Cancer Survivors, Pain Management, and Guilt

I am very interested in issues related to Survivorship -- what happens after a patient is "finished" with cancer. Part of why I find it interesting is because it's so hard to know when Follicular Lymphoma is "finished." Since it's still considered incurable, we're kind of always "patients" rather than "survivors," at least the way most people use those words. Personally, I call myself a "patient," to remind myself that there's no guarantee that it's not coming back.

But the other reason I find Survivorship so interesting is because I hear stories from so many patients (through email, on Facebook and Twitter, etc.) about the problems they encounter after their cancer is "finished." There are hospitals that have Survivorship programs, to help patients who have finished treatment. the best ones deal with a whole range of issues -- physical, emotional, even financial. But any help is great. So when I hear negative stories, especially about patients whose doctors have dismissed their concerns, it makes me sad and angry.

All of this was prompted by an article that just came out in the Journal of Palliative Medicine. "Palliative medicine" is often thought of as only related to hospice, which is a shame. Palliative medicine focuses on pain management and making patients comfortable, no matter where they are with their cancer (early on, still in treatment, out of treatment, or elsewhere). 

The article is called "'It Is So Easy For Them to Dismiss': A Phenomenological Study of Cancer Survivors with Chronic Cancer-Related Pain."I actually learned about from a Twitter thread written by the lead author, Dr. Katie Fitzgerald Jones, who went into depth about what the article says.

It's an important topic for survivors and patients -- whichever word you want to sue for where you are. Cancer as a disease, and cancer treatment, and the treatments that help us with side effects -- all of them can cause us pain of different kinds. And a lot of times it is chronic pain -- pain that stays with us even when cancer and its treatments go away. The research for this article is based on deep interviews with 13  cancer survivors (with different kinds of cancer, not just FL or even blood cancers). Their experiences were very similar.

The researchers found three main themes in the interviews.

First is the emotional relationship that patients had with pain. Many of them found that the chronic pain was accepted as a kind of trade-off for being alive. In other words, they felt like they just had to deal with the pain, and some even felt guilty for complaining about it. Doctors have a hard time with pain management in survivors because there isn't necessarily an easily identifiable source. A tumor may be gone, but pain remains, and it's hard to know why. the researchers call his "invisible suffering," and it's a complex thing.

Second is what the researchers call "the opioid paradox." Opioid pain killers can be very effective. But at least in the U.S., we have a large societal problem with opioids, with them being over-prescribed for some patients. So some doctors are anxious to get their cancer survivor/patient off of opioids, to avoid possible addiction. But then doctors assume that because a patient is not on pain medication that everything must be OK. And that's the paradox -- pain is better management when you do something "bad" and pain is worse when you do something "good."

Third, oncologists are not pain management specialists. They're great at helping patients who are in active treatment, and less great when treatment is done. So it's often up to patients to figure it out themselves. 

The researchers conclude that the research might help make this situation better in several ways: first, pain management has many different sides to it, and will need many different solutions, not just for all patients, but maybe for each individual patient. Second, there needs to be better communication between patients and doctors and other supporters. Finally, doctors need to know more about pain and its management, and to develop skills to better help patients.

How does all this affect us as patients/survivors? (And let me remind you that I have as much expertise in palliative medicine as I have in oncology, which is to say Zero.)

I think (and again, this is my opinion) that most of us should pay more attention to whatever Survivorship resources are available to us. If you are seeing an oncologist that is affiliated with a large hospital, check to see if they have a Survivorship program. Lots of them do. If you see an independent oncologist in a clinic, ask if they have resources they can recommend. Most do -- they can recommend a social worker or counselor that works with cancer patients, or can recommend a pain management specialist. If you are hoping to avoid more medication, lots of Survivorship programs can recommend other options, like yoga, or acupuncture, or massage. A good Survivorship program will be open to all of those possibilities.

What strikes me most about the research in this article is the emotional aspects of all of this. Especially the guilt.

