R-CHOP 15 Year Follow-Up: A Cure for FL?

The big news in the world of Follicular Lymphoma this week is an article in JAMA Oncology describing results of a 15 year follow-up of FL patients who received R-CHOP (or CHOP + Radioimmunotherapy). The study suggests that 42% of the patients in the cohort have been cured of their FL. It's a big deal because it's really the first time anyone had seriously suggested that FL might be curable.

There's a lot going on in this study. It's worth looking into a little further.

The article is called "Treatment of Follicular Lymphoma With CHOP and Anti-CD20 Therapy: 15-Year Follow-Up of the SWOG S0016 Trial." The goal of this analysis was to see how many of the patients in the trial were cured after 15 years. They determined which patients were cured by a statistical method called "cure modeling," which provides an estimate of how many patients were cured.

I think that's important to note here. Part of the problem with determining whether someone is cured has been the nature of FL. With many other cancers (as I'm sure you are aware), if a patient is disease free after 5 years, they are often considered cured. That's harder with FL, since some patients will have the disease return after 6 years, or 10 years, or 15 years. So it's risky to say someone has been "cured" of their FL. 

And it's why many FL experts use the term "functional cure" instead. Someone can be diagnosed at 65, get a Complete Response, and never need treatment again, and die of something unrelated at 85 years old. Were they "cured"? It's hard to say. But they lived a life as if they were cured -- it was a "functional cure."

So this study defined "cure" using statistical methods because it's really difficult to say whether or not someone was cured the way they could for patient with something like colon cancer.

I won't pretend to understand the statistical analysis of the cure modeling, but I will say that since the article was peer-reviewed, it would have been approved by other experts in statistics before it was published, so I don't have any doubts about the analysis.

The SWOG study itself involved 531 patients. They received either R-CHOP or CHOP-RIT between May 2001 and October 2008. I don't write about CHOP much these days, so a reminder: CHOP is a traditional chemotherapy made up of four components (Cyclophosphamide, Hydroxydaunorubicin/doxorubicin, Oncovin, and Prednisone). It's been around for a while, and it's still a very popular treatment. R-CHOP is CHOP combined with Rituxan (rituximab/mabthera). When R was added to CHOP about 30 years ago, it increased its effectiveness. It's pretty standard now to include R with CHOP. RIT, RadioImmunoTherapy, is a treatment like Zevalin. It's essentially something like Rituxan, which can find the CD20 protein on a Lymphoma cell, but with a tiny bit of radiation attached to it, so the radiation can be delivered directly to the cancer cell. 

So of the 531 patients in the study, 267 received R-CHOP and 264 received CHOP-RIT. The 15 year Overall Survival rate was 70%, about the same for each of the two groups, though the RIT group had a better 15 year Progression Free Survival (the cancer didn't come back for 15 years for 47% of the CHOP-RIT patients, versus 34% of the R-CHOP patients). 

The cure modeling estimated that 42% of the patients in the study had been cured. The highest cure rates were in patients with low FLIPI scores and normal β2 microglobulin levels, essentially the patients with the lowest risk. (You can read more about FLIPI levels here, but keep in mind that it doesn't say anything about you as an individual, even though it seems like it does.) This isn't a surprise, really -- we expect less aggressive version of FL to be less problematic and more successful with treatment.

One important finding of the study was that the rate of relapse declined over time. For the first 5 years after treatment, 6.8% of patients in the study relapsed. But between years 15 and 20, just 0.6% of patients relapsed. So the longer the patients went in the study without relapsing, the less likely it was that their disease would come back. 

That's really important. Think back to the idea of "functional cure." It's hard to say someone is "cured" because the disease might come back after 10 or 15 years. But this study shows that it's much less likely to happen, so someone can be more confident after 15 years that the "functional cure" is an actual cure.

Te conclusion to all of this from the researchers is that maybe FL isn't incurable after all. The call this a "paradigm shift" -- a complete change in the way we think and thus the way we act. It could mean that doctors have very different conversations with patients, and that maybe R-CHOP is presented as a possibility for someone who might want a cure. It also has implications for future research.

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As I said, there's a lot happening here. This article was published about 4 days ago, and I've been waiting to hear what other FL experts have to say. So far, I haven't seen or heard much, but I think everyone is trying to take some time and digest it all. Paradigm shifts don't happen in 4 days -- they take years for everyone to break out of the way they have been thinking for so long (at least according to Thomas Kuhn).   

And I absolutely understand that. We (meaning much of the Lymphoma community) get so locked in to the idea that "newer is better" -- that every new CAR-T or bispecific or inhibitor must be an improvement over chemotherapy -- that's it hard to see a study like this and not be skeptical. It's certainly my own reaction to it, and I immediately start with a long list of "Yes, but" statements. "Yes, but it's just a statistical estimate, not an actual look at the patients." Or "Yes, but 42% is hardly a cure for all of us." Or, "Yes, but it's still a fairly small number of patients in the study, compared to the thousands that are diagnosed every year."

Particularly for me as a patient who was diagnosed 18 years ago, and who has been told this is incurable for all of that time, it's pretty tough to suddenly think otherwise, and even tougher to think the cure might be from chemotherapy.

That's why I'm especially impressed with the statement from Dr. Jonathan Friedberg from the University of Rochester Wilmot Cancer Institute. He was one of the authors of the study, and he's the one who is talking about paradigm shift (see the story that came out of the Fred Hutch cancer center where he is quoted). He's a Lymphoma Rock Star, doing cutting edge research on FL, and he's willing to look at the data and say "Maybe it's chemotherapy after all." 

The few comments from Lymphoma specialists that I have seen have been positive. It's clear that no one expects R-CHOP to suddenly replace bispecifics and CAR-T. But it could mean that conversations with patients are different. For some patients with low risk disease, and who are otherwise healthy and can tolerate the side effects, maybe R-CHOP is an option. CHOP contains an anthracycline, a type of drug that can be very effective but can also cause long-term heart issues. That kind of factor will need to be taken into consideration. 

I saw one commentor who said this study will have an effect on future research in a couple of ways. First, long-term studies of FL treatments will be measured against this. It's really interesting that this come out just after a 15 year follow-up of R-Squared. It's a much smaller study -- only 79 patients. But could the same cure analysis be applied to it? Could it be applied to a larger study of 500+ patients? If it was, could we make a direct comparison between the two treatments? It will be hard to look at any long-term study of an FL treatment now and think "Yeah, but....does it have a better cure rate than 42%?"

