linnea olson's hackathon updates
Weekly Update Meetings
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Table of Contents
April 9, 2021 - Launch & Introductions
Thanks again for your interest in the Linnea Olson hackathon.
We had a great launch Friday with about 30 people participating. It was inspiring to hear from Linnea and the broad range of backgrounds and interests of people, from lung cancer patients to highly trained researchers, who are joining to find Linnea’s next best treatment and create a learning network for patients like Linnea.
If you didn’t get to participate and would like to see the recording, you can see it above (April 9, 2021). It runs for a half hour.
This Friday Linnea will be presenting her medical history and the data she has available for analysis. We are particularly interested in hearing from you what additional data we should gather to open up possibilities for novel insights and therapies. The session will be longer than the usual lightning update; it has been budgeted at a half hour, but may run longer. You should have received the calendar invitation with the Zoom link, starting at noon Eastern. Please let me know if you have any questions.
We are also launching our online discussion forum on Slack. This is the place to continuously raise questions, make comments, and suggest ways we can improve our process.
(Please note: If you’re not part of this Hackathon but would like to be, please fill out this form.)
April 16, 2021 - Medical History Sets the Stage
Yesterday Linnea Olson set the stage to find her best next treatment with a description of her medical history and available data.
To kick the meeting off, Linnea diligently presented her history (which took about 15 minutes), then the crowd of two dozen participants asked useful clarifying questions and discussed possible therapies (another 15 minutes), and then (not recorded) we had a fascinating discussion among the participants.
As you may know, Linnea has been on five clinical trials, and is facing a difficult decision.
While she has learned to live with her disease as a manageable, chronic condition, she was just booted from her fifth phase 1 clinical trial (a MEK inhibitor combined with an ALK+ inhibitor, lorlatinib) due to retinopathy (eye damage). She is staying on an ALK inhibitor, whose side effects she tolerates, and then will rescan and also explore the possibility of enrollment in another phase 1 trial–this one a combo of lorlatinib and a SHP2 inhibitor. Her concern is that SHP2 is on the same pathway as MEK and has the potential for eye issues as well. She would love to have other possibilities for treatment. At 16 years, she is very far out on the skinny branches when it comes to options.
The recording above has much more detail that Linnea puts on a timeline.
In the discussion which followed Linnea’s medical history presentation, the crowd discussed dosing, tissue access, and two possible treatment options: ERK inhibitors and a fourth generation ALK inhibitor.
Kimary Kulig asked about dosing as an option (to minimize the negative side effects) and compassionate use. Grace Cordovano asked about Linnea’s biopsy history and access to tissue for analysis. Linnea said that her tissue was used for research, and she didn’t have access to it. Kimary Kulig suggested Linnea could withdraw her consent. The amount of excess tissue was small since it was a needle biopsy. Tim Stuhlmiller offered suggestions for possible drugs that target the MEK pathway, with the proviso that the eye issues side effects may be an issue with all of the options targeting that pathway. He also introduced the option of ERK inhibitors, which are the next drugs down the MEK pathway. xCures (where Tim works) is running an expanded access basket trial for ulixertinib from BioMed Valley Discoveries to access this drug and novel combinations. Emily Venanzi introduced another option: a fourth generation ALK inhibitor, TPX-0131, that the ALK+ community has been working on with Turning Point and which is in a phase 1 trial in Australia. Willy Hoos added that you can get compassionate access if efficacy has been proven, even as the company is working through the dosing experiments.
To me, the highlight of the informal discussion which followed was when Lars Engstrom, a researcher at pharmaceutical companies where he has been developing the drugs that Linnea has been using, gave an emotional testimonial of how he thinks of Linnea when he does his work. It was also interesting to hear from Emily Venanzi about her ALK+ patient group, founded on Facebook 5 years ago, which has grown to gather patients’ data and fund research.
The recording is listed above.
Next week Linnea should have results from the Foundation Medicine and Lucence liquid biopsy tests to report. She had her blood draw on Wednesday.
