Nhi from NY - Dx June 2016

[ntran727]

I had a meeting with Dr. Ming-gui Pan who is the sarcoma specialist at Kaiser within the Northern California region. My oncologist also spoke with Dr. Schwartz (my prior oncologist in NY). The general consensus is to resume Pembro + SBRT to the 5 growing bone Mets (Manubrium, T12, L4, L5, S2). I met with Dr. Amy Gillis who specializes in radiosurgery body and brain also with Kaiser in South SF who has an impressive background and seem to be very knowledgeable in her field. She recommended the same treat I had to my right iliac met with Dr. Choi at Columbia, 3 fractions of 10 grays each over 3 days for total of 30 grays to all of the bone Mets. The one she thinks is causing my pain is the S2 lesion which I agree with but since I responded so well to radiosurgery in the past, she recommended to treat them all before the become a problem even if no symptoms. Ultimate plan is to add Axitinib once I am able to tolerate Pembro + radiosurgery. My oncologist is very experienced with immunotherapy since she is the chair of the melanoma department and also treats RCC, lung cancers requiring immunotherapy. She thinks that if by month 3 I haven’t had any major side effects from it that it will less likely happen overall. The main concern is my grade 3 hepatitis I had from before that we have to monitor. We will scan again likely in a month since I will be off the TKI to watch for any major rebound growth and potentially to start Axitinib earlier than the 3 month period, of course with risk of increased toxicity. We did consider other options including other ICIs and TKIs and combos like Tecentriq + Avastin combo but ended up choosing Pembro + Axitinib since I responded in the past and the combo has been studied and safer to use than if we chose a random ICI + TKI. I had issues obtaining it in NY hence why we ended up doing Pembro with addition of Pazopanib instead when my Mets grew on Pembro alone. I am hoping the same issue won’t arise since I will be getting Pembro + radiosurgery vs just Pembro alone like last time which I felt made my mets grow while waiting for it to kick in. I will be preparing with diet, exercise, etc. to maximize the effects of Pembro.

In regards to finding another sarcoma specialist, I think I am ok with seeing Dr. Pan, my oncologist now with the help from Dr. Schwartz if we need him. Dr. Pan only has only one other ASPS patient who I think is active on this forum. They went through the same ordeal with trying to go outside of the Kaiser network and was denied, probably because we do have a Sarcoma specialist within Kaiser, Dr. Pan. I will ask my insurance if perhaps I can consult Dr. Schwartz if needed but I know he doesn’t mind giving his expert opinions in the future.

I am hopeful that I will have some result and limited adverse reactions.

[D.ap]

Hello Nhi,

With your LNR being as a rule on the low side , what is the reason for having the radiation first as opposed to the Keytruda ? Is that the plan? If so does the radiologist and team, feel like the toxicity will be less with that scheduling ?

[ntran727]

Keytruda infusion first, then radiation closely following likely a few weeks apart which should still allow for the synergistic effect but without doing it almost at the same time as last time which increased toxicity. However last time I also didn’t hold the TKI which according to the rad onc I spoke with can also be synergistic and with radiation and increase radiation toxicity which was the main reason for the hospitalization. The immune reactions occurred relatively soon after. So we are hoping that without the TKI given concurrently with ICI + radiation that we won’t have the same toxicity. Plan is to add the TKI 2-3 months later If and when I’m able to tolerate ICI + RT.

[D.ap]

Thank you for the clarification.

Good to hear that the scheduling is being changed up a bit. I couldn't remember the exact sequence but I do remember you were hospitalized for a good 5 days. :{

I've been reading on radiation affects on the peripheral white blood cells , specifically the CD4 suppression and how low Lymphocytes are lower ie immunosuppressed quite quickly , inthe body during the initial hours following the treatment, and then some subsequent infections follow. It was with HIV patients.
But having a melanoma / RCC oncologist is really good news to hear, as we as ASPS patients have learned a lot about how to and not to treat our similar but not exactly the same , cancers .

[D.ap]

Ps
Here’s a great article Olga posted in 2019, in refer to RCC
trials with ICIs

viewtopic.php?p=14349#p14349

The Evaluation of Response to Immunotherapy in Metastatic Renal Cell Carcinoma: Open Challenges in the Clinical Practice

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747319/

[ntran727]

Thank you for the article. Dr. Pan sent me one about ICIs as well discussing the primary and secondary resistance as well the host and tumor factors that make ICIs more successful in some patients over others. Many of the things discussed in the article such as NLR, low LDH level, high tumor burden etc. have been mentioned before but I liked that it was all summarized.

Here is the attachment link to the article:
IO Review Article.pdf[/attachment]

[Olga]

Nhi,
The plan sounds good overall but the radiologist might not pay enough attention to the immune system interaction to both, SBRT and ICI. As I understand, it is very desirable to schedule the SBRT as close to ICI day as possible and try not to get further away from it - like +/- few days, Ivan had the first treatment day on the same date - it was hard to schedule but we had a very supportive radiosurgery doctor very enthusiastic re. synergy of the two modalities and he really tried to get most benefit from it.
Also if you treat all the bone mets at once, the immunosuppressive effect from having to much necrotic tissue might be counterproductive. Is she proposing to treat all 5 of them at once? with the safety margins it is a pretty large area. I understand that she does not want to risk by the possible progression of the non-treated bone mets in case there is no response to Keytruda though, as the radiosurgery is most effective on a smaller sizes.

