Patient-Centered Decision Making (Video Series)

A website called The Cancer Network has a new short video series for doctors called "Around the Practice: Patient-Centered Decision-Making in Relapsed/Refractory Follicular Lymphoma." It is meant for doctors, but not Lymphoma specialists. So it's general enough to be understandable.

The focus is on Relapsed/Refractory Follicular Lymphoma, so it's about making treatment decisions after at least one treatment. I find these kinds of discussions interesting, because, of course, I have already had treatment. But there is also a sense that the patient already knows what's happening. It's a different kind of discussion. I'll explain what I mean below.

The videos feature three oncologists -- Dr. Reem Karmali of Northwestern University, Dr. Daniel Landsburg of the University of Pennsylvania, and Dr. Geoffrey Shouse of City of Hope. The video series includes 4 videos, all fairly short. The first gives a general overview of Follicular Lymphoma, especially Relapsed/Refractory FL, and the notes for doctors underneath the video gives some advice for doctors about what they should look for to determine if a patient has relapsed. There are no surprises here -- swollen lymph nodes, for example, or "B symptoms" like fever, night sweats, and unexplained weight loss.

What I find really interesting is the assumption that doctors would find those things before a patient found them. This is R/R Follicular Lymphoma -- people who have experience with this. Of course, not every patient has had B symptoms the first time around (including me). But I get the sense that most of us know our bodies well enough that if something unusual popped up, we would probably know there was an issue before we ever got to a doctor's office.

That's not a criticism of the video series -- the second video opens with the advice that the panelists would give to their patients about what to look out for, so this is truly "patient-centered" as the title suggests. It just strikes me more and more that R/R FL is different in many ways than first-line, untreated FL.

The videos also get into what doctors should do if a patient does seem to be relapsing, including what a new biopsy might reveal. Here they discuss things like POD24 or transformation, as well as the possibility that a patient might no longer be CD20 positive, meaning something like Rituxan would not work, and different treatment should be considered. So I'm not suggesting a patient knows everything here; obviously, a biopsy or a scan or new blood tests are going to tell the doctor things that a patient can't know just because they sense that something isn't right.

The third video really gets at the "patient-centered" focus of the video series, and the idea that, by the time someone needs a third-line treatment, there are lots of decisions that need to be made. One of the panelists says that his approach is a "partnership" with the patient. It's a recognition that his own goals might not match up with the patient's goals -- how much time they need to take to travel, how much they will need a caregiver's help, etc. And Dr. Shouse does recognize that many patients at this point have a good understanding of the process of deciding on treatment. 

The final video puts all of this into practice, presenting a case study of a patient with FL who needs a third-line treatment. I always enjoy videos like this. I like to see the thought process of experts and all of the different factors that they balance when they recommend a particular Treatment to a particular patient. Again, this is where the patient-centered focus comes in. The case study describes all of the lab and test results as well as her physical characteristics, and her treatment history. It also includes some information about her general treatment preference, given her personal circumstances. This is kind of the fun part for me, trying to guess what the Lymphoma specialists would recommend.

I won't give you any spoilers, but I will say this -- my guess about her treatment was wrong. You want to know why? Because I'm not a doctor. And that might be the most important lesson of all here. As much as we (and certainly I) know about the disease and about my own body, the best person to talk to about all of this is our oncologist. 

This last video was posted just today, so there might be more in the series (I suspect there is, because one of the panelists has not yet given an opinion about the case study). I'll keep an eye out for a potential part 5.

But for now, I recommend the series as a nice refresher about what needs to be considered when third-line treatment becomes necessary, and a nice reminder that a patient-doctor partnership is essential when that time comes.

R-Squared: 10 Year Follow-Up

The journal Blood Advances just published an article called "Six-month rituximab-lenalidomide regimen in advanced untreated follicular lymphoma: SAKK 35/10 trial 10-year update." It says some excellent things about R-Squared, as well as about Rituxan.

The article reports on a phase 2 clinical trial conducted by researchers in Switzerland. It compares R-Squared (Rituxan plus Revlimid, also known as Lenalidomide) to straight Rituxan as a first treatment for Follicular Lymphoma patients. There were 154 patients in the trial, with grade 1 to grade 3A FL. Half were given Rituxan and half were give R-Squared.The data looks at results of the trial 10 years after it started -- a very long time for cancer research.

The study found that overall, the R-Squared combination worked better than the Rituxan.  The primary endpoint (the most important outcome being measured) was Complete Response at 6 months and then at 30 months. By comparing the two time intervals, researchers can get a sense of Duration of Response -- how long the response lasted.

