Nhi from NY - Dx June 2016

[ntran727]

Thank you all for the very useful information. I am glad to know the side effects aren’t worse with TKI + ICI together. Olga, would it be SBRT for all the Mets including bone Mets? I don’t know much about this topic and would definitely need some expert advise. I am not sure that my oncologist is aware that the radiation should be done at a certain time either as I think he is mostly counting on the radiation oncologist he sent me to. Her expertise with ASPS is likely any other normal radiation oncologist, so I am not sure how to go about finding someone who knows what they’re doing in the big picture with ASPS. I meet with her next Tuesday and will bring up all these points. Olga, I read up on your post about Ivan, but can you please elaborate more on the exact schedule of the SBRT treatments he received in conjunction with the Keytruda? Did you complete the radiation or do you keep doing it with each infusion? Could you link me to the supporting documents in regards to the timing and type of radiation to be done to achieve an abscopal effect? Also, I forgot to mention I will be taking Zometa, a biphosphonate, to help with the bone Mets. It is infused every 12 weeks.

[Olga]

In an attempt to improve the possibility of the response and elicit the abscopal effect, one metastasis in the soft tissue was treated by the radiosurgery short course concurrently with the second dose of Keytruda, starting on the day 1 and given every other day, 4*8Gray (this 20 mm met was accidentally found on the abdominal CT, and was located deep in the gluteus maximum). So it was only 4 treatments, done in one course over a week, SBRT
some reading:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366147/
with the SBRT, every met is treated separately

[D.ap]

Nhi

The plan sounds excellent . Olga has given you lots of good articles .

I was wondering how your calcium levels have
been looking ?
You were dx’d with being hypothyroid ,correct ?
How long have you been off synthroid?

[Bonni Hess]

Hello again Nhi, I know that you are understandably anxious to begin treatment of your spinal mets, but as with everything with this disease, it is vitally important to be as well researched and as knowledgeable as possible before undergoing any new treatment. As Olga and the articles that she helpfully provided indicate, timing and coordinating of the RT with the ICI infusion is critical to try to successfully achieve the abscopal effect, so Hopefully this can be discussed and coordinated with your oncologist and radiologist prior to your beginning your RT in order to obtain the optimum benefit and treatment success. With special caring thoughts, healing wishes, and continued Hope, Bonni

[ntran727]

My calcium levels have been normal, ranging between 9 to 9.5 @ Debbie.
Yes Bonni, I plan to research as much as possible before my appointment with the radiation oncologist on Tuesday. I will get a second opinion at MSK if she doesn't seem to know much about the abscopal effect of combining immunotherapy with radiation. The only difference between Ivan and I is that I have a symptomatic bone met, so we are trying to treat it and achieve the abscopal effect at the same time, so I am not sure what course of radiation would be appropriate. I will at least push for the timing if not the dose of radiation. My back pain has been getting worse lately, limiting my function, but I plan to go back to yoga very soon to see if I can improve my range of motion. I took off the past 6 weeks because of babies.

[Olga]

Nhi, basically the best schedule for the abscopal effect is now studied in the clinical trials, and I was looking for the recently adopted ones for the studying - they are obviously trying to pick the most promising one as their understanding evolves. I contacted one dr leading one of the most recently open trials to ask what schedule/location he would choose and he actually said - just treat the met that needs to be treated simultaneously with the ICI dose - act with the intention to treat first and with the hope for the abscopal effect second. The problem in Ivan's case was the location of the met that urgently needed to be treated - heart and pancreas. So we picked this soft tissue met just because it was the only one in a safe location. So in you case you can start from the safest located met out of all that need to be treated and see what the next scan shows, if the rest of the mets would react as well.

[ntran727]

Thank you Olga for the information. I read online that the recommended RT to the vertebral body would be SBRT at around 8 or 15-24 Gy given in a single dose.

Here is the link: https://www.ncbi.nlm.nih.gov/pmc/articl ... o=0.943396

I don’t know which would be better in this case given that there is more relapse with the 8 Gy since we are trying to also relieve my pain. The plan is to treat one of the spinal Mets (either L5 or S1 or maybe both?) I have to ask the radiation oncologist if those are the best ones to treat or perhaps we can radiate the right iliac one which would probably be safer. I’m not sure. Would you be able to give me the name of the Dr. you spoke with or comment on which trial it is so I can bring this up during my meeting with the Rad Onc? The important thing I see is that it has to be given on the same day as the next day of my Keytruda infusion, correct? Do you think there are any limitations or additional risks because I’m also taking the TKI?

[arojussi]

As far as I know single dose isnt ideal for abscopal effect. Iasked 3-5 fractions for both mandibular and subcutaneous met. 30 gy total, but this can be a Lot for met close to a spine.

[ntran727]

Ok thanks Jussi. I will aim for 4*8 like how Ivan had it done then perhaps starting on day 1 of the next infusion. Will let you all know what the rad onc says tomorrow.

