Western Meets Eastern Medicine: Or Ying Meets Yang?

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cancer, clinical trials, CME, digital media, epatients, evidence based medicine, innovation, integrative oncology, medicine, pharma, physician, research, Traditional Chinese medicine

By Richard Just, MD

In today’s China, both eastern and western medical philosophies and practices exist relatively harmoniously.  Patients with minor, usually self limited problems are treated initially with a seven day course of seven liquid herbal preparations taken each day.  If symptoms subside, usually treatment is discontinued.  If improved but not resolved, formula may be modified.  If worse, regimen can be changed and/or referral to specialists arranged.  There are hospitals that practice purely eastern or only western medicine.  But it is becoming more frequent to find hospitals that integrate both disciplines.  Chronic conditions, like cancer, tend to be treated with western techniques, with Traditional Chinese Medicine (TCM) used in a supportive or complementary role.

I was somewhat surprised to hear that the 2 largest cancer problems are breast cancer and liver cancer (mainly the former but not the latter).  Before I left, one of my patients had brought an article to my attention about a low incidence of breast cancer in China  compared to the West.  This may not be the case.  Primary liver cancer, hepatocellular carcinoma), has long been the number one cancer in frequency in the world due to a high incidence of hepatitis, especially in Asia.  This results in chronic active hepatitis, cirrhosis and, finally, cancer.  Even though we stayed at 5 star hotels, we didn’t brush our teeth or rinse our toothbrushes with tap water, and avoided ice.  Sanitation, or lack of it, is an issue.

Everywhere in China, especially big cities, there are forests of skyscrapers.  Private homes are essentially nonexistent as the government owns all the land.  New construction is ubiquitous, so cranes are numerous.  Many of these apartment spaces are empty due to high prices, and those that are bought or rented are shared by several families.  Same with kitchens and bathrooms.  Public bathrooms may lack toilets and simply be holes in the ground.  In some buildings, one bathroom per floor exists.  We saw the interiors of 3 residences.  First, the home of one of four of the farmers that first discovered the terra-cotta warriors outside Xi’an.  Clean.  Very little furniture as you buy empty spaces which you have to furnish yourselves.  But several generations of the family lives there.  Second, a more modest quarters of a woman in the old section of Beijing.  Bathrooms were down the road apiece.  The last was a tiny, single room in what used to be the French Concession section of Shanghai.  Five people slept on one cot.  No mystery why hepatitis and liver cancers are still issues.

Another surprise is lack of mention of lung cancer.  Cars everywhere.  Their gridlock is continuous and called “rush days”.  Mist or fog (mostly pollution) gives a surreal appearance to the landscape of high rises.  Seemingly everyone coughs.  Lots of spitting.  A perfect setup for respiratory problems including lung cancer.  There are several hospitals in major cities devoted to respiratory diseases, however.

An excellent article appeared in the Wall Street Journal, Tuesday, April 3, 2012, pg D4, entitled “Chinese Medicine Goes Under the Microscope” by Shirley S. Wang.  The main topic is a clinical trial studying a four herb combination, called huang qin tang in China and PHY906 in this trial, in combination with chemotherapy to see if effective in reducing side effects of chemo (nausea, vomiting, and diarrhea).  If so, patients might be able to tolerate higher doses of chemo with better results.  Trial design and quality control are issues when doing studies such as these:

One challenge with using herbal medicines is that the ratio of the chemicals they contain isn’t consistent when plants are grown under different conditions.  After testing various suppliers, Dr. (Yung-Chi) Cheng ended up creating a biotechnology company sponsored by Yale called PhytoCeutica to carefully monitor growing conditions to ensure plants from different batches were pharmacologically consistent and to continue clinical development of the compound.

Finally, an article that appeared in the China Daily entitled “There’s More to Life Than Money” by Cai Hong, a senior writer for the paper, cites the first World Happiness Report   released by the Earth Institute last month.  Not surprisingly, the top 4 rated are northern European welfare states:  Denmark, Finland, Norway and the Netherlands.  China doesn’t make the top 100.  One of the benchmarks evaluated is health:

……Increased insurance coverage has not yet been effective in reducing patients’ financial risks, as both health expenditure and out-of-pocket payments continue to rise rapidly.  And there are many reports of disgruntled patients and their relatives attacking the medical staff in hospitals.  Reform of public hospitals is essential to control health expenditure because such institutes deliver more than 90% of the country’s health services.  But Health Minister Chen Zhu said the cost of improving care remains an obstacle, and China is looking to other nations for cost-effective solutions.

While this notice appeared in the WSJ this last weekend:

U.S.-China Pharma: Some big pharmaceutical firms are partnering with Chinese companies in trying to discover the next blockbuster drug.  This Philadelphia conference will include venture capitalists and such Western firms as Novartis and Abbott Labs. Wednesday-Thursday, Hub Cira Centre.  Regular admission:  $1,799.00.

