Sunday, September 30, 2012

Whose opinion matters in medical decision-making?

Caring for patients involves the formation of multiple opinions. Traditionally, the patient's physician generates the first opinion, with other clinicians offering second opinions. However, an opinion at least as important must also be recognized in this traditional rubric—that of the patient and family members. Just as the conscientious health care practitioner is constantly reformulating his or her opinion based on many factors, so too is the patient.
 --Recognizing an Opinion: Findings From the IOM Evidence Communication Innovation Collaborative JAMA. 2012;():1-2. doi:10.1001/jama.2012.13369

How important is the opinion of the patient and/or family in medical decision-making? And how can these opinions and preferences be better integrated into clinical care? A discussion paper published this month from the Institute of Medicine (IOM) entitled Communicating with Patients on Health Care Evidence attempts to tackle these questions and other issues related to improving the quality of medical decisions. The impressive list of authors, who are all thought leaders in areas as diverse as academic medicine, public policy, and consumer empowerment, were participants in the "Evidence Communication Innovation Collaborative of the IOM Roundtable on Value & Science-Driven Health Care." (Now, there's a title.) Props to the IOM for releasing the full text of the paper as a freely available PDF and to JAMA for posting the Viewpoint summary article from Novelli et al also with free access to full text. 

A few key takeaways from the report:

  • 8 in 10 people want their provider to listen to them.
  • 8 in 10 people want to hear the full truth about their diagnosis.
  • 7 in 10 people want to understand the risks of treatments.

  • 8 in 10 people want their health care provider to listen to them, but just 6 in 10 say it actually happens.
  • Less than half of people say their provider asks about their goals and concerns for their health and health care.
  • 9 in 10 people want their providers to work together as a team, but just 4 in 10 say it actually happens.
The report defines the three components of informed medical decisions as medical evidence, clinician expertise, and the patient's goals and concerns. In Figure 4, survey data are shown demonstrating that patients place nearly equal weight on each of these, with a slight edge to medical evidence as the leading component. Interestingly, women were somewhat more likely than men to say that their personal goals and concerns were "very important" (64% vs. 50%).

In addition, the following language was deemed in patient interviews and focus groups to "resonate best" in regards to medical evidence:

Making sure you get the best possible care starts with you and your doctor making the best decision for you. Your doctor can help you understand what types of care work best for your condition, based on medical evidence. Because there are always new treatments, doctors use this evidence to keep up with which work best. Your doctor's experience helps him or her evaluate and apply the evidence to your situation. The doctor also needs to listen to you so he or she understands your values, preferences, and goals. This is important because every patient is different, and when there are options, it is important for the doctor to know what is important to you.

In the conclusion, the authors call for the following actions:
  1. Cultural changes - providers should recognize existing gaps and adopt decision aids when available and other tools, including mobile technologies, to facilitate the presentation of knowledge and care coordination
  2. Incentive alignment and infrastructure support - patient-centered medical homes and EHR's that promote "meaningful choice" are singled out
  3. Quality standards and accountability - including a suggestion for professional licensing/accreditation bodies to incorporate criteria encompassing patient-centered medical decision-making
So is there anything new here? And what are the lessons for oncologists in particular? As a busy clinician in a breast cancer practice at an academic medical center who every day tries to guide patients through difficult decisions - whether or not to receive adjuvant chemotherapy for an ER positive cancer, whether to enter a Phase I trial when conventional options are exhausted for refractory disease, whether to be hospitalized for IV hydration or pursue a purely palliative approach at home with hospice - my first reaction, and admittedly not my best reaction, is to go into Defensive Mode. Of course, I always consider patient preferences. Of course, I always give people the full truth about diagnosis and prognosis. Of course, I explain risks adequately. And so on. But based on this paper and numerous other examples, it doesn't take much self-reflection to acknowledge that my colleagues and I probably aren't hitting the mark nearly as often as we would like to give ourselves credit. The one concept from this paper that resonated the most with me was the emphasis on the idea that patients want to know all of their options for a given decision, not just the ones that I as the provider favor. Using the example of trying to decide whether to administer adjuvant chemotherapy for an ER positive, node negative breast cancer (let's make it more complicated and say the Recurrence Score is 22, and there's no trial avaiable), what options might I present to a patient, who is otherwise fit for chemotherapy and willing to receive it? Well of course I tell them that tamoxifen or an AI alone may very well be sufficient treatment. And then after trying to put the use of adjuvant chemotherapy into an historical perspective, I discuss with them the option of a standard regimen like TC x 4. I do usually tell them that no systemic treatment is also an option, although not one I advise. And within the limits of our knowledge and predictive ability, I try to estimate the risk of recurrence and the potential benefit of the intervention in numerical terms, trying to emphasize absolute benefits instead of relative. (I confess, I have been known to start the conversation by saying that an AI will "cut the risk of recurrence by half." I'm not immune to sound bites.) But along this vein, do I give them the option of TAC x 6, even if in my opinion the potential benefit is not high enough to justify the greater toxicity of a 3rd generation regimen? Not often. Do I mention regimens that I just don't use, like CMF or M->F, knowing that there are a few places that still do use them, and there is some evidence to support their use? No, I don't. Or do I regularly discuss a possible role for adjuvant bisphosphonates, recognizing they are not FDA approved for this indication, and I am personally not convinced that we have enough data, even in postmenopausal women, to demonstrate a net benefit? No, not usually, unless asked.

