The Shell Answer Man

Tags

cancer, clinical trials, clinicaltrials, CME, digital media, evidence based medicine, health, Just Oncology, oncology, participatory medicine, social media, twitter

By Richard Just, MD

Over the past 37 years in practice, I’ve received thousands of requests from patients, family and friends to interpret results of clinical trials.  These requests have increased dramatically with the advent of the Internet.   Many of these reports involve poor trial design or are inappropriate for the patient under consideration.  Sometimes I’ve mumbled to myself “I feel like the Shell Answer Man”.  For those too young to remember, I’m referring to a Shell Oil Co. ad beginning in the 1960’s in which the ‘Shell Answer Man”, replete in his Shell gas station uniform, answered common questions about driving and the uses of gas and oil. He just memorized a script; sometimes I wish I had one.   

Over Labor Day weekend, while in Chicago for a family event, we turned on TV to catch up on the day’s news. As fate would have it, we stumbled upon a healthcare segment on the NBC affiliate.  The reporter was listing items individuals should consider in evaluating results of clinical trials.  It seemed to me that knowledge of these items would be very helpful to people who are not healthcare professionals; people who need some way to filter trials worth pursuing with their physicians.  The following are those questions:

1. Are the patients in the trial separated into groups, with one receiving the drug or regimen being tested (“Experimental Group”) while the other is treated with the agent(s) considered standard treatment (“Controls”)?  These groups are many times labeled “arms.”  The Control Arm may be a placebo if there is no known standard treatment.  This does not mean the patient receives no treatment at all.  These types of studies are considered the “gold standard” of clinical trials in that they involve large numbers of patients who are followed for long periods of time.  This increases the likelihood that resultant findings are valid.  The downside is they take a long time to complete and are very expensive (about $1 billion from start to finish).
2. What is the total number of patients entered into the trial?  As alluded to above, the more the better.  If one study includes 50 patients while another 350 (all other factors being equal), place more trust in the larger trial.
3. What is the length of the study? In other words, how long are the patients followed? Again, the longer the better.
4. Were the patients included in the trial representative of the proposed population to be studied?  For example, if the population to be studied involves pediatric patients, someone over 18 years of age should not be entered into the trial.
5. Who is funding the study? Pay attention here. If the study is paid for by the company who developed the experimental agent, how likely are they to give a completely unbiased report? Of course we want to assume that they will, but unfortunately, some won’t.  A government supported trial is more likely to report balanced findings than an industry funded one. The reporter added that patients should note what the authors say about their study, i.e., do they make overly optimistic claims for their treatments?  Most investigators add some type of cautionary note, like “the proposed treatment looks promising pending further studies.”  This disclaimer recognizes that no study is perfect.  In fact, there has been a marked increase in the number of studies initially reporting positive results that were retracted when similarly designed trials were subsequently negative.  The end result has been a delay in patients receiving appropriate treatments and a horrible waste of money.
6. I’m adding this one on my own. I’ve noticed that one of the most common mistakes people make is to search for clinical trials involving the wrong cancer, not realizing that we identify cancers by their organ-of-origin, not the organ where they spread (metastasize).  An example would be to collect articles about liver cancer instead of colon cancer that metastasized to liver.

As chairman of our hospital’s Investigational Review Committee, I and our members are in charge of reviewing proposed clinical trials conducted in our hospital district.  The above factors, as well as many others, are considered before studies are approved, denied or amendments recommended.  Consideration of the items discussed above could save everyone a lot of wasted time, and even lead to the retirement of the Shell Answer Man.

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Why Cancer Research Requires Constant Vigilance

Tags

cancer care, clinical research, conflict of interest, evidence based medicine, oncology, publish or perish, scientific fiasco

By Richard Just, MD

One of my favorite writers on medical subjects is fellow ASCO colleague George W. Sledge, Jr., M.D.  I make it a point to read his essays in Oncology Times as they are always informative and well written.  One that caught my eye appeared on May 25, 2012 entitled “Fraud, Poor Ingredients, and Shortcuts in Cancer Research.”  Also in that issue is an article by Wendy S. Harpham, M.D. called “Scientific Fiasco.”  Whoa!!  Worth a second look. 