I find it interesting that both the U.S. and Chinese governments are investigating hospitals for price gouging in the sale of drugs. Further, given the emerging cost and access pressures they’re witnessing, might mainland China by eying the health system reform experiment underway in Taiwan?

China Bound: An Appeal to the China Clinical Trials Consortium (CCTC), et al

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cancer, china clinical trials consortium, clinical trials, clinicaltrials, evidence based medicine, integrative oncology, medical education, medicine, oncology, research, Traditional Chinese medicine

By Gregg A. Masters, MPH

Dr. Just will be heading to China this week and has an interest in connecting with clinicians associated with the China Clinical Trials Consortium, other academic or established medical group practices’ specializing ‘integrative oncology’, or solely traditional Chinese medicine for the care of cancer patients.

For a brief personal invitation please watch the video above. Dr. Just’s Twitter handle is @chemosabe1, if you are available during the timeline below and interested in meeting with an American colleague please follow @chemosabe1 on Twitter, he will follow you back and enable direct message sharing. Otherwise an @reply will work as well.

Travel dates and cities are: arriving Beijing, Thursday, May 3rd, and departing Shanghai on Friday, May 18th, 2012.

More To The Henrietta Lacks Story

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cancer, clinical trials, elder wisdom, epatients, evidence based medicine, health, Henrietta lack, medical education, medicine, physician, physicians, research, social media, twitter, wellness

By Richard Just, MD

A few weeks ago, my wife and I attended “A Conversation With David ‘Sonny’ Lacks” at the California Center for the Arts, Escondido.  The event was a sellout with 900 attendees.  As it turns out, most of the colleges and universities in San Diego County designated “The Immortal Life of Henrietta Lacks” as the book discussed by students and faculty this past academic year.  The conversation was sponsored by California State University, San Marcos.  As an added bonus, Mr. Lacks’ daughter appeared with him on the podium.  I had previously attended a similar lecture with the author, Rebecca Skloot, at UCSD.

The story of Henrietta Lacks can be viewed from several vantage points.  As a medical oncologist, and Chairman of the Investigational Review Committee as well as Medical Director of the Research Institute at Palomar- Pomerado Health, ethics in medical research certainly occupies a position of paramount importance to me.  In fact, the book is being discussed locally primarily from this perspective.  Ms. Skloot points out that obtaining ‘Informed Consent’ from patients to do research on their tissue was not required, nor was it considered, in 1951 when Mrs. Lacks’ biopsy was obtained for research purposes.  Mr. Lacks stated he did not feel the family should receive financial compensation for using her tissue for research purposes.  But, Henrietta and the family should have been told that her cells were going to be used for research purposes, what the research involved, and knowledge of the results.  In other words, essentially informed consent as we now require in all patients undergoing clinical trials.

On the other hand, he did feel that the family should receive financial remuneration from the companies that commercialized his mother’s cells by selling them to labs around the world.  This proposal seems fair.  To date, no financial restitution has occurred.

But despite all this, Mr. Lacks maintains an air of dignity that engenders respect.  Throughout the evening, there was no expression of anger or hostility; no complaining.  When asked if he thought that racial discrimination played a role in how they were treated, Mr. Lacks said no, people of all races were treated the same at that time.  Sonny said that although no one from Johns Hopkins has ever formally apologized, they have honored his mother in other ways.

Sonny Lacks was 3 years old when his mother died.  So, he has no direct recollection of her.  In fact, the picture on the front of the book is the only picture of Henrietta in existence.  All that he and his daughter know about her they learned from his older siblings and Ms. Skloot’s research for the book.  When Henrietta was treated, Johns Hopkins was the only hospital in the state of Maryland that treated the uninsured.  Fast forward to the present and this sore is still festering in our country.  Mr. Lacks stated that he recently required stents placed in his coronary arteries on an urgent basis and he, like all the members of his family, is uninsured.  This brought an audible gasp from the audience.  He said he had $100,000.00 in unpaid bills, and he opined that health care should be a right as it is in other countries, not a privilege for only those who can afford it.  This elicited a vigorous round of applause from the audience .  I would add that the number of people in the U.S. who can afford access to healthcare is dwindling also. [Editor’s Note: For specific discussion on the impact in the Black community, see: ‘Blacks See Largest Decline in Health Insurance Coverage.’]

