We will be discussing two separate but related articles today. The first is a detailed assessment of skin cancer risk in CLL patients. The second is an intriguing paper that links Vitamin A supplementation to reduced risk of aggressive melanoma. I am sure this is not the last word on the subject and I do not want you to rush out and take massive amounts of Vitamin A without consulting your physicians. But anything that gives a bit more protection to our guys and reduces the risk of having to fight a two front war with CLL and skin cancer is definitely worth a second look.
Expert Review: Skin Cancer Risk in CLL Patients
In case you were a skeptic, here is a detailed “Best Practices” article from no less than the Mayo Clinic that talks about skin cancer in CLL patients. There is no doubt our guys are more at risk of skin cancer. And garden variety squamous cell carcinoma (SCC), basal cell carcinoma (BCC) are more likely to be aggressive in immune compromised patients (read, CLL patients) and therefore require more extensive Moh’s surgery. The Mayo article goes beyond that and discusses the impact of malignant melanoma (MM) and Merkel Cell Carcinoma (MCC) (see image alongside) on overall survival in CLL patients. As you would expect, it is not a good idea to have to fight melanoma or merkel cell carcinoma, while you are also struggling with the “good” CLL cancer.
Merkel Cell Carcinoma
Since Merkel cell carcinoma may be a new one to some of you, it may be worthwhile to get some details about this form of skin cancer.
- Merkel cell carcinoma is often observed as a fast-growing, painless nodule on your skin. The nodule is often shiny and may be skin colored or shades of red, blue or purple.
- The majority of Merkel cell carcinomas appear on skin surfaces frequently exposed to UV radiation (sun exposure, tanning beds etc) but they can develop anywhere on your body, even on areas where the sun don’t shine.
- People with weakened immune systems — such as those with CLL, HIV infection or those taking drugs that suppress the immune system — are at increased risk of Merkel cell carcinoma.
- Other risk factors are: people with pale skin, older individuals (risk increases after 50, though even younger people can get it), those that have already had basal cell or squamous cell carcinoma.
- Merkel cell carcinoma has a nasty habit of metastasizing quickly, even while it is under treatment. often, it travel first to nearby lymph nodes and then may spread to your liver, bone, lungs or brain.
- Recently, it has been shown that Merkel cell carcinoma may be triggered by a virus, the Merkel cell polyomavirus. As immune compromised people, CLL patients are more at risk of all sorts of viral infections, including this polyomavirus. Here is the link to a detailed article discussing MCC and viral connections.
Below is the abstract from Mayo. If skin cancer is something you worry about (and in my humble opinion every CLL patient should be aware of increased skin cancer risk), the full length article is something you should read and file away for future reference. Send me a personal email and I will help you locate it.
J Clin Oncol. 2012 Feb 21. [Epub ahead of print]
Chronic Lymphocytic Leukemia Is Associated With Decreased Survival of Patients With Malignant Melanoma and Merkel Cell Carcinoma in a SEER Population-Based Study.
Brewer JD, Shanafelt TD, Otley CC, Roenigk RK, Cerhan JR, Kay NE, Weaver AL, Call TG.
Mayo Clinic, Rochester, MN.
PURPOSE: To delineate outcomes of malignant melanoma (MM) and Merkel cell carcinoma (MCC) in patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin’s lymphoma (NHL).
PATIENTS AND METHODS: We identified patients with MM or MCC reported to the Surveillance, Epidemiology, and End Results program and analyzed the effects of history of CLL/NHL on overall (OS) and cause-specific survival after MM or MCC. Expected survival was derived from patients with MM or MCC without CLL/NHL.
Results: From 1990 to 2006, 212,245 patients with MM and 3,613 patients with MCC were identified, of whom 1,246 with MM and 90 with MCC had a prior diagnosis of CLL/NHL. Patients with MM and a history of CLL/NHL had worse-than-expected OS as measured by standardized mortality ratio (SMR; SMR for CLL, 2.6; 95% CI, 2.3 to 3.0; SMR for NHL, 2.3; 95% CI, 2.1 to 2.6). MM cause-specific survival was worse than expected for patients with a history of CLL (SMR, 2.8; 95% CI, 2.2 to 3.4) or NHL (SMR, 2.1; 95% CI, 1.7 to 2.6). Among patients with MCC, OS was worse than expected for those with a history of CLL (SMR, 3.1; 95% CI, 2.2 to 4.3) or NHL (SMR, 1.9; 95% CI, 1.3 to 2.8). MCC cause-specific survival was worse than expected for patients with a history of CLL (SMR, 3.8; 95% CI, 2.5 to 5.9), but no difference was observed for NHL (SMR, 0.9; 95% CI, 0.4 to 2.1).