Another way this might change research is that there might be a greater emphasis on second-line treatments. That emphasis already exists, in some ways -- most new treatments get approved for relapsed/refractory disease first, and then as first-line treatments. But this cut back on the number of treatments that do that second step and get approval as a first-line treatment. In other words, we could possible have something closer to an agreement on how newly diagnosed patients are treated, and that treatment could be traditional chemotherapy. 

That's not to suggest that everyone will be getting chemo from now on. There are and will be lots of options out there, and more to come, for a long time. But I expect those conversations to happen.

I'm going to keep an eye open for more commentary about this. I expect some of the oncology websites to have videos of experts discussing this. I'm hoping for more debate-style videos, with multiple experts arguing for and against using R-CHOP. They would be more enlightening to me.

But I think the main take away for all of us should be the same thing. For at least some FL patients, a cure may be possible. For the first time, people seem willing to say so. 

FLF Webinar: Charting our Progress Towards a Cure

The Follicular Lymphoma Foundation held a webinar a couple of weeks ago called "Charting our Progress Towards a Cure." It's an excellent webinar -- lots of information and lots of things to think about. 

The webinar provides some updates on FL research from a symposium that the Foundation sponsored at the 18th International Conference of Malignant Lymphoma (ICML) in Lugano, Switzerland last month. The ICML is one of the most important Lymphoma conferences in the world, and for the last few years, the FLF has held an event like this that provides up-to-date information for doctors about Follicular Lymphoma. 

Among the topics that the Expert Speaker, Prof. Jessica Okosun of Barts Cancer Institute in the UK, discusses are CAR-T, Bispecifics, and combinations that use multiple treatments together to target the FL cells in lots of different ways. The goal is to give patients the longest Progression Free Survival possible.

Prof. Okosun gives a very optimistic overview of several newer treatments and treatments in trials now. There are enough newer treatments in the pipeline, she says, that in 5 to 10 years, we may not even be using traditional chemotherapy or Rituxan anymore. There may be enough advances that these "old" treatments have been surpassed by newer, more effective and safer treatments.

And that brings up an important topic, and really the focus of the webinar -- the idea of curing Follicular Lymphoma. It's a controversial topic, in some ways. FL is still considered by many to be incurable, which means there are lots of treatments that can put the disease into remission or partial remission or keep it stable, but not necessarily wipe it out permanently. Individuals might be "cured," but not enough patients are in that situation that the entire disease is considered curable. 

When I say the idea of a cure is controversial, I mean that there are disagreements about whether or not that's true. There are some experts that say patients can be cured outright. There are others that speak about a "functional cure," meaning that a patient might not be technically cured, but are living with the disease for many years (perhaps the rest of their lives) without needing treatment.  

Part of what makes this all so difficult is that we can't say for sure what the future holds. We don't know if the disease will come back for any individual. I'll give a very personal example -- me. I haven't needed treatment in 15 years. But I also haven't had a scan in many years, and the last time I had one, there was still some evidence of the disease being present. Am I cured? Was this a "functional cure," since I'm living for so long without treatment? 

Personally, I don't consider myself "cured." It's always in the back of my mind that it might come back. 

But I live my life in many ways as if I'm cured. I have long-term plans for my life. I don't act like it's going to come back, even if I acknowledge the possibility. I think it's a good way to live.

In addition to the Expert Speaker, the webinar also features a patient speaker, Paul Christopher Mollitt. He does an excellent job of talking about what a cure would mean to him, and also talks about how he has made treatment decisions since her was diagnosed in 2017. (And he let viewers know that he was recently declared in remission after Bendamustine and Rituxan!!!!)

There's a third speaker for the webinar, Dr. Mitchell Smith, the Chief Medical Officer for the Follicular Lymphoma Foundation. If you've attended or watched these webinars, you know what an excellent job he does of moderating the discussion, connecting ideas from the speakers, and answering questions. 

There's a lot more detail in this webinar, especially about some of the very interesting research that came out of the ICML conference. It's certainly worth spending the hour or so that it takes to watch the entire thing. Lots of good information, and lots of reasons to be hopeful. 

 

ASH Review: 5 Year Follow-Up for CAR-T

Continuing our look at what Lymphoma experts have to say about presentations at ASH a couple of weeks ago. I'm seeing lots and lots of commentary about Tafasitamab + R-Squared (the excitement was there even before the ASH meeting began, so no surprise there).

One commetary caught my eye this morning. It's from the lead researcher for abstract #864, "5-Year Follow-up Analysis from ZUMA-5: A Phase 2 Trial of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma." 

The commentary is from an article website Health Day, and features a video (with written transcript) from a Leukemia specialist and a Lymphoma specialist.  The Lymphoma specialist is Dr. Sattva Neelapu from MD Anderson, who discusses the abstract above.

The presentation looks at data from the ZUMA-5 trial. There are a series of ZUMA trials, each looking at the CAR-T known as Axi-cel or Yescarta, but looking at the effects from different patient populations. ZUMA-5 focuses on patients with indolent NHL, including Follicular Lymphoma, who had relapsed or refractory disease. The ZUMA-5 trial actually resulted in Axi-cel being approved for R/R FL in 2021, so this research isn't about trying to show the FDA that it is safe and effective. We already knew that.

Instead, this presentation is meant to show that Axi-cel remains safe and effective. 

The study involved 159 patients, with 127 of them having been diagnosed with Follicular Lymphoma. The patients in the study had already received at least two other treatments, including immuno-chemotherapy (like R-CHOP or B-R). This presentation looks at what happened to the patients after 5 years. 

In the video, Dr. Neelapu says the Overall Response Rate was 90% and the Complete Response Rate was 75% -- even higher in patients with Follicular Lymphoma at 79%.

The median Duration of Response -- how long it kept the cancer away -- was a median of 60.4 months, or a little over 5 years. (Median means half had a longer response and half had a shorter response).

Among patients who achieved a CR, 58% remained in response after 5 years. The Progression Free Survival rate was similar at 50.4%. For patients with a Partial Response, the PFS was 6.9 months. The median Overall Survival was not reached. To get a median, you need half of the patients to have died, so after 5 years, more than half were still alive -- the researchers estimated 69% of the patients were still alive after 5 years.

Among patients with Follicualr Lymphoma, the OS was estimated at about 65%, meaning 35% of the patients had died, whether from disease progression or from some other cause. These other causes included some secondary cancers and infections, as well as non-cancer-related causes.

