A consensus statement issued today on the topic of ovarian cancer symptoms has garnered a good deal of media attention.

The statement, developed by the American Cancer Society, the Gynecologic Cancer Foundation and the Society of Gynecologic Oncologists makes the point that women who have bloating, pelvic or abdominal pain, difficulty eating or feeling full quickly, or urinary symptoms including urgency or frequency should see their doctor (preferably a gynecologist) if the symptoms are new and persistent. (I regret that I can't find a link to this statement at this time.)

This is a step in the right direction, but we have much further to go if we are to make a significant impact in reducing suffering and death from this disease.

Ovarian cancer is not an uncommon cancer in women. 

The American Cancer Society estimates there will be 22,430 new cases diagnosed in the United States in 2007. It is the 8^th most common cancer in women.  The Society estimates there will be 15,280 deaths from ovarian cancer this year, making it the 5^th most common cause of cancer death in women.

Unfortunately, ovarian cancer is usually diagnosed after it has spread from its primary site in the ovary.  When that happens, the chances for survival decrease considerably.

According to our publication Cancer Facts and Figures 2007, the 5 year survival for all women who present with ovarian cancer is 44.7%.  When localized to the ovary, the five year survival is 93.1%.  When the cancer has spread to distant sites, the five year survival drops to 29.6%.

The problem is that only 1 in 5 women with ovarian cancer are diagnosed in the early stage.

For years, doctors have been concerned about how to diagnose this disease earlier, when the chances of cure are greatest.

There are some women—in particular, those with a genetic abnormality called BRCA 1 or BRCA 2—who are at higher risk of ovarian (and breast) cancer.  These women are candidates for close monitoring for ovarian cancer, and their doctors may recommend that their ovaries be removed after they have completed childbearing.

However, the vast majority of women are not known to be at increased risk of this disease, nor do they have a family history.  The cancer occurs sporadically and spontaneously.  Frequently, these women are older (the risk of ovarian cancer increases with age, and peaks when women are in their 70’s, according to Cancer Facts and Figures).

There are no effective, generally applicable screening tests for ovarian cancer which would diagnose the disease at an early stage in most women.

Routine pelvic exams are not a good way to find ovarian cancer early.  In women at average risk, routine ultrasound exams have not been demonstrated to be an effective screening test, and are not recommended.  CA-125, a cancer antigen that is increased in women with ovarian cancer and can be detected through a blood test, may be recommended to screen women at high risk but is not recommended for women at average risk.

So, in the end, there really isn’t much we can do to find this disease early.

Which brings us to today’s statement about the importance of symptoms as something to be considered in helping to make the diagnosis of ovarian cancer.

For years, doctors have known that the symptoms of ovarian cancer can be vague. 

Personally, when I practiced primary care internal medicine, this was something that I considered as part of my diagnostic evaluation.  However, the odds of any particular patient in my practice with these symptoms having ovarian cancer were remote.

[One aspect worth pointing out is that when you consider the number of primary care physicians and clinicians in the United States today (not including the gynecologists), it is unlikely that any one physician is going to primarily diagnose many patients with ovarian cancer during their professional careers.]

Over the past several years, there have been several published reports which indicate that women with ovarian cancer—usually on retrospective analysis—do have symptoms that can last for several months or longer before the diagnosis is made.

The problem has been that the symptoms which suggest the possibility of ovarian cancer may be vague, and as a result women may not pay much attention to them and doctors may diminish their significance.

So how do you get patients and clinicians to put ovarian cancer on their list of concerns in a woman with these symptoms?

The process of establishing what we call a differential diagnosis can at times be a complex undertaking, understanding that patients frequently present to their doctors with complaints that don’t exactly point to the underlying problem.  We call this “the undifferentiated patient.”

More recently, a research report has suggested that there are certain symptoms that may be more suggestive of ovarian cancer than others.  Thus, the list noted at the beginning of this blog.

Given the fact that these symptoms can be vague and common, the consensus statement goes on to emphasize the fact that these symptoms need to be persistent and represent a change from normal for a woman and her body.  The statement goes on to say that these symptoms should last daily “for more than a few weeks.”

There is also a list of other symptoms that have been reported in women with ovarian cancer, according to the statement, but which are not more frequent in women with ovarian cancer compared to women who do not have the disease.

These symptoms include: fatigue, indigestion, back pain, pain with intercourse, constipation and menstrual irregularities.

So what does all of this discussion really mean?

First, from my perspective, this is a statement that is meant to make women (and their doctors) aware of the fact that seemingly common or relatively minor symptoms such as those noted above could be related to ovarian cancer.

In the busy lives that we lead as patients and as doctors, it is sometimes easy to dismiss something that doesn’t seem important.  As patients we put off going to the doctor (most people I know don’t like going to the doctor).  And, when we get to see the doctor they may be rushed and not pay much attention to the problem when no cause is obvious.

What this statement does not say is that every woman with these symptoms needs an ultrasound or a CT scan or a CA 125.  What they do need is a thorough examination and a plan of follow-up, and consideration by their health care clinician as to what studies should be done, and what to do if the symptoms do not resolve promptly.

The organizations who crafted this statement also say that the evaluation should preferably be done by a gynecologist.

Ovarian cancer is a lethal disease for many women who develop this cancer.  However, these symptoms are not uncommon, and I for one will be interested to see how this statement impacts women’s health care.

Will women read this and think that if they have these symptoms that they have ovarian cancer and insist on having tests that may not be medically indicated?  Will we be able to truly improve the stage of disease at the time of diagnosis and increase survival as a result of this increased awareness?

The reality is, as noted by one of my valued colleagues in the initial news report this morning , what we really need is a test that will find this disease early and hopefully be available as an effective screening test for all women.

