linnea olson's hackathon updates
The mission of CancerHacker Lab is to help people with a cancer diagnosis choose the best options for their treatment, including:
- Engagement: Increase active involvement of people with a cancer diagnosis and their caregivers by providing information and resources, especially apps and online services. Read more about engaging in your own treatment.
- Personalization: Accelerate adoption of better cancer treatment processes which are tailored for each patient, based on extensive health data. Read more about getting personalized treatment.
- Leaders: Accelerate adoption of services pioneered by innovators (pioneers, start-ups, entrepreneurs) who want to revolutionize treatment. Read more about promoting leaders.
Weekly Update Meetings
** Click on any date to drop down to that section of the page
Table of Contents
Linnea Olson Hackathon (Updated as of June 11, 2021)
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 14, 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.
May 21, 2021 - The Case for a Biopsy
In the weekly update meeting on the Linnea Olson Hackathon on Friday we learned:
- Linnea is interested in complementary therapies (e.g., adjuvants like metformin, nutrition), as well as the therapies that are targeted at molecular variants. Will LaValley explained the role that these additional therapies can play in controlling cancer.
- This coming week on Sunday (May 23) Linnea will be getting a scan and will be meeting on Thursday (May 27) with her oncologists (Dr. Lin and Dr. Shaw), where she will raise her interest in getting a biopsy.
- The proteomic testing from SomaLogic needs a form for sharing results (an IRB). Grace Cordovano will help resolve it with Brad offline this week.
- Linnea will follow up with Natera to get their blood biopsy.
- Linnea went to Mercy BioAnalytics to learn about their blood biopsy, which is focused on early detection, to date for ovarian cancer, but they are interested in going into lung cancer.
- Kimary Kulig will look into other testing companies that may be more mature that also use “extracellular vesicles”, or EVs.
- Gail Thornton believes there is potential for an article on “Tissue is the issue”. One angle might be a letter to the editor in a top tier newspaper, calling attention to the issue of tissue and patient rights, and another angle might profile the purpose of the hackathon, of advocacy in treatment, and helping the patient navigate, for something like the New York Times Be Well or a top tier reporter who covers healthcare. Please let us know if you have any contacts or suggestions.
You can see the recording (11 minutes) of the formal part of this meeting below.
In the roundtable discussion (a half hour), we focused on helping arm Linnea with the benefits of getting a biopsy for her conversation with her oncologists on Thursday.
Here are my notes from that conversation:
Linnea: I see asking for a biopsy as taking back my agency and power.
Grace Cordovano: You’re rare. In your conversation, you should position the biopsy within the context of your life, not a clinical decision.
Kimary Kulig: This is an elective procedure. Can you get reimbursement?
Grace: You can get a preview of whether this will be covered by talking to your insurance company.
Will LaValley: When and where was your last biopsy?
Linnea: My last biopsy was a year ago, but there was no return of information. The tissue went to Japan. There have been two failed treatments since then. Prior to that my previous biopsy was two years ago. This is the longest time I have gone without a biopsy.
Will: Therefore there has been evolution, and you want an update on the molecular profile.
Brad: Are there super technologies (robot-assisted) for doing biopsies at other institutions that would reduce the risk?
Kimary: Be sure there is tissue left for yourself.
Brad: Can you ask the pathologists to gather more tissue than usual?
Ricardo Salgado: The tissue access challenge is a good topic to expose.
Kimary: What should we do with the tissue? We should add IHC testing. Please put all ideas on the Slack. Personalis is another option.
Brad: We can discuss next Friday what to do with the tissue and determine priorities.
May 28, 2021 - How Should Linnea Manage the Biopsy?
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.
June 4, 2021 - Lightning Update 9
June 11, 2021 - Lightning Update 10
Following Linnea’s biopsy on June 9 (you can see the report in Slack) and start on her new clinical trial June 10, we held our weekly update call yesterday (June 11) and discussed:
- How Linnea should prioritize the use of her biopsy tissue – which tests to send it out for. Jess Lin has prioritized Foundation Medicine, Caris, and mProbe (proteomics). If there is enough tissue, she will add other tests.
- An article on “the issue of tissue” – highlighting the challenges a patient faces in making sure that tissue is used for guiding her treatment (vs. research uses). Sophia Cornew of Ciitizen (and Ciitizen’s PR agency) and Gail Thornton are leading this effort.
I have summarized the meeting conversation and some subsequent emails in more detail in the notes below, and you can see and hear the recording of the conversation (1/2 hour) below as well.
As always, please review the ongoing conversation and leave a comment at our online forum (on Slack). And check out the “poster” below of the Linnea Olson hackathon.
- Kimary Kulig: Are they saving any tissue?
- Brad: We included the request to save 1/3 in the instructions (courtesy of Grace).
- Kimary: Did the clinical trial request any tissue? Was it a request or part of the inclusion criteria? (If it was a request, it could be declined to save the tissue.)
- Brad: We’ll ask Linnea.
- Kimary: I noticed on the report that Linnea shared that the pathologists who signed were not thoracic experts. I was surprised by that. I assume that in a final report that thoracic pathologists will weigh in. It also seemed that there weren’t any IHC tests performed. I presume that’s probably in the works there. And while I’m not a pathologist, the “acinar and micropapillary patterns, and mucin production” findings from the biopsy indicate that it might not be an ALK positive tumor.
- Rene Roach: Why is Linnea having tissue sent to both Foundation and Caris? Aren’t they pretty much the same tests? Is there something different?
- Kimary: I wouldn’t do that either. I put that instruction at the top of the list to avoid redundant tests.
- Brad: Is there value (if you have enough tissue) in sending to multiple labs to confirm results?
- Kimary: That would be true if it were a non-validated test that doesn’t have FDA approval. These tests have had to show their reliability. If it were my tissue, I would get Caris or Foundation, and choose the one that gives me more results from the tissue.
- Rene: I agree. I would save the tissue. You’re only going to find some variants of unknown significance that aren’t driving her cancer anyway.
- Kimary: A clinician will be curious to see how the tests are different and feel it’s more valid if two tests come up with the same answer. I hope we are empowering Linnea to say, “I don’t want that redundant testing.” Has the tissue already been sent?
- Brad: I don’t think so. I know that Jamie Holloway at Caris is still working on the requisition paperwork.
- Kimary: If Linnea is up for it, I would ask the question, or at least stagger the tests. If the quality of the tissue is bad, you might have two failed tests, but if you hold the second, you could do something different with it.
- Linnea (via email after the meeting in response to a question from Brad summarizing the above discussion about Caris and Foundation being redundant): Wasn’t one RNA and the other DNA? Dr. Lin felt they covered different bases.
- Kimary (via email in response on June 12): Foundation One CDx uses DNA and covers a gene panel. Info is here. Foundation Medicine does offer the HEME panel as a CLIA lab test. It does both DNA and RNA. Someone would have to compare the Caris and FM gene lists side-by-side to see any differences. By its name, the HEME panel may be more targeted towards hematologic malignancies, but it says it can be used for solid tumors as well. Jamie Holloway from Caris also told me she’d be sure Dr. Lin gets their more comprehensive “research report” from your test results. This would include non-clinically actionable findings. We should be sure Foundation could do the same if that test is chosen. The Caris test does both DNA and RNA and those details are here and Jamie Holloway is on standby and already in communication with Dr. Lin. Dr. Lin is not releasing your insurance information to Caris/Jamie without your permission. Thus, Jamie cannot put in the tissue requisition without the insurance info. Any company with an FDA-approved product cannot technically NOT BILL for their test. This would be considered an “inducement” to the physician to use their test preferentially over any other and is highly non-compliant and could get the company in trouble. However, Jamie has assured me that Caris doesn’t go after patients for co-pay and said their patient navigator can help with all of this. I am a blunt person, so I will just go out on a limb here and say…I would save tissue and not do both tests. I would do the more comprehensive of the two and that seems to be Caris. Caris will also return any unused tissue if you ask them to do so. (I’m sure Foundation would as well, but I was told this by Jamie). Information that would be important for the Hackathon to know is how many core needle biopsy blocks were collected in total (i.e., how many slides might you have in total)? I would not let MGH use them all!!! Apologies for my stern, direct language, but… time is of essence as these tests take a couple of weeks and you need these results ASAP.
- Linnea (via email on June 12): I shall bring this up with Dr. Lin and inquire about the health insurance as well. I may have misunderstood–so I shall ask for clarification. I do know that there is a well established relationship with Foundation and that could be part of it.
- Brad: Gail Thornton has been proposing that we work on an article or letter to the editor on the issues that Linnea has been having with her tissue. And Ciitizen has been very strong in advocating for patient access to their data and tissue, and Sophia Cornew has been speaking with their PR agency about helping draft something.
- Sophia Cornew: I’ve had conversations with our internal team and PR agency about slotting this in. I will have another conversation on Monday. Deven McGraw [Chief Regulatory Officer] and I believe this is a wonderful story of patient control over their data that needs to be told. Patient stories have had tremendous success for us. For example, we have a CBS interview with one of our clinical trial matching patients. The reporters want patient stories. The hackathon and the issue of tissue need to get out there. The agency will figure out what’s the best approach — video interview, letter to the editor — to pursue.
- Gail Thornton: I’ve spoken to a few reporters on the hackathon, what it means for treatment and a new way of thinking, different options. I’ll be writing that pitch this week. I would like to know more about Linnea’s personal story.
- Brad: Linnea is quite public with her blog, articles, and interviews. If you do a Google search, you’re sure to find previous articles that will give you some color.