I've written about this before. I think guilt might be the most destructive but under-recognized emotion that Follicular Lymphoma patients have to deal with. Lots of us can feel guilty for having a cancer that doesn't need treatment right away, or for not needing as aggressive treatment as patients with some other cancers. We don't need more guilt that comes with needing help once treatment is over. There's no reason to suffer when help is available. Nobody deserves to live with pain.

So I hope some of you will look into the kinds of resources that are available to you, even if you don't need them right now. It's nice to know that they are there if they are needed in the future.

You certainly deserve the help.

Relapsed and Refractory Follicular Lymphoma (Video)

The Lymphoma Research Foundation sponsored an online webinar last month on Relapsed and Refractory Follicular Lymphoma, featuring Dr. Bruce Cheson. If you've been reading the blog for a while, you might recognize the name. I believe he is retired now, but still very active in the Lymphoma community. I've always found him to be very informative and very entertaining.

This webinar (which you can watch by clicking the link above) is aimed at R/R FL patients, and Dr. Cheson addresses them directly. It's a very good overview of the landscape of what is happening for R/R patients -- those whose first treatment stopped working, or didn't work at all. (I think the webinar took place last November, but was posted online last month.)

Some highlights:

He begins by giving some statistics about R/R FL: the overall survival rate at 10 years is about 80%, and patients who are not POD24 have a lifespan that is very similar to the overall population.

He also shows some statistics that discuss older treatments (that is, it doesn't include things like CAR-T and bispecifics). At one time -- and I remember this very well -- it was thought that the typical path for most FL patients was that we would need many different treatments over time, and that each treatment would give us a shorter Progression Free Survival. In other words, we might have chemo, which would put us in remission for maybe 5 years. Then another treatment would work for 3 years. Then another for 1 year. That was definitely what I expected to happen 15 years ago. But that's not the case anymore. We get much longer times between treatments these days.

Dr. Cheson also spends some time discussing current treatment options, with their strengths and weaknesses: Rituxan/Obinutuzumab, RIT, Bendamustine, R-squared, Tazemetostat, PI3K inhibitors (no longer available), CAR-T, and Bone Marrow Transplants (which Dr. Cheson hasn't used in a very long time). He discusses many of these in detail, including PI3K Inhibitors. He is enthusiastic about Zandelisib, though this isn't being studied much anymore.

He moves on to some of the "more exciting stuff," including bispecifics. He's careful to spend some time on side effects of these treatments, as well as their effectiveness. It's nice to hear the excitement in his voice. He gives a similar discussion of CAR-T, explaining what it is, and reviewing some studies and discussing their effectiveness and side effects. He also gives a nice comparison between CAR-T and bispecifics.

Finally, he looks at some of the treatments that are currently in development. His conclusion about Relapsed and Refractory FL: chemo should not be considered an option, because there are so many non-chemo options. And with more options coming available, "newer approaches will clearly improve outcomes." Patients should consider clinical trials as a way of getting access to these treatments and helping them along the process. 

It's a nice overview of where we are with R/R FL, and as I said, I have always found Dr. Cheson to be entertaining. [Watch for his joke about "transformation" at about the 10 minute mark.] Most importantly, he is hopeful, and that's what I like most about him (and his presentations) -- he sees a very big picture, knows where the world of Lymphoma has been, and can see where it is going, and he is very happy about the direction it is moving in. 

This is a useful video for anyone with FL, but especially those who have had a first treatment. It should give you lots to be positive about.

Live Life Deliberately: Lessons from Jimmy V

 Where I am now, the NCAA basketball tournament is in full swing. This happens every year at this time -- it's known as "March Madness." I'm with family who are obsessed with basketball, and I spent a pleasant day yesterday watching games with them.

While we were watching, an advertisement came on that featured some clips from the 1983 championship game (30 years ago!), which was won by North Carolina State University. No one expected them to win the tournament, and they are still considered one of the great Underdog stories in sports.