The three examples of fraud cited by Dr. Sledge all involved deliberate falsification of data and elaborate attempts to cover up deceit.  In fact, they could have been the basis for episodes of “Law and Order.”  Interestingly, these examples all occurred at respected academic institutions:  the University of Montreal in Canada, the University of Witwatersrand in Johannesburg, South Africa, and Duke University in North Carolina.  The most severe consequences to patients occurred in the South African example.  A toxic and sometimes lethal treatment (high dose chemotherapy + bone marrow or stem cell infusion) was given to women with breast cancer who should have received less toxic standard chemotherapy.  The toll in injuries and deaths that resulted was enormous.  The other two cases also impacted highly respected research institutions: the National Surgical Adjuvant Breast Project or NSABP was closed down for two years pending audit of all their trials, and Duke had to repay all grant money given to the researcher and suffered severe damage to its reputation.  Sad, but fraud and greed are an international phenomena, even in the field of cancer research.

As Dr. Sledge states:

My major concern with fraud is how long it takes us to catch on.

How can we prevent these atrocities from occurring? One would think that our peer-review process would be a good place to start. But as Dario Maestripieri explains in his work,  Games Primates Play, as cited in Dr. Harpham’s article, academic politics get in the way. Because of the need to “publish or perish”, some reviewers will review anonymously in order to trash the competition to give themselves an inside track. Obviously, when there is transparency and all reviewers are named, the review is less likely to be slanted and more likely to be honest and fair. Even more insidious and dangerous is when researchers and others in the industry of cancer research take shortcuts.  Basic sloppiness is responsible for the epidemic of retractions of published papers when initial reports cannot be validated in different labs or institutions.  The system encourages “getting published first rather than getting the science right.”  This type of behavior is unfortunately common. Again, it is sad that this takes place in an area that is supposed to be concentrating on the health and safety of human beings.

The issue of faulty cell cultures and contamination of tissue samples, which I’ve written about in previous blogs, result in poor ingredients.  An extensive article in Wired Magazine a few years back documents how antiquated our tissue storage techniques are, and that a high percentage of specimens are no longer suitable for research purposes when needed.  The entire field of Individualized or Personalized Oncology (indeed Medicine in general) depends on viable tissue specimens that may require storage for long periods of time in tissue banks.  A related issue is actual contamination of cell cultures by HeLa cells, highly malignant and rapidly growing cervical cancer cells.   All this leads to inaccurate results and slows progress in the field.

The committee at each institution responsible for overseeing the conduct of clinical and laboratory research is the Investigational Review Board (IRB) or Committee (IRC). This is where the peer review process for research occurs.  I have been Chairman of our IRC for the last 24 years.  Clinical Research has become a complex industry, both scientifically and administratively, during this time period.  As a result, our IRC’s workload and responsibilities have increased dramatically.  It’s easy to see where items can “fall through the cracks.”  Since our charge is to protect the safety of research patients, eternal vigilance is mandatory.

My Struggles With Our Electronic Health Records System

Tags

cancer, creative destruction of medicine, digital media, ehr, emr, eric topol, healthIT, oncology

By Richard Just, MD

My group purchased our Electronic Health Records system (EHR) about 5 years ago.  We had 4 clinical practice locations (soon to be 5 ½) with 1 administration office.  None of these sites are close to each other.  A major reason for purchasing an EHR was, and still is, to collect and analyze all data from our entire practice for the purpose of determining outcomes of our treatments. In other words, we wanted to know how our patients were doing in all of our offices, which treatments were working and which were not, and then use this information to refine and practice the best medicine we could. This was the promise of EHR.