CONCLUSION: Patients with CLL before diagnosis of MM or MCC have significantly worse OS and MM or MCC cause-specific survival than those without a history of CLL/NHL.
PMID: 22331952
The bottom line is quite clear. In this large retrospective study with more than a thousand patients with malignant melanoma and another 90 patients with merkel cell carcinoma – all of whom also had CLL / NHL, patients with CLL diagnosis before diagnosis of MM or MCC had significantly worse overall survival. And conversely, CLL / NHL patients were more likely to die of these two types of skin cancers than people who did not have CLL / NHL.
The first graph above shows overall survival of CLL and NHL patients from the time of diagnosis of malignant melanoma (MM). Notice how much steeper the colored lines are (gold for NHL, blue for CLL) when patients had to fight a two front war complicated by melanoma. The black lines are for reference, where the CLL / NHL patients did not have melanoma. Likewise, the second graph shows the same information but with reference to merkel cell carcinoma (MCC). These two skin cancers – MM and MCC – are the two most deadly form of skin cancers and something I would not wish on any of you.
Below is the take-home quote from the Mayo experts that is worth its weight in gold:
Our analysis provides strong evidence that patients with a history of CLL or NHL are at a higher risk of death as a result of MM (malignant melanoma) or MCC (merkel cell carcinoma) once one of these cancers develops. When considered with the higher risk of and more aggressive behavior of other skin cancers (eg, basal cell carcinoma, squamous cell carcinoma) in patients with CLL and NHL, an annual dermatologic skin examination and patient education regarding sun protection and skin self-examination seem appropriate for patients with these lymphoid malignancies.
I have been preaching all these points for about a decade now. It is good to have this kind of expert guidance clearly spelled out.
Link between Vitamin A and Melanoma risk
Now for the second article I want to discuss today. It takes a more positive look at melanoma risk, namely at a potential way of reducing the risk.
J Invest Dermatol. 2012 Mar 1. doi: 10.1038/jid.2012.21. [Epub ahead of print]
Association of Vitamin A and Carotenoid Intake with Melanoma Risk in a Large Prospective Cohort.
Asgari MM, Brasky TM, White E
1] Division of Research, Kaiser Permanente Northern California, Oakland, California, USA [2] Department of Dermatology, University of California, San Francisco, San Francisco, California, USA.
Laboratory data suggest that intake of vitamin A and carotenoids may have chemopreventive benefits against melanoma, but epidemiological studies examining the association have yielded conflicting results. We examined whether dietary and supplemental vitamin A and carotenoid intake was associated with melanoma risk among 69,635 men and women who were participants of the VITamins And Lifestyle (VITAL) cohort study in western Washington. After an average of 5.84 years of follow-up, 566 incident melanomas were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of melanoma associated with dietary, supplemental, and total vitamin A and carotenoid intake after adjusting for melanoma risk factors. Baseline use of individual retinol supplements was associated with a significant reduction in melanoma risk (HR: 0.60; 95% CI: 0.41-0.89). High-dose (>1,200 μg per day) supplemental retinol was also associated with reduced melanoma risk (HR: 0.74; 95% CI: 0.55-1.00), as compared with non-users. The reduction in melanoma risk was stronger in sun-exposed anatomic sites. There was no association of melanoma risk with dietary or total intake of vitamin A or carotenoids. Retinol supplementation may have a preventative role in melanoma among women.
PMID: 22377763
While this is an interesting study, I would like to caution you about massive doses of Vitamin A without first checking it out with your physicians. Vitamin A is a fat soluble vitamin and unlike water soluble vitamins (vitamin C is a good example of a water soluble vitamin), it is not easily excreted from the body along with urine. In other words, it gradually accumulates in your body, in the fatty tissues. Too much of anything is not a good thing.
It is also worth noting that the results are not quite crystal clear. The authors saw a reduction of melanoma risk only with high-dose supplementation with retinol, compared to to those that did not get the retinol. Women seem to benefit more than men. The benefit was also more pronounced in those parts of the body that were more sun exposed. All in all, I found this study raised quite a few more questions than it answered. For example, if retinol reduced melanoma risk, it is kind of hard to see why a similar relationship was not seen in the case of overall dietary intake of vitamin A. Perhaps it has to do with the bigger oomph of high dose retinol supplementation. As always, prudence is the better part of valor. Send me a personal email if you want my help in locating the full article.
Imiquimod, anyone?