I their conclusion to the abstract, and in the video, the researchers say that the results show that Axi-cel may have the potential to be a cure for a certain subset of patients.

I have a couple of thoughts.

First, looking at the numbers, it's clear that CAR-T is improving. The early results from CAR-T showed that roughly 33% of patients had a long duration of response, 33% had a duration of about a year, and 33% did not respond at all. The numbers here after 5 years are a lot better. CAR-T is working, and after some time, oncologists are getting better at dealing with side effects and with identifying who will be helped by CAR-T. 

Second, that word "cure." It's a funny word when it comes to Follicular Lymphoma. Clearly, CAR-T was not a cure for a whole lot of patients in the study. But clearly, it has been a huge help to a whole lot of others. The problem with using that word is that "cure" is hard to measure. In other cancers, the 5 year mark is often used to declare someone as "cured." But FL has a habit of coming back even after 5 years, at least for some people. 

But many oncologists use the term "functional cure." If an FL patient is diagnosed at a later age and has a treatment that lasts for as long as they live, we can call that "cured." And for others, the disease may return, but in a less-aggressive way that doesn't require treatment. That makes them "cured," in a sense.

Many FL patients use the phrase "Dying with the disease, not from the disease." And that amounts to a "cure" in a way, too.

I have my own issues with the word "cure," obviously, and I may write more about that sometime soon. But for now, we at least agree that for many patients, Axi-cel CAR-T has been very successful.

I'm still sifting through some other post-ASH commentaries. I'll share more soon.

ASH Abstracts Are Here!

Before I get the Cancer Nerd stuff, I want to remind you about the Follicular Lymphoma Foundation survey that I linked to in my last post. 

The survey is about how patients with FL make decisions about treatment. It should take about 10 minutes to complete, and will provide valuable information that hopefully will be presented at a medical conference next year, where it can be seen by oncologists and researchers and those who manufacture the treatments. 

This link will take you directly to the survey.

UPDATE: The FLF is getting a good response from this survey from patients, but they'd love to hear fro more caregivers -- a spouse or partner or family member or friend who helps you as a patient. If you're a patient, could you please share the link with your caregiver and ask them to take it? Caregivers don't get enough credit for how important they are in the decision-making process. This is a great opportunity for their voice to be heard.

 Thanks for considering it.

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Now, back to that Cancer Nerd stuff.

The abstracts for the ASH meeting are now available!

ASH is the American Society of Hematology, and their annual meeting is the largest gathering of blood cancer specialists in the United States. It takes place in early December every year. This year is it December 7-10.

Much of the meeting involves presentations of research on blood cancers and other blood-related diseases. (It's in San Diego, California, so I assume some of the meeting involves brightly-colored drinks with little umbrellas in them, too.)  About a month before the meeting, ASH published the abstracts -- summaries of what the presentations will be about, so those in attendance can plan out which sessions they want to go to. 

Every year, I like to go through the abstracts related to Follicular Lymphoma and preview some of the more interesting ones. My quick search says there are 329 abstracts for Follicular Lymphoma. You can see them yourself here.  

Some years, there isn't much that's very interesting. But this year, even a quick look at the titles is getting me excited. 

First, though, a few things that I am not seeing in my quick look at the abstracts.

First, I'm not seeing any game-changers. Some years there's a presentation that is so important that they move it to a very big room so they can fit all of the people who want to hear about it. (The last one of those for FL was when they discussed the results of the R-squared trial.) I don't see any of those this year. And that's OK.

I'm also not seeing too many new treatments. There are a few, but not as many as some years. These re usually reports of phase 1 and 2 clinical trials, which means they are very early in their process. They're always exciting, but don't always play out as one would hope, and they aren't heard from again. I do see a few, though, and I'll try to highlight the exciting ones.

What I am seeing is a lot of research on treatments that have already been approved. Some are "real world" studies, looking at a treatment outside of a clinical trial, so there are fewer restrictions on who can actually receive the treatment. Some are combination studies, looking at treatments that have been approved on their own to see how they work together. Some are long-term follow-ups to approved treatments.

Those kinds of presentations are really interesting, too, because they teach us more about the treatment and how effective it is for certain patients. They can be less exciting than a presentation for a treatment that hasn't been approved yet, and that comes with the promise of big change. But those less-exciting presentations often give us incremental change. No big leaps forward, but they do move us forward. And that's a great thing, too.

I'm also seeing some presentations about Quality of Life issues. That's excellent -- researchers are paying attention to it, and oncologists will be hearing about it. There's more to treatment than just how effective it is. There's everything that happens when we live our lives outside of the treatment room. That matters a lot.

I see a couple of presentations about watching and waiting that I'm excited about (and might start off with, since I'm always interested in it).

Finally, there's an "Education Program" about FL that;s in a big room. It's not presenting anything new, just educating oncologists about what the latest is for Follicular Lymphoma. There's one presentation during the session called "Follicular Lymphoma: In Pursuit of a Functional Cure."  The description of the presentation, from Dr. Judith Trotman, and Australian oncologist, says "In this talk, Dr. Trotman will provide the survival data to equip clinicians in framing optimistic initial conversations with most patients at diagnosis of advanced stage FL. She outlines the expectations of longevity and a"functional cure" for many." A functional cure is the idea that many of us will get a treatment that lasts so long that we don't need another, even if we still have some evidence of the disease still hanging around and remaining stable.

That one looks great, and I hope I can get access to a recording of it after it is over. Unfortunately, ASH doesn't provide special registration rates for independent cancer advocates the way ASCO does, so I'd have to pay for access. Maybe I'll get lucky and they'll post the video for free someplace.

So look for some interesting ASH previews in the next few weeks. Always a special time.

(And don't forget that FLF survey! Caregivers, too!)

More to come very soon.

 

FLF Webinar: Close to a Cure?

The Follicular Lymphoma Foundation has posted the video of its second webinar on their web page. The webinar is called "How Close Are We to Curing Follicular Lymphoma?" 

It's definitely worth watching. And I'll spare you the suspense for an answer -- we're on the right path, but not really close. As in, we're at least a few years away.

The webinar features Dr. Mitchell Smith, who is the Chief Medical Officer for the FLF, along with Dr. Loretta Nastoupil from MD Anderson. At one point, they are interviewed by Nicky Greenhalgh, who founded the Living with Follicular Lymphoma group on Facebook (I know some of you are members of the group, as am I.)

