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?
Can you possibly wait till after your next Keytruda infusion ? Then schedule your SBRT ?
How long have you been off pazopanib now ?
What kind of scan sched will you be on?
My closing thought is I can only image, how extremely scary this is for you . However you have to use this time to boost your immune system with everything you’ve got available . As well as be able to eliminate the most offending tumor you have at this moment at the your window of opportunity , and at its smallest size.
The use of Keytruda and SBRT till further need arises would create the best cost / benefit , in my opinion .
Q.“Can immune therapy work within a couple days ?
A. Clinically I would venture to say that inflammation certainly can and could start immediately . Then consequently the immune response begins .
Q.”Start Tki”
A. I feel as I’m understanding Olga is saying , wait and see what your scans that are scheduled, tell you . Hold off on axitinib.
There are articles re. what is happening after irradiation from the immunological point of view that show, that adding SBRT should be done at the right moment around ICI cycles (as Keytruda removed the breaks from all the components of the the immune system you want them to be removed at the right time) and in the volumes that are not immune suppressive - large amount of the necrotic tissue is immunosupressive. AS of now based on the schedules in clinical trials, the most safe is considered concurrent one with another i.e. +/- 3 days. I would irradiate one met on the dates close to the next K date as we have done (Ivan had it on the second K date, started the same day and proceeded every other day after, 4 treatments in total, each at 8 GY).
Ivan felt the response to K very soon, he started to gradually feel better almost immediately as his heart met started to regress. I read the blog by Brittany Sullivan that her subcutaneous met was regressing visibly very soon. Your first encounter with K was a very dramatic one so there are reasonable expectations it is active in you, just be careful.
In your case the met is in the bone, it can expand a little with the inflammation as the immune cells arrive to eat it, initially and then it should get better.
Olga wrote: ↑Mon Jun 15, 2020 11:03 am
There are articles re. what is happening after irradiation from the immunological point of view that show, that adding SBRT should be done at the right moment around ICI cycles (as Keytruda removed the breaks from all the components of the the immune system you want them to be removed at the right time) and in the volumes that are not immune suppressive - large amount of the necrotic tissue is immunosupressive. AS of now based on the schedules in clinical trials, the most safe is considered concurrent one with another i.e. +/- 3 days. I would irradiate one met on the dates close to the next K date as we have done (Ivan had it on the second K date, started the same day and proceeded every other day after, 4 treatments in total, each at 8 GY).
Ivan felt the response to K very soon, he started to gradually feel better almost immediately as his heart met started to regress. I read the blog by Brittany Sullivan that her subcutaneous met was regressing visibly very soon. Your first encounter with K was a very dramatic one so there are reasonable expectations it is active in you, just be careful.
In your case the met is in the bone, it can expand a little with the inflammation as the immune cells arrive to eat it, initially and then it should get better.
After considering all my options, I decided to keep the treatment schedule as they were to minimize any potential adverse reactions that may disqualify me from taking pembro in the future. Here is the recap:
6/10 - 1st Pembro infusion 2mg/kg (~95mg), no side effects
6/17 - Zometa infusion: developed horrible headache, dizziness, extreme fatigue, muscle aches/cramps, neck pain for about 48 hours. The neck pain and muscle cramps carried on for almost 5 days. Was told this is worse the first time you get it. Now makes me think that when I got it last year, this drug was responsible for many symptoms.