- Kimary: Following the discussion we just had on the patient prioritizing tissue uses, we wouldn’t want any physician to shy away from this kind of effort and feel like their decisions are being challenged.
- Brad: It’s a fundamental tension that is underlying this whole effort and getting second opinions. For example, in the Kasey Altman hackathon, Dr. Lenny Wexler, her oncologist at MSK was brave to host the discussion of Kasey’s medical history, and take questions, some of which might be seen as second-guessing his decisions. It was very brave of him to expose himself in the way he did. And on the other side, the patients hesitate to get a second opinion for fear of being rude to their oncologist. We’re all trying to get the best answers for the patient. Collegiality and openness need to be the philosophy.
- Gail: Kasey’s physician was very open, yet Linnea’s physician might ask, “Why are you questioning me? Why are you stirring up the pot? You should trust me and my judgment and years of experience and expertise.” You have to be ginger when you write this up.
- Brad: With the Bryce Olson hackathon, Rana McKay of UCSD said, “You’re going to bring a crowd to this? Great! I’ll learn something.” In my consulting I have had clients who were learners and clients who were defensive. They are pre-wired that way. You hope you get people who want to learn because for them, this couldn’t be better.
- Sophia: This is a line we walk every day. We are building a technology platform that challenges the status quo and puts patients in a position of power over their health data. That itself is an aggressive move in the eyes of some oncologists, and there is some pushback. It’s part of the broader move to give patients access to their notes and other changes. There might be six stories here. What are the benefits of patients having a say, or of crowdsourcing? This is happening. Get on board, or not.
June 18, 2021 - Tissue Is Out for Analysis
In our weekly update call (#11) with Linnea Olson, we learned from her that:
• She had her biopsy and started her latest clinical trial a week ago. These were layered on top of a tsunami of other demands in her life that she doesn’t have time for, but must deal with. She is tolerating the clinical trial drugs.
• The biopsy was very successful — they got 4 plugs and 2ccs of fluid. Her tissue from her biopsy has been sent to Caris (for DNA and RNA sequencing) and to mProbe (proteomics analysis), Jess Lin closely paid attention to the hackathon team’s advice on prioritizing tissue from testing, including prioritizing sending data to Caris, whose test is somewhat redundant with Foundation Medicine’s test at this time.
• She has learned from her oncologists Jess Lin and Alice Shaw about two promising clinical trials that are upcoming: a 4th generation ALK inhibitor – TPX, and a tumor-infiltrating lymphocyte (TIL) trial (through Iovance) which will be at MGH in the fall. She may not meet the entrance criteria for either of these clinical trials given her multiple instances of having already been on clinical trials.
In our roundtable discussion, we talked about:
• How Linnea might use “compassionate use”, “expanded access”, or “named patient” protocols to get access to her desired clinical trials when she doesn’t meet the clinical trial entrance criteria. “It’s appalling that they would lock me and others out when these therapies are so needed by someone who has come this far.”
• What other information Linnea might glean from previous tests. Peggy Zuckerman asked about information that might have come from earlier biopsies that could be useful. Linnea responded that she learned — to her surprise — that the biopsies used for clinical trial research processes return no results to the patient or the principal investigator — only the sponsor. Kimary Kulig added that is why she would refuse all requests for research use of tissue since it will use up scarce tissue and provide no direct benefit to the patient.
• What additional tests Linnea might get. Linnea will check to see whether she has had tests for PDL1/PL1 and other immunotherapy responsiveness. She will also check to see whether she has had or could get tests to see whether TIL will be useful. Kimary Kulig and Ally Perlina recommended that Linnea request another blood biopsy to monitor progress and add more information on variants, especially post her cancer’s recent aggressiveness and the new treatment.
• How we could organize a scan and radiology review of Linnea’s many scans and radiology. We have several pathologists already engaged in the hackathon and can recruit more with Devon Snedden’s help through the College of American Pathologists. Kimary Kulig will check again about interest in catalyzing a group.
• How the hackathon is exploring how far we can push on many fronts.
• How hard it is to donate your body to science. Lila Joseph mentioned the “rapid autopsy”.
You can see the recording of our update conversation (15 minutes) below, as well as see notes from previous weekly meetings and recordings (above).
As always, please review the ongoing online conversation and leave a comment at our online forum (on Slack).
June 25, 2021 - Candidates for the Virtual Molecular Tumor Board
In our weekly update call (#12) with Linnea Olson, we learned from her that — despite trepidation going in — she is tolerating her latest clinical trial therapy (started June 10) well — There have been no side effects. But she is also not perceiving any benefits, and she is feeling poorly physically — breathing is hard and she has pain. It’s difficult. The concept of death is increasingly present. She hopes the trend reverses. She is also struggling with some personal issues. We are waiting on the reports from the tissue biopsy at Caris and mProbe.
We spent most of our time talking about the candidates for Linnea’s “review board” — the people who we would like to invite to help her choose her best next treatment and prioritize her treatment options.
- Ricardo Salgado kicked off the discussion of Linnea’s review board with a question about how it will work and who will be on it.
- Kimary Kulig suggested we should look for “Phase 1 trialists” (a term I hadn’t heard), experts in lung cancer who are leading relevant clinical trials, which we might find by searching on clincaltrials.gov.
- Kimary added that we should organize the review board candidates by specialty, e.g., research oncologists, pathologists.
- Ricardo reminded us to look at Emily Venanzi’s ALK+ clinical trials lists for names in the Slack.
- Rene Roach recommended we add Stephen Liu to the list.
- Will LaValley encouraged us to prepare and share in advance documentation like clinical notes with the review board.
- Sophia Cornew said that Ciitizen has put together a list of solid tumor clinical trials from clinicaltrials.gov. And their files and reports could prepare the review board. “ECOG Performance Status” (are you up and about for greater than 50% of your day) will make a difference on which trials Linnea will qualify for.
- Jeff Waldron suggested that Linnea get the results of any Mass General molecular tumor board as input to the review board.
- Linnea commented that she has never been invited to her molecular tumor board. There seems to be a policy that no patient is ever in the molecular tumor board.
Since the meeting yesterday Kimary (fast mover!) developed a first draft of the review board candidates, and I added all the names that I had received from Ricardo, Linnea, and others.
Please review and edit the review board candidates here.
I have also drafted a working document on Linnea’s treatment options, which lists the treatments I have heard about as a start. I incorporated suggestions from Emily Venanzi and others.
Please review and edit Linnea’s treatment options here.
You can see the recording of our update conversation (15 minutes) below, as well as see notes from previous weekly meetings and recordings (above).
As always, please review the ongoing online conversation and leave a comment at our online forum (on Slack).
July 2, 2021 - An Urgent Need to Find a Fast Path to Advice on Linnea's Best Next Treatment
Linnea Olson has taken a turn for the worse: she is in the transitional ICU, and has just gotten 1.5 liters of fluid removed from her lung and is taking antibiotics for pneumonia.
As a result, she will likely be taken off of her current line of therapy.
On the weekly call today, we discussed how we can accelerate the path to get her advice on her best next treatment.
There were three main topics:
- Getting access to the latest test results: Reviewers will want the latest information from the Caris test on Linnea’s recent biopsy, e.g., is Linnea still ALK positive?
- Preparing reviewers: Inviting them, getting information to them, one-on-one interviews, helping them understand the hackathon process
- Discussion process design: how to engage a broad range of people in an open discussion ASAP.
Our (Urgent) Requests: Actively Engage over the Next Week
- Please jump on our online discussion forum (Slack) over the next week to review and discuss Linnea’s treatment options, which is available asynchronously 24/7.
- Please review and add to the list of Linnea’s external review board candidates. And if you know anyone whom you think could help, please invite them to participate.
- Stay tuned for a virtual external review board meeting (Zoom), possibly for next Saturday, July 10, in the afternoon. (The timing of the external review board meeting will be dependent on getting access to the Caris test results, which should hopefully be sorted out in a day or two, and on engaging with Linnea’s medical team at Mass General, Jess Lin.)
Here are my notes from the call today.
You can see the full recording of the weekly meeting (#13) (55 minutes) at the CancerHacker Lab site on Linnea Olson Hackathon updates below.
Kimary Kulig: The key is grounding the participants before they participate in the review board meeting.
Jeff Waldon: How do we work with Jess Lin/Mass General? They must have ideas on what Linnea should do next. Whatever ideas the hackathon comes up with, they will have to go through Linnea’s care team at MGH.
Kimary: We should call it an “external tumor board” to distinguish our contribution from their tumor board. We could work with Jess Lin to prioritize people on our review board candidates list in different disciplines.
Peggy Zuckerman: Maybe Rana McKay, who was Bryce Olson’s oncologist and actively participated in the hackathon, could reach out to Jess Lin to share her experience?
Kimary: Thinking of a workaround for Linnea having to provide access to her data to everyone: Maybe Ciitizen could provide access through their consent coverage that Linnea has already provided? Linnea needs permission to provide access to her data to any hackathon participants.
Robin Yano, Tony Cardillo (Ciitizen): We can check on the agreements we have and get back to you.
Ricardo Salgado: We need to ensure access to all patient data to the hackathon participants upfront.
Kimary: For future hackathons, this should be done in writing by the patient. I’d like to be able to call MGH on Linnea’s behalf and take some of that load off of her.
Kimary: There needs to be a proxy/controller who can request and share data on the patient’s behalf.
Jeff: Brad, you should call Dr. Lin to make a connection with the hackathon. Her assistant would know about her availability, and given the urgency, you should speak to her ASAP.
Kimary: Linnea needs to provide written authorization to share.