The R-Squared combination had a longer duration of response. The median was not yet reached after 9.5 years (meaning more than half of the patients continued to have a response), while the duration of the Rituxan group was 3.2 years (still very good).  The median Progression Free Survival was also very good for the R-Squared (9.3 years versus 3.2). 

As far as efficiency goes, the R-Squared clearly won that comparison.

As for safety, things were a little bit different. There has been much research on the two types of treatment already, so the side effects are well-known. As expected, R-Squared tends to have more side effects than Rituxan (since there are two treatments being combined, each with its own set of side effects). No new side effects were noticed, and the R-Squared side effects were "manageable." Each of the groups reported a similar number of deaths after 9.5 years, with 15 in the R-Squared group and 14 in the Rituxan group, though one of the R-Squared deaths came from sever side effects. 

It's important to note here that deaths are from any cause, not necessarily from the disease or the treatment, with the exception of the one that was mentioned.

Along those same line, the Overall Survival of both groups about the same after 9.5 years: 77% for the R-Squared group and 78% for Rituxan. That's also not a surprise. The Overall Survival of most treatments for FL is about the same. It's very hard to show a survival benefit among treatments. If there was a big difference, we'd probably all be gravitating toward that treatment instead of arguing over which one was the right one.

And that's important to note, too. If the goal is to live as long as statistically possible, then there are lots of choices. So other factors have to be considered when choosing a treatment. If the goal is to avoid side effects right now and sacrifice a long PFS (meaning you'd need to get a second treatment sooner), that's different from tolerating harsher side effects now for the chance at a longer time until another treatment. that's why it's important to talk things out thoroughly with your oncologist before choosing a treatment. We all have different goals.

It's important, too, to remember that all of these numbers are medians. That means whatever they are measuring, the median is the exact middle. So if the median PFS for Rituxan is 3.2 years, then half of the patients had their disease progress before 3.2 years, and half went longer than 3.2 years. I've known people who didn't respond at all to Ritixan. And then there's me -- I had Rituxan 15 years ago and I haven't needed treatment since.

It's all very complicated, isn't it? 

I wish that wasn't how it is, but that's what we're dealing with. As I said, the best thing to do is keep up-to-date, including regular conversations with your oncologist. You have choices. It's best of they are informed choices. 

Phase 2 Trial of Opdivo for FL

An article in the medical journal Blood Advances from this week had some very intriguing results.

The article is called "Nivolumab and rituximab in treatment-naïve follicular lymphoma: the phase 2 1st FLOR study," and it gives the results of a phase 2 clinical trial being run in Australia. If you read the blog, you probably know what rituximab is (also know as Rituxan or MabThera, depending on where you live). But you might not know about Nivolumab, and that's what makes this so interesting to me.

Nivolumab is also known as Opdivo. It's a very widely used cancer treatment, and works as as a PD-1 inhibitor. PD-1 stands for "Programmed Death." Our cells are not meant to live forever. Some only live for a few days, like skin cells, which do a lot of work. Cells have a mechanism built into them so they will die off after a certain time. When they don't die off -- when they keep living, growing, and making more cells -- what you end up with is cancer. PD-1 is a protein on the surface of cells tat helps with this signaling. When there are problems with PD-1, cells don't get the signal that it's time to die off. A PD-1 inhibitor works to stop (or inhibit) that problem from happening, so cells are able to die off as they are supposed to, and thus prevent cancer. 

What makes Opdivo so interesting is that PD-1 affects lots of different types of cancer. We often think of cancer in terms of body parts -- breast cancer, colon cancer, skin cancer -- and most cancer treatments work on only a very specific type of body part cancer. But because PD-1 problems can result in lots of different cancers, a PD-1 inhibitor like Opdivo isn't confined to just one body part. It has been approved to treat different specific subtypes of cancers of the skin, lungs, kidneys, stomach, blood, and others. There are other PD-1 inhibitors as well (Keytruda is probably the best known one), and they have helped thousands of cancer patients. 

And while they are successful in treating lots of different types of cancer, they aren't always successful. Early attempts at treating Follicular Lymphoma with Opdiva and Keytruda were not successful (most recently last fall).

But this study suggests that a different way of using Opdivo might have found a way of using the PD-1 inhibitor successfully.