6/22, 6/23, and 6/24: SBRT to 5 sites (manubrium, T12, L4, L5, S2), about 28-30 grays in total at each site. Had some fatigue but otherwise tolerated well. Only required ibuprofen for pain and did not take decadron
7/18: Had 6 week CT chest to watch the lung nodules since they were the only area not yet treated. Had 1-2 mm growth in 4 out of the 15 lung mets, no new mets. Decided to continue on pembro alone and held off on adding axitinib
Back pain improved but stiff. I started to swim about 4 days a week, about 40-60 laps around my pool. Then for the past 3 weeks, started daily meditation, yoga and/or swimming for at least 30 minutes daily, and went on all vegan diet, mainly raw but some cooked. It felt so good my back pain went away completely after just 1 week of doing it. I started juicing this week as well to supplement my diet. I lost only 3-4 lbs and have been able to maintain my weight with plant protein and whole grain foods like oatmeal, brown rice, etc. I also quit caffeine and marijuana (which I would smoke sometimes at night to help with sleep). The first few days was rough but the meditation helped me through it. I was able to get back to yoga almost the same as before the pain and have gotten much more flexible and mobile. Before I used to have shooting pain down my buttock every time I would bend over, now I can bend and touch my toes again without any problem. I can also go for walks now without pain. Basically I have no pain anymore, just numbness on my left glute when sitting for too long. I scheduled an appointment with a naturopathic oncologist to gain more insight into lifestyle medicine so I can best support my body through the treatments.
I have had 3 more doses of pembro, still with no side effects. The 5th dose will be on 9/2.
8/26 - MRI brain - stable skull mets x 2, however new 7x5mm bone met adjacent to my previously treated bone met in the clivus (which caused my tongue dysfunction previously).
8/29 - CT neck, chest, abdomen, pelvis: all stable bone mets including the treated (manubrium, T12, L4, L5, S2) and untreated areas (sternum and punctate lesions in T5, T6 and T11); Lung mets: 1-2mm growth in 8 out of 15 lesions, largest 1cm and 1.4cm. Others are still all under 1cm.
It is decided that we would treat the new skull met due to its location. Will speak with the rad onc but likely gamma knife as before.
My oncologist suggested to add axitinib now but would also be ok with waiting longer if I wanted.
I agreed on starting axitinib with hope for some synergistic effects since the lung mets are clearly growing.
The SBRT seems to work and stabilize disease, so that will likely be my go to treatment for any problematic bone met.
I am thinking maybe this time I could time the gamma knife with the pembro infusion.
I am still doing the weight based pembro infusions which is half of the regular 200mg dose. She does not think it's wise to give me 200mg.
Sorry for the lengthy details. I hope this is a good plan. Any input would be greatly appreciated.
Hi Nhi.
Thank you for the detailed update. We were wondering how are you doing, and it is good to hear that unlike first time disastrous pembrolizumab attempt, you are doing so much better this time. It is hard to say whether adding axitinib to your treatment plan is going to be beneficial. There was no separate trial for the K alone versus K+A so really hard to say. May be try to go slowly, not to overload the immune system with the axitinib side effects. As you realize, the overall health is important in accruing and maintaining the immune system response to sarcoma. The slight increase in some mets might be caused by the inflammatory changes from the immune infiltrates, not the actual mets growth. Perhaps, go for one more cycle of the K only especially if you get to treat the head met with the radiosurgery at the same time. What is the blood work numbers - NLR?
I was thinking the same, hence my hesitation to start axitinib. If it did work, it would only be for a short period of time until I became resistant again and I cannot rely on the TKIs alone. My goal is to get the immunotherapy to work. However, it is difficult to know if K is working for me or if my mets are growing at its normal pace, about 1mm a month on average for the lung Mets. They are still small and not problematic, so I feel waiting a few months will not be the end of the world to see if my lifestyle changes will help boost the immunotherapy effects. I could also time the radiotherapy treatment with K this time around (Which would be with the next cycle on 9/23). My oncologist said we would rescan at 2 months if I chose to hold off on axitinib. I think I will do that since I know my body is going to struggle with the side effects of axitinib and it would be harder for me to maintain my health at this level. The only thing is that I have read about the synergistic effects of the TKIs and Immunotherapy in combination. What do you think about that? There are also the CTLA inhibitors like yervoy that is unlocks the brakes at an earlier level to unleash the immune system and therefore allow the PD-1 and PD-L1 inhibitors to kick into gear. But because of it working earlier, it tends to cause much more side effects. Dr. Wilky told me she does this for some patients resistant to the PD-1, PD-L1 inhibitors. This combo of yervoy + opdivo worked well for Carolyn Cave who had multiple lung and bone Mets. That would probably be my next plan if this didn’t work.
