I can’t believe I just said that … Activating the autocringe loop

Sometimes, I experience an internal conflict between the clinician/researcher in me, and the administrator in me.  Indeed, because of this split existence, there are some phrases that make me cringe even when I use them myself.  Taking a clue from the term in biology that means “self-activation,” one could call this an “autocringe loop.”  For me, an autocringe loop tends to occur most often when the clinician/researcher in me is listening to the administrator in me talking.  For example, I feel a very robust autocringe loop get activated when I hear myself say “no money, no mission.”

My cringe response to this statement is something I learned early in my career.   I, like many young faculty, would roll my eyes whenever an administrator mentioned a lack of resources as a reason for not supporting a request.  I saw great value in the work I was doing, and what seemed to me to be essentially unlimited resources all around me.  My goal was simple – to convince those who controlled the purse strings to understand the importance of my mission.  If they really understood, the money would flow and I could get on with my work.  Those who did not support my efforts were clearly misguided, and just didn’t appreciate the importance of what I was aiming to accomplish.  I still feel the same way at times, such as when seeking research grant funding from the federal government or advocating with my institution to provide more staff in our cancer clinic.

On the other hand, I now understand there are limits to resources at each and every level that can impact availability of support for even the most important and valuable proposals.   In my role as a cancer center director and on national committees, I participate in choosing how limited support should be distributed among many superbly designed proposals that address various aspects of our joint effort to reduce the burden of cancer.

As a clinician and researcher, looking for funding to support cancer care or cancer research often seems like wasted time when there are so many more important issues at the center of our mission.  As an administrator, I know that without the money, we can not address this mission.

So … I don’t think that I will be able to break my autocringe response to “no money, no mission” any time soon.  I still cringe when I hear that a very important effort can not be supported because of a lack of resources, while I also highlight the vital need for funding when talking to others about why a very admirable proposal can’t be supported.

There is an escape valve that sometimes helps me when I am caught in this autocringe loop.  After I say “No money – no mission,” I follow it up with “but … money is not the mission.”    Sometimes I listen and understand.  Other times, I just roll my eyes.

Disruption – usually challenging, often upsetting, sometimes beneficial

Last month I attended a series of meetings at the National Cancer Institute (NCI) in Washington DC.   As was the case many times this winter, weather created havoc with air travel.   This disruption caused me considerable anxiety as I rode to the airport after my last meeting.  I wondered if my flights would be delayed or cancelled.  As it turned out, I scrambled and got on a flight as soon as I arrived at the airport.  This flight was scheduled to leave earlier in the day but was delayed because of weather.  So …  I left Washington for home earlier than planned.  In this case, the disruption in air traffic worked in my favor.

Disruption of a different sort influenced my meetings in Washington where a common theme was the impact of disruptive technology on cancer research.  Disruptive technology refers to the new ways of doing things that disrupts or overturns standard methods or practices.  For example, information technology and the incredible improvement in our ability to understand cancer at the molecular level (that I have discussed in prior blogs) are having a major impact on cancer research. These disruptive technologies make planning for the future both exciting and challenging.

My first NCI meeting was a retreat where the Cancer Center Directors met with NCI leadership to discuss a broad range of cancer research efforts.  We considered approaches to sharing massive amounts of cancer genetic information that cancer centers across the country are generating on individual patients.  Our goal is to share this information so we can accelerate the speed of cancer research while also protecting the privacy and rights of individual patients.   Some of the concepts on the table are based on new disruptive technologies that were not even conceivable just a few years ago.

At the second meeting, I was part of a working group charged with providing advice related to prioritizing extremely large  clinical research trials designed to determine which type of “adjuvant therapy” (therapy given to reduce the chance of a cancer coming back) is best for patients with a given type of cancer. These trials are very expensive to run because they require a large number of patients and careful follow-up for many years until we know which treatment is best.  Cancer research is moving so quickly that it is possible the treatments we would like to compare in such trials today will be considered obsolete by the time the trials are completed.  Do we invest in a trial to figure out which of our current approaches to treatment works  best with the understanding that the value of the trial could be disrupted by new more effective treatments, or do we invest in research designed to create those better treatments for the future?  The potential for disruption makes this a very difficult decision.

