Wednesday, December 3, 2014

ASH: Watching and Waiting (We're Still Talking About This)

It's amazing how some topics just won't go away.

Watching and Waiting is one of them. It's especially interesting to me because I watched and waited for two years. I suppose I shouldn't really care anymore, since that ship has long since sailed, but I'm still interested in what research has to say about whether or not I made the right choice. (It certainly seems like I did, almost 7 years later....)

Researchers at the National Cancer Center Hospital in Tokyo are interested in whether or not Watching and Waiting is still a valid strategy in the Rituxan Era. This has been the way the subject has been thought about for a while: the idea behind watching and waiting was that it was better to do nothing because the alternatives could do harm (when the alternatives were traditional chemotherapy). But with Rituxan, and its minimal side effects, is there really a reason to wait? Another reason for W & W: with a limited number of available treatments, isn't it better to hold them in reserve until absolutely necessary? But now, we have so many new treatments available and in the pipeline, why not just treat immediately?

There have been lots of responses to those questions in the last 5 years or so, with answers on both sides. But neither side has been able to come up with research that shows that their side is the winner of this debate.

So the latest attempt, to be presented at ASH, says this:

The study looked at 348 patients treated between 2000 and 2012 (101 watched and waited, and 247 were treated immediately). Of the Watch-and-Waiters, 45 patients received treatment for lymphoma within a median of 16 months. Looking at Time to Treatment Failure (how long it took until a second treatment was needed), the 45 who had watched and waited before treatment had a TTF of 92 months, while the patients who had immediate treatment had a TTF of 85 months. Statistically, there's no difference between them. Other measures had the same result: Overall Survival was essentially the same between the groups, and so was risk of transformation.

So, basically, there is no negative impact to Watching and Waiting, at least in looking at these particular factors, for this particular population. That seems to be about the same result that we've kept getting for the last five years.

Of course, the numbers don't really tell the whole story when it comes to deciding whether or not to watch and wait. Numbers can tell your head that it's an OK choice, but there's an emotional aspect to that decision, too. If you think you can handle the not-knowing, and you don't feel the need to just do something, then watching and waiting is an especially valid choice. But that's a hard thing to measure with numbers, especially in the heat of a new cancer diagnosis. That's got to come from deep inside.

So it's good to know that I made an OK choice seven years ago. Not that I would have regretted it if the numbers have come out differently. No point in regretting our choices. We have enough to worry about without adding guilt to it.....


Anonymous said...

Dear Bob

Thank you for your blog. I have been reading it ever since I was diagnosed with FL grade 1a, stage 2 in 2013, after 3 years of annual scanning and not knowing.
Today I received the lab results of my biopsy in 2013. I got them from my hospital to hand them over to my health insurance company, who would thus recognize my disease as serious (sic!).
What terrifies me, however, is the
result of up to 50% Ki-67 colouring, which nobody ever mentioned to me.
Are you aware of any revealing literature on the matter, for not being sure seems to be the worst.

Best wishes


Lymphomaniac said...

Hi Christina.
Thanks for reading the blog.
I've said it before, but I'll remind you again: I'm not a medical doctor, so take whatever I say with that in mind.

It seems like you know something about Ki-67: it's a protein that has to do with cell reproduction, and more of it generally means a more aggressive form of lymphoma. The suggested cut-off is 45%. That is, when a biopsy of cells is stained with a certain substance, Ki-67 will show up stained. More than 45% of the sample showing up as Ki-67 often means the lymphoma is aggressive; less than that means it's indolent.

You're obviously worried that the 50% means you have something more aggressive than it appears.

Two thoughts on this:

First, grade 1a, stage 2 would indicate a pretty indolent form of FL: slow-growing, and fairly well contained to a couple of places. The biopsy would have been examined for a bunch of things besides Ki-67, and all of them, taken together, would result in the grading and staging. So whoever looked at the biopsy must have thought the Ki-67 was not far enough out of indolent range to change the stage and grade. (45% is a statistical cut-off, but 15-20% of people are higher than 45% and are still considered indolent, in the research I have seen.) I think if your lymphoma was aggressive, you'd have known by now, and changes in the scans over 3 years would have picked something up that showed it was aggressive.

A second thought: there's a lot of variation in the counting of Ki-67. It's basically done by looking at the slide and saying "Yeah, that looks like about half. We'll call it 50%." It could very well have been 45%. Coming up with that percentage is as much art as science, and a study that gave the same FL slides to a bunch of lymphoma pathology experts showed that they had a tough time agreeing on Ki-67 percentages. In other words, if someone different had looked at your sample, they might have come up with 45%. (Or 40%. Or 55%.) Which is why they use more measures than just Ki-67 to determine stage and grade -- it's not a really accurate way to measure things. (If you want to see that study, it's at

If you're worried about transformation, I don't know of anything that says the Ki-67 number AT DIAGNOSIS is a marker for later transformation. If it was, it would have been made a bigger deal of by now. There is a higher Ki-67 in people who have already transformed, but that's not the same as saying "You're at 50%, so you are going to transform some day." There's no connection between initial Ki-67 level and future transformation, as far as I can tell.

So I think the fact that no one mentioned it to you was probably for a good reason -- it's probably not something that they were worried about.

Again, I'm not a medical doctor. If it's worrying you still, ask your oncologist about it. You can ask to have the biopsy taken to a different lab and re-analyzed for a second opinion. Or your onc may be able to explain the bigger picture, and what some of the other numbers mean.

Be careful with those numbers, Christina. Any time I've gotten depressed about my lymphoma, it's because I started thinking too much about numbers. It's easy to focus on just one bad one and ignore all of the good ones.

Talk to your oncologist. It might give you some peace of mind.

Hope this helped just a little.

Anonymous said...

Dear Bob

I'm ever so grateful for your - as always - wise comment. It certainly gives me peace of mind. The sharpest edge of my worries has been filed.

I have phoned my oncologist, but as he was seeing patients I haven't been able to speak to him yet. I'll try again later.

I wish you the happiest of Christmas and New Year's family days all the way from Europe.