We do not have that test today, but clearly we need it.  There is certainly a considerable amount of research currently underway to find just such a test.

That is something that would potentially make a huge impact on this disease.

Until that time, unfortunately, we are left with a less than perfect way of trying to find ovarian cancer early by relying on symptoms that can point in many different diagnostic directions.

Hopefully, by increasing awareness among patients and their clinicians, we will be able to make some progress in improving the outlook of woman with this deadly cancer.

If you had any doubts that health insurance makes a difference when it comes to survival from cancer, then articles released today in the medical journal Cancer should erase the question from your mind.

In two research papers and an editorial, investigators from the American Cancer Society and the Society’s President make it very clear that if you don’t have adequate insurance, the odds are considerable that as far as breast and head and neck cancer are concerned, you are more likely to be diagnosed with your cancer at a later stage when treatment options are either more limited or more toxic, and the odds for survival are substantially less.

With more than 46 million Americans uninsured, these reports are certain to add fuel to the growing debate over the state of our health care system in the United States now and in the future.

In the first report, the researchers looked at information regarding health insurance and other demographic factors in over 553,000 women diagnosed with breast cancer from 1998 to 2003.

The source of their information was from over 1400 hospitals that participate in a program called the National Cancer Database, sponsored jointly by the American Cancer Society and the American College of Surgeons.

This program is unique because, unlike other state and national cancer surveillance and registry programs, this one collects information regarding insurance among other patient-related characteristics.

The authors examined the stage of breast cancer diagnosis as it related to the type of insurance the patient had at the time of diagnosis.  They broke the insurance categories down into several types including Medicaid, Medicare, uninsured, and private insurance.

They also looked at race, age, and income and education as determined by the zip-codes where the women lived.

They found that in this large sample of women, 55% had private health insurance, 37% were over 65 and had Medicare, 2% of the women were under 65 and had Medicare, 2% had no insurance, and 3% had Medicaid.

When the information was examined by stage at diagnosis (with stage I being limited to the breast through stage IV which means advanced disease spread to other parts of the body), 55% were stage I, 36% were stage II, and 9 % had advanced disease with stage III or stage IV.

So what was the impact of insurance type (or lack of insurance) on the stage at diagnosis?

Remember that this is a very important question, because women who present with stage I disease have a 5 year survival from breast cancer that is now about 98%, while women who present with stage IV disease have about a 26% 5 year survival.

When compared to women with private health insurance, a woman with Medicaid or no insurance had about a 50% greater chance of having stage II breast cancer.  With Medicare, the odds of having stage II disease were actually about 10% LESS than women with private insurance.

When looking at women diagnosed with the most advanced stages of breast cancer (3 and 4), the chances were about 2 ½ times greater that a woman with Medicaid or no insurance would present with advanced disease, when compared to a woman with private health insurance.  (In this comparison, women age 65 and over with Medicare had about the same chances of stage III/IV disease at diagnosis when compared to women with private health insurance.)

The researchers also found that race, income and education played roles in the stage of diagnosis.

Black women had about a 52% greater chance of being diagnosed at Stage II and 85% greater chance of being diagnosed with advanced (III/IV) disease compared to whites.  Hispanic women also had an increased likelihood of being diagnosed with more advanced disease compared with whites.

Areas with a lower proportion of high school graduates also had more advanced stage at diagnosis of breast cancer.

In a companion article, the authors looked at the impact of health insurance on the stage of diagnosis of head and neck cancer.

The researchers noted in their introduction that when these cancers are diagnosed early, they can be treated with limited impact on routine function.  But, when diagnosed at a more advanced stage, the impact on quality of life and survival can be substantial.

These investigators used the same database as they used in the previous paper.  They studied about 40,500 patients diagnosed from 1996-2003.

And, not unexpectedly, the results were similar to those found in the breast cancer study.

Patients who were uninsured or had Medicaid had a 37% greater chance of presenting with more advanced disease compared to patients with private health insurance.

They also found that men, people age 52 or older, or residence in an area with a low proportion of high school graduates also had greater odds of presenting with more advanced head and neck cancer.

Unlike the previous study on breast cancer, patients who were 65 years of age or older and on Medicare did not have more frequent early stage presentation than patients with private health insurance (the chances of presenting with early stage disease were similar in both groups).

The real question is what does all this mean, especially in this time of heightened concern about health insurance costs and availability? 

Certainly, the presidential candidates are aware of the issue—although no breathtaking plans have yet emerged from any of the many candidates in both parties.

In the editorial that accompanied these scientific reports, the current President of the American Cancer Society, Dr. Richard Wender, places the issue squarely on the table.

Dr. Wender points out that the Society has adopted guiding principles to evaluate health insurance reform proposals that may be forthcoming now or in the future, with an emphasis on looking at these proposals “through the cancer lens.”

• We know that without health insurance, prevention and early detection of cancer is a wish and not a fact.
• We know that without adequate health insurance, having an identified source of primary care is also a wish and not a fact.
• We know that without adequate health insurance, timely treatment for cancer is a wish and not a fact.

In the editorial, Dr. Wender reports on the experience of the American Cancer Society’s national call center (which, by the way, can be reached at 800-ACS-2345 24 hours a day, seven days a week). 

He notes that the Society is unable to provide assistance to about 30% of the callers who need help with finance and insurance problems.

Of those who had options, according to his editorial, 70% found the options were either unaffordable or inadequate for their medical needs.

As stated by Dr. Wender, “Our inability to help these individuals obtain and maintain affordable coverage is tragic.  The stories of those with inadequate insurance should add another dimension to the health care reform debates.”

I have written often in this blog about the cost of our miracles.

