I may have to stop going to the doctorPlease I need help

Physical Health Cancer
1

Everytime I go, I get worse news. I made the switch to my new doctor at the James Center in Columbus, OH. She is a talented, smart doctor who specializes in large cell lymphomas.

I went to her to get a second opinion and she laid on me some bad news. She said I likely have a form of Burkitt's like lymphoma not simple DLBCL. I have what is called the "double hit" with MYC and Blc2 issues. It is very aggressive. Ross, you talked about a "freak like" form of lymphoma and I guess this is what you meant.

She also said that the mutiple bone lesions on my bones count as more than one extrandoal site and therefore I have two points on the IPI. She also said she doesn't follow the R-IPI which gave me an even better prognosis.

Her prognosis is 50/50 on the frontline treatment which is now EPOCH - R. I will be hospitalized for five days during each treatment.

Now, there are many reasons to feel blessed. One, the second opinion is very different than the original (too bad it was worse), but at least I will get the correct treatment.

Second, she is using an advanced treatment. As she told me, this disease often relapses and this treatment is designed to prevent that. She has only been using it for one year.

Third, even if I relapse, I can do stem cell and that is 50/50 so, coupled with the 50/50 of the frontline, I have a 75% of making it through.

This lymphoma thing is a roller coaster and I am now on the down slope. Thank God I have you people.

2

Cowboy--
Well this is a setback. And it does, for all intents and purposes, rule out use of the RIPI because of its narrow treatment and diagnosis parameters. As for the bone counting as more than one extranodal site, I'm sure she's right, but I would never have told you that it counted as one if I didn't have a reliable source to back it up so I'll backtrack and find my source.

Dose-adjusted EPOCH-R for newly dx'ed aggressive lymphomas was established in 2003, and the patient population studied all had DLBCL.

On the plus side, combination chemotherapy is tailor-made for highly aggressive cancers-- this is where chemo works the best, when cancer cells are dividing at a rapid pace, the more often they go through mitosis, the more often they are exposed to the mechanisms of cytostatic drugs.

More to you shortly Cowboy-
Ross

3

Cowboy, we are here for you, man. I have no help for you but you have my support and regard. Stay strong and get the facts you need to be your own best advocate. We will be here to back you up any way we can.

Good health,

Kermica

4

Ross-

Three doctors at the other hopsital also said it didn't matter if I had spots on more than one bone - it would count as one extranodal. This may be an issue that is somewhat open to interpretation. She was, however, emphatic about it.

Okay, I may have spoken to fast about the "Burkitt's like" diagnosis. Looking over my notes, she thinks it is DLBCL with positive C-Myc and BLC2 markers. Does this improve my situation?

She said it "could" be Burkitt's like, but she would expect other symptoms - raised LDH. CVS involvment, etc.

My doctor talked about curing my disease and said I have a 50/50 chance during the frontline treatment and another 50/50 on the second line. She didn't seem excited to tell me about the change in diagnosis, but she didn't make it sound like I had but a very slim chance.

She said there is a chance that it Burkitt's. I asked her he which I would prefer and she said DLBCL. It seems like it has a much better outcome.

Also, she isn't planning on doing a PET scan until after the fourth chemo and she seemed in no hurry to do any advanced testing anytime soon. Finally, she said after treatment, she would see me every three months - pretty standard.

Now I know she is concerened about relapse. In fact, she indicated she expected me to do well with treatment, but relapse is an issue with this. That's why she is doing the EPOCH - R including spinal injections.

I apprecaite any thoughts.

5

Cowboy-
OK, I'm not pulling any punches here, so be ready.

There appears to be a convergence of B-cell diagnoses when you get up into the really aggressive forms: there's the most preferable one, which we might call your everyday average DLBCL. preferable because the most is known about it, because treatments are known to work well, etc.

there's also Burkitt's. Dr. Judith Ferry (a pathologist with Harvard and Mass General) wrote in the journal The Oncologist in 2006 that "Among human neoplasms, [Burkitt's] has the shortest doubling time." In other words, it grows faster, or is more aggressive, than any other known cancer. I knew Burkitt's was up there, but I wouldn't have guessed that it was number one.

Then there's what you mentioned, "double hit", which as a term was 100% new to me. Also called 'dual fusion', what 'double hit' means is that the lymphoma subtype has so-called "dual gene translocations" and these are what you mentioned, the MYC and the Bcl2. So it's often referred to as either MYC/BCL2 (or M/B) high-grade B-cell lymphoma. It could have evolved from a previous B-cell lymphoma or appeared on its own out of nowhere. Extranodal involvement is not uncommon, and it's not uncommon to relapse or for the disease to be refractory (as your onc has mentioned). The reason it's believed to be so fucking aggressive is because of the meeting of those two translocations—MYC promotes rapid proliferation, or speedy growth, while BCL2 discourages (for lack of a better word) apopotosis, or the kind of programmed cell death that every cell is supposed to go through, but do not go through when cancerous.

