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Old 03-24-2011, 10:25 AM   #1
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Thumbs up Statins and radiation therapy

Just a day after launching a thread on cholesterol and prostate cancer I have become aware of a new, very encouraging study about the anti-cholesterol drug class "statins" and better results for prostate cancer patients having radiation. I'll cross reference this new thread, but this specific advance is too good to bury in that most encouraging but more general thread of yesterday.

For those who like to do their own research, here's the citation.

Int J Radiat Oncol Biol Phys. 2011 Mar 1;79(3):713-8. Epub 2010 May 6.
Improved biochemical outcomes with statin use in patients with high-risk localized prostate cancer treated with radiotherapy.
Kollmeier MA, Katz MS, Mak K, Yamada Y, Feder DJ, Zhang Z, Jia X, Shi W, Zelefsky MJ.
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.

The senior author is Dr. Michael Zelefsky, the highly respected radiation oncologist from the stand-out department at Memorial Sloan Kettering in New York City, the site of a number of major advances in radiation treatment for prostate cancer.

They looked at 1,681 men who had had radiation for clinically localized prostate cancer (stages T1-T3) who were all treated with conformal radiation at a median dose (meaning half got lower, half got higher) of 81 Gy (the modern dosing range that has proven much more effective) between 1995 and 2007, and for whom lists of pre-radiation medications were available. About half of the men had had a short course of androgen deprivation therapy (hormonal therapy) in support of their radiation.

What they found was that the five year PSA relapse free survival rate for those on statins was 89% (very good for external beam radiation at the five year point, especially considering that there were some higher risk stage T3 patients involved and probably some higher risk stage T2b patients) compared to 83% for for those not taking a statin. They also took a snapshot at eight years, finding that the success rate was 80% for statin users versus 74% for non-statin users. A statistical test showed an extremely small possibility that the results were due to chance and artificial, which is encouraging.

Now for the drum roll: among the men taking statins, only high risk patients showed improvement in the success rate! That is a great finding as other patients are likely to have been cured by the radiation, whereas the high risk group is the group that really needs extra help! It appears that the improvement in results was nearly 50% (hazard ratio 0.52, p-0.02 for those with a statistical bent).

The authors also commented that their results suggest not only anticancer activity for statins but also that statins sensitize prostate cancer cells to radiation!


The two questions I have about the study are whether the distribution of the riskier patients was even, especially the stage T3 patients, and whether both groups got about the same radiation. Hopefully they were more or less equally distributed between the statin and non-statin groups, as a preponderance of T3 patients in the non-statin group could have skewed the results. Similarly, if a preponderance of patients in the non-statin group got radiation doses of significantly less than 78 Gy, that too could distort the results. I'm quite confident that neither distortion occurred as Dr. Zelefsky is a noted researcher who almost certainly would have paid attention to a substantial imbalance and commented on it. They did perform the kinds of statistical tests that should have teased out the real relationships. I would like to know the risk distribution of the patients in the two groups; all had localized though not always confined prostate cancer, but the PSA and Gleason characteristics were not provided in the study abstract.

As far as I know, knowledge of the relationship of statins and radiation for prostate cancer is fresh, though the report was electronically available about a year ago. I haven't seen this news in any of the newsletters I follow, though I may have missed it. Dr. Freeman, who spoke at the IMPaCT conference described in the thread on cholesterol did not mention it either. That leads me to conclude that we are dealing with a great advance in knowledge here. Moreover, it seems reasonable that statins would also boost results for patients having other forms of radiation. This looks like a game-changer to me!

I'm interested what our radiation veterans think about this and whether they had been aware of it.

I'll sum up my reaction to this study in one word: Wow! Okay, I need to add another word: AWESOME.

Take care all,

Jim

Last edited by IADT3since2000; 03-24-2011 at 10:30 AM. Reason: Added comment about making PC more sensitive to radiation.

 
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Tall Allen (03-24-2011)
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Old 03-24-2011, 12:32 PM   #2
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Thumbs up Re: Statins and radiation therapy

Let me add my voice to your own on this. Because of the research you cited, I emailed it to my RO in August (it was first published last May in pubmed) and asked him to put me on statins stat . I wanted to be very careful about any supplements I took that might interfere with the radiation treatment I was about to have. This research did away with any fears I might have, because statins are radiosensitizers, which was also known from previous lab studies. There was also the following study from the U of Chicago in April 2010: http://www.ncbi.nlm.nih.gov/pubmed/20421534
In that study, the authors did see improved outcomes after radiation in low, middle and high risk groups, although, like Zelefsky, they found the improvement was most marked in high-riskers. This Johns Hopkins study also found that statins seemed to reduce the number of men who were found to have non-organ confined disease at surgery or pre-surgery PSA>10: http://www.ncbi.nlm.nih.gov/pubmed/21334020

Statins do seem to convey more benefit to high risk disease. In this Johns Hopkins cohort study, they found no association with PC overall, but found a very strong association with high risk and metastatic disease, and the reduction increased the longer they took statins: http://www.ncbi.nlm.nih.gov/pubmed/17179483 This case control study had a similar finding: http://www.ncbi.nlm.nih.gov/pubmed/16014776 There are lab studies that show that statins have a greater effect on PC3 cells- the ones most often implicated in metastatic disease. The mechanism may have to do with the downregulation of the androgen receptor or the effect of reducing PSA. Also, they may prevent advanced disease because of their anti-inflammatory effect: http://www.ncbi.nlm.nih.gov/pubmed/20160265