But there clearly is another aspect to cancer care in this country, and that is the basic “blocking and tackling” that needs to be done to ensure that every person in this country has the opportunity to have their cancer diagnosed at an early stage, when treatment is least disfiguring and disruptive and has the best opportunity for cure.

These studies clearly point out the need for us to move forward on this issue, and address the needs of millions of our fellow citizens.

Forget about the miracles for a moment.  We clearly need to be thinking about the fundamentals.

Maybe if we got the fundamentals right, that would be the greatest miracle of all.

A report in the current issue of the American Journal of Clinical Nutrition is certain to raise once again the role of vitamin D in preventing cancer.

The researchers, from the Osteoporosis Research Center at Creighton University in Omaha, Nebraska did a study primarily designed to study the effects of calcium and vitamin D on osteoporosis.

However, when they decided to look at the same study group to determine whether calcium with or without additional vitamin D supplementation had an impact on the incidence of cancer, they found a stunning 78% decrease in the risk of developing cancer in those women who took both calcium and 1000 units of vitamin D3 daily for four years.

This is essentially the first study that has provided any evidence from a forward looking, randomized controlled trial which randomly assigned study participants into various treatment groups. 

One third of the 1179 post-menopausal women—who lived in Nebraska—received a placebo (or dummy pill), one third received 1400-1500 mg of calcium supplements daily, and one third received the calcium with the addition of 1000 IU of vitamin D3 (on further chemical analysis, the researchers found that the actual amount of vitamin D3 in the pills was 1100 IU).

The women were all post-menopausal, with an average age of 66.7 at the time they entered the study.  As a group, they were overweight, bordering on obesity with an average BMI of 29 (a BMI of 25 to 29.9 is considered overweight; greater than 30 is obese).

The researchers determined how many women in each group developed non-skin cancer AFTER having participated in the study for one year.  The researchers made that arbitrary cutoff in order to eliminate cancers that, in their opinion, may have already been present at the time the study began.

As I mentioned, the results were stunning: the risk of developing cancer over the four year time-frame in the women who took both the calcium and vitamin D was 78% compared to the placebo group. 

For women who took only calcium, there was a decrease of about 41% in the risk of developing cancer.

The numbers of cancers diagnosed from year 2 to 4 of the study were actually small (as would be expected in a study of this size): there were 18 cancers diagnosed in the placebo-treated arm of the study; 15 cancers in the calcium arm, and 8 cancers in the calcium/vitamin D treatment group.

The numbers of cancers for any particular tumor type were also small, and included cancers of the breast, colon, lung, lymphoma/leukemia, uterine cancer and “other” cancers.

Because of these small numbers, it was not possible to determine whether any particular cancer type was especially affected by treatment with vitamin D.

What was apparent from the study was that taking vitamin D tablets did increase the blood levels of vitamin D, and that there was a direct correlation between these levels and the reduction of cancer incidence.

So where does this study fit into the bigger picture of vitamin D in relation to cancer prevention?

First, it is certainly a very intriguing and provocative report.

There have been many studies reported over the past couple of years suggesting that vitamin D can reduce cancer risk, and that more vitamin D in the body is correlated with a lower risk of several cancers.  In fact, in a previous blog, I mentioned that although I had initially been a skeptic of that relationship, I had been converted into a “believer” that in fact there may be such a relationship.

This study adds to that body of evidence.

Unfortunately, this study is simply too small to make an absolute conclusion that the relationship does in fact exist.  It is not sufficient in my opinion to make a major recommendation that everyone should start taking 1000 IU of vitamin D3 every day.

Why am I not convinced?

Bottom line, as I have written and commented previously, we need more research in this country to understand the basics of vitamin D in our United States population.

We need to understand the impact of geography, ethnicity, personal habits and many other factors on vitamin D levels. 

We need to determine whether we should in fact be measuring vitamin D levels routinely as part of preventive medical care. 

We need our major national research organizations who monitor this literature to get on with the process of reviewing the data and making evidence based recommendations on what the correct amount of vitamin D supplementation—whether in our diets or through pills—should be for our daily intake.

Perhaps most important is, in my opinion, the need for a well-designed, prospective trial to determine whether or not vitamin D actually reduces cancer risk.

There are too many other instances where the data has appeared compelling that a particular vitamin or drug that might prevent cancer.  This evidence is frequently based on what I will call indirect evidence.  Once the appropriate prospective trial was conducted, we too frequently find that the results were negative or worse.

The research into beta-carotene comes to mind.  A “harmless” vitamin, beta-carotene was thought to reduce the risk of lung cancer.  When it was put into a randomized, controlled prospective trial, however, it was found to actually INCREASE the rate of lung cancer.

In regards to the present vitamin D study, 4 years to me seems an awfully short time to demonstrate a true preventive effect of vitamin D. 

We know that many cancers take years to develop.  In fact, in my personal opinion, many of the cancers that this study concludes were “prevented” in fact were present at the time the study was started.

I suspect there is something else going on here, and it is not prevention.  It is more likely a direct effect on the pre-existing cancer, a slowing of growth, or some other phenomenon, but not prevention.  It is also possible that the effect may be due to some other, unrecognized factor (I want to be clear that this is not a criticism of the researchers, who are considered to be excellent clinical scientists by their colleagues).

Four years is simply too short a time to have this dramatic effect if prevention was the primary effect of vitamin D supplementation.

Finally, what we definitely do NOT recommend is that people start seeking the sun or use tanning beds as a source of vitamin D with the intent to decrease their risk of cancer.

Small amounts of sun exposure for this purpose are OK for most people, but each person has their own vitamin D and skin “personalities” that dictate their risk of skin cancer, and dictate how much sun exposure they need to get an adequate amount of vitamin D.  Where you live also has an impact on skin cancer risk, as well as the amount of vitamin D you might produce from a particular amount of exposure to the sun.