But it's their coach, Jim Valvano, that has had a bigger impact on me.

I want to share this piece that I wrote 5 years ago for The Mighty. I had originally called it "Live Life Deliberately: Lessons from Jimmy V." The editors changed it to "What It Meant to Hear Jimmy V's ESPY Speech Again as a Cancer Patient." I like my title better, but that's fine.

Coach Valvano, also known as Jimmy V, eventually became a television commentator, and after a few years, was diagnosed with stage 4 metastasized Adenocarcinoma, a glandular cancer. Shortly before he died, he was given the Arthur Ashe Courage and Humanitarian Award at the ESPYs, a sports award program. The speech he gave became famous.

I wrote about in the 25th anniversary of the speech. You can read what I wrote by clicking the link above. In my story, you can watch his speech, too. It's worth taking the time to watch it. 

Jimmy V says we should "live deliberately," being aware of the things we do, to make sure we live a full life. There are actions we can take every day to make that happen. It's advice for everyone, not just cancer patients.

I really like his advice, and I like getting the reminder. Every now and then, when life gets busy, or when distractions get in my way, Jimmy V's speech will come into my head. Sometimes I'll take a few minutes to watch the speech again. It's good to have the reminder.

I guess these days we'd call it "mindfulness" -- being aware of our actions and making deliberate choices to do certain things, and not do others. Being overwhelmed by cancer can make that hard.

So I hope you all are able to get into a good place in your minds where you can live deliberately, with mindfulness, making choices that help you live a full life. 

Have a good day.

The Problem with Electronic Records

 Interesting article in this month's JCO: Oncology Practice, a journal aimed at clinicians (the oncologists that we see in their offices -- the ones that deal with us directly). It's called "Communication Skills Training for Oncology Clinicians After the 21st Century Cures Act: The Need to Contextualize Patient Portal–Delivered Test Results." It's aimed at oncologists, but it has some important lessons for patients, too.

The article looks at the complications that have come with a United States law called The 21st Century Cures Act, which was passed in 2016. The law made a lot of changes, especially in ways that allowed the FDA to approve treatments and medical devices more quickly and incorporate more patient experience into the process. 

But another big change had to do with patient access to medical records. Changes had already been put into place that gave patients much more access to records by encouraging electronic medical record-keeping. I'm sure all of us are familiar with MyChart, or MyChartPlus, or FollowMyHealth, or PatientNow, or ModMed, or whatever Electronic records platform your doctor and hospital use. (Or, more likely, you have records with a bunch of different platforms, like I do. And none of them connect to each other very well, so one doctor has to print out a record and fax it to another doctor, who has to scan it and add it to my records, so everyone has everything all on one place. It's ridiculous.)

Anyway, aside from the lack of communication among all of these platforms is the problem that comes from patients having too much access. Before the 21st Century Cures Act, patients usually had about 24-48 hours before their test results (or other information) were available to them. The Cures Act changes that so the results were instant -- once the test was complete, it was put into the Electronic platform, and patients would see it immediately. 

As the article points out, this can be a problem. Maybe this has happened to some of you -- you had a scan, or a biopsy, or a test, and you were nervous about the results, so you checked your records every 5 minutes, and then when the results were posted, you had no idea what they meant. Or maybe the results were really clear, but you didn't know if they were good or bad, or just how good or bad. 

I think this happens a lot. There's a real tension between two important things. Patients should have access to test results. They are, after al, our results. But the other thing is that a doctor needs time to look them over, too, and be able to explain them. And maybe that phone call with an explanation is going to take a few hours, because the doc is seeing other patients. Or worse, the explanation is going to mean an in-person visit, and that could takes days before it happens.

The article offers some possible solutions to this, including going back to the 24-48 hour delay, so the doctor has some time to look things over and explain them. Or another solution: include links to videos or other resources that can give general explanations to some of the things in the chart. Some information might be better than no information.