The closest we have to universal healthcare provided by government is Medicare and Medicaid (MediCal in California), see: ‘Medicare: The Basics.’  I recently crunched the numbers in my own situation at age 70 to decide whether or not to convert from my medical group’s health plan (since I’m still working to full Medicare coverage.  Plan A is free and mandatory at age 65.  But I needed Plan B, a Medicare Supplement Plan and Medicare Part D for prescription drugs.  Part B involves an annual fee of $140.00 + monthly premiums of $99.00 + something called “Modified Adjusted Gross Income” (MAGI).  The IRS now sends Medicare a report of my income and a graduated monthly charge is added to my premium.  The monthly total amounted to $259.70.  Added to that is the cost of the Supplement and Medicare Part D.  Then the out of pocket expenses including cost of drugs in the donut hole and now you’re talking “real money.”  Of course, you can opt for a Medicare HMO but choices are limited. So for effect, I will quote myself (drum roll please!):

My conclusion was that being insured does not equate to being covered, and I needed to be a CPA to figure this out.  So, I stayed with my group health plan.

The most poignant moment of the evening occurred when Henrietta’s granddaughter was asked how she felt her grandmother should be remembered.  Her answer:

The gift that keeps on giving.

Not a dry eye in the room.

More On Screening: Barrett’s Esophagus

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Barrett’s Esophagus, cancer, CME, epatients, GERD, medical education, medicine, oncology, participatory medicine, patients, physicians, research

By Richard Just, MD

Recently, a friend of mine asked me for medical advice concerning his condition, Barrett’s esophagus.  When the diagnosis was initially made, he was advised he would require annual screening endoscopies with random biopsies.  But, on his last visit, my friend was told he didn’t need another procedure for 5 years, with no explanation.  “What’s up?”  Since he had a copy of the biopsy report (not with him, but at home), I advised he read it and look for the word dysplasia.  Wikipedia defines dysplasia as

maturation abnormality.

So far, I haven’t heard back.  But this stimulated me to review current recommendations on the subject.

Between 2-3 decades ago, there was a sudden increase of adenocarcinomas (“glandular cancers”) of the lower esophagus usually in Caucasian males.  This event was noticeable in that the usual esophageal cancers were a different cell type, squamous cell carcinomas, that tended to occur in Black males.  Adenocarcinomas appeared to be correlated with gastroesophageal reflux disease (GERD), while squamous cell carcinomas (SCC) are associated with smoking and alcohol consumption.  These are tends, not absolutes.  GERD causes irritation of the cells of the lower esophagus resulting in conversion of the cell type (metaplasia) from squamous cells to columnar cells, the definition of Barrett’s esophagus.  Barrett’s, in turn, can progress to low grade dysplasia, high grade dysplasia, and adenocarcinoma.  Thus, it has been proposed that patients with at least weekly GERD symptoms (heartburn, regurgitation, and dysphagia, meaning difficulty swallowing) that have been present for at least 5 years, and who have multiple risk factors for esophageal adenocarcinoma including white ethnicity, male sex, older age, obesity and long duration of GERD undergo screening for Barrett’s esophagus.

Management of Barrett’s esophagus involves 3 major components:

1. Treatment of GERD:  Recommended to be initiated prior to surveillance endoscopies to minimize confusion caused by inflammation in diagnosing dysplasia.  Not thought to reduce incidence of esophageal adenocarcinomas.
2. Endoscopic surveillance:  If no dysplasia found, next scope in 3-5 years.  Follow up for low grade dysplasia is 6-12 months  For intensive endoscopic surveillance of high grade dysplasia, scope every 3 months.
3. Treatment of high-grade dysplasia:  Recommendations can include esophagectomy, endoscopic ablative therapies, and endoscopic mucosal resection in addition to intensive endoscopic surveillance.

Since the above recommendations were updated in 2011, my assumption is that no dysplasia was discovered on any of the 3 studies and risk of progression to cancer is low.  For the general population of patients with Barrett’s esophagus, the risk of esophageal adenocarcinoma is 0.5% per year.  Contrast this with 5-8% per year in patients with high grade dysplasia.  The risk for low grade dysplasia falls somewhere between these 2 extremes.

I’ve written previously about the limitations and risks of mass screening techniques, e.g., mammography for breast cancer, PSA testing for prostate cancer and PAP smears for cervical cancer.  The same applies to screening endoscopies for Barrett’s esophagus.  The procedure carries with it risks, including perforation and bleeding.  It’s also not very comfortable to have a hose snaked down your throat so that pre-anesthetics are sometimes necessary, creating more risk.  Random biopsies are performed because it’s sometimes difficult for the endoscopist to identify areas of dysplasia from just metaplastic cells, leading to falsely negative results.  In his new book “The Creative Destruction of Medicine”, Dr. Eric Topal opines “We’re not very good at detecting and fighting cancer.  The mass screening model, as with mammography or prostate specific antigen (PSA) testing……..is enormously expensive and leads to an untold number of false positive results and more unnecessary biopsy procedures.  Doing serial sensitive scans like PET or CT would likely make this problem worse, both by increasing the false positives and incidental findings and by exposing individuals to ionizing radiation that itself causes cancer.”  The use of innovative technologies such as circulating tumor cells (CTC), genomics (circulating DNA and RNA) and wireless sensors including implanted nanosensors are described.  Obviously, hope runs high that at least some of these techniques will be validated so that the ultimate goal, prevention, is achieved.