As the article says, the research describes results from a phase 2 clinical trial, so it's fairly small -- 39 patients with Follicular Lymphoma who had not yet received treatment. The patients were first given 4 cycles of priming Nivolumab. The idea here is that a few doses on Nivolumab on its own will prime or prepare the immune system by removing some cells that have PD-1 problems. That's the part that's a little different from what is usually done. And the priming process actually resulted in a few patients getting a Complete Response. In fact, 5% of them had CR, 26% had a Partial Response, 28% had stable disease, and the rest (41%) saw their FL get worse.

But then came the next step -- the patients who had a CR after those 4 rounds continued to receive only Nivolumab. The rest were given a combination of Nivolumab and Rituxin. The combination continued after they achieved a response -- one more year of Nivolumab and two years of Rituxan.

The results were very good. For the whole group, 92% of patients had a Response, including 59% having a Complete Response.  The median time to a Complete Response was 6.5 months, and 7 patients who had initially had a Partial Response eventually had a Complete Response. After following up for a median of 51 months, the median duration of response was 59 months, and Progression Free Survival was 61 months. However, 19 patients (36%) did eventually have their disease get worse at some point during the study, and 14 of them required additional treatment. 

Interestingly, the Primary Endpoint of the study -- the factor they use to determine if it is a success or not -- was not something like PFS, which is typical. Instead, it was measuring safety instead of efficacy -- how well the patients tolerated any side effects. This was a success -- the study met its primary endpoint. Only 33% of patients had a grade 3 or higher Adverse Effect (in other words, a serious side effect) during the first part of the study, and 59% during both parts of the study. It's unusual to focus on that, since it's usually a concern in phase 1 trials. But there was no phase 1 for this study, since both treatments have already been approved. But it's the first time they have combined in this way, and any combination of two treatments means there is a possibility for doubling the seriousness of side effects. This study showed that it didn't happen.

It will be very interesting to see where this research goes from here. They don't explicitly say that they are planning a phase 3 trial, though they do think this has some lessons for "future research." One of those lessons is that they saw a connection between patients who did well with this combination and having high CD8A gene expression. In other words, they think they found a biomarker that would help determine whether this kind of combination might work on an individual patient. They are also pleased that their Primary Endpoint was successful -- they showed that  combining a monoclonal antibody and an PD-1 inhibitor was safe, and that other combinations might be worth trying.

So I'm not sure we'll see this combination in the clinic any time soon, but it's certainly helps move our knowledge along. And that's always a very good thing.  

Patient Portal Access

A couple of weeks ago, I wrote about getting a phone call from my dermatologist, and getting the news that a biopsy was negative, and I was fine. I wrote about those few seconds before she gave the actual news, and trying to find clues about what the news will be.I think that's a very common experience.

A reader named JM left a comment: "This why I like messages in my Portal 😂 I can skim the info and don't have to do the voice interpretation."JM included a laughing face, though I think this is a common experience, too. 

I was going to write a comment back to JM, and by the time I got around to it, I had found a new article from the Journal of the American Medical Association called "Unintended Consequences of Patient Portal Access." It summed up pretty well what I was going to write to JM.

For those who need a reminder: starting in 2021, a law in the United States required that patients get immediate access to doctor's notes. In the past, this wasn't so easy. You could request access to doctor's notes, but because they were handwritten, it would mean sending a written request to the doctor, and then having to wait until someone in the office could get around to photocopying what was in the paper file. If you were switching doctors, this was fine. But if you wanted immediate access, this was almost impossible.

That changed in 2021. By that point, records were electronic. All of a doctor's notes had to be put into a "patient portal," on online database for each patient that could be accessed as soon as the notes were entered. Same with test results like blood work or PET scans. 

The idea, of course, was that patients have a right to information. Anyone who tried to get records from a doctor 10 years ago knows how frustrating it could be. In my experience, getting records didn't seem like a priority, so it could be days or even weeks to get the information I wanted.

Of course, if the purpose of getting the doctor' notes was to find out a diagnosis or test results, I was likely to get an appointment with the doctor to discuss them face-to-face long before I got any photocopies in the mail.

But Patient Portals change all of that, and make it more complicated, as the JAMA article points out.

For example, a cancer patient can get blood test or scan results even before the oncologist has seen them. That's great, in terms of transparency -- we have a right to information about our bodies. 

But the downside, as the article says, is that we sometimes get data without context. Raw numbers might not tell us much, or we might not understand them. So we go to our favorite health website to find out what something means, and it says we have a higher than normal level of that thing, and we then we read about the potential bad things that the high level can mean. In the hours or days before we get a call from the doctor (or a message in the portal), we might have caused ourselves unnecessary panic.