I'm not sure there's an easy solution, other than having a doctor always be available to talk about what's in your chart, which is impossible. 

The solution, from our end as patients, would be to all agree to just hold off looking at the chart until the doctor had time to look at the results and get back to us. But that's pretty much impossible, too. Information is available, and we're going to look at it. (It's a lot like some doctors who tell their patients not to Google things. That's just not realistic. Our computers and phones are right there in front of us, and we have questions.)

But we can at least understand the consequences. The article recognizes that, for some patients, this is a good thing -- it can be empowering to have information, and to then find answers to the questions we have, without waiting for the doctor.

The problem comes with where we find those answers. I've seen lots and lots of patients go to other patients in online groups and ask questions. There are often lots of answers provided, and one of them is correct. But how do you know for sure which one?

I think the answer, in the end, is that we all have to deal with the difficulties that come from trial and error. The first time we do this, we panic and until we talk to the doctor and get the answers we need from (hopefully) the person who understands our situation best. After that first time, ideally we'll know what works best for us -- waiting for the doctor, finding answers on our own, or just not reading the chart. 

In the end, this is about understanding ourselves. And in an ideal world, that's what having cancer does -- give us a chance to get to know ourselves better, and understand what we need as patients, and how to get it.

 

A Future for PI3K Inhibitors?

In my reading about cancer (which I do way more of than I would like), I've been seeing some articles about PI3K Inhibitors. Coincidentally, the journal Blood and Lymphatic Cancer: Targets and Therapy just published a review of PI3K inhibitors for CLL and Indolent Lymphomas. As a review article, it isn't offering any new research. It's more of a "here's where we are" article. But it's been a little under a year since the FDA pulled its support for PI3K Inhibitors for Follicular Lymphoma, so it's worth thinking about their possible future.

The article is called "PI3k Inhibitors in NHL and CLL: An Unfulfilled Promise," and I think that's a really great way of describing this class of treatments. One of the things that always struck me about this type of treatment was how excited oncologists got when they discussed it (at least in the videos I have seen, many of which I have posted). In theory, it's an excellent treatment. "Inhibitors" are things that inhibit, or stop something from happening. PI3K inhibitors stop an enzyme called Phosphatidylinositol 3-kinase. This is an important part of a chain of enzymes and proteins that turn switches on and off in a cell that allow the cell to grow and live. When something does wrong with the chain, the cell refuses to die. That's what cancer is, in its simplest form -- a bunch of cells that refuse to die. A PI3K Inhibitor stops that process. That's exciting -- especially since some of them were given as pill that a patient could take every day on their own.

The discovery of that chain of events, and the role of Phosphatidylinositol 3-kinase, was very important for Follicular Lymphoma research, since PI3K was especially important in B cells (the cells that become cancerous in FL). Several PI3K Inhibitors were developed, with slight but important differences between them.

Eventually, four of them were approved for Follicular Lymphoma patients. Because they showed promise in early trials, and were treating cancer in new ways than treatments that were already available, they were given accelerated approval by the FDA. This meant that they could be given to patients based on the results of a small phase 2 clinical trial. However, this approval came with the understanding that a larger phase 3 trial would be necessary for full approval.

And that's where the problems started showing up. You can go back and read what I wrote about the PI3K Inhibitors having problems and then having their temporary approvals taken away by the FDA -- Duvelisib in December 2021, Idelalisib in January 2022, Parsaclisib also in January 2022, and Umbralisib in February 2022.  then in March 2022, the FDA discouraged the makers of Zandelisib from seeking Accelerated Approval.

The reason for all of this? Some of the phase 3 trials, which were supposed to confirm the good results from the smaller phase 2 trials, did the opposite -- they showed some new problems with side effects, including an decreased Overall Survival. In other words, instead of keeping people alive longer, there were a greater number of people dying in the trial than had died in the trial that they were comparing themselves to.