Why don't I do these things? I suppose I partially justify it by saying that I simply can't recommend and discuss as a viable option a treatment that I don't feel passes my own evidence test - not necessarily my own experience. And, being realistic here, time constraints do play a role. In a perfect world, a new consultation would last 2 hours, 3 hours, or however long was needed to convey all of this information, or would extend over multiple visits. But if I did that with everyone, my new patient slots would dry up, and it would take weeks and weeks to get an appointment with me, which means the next patient needing consultation would be kept waiting in frustration. Furthermore, no matter how skillful a presentation of options is in a clinical encounter, a recitation of treatment choices rendered without context or hierarchy is frequently meaningless and confusing to even highly sophisticated patients. So does this mea culpa make me a non-patient-centered oncologist, and guilty of the failings described in the IOM report? Like most of us I would hope, I have an infinite capacity for self-criticism and second guessing, so I suppose the answer is that, yes, at times I indeed need to be more mindful of the alternative approaches and considerations illustrated in this piece. But I offer this reflection to illustrate how complex and nuanced the physician perspective is in the spectrum of informed decision-making. 

Lest my comments be interpreted as critical of IOM or suggesting this discussion paper is some ivory tower assessment devoid of the realities of practice in the modern era, far from it. I salute the IOM for focusing on this issue with the right combination of balanced analysis and practical suggestions. I will try to reflect on the recommendations they put forth in all of my patient encounters this week and put the principles of patient engagement front and center. I challenge all of my clinician colleagues reading this blog to do the same. And to our patients in the difficult situation of being on the receiving end of these discussions, I salute you and recognize you are the ones thrust into this situation unwillingly and often with little time to prepare for such weighty decision-making. Help us your caregivers help you. Tell us what you need and when we have failed to include you.

Wednesday, September 26, 2012

I'm on BlogTalkRadio 9/26/12 5PM EDT with Dr. Richard Just

I'm honored to be asked to appear on Internet radio with San Diego area oncologist and social media triple threat Dr. Richard Just, Wednesday 9/26/12 5:00 pm EDT for a 30 minute chat ranging from social media for oncologists to breast cancer. You can listen in live here. And be sure to check out Dr. Just's lively Twitter stream with the handle @chemosabe1 (wish I'd thought of that one) and blog

Saturday, September 22, 2012

The Virtual Choir

[This weekend, while trying to work on my Department of Medicine Ground Rounds talk at UC Irvine for next month ("#UCIMedGrandRounds – Social Media and the Digital Physician"), I've been listening to some soothing Eric Whitacre pieces with hopes that it would inspire me to get most of my slides done. Not sure that is working yet, but it inspired me to share a blog I did for ASCO Connection earlier this year about artistic vision, collaboration, and illness.]

In a previous life I used to be a church musician. I started piano in the 1st grade, and since I attended a pretty traditional parochial elementary school, it was natural to gravitate in this direction. Over the years I’ve been involved in church and school choirs as a pianist, organist, singer, arranger, composer, and conductor, and I did this in high school, college, med school, and beyond, as recently as about four years ago. Lest you confuse me with someone with real talent, let me say I was never classically trained and I would probably embarrass myself pretty badly today if I tried to perform anything complicated. But I’ve long maintained my love for classical choral music, both sacred and secular, and I’ve always greatly enjoyed listening to choral works on my iPod.

A few years ago, while browsing the iTunes store, I discovered a composer and conductor named Eric Whitacre, who has had a somewhat meteoric rise to fame and international acclaim in this genre. He has an interesting personal story. He grew up in rural Nevada in the ‘70s-‘80s and attended UNLV, not exactly known as a powerhouse for classical music. As he tells it, even though he could sing, he couldn’t read music when he started college. On a whim, he joined a college choir and almost immediately had a transformative experience with the music and the blending of voices that led to a BA in music, then a Masters at the Juilliard School, and over the next 20 years lavish praise, fame, and multiple awards as a prolific composer and conductor of choral and symphonic music. I’m sure it doesn’t hurt that, now at 42, he is described as “boyishly handsome” and is an articulate and passionate speaker. His music is known for its dense harmonies, dissonance, and unusual rhythms. I find it very beautiful and challenging. But what I really found fascinating was an experiment he started in 2009 with something called the Virtual Choir. It’s probably easier to watch this 11-minute “TED Talks” video, which went insanely viral last year, than read my summary, but I will try to be brief. It seems that a young girl sent him a fan video on YouTube of her singing the soprano part to one of his pieces called Sleep. He was struck by the tribute, and he recognized the purity and sweetness of her artistry. He then had an inspiration about how to harness the creativity of multiple other would-be performers who might be singing to their video cameras and uploading to YouTube, hoping to create something beautiful that would make them famous. So what he did was to put out a call, using social media, encouraging singers all over the world to video themselves singing one of the parts of his work Lux Arumque. He ended up receiving almost 200 hundred videos from a dozen countries. Then with a collaborator, he assembled his Virtual Choir into a single video, with himself conducting these virtual voices, and the results are, well, astounding. He went on to produce Virtual Choir 2.0, with over 2,000 separate singers from dozens of countries, and then just this week released the video of Virtual Choir 3.0, with 3,746 singers from 73 countries performing his work Water Night. I know you are busy people, but take 30 minutes out of your evening to view all three of these videos. Even if you are not a fanboy like me, the artistry is remarkable, and the music sublime and exhilarating.