And so my nightmare began.  Some of my patients define nightmare as something you didn’t wish for and it never seems to end.  Volumes could not fully describe my experiences.  I’ll just mention one “glitch”:  I noticed that some of my notes were disappearing into the ‘ethernet’ on a seemingly haphazard basis.  Sometimes I could locate them in another section of the chart; other times I wasn’t so fortunate.  Despite my staff spending weeks trying to find the defect, we had no success.  Our vendor monitored my work processes for two weeks.  Again, clueless.  To add insult to injury, I was told that I was the only one experiencing this problem which, of course, I took personally.  Turns out the problem occurred only when I started my note before my Medical Assistant entered vital signs.  So we had the explanation, but no fix.  As a result, I wait for my MA to enter her data, which frequently delays my ability to see patients on time.  Recently, we have added 2 physicians to our practice.  One of them asked me what he was doing incorrectly that caused some notes to disappear. This time I had the answer!! What’s more, I was now informed that it was a system wide problem for which there was still no fix.

When I was a kid, there was a TV show called the Naked City.  When episodes ended, the announcer said: “There are 8 million stories in the Naked City; this has been one of them.” I do know that my story is just one among many. But it’s still so annoying.  Because of the flawed design of this particular EHR system, we have been burdened with huge financial costs resulting from lost time, the need for extra IT support, and the hardening of my right carotid artery. I don’t need the added stress in this era of decreased reimbursements for providing clinical care and chemotherapeutic agents.  One of my partners has gone back to hiring a transcriptionist rather than using the EHR.  Another is chronically behind in his data entry.  To this date, we are not set up to pool and analyze our data for outcomes.  Soon, we are beginning the gut-wrenching process of converting to a new, and hopefully more user friendly, system.

A few weeks ago, I had the pleasure and honor to have a conversation with Eric Topol, M.D. on ‘this week in oncology‘ radio radio show. We were both intrigued by two articles that recently appeared in the New England Journal of Medicine on this subject.  The first, entitled “Escaping the EHR Trap—The Future of Health IT”, discredits the myth propagated by EHR vendors that health IT is different from industrial and consumer IT.  The authors suggest that vendors have alleged this to be fact “in order to protect their prices and market share and block new entrants.”

The second article is also quite enlightening:  “Unraveling the IT Productivity Paradox—Lessons for Health Care.”  In the 1970’s and 80’s, many industries adopted computers with the expectation that they would increase productivity.  To everyone’s surprise, digitization resulted in a significant reduction in efficiency. This was called the Productivity Paradox.  Subsequent research revealed that productivity attributed to computerization was underestimated due to defects in measurements, mismanagement of processes (such as summarized in the “glitch” in my system above), and poor usability.  Most systems, including mine, don’t have spell-checking capability.  Unbelievable!!

In chapter 7 of his must read, “The Creative Destruction of Medicine”, Dr. Topol discusses the benefits and challenges of Electronic Health Records and Health Information Technology in detail.  Despite the fact that digitization initially can be associated with an increase in errors, which doesn’t ease my pain, and many other challenges, he concludes:  “While some may consider the topic of electronic medical records prosaic, it should now be abundantly clear that their ultimate adoption and full interoperability will prove fundamental to the future of medicine.  Only via full electronic convergence can all the tools of digital medicine be in sync and immediately useful.  With the torrent of individualized data flow that is coming from whole genome sequencing, remote physiologic monitoring, and medical imaging, electronic information storage and processing will become more essential than even envisioned today.”

I have to agree with him. While this current transition period can be a frustrating, even painful experience, the alternative of a failed health care system is unacceptable.

CDC Cancer TweetChat

Tags

cancer, CDC, epatients, medicine, oncology, social media, survivorship, Tweetchat, twitter

By Gregg A. Masters, MPH

On Tuesday June 19th, 2012 from 2:00 to 3:00 PM Eastern the Center for Disease Control’s (CDC), aka @CDCgov, Division of Cancer Prevention and Control aka @CDC_Cancer  hosted a ‘Tweetchat’ on cancer survivorship. Subject matter experts including Blythe Ryerson, MPH and Dr. Elizabeth Rohan moderated the session and answered questions posted via the Twitter hashtag #CDCcancerChat.