As the speakers acknowledge, it's kind of difficult to determine if or when FL is "cured." It's not like other cancers, where very often, someone who has been in remission for 5 years is considered cured. With FL, many patients get 5 or more years of remission, but then have the very slow-growing disease show up again. So traditional notions of "cure" don't really apply.

Some oncologists (including the two speakers) refer to "functional cure" for FL. This means a patient might still have the disease, or still has a chance of it returning, but lives a normal life expectancy with a decent quality of life, and dies with the disease rather than from it. It's not hard to imagine -- a 65 year old person in the U.S. is diagnosed with Follicular Lymphoma (let's say grade 1, stage 3 for this example). Didn't know she had it. She watches and waits for two years, then has R-Bendamustine and gets 10 years of remission. Some nodes pop up, but not enough to treat, and stays that way for 2 years. So that's 2 years + 10 years + 2 years = 14 years living with the disease. 65 years old + 14 years = 79 years. Just about a normal life expectancy. 

Was she cured? No. Did she live with the disease in such a way that she might as well have been? Some would say Yes.

Of course, I say this as someone who has gone 13 years without treatment. I've never had a clean scan -- there has always been a little disease luring about. So I don't consider myself cured, and I expect that at some point, I'll need treatment again. I am nowhere close to a "normal" life span, but I expect to love that long, at least.

The speakers identify some of the things that make a cure so difficult. One big issue is the lack of "patient-specific tools." Because FL is so heterogeneous -- it's almost like a different disease for each patient -- it's hard to think of one thing that will result in a cure. It's more likely that we'll have a bunch of different treatments that result in long-term remissions for different patients. What works for me might not work for you.

But for that to happen, we need to identify biomarkers -- a gene or a protein that can be targeted with a specific treatment. But different patients will have different biomarkers, so one treatment won't work for everyone. Researchers are having a really hard time identifying those biomarkers. But they're making some improvements. 

Another problem is figuring out why FL keeps coming back. Is it because some cells are missed by treatments, but they are too small to see on a PET scan? (Maybe a liquid biopsy will help with that, but we don't have an accurate one ready yet.) Or is it that all of the cells are wiped away by treatment, but there is some mechanism that is untouched by treatment that causes new cancer cells to form later? Obviously, knowing the answer to that question will help with a cure.

So, an interesting webinar. It raises more question than it answers, really, but it does give a good sense of which questions we still need  to know more about. And that's not a bad thing.

If you can find 45 minutes for the webinar, it's worth the time. Aimed at patients, so it's fairly easy to understand.

ASCO: Uncertainty and Coping

 More research from ASCO:

"Uncertainty and coping in patients with newly diagnosed indolent non-Hodgkin’s lymphoma (iNHL)."

The title of this presentation gives you the basics of what it's about, and it's pretty likely to make you say something like "Do you really thinkmI needed an ASCO presentation to tell me that?" Basically, what it says is that patients with indolent lymphomas (like Follicular Lymphoma) are anxious and uncertain because they have a slow-growing but usually incurable cancer, and need some help with developing coping strategies.

Yes, we do know that this is true.

One of the nice things about being able to register for ASCO as a patient advocate is that I get access to some additional materials besides the abstract/summary. So while it all seems pretty obvious -- yes, we are anxious -- the additional materials help round things out a little bit.

So here's the rundown:

The research focused on newly-diagnosed patients with indolent NHL. They collected PROs (Patient-Reported Outcomes), with patients giving their own thoughts about how they were feeling. They used several different surveys to do this, including Functional Assessment of Cancer Therapy to measure Quality of Life; the Hospital Anxiety and Depression Scale to measure psychological symptoms; the Prognostic Awareness Scale to measure how well they understood their prognosis; and the Brief COPE to measure their ability to cope with the diagnosis.

[Import note before we move on -- the links above will take you to either descriptions of the surveys, or the surveys themselves. If you are thinking about taking one of the surveys yourself, think carefully before you do. They are meant to be reviewed and discussed with a mental health professional. It might not be a good idea for some of us to start looking at issues on our own that we can't explore without some help. As you know if you've been reading for a while, I'm a huge believer in taking care of our mental health -- that's why this presentation was so attractive to me. But I think it's better to deal with these issues with some help.]

Then they looked at the ways the patients tried to cope with their diagnosis. They categorized the strategies as one of two approaches. The first is called "approach-oriented," including doing things like active coping, using emotional support, positive reframing, and accepting the diagnosis. The second approach is "avoidant" -- disengaging, denying, and blaming themselves for the diagnosis. Essentially, they think it's good to deal with the diagnosis, and bad to avoid dealing with it. They're probably right about that, though I think we all deal with it in the way that makes the most sense. I know people who coped very well by disengaging, for example. 

The study looked at 48 patients; about one third of them had FL (the rest had CLL, another indolent blood cancer). At the time the the patients entered the study (within three months of being diagnosed), they were given the surveys. The results of the surveys:

31.2% were found to have symptoms of anxiety and depression.

45.8% said the uncertainty about their prognosis was "the most stressful part of being a patient."

31.2% said they had "difficulty letting go of thoughts about their prognosis."

47.9% reporting that they thought a cure was at least "somewhat" likely (even though they were told it was an incurabe cancer).

None of that is very surprising to me. One thing that does surprise me, though, is that the researchers seem concerned that almost half of the patients think a cure is "somewhat likely." And I guess that is concerning, especially with patients that are less then 3 months out from a diagnosis. But that's a tricky thing. I think of myself as being just about as informed as a Follicular Lymphoma patient can possibly be, and I do think that a cure is somewhat likely to happen in my lifetime. I also have 15 years of experience with living with this disease, and the knowledge that I probably have a fairly slow-growing version of it, and as a result, I expect my "lifetime" to be pretty close to "normal." That gives researchers some time to work on this.

I'm less certain that, at 3 months, I would have felt the same way. But I also think that Hope is being undervalued here. It's an awfully hard thing to attach a number to, and numbers matter in something like an ASCO presentation. But Hope -- in this case, the uninformed or under-informed belief that everything will work out OK -- is something that I would consider an active, positive coping strategy. I'm all in favor of whatever helps a newly-diagnosed cancer patient get out of bed and face the day. (And I'm happy to talk more about that in the comments if anyone wants to.) 

As for what happened after the patients started using coping strategies:

56.3% used acceptance.

47.9% used denial.

47.9% used emotional support.