And for those who have had surgery for PC, statins seem to help with that as well. In this Duke University study, statin users had a 30% lower risk of recurrence vs non-users: http://www.ncbi.nlm.nih.gov/pubmed/20586112

Even though it was a drop in the bucket for low-riskers like myself, there was another reason I wanted to take them prior to radiation. While statins radiosensitize cancer cells, they protect many kinds of healthy cells from the effects of ionizing radiation. In lab studies, they are radioprotective of endothelial cells -- the tissue that makes up most of our internal organs. They also seem to protect the colon, and stave off radiation-induced fibrosis. Fibrosis is the cause of the long-term bad side-effects of radiation. For any who are contemplating radiation, you may be interested in my post entitled:"Supplements that may help with Radiation"

By the way, it doesn't seem to matter much which statin one takes -- go with the least expensive. I asked my doctor for 40 mg pravastatin and cut it into quarters to save even more money.

- Allen

 
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Old 03-25-2011, 07:55 AM   #3
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Re: Statins and radiation therapy

Hi again Allen and all,

I was looking in detail at the links you posted (all okay on this board because they are sponsored by the Government) and found something interesting about the Johns Hopkins study in the following link:


Quote:
Originally Posted by Tall Allen View Post
.... This Johns Hopkins study also found that statins seemed to reduce the number of men who were found to have non-organ confined disease at surgery or pre-surgery PSA>10: http://www.ncbi.nlm.nih.gov/pubmed/21334020

...
This seemed familiar, and I looked in some files and found that this research had been covered previously in poster abstract #LB-125 at the "2007 AACR Annual Meeting" (American Association for Cancer Research, the largest cancer research organization in the world, and international, despite its name) in Los Angeles. The poster had a slightly different title, "Association of statin use with pathologic findings on prostatectomy and prostate cancer progression", and the author list was shorter (just Mondul, Walsh and Platz). It is typical for researchers to first present their findings as posters at medical research conventions; among other benefits, they get to interact with fellow attendees, often learning of associated research and perhaps learning of weak points that they need to address prior to formal publication. I was at the meeting as a survivor representative in the Scientist↔Survivor Program sponsored by the AACR.

What strikes me as especially interesting is the long lag between presentation of virtually the same research as a poster at a medical researchers convention in April 2007 and eventual formal publication electronically in the Journal of Urology on February 22, 2011, nearly four years later, with the printed publication due in April. Ouch! That's a long time to wait for broad publication of important research! I can understand that posters are somewhat informal and do not have to have all the bugs worked out, but I'm still surprised by this long a lag for a study involving very respected researchers. Seeing this gap makes me realize that we survivors can do a service to our cancer communities by representing survivors at these conferences and reporting highlights.

It's also interesting that the poster abstract provides additional detail that is not contained in the final abstract for the paper. None of it is important for a basic understanding the key points though.

By the way, I had been hesitating whether to take a statin medication at the time of the conference. I've just looked at my records, and I had had an annual physical shortly before the conference, with my total cholesterol well elevated but with a good HDL. My doctor had mentioned that a statin might help, but we both recognized that my HDL and cholesterol ratio were good, and I had once again decided against going on a statin. However, shortly after attending the convention, I asked for a prescription and started simvastatin. I believe this abstract was probably the key persuader.

Take care,

Jim


 
Old 03-25-2011, 11:35 AM   #4
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Re: Statins and radiation therapy

In my case, my doctor told me verbally his findings that he was at that point submitting for publication. At my next visit, a month later, he gave me a draft of the paper and said the journal was still reviewing it. Three months later, an abstract appeared ahead of publication, and publication followed over a month later. So it was at least five months between the time he knew the results and the time he shared them with the world. Interestingly, the paper he initially gave me was different from what finally appeared, although the results and conclusions were virtually identical. (He had decided to merge his sample with those of a different clinical trial to get a statistically relevant total sample with five-year results. A good call, imho.)

Peer review takes time. Copies of the draft are sent to the reviewers who comment and ask questions and may ask to see original data. The drafts are revised and re-revised with all the authors and all the reviewers approving each revision. Then it has to be scheduled for publication in the journal, and there may already be a backlog of a month or more. With a conference, which are fewer and further between, it's the luck of timing whether the paper will be ready by then.

I have also noticed that the same papers will appear in different journals at different times. I know researchers are eager to publish as often as possible. It leads to a better reputation, better job offers, and tenure, in some cases.

I think that peer review gives us better information, but we pay a cost in delays. For those of us for whom the information is literally a matter of life and death, this is unbearable.

 
Old 04-03-2011, 06:38 AM   #5
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Re: Statins and radiation therapy

Hi Jim, glad to see you still here. I'm in hospital for a week for diabetes treatment so have had plenty of time on-line. One of the thinks I've done is look up PC on Wikipedia - it reads as though you could have written it! Do you check it out / add to it / correct it at all?

All the best,
__________________
Peter, Brachytherapy in Guildford, England March 2008

 
Old 04-12-2011, 02:01 PM   #6
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Re: Statins and radiation therapy

Hi tumbleweed,

No, I haven't done that, but I'm tempted.

Take care and thanks for your kind words,

Jim

 
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