We have several articles on our websites regarding a topical cream called imiquimod (brand name in the USA is “Aldara”). Imiquimod is thought to work through improving the patient’s own immune system via facilitating the release of several important cytokines. Initially imiquimod was approved by the FDA for genital warts and actinic kertosis. More recently it has been seen to have benefits in a number of different skin diseases, including SCC, BCC, herpes skin lesions and even malignant melanoma. Here is the link to the article. You can read it for free by just clicking on the link. Even if the language is a little dense, there are a whole lot of before-and-after pictures of patients with malignant melanoma treated with topical imiquimod cream – pictures that will knock your socks off. Here is an example.
A, Right lower leg showing multiple papules and an ulcerated nodule of cutaneous melanoma metastases.
B, After 4 months of treatment with 5% imiquimod cream, complete remission with residual hyperpigmentation is seen.
We need your help
In a recent slew of articles we discussed the issue of potential for conflict of interest when important clinical trials are paid-for entirely by pharmaceutical companies that have a lot of money riding on the outcome of the trials. There is a reason why prestigious professional journals now require authors to disclose their financial or other relationships with drug companies. There have been enough scandals over the years to satisfy even the most ardent conspiracy buff!
Unfortunately, well conducted and large scale clinical trials cost a lot of money and effort. Money is always in short supply, that goes without saying. But increasingly, I am worried that even many of our expert centers and CLL experts are finding it easier to conduct research that is almost entirely paid for by the pharmaceutical industry. Smaller trials conducted by lesser known institutions without this massive support of industrial patronage suffer due to lack of funds, lack of visibility and ultimately lack of ability to recruit patients.
Literally a beacon of hope in this grim scenario are the excellent clinical trials conducted at the National Institute of Health (NIH), National Cancer Institute (NCI), National Heart, Lung, Blood Institute (NHLBI). If you are not familiar with the excellent work done by these tax-payer funded research institutions, please check out the member comments that follow each of the articles where I reviewed clinical trials at the NIH / NHLBI. Here are the links to the articles for your convenience. To say these clinical trials and the researchers involved in conducting them get rave reviews would be a huge understatement.
A well designed PCI-32765 clinical trial
A clinical trial perfect for our times
I received a request for getting people to sign a petition authored by Dr. Meltzer of Johns Hopkins, for more robust financial funding for the NIH. The request is attached below and pretty self-explanatory. You may have to visit http://www.whitehouse.gov/ and register to get an active account on the “We the People” website (if you do not already have one) before you can sign the petition. May I add my voice to that of Dr. Meltzer. As patients with an incurable cancer, as members of a community that is small potatoes compared to more lucrative “solid” cancers such as breast cancer, prostate cancer etc, we are at a huge disadvantage when it comes to new drug development and trustworthy analysis of clinical trial outcomes that are not at the mercy of commercial interests. We need a vibrant and well funded NIH / NCI / NHLBI. Signing this petition is in our own self-interest. The deadline is March 18th. Please sign the petition yourself, and get the word out to your friends and family.
Stephen J. Meltzer, M.D.
The Harry & Betty Myerberg/Thomas R. Hendrix Professor
Departments of Medicine (GI Division) and Oncology
The Johns Hopkins University School of Medicine & Sidney Kimmel Cancer Center
1503 E. Jefferson Street, Room 112
Baltimore, MD 21287
smeltzer@jhmi.edu<mailto:smeltzer@jhmi.edu
I was on a recent conference call with White House officials, during which research funding was discussed. It seemed to me that these officials did not fully understand the central importance of NIH funding to our national research enterprise, to our local economies, to the retention and careers of our most talented and well-educated people, to the survival of our medical educational system, to our rapidly fading worldwide dominance in biomedical research, to job creation and preservation, to national economic viability, and to our national academic infrastructure. In response to a question from a participant, they staunchly defended the proposed flat $30.7 billion FY 2013 NIH budget as being perfectly adequate, remarking that “The NIH receives more funding than any other research entity; it will continue to be strong; it will do just fine.”
This statement is patently false. The proposed flat NIH budget will severely exacerbate a catastrophic crisis that has been ongoing since 2003, when growth in NIH funding fell (and has continued to fall every subsequent year) behind the rate of inflation. As a consequence of this deeply flawed public policy, promising careers have been cut short, amazing research projects have been aborted, hundreds of laboratories nationwide have shrunk or been shut down, established and accomplished senior researchers have been forced to abandon their programs, young scientists have departed from research of even left the country (even after many years of productive training), thousands of ancillary jobs have been lost, our worldwide medical research dominance has been eroded (ceded to China, India, and other nations), and a large support network of laboratory supply and biotechnology companies has been drastically attenuated.