The stats tracked represent Tweets posted to #CDCcancerChat hashtag in the 24 hours before and during the actual Tweetchat and certainly represent an impressive potential reach of the message!

The ‘Cancer Survivorship’ Tweetchat began with the following Tweets:

Below are  the influencers:

 

 

 

 

 

 

The last series of ‘long tail’ Tweets are represented below:

Clearly we are early in the application of social and/or digital media to influence, shape if not resolve many lingering chronic healthcare financing, delivery and public health concerns. Kudos to the CDC!

For recent timely topical reflections from @chemosabe1 aka Dr Just, click on ‘Cancer Survivorship.’

China: A report from the journey

Tags

cancer, digital media, evidence based medicine, integrative oncology, medical education, oncology, participatory medicine, physician, social media, Traditional Chinese medicine, wellness

By Richard Just, MD

China is nothing like I imagined! The evolution of healthcare mirrors major events in Chinese history.  Traditional Chinese Medicine (TCM) dates back 5,000 years when the first documentation appears.  What is currently called TCM goes back 3,000 years, and was essentially passed from one generation to the next.  Another factor that resulted in fragmentation of medical practices was that China was a feudal society whose states were constantly at war with each other.  The emergence of the Qin state resulted in a single state system with a single script and standardized weights and measures.  But their reign was so oppressive it lasted only 15 years, overthrown by the Han Dynasty in 210 BC.  During this time fragments of the Great Wall were fused into one continuous structure, and the underground mausoleum of the terra-cotta warriors was constructed near modern day Xi’an which was China’s capitol at that time.

In my mind, China was still a monolithic society under a Communist regime and TCM was available to the masses while western medicine was for the ruling class.  Well that’s not exactly the case.  Prior to 1949, there had been a widening chasm between those who had access to healthcare and most everyone else who didn’t.  When the Party came to power, most workers were employed by the government and had access to healthcare.  All through the Cold War era, the only major leader who never left his country was Mao.  He was mainly concerned with unification of the country and building a strong infrastructure.  Many lesser officials did interface with the West, and when they returned with different ideas, the Cultural Revolution (1966-1976) ensued.

We all know that intellectuals, including doctors, suffered.  But Mao realized he needed some physicians to treat the population.  He also realized that TCM needed to be standardized so it could be disseminated to as many doctors as possible.  In this process, much of the practice of TCM was changed in China, but it continued as it had been practiced for 3,000 years in Japan.  In 1980, with the end of the Cultural Revolution, two policies were instituted that have resulted in major changes in society:

1. One child per family rule:  There are certain exceptions to this rule.  But, in general, if a family has more than one child they are fined, heavily.  And, if the practice continues, a sterilization procedure results.
2. Opening up China to western ideas and businesses:  One of the first businesses allowed into China was health insurance.  Hard  to believe but true.  What has resulted is a system resembling ours.  Government employees and  officials  have  government insurance, which is essentially free.  They have access to everything necessary for their care, and it is funded by taxing the entire population.  Non-governmental employees buy private health insurance which generally covers 70% of  costs, leaving 30% out-of-pocket.  These policies consume a  good  chunk of income, and are renewed for 25 years after which all costs are covered by Social Security and the government.  Again these funds derive from taxes.  Parents pay for healthcare of their children, and rural farmers who can’t afford insurance are eligible for something like Medicaid/MediCal with “bare-bones” coverage.  This latter situation is also not free.  Obviously, most young people prefer a government job.  These are hard to come by unless you know someone, and contribute to his “Red Pack.”  This is the local phrase for payola or bribe.

Does this sound familiar?  I found no one who felt the system was fair.  But I didn’t speak with a government official.

