Corey
From Computer Tyme Support Wiki
This is a discussion between Marc Perkel and Corey Zandowsky of Varian who makes the Varian ration equipment used by Kaiser. Corry is the guy who designs the equipment.
https://www.varian.com/about-varian/leadership-and-governance/executives/corey-zankowski-phd
Contents |
My Initial Email
Hello Dr. Zankowski,
This is somewhat of an unusual request coming from a cancer patient, but I'm very high tech and hope to get your interest.
I am a patient at Kaiser and I have stage 4 NSCLC lung cancer. I talked my oncologist into trying something experimental as I am facing certain death otherwise. Have you heard of the "abscopal effect"? If not you can Google it but the idea is to use immune system stimulators with radiation to cause the immune system to recognize cancer as a target and go after it.
The abscopal effect has been noted a lot retrospectively where a patient is getting immunotherapy and then gets palliative radiation to stop a tumor from bleeding and a few month later the patient is cancer free. My goal is to try to trigger this effect. Kaiser is using your product and that's why I'm contacting you.
As I said, I'm high tech. I'm not a doctor but I learn really fast. My theory on what is likely to trigger the abscopal effect is not to try to kill the tumor but damage it in a very specific way. What I'm looking for is a pattern of radiation damage that puts necrotic dead cancer and dying cancer in contact with healthy tumor tissue so as to allow good interaction between the white blood cells and damaged and dead cancer tissue. I'm thinking that the damage should be towards the center of the tumor so that the collateral radiation damage will still be mostly within the tumor.
I have asked Kaiser for this and they say they understand what I want and can do it. I am contacting you however because I think the geometry of the radiation is very important and this technique has a good chance of working. I am wondering if you and your engineers want to get directly involved in planning a radiation geometry specifically to trigger the abscopal effect? If this works it will be very popular.
Marc Perkel Random Genius Gilroy CA.
Corey's Initial Response
Marc, I am sorry to learn about your diagnosis and I know how difficult it is to navigate the technical and medical fields to find the right option. Thank you for reaching out to me, and I hope that I can provide you some more understanding about the abscopal effect. Kaiser in Northern California has a very good radiation oncology organization, so you are in good hands.
We are very familiar with the abscopal effect, and you are correct that it is currently something about which we hear a lot recently. I am copying my colleague, Dr Deepak Khuntia who may be able to explain the effect in more detail. You seem to understand the concept very well. What we understand is that when a large enough dose of radiation is given to a tumor it is able to release a spectrum of dead, dying and damaged tumor cells along with their contents. These bits of cells lose much of the "cloaking" benefit they receive when they masquerade as normal cells, can are detected by the immune system. With the right type of immunotherapy agent, you can alter the immune system's self-regulation mechanism that normally prevents it from attacking tumor cells and it develops antibodies that circulate throughout the body attacking abnormal cells (hence the term "abscopal"). In some cases a second immunotherapy agent is used to cause the immune system to go into overdrive.
With respect to the geometry and targeting of the radiation, you are correct that it needs to be done carefully. For stage 4 NSCLC it isn't possible to irradiate every cancerous lesion because your body could not tolerate that much dose. I have heard of clinics treating the main tumor to a palliative dose (to reduce symptoms and discomfort that you feel), and to target small metastatic lesions with very high doses to stimulate the abscopal effect.
I will tell you about something that isn't generally known, but that Dee and I have started to hear about. You should discuss this thoughtfully with your doctor. The immune response is mediated by t-cells, which are very sensitive to radiation. The larger the volume of your body that is irradiated, and the longer the irradiation time, the higher the likelihood that the treatment actually impedes the immune response. You may be better served irradiating a few small lesions that are furthest away from high volumes of blood flow, with the highest dose rate available on the machine (flattening filter free, 6FFF or 10FFF, where 6 and 10 refer to the energy of the beam 6 and 10 mega-electron volts, respectively). The highest dose rate comes from the 10FFF, but the energy is selected often by the depth of the lesion below the skin surface. 10FFF is more penetrating.
Now, we employ some excellent dosimetrists who make the radiation treatment plans, and I'd be willing to have 1 or 2 of them look at your plans as long as you sign a consent form. But the treatment strategy needs to be decided by you and your doctor.