[ntran727]

Okay, so I met with Dr. Choi today. They had a tumor board this morning regarding my case. She definitely sounds knowledgeable about the topic and gave me all different angles. Essentially, not much is known about the specific doses of radiation in order to achieve an abscopal effect as mentioned in this forum. However, after gathering all of the info and reviewing the images in regards to where my bone mets are, it seems I have involvement in the L4, L5, S1 and the right iliac bone (near the SI joint). We sat down to look at the images together. She believes that the right iliac/SI joint met is the source of my pain as it is too lateral to be L4/L5/S1 and very focal. This changes things a bit as my onco was thinking to radiate the L5/S1 met as he thought that was the source of my pain. She said either we can target 1 bone met with SBRT and do 3*9 grays in hopes of achieving an abscopal effect that way or to do a smaller dose of radiation of 5*4 grays to the general area which would encompass all my bone mets in the spine/right iliac. She believes that this would also be enough to achieve an abscopal effect. The 2nd option would be a total of 20 grays vs. the 1st option of 27 grays total. She is leaning more towards the 2nd option as she believes in starting with the less aggressive approach, which she believes can cause an abscopal effect, and add more radiation if necessary later on in order to minimize toxicity so that I can better tolerate my systemic treatments with the ICI/TKI. Please let me know your opinions on whether the 1st or 2nd option is better. From what I read, they both seem to be reasonable, but I am not sure which technique would be best in my situation.

[arojussi]

This is difficult question. For abscopal effect I would use 6-8 gy fractions 3-5 times. So 9 gy 3 times is little high dose, but 5 gy 4 times little low, but there is no definitive answer, to what dose is ideal and starting to agrue about wanting 6 gy instead of 5 can just pointlesly irritate your doctors and of course you can add radiation later if you have to. So I dont know which option would be better. Basically 9x4 is more risky. As you know I have taken risky road many times and it hasnt always rurn out well.

Right before starting radiation for my brain mets I asked nurse, what dose rhey planned to use. I thought that dose was too low and said so. So radiation doses were radically chanded like 5 minutes before treatment started. Changing radiation dose is simple as it basically reguires just a click of a computer buttom. So maybe carefully ask 6 gy 4 fractions.

[arojussi]

This was in private hospital. That couldnt have worked in public hospital.

(Sorry I think I accidentally wrote 9 gy 4 times, when dose was 9 gy 3 times. I corrected that already.)

[D.ap]

Hi Nhi,

Our family isn't familiar with spine mets, knock on wood, but in reading 8 gy is being explained as the top of the spectrum? I think Jussi has a good point to ask for an adjustment?

Could your S1 pain be partly to blame on the methotrexate/cytotec acting on your utereus ? Lateral pain? Inflammation? from contractions? The increase of the s1(previously reported L5) tumor was compared to 2/27/19, correct? (1.4 x0.8 cm to 2.3 x 1.8 cm).? The scans were taken after the procedure? May 29ish?



When is your next infusion scheduled?

My heart and prayers as you make a decision .
Love

[D.ap]

On another note , it looks like the bisphosphonate ( zometa) can play a factor in the radiation reaction?

“ Zoledronic acid and radiation: toxicity, synergy or radiosensitization?“

https://www.ncbi.nlm.nih.gov/m/pubmed/23443898/

[Olga]

Nhi, while we discuss the doses, in my opinion it is more important to discuss the radiation treatment plan in general - treating concerning bone mets one by one as necessary with the radiosurgery versus covering a much bigger area at once with the radiation treatment. An advanced radiosurgery would only target the painful met in the iliac bone. As I understand Dr. Choi preferable choice is to irradiate the much larger area including all the mets with the lower dose.
What I can see there are probably two fundamental mistakes here, first - ignoring the nature of the treatment you are now on - immunotherapy, and second - the morphology of the ASPS mets.
1. Covering the larger area would affect the larger intestinal area killing the microbiome that is essential to have healthy for the immunotherapy response. The response starts in the guts. Besides the larger area covered would result bigger immune-suppressive effect overall.
2. ASPS mets are encapsulated (it is rather pseudo-capsule of the dense tissue surrounding the met formed by the slow growing met pushing the tissues aside), well defined. It does not make sense to cover the broader area as it would in any abdominal cancer spread where there are most probably undetected smaller implants in between.
My questions to the radiologists comparing two plans would be:
-what are the advantages of covering the larger area with lots of healthy tissue in between versus treating all the targets separately?
-what is the planned scattering dose to intestines in each approach?
-how would be the other abdominal organs at risk affected in each approach - including the skin, as the skin should also be protected in the immune-therapy treatments.
The location of the bone met close by the joint is concerning. It can break from the SBRT. May be consult with the cryoablation drs re. possible cryo to that met versus sbrt, I think there is some good cryo dr at the MSK now. The advantage for the cryo is no damage to microbiome.
so overall I do not see an advantage of having the larger area covered. The radiosurgery units are very advanced now and they can minimize the radiation damage to the surrounding organs a lot with the careful planning.