Meanwhile, my wife and I had a personal experience with TCM.  Prior to our trip, Dee Dee fractured two metatarsals in her left foot.  This was healing when we left.  But, I’ve dubbed China as the country of stairs.  Lots of walking and climbing.  This time both feet and ankles were extremely painful and swollen when we boarded the Yangtze River cruise.  Fortunately, there was a doctor on board who saw her the next day.  Her treatment consisted of acupuncture, acupressure, placement of antifungal patches on the tops of her feet and cupping.  Not what I learned in training.  It was recommended that she soak her feet and legs up to mid-calf level each night in very warm to hot water for 20-30 minutes.  The whole process lasted one hour and cost 550 yuan, equating to roughly 90 USD.  She was much improved by the following morning.  That afternoon, Dee Dee had a second treatment.  Both treatments were very painful, especially when the needles were inserted.  It turns out Chinese needles have a much larger bore than those used in the U.S.

We listened to a lecture on TCM given by the same doctor.  TCM involves not only acupuncture, acupressure and cupping, but also herbal medicine, Qigong, and Tai chi.  He discussed the use of TCM modalities in treatment of migraine and other headaches, motion sickness and back pain.  Every morning, the same Dr. John Lee gave Tai chi lessons on board, which we both attended.  The only excursion Dee Dee has missed was to the temples at Fengdu which involved over 500 stairs and inclined walkways.

Now for the big question:  “Is there any role for TCM in the treatment of cancer?”  He said that TCM is of little benefit in treating or preventing cancer, but may have some benefit as an adjunct to surgery or other conventional treatments.  More on this when we reach Shanghai.

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

Tags

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 On Screening: Barrett’s Esophagus

Tags

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.

@JustOncology Acquires Top Level Domain ‘TumorBoard.com’

Tags

cancer, cancer program, clinical trials, CME, digital media, evidence based medicine, innovation, medical education, medicine, oncology, physician, social media, tumor board

By Gregg A. Masters, MPH

Since the beginning of this blog, including @Chemosabe1 and @JustOncology Twitter participation, and the launch of ‘This Week in Oncology‘ on the BlogTalk Radio Network we’ve been developing the concept of @TumorBoard. The idea is to ‘up-level’ the traditional hospital based ‘bricks and sticks’ tumor board to the web for real time consultative access to peer sourced and evidenced based best practices.

Once the center piece of any community hospital with ‘cancer center’ aspirations, and a value added incentive for staff physicians to journey from the office to the hospital for either breakfast, lunch, or dinner as the case may be, for peer networking, education, including Category 1 accredited CME, and periodic guidance and support on difficult cases, the popularity of tumor board had waned somewhat. We believe this is due in part to the increasing complexity and demands on physician time particularly in community based practices.

Yet we reasoned, with the introduction of smart phones and devices such as iPads or their tablet derivatives, to the near universal prevalence of desktops and laptops in medical practices, plus a small but steadily growing interest and participation of physicians in social media applications, why not attempt to bridge the either/or ‘workflow divide’ via these ubiquitous devices and secured web based access?

We thought the experimentation to be well worthwhile, and that the technology, people and macro-economic trends were on our side. As a result, we met with several ‘infrastructure’ partners and vendors to evaluate the state of the art so to speak, and were pleasantly surprised. We have certain specifications and needs lined up but remain open as to our preferred relationship at this time.

To date, we’ve opened the Twitter account @TumorBoard, acquired the domain names TumorBoard.co and TumorBoard.tv, since TumorBoard.com was owned by someone else, though only in a ‘parked’ and passive status. But the ‘gold standard’ from a branding perspective remained the outside our reach dot com version. After some preliminary domain brokering exchanges, we finally settled on a price, and are now pleased to announce the acquisition of TumorBoard.com. We will be activating the site shortly.

There is lots more to come. So stay tuned!

A Glitch On the Road To Personalized Oncology

Tags

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.