I write to let you know about a recently created petition on “We the People”, a new feature on WhiteHouse.gov , and ask for your support. If this petition gets 25,000 signatures by March 18, 2012, the White House will review it and respond!
We the People allows anyone to create and sign petitions asking the Obama Administration to take action on a range of issues. If a petition gets enough support, the Obama Administration will issue an official response.
You can view and sign the petition here:
Here’s some more information about this petition:
Increase NIH budget to $33 billion dollars next fiscal year! A flat $30.7 billion will kill jobs and hurt research.
Increase NIH spending to $33 billion! The proposed flat NIH budget will close labs nationwide, kill good-paying jobs, damage our worldwide medical research dominance, and hurt state economies. NIH jobs cannot be outsourced. NIH funding created 350,000 jobs and contributed $50 billion to the national economy in 2007! In-source our jobs!!
21 comments on "Skin Cancer and Vitamin A"
It is a bit daunting on the petition website to see that over 1,000 signatures will be needed each day to reach the required number for response. If that cannot be achieved at this late date, can the petition be re-posted?
To complicate the intellectual and practical puzzles, Vitamin A is a recognized antagonist to vitamin D and excess A can seriously impact D levels.
QB:
I do not know what is involved in re-submitting the petition.
In the meanwhile, may I request you guys to bring this to the attention of CLL patients who visit other CLL websites. We are all in this together.
Vitamin A in sunscreens has been proven to stimulate the growth of skin lesions and tumors. Is a topical application that much different than taking oral supplements or is this a potential conflict with the vitamin A/melanoma study?
I just added a new section to the article, on the potential use of Imiquimod to treat malignant melanoma.
“We have several articles on our websites regarding a topical cream called imiquimod (brand name in the USA is “Aldara”). Imiquimod is thought to work through improving the patient’s own immune system via facilitating the release of several important cytokines. Initially imiquimod was approved by the FDA for genital warts and actinic kertosis. More recently it has been seen to have benefits in a number of different skin diseases, including SCC, BCC, herpes skin lesions and even malignant melanoma.
Here is the link to the article.
http://archderm.ama-assn.org/cgi/reprint/139/3/273.pdf
You can read it for free by just clicking on the link. Even if the language is a little dense, there are a whole lot of before-and-after pictures of patients with malignant melanoma treated with topical imiquimod cream – pictures that will knock your socks off”.
Chaya,
This is a very timely message for me. Today I had to have several actinic keratosis sprayed and a biopsy. My dermatologist wants to see me every six months.
I signed up for We the People and it is very easy to do.
Thank you for this informative update.
Jean
Thanks Chaya for bringing to our attention how much NIH funding needs our proactive push. This is probably a good place to bring up another issue of Pigs gathering at the trough. Taxpayer funded research papers are currently able to be viewed free after one year from publication by the public. All taxpayer research is now threatened to be placed behing a “paywall”. Rep Carolyn Maloney NY Dem. has co-sponsored H.R.3699 which would end free access to vital research papers by all of us. They should be immediately available as it is.
Please check out this new website in support of free access for research we have already paid for.
For a detailed account of the skullduggery behind H.R. 3699 click on this link below:
http://e-patients.net/archives/2012/01/open-knowledge-saves-lives-oppose-h-r-3699.html
WWW
Very interesting. I cannot support the petition, being Norwegian, but do hope you succeed! We have similar problems in GB where I live…..but the US is blamed for “taking” the local super-brains. Well, whatever, we all need their efforts to survive.
I am also being seen 6-monthly for potential “skin-problems”, being extremely white and susceptible to tomato-colour when in the sun, where I love to be.
As ever, thanks.
Mette
I have skin coloured nodules on my face, but assumed they were simply warts. One in shiny. Better go in for a check up. Wonder how the imiquimod cream would work with warts??
Krazyleggs:
One of the indications for which imiquimod was approved very early is warts. Regular warts and genital warts; HPV instigated warts. Discuss it with your doctor.
One of the results of the low level of NIH funding is a clear brain drain taking place there. While at my Natural History Study of CLL visit several weeks ago, the Fellow doing my physical said he would most likely have to leave rather than continue on the very promising prostate cancer vaccine he had been a part of. No funds. My wonderful primary care physician has a brilliant nephew who is head of one of the research labs there and who has just interviewed in the pharma private sector .. again, no funds, lowered staffing. We NEED NIH and their addressing of the tough diseases. Let’s not continue this return to the Dark Ages. I encourage everyone to pass Chaya’s petition link on to all their friends, family and ask them to spread it as well. http://wh.gov/81O is a re-post of Chaya’s link. THIS IS TERRIBLY IMPORTANT !!
We were short of the required total of 25,000 votes by a mere 440 or so signatures before the time ran out.