The third and final meeting was the 22nd meeting of the NCI “Clinical and Translational Advisory Committee Meeting” where we provided advice to the NCI on a broad range of issues related to clinical trials. This committee reviews how clinical cancer research is done across the country, including research at academic cancer centers such as Holden and research taking place in the offices of private practice oncologists.  Rapid changes in health care are disrupting the traditional approach to clinical cancer research.  At the meeting, we discussed ways to assure the disruption caused by these changes is managed so it has a positive impact on our ability to conduct innovative clinical cancer research.

It was a productive two days, and we made considerable progress in determining the best way to try and take advantage of disruption.

There are some circumstances where disruption has no upside.  Underlying all of our discussions was the incredibly disruptive effect of the cuts in funding to cancer research support by the federal government.

And, those of you who are “road warriors” and travel frequently know that the disruptive effect of weather on travel is very rarely constructive.  Indeed, I only shared part of my travel story with you.   Although I was able to get from Washington, DC to Chicago earlier than planned, my earlier flight from Chicago back home to Iowa was cancelled.   In the theme of making the best out of a disrupted situation, at least it gave me time to work on my blog.

 

Required Forms Form

I spent a fair amount of time this past week filling out what seemed like an endless string of forms.  In addition, I was asked to review and approve some forms being developed by the Cancer Center.   This effort, and the date of April 1, led me to consider an additional form that, if broadly implemented, would limit the growth of required forms everywhere and so have a huge and positive impact on the efficiency of complex organizations (including cancer centers!).

Happy April Fool’s Day!

 

Completion of this Required Forms Form is required before developing a required form

1) Proposed required form

1A) Name of required form (must include a minimum of 3 undefined acronyms) ______________________________________________________________

1B) Unique identifier for required form (minimum of 10 figures with at least 3 capital letters, 3 numbers, and 3 symbols) ______________________________

1C) Confirm unique identifier for required form (minimum of 12 figures with at least 4 capital letters, 2 numbers, and 5 symbols) ______________________________

1D) Purpose of required form (optional) __________________________________

2) Information on required form developer

2A) Name (Last, First, Middle, Maiden, Alias, Facebook ID)_______________________________

2B) Department/Division/Section/Office/Cubicle number_____/______/______/______/______

2C) Provide answers to at least 3 of the following 4 items

  • 1st, 3rd and 7th digits of SS# ______________________________________
  • Maternal Great Grandmother’s Gender Male ______ Female ______ Other _______
  • Winner of the World Series the year you were born __________________
  • Color of socks worn last Tuesday* ____________________________________________

*May not select this option if you wear black shoes

Page 2 (Unique identifier) ________________ (Unique identifier backwards) ________________

3) Required form developer competency certification

3A) Required form design training
Date training completed (month/year/day) ___________

  • Location __________
  • Instructor _______
  • Instructor certification # _________

3B) Required form font selection training

  • Date completed (day/month/year) ___________
  • Location __________
  • Instructor _______

3C) Required form conflict of interest training*

  • Date training completed (year/month/day) ___________
  • Location __________
  • Instructor (if self, please enter “self”) _______
  • Instructor certification # _________

*Training must include addressing conflict if the individual developing the proposed form is subsequently required to complete the form

3D) Required form useless data long-term storage training

  • Date training (year/day/month) ___________
  • Location __________
  • Instructor _______
  • Instructor certification # _________

3 E) Location where record of completing required form useless data longer-term storage training is stored (must check 1)

  • Costa Rica ___________
  • Antarctica ___________
  • Lone Tree, Iowa ______

Page 3 (Unique identifier) ________________ (Unique identifier backwards) ________________

4) Information about those who will be required to complete required form

4A) Percent of individuals who have provided the same information on a different form

  • 100% _____
  • 98% ______
  • 96% _______
  • Other _________

4B) Relative work-load of those completing required form relative to those developing required form

  • Individual completing form has 2x responsibilities of form developer _________
  • Individual completing form has 1.5x responsibilities of form developer _________

4C) Projected number of required forms to be submitted

  • Forms Per Hour _____
  • Forms Per Day _____
  • Forms Per Week _____
  • Forms Per Month______
  • Forms Per year (calendar) _________
  • Forms Per year (fiscal) _________