A Glitch On the Road To Personalized Oncology

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biobanking, biomarkers, cancer, clinical trials, health, HeLa cells, medical education, medicine, oncology, participatory medicine, research

By Richard Just, MD

We receive a quarterly magazine in the office called CURE, which stands for Cancer Updates, Research & Education.  Browsing through the Winter, 2011 issue, I noticed a short article entitled “Lacks’ Legacy” with an accompanying picture of Henrietta Lacks.  I’ve previously published a blog on HeLa cells, the cell line cultured from her original cervical cancer.  These cells are immortal in that they contain an enzyme at the tips of their chromosomes which prevents them from undergoing programmed cell death (“apoptosis”).  “Lacks’ tissue has since spawned an estimated 50 metric tons of HeLa cells, and the total number of HeLa-related medical studies-roughly 60,000 to date-is growing by about 300 per month.”  These cells were so malignant they were able to rapidly proliferate despite primitive tissue culture procedures.

It then occurred to me that the article was actually a sidebar to another piece called “Why Banks Need Your Tissue for Research” by Paul Engstrom, about tissue repositories.  One major message is the wide gap that exists between knowledge generated in the laboratory (meaning biomarkers and targets for new therapies) and biobanking.  A partial list of problems includes “inconsistent collection, processing and storage of tissue, which can alter its molecular composition and skew experimental outcomes; shortages of high-quality tissue; outdated preservation techniques; the high cost of and inadequate funding for repositories; patients’ lack of awareness about tissue donation; and, for competitive and other reasons, institutions’ hoarding specimens they might otherwise share with researchers elsewhere.”  These are major issues.  Since it is becoming a standard practice in clinical trials to collect, store and study tissue, then maintain these specimens for future investigations, addressing these concerns is essential.  The recently completed TAILORx study of 10,000 newly diagnosed women with early stage, hormone receptor positive, node negative breast cancer is a good example.  The Oncotype DX Assay to identify patients who might benefit from the addition of adjuvant chemotherapy to hormonal therapy as opposed to those who won’t was obtained from archived tissue specimens.  It is therefore vital that all efforts are made to assure that all institutions supplying these tissues and the repositories processing and storing them follow standardized procedures to validate that results are accurate.

All of this sounded familiar to me.  Then, I remembered an article I’d read previously in one of my favorite medical journals, WIRED magazine, entitled “The FLESH FILES” by Steve Silberman, June, 2010, pg. 156.  This is when I first became aware of the extent of these problems.  In 2005, the NCI announced the plan to create the Cancer Genome Atlas using the same techniques employed to delineate the human genome-high-throughput DNA sequencing, lab automation and computational biology.  The pilot phase would catalog genetic mutations in three of the major cancer killers:  glioblastoma multiforme (the most malignant brain tumor), serous cancers of the ovaries, and squamous-cell lung cancers.  This Atlas could reveal new tests, like the Oncotype Dx test, that would help determine treatment, develop novel agents directed against these mutations, and new methods to detect these cancers at an earlier stage.  Unfortunately, the Atlas was put on hold not because of difficulty with scientific techniques, but due to lack of viable tissue specimens to test.  In short, the biobanking system was in shambles.

Reasons for the sorry state of tissue repositories are numerous.  Focusing in on one aspect, freezing and thawing of tissues, classical solutions used to cryopreserve cells and bodily fluids are glycerol and dimethyl sulfoxide (DMSO).  Tissue requires a different preservation method, using two relics from the Victorian era:  formaldehyde (in a diluted form called formalin) and paraffin.  Formalin acts as a fixative, arresting all cellular metabolic processes, while paraffin prevents oxidation.  Under the microscope, these substances preserve cellular structure.   But they play havoc with genetic material inside cells.  “Some cells get so stressed that hours after they thaw, they take themselves out of the gene pool permanently” by undergoing apoptosis, the same “programmed cell death” that is not seen in the immortalized HeLa cells.  Even cells that don’t die experience genetic changes in the freeze-thaw cycle that can lead to an overestimation of the quality of biospecimens.  The result is corruption of the genomic data.

Additionally, formalin causes significant alterations to cellular RNA, a major probe used to decode the genetic mechanisms of cancer.  And DMSO can actually accentuate the metastatic potential of a cancer.  If infused into patients, DMSO can result in chills, nausea, kidney failure and cardiac arrest, especially in children.  Use of DMSO can be reduced by “chilling tissue at a carefully controlled rate immediately after harvesting (using a technique appropriated from Eskimos in the early 1900s by Clarence Birdseye, father of the frozen-food industry).”  But, adoption of this procedure would disrupt the routine of already overworked hospital staff.