So you ask if those markers improve your situation, the straight up answer is no.

You might be wondering just how they're coming to all these minute conclusions when it seems like it would be fairly straightforward-- either it's Cancer X or it's not. But lymphomas are not like that. Several decades ago, someone made a huge mistake: they started grouping cancers that affect the lymphocytes under the same banner, 'lymphoma'. this is a mistake because so many of the dozens of lymphoma subtypes are known to be heterogenous- or totally different- cancers from one another.

I wrote about the huge obstacles facing pathologists in lymphoma a month or two ago ("A tale of two t-cells"), and those two pictures I included illustrate the problem; they look pretty fucking similar, but they are as different as night and day. So in order to make diagnoses and treatment modalities more accurate in lymphomas, pathologists now need to tease out what molecular markers are expressed on the cell surface-- which is why we tell everyone diagnosed with lymphoma to get a second opinion from a qualified blood pathologist at a national comprehensive cancer center (NCCN) because an average pathologist lacks the experience.

If interested, go to PubMed's home (http://www.ncbi.nlm.nih.gov/pubmed/) and enter this in the search field, "Tibiletti MG Hum Path". You should land on a 2009 paper about the clinical relevance of BCL2, MYC, and three other rearrangements in diffuse large B-cell lymphoma. It's just an abstract. But it's plenty.

The last thing to keep in mind here is that whether it's Burkitt's, Burkitt's-like, or DLBCL, every source says the same thing-- they're curable. this is likely due to their aggressiveness and the fact that this is what combination chemo was made for.

Ross

6

I appreciate your candor. Based on what I've seen, I wouldn't guess that I have a 50/50 on frontline and anthother 50/50 on secondline treatment. Can you think of why my Dr. would give such a postive assement in light of the terrible track record of the prognosis? She is at one of the foremost cancer hopsitals in the country, I can't beleive her prognosis isn't what she believes is accurate.

7

I can offer a couple suggestions, the first being the more important-- she's basing it on what she knows and it IS accurate, and as a pro she knows better than any of us, either through reading the literature or through the results in her own practice or both.

The other suggestion comes from this small study about the behavior of hematology oncologists during a first consult.

8

Ross -

I had to speak to my Dr. I had too many questions and wouldn't sleep a wink until I spoke to her. She was awesome and called me back within the hour.

After speaking with her, I feel much better.

Here is what she said (I'd like your take) -

•What is your prognosis based on?
"The IPI and patients with the same diagnosis"
(She doesn't subscribe to the R-IPI - she would like the sample size to be larger...typical researcher)

•Does the addition of Rutaxin factor into it?
"I don't count it, but there is reasearch that it does have a favorable impact on outcome...you could add 5-10% to your prognosis"...I took 10%

•Double Hit seems to have devastating outcomes – How do I reconcile that with the prognosis?
"There are two primary reasons. First, most of the data pertains to Burkitt's, B-Like or Grey Zone Lymphoma. Clinicians have only been looking at DLBCL markers at the time of dx for the past year or so. The other studies are backward looking and usually pick the patients with the poorer outcome...those with good outcomes often move on."

•You mentioned I have a 50/50 chance of frontline and 50/50 chance of secondary – stem cell. If I’m doing the math correctly that’s 75% - is that of curing the disease?
"Curing and I feel comfortable with that because it is likely DBCL"

•I wasn’t clear on whether you think I have “Burkitt’s like” or DLBCL
"DBCL"

•Is this type of lymphoma considered “grey zone” lymphoma?
"No"

•You mentioned it would be better if I had DLBCL rather than Burkitt’s – why?
"DBCL has a better outcome"

•Is the reason you suggest the more aggressive treatment regime generally to help prevent relapse?
"Yes, relapse and refractory. Studies show an agressive treatment is warranted in this case."

•How often do people generally relapse – or is treatment fractory?
"In your case 40-50% which includes 10% refractory"

Additional -
•She has six patients that were dx with DLBCL and had myc/bcl2 markers. They completed treatment from more than a year to six months. Using the treatment R-EPOCH, she has yet to have any patient relapse. (I know that is a small sample, but that is encouraging).

•"There isn't a lot of data on your situation - DLBCL with myc/bcl2. This 'could' act in the same way as every other DBCL. We really just started looking at this last year."

