Cancer Tissue Testing: A Patient's Guide to Molecular Profiling

eyond knowing which proteins are present, which could help predict therapy effectiveness, such as chemotherapy sensitivity, effectiveness of drugs, such as antibody drug conjugates, and immune system dynamics. For example, Brian has

“Brian McCloskey’s Tissue and Testing” (Brian McCloskey) [#22] elevated levels of a biomarker (TDO2) which creates an immune suppressive environment. ●Functional testing : While functional tests that try out drugs on fresh tumor tissue “ex vivo” could provide confidence in choosing drugs that perform well, including drug combinations, Brian’s oncologist doesn’t trust these tests.

●Spatial analysis: Brian’s oncologist is unenthusiastic. Brian is looking to align with his oncologist on these tests, or find another physician, to push the envelope in trying innovative tests.

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You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health.

“Brian McCloskey’s Tissue and Testing” (Brian McCloskey) [#22] Meeting Notes Brian McCloskey: I'm reaching out to you because I need your collective wisdom to help me navigate a really important part of my journey. My cancer is growing in the soft tissue of my peritoneum. That's the bad news, just the way it works.

The good news is that it's going to present an opportunity for me to collect tissue. And so the reason why I want your help is that I need to figure out: what am I going to do with this tissue? There are lots of different ways that tissue can be used, and it's a precious resource.

I want to make sure that I am using it to do a couple things: one to make sure that I get greater depth of understanding regarding my cancer, and the second is to inform my treatment decisions. Some of you may be more familiar with my journey than others. I want to make sure that everyone’s on the same page. My journey started in 2016. I had a prostatectomy. We thought we got it all. We didn't.

I had a biochemical recurrence and started first line androgen deprivation with Lupron. I got radiation. That took me all the way through to 2018, when I went on a holiday. You can see that I had a pretty significant spike. I had a Gleason nine. That might explain the rapid rise in my PSA.

“Brian McCloskey’s Tissue and Testing” (Brian McCloskey) [#22] I started apalutamide and saw an immediate response from that. I then took another holiday in December of 2019, ending everything. Shortly thereafter, I had a repeat performance of what I got in 2018, where I saw a rapid rise in my PSA. We did some imaging.

sue and Testing” (Brian McCloskey) [#22] I started apalutamide and saw an immediate response from that. I then took another holiday in December of 2019, ending everything. Shortly thereafter, I had a repeat performance of what I got in 2018, where I saw a rapid rise in my PSA. We did some imaging. We discovered that I had six metastatic lesions in my peritoneum. That was July of 2020.

I had surgery to remove them. They couldn't get everything. There were complications, and this will play into where we're going to go with this discussion. Due to the salvage radiation that I had back in 2017, the tissue gets sticky. It was hard to get margins around the lesions. There are a lot of nerves in that area of the pelvis. You have to be super careful. My doctor at UC San Diego, Dr.

Kane, resected six lesions. I had DNA sequencing. I have three different mutations, TP53, PBRM1, and TMPRSS-ERG. Fast forward to my second surgery on these metastatic lesions, and the DNA alterations remained the same. We also did some RNA seq analysis, where we looked at my RNA gene expression relative to a pan cancer cohort of 12,000 patients and a prostate cancer cohort of about 350.

This was done with Rick Stanton, myself, and folks at Tempus. We noticed that there are four major genes that I am at least in the 90th percentile ranking relative to those two cohorts. After surgery we knew that we didn't get it all. So I needed to start chemo, or at least that was the course of action that we took. We decided to combine that with pembrolizumab.

I started that in October of 2020. There were six rounds of chemo. I ended chemo on January 25th, and I maintained pembro all the way through to October of 2021. I saw that I was becoming resistant. We knew that we needed to do something else. I had more imaging done in October of last year. We discovered that I had three metastatic lesions.

I should also note that during that year I had imaging done, and there was actually no evidence of disease. So we did a pretty good job, but we knew it was there. It just didn't show up in significant lesions. I had three metastatic lesions by October of 2021. We started a second line hormone therapy, abiraterone, in November of last year. That's what I'm on today.

I've had a pretty good response. My nadir is a little hard to read, but it was at 0.45 in March of this year. It has grown slowly to 0.49, 0.54, and then 0.69 last week. We're recognizing that I'm moving into, or I have moved into a castration resistance setting. I'm going to need to do something. I've had a number of different imaging techniques. I've had a PSMA PET and a CT scan.

I just had a three Tesla MRI done. It's much more powerful than a standard 1.5. The fidelity of the imaging is really important because the lesion in the peritoneum is very close to the bladder, and we needed to understand whether or not the cancer has infiltrated the bladder, or intermeshed with it.

t had a three Tesla MRI done. It's much more powerful than a standard 1.5. The fidelity of the imaging is really important because the lesion in the peritoneum is very close to the bladder, and we needed to understand whether or not the cancer has infiltrated the bladder, or intermeshed with it.

If there’s enough margin between the bladder and the lesion, I would look at radiation and maybe even surgery. The path that we're currently on with my oncologist, Rana McKay at UC San Diego, is that I'm going to get a biopsy. For me, it's really important to understand what is the nature of my disease and how can it inform my treatments? I'm scheduled for a biopsy a week from today.

“Brian McCloskey’s Tissue and Testing” (Brian McCloskey) [#22] At the Prostate Cancer Lab we've developed an amazing consortium of providers that take all of our EMR information and genomic information and come up with various treatment options. We've worked with Massive Bio, Cancer Commons, xCures, and CureMatch.

Interestingly, across those vendors there was no overlap on the recommended treatment options. I then had a conversation with my oncologist last month where we reviewed those 21 options. All of them. She was amazing. We netted them down to about 8. I won't go into all the reasons right now. Then I had another conversation with he just a couple weeks ago, and we netted them down to five.

The five that we're currently looking at are SBRT (radiation), surgery, chemotherapy, ARV766, and a PSMA bispecific. She ruled out BAT (bipolar androgen therapy). I'm putting BAT back on the map because I want to explore that option with her again. While I am newly castration resistant, my AR expression is also very, very high.

I don't know if I have AR copy number gain, but I know that I have a high expression of AR, so I don't want to quite dismiss that. My oncology team has been focusing more on radiation, but I'm not going to give up surgery, because after speaking to the radiation oncologist, I'm definitely concerned about the side effects of radiation given the tumor's proximity to my bladder.

The surgeon was not really stoked to do surgery, given the stickiness of the tissue and a few other things. The MRI revealed that my index lesion has actually grown fairly significantly in the past year. It's gone from three centimeters to five centimeters, which is odd because my PSA hasn’t increased that significantly and is still lower than where it was when my lesion was 3cm.

Now it's beginning to rise a bit more rapidly, but the correlation between my PSA and my tumor volume doesn't seem to correlate. In any event, I do want to put surgery back on the table as an option. Essentially we're down to maybe five or six treatment options. There could be others. We don't have vaccines on here, which is certainly something that I would consider.

I guess Provenge to a certain extent.

“Brian McCloskey’s Tissue and Testing” (Brian McCloskey) [#22]