The patients who used multiple approach-oriented strategies (the active ones) reported fewer symptoms of anxiety and depression, and reported a higher Quality of Life. This makes perfect sense to me. An active approach gives a patient a feeling of control. That's why I've been writing the blog for 15 years. It's always made me feel like I'm doing something, especially at a time when I could do nothing but watch and wait. I don't think an avoidance strategy would work for me. Though, as I said, I've known and heard about patients who have used it very effectively. I think for someone with an incurable cancer, the ability to not think about it every day could absolutely lead to a better Quality of Life. Indeed, the study found that patients who use avoidance strategies had higher symptoms of anxiety, but not of depression, and did not have a lower Quality of Life. They are living their lives despite the cancer. (And maybe to spite the cancer.)

The researchers conclusion isn't to recommend any particular strategy for coping. Instead, they suggest that interventions are necessary. And that seems right to me, too. And strategy can work, even denial or avoidance. As long as the avoidance doesn't do any harm, then it's OK. And for me, the harm would be avoiding treatment. I've seen that up close, with people that I love denying that there was a problem until it was too late to do anything about it. But getting a diagnosis, and then putting it out of your head until a problem pops up? That's fine with me.

It makes me think about a patient that my oncologist told me about very soon after I was diagnosed. He said this patient had been diagnosed with FL about 30 years before. He retired and moved to the Bahamas, and once a year, would come back to the New York City area to see his oncologist, and then see a couple of Broadway musicals, and then head back to where it was warm and sunny for another year. 

I have to be honest -- that sounds a whole lot nicer than being hunched over a keyboard all winter, reading medical journals and writing bad news to you about PI3K Inhibitors. 

But we all find the best ways we can to cope, and to maintain the best Quality of Life that we can.

So if it's working, keep doing what you're doing.

And if it isn't -- talk to someone who can help you figure out what might work for you. Your oncologist is a good place to start. They might know about resources that are available to you.

And remember that I'm always here and happy to listen.

Take care.

 

R-Squared and the C Word

Interesting video (with transcript) from the Oncology Learning Network last week. It's called "Dr Strati Highlights Lenalidomide Plus Rituximab for FL," and it features Dr. Paolo Strati from MD Anderson Cancer Center. He talks about the use of R-Squared (Lanalidomide + Rituxan) as a first treatment for Follicular Lymphoma. 

This isn't new research that he's discussing. (This seems to be a discussion of some research from ASH in December, which was a 10 year follow up of a study of R-Squared. The research has been around for a while, in some form or other.)

A quick recap of that research (though the results of the research aren't really what I want to focus on here): There were 70 patients enrolled in the study ( a fairly small number), and after 10 years, 70% of them were still treatment-free after 10 years. There was no common feature of the disease (like a biomarker) that could predict which patients would have such a long time without treatment, though it was much more likely to happen if the patient had a Complete Response to the R-Squared. 

All of that is great, and I've talked about it before. What really caught my eye was something Dr. Strati said about the "c word":

"What we saw was with immunotherapy, up to 70% of patients were still treatment-free 10 years after initial treatment. We tend to say that FL remains incurable. Findings like this challenge this paradigm."

Just to be clear, he says it again soon after:

"The most surprising outcome, in my opinion, was very high disease-free rate (of) 10 years after initial immunotherapy. As mentioned before, we keep saying that patient with FL cannot be cured, but in immunotherapy, and more recently also cellular therapy, may completely change this narrative."

Now, I have also given my thoughts here about the "c word," and the idea of a cure for Follicular Lymphoma. I think we're moving our way towards a cure, though I personally have a hard time thinking about FL being curable.

Let me be clear about that -- for me, it's a personal thing. I've lived with the idea that Follicular Lymphoma is not curable, that I will likely have it for the rest of my life, and that treatments are available now and will continue to become available over time that will help me deal with my FL, for as long as I have it. It's really hard for me -- again, personally -- to get past that. I haven't needed treatment for over 12 years. I'm not cured -- I was just looking at the electronic notes from my last oncology visit, and I was reminded that my last scan (several years ago) showed some small amount of disease still lurking around in there. I might go another 40 years and not need treatment. But I'll probably still be eating my 90th birthday cake, thinking, "Gosh, that FL could come back any time...."

Dr. Strati's comments highlight for me just how complicated it will be to define what a "cure" is for FL. Is it that 70% of patients go longer than 10 years without treatment? Because that's happening not for a lot of R-Squared patients, obviously, and for some CAR-T patients with leukemia. 

As I mentioned when I wrote about problems with inhibitors recently, I think having more durable treatments (that is, treatments that give patients long periods between treatments) will become much more common as we move along. It's going to be seen as an important, achievable goal. Doctors and patients aren't going to be satisfied with an exciting new treatment that gets at FL cells in a new way, if that treatment only lasts for 18 months. There are going to be other, better options available. there already are.

Which brings up one of the big complications of saying an FL patient is "cured" -- our median age at diagnosis. Most FL patients are diagnosed in their 60's. If a patient is diagnosed at age 70, has R-Squared or CAR-T and never needs another treatment, and then dies of something else at age 80, were they "cured"? Some lymphoma experts call this a "functional cure" -- maybe not a long enough time to measure whether or not they would have continued to live without treatment, had they been diagnosed at a younger age. But, on the other hand, they died at or near the average lifespan for the general population, without ever needing treatment again. That's pretty close to "cured," isn't it? It's what we all hope for, right?

And since a very large portion of FL patients are diagnosed late in life, it's very likely that many more of them will be "functionally cured" in the years to come. 

But that makes it had for someone like me, diagnosed at age 40, to wonder if and when I'm cured. Like I said, 90 candles on my birthday cake, and I'll be making the same wish.

The good news with all of this -- to get back to Dr. Strati -- is that we have treatments with long durability, and more coming. When I say I think that's going to be the goal of treatment in the future, keep in mind that I'm saying that as a non-expert. Just my opinion. But we're seeing more of that long durability with new treatments, and I suspect we will see more of it still. 

That's a very good thing, no matter what word you want to call it.

Some Thoughts on Being "Cured"

I appreciate the comments on my last post about how hopeful it was. I always love hearing a Lymphoma expert get excited about a treatment. And I love it even more when two experts are fighting over which of two great treatments is better. 