My numbers are looking good. NLR between 1.5-3. LDH is low along with my other inflammatory markers. I am actually off my thyroid medication as well with a normal thyroid function testing. Calcium hovers around 9.4 so relatively normal. I am continuing on Zometa as well q3months.
Nhi, there is obviously a synergistic effects of the TKIs or CTLA inhibitors and Immunotherapy in combination in some patients. That comes at the cost of the increased toxicity and it is unknown if ASPS patients might have responded better to a single drug due the increased toxicity of the combination. I know that combining TKI with the radiation therapy increases toxicity for sure so it is reasonable to go trough this cycle as it is hoping the immune system will recognize the ASPS cells as they will be damaged trough the radiosurgery treatment.
With your SBRT treatment, did you experience much swelling and or did you have to take any steroids prior ?
When will you rescan for your SBRT results ? They were stable after 8 weeks ?
6/10 - 1st Pembro infusion 2mg/kg (~95mg), no side effects
6/17 - Zometa infusion: developed horrible headache, dizziness, extreme fatigue, muscle aches/cramps, neck pain for about 48 hours. The neck pain and muscle cramps carried on for almost 5 days. Was told this is worse the first time you get it. Now makes me think that when I got it last year, this drug was responsible for many symptoms.
6/22, 6/23, and 6/24: SBRT to 5 sites (manubrium, T12, L4, L5, S2), about 28-30 grays in total at each site. Had some fatigue but otherwise tolerated well. Only required ibuprofen for pain and did not take decadron
7/18: Had 6 week CT chest to watch the lung nodules since they were the only area not yet treated. Had 1-2 mm growth in 4 out of the 15 lung mets, no new mets. Decided to continue on pembro alone and held off on adding axitinib
“It is decided that we would treat the new skull met due to its location. Will speak with the rad onc but likely gamma knife as before. “
Question
Could the skull met being seen possibly be collateral damage from the SBRT?
The 1-2mm could be a difference in viewing of radiologist huh ..
You’ve been on Keytruda for about 4 months now?
5 cycles?
My radiation oncologist talked about giving me decadron prior to treatment and even after, but I decided against it. Out of the 5 locations I had SBRT to, only my sacrum met caused discomfort leading to numbness in my whole left buttock/leg, shooting pain, and caused me pain. Despite that, I treated it with ibuprofen, and only took it on and off for a week after radiation. I did not need the steroid. The pain seemed to get better, then it came back again about 1-2 months out. Had more severe pain which was limiting my function. I then decided to start meditation (1 hour a day), eating a mostly whole plant, vegan and inflammatory diet, and added more yoga each day until I regained my flexibility and function. It only took 1 week until my back pain was completely gone. I now have on and off numbness only. I also started juicing, about 60oz a day to supplement my meals. Have only lost 3-4 lbs and since then maintained my weight.
In regards to the skull met, it was a new one that grew near the one I had last year when I had gamma knife along with SBRT to the right iliac lesion. All of the previously treated sites have been stable. The recent SBRT I had in June were for the new 5 sites that were growing as I listed them in my post, which are all stable with the recent scans. So the only mets growing are some of my lung mets, about 1mm growth per month on average plus the new skull met I will be getting treated. There are no other new mets.
I will be getting my 5th cycle of pembro today.
The lung mets have definitely grown in size steadily since they were all smaller than 9mm, and now the largest is 1.4cm and I have another that has reached 1cm, so I don't believe it is a difference in viewing of the radiologist.
I think that the SBRT worked to control my bone mets, and that the lung mets are just growing as they are, meaning pembro has not fully kicked in yet, hence why the need to add axitinib.