Please understand that today, the abscopal effect is not well understood, and there is no guaranteed method to achieve it. But we don't always need to know how it works to make it work.
Regards, Corey
My Reply
Hi Corey,
We are definitely on the same page with regard to everything you said.
the plan is to target the very center of the main tumor only with a high dose of radiation and create a pattern where there is a variety of dead, dying, wounded, and pissed off tumor but right next to good healthy tumor so as to create interaction between the immune system and the cancer. And - as you said - to not create a radiation burden that would suppress the immune system. I explained that my main tumor was going to be a "school" and not a "battlefield". I walked to the radiologist and their "chief physicist" and he sounded like he understood what I wanted.
However ....
I have had an unusual life and, quite frankly, I'm a lot smarter than most people. And it's not unusual for me to be far ahead of the experts. So I had already figured out most of what you are talking about, but you do have some new details that seem helpful. And I'm smart enough to email the people who designed the equipment figuring you had a deeper understanding - which you clearly do.
I have some license to do what I want because the first round of treatments I took were also a home brew cocktail of several drugs targeting RET fusion where I repurposed a thyroid cancer drug for lung cancer (Caprelsa) with Affinitor and 4 other substances. And it did rid me of RET fusion cancer. But I have non-ret-fusion cancer left.
Immunotherapy was always going to be my second line but I have no PD-L1. Then I ran across the abscopal effect which seemed perfect.
I understand that no one knows how to trigger it. So my job is to figure that out. But everything else about the abscopal effect is somewhat well understood.
My idea - try everything till it works. If I get it to work - I win.
I got an infusion on ipilimumab Thursday and starting radiation Tuesday. I'm thinking about getting nivolumab next thursday. Also going to try some hypothermia too and whatever else I can come up with. Then wait a month and try something different.
But ...
this is where I'm hoping to get you interested.
I think the key to triggering the abscopal effect is the geometry of the radiation. And I think you also have figured that out. I'm thinking something like disks of 2 dimensional damage near the center of the main tumor. I'm interested in the geometry you envision if you were going to trigger the abscopal effect in an 8cm tumor.
What would you design? And would you work with my team at Kaiser.
I think this has a reasonable chance of working, especially with the right talent involved.
Interested?
His Reply
Marc, I'd be interested in trying to help out. Dee is a practicing radiation oncologist with a great network, so we could bring a lot of talent to the table. You take the lead and we'll help as much as we can.
A 2-3 cm spot should generate enough damage to trigger the immune response without over-exposing too much healthy tissue, including the blood cells. I'd say the geometry is key to sparing healthy tissue. The total dose in a single fraction is more likely the key to triggering the abscopal effect. From what I've read from Zvi Fuks at Memorial Sloan Kettering in NYC, you want to deliver between 18-24 Gy in one shot. (A normal course of radiation is given in 30-40 shots of 2 Gy, so 18-24 Gy can freak out a lot of oncologists.)
Let me know how we can help, we're here for you.
Regards, Corey
My reply
What I'm thinking is that the right radiation pattern to optimize for abscopal is very different that that of any standard treatment. The idea is to create shock and damage to get the tumor to send danger signals. I want to make the tumor look like an organ transplant. I want it to feel like it was beat up by the mob.
I think you know what I'm talking about and you could develop a radiation protocol specially to create that effect.
This is doable.
His Reply
Marc, I think we can deliver almost any pattern that we need. We need to combine our heads to develop the right dose distribution that gets you some frighteningly high doses to some small active volumes. The penumbra, or normal dose gradient will create high to low doses that will create a spectrum of damage to the tissues, releasing a lot of antigens for the immune system to grab.
Let's do it!
Corey
My Replies
Also ....
All cancer are cells that somehow escape the immune system. So the immune system is the key to going all the way to a complete response. Also - I have no illusions, and I understand that what I have is considered short term 100% fatal, and the chances of a non-doctor like myself of figuring out how to cure it is a long shot at best.
But ... this is not that unusual for me as I'm used to doing things others consider impossible.
And ....
This abscopal effect almost seems too good to be true. It's like finding a football laying on the 1 yard line and walking it across the goal. All the had work is done. It's like it's just sitting there and all I have to do is trigger it.
How hard can that be?