Kimary: You should consider not recording the review board meeting to encourage more openness. Maybe you can use good notetakers.
Ally Perlina: We should start knocking on doors to see which ones open.
Grace Cordovano: Linnea should provide consent for release of results to one point person. Does she have a point person? It can be as simple as a signed document at her bedside. Her care team needs to know what is going on in the background. She needs a designated point person.
Tony: I’m looking at her documents, and I can see that she does have an existing healthcare proxy. I will discuss it offline.
Brad: I sent a text to Linnea just now: “It would help if we could speak with your designated point person proxy for your care. Could we connect them with Grace Cordovano to represent the hackathon to work on your behalf? (It is preparatory to talking to Jess Lin.)” She responded, “Of course. I need to figure out who that person is.”
Kimary: The simplest approach I’ve used is to use an institution-specific form to designate a proxy. The person needs access to medical records and to ask questions on Linnea’s behalf.
Grace: We should find out who the care point person is for Linnea, and I would be willing to speak to them before approaching Dr. Lin. There needs to be authorization for treatment.
Brad: I sent a text to Linnea: “If you have energy, could you please ask a nurse to have you sign a HIPAA authorization form for Kimary Kulig and Grace Cordovano?
July 8, 2021 - Twitter Post from Harvard Health
Developing New Cancer Therapies: Patients as Partners - MONDAY, JULY 12, 12 PM ET
A seismic shift in cancer drug development is partnership with patients. Join #HarvardHealth for an exciting discussion on patient-centric drug discovery w/ industry leaders & patient advocate Linnea Olson, blogger, activist & artist living w/ lung cancer: https://bit.ly/3w8ZhzJ
Linnea Olson is a patient advocate, activist, blogger and artist. She has been a participant in six phase I clinical trials for ALK-mutant non-small cell lung cancer (NSCLC) – three of which led to FDA approval of new targeted therapies. Her experiences and wisdom have made her a trusted source of insight for countless patients, researchers, clinicians, biotech and pharmaceutical companies, and learners at Harvard Medical School.
In this special event, we will premiere a brief video outlining Linnea Olson’s remarkable journey. This will be followed by a panel discussion in which Linnea will be joined by two senior drug development leaders whose therapies have played such an important part in Linnea’s story. Join us for a wide-ranging discussion on patient-centric drug discovery and development, exciting advances in cancer treatments, and living with cancer.
July 9, 2021 - Preparation for Linnea's Virtual Review Board Meeting
- Linnea’s physical condition means that the options she can realistically consider are limited to those with compassionate use or off-label uses, as she won’t meet the qualification criteria for clinical trials, e.g., cell-based therapies like TIL and CAR.
- The Caris report (including the KEAP1 marker, low tumor mutational burden, microsatellite stable, and negative tests for PDL1 and other antibodies tested by IHC) indicate that some treatment options, e.g., immunotherapies and chemotherapy, are less likely to be responsive.
- Linnea’s strategy should continue to be to bridge to the 4th generation ALK clinical trial from Turning Point, which will be available in the fall at MGH. (Expert Ross Camidge of the University of Colorado recommended this option in the last week, and it was also recommended by Linnea’s oncologists, Jess Lin and Alice Shaw, and Emily Venanzi.)
- The most fruitful path looks like attacking KEAP1, for which there is a clinical trial by Calithera, which could be accessed through their expanded access protocol. Kimary’s bold opinion is that KEAP1 may be more important to address than the ALK pathway.
- Please review our shared working document on Linnea’s treatment options, and leave questions and comments there.
- Please join the conversation on our online forum (Slack) to review and comment on Linnea’s treatment options.
- Please join us on Sunday at 7:00 Eastern, for our virtual review board discussion on Linnea’s best treatment path. The link is: Join Zoom Meeting, ID: 81674329906, Passcode: 240361.
- Will LaValley: Do we have downstream Nrf2 activation from the KEAP1? [Toxicology Reports: The Nuclear factor erythroid2-related factor2 (Nrf2), a master regulator of redox homoeostasis, is a key transcription factor regulating a wide array of genes for antioxidant and detoxification enzymes. It protects organs from various kinds of toxic insults. On the other hand, activation of Nrf2 is also correlated with cancer progression and chemoresistance. Downregulation of Nrf2 activity has attracted an increasing amount of attention as it may provide an alternative cancer therapy.]
- Kimary Kulig: We don’t. The Caris report indicated that she’s got wild type for STK11. [Wikipedia: Serine/threonine kinase 11 (STK11), also known as liver kinase B1 (LKB1), which encodes a member of the serine/threonine kinase family, regulates cell polarity and functions as a tumor suppressor.] However, it doesn’t mean the LKB1 protein is being expressed. So we don’t know if STK11 is being hypermethylated. [Wikipedia: DNA methylation in cancer plays a variety of roles, helping to change the healthy regulation of gene expression to a disease pattern.
Silencing of a DNA repair gene by hypermethylation may be a very early step in progression to cancer. Such silencing is proposed to act similarly to a germ-line mutation in a DNA repair gene, and predisposes the cell and its descendants to progression to cancer.] Often KEAP1 co-presents with STK11 mutations, so I wish we could do an IHC for LKB1. [Immunohistochemistry (IHC): Using the principle of antibodies binding specifically to antigens in biological tissues to detect the antigens (e.g., proteins) in cells of a tissue section.] We could then determine whether she will have a response to immunotherapy and chemotherapy.
- Brad Power: Over the last week you led work to take the load off Linnea in her quarterbacking role, since she has been incapacitated. With help from Grace Cordovano, you tried to get a HIPAA [Health Insurance Portability and Accountability Act] authorization.
- Kimary: I felt this was an emergency, so I dropped everything and went online to find a HIPAA form that would allow Brad, on behalf of the hackathon, to get access to Linnea’s medical records, radiology images, NGS reports, Caris report, or anything like that. I sent it to Linnea and Dr. Lin with a note that she could use this form or something similar that they typically use. I got a thank you from Linnea, and no word from Dr. Lin. I also called Dr. Lin’s office and left messages, but haven’t heard back, and I don’t think anything was signed.
- Brad: We have identified that we need to prepare for these eventualities in the future by having backups/partners/proxies for data, tissue, and care.
- Will: I have seen in her document the suggestion for adding off-label treatment options, non-targeted therapies, metformin, and others. It’s important to consider them much earlier in the sequence of events, to run in parallel. They are low affinity binding in affecting the molecular activities, and they are multi-targeted, such as metformin. It may not be viable now. If she’s in the hospital it won’t happen there.
- Jeff: Have you connected with her care partner?
- Brad: I got her name. I asked Linnea if she would like to engage her. Linnea said she would. But Linnea hasn’t given me her contact information. I will ask again, though I don’t want to bother Linnea.
- Jeff: It’s a way to offload some of Linnea’s work. They can provide some of the backup.
- Ricardo Salgado: Supporting Dr. LaValley’s comments, I think that there are complementary therapies that would have been useful earlier.
- Brad: This is consistent with Linnea’s expression of interest in any lines of therapy, beyond traditional western medical therapies.
- Ally Perlina: If at some point if some kind of nutraceutical is in consideration, even though I wouldn’t hang my hat on it for the most effective treatment, I can suggest some things that would be beneficial biologically for addressing the KEAP1 and Nrf2 pathways, or at least wouldn’t be harmful, because we know of the reactive oxygen species and different oxidative damage that can be protected from simple nutraceuticals that exist right now, including some that act like metformin.
When I am speaking about that, I am not representing CureMatch. If Linnea thinks it will be useful, I can present some supplements that might be useful. This is not the therapeutic strategy, this would be an adjuvant.
- Brad: This reminds me of the Kasey Altman hackathon, where Kasey is taking an extra round of chemotherapy to bridge her to her next round of treatment — an immunotherapy clinical trial in the fall. We similarly need to get Linnea to the fall when the other clinical trials at MGH will be ready. And we also heard yesterday from Damon Reed of Moffitt Cancer Center, who advocates an evolutionary biology approach to cancer treatment of multiple strikes, rather than thinking of a knockout punch.
- Ally: I am trying to put something together on label therapies in some synergistic combos, even two- or three-drug therapy options.
- Brad: You have multiple opportunities: discuss it now, there’s Slack, our working document on treatments, and our review board meeting at 4:00 Pacific on Sunday.
- Ally: I will have our CureMatch report ready by Sunday, and I can present it then. I am thinking we could address other mutations, e.g., P53, which could also be addressed by some of the TKIs [Tyrosine kinase inhibitor, a substance that blocks the action of enzymes called tyrosine kinases. Tyrosine kinases are a part of many cell functions, including cell signaling, growth, and division.
These enzymes may be too active or found at high levels in some types of cancer cells, and blocking them may help keep cancer cells from growing.], or bevacizumab [Epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab significantly improved progression-free survival and overall survival for patients with EGFR-mutant non-small-cell lung cancer]. And if we are considering DNMT3A, as the second tier of therapies.
- Brad: I sent 25 invitations to the experts identified mostly by Ricardo Salgado, Emily Venanzi, Linnea, and Kimary, and got a few responses, but none are available for our meeting on Sunday. So we will have time for you to share your options.
- Kimary: Bevacizumab sounds great, but I’m not sure if Linnea would tolerate it right now. I’m a big fan of metformin and hydroxychloroquine, but I don’t think her doctors will go for that.
- Ally: I have a nutraceutical alternative that has similar targeting to metformin, but is weaker. The reason I mentioned bevacizumab is that it’s a monoclonal antibody, and if we have a rationale for a monoclonal antibody that could be more easily tolerated than a multi-kinase inhibitor and small molecules in general.