April 23, 2021 - Linnea gave an update on her progress
On Friday (April 23) Linnea gave an update on her progress, and we had another roundtable discussion of about two dozen participants. Again, the power of this diverse crowd and the offers of support for Linnea were inspiring.
Linnea reported that she submitted blood for two liquid biopsies and has received the results of the Foundation Medicine liquid biopsy — there was nothing found that was diagnostic – clinically actionable. Linnea reviewed the results with her oncologist, who said those results were not surprising since her tumor burden is low. Linnea asked her oncologist about the possibility of getting a tissue biopsy since she hasn’t had tissue results for her use for 3 years. The oncologist wants to wait for the results of the liquid biopsies. She is concerned about risks, such as a collapsed lung, but would support getting one if Linnea would like to. Linnea is also getting her data set up on Ciitizen to facilitate data sharing.
On a bright note, Linnea said she’s feeling great and spending as much time as she can in her studio.
We heard additional commentary, mostly on testing:
David Marshak of Foundation Medicine said that they would be doing some additional analysis.
Jack Challis said that Lucence is working on the blood biopsy analysis.
Kimary Kulig talked about how PathPresenter could facilitate analysis of Linnea’s large library of images.
Sophia Cornew updated on the progress Ciitizen is making on loading Linnea’s data for sharing, and developing a summary report, which should be ready by the middle of next week.
Tim Stuhlmiller described similar services that xCures and Cancer Commons are offering.
You can listen to the recording of the formal session (15 minutes) above.
Here are my notes from the group discussion which followed the update.
Grace Cordovano: If you think you might get a future biopsy, you should develop a plan to prioritize the tests you would want to apply to them. How long would it take to process and get results?
Rick Stanton: For example, Akoya Biosciences has spatial testing, which looks at the cancer cells in the microenvironment. You can test for immunotherapy responsiveness. PDL1. RNA sequencing can determine if it’s a hot or cold tumor.
For example, Certis Oncology could develop a mouse model.
Grace Cordovano: You should search for unprocessed cut slides, other slides, and digital files.
Grace Cordovano: You should consider SomaLogic, which analyzes proteomics. Not sure on cost and whether they need tissue or blood.
Grace Cordovano: You should consider interventional radiology — as they go in to biopsy the material, they can also zap any cancer they find with radiation.
Devon Snedden: We have pathologists engaged who could review and advance the science.
April 30, 2021 - Blood biopsy results, tissue biopsy possible, proteomics, treatment options, medical data
In our weekly lightning update meeting on the Linnea Olson Hackathon on Friday we learned:
Blood Biopsy Results: The Foundation Medicine blood biopsy report is in and can be seen on the Slack, and Linnea has received the Lucence report. Foundation Medicine reported variations of unknown significance. David Marshak noted that two of the variants included MCL1 and BNMP3A, and noted that these are potentially worth researching. Lucence identified a pathogenic mutation at a very low frequency in the TP53 gene. It is not directly druggable. Lucence tests 80 genes. The low frequency TP53 is consistent with other lung cancer results. The Lucence test goes deeply on their 80 genes, while the Foundation Medicine test looks at 300+ genes. The variations of unknown significance on the Foundation Medicine panel were not examined on the Lucence panel. We will be posting the Lucence results to the Slack soon.
Tissue Biopsy Possible: Linnea will be talking soon to her oncologist about getting a tumor biopsy, which will open up options for testing. We will be taking time on our next call about the testing options this will open up and prioritizing them.
Proteomics: Grace Cordovano has arranged with SomaLogic to get a proteomics analysis of a blood sample from Linnea. We need to organize a group to interpret the results (proteins that are up- or down-regulated) when they become available. This will be the subject of a future call.