For example - if you had a bad radiation machine, I could repair it. And I've never seen it. How? You have a service manual and start swapping out parts. And I could make good guesses about which ones to swap out.
The abscopal effect is the same thing. We understand that one of the steps is the bringing together of the immune system and dead cancer. That's all about geometry. so we (you) can create a pattern that optimizes just on creating that kind of contact.
Once that is done we try all the drugs and all the timing till we get lucky.
I have no idea if this will work for me. But I'm convinces that if we took 100 people and tried this that a lot of them walk out cancer free.
So ....
The solution is just sitting there. All we have to do is pick it up and claim it. To me - this almost looks too easy.
What am I missing?
What I'm thinking is that the right radiation pattern to optimize for abscopal is very different that that of any standard treatment. The idea is to create shock and damage to get the tumor to send danger signals. I want to make the tumor look like an organ transplant. I want it to feel like it was beat up by the mob.
I think you know what I'm talking about and you could develop a radiation protocol specially to create that effect.
This is doable.
Obviously you are both a doctor and an engineer. I'm more in the engineering world. I see this as an engineering problem. I think the geometry can be calculated and we (you) can publish pattern files for anyone trying the abscopal effect.
In my case I'm looking to try and get lucky and they can figure out why it worked later. And this can work on a very wide variety of cancers. I see this as something that moves the needle.
First I want to say that I can not thank you enough not only for answering my emails, but understanding what I'm talking about. That's rather amazing. I feel like you totally get the abscopal effect like no one else I've talked to.
But there's a scheduling issue.
Last Thursday I got an infusion of ipilimumab and I'm scheduled to get my first radiation treatment on Tuesday. I don't know what kind of treatment they came up with because it's not traditional that they share that with the patient. But - I do have CT scan images and feel free to share these with anyone. These images are about 2 months old.
So I'm hoping they have something that's good enough for a first try. But I want to make your protocol my second attempt. I'm concerned that I don't want to waste a try because of delays.
Do you agree?
Also - I won't be able to contact anyone until Tuesday morning and they probably have work backed up. So I'm thinking I go with the flow on Tuesday.
I also want to say that I'm willing to sign anything that you need signed. These are my choices and I take full responsibility for these decisions. This is all a guess and I'm guessing that you are in a position to make the best guess - even if you turn out to be wrong. And I'll keep confidential any sensitive information that you don't want disclosed.
I am 100% sure that my team at Kaiser would be very interested and thrilled to work with your team. My oncologist is a very sharp doctor and he has always been willing to go along with anything that makes sense. My radiologist is very interested in this as well and she goes out of her way to educate herself and to bring in her "head physicist" to meet me. So I think they would be very cooperative.
And then there's me and I learn very fast. I think so far outside the box that I don't even know what the box is or how anyone git in it in the first place. My background is electronic repair and design, computer hardware and software design. I'm self taught and self employed in the junk email filtering business. Sort of an electronic version of the immune system. I tend to think big and they idea that I'm not a doctor and trying to cure cancer is not something I see as an issue for me. And I'm hoping that you also see this as a solvable problem.
I personally not only think beating cancer is doable - but the solution is just sitting there waiting for someone to do the last step - just trigger it. And that looks to me like one of the easier steps. I think that this should be solvable with the right minds and I feel like you really get it as to the geometry part.
I'm available as well over the next 2 weeks. Let me know when your free and I'll be there.
His Reply
Marc, I am a medical physicist by training, not an oncologist. Dee is the oncologist, and I think he should be a part of this conversation because we work closely as a team-- and I cannot prescribe radiation.
I certainly don't mind you sharing this conversation with your oncologist and the radiation team. They should working closely with your immune-oncologist in order to get the sequencing of the treatments just right.
To answer your question about coming to Palo Alto, we can arrange something, but we'll need to see your treatment plan and the CT images from your oncologist. We could share a screen and review your treatment plan together that way.
I am in town for the next two weeks, with some half day meetings throughout, but should be able to juggle a few things to make some time. Let Dee and me know when you've talked this over with your care team, have them send us the treatment plan and images to look at, and we'll all review together. On the Varian side, we'll also have to enlist one of our dosimetrists who is expert at designing treatment plans. All together we'll come up with a great strategy for you.
All the best, Corey