Ultraviolet rays have their own harms and are not a good way to get vitamin D.  That doesn’t mean you should be a hermit, but when you go outside—particularly when the UV index is 3 or greater—you should engage in sun-safe behaviors, such as wearing a shirt, wearing a hat, using plenty of sunscreen, and wear UV-protective sunglasses.

In the interests of full disclosure, my Canadian colleagues (and friends) at the Canadian Cancer Society have come out with an advisory today that suggests all Canadians take a daily supplement of 1000 IU of vitamin D.

The Canadians decided to move forward because of the fact that sun exposure in Canada is limited. 

My colleagues here at the American Cancer Society have decided not to make such a recommendation, pending additional research discussed above. 

We need our governmental agencies that review the evidence and determine the recommendations for dietary guidelines to start taking a careful look at their current vitamin D recommendations, so we can have clear guidance--based on currently available evidence on the role of vitamin D in cancer and other diseases—as to whether or not we should make a nationwide effort to increase vitamin D intake.

In the meantime, what should you do?

I can’t make a recommendation outside of the current guidelines, which are age and dose dependent.  It is up to you and your health clinician to determine whether or not you should be taking more vitamin D, based on your own personal risk profile.

You should be aware that the current study used 1000 IU a day of vitamin D3.  Other studies have shown lower doses of 400 IU daily did not decrease the risk of colon cancer in post-menopausal women (there were some issues with the design of that study), while another study looked at pancreatic cancer risk in men and found that 400 IU a day significantly reduced their risk of that disease.

In my opinion, it is time to make the investment in getting the definitive answers to these questions.

As I mentioned, the results of the study discussed here were impressive, but they are limited in their practical impact in my opinion.

We need to expand our understanding of the role of vitamin D in our health, and get solid answers to our questions so that we can find out once and for all whether or not this vitamin is truly the miracle that some claim it to be.

I did something the other day that has bothered me for the past 72 hours: I decided not to publish a comment in my blog because of fear of retribution or possibly retaliation.

Today, I decided to correct that decision and discuss my concerns.

Although it may not be a momentous piece of information, it nonetheless made me think long and hard about why I made the decision I did at that time, and what the implications were for providing information to the public about current controversies in oncology.

The topic of my blog this past Saturday was about the changing face of oncology, as reflected in the annual American Society of Clinical Oncology meeting.

What has concerned me were the comments in my draft about an investigational cancer vaccine called Provenge.

As I noted in that blog draft, we live in a different world today than we did years ago when it comes to public knowledge and influence on the drug approval process.

We have more information readily available, with many more people having access to that information.  I call this phenomenon the “democratization of information.”

Along with that democratization (if there is such a word) comes the sense among many that they want information provided to them so that they can make up their own minds regarding the validity, value and implications of that information.

It is one thing to have that information about, for example, a presidential candidate or a new car.  It is something else, in my personal opinion, when it comes to a new medicine or a new treatment. 

I agree with my colleagues that it is important that people have access to the information, but the subtleties of interpretation do require knowledge, training and expertise that are not possessed by most people who have not had training in medicine.

This brings us to the Provenge story.

I will admit that I am not privy to all of the information and primary data related to Provenge, an investigational vaccine being studied in the treatment of men with advanced prostate cancer. Much of what I do know comes from other sources that have reported on this topic.

That said, in a nutshell the story is that several years ago the company that has been working on this vaccine reported that their clinical trial intended to demonstrate that Provenge was useful in the treatment of advanced prostate cancer did not meet its goal.

Subsequently, on reanalysis, they concluded that there was some information in that “failed” trial which suggested that the vaccine may have in fact increased the lifespan of the men who received the vaccine.

The company then supplied the data to the Food and Drug Administration for review and possible approval of the vaccine.

Within the past several weeks there have been several news reports about the developments surrounding the FDA’s analysis and decision.

First, one of the FDA’s outside advisory committees suggested the vaccine be approved, despite some problems with the quality of the statistics that are normally used to determine whether or not in fact a drug (or vaccine, in this case) is effective for the disease in question.

A report in a widely followed cancer newsletter called The Cancer Letter reported that the advisory committee meeting was apparently raucous, with the advocates present in the audience making their opinions known very vocally when someone agreed or disagreed with their position that the vaccine should be approved for general use in the treatment of prostate cancer.

Subsequently, as again reported in the Cancer Letter, some highly respected cancer specialists wrote the FDA regarding their concerns about possible approval of the vaccine.  They felt that the data did not support effectiveness, and pointed out that there were ongoing clinical trials that would directly answer these questions, without the statistical problems of the current data.

The FDA decided to not approve the vaccine, and await the results of the ongoing clinical trial.

That apparently led the advocates in favor of vaccine approval to develop a series of actions with the goal of changing the FDA’s mindset. 

The advocates had posted an announcement on a website that they were planning a rally for Saturday morning at ASCO. They also planned a rally in Washington yesterday and today to meet with Congress and the FDA. 

Their position is that someone who wanted access to Provenge should be able to receive the vaccine.  The argument they make is that if it appears the vaccine may be effective, then why should men who are facing a fatal disease be denied the opportunity to receive the vaccine when it may improve their survival?

This is the question that piqued my interest in this topic, and how our standards may be changing when it comes to the decisions we make in caring for our patients.

For years, much of what we did as doctors—in treating ALL types of illnesses—was based as much on tradition and expert opinion as it was on science.  Now, as physicians, we are trying to move our care into more of an evidence based model, where we develop the science to back up our actions.