I had this happen a couple of months ago. I wasn't panicked by it, but a routine blood test for my annual physical showed a higher than normal level of "bad" cholesterol, and I dreaded the conversation with my doctor about having to add another pill to my routine or change my diet. When she did call, she said it was fine -- my last 5 blood tests had all showed an elevated level, all within the same small range. So it was more important that it wasn't spiking -- it was high, but level. That context mattered.

Cholesterol isn't a big deal, but that same situation involving cancer could be. 

The article brings up another interesting perspective, though -- how much the Patient Portals have affected doctors. I know it takes them much more time now than it did in the past. I've heard this from several doctors, and I've had two oncologists who left their practice because the electronic records became so overwhelming (one retired and one transferred to a new job with more research and less patient interaction). So that's one way it has affected  oncologists.

But the other way, according to the article, is that Patient Portals and Electronic Records might make doctors less empathetic. It's not just a matter of doctors having to take time away from patients (I've had doctors who barely looked up from their laptops during an appointment as they tapped away at the notes they were taking). But less interaction with patients can mean less time getting to know them, and over time, doctors might lose the practice they get in understanding a patient's emotions. If a patient gets the news, processes it on their own, and then meets with the doctor afterwards, it's less about figuring out how to deliver news and more about answering questions and correcting mistakes. Those are two different ways of thinking when a doctor is preparing to meet a patient.

So maybe JM is better off this way, getting news from a Patient Portal message. The message provides some content, anyway. It could be the best of both worlds -- you don't need to wait for a face-to-face appointment, and you still get to hear from the doctor with an explanation, and not have to guess on your own. But this requires some ability to ignore the notification that test results are in the portal, and wait for the notification that there's a message from the doctor.

I'm sure we all know by now that there are trade-offs when it comes to technology. For every problem that is solved, a new one is created. 

I hope you are all able to find some balance with this.

Survivorship (Yale Cancer Answers)

As most of you know, as I get farther away from my diagnosis (it's been 17 years now), I am more and more interested in the idea of Survivorship -- what happens after the diagnosis, and the treatment, and maybe even the cure. The assumption is often that we're "back to normal," whatever "normal" means. But most of us need some help to get there, or to accept whatever counts as normal.

And that's what "Survivorship" is -- everything that goes into being someone who has experienced cancer and is now living that life. 

For this, I want to share an episode of Yale Cancer Answers. This is a local radio show that makes its episode available online. It is put together by Yale Smilow Cancer Center, which is where I go for my appointments. Each week, a different cancer specialist is interviewed for the show. Lately, they've been doing a "50 Years of Progress" series, asking the guest to talk about how their specialty has changed over that time. (Yale Cancer Center is celebrating its 50th anniversary this year, so this is part of their way of looking back.)

Their recent episode on Survivorship features Dr. Tara Sanft, who directs the Survivorship Clinic at Yale Smilow. You can find a recording of the episode here, and a written transcript here, but there are a few things that I want to highlight.

First, Dr. Sanft says the Yale Survivorship Clinic is "one of the nation’s only multidisciplinary clinics specializing in cancer survivorship." That's probably true, which is a real problem, given how important survivorship is. But even if a cancer center doesn't have a separate clinic, many do offer survivorship services through other departments -- maybe social workers or other mental health support, or a dietician, or post-treatment support groups. So if you go to your own cancer center's website and you don't see a Survivorship Clinic, it's worth asking your oncologist if there are other services available to you. Doctors often don't tell patients about those services unless they are asked, so ask.

(You might find something really good. I found out once that someone had donated free theater tickets to a popular show to the survivor clinic, thinking that people recently finished with treatment might like a free night out.)

Second, I think it's interesting that Dr. Sanft, looking back 50 years ago, characterizes Survivorship in the past as being nonexistent. Not so long ago, maybe 20 or 25 years ago, cancer patients were supposed to feel grateful for surviving. The idea that we were supposed to be offered something extra, like counseling or diet advice, was just not something anyone thought about. And as she pints out, patients are still grateful when treatment is over. But that doesn't mean our needs are all gone. We have a whole new set of things that we need. 

I find that change in attitude to be fascinating, especially if we look back 20 years -- not so long before I was diagnosed. It's not all that long ago. You don't need to look back much longer than that -- maybe 50 years -- when cancer patients weren't even told that they had cancer, because it was thought that their delicate selves couldn't handle the news. The families were told, but the patients were told with different words. You didn't have a tumor, you had an "abnormality." We've come a very long way.