Jacquline's comment was interesting: "I belong to several Follicular Lymphoma groups on various social media sites. There is a gentleman who swears that CAR-T cures fNHL. He apparently was "cured" because of it. I know someone who was not helped by CAR-T and eventually passed away. As with all treatments, some work for some people and don't work for others. That is why this article was so uplifting, it offers us many wonderful and promising treatments that are in the "pipeline". It is an exciting time, I feel fortunate to be living during all of this." 

As much as I want to be as enthusiastic as the gentleman that Jacqueline describes, I'm with Jackie on this one -- hopeful but a little skeptical. I do think CAR-T is a miracle for a lot of people, and may very well cure them (whatever that means -- it's a complicated word). But I also know that there are a lot of patients who don't get a long-term benefit from it. 

I want to focus on the word "cure." It truly is a complicated thing, and has a few different meanings. Some cancers are considered "curable," meaning there are treatments that have a very good chance of working, for a long time, for a large number of patients. I don't think there's an official definition of "cured" for cancer (not one that I can find). But there are certainly some patients who have received a treatment that lasts for their lifetime. That's "cured." And there are some cancers that have a larger number of patients in that situation. that makes the cancer "curable."

Follicular Lymphoma is, unfortunately, considered not curable. We just don't have treatments that work for many years on a large percentage of FL patients. 

Here's where it gets complicated. Some Lymphoma specialists talk about patients being "functionally cured." In other words, they might not have entirely eliminated all of their cancer cells, but they haven't needed treatment again. Think about someone who is diagnosed at age 70 (pretty common), has B-R and then R-maintenance, and then a scan turns up some cancer cells at age 80. Not enough to need treatment again -- it's still growing slowly. That patient then dies a few years later, at age 84, about average life expectancy for the general population.

Was the patient "cured"? No -- there were still some cancer cells in their body. BUT, that B-R + maintenance lasted a very long time, long enough that they didn't need another treatment. Which is the definition of "cured," isn't it? This is called a "functional cure." Not technically cured, but living the same life as someone who was "cured."

(Incidentally, this is where I am now. 13+ years without treatment, but still had some bright spots on my last PET. I do not consider myself cured. There's always going to be a little part of me that expects it to come back.)

So while there aren't enough patients who will get treatment, and then go for their lifetime without cancer, to have FL be considered "curable," there are individual patients who may very well be "cured." But because the disease isn't considered "curable," it's hard to know for sure.

How does CAR-T fit into all of this?

Well, when CAR-T treatments were first approved, the clinical trial results were kind of 33/33/33. About one third of patients did not respond to treatment, one third had a response that lasted a year, and one third had a response that lasted longer than a year. (Those are very rough numbers.) Those numbers are improving, slowly, especially those whose response lasts longer than a year. In my last post, I write that Dr. Cheson says about 35% of patients in one study had a PFS of 5 years. In another follow-up, 10 patients with indolent (slow-growing) lymphoma who were given CAR-T had a median Complete Response rate of 5 years -- that's no cancer at all. The range for those 10 patients was between 1 and 114 months. So for at least one patient, it really didn't work at all. And for at least one more, it lasted almost 10 years.

To get back to Jacqueline's comment: the gentleman who believes CAR-T is a "cure" might very well be the patient who has had a 10 year response from it.  The patient with the 1 month response would probably disagree.

So, as I said, a "cure" is complicated. Some patients might very well be cured.

But for me, the numbers are a little less hopeful. Too many patients who don't get the benefit.

Which isn't to say that there will never be a cure, or even that CAR-T won't be the treatment that turns out to be a cure. I'm still hopeful that the day, and the treatment, will come. I think there's even a good chance it will come during my lifetime. (Remember, I plan on living a very long life.)

In the meantime, I'll stay hopeful, keep learning all I can about this disease, and be ready when the time comes to choose a treatment to give me the best chance at a cure.

ASH: Are FL Patients Being Cured?

OK, I'm finally getting to the link that Jacqeuline sent a few days ago, with a press release about an ASH presentation. Drug companies and universities send out press releases after the conference when they think they have something to brag about that cancer news sites might want to to share.

This one is certainly going to get people talking.

The presentation is called "Long-Term Follow-up of Follicular Lymphoma (FL) Patients (pts) Demonstrating Undetectable Minimal Residual Disease (MRD) Using a Next-Generation Based DNA Assay: Support for FL As a Curable Disease."

If you look again at the last line of the title, you can see why Jacqueline (and the researchers) are excited: "Support for FL As a Curable Disease."

So here's the deal. As I'm sure we all know, Follicular Lymphoma is considered an incurable disease. There are some circumstances where FL might be cured (see below), but for the most part, we're stuck with it. How the disease behaves is a different matter, and there's a wide range of behaviors: for some of us, it's really aggressive, and a patient might need treatment within a couple of years of having chemo. For others, it can grow slowly over years and years, and treatment might never be necessary. And then there are hundreds of variations in between.

But whatever little (or big) quirks our individual disease gives us, we all pretty much live with the idea that we either have active FL, or it's probably coming back at some point.

This research asks you to rethink that idea.

The study involved 60 patients. All of them had received treatment that had put them in clinical remission (meaning there were no signs of relapse in a blood test, a physical exam, etc.). The patients received a pretty wide range of  treatments -- R-CHOP, B + R, RIT, Stem cell transplant, double MAB (Rituxan plus another monoclonal antibody). There weren't any that received just Rituxan in this study (which would have been very interesting to me, as someone in that situation.)

The 60 patients had their biopsy samples looked at -- that is, the samples that were taken before they were treated -- and had the samples put through a new type of analysis that can identify changes in the genes that are related to FL. The analysis allows the researchers to identify MRD, or Minimal Residual Disease -- the changes in genes that remain even after the cells look like they're all cancer free. (See the Leonard List post for more on why MRD is becoming more important.)

After treatment, and after patients were said to be in clinical remission, another sample was taken so the FL-related genes could be analyzed again. The idea is, we have a good idea of some of the genes that get messed up when a patient has Follicular Lymphoma. Because certain genes do things like control when a cell is supposed to die, a messed up gene can keep a cell alive, and that's when you get cancer. So a test that can look at those genes can basically tell you if they're still messed up, so even if a patient seems to be in remission, the cancer might come back later (like we assume it will do with the incurable FL). Everything might be OK for now, but those genes that keep cells alive forever are still there, waiting to be jerks.

But what this test found was that some of those genes, two years after getting treatment, were back to normal. They aren't waiting around to tell the cells to stop dying at some later time. No MRD.

There were 43 patients whose samples were analyzed after treatment, and 38 of them did not show any genetic evidence of disease.