- Kimary: She is being treated at a very conservative institution. Anything we present that is not listed in the NCCN guidelines or is published in a reputable journal won’t be accepted.
- Will: Many of the supplements require oral administration, which is a problem. And therapeutic dosing is hard with these treatments. It’s not an option where Linnea is now.
- Kimary: There is also the issue of insurance reimbursement. If her physicians aren’t on board, then she won’t get reimbursement.
- Will: That’s why this molecular integrative oncology therapy should have been considered much earlier as a parallel branch of her therapy with precision oncology targeting.
- Ally: I was thinking about berberine with flavonoids, with good combinations and sources.
- Will: I was asking about KEAP1 and Nrf2, because they could be upregulated with supplements, rather than being downregulated. It’s tricky.
- Kimary: Regarding the list that we have, the only thing that I think is practical is the Calithera treatment via expanded access. It’s something we could get Linnea’s doctors to sign up for while Linnea is waiting for the Turning Point ALK drug in the fall. That’s a lifetime for Linnea. Having an open access program bodes well. And I would add metformin.
- Jeff: The dietary restriction model of Filtricine has shown improvement. It’s another long-term candidate.
- Kimary: As we do a retrospective on lessons learned, the management of Linnea’s tissue between the pathologists and Caris had a breakdown. Linnea should have had a tissue sherpa/bird dog/proxy/advocate. We are missing analyses I would have wanted to get. There were 4 blocks, or was it 4 slides exchanged? What was the cellularity of the tissue? There wasn’t enough sensitivity to not exhaust the tissue. They should return any unused tissue, but I imagine they throw it away or use it for their research.
- Will: You should write a protocol that patients could use to manage their tissue.
- Brad: As a patient who is learning all the time, I would struggle, even with a protocol, to manage my tissue. I don’t have a concept of a block vs. a slide. How big is a block? I imagine something that is an inch by an inch, but I know that it is from a needle biopsy, so it is much smaller. I may have seen a slide in biology in high school, but not since. The bigger issue is that without patient involvement or a sherpa/bird dog, the patient’s interests get short attention in the dynamics.
- Will: We talk about patient centricity, but I heard a saying that sums it up well, “Patient preference matters.”
July 11, 2021 - Linnea Olson's Best Next Treatment Option - External Review Board Meeting Recording
Treatment Strategy: There is a general consensus from Linnea’s physicians, Ross Camidge (ALK expert), and many of the hackathon contributors, that the 4th generation ALK inhibitor drug being offered by Turning Point (TPX-0131), which will be available in the fall in a clinical trial at MGH, is the best next treatment option for Linnea. Kimary Kulig noted from her reading of the Caris report that Linnea is “Still highly ALK+ (IHC score 3+), but with a resistance mutation making continued lorlatinib therapy possibly futile = search for newer generation ALK inhibitors with at least preclinical evidence of working on the Exon 23 G1202R point mutation.” Jess Lin is concerned that the clinical trial will not provide a therapeutic dose.
Draft Questions for Linnea to Discuss with Jess Lin and Alice Shaw on Thursday
- [Kimary Kulig] Chemo: Is chemo a viable bridging option given the KEAP1 mutation?
- [Will LaValley] Chemo: Is low dose chemo a possible consideration?
- [Kimary Kulig] Pathology: Were IHC stains done at MGH for N-Cadherin, Vimentin, Zeb 1, and LKB1?
- [Kimary Kulig] Pathology: Is there anything that can be analyzed on the existing slide?
- [Ally Perlina] Drug Options: What about avastin (bevacizumab), which correlates with sensitivity in this lung cancer type with TP53 alterations, + combined with a different ALK inhibitor (like alectinib or brigatinib) and + chemo (if appropriate/ relevant)?”
- [Kimary Kulig]: Drug Options: Is KEAP1 druggable and is the Calithera drug a reasonable treatment option?
- [Grace Cordovano, Kimary Kulig, Brad Power]: Care Partner: How can we offload some of the burden and decision-making for Linnea, e.g., have Kimary talk to Linnea’s pathologists and shepherd the tissue analysis. Does MGH have a HIPAA consent document Linena can sign, or is the form Kimary prepared acceptable?
What would you add, delete, or modify?
July 16, 2021 - "What do we do now?" and "What have we learned?"
- Please send positive energy Linnea’s way. Watch Linnea’s blog.
- Please review and comment on the template for a patient’s decision support tool for testing that Grace Cordovano has shared here.
I am exhausted. Spent, if you will. Therefore today’s blog is a cut and paste–taken from a message I sent out to my siblings and some close friends.
Another update. Not the kind I like to give. I had scans and saw both of my oncologists today. In short, it is still a shitshow in my left lung. Pleural effusion, partial collapse, possible pneumonia and a super aggressive cancer (Alice compared scans that were eight days apart and it had grown). And, unfortunately, my fever returned today–still low grade but not a good sign.
Next week I shall have a drain installed in my left lung and on the same day, I shall start back on the same drug that likely caused the pleural effusion–TNO-155–at a lower dose and with the hope that if my lung blows up again, we can control it with the drain.
My oncologist applied for (and received) compassionate use for the 4th gen ALK inhibitor that I had been precluded from (due to too many prior treatments)–TPX-0131. This is a great scenario as she gets to write the protocol. However, with paperwork it will be four to five weeks until I can start. Our goal–bluntly put—is to try to keep me alive that long.
This is brutal, I know. However, I thought it best to let you all know. If things don’t change course, I am wrapping it all up and sooner than I expected.
Please know how much I love you all and also that I am going to continue to fight like hell. I just need a miracle And–an ask–please look after my kids. They are having a really tough time–Peter told me tonight he is barely holding it together. In the end, it doesn’t matter how much time you’ve had to prepare. None of us are ready.
- Jeff Waldron: It shouldn’t take 4 to 5 weeks. You can do this by phone. If it is an emergency situation, the FDA will approve this compassionate use over the phone. I sent a link to the process (here).
- Peggy Zuckerman: Pharmaceutical companies also have processes for compassionate use. Patients get approval 98% of the time.
- Grace Cordovano: We don’t have weeks; we have hours and days. This has to be escalated. Why does it take so long? What can we do to help?
- Jeff: I reached out to the CEO of Turning Point. I know an expert in compassionate use, Naomi Litchfield, who is based in the UK, and knows about rules in the US.
- Kimary Kulig: Her doctors should be using this emergency procedure, but they need to fit it into their workload.
- Peggy: Is there anyone at Linnea’s side who can be this person pushing for acceleration and escalation?
- Brad Power: There is a named person, but we don’t have access to that person or Linnea’s doctor.
- Will LaValley: For each patient and hackathon, we should take into account the speed with which a tumor type can turn aggressive and develop a fitting timeline with which we can respond. Biology is often on an S-curve. Once we are going down the steep part of the curve, it is exponential. It can be anticipated. People may not want to discuss it. People should prepare options in parallel, rather than waiting.
- Brad Power: We need to have plans and resources in place that we can call on when urgent demands hit. We need to be able to move fast to respond.
- Grace Cordovano: We need to make it easier for patients and families to keep track of the complex types of tools, technologies, and tests patients could get, what the benefits of each are, how you select one vs. the other, as you consider cost, tissue management, and turnaround time. Where is there overlap, what is accessible, what is different? If we can take all of the wisdom from the hackathons and make it available to patients as an infographic, that is tumor-agnostic, as a patient decision-support tool. The current disease-specific and diagnosis-specific materials patients get cover the basics, but patients need the more complex information. I will be happy to collaborate and create a spectrum. (Please see Grace’s draft template guide here.)
- Jeff Waldron: I would add that providers need this guide too as they are as overwhelmed with the diagnostics and tests as patients and their care partners.
- Kimary Kulig: The oncologist will call the shots in the end. In the hackathon we were about putting options on the table with scientific backing and testing options. Does the hackathon want to extend itself into other aspects of care? We are talking about proxies and medical release. Should there be a line? There isn’t much a group like us can do as strangers with physicians. But if individuals step forward and want to get that involved, that would be great.
- Brad: We should structure the ideal team structure for the patient, whether the hackathon should be involved or not. We should provide the wisdom to the patient to guide them when they are in territory where they have no map.
- Peggy Zuckerman: Patients need someone to speak to doctors on the patient’s behalf, both the medical side and the emotional side.
- Will: There is a need for medical guidance, a roadmap of things to think about, and someone to manage relations with all of the people on the medical side. It is an educational challenge, maybe a video or videos.
- Brad: I have a manual from Cancer101.org, which provides basic education when people are diagnosed. Grace is right that people need access to deeper knowledge too when they have more complex decisions to make. The NCCN guidelines are good for educating people about the standard of care, and for clinical trials. We need to stand on the shoulders of these good education materials. Personalization makes the needed information very specific very fast. Every cancer has different biomarkers and tests. For example, Bryce Olson needed a PSMA-PET scan, which is specific to prostate cancer. Making anything that is both generalized and specific is complicated and a paradox. How do we create a health learning system?
- Sophia Cornew: In the future we should consider partnering with Triage Cancer, a law firm that specializes in the legal issues around cancer care; everything from insurance filling to disability to consent management. Joanna Morales is a terrific lawyer based in DC, and this is her non-profit.
- Brad: I’ve been waiting for someone to come forward to help us address the breakdowns we have experienced in having the right patient-friendly consents in place.
- Peggy: They have put up a lot of resources that we can all look at.