Finally, Dr. Sanft talks about "the role of health behaviors in survivorship" -- the things like diet and exercise that we can do to help our recovery, make ourselves stronger, and allow ourselves to keep living the lives we want to, that we are able to. This is her big focus as a researcher, and I appreciate it. I like the term "health behaviors," because it gives us some control. Our behavior is something we do, not something that is done to us. There is plenty that we can't control, but we should control the things that are good for us. That's not always easy.

And that relates to one more thing that she points out as she discusses the way things have changed over 50 years. She says people with cancer sued to be called "cancer victims." That one hit me hard.

I remember years ago, when I was first diagnosed, having  conversation with someone I worked with. For some reason, we were talking about labels for cancer patients. She told me for someone who was less than 5 years from diagnosis, they were called a Cancer Victim. After 5 years, you're a Cancer Survivor."

It just made my blood boil. First of all, you're a survivor from the day you are diagnosed. More importantly, I'm not a "victim," and I don't like being labeled as one. 

There's a kind of helplessness that comes with the label "victim." It's very much in line with that 50 year old thinking. You have cancer, you're a victim, you're helpless, and if treatment keeps you alive, you should be grateful and just go away and live like nothing happened.

Nope. I'm going to talk. And part of my talking is to thank the people who have helped me in any way. But there's so much more to be done after the treatment stops. And I want to be an active participant in all of that. I want to make decisions and do what I can to live the life that I want to live.

So I hope you'll give the Yale Cancer Answers episode a listen. If nothing else, it's a good reminder to find out what you want and figure out how you can get it.

Take care.

When the Doctor Calls

Yesterday morning on my way to work, I got a phone call from an unfamiliar number. My wife was driving, which makes it easier to answer phone calls, but I didn't recognize the number and started to put my phone away.

But then I remembered that I was waiting for a call from the dermatologist.

I had an appointment last week so she could check on the surgery I had a couple of months ago to remove a Basal Cell Carcinoma and see if anything new had popped up. She found a couple of Actinic Keratoses on my head, as usual, and froze them off. Then she checked the rest of my body, and finally my face. (I like to think she saves the best for last.) She noticed a small bump next to my eye. It's been there for years. 

"It seems different," she said. "I think I'd like to biopsy it, just to make sure it isn't a Basal Cell."

She removed it and said she'd call me with the results in a week.

So I remembered that when the phone rang. I picked up and put it on speaker phone.

"Hello, is this Robert?" she said. (Doctors always call me "Robert," rather than the more familiar "Lympho Bob.")

"Yes it is."

"This is Dr. M. We have the results of the biopsy...It's benign." She said what kind of growth it was, which I don't remember, and said if it grew back, and it worried me, she could biopsy it again, but it was all fine for now.

I thanked her and hung up.

My wife said, "Well that's a nice way to start the day."

I agreed, and said, "When she started talking, I was trying to get a sense of whether this was going to be good or bad from here tone of voice."

My wife laughed. "Me too. She sounded happy, but I didn't know if that was because it was good news or because she was trying to be positive about bad news."

It's amazing to me that even after 17 years, that same feeling comes back, and those same strategies kick in. I've had several conversations with doctors about blood cancer diagnoses -- the first diagnosis 17 years ago and then results of scans, or of blood work that was a little off. And now I've had two skin cancer diagnoses, and a couple of others that ended with negative biopsies. 

And every time, every conversation, that strategy kicks in of trying to guess what's coming. The actual diagnosis -- yes it's cancer or no it isn't -- comes at the end of the sentence, after about 10 seconds. But somehow our wonderful brains make a thousand calculations in that 10 seconds. Is her voice happy or serious? Does she sound busy and this is a routine positive call, or is she quiet, behind closed doors, where she can focus on giving negative news?

There are even more clues to analyze when it's person. Did it seem like she lingered outside the door, trying to get up her courage? Is she avoiding eye contact? Did she breeze right in, lighter on her feet because this was going to be an easy conversation?

I'd like to say I've gotten better at doing those calculations after 17 years. I'm not sure I have, and I'm not sure it's a skill I actually want. 

But I also know that I'm not the only one who goes through that process, looking for clues and making calculations in mere seconds. We cancer patients are like computers. It's not artificial intelligence. It's about as real as it gets.

And that was my thought as we drove on to work. It just gave me a sense of belonging, of being part of a large group of people who unfortunately don't want to be a part of that group, but are stuck with it. But we've found each other, and that's what matters. The things we go through are not just things that we go through alone. There are things that we share that connect us -- experiences, feelings, desires. We are not alone.

My wife was right. It was a nice way to start the day. 

Take care, everyone.