But with the spread of the internet—and the democratization of information—we find patients and others are beginning to influence our treatment choices, much as is the case with DCA and now with Provenge.  (Other alternative therapies are also driven by this “word-of-mouth” (or perhaps “word-of-internet” would be a more apt description) phenomenon, and are now very much a part of the landscape of cancer treatment.)

So that is what interested me.  I also had expressed in the blog draft my personal opinion that based on what I had read, waiting for the results of the clinical trial was the appropriate thing to do. 

We have seen too many examples in cancer medicine and other areas of medical treatment and practice where the initial thoughts have proven wrong—and even harmful—to ignore good science in this particular situation.  (The current discussions surrounding the potential harms of erythropoietin come to mind as an example.)

On my way to the ASCO meeting, I heard that the situation may have become even more serious than I had realized.

What made me pull my comments from that draft blog was a message I received that serious personal threats had been made against two physician scientists who had urged the FDA to delay approval of Provenge, pending the results of the clinical trial. And, I was told, these were threats of the most serious type.

Because of the risk, I decided not to say anything publicly.  Although I had written my blog on this topic, I edited the comments regarding Provenge out of the final posting which you may have read on Saturday.

For your background, what you see on my blog is generally what I write.  I may make some editorial edits, or perhaps tighten up some comments.  But I have never removed a “theme” from one of my blogs under pressure—either real or perceived--since I started writing it almost two years ago.

But this time was different. 

As I spoke with some reporters who attended ASCO, a common theme emerged. 

They, too, had become reluctant to cover the story because of fear of retaliation.  One reporter said that in their opinion you had to “steel yourself” if you intended to report an opinion or comment in support of the FDA’s conclusion.

Frankly, this troubles me a great deal. 

On Saturday afternoon I decided to give an interview to a major business journal and basically say that this is not the way we should do our science. 

What I said was that we may not always agree on the science, but intimidation is not the answer to making evidence-based decisions regarding drug approvals.  (As I write this, I don’t know if those comments have been published.)

Then, yesterday, the New York Times went public with confirmation that threats of physical harm had in fact been made against the experts who opposed approval of Provenge.  The Times reported that one of the physicians actually had bodyguards with him as he presented at ASCO.

In that interview, the physician indicated his concern that more of his colleagues had not come out publicly to support him in his time of need.  I suspect that, like me, many of his colleagues have been intimidated, and are frankly afraid to make a public comment.

As it turned out, the rally on Saturday had a small number of participants and nothing untoward occurred.

There were no meetings invaded, no sessions disrupted, and no one harmed.

As I said above, my personal opinion based on the information I have read is that it is appropriate to await the results of the current clinical trial to determine whether or not in fact Provenge improves survival in advanced prostate cancer before approving the vaccine for general distribution.

The question of access to investigational drugs is an important one, and one that is currently being debated in multiple forums.  When it comes to drug (or vaccine) approval, we must have the best evidence possible that the drug is effective, and a valid understanding of what risks may be associated with the drug.

But to threaten established, knowledgeable investigators who honestly express their well-reasoned opinions, which in turn “chills” rational discussion is, from my point of view, simply unacceptable.

We will always be subject to those who try to influence our comments, decisions and recommendations.  I personally try to limit those outside influences, and try my best to declare when I perceive there may be a conflict of interest that people should know about when I make a statement in a public forum.

Public debate and discussion is appropriate. Intimidation is not.  Disclosure is essential.

Ultimately, I am hopeful that our decisions whether or not a particular drug should be approved will be based on the best evidence available, and the best quality interpretation of that evidence. 

Yes, there are problems with the system currently in place.  Every human system is subject to personal interpretation and potential error.

That does not mean that those involved in making those decisions and making comments on those decisions are not trying to do the best they can under the circumstances.

Fear and intimidation should not make us hold back the expression of our legitimate scientific concerns. 

I know that the perception of potential intimidation influenced me a couple of days ago, and I hope that sharing these thoughts with you will help assuage the nagging guilt that has bothered me since I made that decision.

In the meantime, I hope that those who disagree with my position will be rational—and, non-threatening.

A presentation this afternoon at ASCO’s annual meeting this afternoon in Chicago  is going to discuss the effectiveness of an oral targeted therapeutic drug called sorafenib (Nexavar) in the treatment of primary liver cancer.

(We need to distinguish primary liver cancer—which originates in the liver and is known by its medical name hepatocellular carcinoma—from cancers that spread to the liver from other organs, such as breast, lung and colon cancer.)

The report is important because up until now there have been no really effective chemotherapeutic agents to treat this form of cancer.  In addition, this treatment is given by mouth, and the side effects were relatively modest.  In fact, the same level of side effects occurred both in the patients who took the drug, and those who took a placebo.

The researchers are going to report that the patients who took sorafenib lived a median of 10.7 months, while those who took the placebo (or dummy pill) lived a median of 7.9 months.  (Median is a statistical measure that means half of the patients lived longer than a particular time, while half the patients died before that time).

Looked at another way, the patients who took sorafenib took about 5.5 months until their disease showed that it was progressing.  Those on the placebo had evidence of disease progression at 2.8 months.

In essence, the drug increased the survival of the typical patients with primary liver cancer about 2.8 months.

That doesn’t sound like much, but it is likely a real finding.  In fact, if you understand what median means, some of the patients in this trial probably lived longer than the 10.7 months. 

And, if you have read my blog previously, you have seen me write that the history of improvements in the treatment of cancer happen much more often in small increments and not in big “one-time” gains.

This report is also important for some of the other considerations beyond extending life for 2.8 months.

First, if you read the information above correctly, you will note that in this particular international clinical trial, the drug was compared to a placebo.   A placebo, more commonly called a “dummy pill” or a “sugar pill” is essentially a pill with no active ingredient and not intended to have a beneficial therapeutic effect.