July 23, 2021 - Waiting for (a) Turning Point
In our weekly update meeting today (#16), we learned from Linnea that her oncologist Jess Lin has cut the time to get Linnea access to her best next treatment (the Turning Point 4th generation ALK inhibitor TPX-0131) from the previous estimate of four to five weeks to two weeks. Linnea will continue on her drug regimen (a SHP2 inhibitor plus lorlatinib) until then.
That’s the good news.
The bad news was Linnea’s experience on Wednesday of going in for a surgery to have a catheter put in her lung, and having the surgeon come in at the last minute to say that they couldn’t do the procedure because insurance would pay for the procedure, but not the supplies.
I was to get a PleurX catheter installed on Tuesday. However, I thought my appointment was in the afternoon whereas it had been in the morning. It was rescheduled for the next day and I spent Tuesday sleeping–exhausted as the day before the rest of the contents of my studio had been moved by (I kid you not) the two slowest movers on the planet. They did a good job though so all’s well that ends well.
My appointment on Wednesday was of the bright and early variety but this time I was where I was supposed to be when I was supposed to be. Johnnied up, on the table, being prepped. And then the surgeon comes in and tells me that they won’t be installing the PleurX because my insurance covered the procedure but not the supplies ($1000 a month to maintain).
I was stunned. ‘Why could you have not told me this before I was on the table?’ I asked. No response. The surgeon then went on to explain my options–another thoracentesis
or a talc procedure, which would require admission to the hospital. He also allowed that after two thoracentesis’ the risk becomes greater than the value.
Fabulous. I asked them to call my oncologist (they texted her). Explained that time was of the essence here–that I would be starting back on the same drug (TNO155) that almost certainly initiated my rapid onset plueral effusion. That the PleurX catheter was being installed so that if my lung started to fill with fluid again, it could be managed.
In the end, I had my third thoracentesis in a two week span. It hurt like hell. This time they were able to extact 250mm of very viscous fluid. The x-ray following the procedure reported ‘residual loculated left pleural effusion.’ So, in short, my left lung is a project.
Yesterday I met with Jess. The good news is that I may be able to start on TPX-0131 in two weeks. Having a horizon line is helpful in these circumstances and now my eyes are set on that. And my blood work looked great.
As for the aborted catheter, perhaps it shall be a non issue. I took my dose of TNO155 on Wednesday, but the way the trial cycle works, this week is my week ‘off’—no TNO155, just lorlatinib. So that alleviates my worries per another massive pleural effusion in the coming days. As it looks now, I may have to go back on TNO155 for only one week. There may be need for yet another thoracentesis, but a catheter may have been of limited usefulness anyway.
I remain exhausted and short of breath (but less so after I get my lung drained). However, this body of mine still wants to live.
I plan on honoring that. Much time has been devoted to getting my affairs in order–a great comfort. But now I need to get back to the good stuff. To that end, dinner out with Diane and her husband Dave last night, a meal with another friend on Saturday and a date on Sunday.
I’m alive I’m alive I’m alive.
- Linnea: I pushed Jess Lin to surgically remove my left lung. I would love to just get rid of it, and work on the cancer in my right lung.
- Brad: The only possible positive side of your latest insult from the health system is that it gives you more fodder for your blog.
- Linnea: They may as well have said to me, “You’re low income. We’re not going to give you this particular option.” I didn’t think they could do that. The whole situation was handled very poorly. It left me feeling very vulnerable. I asked Jess to speak to the pulmonology team. I don’t want this happening to someone else.
- Brad: We all commiserate because we’re all warriors for patients.
- Jeff Waldron: This is great news that in a week or two you will be getting the Turning Point therapy. It’s a very positive development. It could be transformative. With regards to surgery, it might be a good idea not to put your body through that stress. I’m the least qualified person on this call to have an opinion. This therapy will let you decide longer term about surgery.
- Linnea: I have to commend Jess. She has been working very hard behind the scenes with them to get me access to the drug sooner.
- Rick Stanton: Was there any consideration of immunotherapies to combine? If it was me, and it is me with prostate cancer, I’m waiting for the cavalry to come over the hill.
- Linnea: Not at this point. This TPX drug has some potential side effects. So we’ll see. The consensus in much of the lung cancer community is that immunotherapy is very promising, but we’re just not there at this time with lung cancer, and particularly ALK positive lung cancer.
- Brad: There is a trial that is on the list for TIL (tumor infiltrating lymphocytes) that is next up on Linnea’s list and is available in the fall. That’s Plan B, after Plan A (Turning Point).
- Rene Roach: I’m aware that they have a TIL trial [Tumor-infiltrating lymphocytes (TILs) are an experimental cell therapy being developed for treating solid tumors. Lymphocytes, or white blood cells, are an important part of the immune system that helps the body fight off infections or eliminate diseased cells. Lymphocytes, made up of T cells and B cells, are constantly patrolling the body to identify cells that shouldn’t be present, including cancer. As cancers grow, lymphocytes recognize these cells as abnormal and penetrate into the tumor. These are the tumor-infiltrating lymphocytes, or TILs.] with CRISPR [Cas9 enzymes together with CRISPR sequences form the basis of a technology known as CRISPR-Cas9 that can be used to edit genes within organisms.] at the University of Minnesota, and they like big lung (and liver) tumors. You have to be on another treatment for several months while they grow your TILs. It might be worth it to reach out to them to see if you would be a possible candidate. You could do it while you’re on your EAP.
- Brad: It would give you something to do with that left lung you want removed.
- Linnea: I have a big ass tumor in there, and they can have all of it. I’ve been feeling rather nihilistic, in part because I got so sick with the pneumonia and to feel myself failing that way, and these other challenges too. I don’t know if this old body can keep going. I feel my will to live re-emerging. Jess said yesterday that there are still options. It’s always good when you hear your oncologist say “options”, and not just “option”.
- Brad: Is there anything we can do to help?
- Linnea: Not at this juncture. But, again, I want to reiterate that certain things have been so helpful. First of all, the love and support and knowing that people care. Having my records accessible on Ciitizen is a boon. The additional genetic testing we got is going to be very helpful. I’ve gained a lot.
July 30, 2021 - (Still) Waiting for Her Turning Point
- Kimary Kulig received a copy of the HIPAA authorization form back from Massachusetts General Hospital that she had sent to Linnea several weeks ago. I added that I had spoken to Joanna Morales of Triage Cancer, who offers patient-friendly forms on a variety of topics. (Thanks to Sophia Cornew of Ciitizen for the connection to Joanna.)
- Kimary reported on her outreach to Calithera, a young drug company working on one of Linnea’s unique mutations, which had no agents ready to help Linnea.
- Jeff Waldron, Will LaValley, Peggy Zuckerman, and Kimary talked about the ideal design for patients to provide access to their medical records to friends and family they designate. I mentioned that we have solved this through Ciitizen’s hosting of patient data for the hackathons.
After a pleural effusion, a cytology test is performed. The results of my first two were reassuring. No cancerous cells found. However, there was a note of caution: the left pleural fluid cellblock contained ‘rare groups of highly atypical epithelial cells, consistent with metastatic adenocarcinoma.’
My third cytology exam, following last week’s procedure, was unequivocal: malignant.
Acccording to Medscape, ‘Development of a malignant pleural effusion is associated with a very poor prognosis, with median survival of 4 months and mean survival of less than 1 year.‘
Any treatment is considered palliative.
Grim and grimmer. However, my first response was take that twelve months and double it. Unrealistic? Sure, hell, why not. However, little about my last sixteen years has been realistic. Surreal is certainly a better adjective.
And, a week later, I will hopefully be taking my lead in dose of TPX-0131. In my wildest dreams, I shall respond and begin to feel better.
In the meantime, I am still adjusting to, well, limitations. Because of fatigue, I had pushed last Sunday’s date night to this evening. However, after showering in preparation, I immediately felt nauseous and vomited. This is likely a side effect of the pleural effusion.
I called my (very understanding) date, who was already enroute, and told him I would need to cancel. Again. And that, in all honesty, I was fooling both of us in thinking that I was well enough to socialize. As an enthusiast, I sometimes operate under the assumption that I can just power through. However, my body is making it increasingly clear that it is time to rest.
So I shall. Pace myself. But, with not just the hope, rather the expectation, that I shall rise (and date!) again.
There is no video this week.
August 6, 2021 - Update #18 - Handoff to a Turning Point on Thursday!
- Linnea and Kimary Kulig talked about how these targeted therapies can sometimes create deep responses rapidly.
- Jeff Waldron pointed out that Turning Point was unusually responsive in making their drug available through compassionate use as quickly as they did. Linnea shared her “slip up” — bluntly saying that Turning Point was making a mistake in delaying her access, and that Colin Barton of ALK Positive was relentless in making her case for access.
- Peggy Zuckerman suggested that Linnea keep a log of her experience and outcomes on the drug for herself and to share with Turning Point. Kimary Kulig offered some forms for Linnea to use.
- Please send positive energy Linnea’s way. Join us on Friday to see if Linnea is feeling better.
- Please see the surveys Kimary Kulig shared for patient-reported progress on Slack.
DrainedAugust 5, 2021What a busy seven days it has been. Melinda and Sally, Jemesii, Peter and his girlfriend Caroline and my brother Bink and sister John have all visited over the past week. It has been great fun, much has been accomplished and I am exhausted.However, I also have had more baseline energy. A function of restarting TNO155? Perhaps.
This morning I was scheduled for installation of a PleurX-cath–financial assistance approved. My breathing has also been some improved and I went to the appointment hopeful that I should be turned away again–but this time for lack of necessity.