If there are no genetic mutations hanging around in the cells, can we say that these patients have been cured?

Maybe.

The researchers are optimistic, but also caution that this study involved a pretty small number of patients, and a fairly short follow-up. The lead researcher calls it an "important first step."

And it's important to be clear -- this study isn't about a new treatment that might cure FL. It's about a way of letting patients know, two years after treatment, that they don't have any evidence of disease. It's more about being able to lift that emotional weight off of us. We all learn to live with the idea that the FL will probably come back. This way of testing can maybe give patients some peace of mind.

The idea of FL being curable has always kind of floated around as a possibility. Lymphoma Superstar Dr. Bruce Cheson, who is on the team for this research, is always holding out hope that there may be a cure for FL. There is some evidence that patients with stage 1 or 2 FL might be cured with radiation. And Dr. Cheson and others sometimes talk about a "functional cure" -- a treatment can give a long enough remission that a patient dies of old age before they need another treatment (so the FL wasn't officially cured, but the patient lived a cancer-free life, so maybe that's the same thing). CAR-T and maybe some other newer treatments might be able to use the body's immune system in such a way that it can permanently fight off the disease, so even if FL is present, it's held in check.

So we may be very well be on the path to a cure.

Or at least on a path where we can live as if the FL is cured.

One final thought. If the most important thing to come out of this research is that the emotional burden of incurable disease might be lifted, I'm not sure that's going to happen.

I've talked to enough cancer patients -- people with cancers other than FL -- to know that even after years in remission, there's always that little nagging in the back of their minds that the cancer might come back. I'm not sure a test that showed no MRD would get rid of that feeling. Especially for someone ike me who has already lived with it for 12 years.

But maybe a test like this can show that there really are some patients who are being cured, and we just haven't known it yet. Maybe we can go from labeling this an incurable disease to one where we can say "some patients may be cured." So it might not help a cynical old FL patient like me, but people in the near future might have some of that emotional burden taken off of them, even just a little bit.

Even a little extra hope is a very good thing.

Updates on Follicular Lymphoma [Video]

Found a nice video of a talk from the 2019 Great Debates and Updates in Hematologic Malignancies meeting. The video is called "Update on Upfront and Maintenance Therapy in Follicular Lymphoma," and the person speaking is Dr. John P. Leonard of Weill Cornell (and certified Follicular Lymphoma Rock Star).

The talk is aimed at other doctors -- you can tell that by the way Dr. Leonard speaks ("If you are considering certain treatments for your patients...."). It's also pretty thick -- lots of medical terminology.


Dr. Leonard's purpose is to discuss how he typically treats certain types of  Follicular Lymphoma patients, and talks about his decisions in terms of recent clinical trials in FL. Sometimes he agrees with what the trail suggests an oncologist should do, and sometimes he doesn't.

I like looking at videos like this (or reading articles that do the same thing). It gives me a good sense of what a top FL doctor is thinking, and how recent research is influencing his decisions. It  makes me feel like I'm up-to-date on what's happening with my disease.

He says he always looks at the information he has about the patients, and then divides them into three groups. He handles treatment decisions differently for those groups.

The first group is patients with limited stage or localized disease -- usually stage 1 or 2. For these patients, watching and waiting might be fine. There are some patients who could actually be cured with radiation. He comments on the idea of "curing" patients. He says his thinking on this is "evolving." He looks at a 10 year study of radiation versus CVP chemotherapy. The chemo patients had a better Progression Free Survival, but the Overall Survival was about the same for both groups. His personal approach tends to avoid chemo with this group: watch and wait when possible, try radiation when necessary, maybe try Rituxan. But he also tries not to put too much emphasis on a "cure." For some patients, they can get a "functional cure" -- not an actual cure, but also not needing treatment ever again, especially if they are older.

The second group is the advanced stage, low tumor burden group -- stage 3 or 4, but without symptoms. (This is pretty much where I was at diagnosis.) He likes Rituxan for this group (again, this is how I was treated.) Watching and waiting is an option, too. But like the first group, lots of treatments have different PFS, but the OS. In other words, more aggressive treatments might mean more time between treatments, but they won't make patients live longer overall. He talks about Maintenance with this group, too. The RESORT trial showed that, for patients who only had Rituxan as a treatment, Rituxan Maintenance (regularly scheduled doses of Rituxan after the first doses) doesn't help any more than just waiting until Rituxan is necessary.

He thinks watching and waiting is fine for this group, too, and he likes to take that approach, even for a little while, because he thinks it helps the patient get used to the idea of having a chronic cancer, one they may need to deal with for a long time. He avoids chemo if he can, though if a patient needs it, he certainly gives it -- and the patient is OK with the trade-offs that come with longer PFS.
 
For the third group, advanced stage, high tumor burden, he considers chemo. He usually goes with Bendmustine over CHOP -- same OS, but usually fewer side effects.

Again, the Maintenance issue comes up here, though the PRIMA trial found that Maintenance improves PFS but not OS (that is definitely a theme).

He also talk about the GALLIUM study, which looked at chemo + Rituxan versus chemo + Obinutuzumab, both followed by maintenance. No OS difference. The O group had longer PFS but the R group had fewer side effects.

He also discusses the RELEVANCE study, which looked at R-squared (Rituxan + Revlimid) versus R+chemo. This was the first study to show a non-chemo option doing as well as chemo. They had different side effects, so it's a matter of thinking about which option is based for each patient.

He also thinks that, for patients with fairly low risk, PET scans should be avoided as much as possible. An exam, or the patient's own noticing of symptoms, are just as effective, but without ther radiation.

Finally, Dr. Leonard thinks it's important to remember a "return to normalcy" -- because many of us will live with FL for a long time, it's good for us to have long periods of feeling and living "normally."

There are a lot of clinical trial results discussed here, and a lot of medical terms. In a lot of ways, they don't really matter. I mean, if you're a Cancer Nerd like me, sure, they matter, and it's fun watching the video while also typing notes and smiling when you realize that you know what he means when he uses a big word.

But more important are the general lessons that come out of this.

Like I said, Dr. Leonard is a Follicular Lymphoma Rock Star. And that's not just because he has a list of research publications in medical journals that would sink a small boat.

It's because, as he is talking to this group of doctors about research, he is constantly reminding them to think about their patients, talk to their patients, listen to their patients, and make decisions with their patients.

