was a study re. different treatment modalities effect on the immune system activation, and with the radiosurgery they found less robust but more predictable stimulating effect, while with the cryo the effect magnitude was greater but it go either direction - up or down, so in some cases the effect was suppressive. So the SBRT went to trials as the more predictable modality. Although I do not know, may be they incorrectly choose timing and the cryo treatment was done in the middle of the ICI cycle etc. It is all speculations as of now, of course, and we just go over the thin ice here trying to invigorate the immune system and attract it to the spot where the dying cancer is but still not to produce to large of an area of the inflammation (as it would be with the bigger field radiation), not to harm the microbiome but still treat the tumor. The radiation oncologist might be not very well versed in the immunotherapy, even oncologists often do not pay attention to the small details to how it works and what could be other treatment interactions.
The overall volume of the tissue damage is most probably going to be smaller with the few SBRT treating each one of them mets versus a field radiation therapy. Do you know what system is used at your hospital? is MSK in your insurance system? they have some very advanced units there, but I expect that most of the large places in NY will have them.
I looked up the pembrolizumab+SBRT on clinical trials dot gov and they mostly test SBRT in 3-5 fractions *8 given over a week after or before K

[ntran727]

Thank you again for the useful information. I think that I will speak with her about doing the SBRT instead, 8*3 or the 9*3 she suggested. If the trials are doing a week before or a week after the infusion, then I can start the SBRT the week before my next infusion, which would be sooner rather than later. From what I read online, they mostly completed SBRT and then started pembrolizumab after. A lot of studies mention multi-site SBRT which I wonder how long it took to complete. Why did you all decide to do it on the same day as the infusion Olga? Either way, it seems like somewhere within the vicinity is good enough.

I will perhaps look into cryoablation of the other bone Mets later on. MSK is in my plan and I have seeked second opinions from them in the past. I remember seeing a rad onc there who specializes in sarcoma, so I will call them tomorrow and see if I can get an appointment. I hesitate because I am seeing my onc from Columbia so they like for me to have everything done in one place, and they do have good doctors there although not as good as MSK I am sure (besides my onco Dr. Schwartz who worked for them for years before moving to Columbia whom I am very comfortable with).

[Olga]

We decided on the same day because when I was reading - 1.5 years ago - most of the trials were saying simultaneous SBRT+K with the SBRT start 1 day before or after K, and I did not want the radiation to start almost in the middle of the cycle - when you start a week before, it is 2 weeks after the previous one:) I think the design of the clinical trials takes the convenience into consideration too as it is hard for them to schedule the overlaps and the necessary blood works and they probably have the other secondary goals like measurements of the inflammatory factors during the SBRT - their dynamics, and do not want the K to affect that so they can see what is happening, perhaps some other logistical reasons that are important for the trial people but have no meaning in case of the single patient.

Also I was reading on the pharma kinetics of K and on the processes during the SBRT. K maximum blocking effects is reached at 72 hours past administration. The first irradiation dose does not kill the tumor fore sure, it just damages it. The SBRT increases the PD-1 expression in a tumor so I was thinking that having K in the beginning of the SBRT would make the tumor a good target and there is still lots of viable but sick tumor there for the immune system to sniff on. So the overlap would make sense. Most likely the good immunologist would drop dead laughing from all of this speculation though. I am kind of disappointed to see them missing in the general discussion of the treatment interactions everywhere.

[ntran727]

Yes, well it is good speculation indeed. My radiation oncologist does not seem to feel that timing matters as the medication is in me anyway, but yes I know it does peak at 72 hours. I’ve already had 4 infusions, so not sure if it would make a difference in terms of timing. I am meeting with her again Tuesday for the mapping and will ask to do SBRT to a single met instead and aim for the start at the next infusion. I’ll see what she says. Do you think this is a good plan? It seems like the consensus on this forum based on what everyone is saying plus with what I have read as well.