Pity. I am kicking myself for not twisting your arms a bit more to be pro-active about getting this petition signed. If you did not do your bit, sign it yourself and get your friends and family involved in the process, you should be kicking yourself too.
We came so close. Close, but no cigar, as they say.
It’s really a shame to come up less than 500 signatures short. I signed up and sent the link to everyone I knew so that they could get the word out, too. What really surprised me, though, is that there are about 17,000 NIH employees and you’d think everyone would have been rallying the forces – 25,000 signatures really isn’t that many to get when a mere petition signature might mean future funding for your job or for that promising new medical breakthrough…
If they resubmit the petition, I might just have to visit each of my neighbor’s houses and sign the petition for them using their computers to make sure they sign up. It’s far too important of a cause to just lose out because of 440 signatures.
There is a new petition posted so let’s get the requisite 25,000 signatures by 4/17/12. Please resign the new petition and get your family and friends to sign as well. As of now, 22,517 additional signatures are needed and we have 4 weeks to get this done.
Go the We The People Petitions and search open petitions using the key word, NIH.
Improving response at this moment~
Signatures needed by April 17, 2012 to reach goal of 25,000
21,776
Total signatures on this petition
3,224
Posting just to get this bumped up to top of Chaya’s ‘most recent’. Perhaps an email blast could be sent to this site’s registered members?
I recommend we post the link to the petition on our Facebook pages! We pass around jokes … this is so much more important! I know we can get to 25,000 in no time if we truly work together!
Hi Chaya, I can’t thank-you enough for helping to keep CLL patients up to speed..
I wish I could sign the petition but I’m Canadian. I’ve spent some time at the NIH about a year and a half ago as a volunteer with the T-cell transfer clinical trial. I was the fifth volunteer. While I was there I met other people participating in other clinical trails. This hospital is amazing and the doctors and staff are dedicated people. We have excellent hospitals in Toronto but nothing compares to the NIH..I hope enough people sign the petition to keep the funding going for the research for CLL.
I’ve been experiencing an increase in Basal and Squamous cell carcinoma this past year and was prescribed Aldara last week by demonologist. I’ve had some removed surgically in the hospital because I’m neutropenic. I’m going to discuss vitamin A at my next appointment.
I’m new to the CLL Topics community; Missus Olde Hippie was first diagnosed a few months ago – her WBC pushing 200,000 was her first warning. That’s another story for another topic. When I received Chaya’s email yesterday about the renewed NIH petition I clicked on the link and found myself looking at an article on skin cancer. I scrolled through the skin cancer and found the NIH funding discussion way down here. I’m a regular at whitehouse dot gov petitions so I signed the petition and tweeted and was out of there in less than a minute. It’s easier than clicking “Add To Wishlist” at Amazon dot com.
The petition deadline is April 17 and the response so far is dismal, at best. 25,000 signatures is a piece of cake at the dot gov petition site. We need a measly 20,000 and the deadline is less than a month away. A petition to repair the plumbing at the historical town hall in Podunk, USA can grab 25,000 signatures in a couple of days. Come on, CLL Community, let’s get this done. Now.
I visited CLL Topics for a couple of months before signing on as a member. I’ve moderated a few web support groups, other diseases, and I know that there are twice as many “lurkers” than there are registered members. If I hadn’t signed up a week ago, and agreed to receive email updates, I would never have known about this petition because skin cancer is number 4 on my list of “need to know now” topics.
Please give this petition it’s own topic, put it up there with the latest breaking news where it will catch the eye of everyone who passes through, members and lurkers alike.
The Olde Hippie – with permission from Missus Olde Hippie
I had posted the need for NIH funding on my Facebook page a month or so ago and got a good response and some signers. I will do it again today and again the day before the deadline. I also sent a request to all my buddies in my Address Book. A fair response. Today’s number indicates that we need around 16,000 more signatures.
Looking forward to my first trip to NIH May 1 for trial tests!
With regards to vitamin A I note that the Gerber Institute standard treatment uses fresh pressed juice containing carrot juice many times a day – a high dose for sure of Vitamin. Of course they have long since claimed cancer cure particularly mentioning they had good response with Melanoma to their treatment. For the record I’m not a Gerber patient but their results seem supportive to high dose vitamin A for Melanoma.
I’m late in responding to this but wanted you to know that I had a nodule appear a few months ago identical to the ones in the pictures. My dermatologist was concerned and immediately biopsied. I am very fortunate that it was benign, but so appreciate you posting. I read each e-mail thoroughly. I have sent a request to several friends who have signed the petition but noticed today we are still in need of many more signatures.
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