Enter Carolyn Compton, M.D., PhD, director of the Office of Biorepositories and Biospecimen Research at the National Cancer Institute (NCI) in Bethesda, Md.  She is spearheading the effort to establish a central, public-private cancer tissue repository called the Cancer Human Bank (caHUB).  Unfortunately, these plans are on hold due to lack of sufficient federal funds.  Instead, $23.5 million in federal stimulus funds will be used by the NCI to expand research on standards for collecting, processing, storing and disseminating tissue specimens.

Trials and Errors – Part II

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cancer, clinical trials, clinicaltrials, FDA, medical education, medicine, oncology, pharma, research, science, social media

By Richard Just, MD

So, the purpose of the Cancer Genome Atlas is to identify all mutations in the most common cancers.  A massive project.  Several maps have been completed including melanoma, pancreatic, ovarian, and lung cancers.  Activation of these mutated genes results in the 6 characteristics of cancer previously listed.  Therefore, it would stand to reason that aiming novel agents at these targets would inhibit growth and spread, possibly cure, cancer.  But which targets to aim at?  For example, pancreatic cancers contain between 50-60 mutations.  To make order out of chaos, the most frequently identified mutated genes are inferred to be causative or “driver” mutations while the rest are “bystanders.”  Also, by recognizing that driver mutations tend to be found in certain ”core” pathways but not others, this further reduces possible targets to a more manageable number.  Between 13-15 pathways, an average of 13, are affected in a typical cancer type.

Getting back to the issue of causation, this month’s issue of Wired Magazine contains an intriguing article by Jonah Lehrer headlined by the following statement:  “Dead –end experiments, useless drugs, unnecessary surgery.  Why science is failing us.”  The title, “TRIALS AND ERRORS”, persuaded me to read on.

The story starts with Big Pharma’s nightmare:  a failed clinical trial.  The drug, torcetrapib, appeared to be a slam dunk in that it lowered bad cholesterol (LDL) and increased the good (HDL) by inhibiting a protein that converts HDL to LDL. Inferred from these facts was that plaque formation would be reduced, which in turn would result in decreased morbidity and mortality from heart attacks and strokes.  In fact, the opposite occurred, and the Phase III trial was terminated.  Pfizer had invested more than $1 billion dollars to develop torcetrapib plus an additional $90 million to expand the manufacturing facility.  The value of the company dropped by $21 billion in 1 week.  Since 40% of drugs fail Phase II clinical trials, and 25,000 volunteers were participating in this trial alone, both the financial and human costs are staggering.  $100 billion is invested in biomedical research annually.

How could torcetrapib fail?  After all, the entire pathway of cholesterol metabolism had been mapped out and the drug’s exact site of action was known.  Sound familiar?  As the author states, “it is a tale of mistaken causation”.  By lowering LDL and increasing HDL, it was assumed that improved cardiovascular health would result.

“This assumption-that understanding a system’s constituent parts means we also understand the causes within the system-is not limited to the pharmaceutical industry or even to biology.  It defines modern science.  In general, we believe that the so-called problem of causation can be cured by more information, by our ceaseless accumulation of facts.  Scientists refer to this process as reductionism……Once we find the cause, of course, we can begin working on a cure.”

Over the years we have learned that our attitude toward cause and effect is perceptual and that causal explanations are oversimplifications.  We have learned to deal with the issue of causation through statistical correlation.  The central concept is statistical significance, which “defines a significant result as any data point that would be produced by chance less than 5% of the time.”  But significant correlation does not necessarily equal cause.  “While correlations help us track the relationship between independent measurements, such as the link between smoking and cancer, they are much less effective at making sense of systems in which the variables cannot be isolated.”  But the human body is extremely complex with inter-relationships between multiple pathways.  Mapping one pathway and identifying all mutations does not reveal interactions between multiple pathways that are connected.  This is why torcetrapib failed.

We are designing new clinical trials.  We are mapping all the pathways of various cancers.  By inference and statistical correlation, we think we have unearthed the driver mutations and core pathways that cause cancers, whose hallmarks have been identified.  Are we setting ourselves up for another torcetrapib?

When Less is More – Part II

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cancer, clinicaltrials, epatients, medicine, oncology, participatory medicine, pharma, research, twitter, value based medicine, wellness

In my last blog, I discussed the rationale behind and evidence supporting the United States Preventive Services Task Force’s (USPSTF) recommendation to discontinue routine PSA screening for prostate cancer.  Exceptions might be made in circumstances where men are at high risk.  In 2009, the USPSTF found that screening mammography offered no benefit to women in their 40’s.  Previously, screening was recommended every other year between ages 40-50.  Now it is suggested that women between 50-74 years of age be screened every other year rather than annually.  Pushback to all of these recommendations has been “animated” to say the least.  Finally, the annual PAP smear for cervical cancer has been challenged.  Rather than annual exams, the proposed change is every 3 years.