[Olga]

The latest ASCO proceedings are out and I was reading re. pembrolizumab+radiation search
found this article that shows SBRT superiority versus traditional fractionated RT in this combination you can use it as an argument (although the regiment she proposed might be not the traditional also)
https://meetinglibrary.asco.org/record/174508/abstract
and I think it is OK to start the SBRT before of the K day as it takes a week anyways to be done with

[ntran727]

Thank you for the article. Yes, all the articles I found have mostly mentioned SBRT and not traditional RT. What she plans to give me is too low of a dose in general at only 4 grays x 5 fractions I feel and I am not sure if that would be enough to stimulate the pembro. I feel more comfortable going with the SBRT to one of the bone mets and then pursuing the treatment of the other bone mets at a later time. I will see what she says.

[arojussi]

first I had traditional radiation, because met was too close to surface of the skin to be targeted by stereotactic radiation. This most likely failed to achieve abscopal effect. So early this year I had stereotactic radiation for mandibular met and based on my other subcutaneous met this time abscopal effect was achieved. I had opdivo infusion few hours after last fraction of stereotactic radiation. 5 fractions. For timing I assumed, that having infusion and radiation as close toeach other as possible was ideal, but some new studies might have more information about timing.

[ntran727]

Thanks for your response Jussi. So I met with Dr. Choi again today. She is on board with what I want to do which is SBRT instead of the lower dose of radiation to a larger area. I told her about Ivan’s case and she is interested in speaking with his radiation oncologist. Olga and Ivan, would you be able to provide me the contact info for Ivan’s rad onc? She wants to pick his brain to see if we can come to a consensus on the right dose/timing.

[Olga]

I sent an e-mail to our radiologist asking if we can share his contact info with your Dr., will let you know.

[ntran727]

Great, thank you Olga. Please let me know as soon as you find out from him if she can discuss via phone or email. It would be very helpful I think for her to speak with another rad onc that has interest in the subject.

I just finished the simulation with body cast in preparation for SBRT. I told her I wanted to do either the 9 grays x 3 fractions that she suggested or 8*4, which is what Ivan got. She even suggested 6*5. We are going to radiate the right iliac met as that is the safer one to go with and is the source of my pain. We plan to start it with my next infusion on 6/21 or the day before depending on her schedule. What do you think of this plan?

Votrient is being delivered tomorrow. I will stop the Sutent and switch to Votrient, 400mg daily. I have been tolerating Sutent at 25mg daily + Keytruda with very minimal side effects so I took some doses of 37.5mg in there. Starting to develop a little hand and foot syndrome and minor aches but my back pain has improved significantly. I hope this means something is working. Fingers crossed that radiation will give the boost I need to get some response.

[Olga]

it looks like there is may be an overtreatment happening if you add pazopanib to K and do not check for the result - what if there is a response as it is without the SBRT? If any scans before of the treatment even the planning ones as to compare with the previous ones?
Also there is an interaction issue as pazopanib is a radiosensitizer
you might want to read some
https://ro-journal.biomedcentral.com/ar ... 017-0893-x

[ntran727]

Olga, I did run across that upon reading and read about the combination of Pazopanib/Sunitinib + pembrolizumab. Seems like I have to worry about toxicity a lot more especially with the liver. We are monitoring closely for any toxicity. The RT dose is low regardless so I’m not super worried about the toxicity with Pazopanib especially after reading that article you linked me to. I want to start the radiation regardless if the combo worked in order to maximize the response. I don’t want to waste more time letting them grow and I don’t think we could scan again so soon. I don’t want to miss the chance for RT if let’s say the TKI did work in combo with pembrolizumab as I hope to get off the TKI in the near future if pembrolizumab worked on its own with the help of RT. I plan to consult regarding cryoablation of my other mets afterwards if I don’t have good response, or maybe just do it anyway and take care of 1 met at a time depending on location and risks associated to that.