•"If it we refractory, you would likely see and advancement in the disease (new lumps, symptoms."

•What you have going in your favor - "I like that it seems to be DLBCL, you are young, no increase in LDH, and you are active."

9

Cowboy-
I'm glad you called her, I wish more people would do that, not worry about whether they might be bugging them or not, this is your health, your life. So, good call.

As regards the R-IPI, she is right about the sample size, at least in the paper that established it. I think it looks at under 400 patients. THAT SAID, you gotta love three of the four things she says at the end that you have in your favor:

"your young"(i.e Age)
"no increase in LDH"
"you're active"

Three of the five independent prognostic indicators in the R-IPI.

Regarding Rituxan, that's interesting that she would downplay it so much. It's had a huge impact on B-cell lymphomas like DLBCL that express CD20. Obviously she knows something.

Here your 'typical researcher' comment could use a reprise: When she says 'backwards looking' she means retrospective analysis, which as research goes will always pale in the face of a prospective study, for many very valid reasons. Still this doesn't invalidate retrospective studies.

Her six patients, I agree, that's encouraging. And it, possibly along with the Rituxan issue, goes back to what I said earlier about her own experience of these diseases and drugs and outcomes in her practice.

It sucks that they don't know exactly what you've got going on, but let me tell you man, that kind of uncertainty--uncertainty is the wrong word--that kind of ... flexibility with the unknown, with the not-yet-known, is the mark of maturity in a doctor. Ultimately it sounds like she's a pretty straight shooter. And it sounds like you're in good hands.

And it's important that you're feeling better about this. Are you?
Ross

10

Hey Ross - (I have two questions for you at the end)

I do feel better about things...The "double hit" was devistating because all I found was doom and gloom. She says that is generally in patients with Burkitt's, Burkitt's Like and other undefied lymphomas. I get the sense it is an added risk factor along the line of bone marrow, bulky disease etc. Of course I could be wrong.

Couple of quick points - I wasn't discounting her reaserach mindset. Indeed, that is why she is inquisitive into my particular subset. I was making apoint that she requires adequate data before making a decision (on the R-IPI).

She believes it is DLBCL but with the markers. That is an added challenge and one that has not been explored that much in DLBCL. She says it is only been examined over the past year or so at time of dx.

She has ordered another biopsy of the frozen tumor to validate her opinion. She said the markers won't change because they are very sensitive to the test that they run to identify them.

I don't know that she is down on Rutuxan, but I think she doesn't yet subscribe to the R-IPI and therefore doesn't give it much weight on predicting outcome. She did say it could give me a 5-10% boost which takes me to 60%.

Here is my questions;
1. She said she factors IPI into her prognosis. You are right about being a practical, straight shooter. She all but said her prognosis is on the conservative side. My question, would you think my outcome could be closer tied to R-IPI than IPI. I am not going to march in to her office and demand she change my prognosis, but would another talented dr. use the R-IPI or is my situation so unique, that the modeling is not valid?

2. the bone extrandoal issue is kind of a big deal to me. It takes me from one to two points which really shows up on IPI - Not as much R-IPI. Do you think this is an issue open for interpretation? I've had three doctors and you say it counts as one. I know at the end of the day (which I hope is years and years from now) it doesn’t matter as the only thing that matters is if I'm cured. But it does give me some hope and something to put in the plus column.

Thanks man for all you do!

11

Cowboy, you ROCK. Self advocate. My husband is a FNHL patient. A close friend of ours just beat " Burkitt's" NHL. Love your spirit. In my prayers. Knowledge I do not have, but support, always!

12

Cowboy-
1. It doesn't appear as though she has reached a definitive conclusion about your dx; she's leaning towards DLBCL, Burkitt's isn't likely, Gray zone is out, but there is still a chance it that it winds up as double hit lymphoma, right, with the BLC2 and MYC re-arrangements? this is described as its own DLBCL variant, sharing similarities with Burkitt's, DLBCL and what's known as B-lymphoblastic lymphoma/leukemia. if your cancer turns out to be this ('double hit lymphoma' will get a new name some day soon), then the R-IPI is pretty much out.

But in truth, it's out anyway if you're not getting R-CHOP, and it looks like you're not. The index was modeled according to a rather specific patient body, and you're kind of slowly sliding out of it. so to answer your question, it appears as though your situation will be unique enough to invalidate use of the R-IPI. This doesn't just hinge on the dx, it also hinges on treatment- that population received R-CHOP and radiation, standardized treatment.

