On our weekly update call on Friday we learned that Linnea’s cancer is doubling, she has collateral damage in her lung and is losing lung function, and she is uncomfortable and experiencing pain for the first time in a long time. Her cancer has never behaved so aggressively before.
She needs to get to a new treatment soon (which is planned to be a clinical trial of lorlatinib + a SHP2 inhibitor at MGH – TNO155). She will be the second person on this clinical trial. There is a possible side effect issue of eye damage.
Her tumor burden is not an issue. She will have a biopsy in the next week or two to confirm the course of therapy and identify any new mutations.
If (when) this latest round of therapy fails or the side effects are too severe, we will schedule a virtual molecular tumor board to consider her best next treatment.
We spent most of our time discussing possible uses of biopsy tissue and how to manage the biopsy process.The testing uses of the tissue include: 1/3 reserved for Linnea for future use, Foundation Medicine, Natera (need a small tissue sample to set up their blood test), Personalis, and an MGH mouse model.
For more details, you can see the full recording (1 hour) of the discussion below.
Thanks to Kimary Kulig, you can see the latest list of possible uses of the biopsy tissue and instructions in a shared spreadsheet here. Please review and edit if you have expertise in this area. There has also been discussion in the online forum (Slack) about the biopsy.
Here are my notes from the conversation on Friday – weekly update #8:
Linnea: The lorlatinib/SHP2 trial has been funded by the ALK+ group. Thanks to Emily Venanzi. I will be followed very closely by an ocular expert.
David Marshak (Foundation Medicine): Described the slides that are required for the Foundation Medicine CDx test.
Kimary Kulig: Does Foundation digitize the H&E slides?
Linnea: Alice Shaw was very interested that the Foundation Medicine liquid biopsy has identified variants.
David: We could also rerun your liquid biopsy.
Grace Cordovano: The table of uses of the tissue is very helpful for planning. Will it be a fine needle biopsy in multiple places or a surgical biopsy? You also want to have notes for the interventional radiology or the surgical oncologist who will be performing this procedure for pregame planning. They can look at your scans to determine how much tissue is available.
Linnea: It’s a good question. I would just as soon get rid of that upper left lobe. It’s been the source of much of my issues and is now causing me discomfort. It’s a difficult surgery, but maybe with VATS [Video-assisted thoracoscopic surgery] it would be easier. We will have plenty of tissue. I have a feeling it will start with a needle core biopsy and progress from there.
Grace: Have you talked about radiating that site? That should play into your decision.
John Powers: A surgical biopsy is always better — you always know what you’re getting, though there’s more risk. At SimplSeq we can take a sample, tissue or plasma, bind a single strand of DNA and can make identical copies. If we could get a small sample or send them a kit, we can make copies and preserve it. If you radiate during surgery, it has been very effective. But not all places can do that.
Brad: Would you be able to do it for free?
John: It’s not a commercial product, but we know we can do this. If you have a lab that is willing to work with us.
Kimary: Does it have to be fresh tissue? Or can it be FFPE?
John: No. We haven’t worked with paraffin.
Kimary: How much tissue do you need?
John: We can do it with 10 nanograms or less. We’ve worked with Foundation.
Kimary: It sounds like a good plan to do with any leftover doses.
David: We can schedule a call to discuss the details. Linnea shared the images from her most recent scan, which you can see on her blog or the Slack.
Devon Snedden: Would you like a review by Dr. Spinosa or Dr. Misalek of your plan?
Brad: Kimary, what do you think?
Kimary: It will help if the pathologists can review the table. The tumor cellularity is also important. I would involve pathology in reviewing the cellularity of the slides.
Will LaValley: Has there been any discussion about radiation oncology for ablative therapy, SBRT [Stereotactic Body Radiation Therapy], or palliative radiation that could activate an immune response, especially abscopal activity [the therapeutic effect on a distant tumor resulting from the treatment of local tumor]?