In her New York Times article of October 29, 2011 entitled:  “Considering When It Might Be Best Not to Know About Cancer”, Gina Kolata asks “What changed?”  Her conclusion is that new information is now available.  In regard to breast cancer, mammography finds the cancer in 138,000 women per year.  But between 120,000 to 134,000 have cancers that already are lethal, or cancers that are so indolent they require no treatment.  In the same article, the chief medical officer of the American Cancer Society, Dr. Otis Brawley, states the way we look at screening has also changed.  “No longer is it just, Can you find the cancer?…..Now it is, Can you find the cancer, and does finding the cancer lead to a decrease in the mortality rate?”  Factor in possible harm that can result from screening, e.g, surgical procedures for benign conditions, and increase in cost, resulting in a benefit/risk ratio that is upside down.

While researchers and clinicians are approaching screening from multiple angles, annual mammography has assumed an almost unassailable status from our patients’ point of view.  To many, screening is equated with prevention of cancer, which is untrue.  Tiring of hearing the unsubstantiated claim that “a mammogram saved my life,” Dr. H. Gilbert Welch and Brittney A. Frankel from Dartmouth conducted an analysis estimating a woman’s 10-year risk of developing breast cancer and her 20-year risk of death.  Their calculations included the added value of early detection and benefits from improvements in treatment.  It was concluded that of the 60% of women whose breast cancer was detected by mammography, only 3-13% were helped by the test.  This amounts to 4,000-18,000 women per year out of a total of 230,000 women diagnosed with the disease.  Conversely, of the 138,000 patients found to have breast cancer as a result of screening mammography, 120,000-134,000 are not helped by the test.  In turn, these numbers pale when put in the context that 39 million women have mammograms each year in the U.S.  So, when they did the numbers, claims that mammography saves lives really are untenable.  The paper by Welch and Frankel was published online on October 24, 2011 in the Arch Intern Med.2011.476.

For abstract, click here.

I agree with my colleagues that some women are helped by screening but the numbers are very low.  Also, the premise that early diagnosis saves lives has been somewhat diminished by improvements in treatment of aggressive and even advanced cancers.  Mammography has certainly improved our ability to diagnose breast cancers earlier as reflected by the marked increase in incidence of carcinoma in situ, i.e., pre-invasive cancer.  And these are not lethal cancers.  Do these facts justify the $5 billion spent on mammograms annually?  I think not.  But the reality is until these recommendations become standard of care, I doubt that many physicians would be brave enough to adopt these as policy in our litigious society.  That’s the sad truth.

Drug Shortages: A View From The Trenches

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cancer, clinical trials, clinicaltrials, CME, digital media, Dr Just, drug shortgages, elder wisdom, epatients, FDA, health, health 2.0, innovation, Just Oncology, kris ghosh md, medical education, medicine, oncology, Pacific Oncology, participatory medicine, pharma, physician, research, San Diego, social media, twitter, wellness

A few weeks ago, I had a discussion with Kris Ghosh, MD one of our local GYN Oncologists, (listen here).  We talked specifically about Doxil, the usual second line treatment for recurrent ovarian cancer.  We agreed that the lack of availability of the drug does limit options for these patients, with further increase in already heightened anxiety levels for patients and families.  Add to the mix the increase in stress levels of oncologists and our staffs trying to handle one more insult to a broken healthcare system.  In one patient who was due to start treatment I was able to substitute topotecan (Hycamptin).  Fortunately, she is responding and tolerating the agent very well. We had put her name on our list of patients who were waiting for Doxil when it became available.  So I was able to use the drug allocated to her for another patient with multiple myeloma. The only agent that had controlled his disease was Doxil. I guess the problem worked out well in these cases, but it appears that this shell game is going to become routine.  The question arises:  “Is this the harbinger of rationing cancer care?”

In my residency training in the late ‘60’s/early ‘70’s, I rotated through the Nephrology service when hemodialysis was relatively new.  Just like today, demand for the procedure far outstripped supply.  One of the factors taken into consideration in a negative way was anyone whose renal failure was due to diabetes.  That’s a lot of people!!  Obviously, we were very uncomfortable being put in that predicament.  Hindsight personalized this for me since my maternal grandfather died of sepsis after amputation of one of his legs for diabetic gangrene, my father died of every complication of diabetes and was hemodialyzed for 2 ½ years before his death, and I have type I diabetes and am on an insulin pump but fortunately no signs of renal impairment, yet.  I’m sure my father would never have been treated during my training years.  I’m sure our cancer patients experience similar anxiety and fear when faced our current dilemma.