2. When you first presented the question about whether your lesions would count as one or two, I looked hard to find a reliable source that would tell me which way that goes, and I know I found it. I never would have said it if I hadn't found it-- why I can't find it again I don't know, even though I've thoroughly backtracked. So I'm doing what I can to clarify that for you, and I understand why it's important to you.

I'm going to keep looking, but I also emailed the Vancouver researcher who was the lead author on the paper that introduced the R-IPI. We'll see if she responds to me, I sent it as a media request so we'll see.

By the way, your doc at OSU is saying what exactly, that the five spots you have constitute two extranodal sites? Is this right?

Ross

13

Hey Ross

Well I should have known you were all over this. I just spoke to the dr.'s office and got clarification. They did term it Double Hit Lymphoma. They also said it has recently been given its own category. they used to call is "Burkitt's Like."

Please know I do trust and appreciate the information you provide and I'm sure that you provided documented info about extranodal bones. That's why I'm asking you for your thoughts. I would like to know if other respected professionals see it a different way.

My dr. is pretty sure it is DBLCL "Double Hit" with the two markers. I asked her point plank and she said the characteristics are large cell and that indicates DLBCL. She said it it were Burkitt's I would almost surely have very high LDH levels. I asked her if it was a "Grey Zone" lymphoma and she said no. She said I would be doing R-EPOCH regardless of the new biopsy (unless something totally bizarre happens) because of the two markers. Her main issue with the two markers was more on relapse and refactory, but did say this is a new way of treating this as frontline. Again, she did not have the same issue of the "double hit" in DLBCL that I read in other very agressive forms of lyphoma (BL and BLL).

What is a little strange to me, my dr. gave a 55-60% chance during frontline therapy. The way she evaluates my risk factors for ipi, I have about the same outcome-based on ipi with 2 risk factors.

Do you have any thoughts on this?

On the extranodal, I think that's right - two. I don't think she is counting them as five.

14

Cowboy-
I wouldn't expect her to count the bone lesions as five, I just don't get how she can count them as two-- know what I mean? Either you have extranodal involvement of an organ or you don't, the degree to which you have that involvement does not seem to play well with the index. Furthermore, in the AJCC's staging manual, 'extranodal sites' are laid out by organ- liver, bone, spleen, etc. If you have that involvement, OK, check. If you don't you don't.

While common sense says that the more lesions you have at one extranodal site, the worse the prognosis, the reality is that either this hasn't been measured properly or it has been measured, to some degree, and it has turned out not to make much of a difference in prognosis.

Going back to a previous issue, I'm beginning to see why she's not willing to assert the wholesale potential efficacy of Rituxan in your case-- I read again and again that this emerging subtype has shown to have a comparatively limited expression of CD20-- Rituxan's target. So I can see why she would include it in your combination chemo regimen, but it's starting to make sense to me why she's not envisioning it as being a game-changer.

I think I rambled a bit in this post, sorry about that. but can you restate or clarify your comment about her prognosis on frontline therapy and the IPI? I'm not quite following that.

Ross

15

Ross -

I thought Rutxan also worked on bcl-2 and helped breakdown its resistance to the chemo? Is this not correct?

Speaking of bones, are they any more difficult to treat than other organs?

As far as the IPI - she said when calculating my prognosis, she used the IPI and looked at patients with similar disease to mine. When I pushed her about Rutuxan, she said that I could add 5 to 10% improvement to my prognosis.

Here is what is weird. Using her use of the IPI and my two risk factors, my five-year progression free chance is 51%. Now, even with the "dual hit" she has me a 50/50 or even as high as 60%. Essentially giving no measurable adverse impact on the dual hit.

I spoke with a nursing member of her team today and I told her that the dr. said I could add 5-10% to my prognosis. I asked her if she was typically conservative in her prognosis and seemed like the kind of person that thinks before making a decision. She said I should use her original 50/50. Not sure why she said that...certainly didn't give me a lift to the day.

Looking forward to your thoughts.

16

thanks as always - your responses helps me feel better.

Here is a portion of an article i found:

"Estimating the impact of rituximab on bcl-2-associated resistance to CHOP in elderly patients with diffuse large B-cell lymphoma" - N Mounier, J Briere, C Gisselbrecht, F Reyes, P Gaulard, B Coiffier

Rituximab plus CHOP (R-CHOP) has been proven to increase overall survival in aggressive bcl-2-positive lymphoma patients. Using competing risk analysis, we studied the long-term impact of this treatment in patients from a GELA trial: R-CHOP prevented from progression or relapse in both bcl-2-positive and bcl-2-negative patients without increasing the risk of death in complete remission.

