Jussi from Finland - Dx 2008 - 30.3.1991 - 23.8.2019 R.I.P.

[D.ap]

And certainly just go to sleep
As we can discuss when we are “upright
And mobile “
My children’s grand father , by marriage , was a wise man pointed out many years ago .:)

[arojussi]

Extreme mucle tension in my shoulders and neck today. Especially left srernocleido mastoid muscle. My right latissimus dorsi was removed, so muscle tension in my right side wouldnt be new, but pain in left side also is weirld. Simpliest explanation that Ican figure out would be immunotherapy related muscle pain. Rheumatic IAES seems to be associated with improved response rare, so I am most likely just trying to convinge myself that I am responding. Subcutaneous met shrunk 3 mm before radiation and smaller tumors seem to react faster than bigger ones or at least responses are easier to see. Also pedicardial effusion is virtually gone. Amount of fluid in my pericardium looked practically normal in last cardiologist visit. Heart rate has come down. It is now between 80 - 90 bpm. To me less than 80 bpm, would be a reason to suspect hypothyroidism. My best time in 2.3km in sawdust track is now 29minutes and 5 seconds. Have to be little carefull, because of my hip. In sptember we will know if this has all been just a giant placebo effect. For muscle pain I stiil use 800 -1600 mg of ipubrofen almost daily and lots of massages.

[D.ap]

Hello Jussi
Is the srernocleido mastoid muscle issue associated with any exercise and or repetitive motion?
Weight lifting and or any light acrivity ?

Was it relieved after you took the ibuprofen ( with food:).

Do you take your ibuprofen at one time or over the course of the 24 hour period ?
Prob start with 800mgs..

[arojussi]

I take 800 mg tablet of ibuprofen when needed. Average one tablet before bed. Sometimes more sometimes less.

[arojussi]

There hasnt been any changes in my exercise regime or any other changes in my life. If there would be even finiest change in my lifestyle that would be most likely explanation, but there isnt.

[D.ap]

No exercise changes
However you are on
Opdivio / Ipilimumab and or yervoy : )
As you pointed out . Possible IRAEs

Ibuprofen is pretty fast acting .. so you feel the pain then take it?

Is the pain continuing after taking it ?
How often do you need to bump it to 1200mg?
How long after infusion did u notice it happening ?
It’s all very important to note .
To document .
There is so much to learn about ICIs
Hope you feel better

[arojussi]

First heart symptoms appeared yesterday. After 2.3 km jogging I developed heart rate of 190. It is little high. So to the er. Supra-ventricular tachycardia was final diagnosis as I remember. Electric shock to bring my heart back to rhythm and monitor me over the night and relatively speaking I am fine. Beta-blockers were Started.

[arojussi]

It might have been ventricular tachycardia. It it makes more sense as my tumor mostly surrounds left ventricle. Have to check that.

[arojussi]

Yes it was ventricular tachycardia.

[D.ap]

Hello Jussi
So Glad to hear you got the problem checked and are feeling better .

Were the staff knowledgeable about ICIs and possibly side effects?
What was your BP and heart rate at resting rate ? After the 190 hr?
You said that 190 was alittle high, what have you seen in numbers after a run ?
Did you receive a diuretic as your beta blocker ?
And or propranolol , metoprolol?

Here’s an interesting mice study on beta blockers and ICIs
https://www.roswellpark.org/media/news/ ... -park-team

And an ASCO April 2018 release

https://www.medpagetoday.com/reading-ro ... rapy/72430

Also as you are an avid runner ,I’m sure you are aware aware how running effects the HR before / afterwards and it’s affects are alot like what the med( beta blocker) ultimately creates when ingested .
Just be careful :/

The below link was very descriptive to that fact -

“

Concerns About Exercising While on Beta Blockers
It’s important to remember that your heart rate is being slowed, and to adjust accordingly if before you took these drugs you monitored your exercise using heart rate,” said Dr. Fletcher, who is also a volunteer with the American Heart Association.