The lung mets have definitely grown in size steadily since they were all smaller than 9mm, and now the largest is 1.4cm and I have another that has reached 1cm, so I don't believe it is a difference in viewing of the radiologist
I guess I was talking about the comparative scan /base scan , prior just to beginning pembro?
The clivus is currently 7.5 mm
What was it when you began pembro ?
How much volume of tumors were treated with sbrt to obtain margins ?
Keeping your inflammation markers down bloodwork and symptom wise , is very impressive !
Arthritis aches doing ok?
What is your current tumor load/volume , being figured ?
Treated and non treated?
I’m with Olga in adding yervoy , it’s truly a toxic Med and hard on a person .
Please consider the cost / benefit .
As with the naturopath , be sure and give she or he all you have for info on ASPS.😊
I’d be happy to share what we gave our naturopath 5 years ago .
The scans at the start of Pembro did not show the skull met. It is new from the 3 months scan, adjacent to my previous clivus lesion, measuring 7x5mm in size. So that is concerning it just popped up, meaning Pembro isn’t working alone.
I am not sure how to determine the volume of tumor treated, but they were all between 1.5-3cm in size when treated.
I don’t have any arthritis pain, that was only last year when I had the bad reaction and it went away after a few months of stopping Pembro. I don’t have any pain now.
In terms of tumor burden, I currently have the 15 lung mets I started with 4 years ago, varying between 2mm to 1.4cm, mostly around 5-7mm. Then I have now 3 skull Mets (2 treated and 1 untreated), Manubrium, T12, L4, L5, S2, and right iliac varying between 1.5-3cm which were treated, and punctuate lesions too small to measure in T5, 6, and 11 which have been stable without treatment.
The next step would be adding axitinib and not yervoy but I did just mention it there as a last resort. I spoke with my oncologist and we planned to hold off on axitinib for now with plan to do gamma knife to the skull Met. This time I want to time it with the next infusion, so might not even add axitinib until the cycle after that.
Update on my 3 months scans after adding Axitinib:
Bone Mets are all stable including the numerous lesions in the spine, manubrium, sternum and skull. Unfortunately the lung Mets are still steadily growing, most by 1mm in 3 months but others by up to 4mm change, largest one being 1.3 x 1.5cm. Many have reached 1cm. There are still only 15 nodules and no new bone or lung Mets. So I guess you can say it’s relatively stable.
To recap, I have been back on Keytruda after switching from Votrient 6 months ago alone and then added axitinib 3 months ago. I have no side effects and tolerating the complete dose. I am getting weight based 2mg/mg Keytruda though and not the 200mg. I had minor symptoms the first month of axitinib like fatigue and sensitivity in my hands/feet which went away completely.
My functional status is good and I continue to exercise everyday like yoga and other forms of exercise like walking, HIIT work outs and hiking. I’ve changed my diet completely in the last 6 months and eating very clean. I’m also meditating daily which I think really helps me with my function, pain and positivity. Prior to doing all these lifestyle changes, I could barely stroll my kids around or bend down to touch my toes because my back was in such bad shape. I’m just happy to be living a very normal life without side effects.
I haven’t seen my oncologist yet but don’t think she is going to want to change treatments. I also asked Dr. Wilky who thinks I shouldn’t rush to change it. My question is if you think I should ask to get some of the lung Mets cryoablated or just wait to see what happened with the next scans? They are definitely growing very slowly.
It sounds like your approach to more mobility is truly well rounded plan !😊
In regards to your lung tumors , I’d consult Dr. Auon and Dr.Littrup on what ablative technique to use on your tumors. They are both incredibly well versed with ASPS.
Hi Nhi,
as the cryoablation techniques work better with the certain sizes, I would def. cryoablate couple of biggest/fastest growing ones - right now they can be completely ablated with confidence and minimal side effects. It could provide the in situ vaccine to improve the immune recognition for the rest of the lung mets, as an abscopal effect.