I am not aware of many clinical trials in cancer that compare a new drug for treating a cancer against a placebo.  You just don’t see that happen very often in cancer research these days.  

So why a placebo?  After all, although liver cancer is less common in the United States, there MUST be a standard treatment to offer.

I checked my trusted resource on the topic—the National Comprehensive Cancer Network website—to see what they recommended for standard chemotherapy treatment.

In fact, for metastatic or recurrent or unresectable primary liver cancer, there IS no standard chemotherapy listed.  Nothing at all.

They do recommend clinical trials or best supportive care (that is medical language for making someone comfortable but not actively treating them with chemotherapy or other modalities) if someone can’t be treated with standard methods or has recurrent disease.

So the bottom line is that we don’t have much to offer patients in these circumstances.

That is not to say we don’t have treatments to offer patients with liver cancer.  But those treatments are more surgically oriented such as surgically removing the cancer when possible, or even transplanting the liver in a patient with liver cancer who meets certain criteria.

There are other techniques as well where doctors can “ablate” the cancer by using freezing techniques, microwave or what is called radiofrequency ablation, for example.

Liver cancer is becoming more common in the United States with 19,160 new cases expected to be diagnosed in the United States according to the American Cancer Society’s Cancer Facts and Figures 2007.  The large majority of patients with this cancer are men, and in 2007 we estimate that 16,780 people in this country will die from this disease.

This is, according to one of my colleagues, one of the cancers that is increasing most rapidly in the United States in men.

This is a cancer that is known to primarily be caused by infection with Hepatitis B and Hepatitis C.

Fortunately, in this country, we have a decreasing incidence of hepatitis, in no small part because we are able to offer immunization against hepatitis B to our children.  We have also significantly improved our ability to test blood transfusions for these viruses, which used to be a significant means of transmission on this virus.

But we also must keep in mind that primary liver cancer is a significant world-wide health risk, in no small part due to the fact that immunization is not widely practiced, and personal and medical hygiene habits are much worse in many developing countries than they are here in the United States.

In fact, in 2005, my colleagues at the American Cancer Society who write Cancer Facts and Figures provided an entire special section of this valued reference book devoted to the topic of infectious causes of cancer in the world.  Liver cancer was the lead topic of discussion.

That monograph contained some interesting statistics:

In 2005, it was estimated there would be 667,000 cases of primary liver cancer throughout the world, making liver cancer the 6^th most common cancer in the world.  It is the 18^th most common cancer in the United States.

83% of the new cases of liver cancer occur in developing countries., but in the United States the incidence of liver cancer has been occurring for the past 20 years.

In the developing countries, 37% of the new cases of liver cancer are attributable to hepatitis B infection, 25% to hepatitis C, and 10% to liver fluke infections.

Sharing of needles, poor personal hygiene and direct person-to-person transmission account for many of the hepatitis B and hepatitis C infections.

In the United States, we are able to offer treatment for chronic hepatitis infections, but we don’t know how much of an impact this has on the transformation to liver cancer.  In the developing world, these types of treatments are far less available.

So what does all of this mean?

We are fortunate to have a new drug that is clearly effective—albeit modestly—in the treatment of this previously untreatable disease.  That offers some hope, but more importantly signals the opportunities for real advances in the treatment of primary liver cancer.

We also need to understand this is a disease that, although certainly of concern in the United States, is a major health threat throughout the world especially in developing countries.

Liver cancer is a disease that would occur less frequently if we had an effective international immunization strategy and an educational strategy focused on good health and hygiene behaviors and improvements in medical care delivery systems (such as avoiding the reuse of needles in medical settings).

But this is difficult to accomplish, and many barriers are in place which prevent the adoption of these simple, inexpensive and effective approaches to reducing these infections and in turn reducing the incidence of primary liver cancer.

How we are going to be able to get the benefits of this new drug to developing countries where it is most needed remains the unanswerable question.  This drug is expensive, and probably far beyond the means of those who need it most.

And that raises the larger issue that I have discussed previously, namely how are we going to be able to afford our miracles.

We need to develop a sustainable economic/business model that works for everyone: the companies that discover, market and manufacture these drugs; the insurers and governments who pay for the drugs; and, most importantly, the patients who need the drugs.

Finding a solution to that conundrum is, in my personal opinion, probably one of the most important issues we face in cancer treatment today.

We are now into the third day of the annual meeting of the American Society of Clinical Oncology here in Chicago.

Trying to determine what research and which issues are going to become most relevant to cancer treatment are becoming a bit clearer.  There is even a little bit of controversy to go along with the scientific presentations.

For example, at a presentation earlier today, a researcher from Germany made a comment that received a considerable amount of interest from those in attendance, including members of the media.

The study, which examined the value of MRI compared to standard screening mammography in the detection of non-invasive breast cancer (called ductal carcinoma in situ, or more commonly known as DCIS), concluded that MRI was more likely than mammography to identify high grade DCIS lesions.  This is important, since high grade DCIS is more likely than its low grade counterpart to progress to true invasive breast cancer.

The modest controversy occurred because the researcher was quoted as saying something to the effect that MRI was a better screening tool than mammography, and that the reasons we don’t recommend MRI for routine breast cancer screening are based on politics and finances.

This created a bit of a stir, especially since in another quote the researcher stated what I consider the more appropriate observation, namely, “More research is necessary before we can make any specific recommendations about the use of breast MRI for DCIS in clinical practice.”

In fact, the study performed at the University of Bonn, Germany, demonstrated that when women were screened with both MRI and mammograms, 40% of DCIS lesions were seen only on MRI, and 78% of these were high grade—the type more likely to progress to breast cancer, according to the research report.