Cancer Survivorship

Tags

12 steps, cancer, digital media, epatients, evidence based medicine, health, innovation, medical education, medicine, oncology, recovery, twitter, wellness

By Richard Just, MD

The fact that the term “Cancer Survivorship” is now part of our vocabulary is a testimony to advances made in management of these diseases.  Most cancer survivors, however, are not unscathed by the experience.  As I tell my patients, they won’t be entirely as they were before treatment.  How these issues are dealt with varies from person to person.  But, awareness that chronic problems may persist long after treatments end signals that even though we’ve won the battle, the war is not necessarily over.  We may need to address problems in the physical, mental/emotional and/or spiritual spheres.  After all, quality is as important as quantity.

Certainly, health care professionals are well trained to deal with physical issues.  Attempting to address the totality of needs in an organized manner is a recent phenomenon.  Certainly, in thinking about programs that have been successful in supporting people mentally, emotionally and spiritually, 12-Step Programs come to mind.  The Steps are compelling as they are for anyone affected by the disease alcoholism, including the alcoholic (A.A.) and the “caregiver” (Al-Anon).  Substitute “cancer” for “alcoholism.”  The value of The Steps is that they provide a guideline through the process of recovery.  In fact, I prefer the designation “recovery” over “survivorship” as it implies an ongoing process with relapses and remissions along the way.

At first glance, the verbiage doesn’t seem to be appropriate.  But, The Steps suggest four primary ideas:

• “We Are Powerless Over the Problem of Alcoholism.”  This notion of powerlessness is difficult for healthcare professionals, especially physicians, to accept.  The intention is that we as individuals have no ability to change attitudes and behaviors of others, but we do have control over ourselves.  Think the Serenity Prayer:

God, grant me the serenity to accept the things I cannot change, Courage to change the things I can, And the wisdom to know the difference.

In fact, this is a very empowering concept that releases each of us from worrying about issues that don’t concern us and address our energies to our own lives.

• “We Can Turn Our Lives Over to a Power Greater than Ourselves.”  Many find the idea of a Higher Power difficult to embrace, while others already believe in a Power greater than themselves, but feel that “God has deserted” them.  Both viewpoints hinder recovery as they tend to foster a victim mentality.  Personally, I dislike the designation “cancer victim” for this reason.

The slogan:  “Let Go and Let God” can also be very liberating, recognizing that The Higher Power is in charge of our lives and we are not victims.  The 11^th Step provides details:

Sought through prayer and meditation to improve our conscious contact with God as we understood Him, praying only for knowledge of His will for us and the power to carry that out.

• “We Need to Change Both Our Attitude and Our Actions.”  Both the cancer and its treatments can  result in distorted thinking.  Some are left with severe fatigue and pain; others with long-lasting memory deficits called chemobrain.  Anxiety and depression are not uncommon.  The possibility of recurrence is always present.  Some become angry and blame their situation on others.  Obviously, these behaviors can be self-destructive and ruin relationships.  In these difficult situations, a useful tool in 12-Step programs is sponsorship.  Having someone who has lived through similar circumstances and recovered always there for support and guidance is crucial for recovery.

• “We Keep the Gifts We’ve Received by Sharing Them with Others.”  Probably the most important concept.  Several studies have shown that participation in cancer support groups improves outcomes.  But many patients still are reticent to join.  Some prefer the privacy of one-on-one sessions with a therapist.  On the other hand, they lose the personal experiences of people who have experienced what they’re experiencing.  One compromise is to have a mentor or sponsor who has personal knowledge of the treatment guide the patient and family through the process.

For this reason, 12-Step programs rigidly subscribe to anonymity to encourage participation in meetings and sharing experiences with others.  The most important item in the success of these programs has not been identified, but several reports have suggested sharing at meetings as the major one.

I’m thrilled that we’re talking about Cancer Survivorship these days.  The fact that more people are living longer is very gratifying.  Therefore, formally addressing quality of life issues is the logical next step.  Incorporating 12-Step program concepts into Cancer Survivorship Programs, proven successful in other diseases, merits serious consideration.