Corey

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Revision as of 05:23, 29 May 2017

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

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