Causes of shortages are multifactorial.  In Doxil’s case, the manufacturing plant in Alabama was struck by lightning during the tornado earlier this year.  Hard to believe but that’s the story.  Obviously an unpredictable Serious Adverse Event (SAE).  However, most of the chemotherapy drugs in short supply are older agents, e.g., bleomycin, cisplatin, cytarabine, daunorubicin, doxorubicin, etoposide, leucovorin/levoleucovorin, mechlorethamine, thiotepa, and vincristine.  Many are now off patent and therefore priced lower as generics; so not as profitable.  In some cases manufacturing of the drug was stopped in anticipation of newer and, of course, more expensive replacements.  One of the predictable side effects replacing old, cheaper drugs with newer, more expensive agents is pushback from payors who deny coverage/payment.  We then get on the authorization-denial-authorization-denial merry go round many times leading to a teleconference with the medical director of the health plan.  All this takes time and can delay treatment for quite a while, adversely effecting results.  Especially when used with curative intent and when there are no good substitutes, this is unacceptable.  Another complication is the emergence of a “gray market” where drugs from questionable sources pass through unknown hands to our offices at up to 10 times the usual price.  In the ‘90’s we called this brown-bagging.  Trying to keep inventory straight as to which drug from what source belonged to whom was an added challenge.

From the above, it is obvious that health care is big business.  An invaluable source of health care information is, therefore, the Wall Street Journal.  In last weekend’s edition I learned that “Roche Holding AG has stopped delivering its drugs for cancer and other diseases to some state-funded hospitals in Greece that haven’t paid their bills.”  This policy may extend to Spain, Portugal and Italy.  Patients had to purchase chemotherapy from private pharmacies and bring them back to hospitals for administration.  In the US, we find ourselves in a similar situation in that we can’t afford to purchase some drugs for our patients.  So drug shortages are a global issue involving different causes requiring different approaches directed to specific problems.

I found two articles helpful in defining the problem and proposing possible solutions:

1. Link, M., et. al.:  Drug Shortages Threaten Patient Health and Safety; HemOnc today, vol 12 no 15, August 10, 2011, pg 1, 10-12.
2. Johnson, P.E.:  Drug Shortages:  Impact and Strategies; JNCCN, vol 9 no 8, August, 2011, pp 815-819.

Surprise!!!

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clinical trials, clinicaltrials, CME, Dr Just, elder wisdom, Just Oncology, legacy, medical education, medicine, mentoring, oncology, Pacific Oncology, participatory medicine, pharma, physician, podcasting, research, San Diego, social media, wellness

As I was browsing through the Harvard Business Review the other day (seriously, this is not my usual reading material), I happened on an interesting article.  Actually, the piece was an interview in the “Idea Watch” section entitled:  “Defend Your Research; The Color Pink Is Bad for Fighting Breast Cancer”, HBR, pp. 30-31, July-August, 2011.  Professor Stefano Puntoni, an associate professor of marketing management at the Rotterdam School of Management, Erasmus University, was asked to explain the counter-intuitive findings of his research.  He stated:  “Our original prediction was boring.  My research partners-Steven Sweldens of Insead and Nader Tavassoli of London Business School-and I thought pink and other gender cues would make campaigns against women’s diseases, such as breast and ovarian cancer, more effective.  But we found the opposite”.

Perplexed, they delayed publishing their results and kept running tests.  After 3 years, the same basic finding was validated 10 times.  Initially, women who wrote an essay about gender were less likely to donate to ovarian cancer research than women writing gender-neutral essays (42% vs. 77%).  Then, breast cancer banner ads were placed on a website but not mentioned to the women viewing them.  When the site was feminine-oriented, 33% recalled the ads; when gender-neutral, 65% remembered.  The color pink turns out to be one of many feminine gender-cues, but prior to the 20^th century it was actually associated with the male gender.

Most importantly, “these findings seem to fly in the face of the marketing principle that you should build a strong brand that emotionally connects with consumers”.  So why is this?   Interestingly, ideas or concepts that are regarded as threatening or difficult to comprehend elicit defensive responses, mainly denial.  The color pink tends to connect women with the thought that they could die of breast cancer.  Another fascinating fact is that not all gender-cues result in defensive responses.  Mascara ads were placed on control websites and 76% of the gender-primed group recalled these non-threatening ads, even more than the control group (65%).  Additionally, gender-cues involving prostate cancer are not as threatening in men.  The author postulates that prostate cancer is more a disease of older men and has a longer natural history, i.e., it is not associated with impending fatality.

Finally, since pink is synonymous with breast cancer, “is there any way to preserve it but overcome the negative effect”?  Women found pink ads about breast cancer harder to read than more gender-neutral peach ads.  But, men found pink ads slightly easier to read.  One suggestion that results from this is “that seeing more men wearing pink as part of breast cancer awareness may start to break down the color’s effect as a gender cue”.  Another thought is that pink may empower men to donate more.  Obviously,  work in this field is very preliminary.