4D) Estimated amount of time necessary to complete required form

As outlined in announcement about the required form

  • 5 minutes _____
  • 2 minutes_______
  • less than 2 minutes _________

In reality

  • 1 hour ______
  • 4 hours ________
  • greater than 4 hours ___________

5) Plans for data utilization
(Not required)

Page 4 (Unique identifier) ________________ (Unique identifier backwards) ________________

6) Certification

I hereby certify that I have read and accept the conditions outlined in the “Required Forms Form Agreement” (pages 6-457) and agree to hold the developers of the Required Forms Form harmless. I hereby assume all risks related to my responses in the Required Forms Form. I also accept all risks related to the Required Forms that will be developed as a result of completing the Required Forms Form. I release all rights related to the Required Forms Form and any resulting Required Forms to the developers of the Required Forms Form without exception.

Signature __________________________________

Date and time Required Forms Form completed (year/month/day/Greenwich mean time)

_________/_________/_________/___________

Notarization

Photo

DNA sample

We can’t let the Brain Gain go down the Drain

We are currently recruiting to bring new faculty physicians to the Holden Comprehensive Cancer Center, faculty who will help us care for our patients, teach, and conduct research. The faculty candidates we have had visit the University of Iowa have been outstanding, and we look forward to having a number of them join us this summer.

During this process, I have been struck by the number of superb applicants who began their medical careers in many other countries around the world, completed their medical training at top-notch programs in the United States, and now want to join our faculty so they can practice medicine, teach and do research in the United States (indeed, in Iowa). Uniformly, these individuals were at the top of their class in school, had the drive to come to the United States to pursue opportunities they did not have in their native country, and have been highly successful in their new home.  This represents a true “brain gain” for us.

Unfortunately, there are signs that this “brain gain” could turn into a “brain drain.” Historically, the United States has been the world leader in higher education and research. This has driven our economy forward, and helped attract the best and brightest to our shores.

Yet, in the past few years, US support for innovation has been flat or even dropped and other countries are starting to take up the slack (see an excellent short video on the innovation deficit at http://www.innovationdeficit.org).

The US is still, without doubt, the world leader in biomedical research – a fact that is confirmed by the outstanding pool of physicians from around the world who would like to join our team. In Iowa, ongoing success will be dependent on our ability to provide a congenial and collaborative culture, and the resources and infrastructure needed so our faculty and staff, including those born in the US and those who began their careers elsewhere, can work together toward our shared mission of reducing the burden of cancer.

Providing these tools and environment will have a positive impact on our ability to care for our patients, our ability to conduct research, and our economy. It will also reduce the worldwide burden of cancer as discoveries made by our team are disseminated beyond our shores. We need to continue to emphasize the importance of investing in innovation through education and research. That way, we can prevent the brain gain from becoming a brain drain.

 

What’s in a name? It’s personal and it’s precise

There is a great debate raging among cancer research leaders around the country.

  • It is not about whether this is an incredible time in cancer research that is fundamentally changing our understanding of cancer – we all see advances being made in our centers every day.
  • It is not about whether this enhanced understanding of cancer will change how we approach cancer medicine – we all see research advances that have resulted in dramatic improvements in how we treat many of our patients, and many more are on the way.
  • It is not about whether some cancers have proven to be incredibly difficult to treat – we all know there are some types of cancer where progress has been devastatingly slow.
  • It is not about whether increased funding for cancer research would speed up progress against cancer – we all agree that increased funding is needed to accelerate progress, particularly for the most refractory cancers.

So, we agree … We are making great progress in our understanding of the biology of cancer.   We are learning that cancer is incredibly complex, as is the response of the body to the cancer.  We are now able to test and identify the mutations that cause cancer, and are finding that every cancer is unique.    We are starting to use this information to identify the best possible treatment for each patient.  Support for cancer research is vital if we are to accelerate progress.

Then, what are we debating?  We are debating what we should call this new era in cancer research and cancer medicine.

Some feel the dramatic shift in cancer research and cancer medicine should be identified  with the word “Personalized” since we are improving our ability to identify the best possible treatment for each person.  On the other hand, cancer physicians have always sought to provide personalized cancer care and treat each patient as an individual based on their own medical and personal needs and perspectives, even when our knowledge of the biology of the cancer was more limited.