“Don’t overdo it trying to get your heart rate up to previous levels,” he said.

There are a couple of ways to monitor your exercise intensity.

If you have been using a target heart rate to get to the right intensity, your healthcare provider can help to determine your new target heart rate using a brief exercise stress test . This test is used because beta blockers affect everyone differently.
The second way to monitor your intensity is simpler: making sure you’re not too exhausted.
“Exercise hard – to the point of being tired – but not excessively hard,” Dr. Fletcher said. “If you reach a point where it is hard to talk, that is probably too much.”

http://www.heart.org/en/health-topics/c ... t-exercise

[arojussi]

Beta Blockers May Enhance Immunotherapy Response in Advanced Melanoma

So in my situation beetablocker is indicated for my heart, we should choose b-blocker that has best changes to synergise with immunotherapy. Based on this Propranolol looks most promising and most studied so I would go with that. selective beta1-blockers look like the worst option. I should definitely choose pan betablocker. Selective beeta2-blockers might work. However Propranolol looks like most studied and therefore the safest.

[D.ap]

Absolutely propranol has been studied more. I’m not sure but maybe it’s been on the market longer ?

Has your oncologist weighed in on your recent
happenings ? Propranol may have more side effects?
Are you going back on cediranib ?
The reason I ask is the very first and only time Josh took a tki( sutent) he was on propranol for tremors .
He had severe progression in his lungs and adrenal/kidney area. :/. It was discontinued
It could of been because of his prior liver cryo 4 months prior?? Started sutent 4 months later. On it 6 weeks and had to discontinue .
Nhi thought liver values were off possible cause ?
He of course had 2 lower more the 3cm tumors in left and right lungs .

It’s my understanding that the beta blockers ultimately create larger volumes of blood flow? So my thought ,maybe medicine delivery may be exponentially increased ?especially when using TKIs , when they are known to normalize vessels . Especially at the ASPS tumor site ?

[Olga]

There is the other info from this article that Deb posted re. beta blockers and ICIs is very relevant, regardless of the beta blockers.
That the prolonged exposure to these stress often makes our immune cells much less effective: beta-2 (β2) adrenergic receptors, molecules present in the cells of humans and other mammals, control the functionality of key immune cells. In response to stressors, these receptors turn on the “flight or fight” response. They generate more of the stress hormone norepinephrine, buffering normal cells from some damaging effects but also impeding the immune system’s ability to fight cancer. The response is the same to diff. type of stress - such as fear and anxiety, heat, cold, pain, depression and even attack by cancer cells.

I will make a separate post about the need to limit/control the stress in the ICI practical issues topic.
Perhaps the running now is to much stress for your heart in its physically limited condition?
Reducing adrenergic signaling is an interesting option.

[Olga]

Also it can definitely get worse before it gets better as a treatment related effect - this was my big concern when we started Keytruda with Ivan, and I consulted extensively with the cariologists/surgeons what could be done in the case the tumors swell due to a treatment effect if the immune cells attack the heart tumor and accumulate in that area. Sometimes it looks like a pseudoprogression on the scans. Inflammation surrounds the tumor and it is reasonable to assume it can affect the organ functionality initially, before it gets better, so the high degree of caution should be used initially.

[arojussi]

Thanks. Those words mean a lot to me. That is almost exactly what I said to my dad and myself, when first respondents came to take me into ambulance. Also immune reaction in tumor growing from left side of the heart would most likely irritate the heart, even if tumor doesn't look bigger. Oncologist actually said that side-effects could be worst after 3. Infusion and indeed my shoulder and neck tensions are extremely painful. Makes sense that inflammation in the tumor itself would be worst after 3. Infusion. Effusion is still cone. Logically it looks realistic, that immunotherapy might be working and having huge immune reaction happening right there in my heart, just messed up Heart`s electrical system once. Of course these things can happen again and they can kill me. But if ai die at least I die exactly like I always wanted. Of course I need to take it easy for now, while immune reaction is happening n my heart.