In contrast, 8% of DCIS lesions were seen only on mammograms, and of these all but one were low grade, implying a lower risk of advancing to breast cancer.

In a sense, these results are not unexpected. 

We know that MRI is a more sensitive test than mammograms.   But it also finds many lesions that are not cancerous.

For example, a recent report on the use of MRI in women recently diagnosed with breast cancer but prior to surgery showed the value of MRI in finding previously unexpected DCIS and other breast cancer lesions in the breast opposite from the one where the primary breast cancer was discovered.

More importantly, in a recently released guideline from the American Cancer Society on the use of MRI as a screening tool for breast cancer, the experts who reviewed the evidence concluded that MRI was only definitely valuable in women at particularly high risk of breast cancer, such as those women who are BRCA positive, or who may have had radiation therapy in the past to treat a disease such as Hodgkins disease.

Those experts concluded that the routine use of MRI in screening  women at average risk for breast cancer was not justified based on the evidence.

In addition, the Society report highlighted the concerns of the expert panel that the technology for quality breast MRI is not generally available.  Also, that article noted that it is very important that even in those situations where its use is justified, MRI studies should be performed in centers of excellence that are fully equipped to provide the best images and appropriate follow-up for suspicious lesions seen on MRI.

For now, I suspect that this study—although important and certain to raise interesting questions and stimulate further study—is not going to change the standard of care in the United States or elsewhere.

Another study highlighted for me the fact that what is new is sometimes very old.

The disease in question is acute promyelocytic leukemia (APL). 

When I started my oncology training in 1972, we saw occasional patients with this form of leukemia.  It was a devastating disease, and we had very little to offer these patients.

Over time, the situation changed and subsequent advances made this form of leukemia one of the most successfully treated acute leukemias in adults.

What is interesting about this particular story is that several years ago, a medicine emerged from the far rural reaches of China that was found to be effective in the treatment of this disease.  The medicine, called arsenic trioxide, was a traditional Chinese medicine that was discovered by someone who was doing a Cultural Revolution related sojourn in a rural part of China.

The story behind this discovery is a fascinating one, and was recounted in detail in a 2001 article in the Sunday magazine of the New York Times.

Currently, APL is treated with a combination of chemotherapy.  Arsenic trioxide is used to treat patients who relapse after failing the initial therapy.

In the new study, the researchers reported that by using the arsenic compound as part of the primary treatment, they were able to increase survival significantly at three years, and also significantly increase the time to relapse in patients who received the arsenic treatment immediately after the primary treatment was administered, instead of waiting until the cancer recurred which is the current practice in the treatment of this leukemia.

From my perspective, this particular study points out two major themes:

The first is that you can never tell where the next advance in cancer treatment will be found.  Adapting a traditional Chinese medicine to effective cancer treatment was certainly an unexpected advance, but one that has proven very effective—albeit only for a small number of cancer patients.

The second is that even compounds which at first glance would be assumed to be very toxic—in the case of arsenic, obviously lethal—may in different forms or different doses prove to be very helpful.

Which leads me to the final thought for this blog, namely that you can never make absolute assumptions about anything.  One must always keep an open mind and always keep searching, for you never know where the next new drug or new treatment may come from.

The annual meeting of the American Society of Clinical Oncology has always been one of my favorite medical meetings.

I have been attending this yearly gathering since the early 1970s.  The current meeting underway in Chicago shows how much the practice of oncology has changed, and reflects many of the broader social and demographic changes in our medical universe over the past 35 years.

Many of those changes are laudable and important.  But, some reflect underlying societal influences that have the potential to alter our view of how we conduct our science, and how we apply our knowledge to new treatments.

When I first started attending ASCO in the early 1970s, it was a relatively small meeting with a couple of hundred attendees.  The meeting could be held in small convention centers attached to hotels in various locations around the country.

Getting your arms around the agenda and attending many of the sessions wasn’t difficult to do.  You knew which presentations were important, and there were no exhibits to distract your attention.

I can still recall the debate at ASCO as to whether we would allow exhibitors to have displays at our meeting.   The debate was academic, with strong concern about the potential influence of the exhibitors on our clinical judgment.  The counter argument was the revenue the exhibits would generate.  Revenue won.

Today’s ASCO meeting is much, much different.

There are literally tens of thousands of attendees and exhibitors.  The exhibit hall is huge, and the “booths” are incredible presentations.  Some even include live shows and lectures designed to attract the physicians into the booth.

Many of the attendees are from other countries, further confirming the importance of cancer research and therapeutics throughout the world.

We used to meet in small venues.  Today, we are at McCormick Place in Chicago.  I literally walked a mile (as measured by my pedometer) just to get from the bus area to the registration area, then walked another half mile back to the lecture hall where I am now sitting.

But, and perhaps most important, I can no longer get my arms around the program.  There are hundreds if not thousands of educational, scientific, and research presentations.

One of my colleagues commented that her task was fairly simple, since her area of clinical interest is limited to gynecologic oncology.

For me, as a medical oncologist with broad interests in the clinical practice of cancer medicine, the task is much more difficult. 

There is no way I can figure out which presentations are most important, and where I should invest my time.  There are so many presentations on new targeted therapies that I cannot possibly attend even a fraction of them.

I must say that, as I write this early on Saturday morning at one of the general sessions, I haven’t yet found the “major” story that I am looking for.

Usually, the plenary session has a couple of breakthrough presentations.  Right now, I can’t say that this year’s plenary session appears that it will have that impact.

And I haven’t yet heard “the buzz” about special presentations or other abstracts that may represent real breakthroughs.