Follicular Lymphoma is frustrating in some ways because there is no "best" way to do things. we have lots of options. Many of them come down to Quality of Life. Do we want a treatment that will give us more time until the next treatment? And if we do, are we willing to put up with the side effects that come with it?  That's a decision that we all have to make ourselves, but we can't make it without an honest, informed discussion with our doctor.

I like to think all doctors would be that way with their patients. And this is clearly a talk that's given to a bunch of clinicians, doctors who treat patients, rather than a bunch of researchers. But it's nice to hear a discussion of research where the speaker is always reminding other doctors about their patients. It's very Rock Star of him.

ASH Preview: Quality of Life

The ASH conference is going on this weekend, but I have one more preview. It's a presentation scheduled for tomorrow (Monday, Dec 11): "Changes in Quality of Life in Indolent Non-Hodgkin Lymphoma 3 Years after Diagnosis." Since it hasn't happened yet, it's still technically a preview.

I am indebted to Dr. John Leonard for pointing this one out to me. When I searched for ASH abstracts for FL, this one didn't show up, since it covers "indolent lymphomas," which, of course, includes Follicular.

Dr. Leonard is active on Twitter, and in the days leading up to ASH, he tweets "Leonard's List" -- the 10 presentations he is most excited about. This one is #1 on The List. His comment on Twitter when he named this one as his #1 was this (I'm translating a little bit from Twitter-ese -- I know many FL patients are on the older side, and this kind of this is difficult for you to understand):

Since a large percentage/most indolent NHL patients will live a normal lifespan, here Quality of Life is a key issue/goal in long-term management. The study has important insights for Quality of Life course, reassures patients that Quality of Life likely won't deteriorate despite diagnosis, and patients seem to have psycho-social adaptation.

(Actually, I know most of you could have figured it out, even at your age. I was more concerned with how it would translate for my non-English-speaking friends.)

I appreciate his giving the top spot on his influential list to something that focuses on Quality of Life. As much as we all appreciate research that moves toward a cure (or at least a longer Overall Survival), we need to live with the disease, and the quality of that life can be an afterthought.

So QOL becomes an important factor. There are two approaches to FL research these days. One school of thought says we should go for a cure. But the other approach is to treat FL like a chronic disease, something that will always be with us, but can be managed through medication. I personally am open to either approach. But if I am going to treat FL like a chronic disease, then whatever treatment I receive must take Quality of Life into account.. There's no point in staying alive as long as the general population if I'm going to be miserable doing it.

For this presentation, the researchers acknowledge that Quality of Life can be affected by the disease itself, by side effects from treatments, and from the "psychosocial effects of living with an incurable cancer." (I'll say it again -- Follicular Lymphoma is an emotional disease as much as a physical one.)

Patients with Indolent (slow-growing) Non-Hodgkins Lymphoma (including Follicular) were included in the study. Their QOL was measured at Baseline (from what I can tell, within 9 months of diagnosis) and then 3 years later. QOL was measured using a survey called Functional Assessment of Cancer Therapy-General scale (FACT-G). You can see the survey here. It asks patients to measure their responses to fairly simple statements in 4 areas: physical, social/family, emotional, and functional well-being. So statements for "emotional well-being," for example, include things like "I feel sad" and "I am losing hope in the fight against my illness." Patients respond with how they have felt in the last 7 days.They were also asked to complete a "a single item Linear Analogue Self-Assessment (LASA) for measuring overall QOL."

1050 patients were included in the research (32% of them had grade 1 or 2 FL). At the 3 year follow-up, 577 patients (55%) had received treatment, 42 (4%) transformed, and 53 had an event (progression of disease, re-treatment, or death).

Interesting results:
Emotional Well-being significantly improved over 3 years.
Social/family Well-being  significantly decreased.
Functional Well-being, physical Well-being, and overall Quality of Life were not significantly different. 
The results were similar whether patients got treatment, or they watched-and-waited. 

In patients with an event during the 3 years, emotional Well-being had a significant improvement, but overall QOL decreased.

In patients without an event, improvements were reported in functional Well-being, physical Well-being, emotional Well-being, and overall QOL, but social/family Well-being went down.  

In their conclusion, the researchers say that the increase in emotional Well-being is a sign of "psychosocial adaptation by the patient." In other words, we learn how to deal with it.

I think that's probably true. We don't have much choice to adapt, so we adapt. We are, on the whole, very strong people. Sure, we have our bad days, but we get out of bed and get stuff done. That's just the way it is.  

It's hard to think back to where I was 3 years after I was diagnosed. I was a year past Rituxan treatments. I think I felt pretty good. It always helps to get a pretty clean scan. I was still running, so my physical Well-being was great.  I had support from family and friends. My day-to-day life was OK -- I was still working and playing with my kids. It all matches up for me.

What I found kind of surprising (though as I think about it, it shouldn't be surprising) is that the Social/family Well-being went down. 

As I think about it, this, sadly, makes sense. I hear lots of stories from people whose relationships were changed by cancer. family and friends stopped calling, probably because they didn't know what to say. That happens a lot, no matter what kind of cancer.

But people with FL and other indolent blood cancers face a different set of challenges, I think. 

When we get a diagnosis, lots of people come to our side. They want to help. And then -- nothing happens. Many of us watch and wait. The heat from the diagnosis starts to die down. Some people might feel a little betrayed. That cancer diagnosis had everyone worried, and now you don't even need treatment? Even worse than the people who don't know what to say are the ones who went on the emotional roller coaster ride with you, and got off before the ride started up again.

Are think there are two big lessons here.

The first is for patients. For many of us, we learn how to deal with the emotions that come with the diagnosis. We are, as I said, a strong group of people. We find ways to deal with it, and we do our best. For some us, though, we don't get the social help that we'd like. The lesson is that it's really important to find a social outlet. If family and friends can't help, then some group that understands what you are going through is crucial. Maybe that's a support group at the hospital you are being treated at. Or an online group (which is what worked for me). A Facebook group. Some bunch of people who can hear what you have to say and respond with "Yeah, I felt that way, too." 

The second lesson is for doctors. The physical check-up should be easy. The emotional check-up doesn't always come with the office visit, but it's just as important. And maybe doctors aren't comfortable with that, or aren't trained in that. But having some kind of resources available at hand would be helpful. Just a quick, "How are you feeling, emotionally?" might bring great results. Sometimes just being asked is a wonderful thing.

But the biggest take-away here is that researchers are paying attention to Quality of Life. That's a great thing. Certainly worthy of being #1 on any list.