And indeed a Pleur-x was deemed unnecessary at this juncture. Instead I had another thoracentesis which yielded 150 ml of serosanguinous fluid.
Last night I learned that TPX-0131 would be at MGH no later than early next week. I know my oncologist has been working tirelessly on my behalf to forestall more delays, and my friend Rob Densen and his pals at Senator Markey’s office got involved as well. Moral of the story? Choose your oncologist’s, your friends, and their friends carefully.
To put a dot on that i, I shall take my final dose of TNO155 tonight—and my final dose of lorlatinib on Sunday as I begin washout. And then, next Thursday, my lead in dose of TPX-0131.
There have been moments (hours, days) in the preceding weeks where I felt I was down for the count. I don’t feel that way today. Raggedy and realistic about the fight that lies ahead, but confident that I’m going to get a shot at it.
- Linnea: The manufacturing and labeling delay at Turning Point was helped through the efforts of my oncologist and a number of friends.
- Peggy Zuckerman: This kind of trial delay is more common and more heartbreaking than it should be. I work with a group called SWOG, which puts on clinical trials. It’s a network of doctors, and I don’t think they understand this at all. It’s a story I might use as an example.
- Linnea: If you do, I know a man named Alan Lee, who was EGFR positive, rather than ALK, and there was one drug coming out that was maybe going to offer him a chance. Alan was in his early 30s. He had a toddler and a brand new baby. He died three weeks before that drug came out. We were all contacting the company and pushing them because, as you know, sometimes when these drugs work, they work quickly. Even though it sounds like it’s “last ditch”, it could turn things around.
- Kimary Kulig: People don’t appreciate that these targeted therapies in particular can create deep responses very rapidly. Are you getting the Turning Point drug through a trial, or is it a single patient access?
- Linnea: I use the term loosely. It’s not a trial; I’m getting it through compassionate use. They will also be opening a trial, but it’s still a trial I would be precluded from.
- Brad: I recall that Jess Lin can control the dosing this way, which was a concern you had?
- Linnea: Even in the trial, they would have had dose escalation, and I would have been able to go up in dose. This will stay very much the same. But she can control other parameters, to make sure that I am admitted.
- Peggy: Is there an obligation in compassionate use for you to make a case study or report back to them? Reciprocity is sometimes requested by some of the companies.
- Linnea: I don’t know. They would want the data. But they’re not going to throw it in their pool.
- Kimary: There is not an obligation to publish, but if you have a miraculous response, they’re going to want to do a case study.
- Linnea: I’m going for that miraculous response.
- Peggy: I’m one of them from 17 years ago. I always say, “Follow my example.” You’re more prepared to do this than I ever was.
- Jeffrey Waldron: This is pretty exceptional. The timing is frustrating, but I don’t think they were ready for clinical trials. Normally when someone gets compassionate use, the company is already in clinical trials, and they have the manufacturing up and running. I think they moved pretty quickly, given my pharma perspective.
- Kimary: It’s pretty unprecedented.
- Peggy: Is it a Phase 2 trial?
- Linnea: Phase 1. What has been interesting though is that unlike any trial I have ever seen the mechanics of prior to a trial, there has been this dialogue going not only with my oncologist, but also with the clinical trial group at ALK Positive. Colin Barton is the head of that group, and he very persuasively and articulately pushed back against the conclusions. Months ago we had an email going back and forth, where I didn’t know that Turning Point was copied on it, so I just came right out and said, “This is not humane. And I don’t think it’s a good business decision because it’s going to make accrual more difficult — the preclusions after just three treatments.” I slipped up, but who knows, maybe it did some good. And Colin just kept on them. He used my individual case, and the case of Gina Hollenbeck, who is president of ALK Positive and also struggling. He made it frankly very personal. And that was unprecedented. I had never seen this kind of dialogue behind the scenes.
- Kimary: That’s awesome. I’ve spoken to Colin before too. I think patients know, but don’t underestimate the power that you have over these companies. Your “slip up” was probably a really good wakeup call. It’s not often that pharma hears that blunt feedback directly from a patient. It was a slap.
- Linnea: It called out the elephant in the room. Colin’s first response was to be aghast that I had not been more careful. But then he wrote back and said, “I see what you’re doing. You’re a genius.” Of course, I wasn’t. I just didn’t know they were in the conversation. But it’s not anything I wouldn’t say to them face-to-face.
- Peggy: It’s my experience that the people who are in the lab rarely see a patient. I’ve seen a couple lab people burst into tears when they were introduced to patients because they’ve never seen the people for whom they are working. To humanize the issues and the stories and the urgency outside a weirdly clinical trial world is needed. And that is why patients should be helping to shape trials and clarify the issues from a patient’s point of view. Even a delay of 10 days vs. 12 days can be life and death.
- Kimary: It certainly can be the difference between you qualifying for a trial, or not. I bring up that “performance status” measure again. That’s the biggest exclusion criterion. And even that wait time, e.g., to get your genomic test results back. In that time your health status or performance status can deteriorate and then you are no longer eligible to be on that clinical trial.
- Peggy: I hear stories where somebody is supposed to have a CT scan in 30 days, but they can’t get in for one in 30 days. And rather than the principal investigator or the onsite investigator saying we’ll get you the scan at our place, or make an exception, they should build that exception into the trial in the first place. Or accommodate the patient at a different site. People drop out of trials that they would otherwise qualify for.
- Kimary; If the trial is written well, there is usually a plus or minus number of days on either side.
- Peggy: This is the kind of thing that the SWOG patient advocates fight for.
- Linnea: A very real concern of mine is that I would still be alive, but deteriorate, as in my lung, to the point that there was nothing left to salvage. Those were conversations we were having. I know I can hold on for a long time, but let’s try to stop this progression while it can still be turned around.
- Brad: So, if you start the drug on Thursday, when we meet again on Friday, what are the markers that will tell you that it is improving? Will your breathing improve? Will they do a scan?
- Linnea: From personal experience, I will know by how I feel. I’m not sure when the first scan will be, and I’m also curious if they will scan before starting the drug. I’ve been on these other treatments, and I expect they will want a baseline.
- Kimary: You should recommend that.
- Peggy: If they have some sort of patient-reported outcome or reactions on a log, that would be valuable, for yourself and the company. For six days I was feeling better and better, then on the seventh day things slowed down.
- Linnea: They’re going to be curious about what I have to say, whether or not I’m a member of the trial because I am going to be one of the first people in the world.
- Kimary: That’s a really good idea. There are validated instruments, like the lung cancer symptoms scale, a dyspnea (difficulty breathing) questionnaire. If Linnea felt like it, she could fill that out.
- Peggy: Maybe that’s a job she could share with a friend.
- Kimary: They would be very impressed by that. They are a young company. It could really help what ALK Positive has been doing with them. You are educating them and bringing them along, and helping establish them as a company that is very patient-centric.
- Linnea: It is a great idea to create my own patient-reported outcomes. I’ve never liked the ones that we are given.
- Peggy: If you were the mom of a little one with lung problems, you would be tracking, monitoring, and keeping a notepad by the cribside. You’re the baby here. You can keep the log. You slept well, or you didn’t. All the things that you would monitor.
- Kimary: I can float you a couple surveys. The reason I’m advocating for using some validated instruments that they are already used to is that the FDA acknowledges their validity. It could lead to them having a label claim, such as impacts dyspnea. By the time they get to their Phase 2 and 3, they will be including patient-reported outcomes questionnaires. The common ones that are used include the Lung Cancer Symptoms Scale, and a dyspnea scale that I was trying to validate with Amy Abernethy. [Please see Slack for the surveys that Kimary shared.]
- Peggy: Is there any instrument that is used elsewhere out there that would be reporting daily progress, a log, not outcomes? I see too many of these surveys only capture outcomes at the end of the trial vs. the ongoing issues the patient is facing.
- Brad: I was a patient advisor of a group out of Mayo that is putting mobility measurement devices on patients as another way to measure quality of life. It’s moving to continuous device-reported monitoring.
- Kimary: Linnea, if you have a Fitbit or an Apple Watch, that is information they would love to have. I proposed that Verily do this — that they would have a study watch to capture an objective measure of performance status, such as being up and about. The 50% of the time ECOG cutoff is so damned subjective. [The ECOG scale was developed by the Eastern Cooperative Oncology Group (ECOG) in 1982.]
- Brad: Linnea, what do you need now? How can we help? What is “done”? We were trying to help you navigate to your best next treatment, and that could be this Turning Point drug. And there are many people following your journey, and very keen on how they can help.
- Linnea: It continues to move back. The next couple of weeks are critical — to see how and if I respond. I’m going to be focused on that. And that’s up to the universe. I really like this idea that was broached today about continuing to be an active participant in my role in a compassionate use situation, even if it’s not mandated. I want to use a validated tool, so it is taken seriously, and maybe add some anecdotal comments on the side if I’m feeling whimsical. It’s a good way to continue to hold the reins on the horse.
August 13, 2021 - Update #19 - Feeling Good! (A Turning Point?)
I awaited this weekly update meeting with Linnea with some trepidation. Linnea had said she would know by the way she felt whether the first dose of her new drug (a Turning Point 4th generation ALK inhibitor, which she had received on Thursday, the day before our meeting) was working. And she said she felt it was melting the cancer!
Posted on August 12, 2021
A fourth generation ALK inhibitor provided to me by Turning Point Therapeutics through compassionate use.
At 1:30 pm today I took the first dose. Before handing me the tiny tablet (it is one mg), Dr. Lin and my nurse Heather performed a little ritual—a blessing of sorts. And then, down the hatch.