Others feel the term “Precision” is more appropriate, as it speaks to our goal of providing care that is precisely designed for each individual, and allows us to more precisely target the cancer.  “Precise” treatments that are specifically designed for an individual patient’s cancer should be effective and have fewer side effects compared to the “one size fits all” approach that often only benefits a fraction of the patients who receive treatment.   On the other hand (and there would not be a debate if there was no “other hand”), the term “Precision” is a bit cold, and does not convey the important recognition that we need to look beyond the molecules and consider at the whole patient when deciding what to recommend for each individual patient.

The discussion concerning which name best reflects the incredible change taking place, and the promise it holds for our patients, continues.

Personally, I lean toward the term “Precision,” but acknowledge I don’t have a precise rationale – it is a personal preference.

In upcoming blogs I will review some of the elements of the Precision Oncology program we are developing at Holden.

Mutations – beyond the X-Men

This week, I have been reviewing research grant applications for the National Cancer Institute, including a number of grants proposing detailed evaluation of the gene mutations that can cause cancer. After spending hours looking at figures and data, I needed a break from mutations and decided to watch a movie.  One that has been on my “I should see that someday” list for some time is “X-men.”   So much for taking a break from mutations.  For those of you who are not familiar with “X-men,” it features a group of mutant humans with unique powers.   There are good mutants and bad mutants, epic battles, heroes and villains, etc., etc.   I won’t go into the details of the plot, but simply say it is worth seeing if you like special effects and over-the-top science fiction action, but not so much if you are a stickler for scientific plausibility.

Nevertheless, the movie certainly solidified “mutations” as my theme for the day, and got me thinking about the nugget of scientific truth that is the basis of the movie’s plot – namely the good and bad of mutations.  So … I will put Wolverine, Sabertooth, and Magneto on hold for a moment, and talk about actual mutations.

The simple truth is that mutations happen in our DNA all the time (for those “scientific sticklers,” see a nice, brief review at http://www.nature.com/scitable/topicpage/dna-replication-and-causes-of-mutation-409 ).  The process of DNA duplication is incredibly accurate but not perfect.  When a cell divides, every one of the 3 billion base pairs in DNA is duplicated, and a huge number of cells divide in our bodies every day.  Even a very low error rate will lead to DNA mutations in some of our cells.   Most of these mutations have no effect.  In fact, every cell has molecular machinery that can detect and repair mutations.  Other times, a mutation that gets through will result in abnormal behavior of the cell.  Cells are programmed to commit suicide when something goes haywire as a result of DNA mutations.  The loss of a single broken cell here and there is not an issue and happens all the time.

The problem results when a mutation hits in just the wrong place, and results in uncontrolled growth and survival of the cell.  When those cells divide, the  mutations are passed on each time, so eventually you have billions of rogue cells that all have the same mutation and are no longer playing by the rules – this is cancer.  In fact , some mutations can be even trickier.  They can occur in the genes that repair DNA or in those that induce death of misbehaving cells.  Such mutations are truly evil in the eye of the oncologist, as the bad cells accumulate even more mutations and become harder to eliminate.

How can mutations ever be good?  If DNA duplication was perfect, we would all still be single cell organisms swimming around in the primordial soup.  Evolution is dependent on mutations.  However, mutations that provide an evolutionary advantage are incredibly rare.  Not only do they need to result in a change that improves the change of survival, they also need to occur in the “germ line” cells that are passed from one generation to another.  Thus, a lot of mutations need to occur for the occasional beneficial mutation to emerge.  The study of genetics has demonstrated DNA duplication is accurate enough to allow cells to divide and duplicate effectively, yet with just enough of an error rate to allow organisms to evolve over millennia.

As a cancer biologist and oncologist, it helps me to think of cancer as an unavoidable byproduct of imperfect DNA duplication, which itself was vital for organisms to evolve.    Simply put, without mutations, we would not be here.

So, I still have a bit of “X-men” on my mind but it is time to get back to reality.  Time to call on my inner Wolverine and get back to our battle to defeat the evil mutants known as cancer.

Can we ‘prevent’ cancer?

Is preventing cancer possible? Two announcements on opposite sides of the equation made me think a lot about cancer prevention this week.

The giant pharmacy chain CVS made the brave announcement that they will stop selling tobacco products even though sale of such products contributes to their financial bottom line. Tobacco is the leading cause of preventable cancer deaths. Reducing the convenience of buying tobacco is an effective way of reducing use. The CVS announcement was greeted by well-deserved and enthusiastic approval from a number of cancer organizations including the American Association for Clinical Research, The Association of American Cancer Institutes, the American Cancer Society, the American Society of Clinical Oncology and the Prevent Cancer Foundation.