[ntran727]

Hi Olga,

The last time I had K + radiation very closely together like that, I had a horrible reaction that landed me in the hospital. But at that time I didn’t hold the TKI, so it was more likely to be a division of all those things. So this time I don’t want the radiation to be so close together with the ICI infusion. And yes I am also worried the untreated bone Mets will grow if Keytruda does not work. I hope it is the right decision and that I can resume on a TKI in addition to both of those two then it would be even better.

[Olga]

There were cases of the rapid progression reported when K was given not close to the irradiation cycle. It seems that the immune changes are very dynamic and different between the first days/week after the radiation and in two weeks, when there is a high level of inflammation in the treated tumor and the TRegs are recruited inside of the irradiated tumor. This is why most clinical trials combining SBRT and ICI are given close to each other.

[D.ap]

Hello Nhi,

When is Keytruda infusion scheduled ?
Love and hugs,
Debbie and family 💞

[ntran727]

Hmm now I am worried. I just got the K infusion on Wednesday and then I am going to go meet with the rad onc Friday. I’m worried about the rapid progression in that one case. What should I do? Wait for the next cycle of K in 3 weeks? That’s so long I feel like I’ll have too much growth by then, and then that would just cause more pain. I don’t think I can wait that long to not add any treatment to K. My Med onc says as long as given within a 3 month window it will potentially have that synergistic effect. She says she hasn’t seen it much to be honest. Anyway any suggestions would be great.

[D.ap]

Hi Nhi
With your Keytruda infusion under way , I feel that is a really good first step .😊
It appears as I’m sure you are aware of , that the Abscopal affect is not very well understood and consequently there isn’t a lot of medical bases on scheduling of the adjunctive and or consecutive ablative procedure, in relation to the ici infusion .

I did find this pay wall article that looks quite interesting and maybe could be discussed with your rad onc.

https://www.nature.com/articles/s41571- ... =trueInJun

Thinking of you today .
Love ,

[Olga]

Nhi hi,
Did you meet the radonc? how long does he need for the planning? you might respond to the K alone, the response might happen as soon as few days after the first infusion. How are you feeling? first 72 hours are critical for the acute side effects

[D.ap]

Hi Nhi and Olga ,
I second that thought.😊
I was recalling Joshua’s history and wanted to let you know that after taking sutent , he experienced profound increase in his lungs and thru out his body. The Sutent gave light to the amount of micromets he had in his body, as well as illicited a profound immunosuppressive reaction.😕, progression .

This was 2015

viewtopic.php?p=7910#p7910

This is where we were 2013

viewtopic.php?p=5710#p5710

My recap posted in November of 2016.

viewtopic.php?p=9775#p9775


6 months later after the sutent experience and after his weight began to return , Opdivo was given and we are where we are today.

1 year prior to Opdivo , we had SRS to 3 brain tumors and the liver tumor ablated. Then Sutent ( profound increases in lungs and tumors appeared in Joshua’s kidney gallbladder lower pelvic area. This was after only 2 months on Sutent .

I like Olga’s suggestion to Kyle that with some patients introducing the ici and or a drug, maybe all that is needed. The axitinib may set stage for immunosuppressive reaction ?
Not what you need at this juncture ?
Scans and some time given to see the results ,are defiantly your best tool I feel . When we started Opdivo back in 2016, as a group we realized that an initial 4 month group of scans was a good gage to have a look see to how Josh would react to Opdivo .
I’m glad we did, as a lot of trials ( we were on compassionate use ) had folks scanned sometimes as early as 2 months . The progression ( pseudo ) eliminated them from the Med .😕 When now , we know of those cases had the patient been able to continue , could of resulted to a successful case.

Hugs, as it truly is hard to wait and see.

[ntran727]

Those are very interesting points. Can the ICI work that quickly? Within just a few days? I got the infusion Wednesday, felt a slight itching that resolved after 30 mins or so, then was completely fine the rest of the day with no side effects. Next day, same. Then Friday and Saturday morning I was woken up by pain to my right sciatic nerve at around 5am and then couldn’t get back to sleep because it hurt to lay on it and hurt in whatever position I was in. Then all of a sudden today I work up with no pain, and did a lot of activities I normally would do due to fear I’ll have pain going to bed. But despite how active I was, I really have zero pain. It’s so weird how it just comes and goes and then disappears like that. I have also been swimming almost everyday for the past 4 days for cardio exercise. I had to stop running/walking due to the impact on my spine causing worsening pain. The SBRT is scheduled 3 days in a row 6/22, 6/23, and 6/24. Are you suggesting that I don’t do the SBRT and wait to see if I have response to Keytruda alone? Are you both saying that adding radiation and TKIs can potentially cause an immunosuppressive effect which would then work against the ICI and make the cancer worse?