The FDA's solution to this was to cancel its temporary approval and insist that full approval would only come with a phase 3 Randomized Control Trial. What does that mean? The trials that had been set up were single-arm trials. A number of patients were given the treatments, and the results were compared to a trial from another treatment (the trial probably took place years before). The makers of the Inhibitor could then say, "See? Our treatment is more effective and/or safer than that other one." A Randomized Control Trial has two arms -- instead of looking back at the trial for another treatment, it's set up so that half the people in the trial get that other treatment directly, and half get the PI3K Inhibitor. This way, there can be more control over which patients are in the trial, and a direct comparison can be made. 

But RCTs are expensive, time-consuming, and complicated. They are also the best way to know if a treatment is safe and effective.

However, one by one, the makers of the PI3K inhibitors announced that they were withdrawing their treatments. This was all happening at the height of the Covid-19 pandemic, and they were having trouble getting patients to enroll in their trials. Most decided that the extra expense and time wasn't going to be worth it. It seemed like they had planned on making money and recovering their research costs right away, and they weren't able to. Personally, I think there was too much competition as well, with too many PI3K Inhibitors on the market without enough to distinguish between them. 

Business decisions aside, there were still problems with the treatments that needed to be overcome. As this article says, there are still some possible changes to PI3K Inhibitors that could make them safer without being less effective.

One is to change dosage. When they were approved, most had a daily dosing schedule -- the patient took a pill every day. But that constant treatment meant that their immune system was always suppressed. This led to more infections, some of which were fatal. Zandelisib was designed to get around this, with a different dosing schedule, with the patient getting the treatment for a couple of weeks, and then stopping for a couple of weeks. This seemed like it was helping with side effects. But its makers decided that it would be too expensive to continue to develop the treatment, and stopped all of its research (except in Japan). 

So that's where we are -- an "unfulfilled promise."

It's too bad. From what I read, this does seem to be a business decision more than a medical decision -- the investment just isn't worth what it would cost to make the treatment safer and more effective (or at least, to find out if it can be made safer and more effective).

But the authors of the article still seem to cling to a small amount of hope that maybe something can come of it. My hope is that a small company will take this on, one that hasn't already spent millions of dollars, and will find ways to improve on this promising treatment. 

I also think that failed research is never a failure, and that even if these treatments are never resurrected, researchers will still have learned something that will make some other treatments better. 

We'll move forward, one way or another.

LRF National Workshop

I like to alert you all to interesting online opportunities for education when I can. And as you probably know, the Lymphoma Research Foundation (LRF) does a great job with this.

The LRF does some in-person workshops, and lots of online workshops, sometimes focusing on local patients. But they do some national stuff too, and their next National Lymphoma Workshop is coming up on Saturday, April 1. 

It looks like a good one. You can look at the agenda at the link above.

Some things that I am especially interested in:

• After a general overview of what lymphoma is, there is a special session on Covid-19. It's still with us, and still affecting many lymphoma patients who are immuno-compromised. It will be interesting to hear about the latest research.
• There will be two sessions on Follicular Lymphoma, one for the newly diagnosed, and one for Relapsed/Refractory patients. There are different issues to consider and different treatments available for these two groups. Nice that they are separating them out.
• There's a session on Survivorship, led by Dr. Gita Thanarajasingam from the Mayo Clinic in Minnesota. Some of Dr. Thanarajasingam's research has focused on Quality of Life and Patient-Reported Outcomes. She is an excellent person to lead a discussion on Survivorship -- what happens when treatment is finished, but lives have changed in physical and emotional ways.
• Finally, there is a special session on CAR-T and Immunotherapy. It's the only session on a specific treatment, which tells you something about how important CAR-T is for lymphoma. (Though I'm guessing the "Immunotherapy" part will also get into bi-specifics. Just a guess.

As I said, it looks like it will be a very good day, if you want to know more about Lymphoma in general, and FL specifically.

You can find out more, and register for the workshop, at this link.