Less encouraging were predictions of the growing world-wide burden of cancer. The National Cancer Institute, the American Cancer Society and the World Health Organization all predict the worldwide burden of cancer will nearly double by 2030 due to a growing and aging population, increasing tobacco use, increasing obesity, and the limited cancer prevention and early detection efforts in many parts of the world.

So … Can we really prevent cancer?  The short answer is, “yes and no.”

Yes – our choices have a major impact on our risk of getting cancer. More than 50 percent of cancer deaths are related to lifestyle choices. A healthy lifestyle reduces our chance of getting cancer.

No – we do not know how to prevent all cases of cancer. We all know stories of people who did not get cancer despite doing everything wrong – smoking, poor diet, overweight, never getting screened for cancer. We know of others who developed cancer despite doing everything right – no tobacco, excellent diet, exercise, following cancer screening guidelines. In fact, some folks use such stories to claim “we can’t prevent cancer” and continue poor health choices.

Because the word “prevention” can be interpreted as being absolute (“yes” or “no”), and therefore can be discounted, some advocates and organizations have advised use of the phrase “risk reduction” instead.

C-Change is one such organization. C-Change includes leaders from the private, public and non-for-profit sectors working together to eliminate cancer as a public health concern. It includes experts in marketing and advertising who have explored ways to communicate about cancer risk to a broad range of people (for more information, see http://www.c-changeprojects.org/CommunicationsPlan/CancerMessages.asp ).  I recently agreed to co-chair the group at C-Change that is focusing on comprehensive cancer control, and look forward to learning more about these efforts.

I also will be participating in a webcast panel discussion next week in Washington for the Prevent Cancer Foundation. We will be discussing funding for cancer research, including prevention research, in an era of fiscal restraint. It can be seen live at www.preventcancerwebcast.org on February 13 at 2 p.m. CST and will also be available online afterwards.

Whether we say “prevention” or “risk reduction,” encouraging and supporting healthy choices at home and abroad will be vital to reducing the worldwide burden of cancer.

Meanwhile, I need a small notebook to track my weight and exercise routine as I try to reduce my own risk of cancer and remain as physically fit as possible (not so easy this winter). I think I will make a special effort to pick one up at CVS.

 

Congratulations to Dr. Raymond Hohl

Earlier this month, Dr. Raymond Hohl, the Holden Family Chair and Associate Director for Clinical and Translational Research at the Holden Comprehensive Cancer Center, announced that, starting March 1, 2014, he will be moving to Penn State to become the Director of the Penn State Hershey Cancer Institute.   Ray has been at the University of Iowa since 1991, and has served multiple roles in the Cancer Center, Department of Internal Medicine, and many other units on campus.  The breadth of his clinical and research knowledge and interests made Ray a valued leader and collaborator in many of the activities at Holden.  As a physician, his dedication to his patients was unquestionable.

It is difficult to say goodbye to an esteemed colleague.  At the same time, we are excited for Ray as he pursues this new opportunity.  This is not the first time we have had a senior leader from Holden depart to assume responsibility as a Big Ten Cancer Center Director.  Dr. Timothy Ratliff, formerly Deputy Director for Cancer Research at Holden, left Iowa to became the Cancer Center Director at Purdue in 2007.

We wish Ray success in his new position and look forward to continuing to work with Ray and Tim through collaborative efforts such as the Big Ten Cancer Research Consortium.   While the departure of valued colleagues is difficult, it is gratifying to see them advance and contribute in new ways to our joint efforts to reduce the burden of cancer.  We can also take more than a bit of pride in seeing the “Iowa way” spread across the Big Ten.

Lump or spread?

Sometimes, progress brings uncertainty.  The past few years have seen a steady increase in the number of drugs and other approaches to cancer treatment such as immunotherapy that can be used to treat cancer.  Most of these new approaches do not cure cancer when given as a single therapy.  Nevertheless, many of them are very effective at inducing a temporary shrinking of the cancer.   For many cancers, we have a number of such treatments available.  From a physician’s point of  view, these new treatments create more options for patients. But they raise  a question that cancer doctors have struggled with for decades.  Do we …

“Lump” treatments together and use them all up front at the time of diagnosis;

or

“Spread” treatments out over time and use them one by one as the patient needs them.