Also, I would love to have a discussion about this trial. It seems like this is very promising and, while doesn't specifically take into account specific type of lymphoma, sounds very promising.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409217/

Finally, There is a similar trial (II) looking at DA-EPOCH-R in patients with Burkitt's and C-MYC positive DLBCL.
I am scheduled for treatment Thursday, but is there anyway I could be included? The nurse today said I would be doing EPOCH-R, but not dose adjusted.

17

Cowboy-
Briefly for the moment, I assume on the phase II trial that you're referring to is #NCT01092182. If so, you seem to meet all the eligibility requirements, but I only see three centers where they're recruiting-- Bethesda, Boston and Houston. I left a message with the NCI referral office about whether someone not near these centers but who is treated at an NCCN center like you could still participate. I'll let you know what they say, normally clinical trials don't have the luxury of turning people down, but there are a few major factors to consider, so we'll see what they say. Could come down to your doctor. I have no idea. Either way it's worth finding out.

I'll respond to the rest shortly---
Ross

18

Cowboy-
The NCI called me back today and told me that you could participate in the clinical trial from the James Center through one of the centers listed on the site-- which is Dana Farber, MD Anderson and the NCL HQ. They told me though that each center has slightly different eligibility requirements; I said wouldn't that throw off the data? She said that the differences are very minor but nonetheless in place. My understanding is that the requirements listed on the web site are for the Bethesda location, which would allow you to participate from OSU. So from what I can tell, if interested you should probably get in touch with this guy at the NCI or have your doc do so.

Ross

19

Ross-

Thanks for all your efforts. I will check with my dr. to get her thoughts. Btw, do they know I went through one cycle of r-chop (at the first hospital)? I think i mentioned it, but I'm sure it is hard to keep track of everyone situation.

I did email the person you suggested today, but I never heard back. I even left my cell number.

Anyway, I have my second cycle - epoch-r on thursday. Do I have time?

Also, I was eagerly waiting your response to an earlier post.

Here it is...

1- I thought Rutxan also worked on bcl-2 and helped breakdown its resistance to the chemo. Is this not correct?

2- Speaking of bones, are they any more difficult to treat than other organs?

3 - As far as the IPI - my dr. said when calculating my prognosis, she used the IPI and looked at patients with similar disease to mine. When I pushed her about Rutuxan, she said that I could add 5 to 10% improvement to my prognosis.

Here is what is weird. Using her use of the IPI and my two risk factors, my five-year progression free chance is 51%. Now, even with the "dual hit" she has me a 50/50 or even as high as 60%. Essentially giving no measurable adverse impact on the dual hit.

I spoke with a nursing member of her team today and I told her that the dr. said I could add 5-10% to my prognosis. I asked her if she was typically conservative in her prognosis and seemed like the kind of person that thinks before making a decision. She said I should use her original 50/50. Not sure why she said that...certainly didn't give me a lift to the day.

20

Sorry man-
First off, I guess I overlooked or forgot that you had a cycle of R-CHOP. I think that will disqualify you, but try calling Theresa White at 301-402-5886, she's another contact on the study.

1. I guess I would have thought either that it was still inconclusive, or that you have this backwards, that bcl-2 boosts resistance to rituximab-inclusive therapy. Can you point me to where you're reading this?

2. This is a question that I can't answer, not even close. I can only say that the skeletal system is of obvious importance so you know if you had a choice you'd probably pick a less important anatomical site in the body to have extranodal involvement, like maybe the appendix (kidding), but the key to successfully treating your cancer is not found in the answer to an anatomical question, it's found at the molecular level- what are the mutations specific to that tumor? There was a report out of BC Cancer Research the other day, they'd been approached by a doc who couldn't seem to treat his patient's oral cancer (tongue). So he got BC Cancer to sequence the tumor's genome, and once done they compared it to a database of other sequenced tumors and found it was remarkably similar, not to other oral cancers, but to renal cell carcinoma-- AKA kidney cancer. This is a paradigm shift that will take a while for people to grasp. We're so used to '[anatomical site] cancer', but this is almost surely a flawed approach. Yeah I know I totally dodged your question but beyond admitting ignorance my point is to suggest that maybe this is why the actual extranodal site doesn't seem to make much of a difference in the RIPI. again, there are worse sites in the body- CNS, lungs, come to mind-- but I don't think location is going to matter. It's what they can reveal at the level of the molecule, that highly specific diagnosis.

3. I think I understand what you're saying. I don't quite understand what SHE'S saying, but I get what you're saying. Or it's the other way around. Am I wrong in thinking that this issue with prognosis is causing you to call into question her credibility? Do you feel like she's inconsistent, or ignoring obvious data, or maybe just being too flippant?

Ross