By Dr. Lin’s estimate I am the third person in the world to take this drug (it is in clinical trial in Australia) and therefore it is impossible tp predict side effects.
Truthfully, I am far more interested in efficacy. And the thing is, if this experimental therapeutic is going to be effective for me, I may know very soon. Likewise if there is no response.
After dosing I hung out at the hospital for an additional two hours of observation. I squeezed in my second nap of the day (I had been there since 7:30 am) and when I awakened I just had this sense that something was going on in my body. Something good.
So light some candles. Cross some fingers. Have a chat with the universe on my behalf.
My participation in this, my sixth phase I clinical trial, would not be possible without the concept of compassionate use/expanded access.
That is because I did not qualify–was precluded–from the actual trial. The reason? Because I’ve had too many previous therapies–specifically ALK inhibitors. Three to date. Well, until yesterday Now four.
Fortunately, there was a back door. And I had a crew of people knocking on it for me. Colin Barton, who works so much magic behind the scenes at ALKPositive as chair of the Medical Committee. I talk a lot about goddesses; this man is a god of good. An ALK+ patient himself, he uses his smarts, personal resources and the fervor of a man on a mission to advocate for the other members of this club. He has initiated conversation with the decision makers at various pharmaceutical companies. I shared with him that at first I thought this might be a fool’s errand, but Colin is a visionary and he saw something I did not. And he has assembled an amazing team of fellow patients who work tirelessly to ferret out potential treatments that could benefit the ALK community.
My oncologist Dr. Jess Lin was also relentless on my behalf–contacting the sponsor almost daily. Jess presents as sweet and mild mannered, but she can be ferocious when it comes to her patients.
Of course, this was a time sensitive matter and some of my friends (talking about you Rob Densen) were not satisfied with the pace as I waited for drug. Where I was hesitant to reach out he was not and I am grateful.
So there we have it. Today I took my second tablet and then lay down for an hour so as to better visualize the cancer exploding like a mouthful of Pop Rocks. And, to continue with that metaphor, my mind continues to be blown by what a long, strange trip the last two months have been. I spent a whole lot of time thinking about dying all while hoping it wasn’t true.
Not natural bedfellows–these two thoughts. At least if you are hoping for a good nights sleep.
Therefore I am happy to report that I am still feeling good/better and that my dreams last night were sweet.
- Linnea: I am prone to wishful thinking, but I woke up from a nap, and felt that the cancer was melting away. I asked Jess Lin how long it took for cancer cells to react to the drug. I thought of it like aspirin. That it starts to take effect right away.
- Peggy Zuckerman: There are people who think that our directions to our bodies work. What you’re imagining may be influencing what’s happening.
- Jeff Waldron: You started yesterday. For what duration?
- Linnea: Until I have side effects that are not OK or it becomes clear there is no response. My concern remains that my left lung is a mess. The last draining of the pleural effusion was full of blood. It is going to be hard to recover. I know this is still a long shot. My body has been capable of fighting things, but it had gotten to the point where it needed some help. I hope this is the appropriate help. Going forward, the mysteries will be side effects. I’m the third person in the world so they know nothing about this yet. They’re just guessing.
- Peggy: I serve on a scientific ethics advisory board for Roche, and we have heard there is about a 95% approval by the FDA for patients who were benefiting in a trial to continue to receive the drug.
- Kimary: Do you know the dosage they’re giving you?
- Linnea: One milligram.
- Brad: I’ve heard that very few people aren taking advantage of compassionate use.
- Kimary: If so, that’s because of the paperwork burden. And busy community practices. They have little time to jump through the hoops.
- Peggy: And the community oncologist will be less capable of making the argument. It helps if the oncologist is in a center of excellence.
- Kimary: Who has the time to keep up on what’s in everyone’s pipeline? And even if you do know, it’s hard. I reached out to Calithera, for example, to find out about access to their drug, and their products weren’t ready. I was just a citizen. Maybe a top notch clinician would be more persuasive.
- Jeff: I moderated two panels on compassionate use and expanded access. There is a document on obtaining access in countries around the world. Naomi Litchfield of Bio Emass gets access for patients in the UK. The panel also included Christine McCracken who was at Janssen, and her job was to help patients get expanded access. It’s not like there is no one in pharma on the other side. One of the panelists was from the FDA and was concerned that expanded access might be a workaround that would enable patients to avoid clinical trials.
- Brad: We spoke last week about capturing your own data on a patient-reported survey to feed back to the manufacturer.
- Linnea: They will capture the data if they want to. One of the biggest issues with compassionate use is you have to have a life-threatening disease, and you have to have exhausted all other treatments. So you are likely very sick. I view it as a win-win. They will capture data they think will be useful.
- Peggy: You can provide your own sense of side effects. If you have side effects, you need to know who to discuss them with, and that might be in addition to your current medical team, but those who are working on the drug.
- Kimary: It’s probably too early for them to even have dose de-escalation plans. Expanded access is the big umbrella, and compassionate use is under that. Expanded access can raise concerns for pharmaceutical companies since they can mess up the end points of clinical trials, not only for the pharma company, but for competitors.
- Linnea: What’s unusual about my situation was getting access before there was access through clinical trials. It’s available in Australia, but not at MGH. Jess gets to write and control the protocol.
- Peggy: Is there another site in the U.S. that is also offering this trial?
- Linnea: There is one at UC Davis.
- Brad: What can we do to help?
- Linnea: Stay tuned. In other news: my youngest son got a new job. He will be working for Mercy Bio Analytics as a cancer researcher. I’m hoping I’ll be even better next week.
August 20, 2021 - Update #20 - No word, media relations
Thanks for your continued interest and support for Linnea Olson.
Linnea didn’t join our weekly update call on Friday, and she has been quiet on her blog for over a week, so I don’t have much to report. And I’m concerned.
After my cancer diagnosis, many of my friends get worried when they don’t hear from me in a while. Now the shoe is on the other foot.
- Tests and the issue of tissue: identifying the full range of testing options that were available to Linnea and prioritizing scarce tumor tissue among the many tests.
- Treatment access: the hurdles that Linnea ran into and was able to overcome to get access to her best next treatment, thanks to the help of her oncologist and the ALK Positive community, among others.
- Clinician engagement: challenges in collaborating between the hackathon and Linnea’s oncologists, as well as engaging all the expert clinicians we might have liked in Linnea’s treatment prioritization.
- Proxies and backups: breakdowns in the ability of the hackathon community to help Linnea when she was incapacitated.
- If you know people at media outlets (podcasts, journals, other publications) who might like to share our work and what we’ve learned with their listeners and readers, please introduce us.
- If you are interested in one of these topics and would like to contribute to an article, please let us know.
August 27, 2021 - Update #21 - Hoping for a Positive Response
Linnea didn’t join our weekly update call
- Linnea’s latest drug has caused intense neurological symptoms, and she was (is?) in the hospital. From Sunday: “They are thinking it will take apx 5-10 days for her body to fully metabolize the drug and hopefully return her to normal functioning — and then we will figure out what’s next.” (For more on Linnea’s current state, please see recent Facebook posts by Linnea’s daughter that John Novack posted on Slack.)
- TJ Sharpe noted a Facebook post from Wednesday that Linnea had had a good day — she was present and lucid.
- Kimary Kulig ventured an optimistic interpretation that Linnea may be having a strong immune system reaction (a cytokine storm).
- Peggy Zuckerman shared that she had hallucinations in response to her cancer treatment many years ago, and it was a good sign that she kept from her family and the doctors, for fear that they would take her off the drug. She wants Linnea’s family to know that hallucinations are good!
- If you are connected to Linnea’s family, please pass on our hopes that these drug reactions are a positive sign.
September 3, 2021 - Update #22 - In the Hospital
Linnea is in the hospital but stable, according to a report that John Novack saw from Linnea’s daughter on Facebook.
As expected, Linnea was unable to join the weekly update today.
- Peggy Zuckerman mentioned The Society for Participatory Medicine as a group that is championing patient education, activation, and engagement. (I’m also a member.)
- Will LaValley offered his advice to patients in their initial meeting with their physician to level the playing field by speaking of their goals and values up front, including the key phrase, “This is for my medical record.”
September 10, 2021 - Update #23 - Recuperating
Here’s what Linnea‘s daughter posted Wednesday to Facebook:
I haven’t posted an update in a few days- apologies! here is a photo of Pete and his absolutely precious new pup- we are now neighbors Mom continues to make strides forward and will be moving to/or has moved to a rehab facility to help her make even firmer steps (‘twas happening today but no updates yet). we continue to appreciate the love and care sent her way and I will update again when I have more info. and as always my (fairy)godmother is just that… a godsend. breathe in. breathe out. repeat. repeat. repeat.
September 17, 2021 - Update #24 - Home after Rehab
September 24, 2021 - Update #25 - The Ugly Business of Aggressively Advanced Lung Cancer, Pause on meetings
We will continue to share additional updates on her condition when we can.
October 1, 2021 - Update #26 - Recuperating at home from the neurological side effects of TPX0131
At times, it’s been more than a little touch and go.
Although I couldn’t possibly relay the whole sordid tale, I shall attempt to hit some high and low spots.
TPX0131 and I had a brief and tempestuous relationship. Six days in I would have said no side effects.
And then the shit hit the fan big time. Initially I was admitted to the ER for a lingering pneumonia (fevers–serious ones–of unknown origin.) They did what they could for me (IV antibiotics) and then I was released briefly (and if any of my handlers/editors notice any errors–please let me know. I am not entirely sure this visit was post trial onset).