There are advantages and disadvantages to both approaches.

Lump

Advantage – There is evidence that using multiple treatments that kill cancer cells by different mechanisms can result in long-term remission or even cure that can’t be achieved if the drugs are used one by one.

Disadvantage – Giving multiple treatments together often increases a patient’s side effects, and leaves fewer options if the cancer returns.

Spread

Advantage – Giving treatments one by one is generally better tolerated by patients rather than using them together, and provides a series of options once a given treatment is no longer working.

Disadvantage – Giving treatments as single agents reduces the chance of a prolonged period of remission or even the possibility of cure.

As with so many questions in cancer medicine, the clearest answer as to whether to lump or spread cancer treatments in a given scenario comes from clinical trials.  The challenge is that trials comparing lumping to spreading are difficult to conduct and often have to run for many years before we know which approach is better for a given type of patient.  Indeed, for some cancers, it takes decades before we know if we have really cured patients by lumping treatments together.  By the time such studies mature and provide us with an answer, we often have new and better treatments available.

The professional debate on which approach is best can be lively with informed experts often disagreeing.   When making a recommendation for an individual patient, cancer doctors weigh the available data and use clinical judgment that takes into account the unique health and personal needs of that patient.   I am more likely to lump treatments together and aim for a prolonged remission or the possibility of a cure in a young patient who is otherwise healthy and can tolerate the side effects of such treatments.   For an older patient with multiple other health issues,  I am more likely to spread treatments out so they are better tolerated and only used as needed.   The personal perspective of the patient and their loved ones is also important.  Some are willing to risk severe side effects for even a small chance of prolonged remission or cure, while others elect to focus on quality of life.

When determining how to leverage progress in cancer research to help an individual patient, there is still much to be said for the art of medicine.   The words “lump” and “spread” are sometimes used in discussions between a cancer doctor and a patient in describing a cancer.  A thoughtful and informed doctor also weighs the available data, and works with the patient and the family to use these words in another way, so together, they can decide whether to “lump” or “spread” treatments is the best approach.

 

One piece can change a picture

A picture can be made of many different pieces. Sometimes, a change in a single piece has the potential to change the whole picture. For me, such a picture came together in late December when…

  • I spent the second half of the month in University of Iowa Hospitals and Clinics taking care of patients with leukemia.
  • Congress passed a budget that will prevent another partial government shut down. While everyone involved agrees the deal that was reached leaves much to be desired, it will replace the arbitrary funding cuts in government programs known as the “sequester.”
  • I traveled to Washington, DC for an important meeting as a member of the National Cancer Institute “National Clinical Trials Network Working Group.”

How do these pieces fit together, and what does the resulting picture show?

  • Taking care of patients with acute leukemia reminds me of how far we have come over the past few years in our understanding of the biology of leukemia. However, it also reminds me of how far we have to go with respect to treating many leukemia patients. Additional advances for these patients are within our grasp but will only come through investment in research. For me, this piece of the picture highlights the importance of research if we are to improve care for our patients.
  • With the current dysfunction in Washington, funding for biomedical research in general, and cancer research in particular, has been shrinking steadily for the past few years. The sequester took another big cut out of the cancer research budget. Politicians across the political spectrum say they are supportive of cancer research, but have not been able to get past their differences to actually support it. For me, this piece of the puzzle highlights how important it is to get priorities straight.
  • A major focus of the Working Group meeting I attended in Washington was to advise the National Cancer Institute on which types of clinical cancer research studies to support. Implicit in this recommendation is a discussion of which types of studies should not be supported. This is particularly important but also painful because of the shrinking pool of funding for cancer research. This piece of the puzzle highlights how not getting priorities straight can have real-life consequences.

These pieces come together to tell a pretty bleak picture: We are losing an opportunity to speed progress in cancer research and help more of our patients because of a lack of research funding.

However, another picture is possible. It is possible the latest budget agreement will lead to appropriation of funds that result in a leveling out, or perhaps even an increase, of support for cancer research. If the decision to pass a federal budget is followed by a decision to appropriate more funds for cancer research, then the overall picture is brighter indeed.