As a result of the above article, I tried to think of research where the opposite of the anticipated result was found.  Tamoxifen was approved for clinical use shortly after I started my practice in 1975.  It was marketed as an anti-estrogenic alternative to surgical oophorectomy.  Therefore, the concern was that it could lead to osteoporosis.  To test this hypothesis, studies were initiated in 1980 and completed 10 years later.  If anything, Tamoxifen resulted in slight reduction in the incidence of bone fractures.  But: surprise, surprise!!  Increases in endometrial cancer and deep venous thrombosis, occasionally leading to lethal pulmonary emboli, were found.  These complications led to the realization that the drug had estrogenic properties and was in fact a partial, not total, Selective Estrogen Receptor Modulator (SERM).

Quoting Don Miguel Ruiz from The Four Agreements:

“The Third Agreement Is Don’t Make Assumptions.  We have the tendency to make assumptions about everything.  The problem with making assumptions is that we believe they are the truth.  We could swear they are real.”

This is why we do research.

Victims No More

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It was 1967.  I was an intern in the UCLA-Wadsworth VA Rotating Internship Program when I reported for my physical as part of the Berry Plan deferment.  For the younger set, physicians and dentists could elect to delay military service until completion of their first year of residency training, and we could elect our branch of service we preferred to serve in.  I chose the Air Force.  On the History portion, I stated that I suffered with asthma since childhood.  Within short order, I was notified of disqualification by the Air Force, my Draft Board reclassified my status to IA, and I was drafted into the U.S. Army, losing my deferment!  I sought legal advice, pronto.

After one year of legal maneuvering, during which time an independent physician certified I should be disqualified from military service altogether, my attorney informed me that all appeals had been exhausted.  I had two options:  go in as a captain or be drafted as a private.  I elected the former.  His parting words were:  “At least you won’t go to Viet Nam.  Not with all the documentation”.  My orders read “Saigon”.  Modifying the Sinatra song:  “It Was” NOT “A Very Good Year”.

I resigned myself to serving my time in Viet Nam.  My wife and one year old daughter would live in Hawaii near her father during my tour.  But, my wife admonished me to try one more time to appeal what was obviously unfair.  So, before we left for Ft. Sam Houston, I humored her and called the Pentagon.  I explained the situation to a Major Baker who was new at his post.  He discovered that all of my records had been shredded!  I sent more copies of my documents to a panel of physicians for its review with no guarantee that their decision would change my orders.

On reporting to Ft. Sam, the entire new group was addressed by the commanding officer.  Sighting his rank (a bird colonel), we greeted him with the loudest groan I’ve ever heard.  But I’ll never forget his advice to us:  “Let’s face it, we gotcha.  You can be miserable all this time.  Or you can make the best of it”.  He went on to say that we would have one year (I had two) at a stateside base during which time we should avail ourselves of all the opportunities to do something other than practice medicine 24/7.  Two weeks later, I was called into the same bird colonel’s office and advised Major Baker had called.  I was not going to Viet Nam!  I’ve said a prayer for Major Baker every night since.  And I did everything reasonable to appeal the decision and then let it go.  No longer a victim.

My two years at the Rock island Arsenal were terrific.  One Sunday I was rounding at a local hospital when a general practitioner (that’s what the terminology was in those days) commented about the then recently enacted Medicare legislation:  “Mark my words.  This is the beginning of Socialized Medicine”.  From that point on, any proposal to organize our practices was met with suspicion.  We were victims of external pressures and resisted most changes to the status quo.

Over time, this attitude has shifted to a more proactive position, dealing with the situation at hand (i.e., making the best of it) and trusting in an outcome that can be managed.  I was impressed by an article entitled:  “Oncology patient-centered medical home and accountable cancer care” by John D. Sprandio, M.D. in the December 2010 issue of Community Oncology, Volume 7/Number 12, pp. 565-572.  This medical home model has been adapted to oncology from primary care as both are assuming more responsibilities for patient care and are under severe financial restraints.  For oncologists, the situation is complicated by “by the perverse methodology of paying physician practices for the drugs they administer after discounts from pharmaceutical companies-a model that has eroded over the past several years”.  A detailed description of the model is provided and successes to date listed, giving hope that we can deal with proposed healthcare reform in a positive manner.  Current and future challenges are discussed.  These include:

1. Assessing and improving value in cancer care.
2. Enhancing physician accountability.
3. Standardizing and integrating clinical care.
4. Encouraging payer collaboration.

The author concludes by stating:  “None of the other efforts that payers are considering provides a sustainable business model for community oncologists”.  It was refreshing to read a well thought out plan addressing present issues rather than the old whining and complaining of the past.  Rather than victims, we become survivors.