Treatment options: The list of treatment options is expanding, based on research by Kimary Kulig and others. For example, Kimary thought Linnea might want to look at metformin and hydroxychloroquine. She also found that some of the variants of unknown significance are known in other cancers, and asked if Linnea has a family history of cancer. Linnea said her father had pancreatic cancer and melanoma, and her mother had kidney and breast cancer. Emily Vanzani shared a spreadsheet on ALK clinical trials. Please see the spreadsheet for Slack for more details.
Medical data: Linnea’s medical records from Mass General are now hosted on Ciitizen (5000 pages!), including her scans, and she can grant access to those who want to see them. Ciitizen will be developing a cancer summary — a timeline of care to-date including source data. We are working on a way to host and share Linnea’s raw sequencing data (BAM files). Linnea has access to the files on Foundation Medicine and can grant access to others. Kimary Kulig is checking to see whether PathPresenter might host all of Linnea’s scans for a minihackathon to analyze the scans.
For more details from the update, you can see and hear the update recording above (April 30, Round 4), and the recordings of the previous weekly updates above that.
Thanks again to all of the participants in the Linnea Olson hackathon.
At the request of Grace Cordovano and Glenn Sabin, I will be posting a list of participants: name, affiliation, and email address, unless you ask me not to by mid-week.
The Review Board is my first cut at people I nominate to review the options surfaced by the crowd. We will be looking to add more lung cancer researchers, in case you know any.
Please check the Slack for further background, discussion, and ongoing updates.
May 2, 2021 - A one-page description of our work and who is involved
May 7, 2021 - Scan and biopsy, data, additional test
In our weekly lightning update meeting on the Linnea Olson Hackathon on Friday we learned:
Scan and Biopsy: Linnea will be getting a scan on Wednesday (May 12) and will have a scan review the following Monday (May 17) and a discussion with her oncologist about getting a biopsy.
Data: Ciitizen has Linnea’s images and uploading was finished over the weekend. It’s a lot of scans. There are 5,000 pages. Linnea can give you permission to access the data if you are interested, and there is an API for those who want to connect through software. Ciitizen will also be creating a summary report with a timeline. Terry Cardillo is a lung cancer expert working with Ciitizen part-time, and he will be taking the lead on the report and clinical interpretation for Ciitizen. The report should be ready this coming week. We will have a 5-minute walkthrough next week.
Additional Test: Linnea spoke with Certis Oncology, which is willing to develop a mouse model for Linnea gratis if they can get fresh biopsy material.
For more details from the update, you can see and hear the update recording here (13 minutes), and the notes and recordings of the previous weekly updates.
After the formal recorded session Friday there was a roundtable discussion. Here are notes from Linnea:
Last Friday our fearless leader–Brad Power–joined us from MGH, where he was getting a Mohs skin surgery procedure done. Now that’s devotion. He had to leave after fifteen minutes which left me at the helm–feeling a little hapless. Brad is an excellent host and knows how to keep the conversation flowing. However, we managed.
Of particular interest to me was an in-depth conversation regarding immunotherapy and hot and cold tumors. ALK positive cancers are generally considered cold and thus far have shown little responsiveness to immunotherapy. I had fantasized back when I was first tested for PDL-1 in 2012 (negative) that there might be a way to ‘seed’ a tumor. Evidently a similar concept is now being explored–which gives great hope to those of us with cold tumors. So much of survival is just hanging on until the next promising treatment comes to trial.
We also discussed my oncologist’s feelings regarding the hackathon (hands off but supportive) and how each of them might respond to treatment suggestions from others. I assured the group that I have agency but I also know that I am currently coloring outside the lines. Thus it was suggested that perhaps I shall require advocates when it comes time to present options to my treating team.
Once again I was overwhelmed by the generous offers of assistance and inquiry. And I would like to stress that I am learning so very much by taking part in this process—a deeper dive–rather like the mechanic who last week took me into the shop and showed me the underside of my car. I needed a new exhaust system and this is the first time I have been offered an opportunity to actually look underneath my car. So simple but also so clarifying. And for me, quite similar to the hackathon. One example–my imaging is now accessible to me–in full. Prior to this I have seen the occasional scan but have never had access to all of it. I am hoping we are helping to forge a path for a greater level of engagement in healthcare–that this will become the norm.