Linnea: No. I can raise it again. It has not been an option. At this point I’m not sure they’d consider it in my left lung since I have so much pulmonary fibrosis going on. If surgery is an option then maybe radiation becomes an option for my right lung, which has less aggressive cancer.
I’m realizing that before I get on that table for the biopsy, I need to have written down where I want tissue to go. Even though I feel like I’m getting buy-in from my doctor, there is still a challenge of getting people to do what I ask them to do. I brought up how shocking it was that I do not own my own tissue, and she didn’t say anything. These academic institutions are pretty traditional and have their accustomed ways of doing things.
When I signed the protocol for this new trial, they wanted a second biopsy just for research, and I told her, “No.” I’m going to keep pushing back on those. If there is no return of information then I’m not going to give tissue. We are pushing their envelope. They have not been questioned in this way very often.
Grace: When you have a plan and the biopsy is done, I recommend connecting over the phone or via email with the actual people who prep these samples and ship them out. That’s where bottlenecks happen and balls are dropped. I can connect with you to help you with those calls.
Kimary: Will MGH do their in-house panel as well, or will they forgo it?
Linnea: I think they will forego it and rely on the Foundation test. They will be proactive on the mouse model. I need as much specificity as possible in writing to get it to Jess Lin, to John Lafrete in pathology, and for the surgeon, so that they all know that I am on top of this, and it’s important.
Kimaray: To Grace’s point, and share it with the histologists and the lab techs who are handling your tissue and doing the fixation and the staining, whom you don’t know.
Grace: Patients are stigmatized and often labeled as too lazy, non-adherent, non-compliant, yet don’t appreciate the heavy lift required as a patient with a heavy diagnosis. We are all rooting for you, and please lean heavily on us this week to make sure no ball is dropped.
Linnea: In discussing the hackathon with both of my oncologists, the part that alarmed them the most was having my data hosted by Ciitizen. I think it was that it was opening the gates. I found this rather amusing. They (not them specifically, but MGH) has never had an issue of using my data or my scans in any way they want to do. They are feeling a loss of control that they find threatening.
Lars Engstrom: I’m looking from the discovery side, not the clinical side. I know that Alice Shaw is at the top of the EML4-ALK clinical research, and will enroll Linnea in what’s best. Establishing a mouse model will be extremely difficult. Organoids haven’t been discussed and may be worth looking into. We’re all here to help, and it’s great to see all these people coming out to help Linnea in non-traditional ways.
Emily Venanzi: It’s important now to queue things up for what may be necessary down the line, like Kimary mentioned with the tumor and the cellularity of the tumor. Could an immune therapy be an option later on? Do we have anyone that will do an RNA analysis (vs. DNA sequencing)? That could give some additional information. There are a lot of new phase 1 therapies that target molecules that are on the surface of the tumor cell. Maybe her tumor cells are expressing a surface marker that could be targeted? Proteomics?
Kimary: We should make some slides available for this.
Will LaValley: I agree that proteomic data is really important and surface molecules. Linnea: You need someone to bird dog this for you. The people haven’t seen this, or are changing shifts when this comes in. It’s important to talk to the people who are physically handling the paperwork or tissue. I recommend a 5×7 index card or a piece of paper in a way that they can clearly understand it even when you’re not there, with no assumption that they understand anything at all, with names and phone numbers.
Ricaardo Salgado: Where are we on the tumor board?Brad: We have a running list of names. We are waiting to invoke the virtual molecular tumor board after what happens with the SHP2 trial. We will pull the trigger with a 2-week lead time.
Linnea: I’m still hopeful that I can pull in Alice or Jess. I hope that the hackathon will gain credibility with them. This is a learning process for them too. This has been an emotional and hard week for me. One of the things that has kept me grounded is the hackathon and knowing all of you are pulling for me.
Ricardo: We love you. We’re here for you. Call us 24/7. I’m a patient too. Did Jess Lin agree to participate?
Linnea: Not yet. Maybe if you ask her.
Ricardo: We’ll get there. I’m happy to help with the molecular tumor board design. It will be important to prepare the participants.