But I must say that perhaps I am becoming a bit jaded.  I suspect I am not along.

After all, targeted therapies are no longer the big new thing.  They have become just “the thing.”

That in itself is news, however.  The advances in this area of cancer treatment are so many that they have now become part of the landscape of the meeting, and no longer stand out as the occasional dramatic triumph.

In the meantime, I am going to continue attending the scientific sessions and hope that I will have some exciting and important information to share with you on subsequent blog entries over the next few days.

It has been a very hectic number of weeks of travel, meetings and lectures. .  Cramped spaces on airplane flights haven’t helped matters either. All contribute to the fact that I have not been able to update my blog for a while.

As I write this I am en route to the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.  I look forward to this meeting every year, especially since it provides the opportunity to hear the latest in cancer research and listen to lectures on the current state-of-the-art in cancer treatment.  I expect this year’s meeting will be no exception, and I hope to provide some insights on this blog over the next couple of days.

Right now, however, I am reflecting on something unusual that has happened during these past weeks as I traveled around the country.  And that is the number of volunteers who have stopped me to say hello and let me know about their personal relationships with the American Cancer Society.

I guess this probably wouldn’t be so unusual if this had been occurring routinely in the past.

After all, when I travel my luggage and my various computer and other business bags have American Cancer Society identification tags in plain view. The fact is, it hasn’t happened so regularly in the past as it has in the past several weeks.

The enthusiasm and commitment volunteers bring to the Society is nothing new. 

We are, after all, a volunteer organization over 2 million strong.  The commitment of so many people to Relay for Life and Making Strides Against Breast Cancer—among many related community activities—is well known and well documented.

But there is something different this year, at least based on my experience.  It is more than the number of people who participate, or how much money they raise.  It is the sense of commitment and enthusiasm that appears greater to me than in years past.

For example, the staff in my wife’s medical practice in Thomasville, Georgia enthusiastically embraced Relay, and raised a considerable amount of money through various activities including a massive barbecue where they sold over 125 Boston butts in one day.

Our son—who is 12 years old—decided he wanted to stay into the early morning hours at our local Relay.  He recognized that this was a special event with special meaning, and he wanted to be a part of it.

My wife’s cousin in Douglas, Georgia was chair of their local Relay and was incredibly enthusiastic about the contribution she and her community were making in our fight against cancer.

Those are personal stories, and I suspect many of us active in one way or another with the Society have similar experiences in our own lives.

But I must admit that I was a bit taken aback a couple of weeks ago when I was sitting in an airline lounge in the Atlanta airport working on my computer and a gentleman spontaneously started talking to me about his role as chair of a local Relay event near Daytona, Florida.

He commented that he noted the American Cancer Society logo on my polo shirt, and wanted to know if I worked for the Society.

I replied that I did, and he then told me about his role in his local Relay.  He had his own business, he said, which always absorbed much of his time.   He became involved in Relay several years ago, and now was chair of the event.

He went on to say how much time it took to organize the event, especially in the month or so prior to Relay weekend.   He pointed out, with considerable sincerity, that he thoroughly enjoyed every bit of his effort and was grateful for the work that the Society does for cancer patients and cancer research.

Since that discussion, I have been stopped several more times by people to say much the same thing. 

One time recently on another flight there was a man sitting next to me who noted my Society luggage tag.  He told me about his wife who was active in Relay in one of the local counties near Atlanta, which happens to be one of the largest (if not the largest) Relay events in the country. 

The story he told was much the same as the other gentleman.  His wife’s commitment to Relay took a lot of time from their personal life, but the reward for the effort in their opinion was well worth the sacrifice.

Last week I was at a committee meeting in Washington, DC. 

Just prior to the start of the meeting, a young man came into the office I had borrowed to get caught up on email.  He asked me if I worked for the Society, and I replied that I did.

He then told me about the fact that he was active in Relay at his college, and although he recently graduated he remains committed to the activities of the Society and plans to continue to volunteer.  In fact, he said, he had his Relay T-shirt on that very day, under his dress shirt and tie.  Just like Superman, he showed me the T-shirt (and I have a picture to prove it).  Now, that is what I call commitment!!!!

Even today, while walking down the hallway to my flight, someone stopped me to tell me about their relationship with the Society, and what it has meant to them.

I don’t think anything, though, surpassed meeting the young college students from Virginia Tech who visited with us during our recent Board meeting in Austin, Texas.

These young people had just gone through a terrible tragedy including the loss of their classmates who had been active in planning Virginia Tech’s Relay event.

Despite the tragedy, and despite the fact that the students had left the campus in the aftermath of the shootings, they decided to go ahead and have their Relay.

There weren’t many dry eyes in the audience as the students related what that particular Relay meant to them, to their classmates and the Virginia Tech family.  It brought them together in a spirit of hope and mission, and provided a much needed moment to restore their faith and their direction in life.

I guess what makes me want to share these stories (and there are others) is the fact that there are so many people who take so much pride in volunteering for the American Cancer Society, and in their relationship with the Society.  For them, their involvement is very personal.

I know that, as an organization, we are not alone when it comes to volunteer commitment.  This country is fortunate to have so many people willing to do so much for so many.

I have said many times that when I come to work (wherever that work may be on any given day), I have a sense of pride and gratitude that I am part of this organization.  I know my colleagues throughout the country share that pride as well.

What makes this all so special are the folks who give of their time and their money to help us do the work we do.  As the chance events of these past weeks have demonstrated, there are many of you out there who share that pride in taking part in the activities of this Society.

Thank you for sharing your thoughts with me.  You probably didn’t know it, but when you have shared your spirit with me, you lifted my spirit as well.

Knowing how much you care makes us all feel very special about what we do.

Thank you.