At the request of Grace Cordovano and Glenn Sabin, I have posted a list of the Linnea Olson participants with affiliation and email addresses on the Slack.
Please also check the Slack for further background, discussion, and ongoing updates.
May 15, 2021 - Tissue is the issue
In our weekly lightning update meeting on the Linnea Olson Hackathon on Friday we learned:
Scan: Linnea rescheduled her scan to Sunday (May 23) and will have a scan review the following Thursday (May 27) and a discussion with her oncologists (Jess Lin and Alice Shaw) about getting a biopsy and prioritizing uses of the tissue. Linnea will also ask if they will participate in a virtual molecular tumor board.
Blood biopsy: Natera has agreed to perform their blood biopsy test for Linnea. It will be interesting to contrast their results with the test results from Foundation Medicine and Lucence. The Foundation Medicine and Lucence reports are available on the Slack. Raw sequencing data is available on request.
Proteomics analysis: We are working with SomaLogic to get an agreement with them to run their test. We will need help in analyzing the results.
Data access: Ciitizen should be finishing the summary report of Linnea’s medical history data in the next week or so. 5,000 pages have produced 35,000 “statements” = something happened at this time, which are extracted by an algorithm, over the 15 years of care. Linnea noted this is the first time she has been able to see all of her scans.
Tissue uses: Candidates to use Linnea’s tumor tissue (should it become available) include Oncocyte (measures whether tumor is hot or cold and whether it will respond to immunotherapy), Certis Oncology (will build a mouse model to test therapies), Akoya Biosciences CODEX (characterizes the tissue microenvironment using spatial analysis to understand the molecular and cellular mechanisms driving the disease and therapeutic responses), NanoString (single-cell cancer genomics studies and spatial biology enables insights on tumor heterogeneity, exploration of the complex interactions with the tumor microenvironment), and Foundation Medicine (tumor sequencing oncopanel). [Are there any other tissue tests we should add?]
You can see the video recording below for more details (13 minutes).
Here are some notes from the roundtable discussion — “Tissue is the issue.”
Kimary Kulig: To play devil’s advocate, Linnea’s oncologists may not want to risk the biopsy to get scarce tissue now. They may want to wait for progression.
Linnea: They will be looking at my latest scan to determine progression. I’m afraid that it is progressing.
Kimary Kulig: You will also want to know what clinical trials are requiring tests from biopsies, to know how much tissue to reserve for them. A core needle biopsy can yield 20 4-5 micron sections. A pharma company will ask for 10 slides, which could use half the sample.
Peggy Zuckerman: Is the tumor stable? Will it be heterogeneous?
Grace Cordovano: No more than 30-40% of issue blocks and unstained tissue should ever be used. 60-70% should be reserved for Linnea. Is there anyone who could culture the cells, or create cell cultures?
Kristein King (Certis): We could do this. We will check.
Kimary Kulig: Make sure in the consents that you reserve tissue for your use. You want to own it.
Sophia Cornew (Ciitizen): Deven McGraw of Ciitizen is an expert on this.
Grace Cordovano: We should get a legal review of the consent language.
Jason Crites: I am working with MGH pathology and could possibly avoid the legal formalities.
Devon Snedden: It will help if Linnea has clinicians to argue for this with her oncologists.
Brad Power: Our plan is to arm Linnea with arguments with her oncologists and we will be having a virtual molecular tumor board where expert clinicians can have discussions about the best diagnosis and treatments. Each treatment option should have an advocate.
Brad Power: Kimary, you suggested metformin and several other therapies. Can you explain whether these might be parts of a cocktail? Are there combinations of the various drugs that have been suggested?
Rene Roach: The Care Oncology Clinic has a cocktail of four drugs, of which metformin is one.
Kimary Kulig: Plus fasting.
Glenn Sabin: Will Lavalley can suggest other complementary therapies.