I also know that I was next admitted with mental confusion. And at this point it all goes dark. Later I would realize that I was often hallucinating. All in all a month + in the hospital (lots to relay regarding that) and then two weeks in rehab.
It was hell; all of it. The current conclusion is that I suffered a severe neural injury. Tripping x 1000 (my assessment). And it took more than a month to start coming down.
The entire experience was terrifying. I am back home now trying to relearn simple things, such as typing and walking. My group of friends and family have been amazingly supportive.
I have also been very appreciate of messages, flowers, and food sent my way.
Now I must rest but I shall try to check in more frequently.
November 15, 2021 - Update #27 - Unhappy news: Linnea Olson has passed
Bryce: “I hate seeing friends pass from this awful disease … It just sucks.”
John: “I’m numb, … Strange, but her death has stunned me, so this one hurts. I rewatched this [15 minutes TEDx talk], which took place just days before her 60th birthday. I was fortunate to be in the crowd, and be invited to be part of a celebratory lunch after the TEDx talk.”
Erika always cautions me to remember that when it comes to cancer, we don’t talk about “a cure“. Erika is more experienced than I am in these unfortunate passings of friends. These are relationships we develop because of our connection through cancer, which raises the probability that these friends will die.
December 3, 2021 - A Tribute to Linnea Olson
Evalynn Linnea Olson
11/26/1959 – 11/15/2021
As many already know, it is with heavy heart that we share news of Linnea’s passing.
She was able to pass away at home, her adult children and family members were with her, and her clinicians and hospice team provided the full care and support she needed. It was very important to Linnea to be able to make an anatomical donation to the Mass General Cancer Center lung cancer research lab instrumental in her care. Together, her family and friends were able to help achieve all of her final wishes.
On Friday, December 3rd, Linnea’s family and friends will host a reception in her honor. The event will be held 6PM – 9PM EST at Maria’s Restaurant, 81 Essex Street, Haverhill, MA. For more information about this event, please visit: https://www.mykeeper.com/event/celebration-of-life-evalynn-linnea-olson/
If you cannot participate in person, join us for a Livestream at Linnea’s celebration of life in which we will reflect on her youth, her mission as an advocate for the lung cancer community, and her impact as a visual artist.
Link to the livestream event: https://fb.me/e/2Rg4j4dTe
Amesbury, MA – Evalynn Linnea Olson, known to all as “Linnea”, died at the age of 61 on Monday, November 15, 2021. She was a mother, loved by family and friends for her vast artistic mind and warrior spirit, as well as a fierce advocate and blogger for the cancer community while living with lung cancer for 17 years. Linnea is survived by her three wonderful children, Jemesii Delande and Peter Duff of the greater Boston area and August Kaan of Toledo, OH.
Linnea was born on November 26, 1959, in Ann Arbor, MI, the eldest child of Dr. Hilding Gunnar “Ollie” Olson and Evalynn (Pier) Olson Betzing Goodman. She shared her life with her extended family, including her step-mother Carolyn Olson Kersten of San Angelo, TX, her step-father James Goodman of St. George, UT, and her deceased step-father Richard Betzing of Fort Collins, CO. She enjoyed an active childhood with her six brothers and sisters: John Olson and his wife Amanda (Fort Collins, CO); Kristin “Bink” Owsley and her husband Greg (Fort Collins, CO); Laura Pastor and her husband Andy (Austin, TX); Diana Galvin and her husband Bobby (Temple, TX); Daniel Olson (Anchorage, AK); and Rosalie Olson and her husband Brian Dougherty (Boulder, CO). She is also survived by her nine beloved nieces and nephews, including Shannon Olson Payne; Mesa and Zola Owsley; Jacquelynne Amaro; Max, Eli and Hale Pastor; Magnus and Alma Dougherty; her grandniece Jordynne Amaro and grandnephew Iverson Mentel. Being with her family brought Linnea tremendous joy and fueled her incorrigible zest for life.
Linnea graduated from Poudre High School in Fort Collins, CO in 1977. She pursued her passion for oil painting and received a bachelor’s degree in Art, Painting Concentration from Colorado State University in 1981. Following this, she lived in Fort Collins and later the San Francisco Bay Area where she began raising her children and working at the Palo Alto Public Library. In 1996, Linnea and family moved to Ipswich, MA, later residing in Meredith and Amherst, NH, and Lowell, Haverhill and Amesbury, MA. As a lifelong artist, Linnea had an incredible eye for finding beauty in the ordinary – which she captured in her paintings, curated collections and nature photography. She found inspiration in beaches and sidewalks, rivers and train tracks- constantly in a state of creation.
In 2001, despite her active, healthy lifestyle, Linnea began experiencing challenges with her health, progressing to a long bout with pneumonia. As an otherwise healthy, young, non-smoking female, accurate diagnosis was elusive. After several years of medical evaluations, her life was changed when she was diagnosed with stage 1B lung cancer. Her youngest child was still in elementary school. Determined to be present for her family, she pursued clinical care at Massachusetts General Hospital (MGH), where she was followed by the oncology teams of Douglas J. Mathisen, MD, Thomas J. Lynch, Jr., MD, Alice T. Shaw, MD and Jessica J. Lin, MD.
Due to the advanced nature of her cancer, Linnea found herself as a patient at the forefront of cancer treatment and research. With deep belief in scientific research and a voracious need for more time, over the space of 17 years she was a participant in six clinical trials, which served as landmark studies that changed the course of lung cancer targeted therapy the world over. Her body responded well to the novel therapeutics, to the extent that medical imaging scans of her lungs, before and after treatment, are still shown on display at the Paul S. Russell Museum of Medical History and Innovation at MGH.
In 2005, Linnea’s natural inclination to connect with others, along with her poetic yet precise way with words, led her to create a blog entitled: “life and breath: outliving lung cancer – for the terminally optimistic” (outlivinglungcancer.com). Her blog soon became a resource for more than 4,000 followers, from patients and caregivers to physicians and biomedical researchers. Her well-informed and bravely candid writing shared essential resources and medical knowledge, while also giving voice to what it is often like for patients living with cancer. With honesty and humor, her writing created a community which stands as a testament to who she was. Linnea had a curiosity for life and learning, a talent for teaching, and an unyielding desire to share her unbiased, truthful observations of the world around her.
Always a strong patient advocate, Linnea’s work touched the lives of people around the world. She presented at numerous forums, including Harvard Medical School, TED Talks, industry presentations and international conferences. In 2016, Linnea was awarded LUNGevity’s Survivor Face of Hope award for her tireless work on behalf of fellow patients and served on the External Advisory Board of their committee “Patient FoRCe.” She was also honored as the 2020 Recipient of the LUNGevity Annual Fan Award. In 2019, she served on a group panel at the World Conference on Lung Cancer in Barcelona, Spain to address best ways to support patients and clinicians in their search for clues to combat lung cancer. She joined the board of trustees of the Israel Cancer Research Fund (ICRF.org) shortly thereafter. She was a 2020 recipient of A Fresh Chapter foundation grant to visit with fellow cancer patients in Peru. Additionally, she was on a Hackathon in 2021 to promote efforts to find new drug therapies.
Linnea identified equally as both advocate and artist. Between 2012 and 2019 she lived at the Western Avenue Studio and Lofts – an artist’s community in Lowell, MA. Linnea was well known to all as a friend, an informal counselor and generous spirit. While she spoke of herself as a painter, Linnea’s artistic identity was as often defined by an insatiable desire to collect and curate. Linnea packed her studio with fascinating collections of shells, sea glass, bell jars, books, antique doll heads, globes, vintage clothing, rusted bits of metal, pieces of discarded paper and wood and an impressive array of other interesting things she found on her frequent walks, thrift store trips and eBay scourings. She had an incredible eye as curator, turning seemingly unwanted, discarded items into stunning collections. 2018, her last exhibition, Found, at the Linda Hummel-Shea ArtSpace Gallery of Northern Essex Community College presented dozens of assemblages — combinations of found objects that together create new poetic meanings. These works embodied Linnea’s drive to find deeper meaning in her life through her art and collections- and her deep love for the often overlooked or forgotten.
One of Linnea’s most sacred daily routines was a long, wandering walk which became even more important after adopting her energetic Shiba Inu, Kumo. Linnea often documented her walking observations in a series of Facebook posts she called “Notes from the Field.” Reading them offered a glimpse into Linnea’s heart and mind. On March 21, 2021, Linnea wrote:
• Tree trunk, knot like a navel.
• Sun wraps the back of my head.
• Plastic bag caught on a branch; pale ghost.
• Wind chimes sounding like summer.
• Sunday morning paper.
Her friends will carry Linnea’s inspiration in every walk while she reminds them to keep their eyes open to the beauty of the world around them and to remain always curious.
Linnea’s family and friends offer their deepest thanks to the incredible team of providers at the Mass General Cancer Center. Their intellect, kindness and devotion to patient care is exemplary. Gratitude for the kindness of friends who helped Linnea throughout her journey. Sleepovers, rides, dinners, unanticipated flower bouquets, dog walking and assistance in many forms enabled Linnea to live fully and vibrantly. Know that each act of kindness meant the world to her.
A celebration of her extraordinary life will be held on Friday, December 3 from 6PM – 9PM at Maria’s Restaurant – Galleria Banquet Room, 85 Essex Street, Haverhill, MA.
For more information, please link to: rememberinglinnea.com. Out of an abundance of caution for family and fellow guests, attendees must be fully vaccinated against COVID-19 and wear masks. Donations in Linnea’s honor can be made to LUNGstrong.org (which will be directed to MGH lung cancer research), LUNGevity.org or ICRF.org.