So what in the world does this have to do with medicine, oncology, or ASCO Connection? As I followed this story, it struck me how there are some parallels with health care and the experience of illness. In the Virtual Choirs, Whitacre and thousands of others with the common interest of choral music were coming together to share an artistic vision and create a larger work. While each singer was recording an individual vocal track in the privacy of his or her own bedroom, there was an undeniable social connection. The need to connect with other people who share our interests and experiences is one of the strongest forces of our humanity. And I see this every day in the practice of oncology. Yes, this is the era of personalized medicine, but so many of our patients have a fundamental need to connect with other patients and families that are going through the same thing they are, a need that we as health professionals can’t possibly fill. People need to learn from each other in a social and collaborative fashion, and the wonders of the Internet and the explosion of so many social media channels today have enabled this to a degree never before possible. Much research has confirmed this, and while patients will usually come to their physicians for the authoritative voice we have, they still need to process this knowledge through the filter of other people. As oncologists, we would be foolish to deny this reality, and I would maintain that a much greater good could come from our efforts to facilitate it, if not harness it for a larger purpose.

But for us as physicians, it’s more than simply allowing patients to share their war stories and their tips on dealing with treatment, with some type of blind but vaguely disapproving eye. I think this social urge is a greatly underutilized resource for discovery. Think of the whole concept of patient-reported outcomes. As physicians, we know or should know that we generally do a lousy job in assessing the patient experience of illness. In our field this very pointedly is the patient experience of treatment toxicity, fear of the disease process, and loss of control. The data are so much better when we let patients tell their stories directly. And think how easy it would be to enable this with all of the simple and widely accessible technologies available today, like YouTube and cell phone texting. As investigators, we could create our own Virtual Choir of our patients, individually and collectively, contributing content that we can amass and analyze for trends and causality. Think how simply elegant an experimental design could be. Say we wanted to know the temporal trend of patient-rated bone pain following a Neulasta injection. Sure, we think we know this from existing clinical trial data, but mostly it’s what we’ve asked our patients to tell us. What if we told every breast cancer patient getting dose-dense AC starting on day 2 of each cycle to text an integer value from 1-10 corresponding to their level of bone pain to 11435? And what if the data were displayed real time on a website that refreshed every ten seconds with all other participants’ results, so that people feeling lousy in their homes that night could see other peoples' scores and know they weren’t alone? I would predict that this collaborative content creation would enhance study compliance like no $25 Starbucks gift card ever could. And if instead of a Virtual Choir of 2,000 or 4,000, we had tens of thousands of patients doing the same thing? Talk about Big Data! Yes, our current broken clinical trial system can’t support something like this. But I believe we can figure out a better way to harness the power of social media, collaborative data creation, and the patient voice to overcome these barriers and transcend our current maddening limitations.

Whitacre had a vision of musical creation that transcended a single concert hall or venue, and the results were breathtaking. In our field, I believe we are no less creative and passionate. What are the provocative questions we can answer by being as visionary and bold?

Tuesday, September 18, 2012

The evolution of the inpatient attending physician: JAMA Viewpoint

I enjoyed this recent perspective article in JAMA by Dr. Bob Wachter of UCSF and Dr. Abraham Verghese of Stanford about the role of the inpatient ward attending in the "modern era" of hospital medicine, with the rise of the hospitalist movement and housestaff duty hours restrictions. Full text is available here. Again, I am sorry this is only available to JAMA subscribers or institutional members. However, you can listen to a very nice audio summary interview by JAMA editor Howard Bauchner and the two authors free of charge (scroll down to the 9/11/12 podcast).

When I was an internal medicine intern and resident at UCSF in the late 1980's - and coincidentally Bob Wachter was one of my chief residents at the time - the ward attending was a senior physician who was supposed to be in charge of our team of residents (usually 2-3 interns and 1 second-year resident) and would "supervise" us. But the reality was that we had tremendous autonomy in those days, and it seemed as if most if not all of the medical decisions on the patients on our service were made by us, the housestaff, all of whom had been out of medical school 2-3 years at the most, and not by the senior guy. His/her job was to spend a little time teaching, often about topics related to his/her subspecialty, whether relevant to the patients at hand or not, to write the daily attending progress note, and then to get out of the way and go back to the lab or office. The non-physicians reading this will no doubt find that level of (non)-supervision deplorable, and now with the perspective of almost 30 years behind me, I would have to agree with you. We did have too much autonomy, and it was not an ideal situation from a patient safety or quality of care standpoint. I'm glad it is so different now. However, lest you think it was unconscionably reckless and bordering on malpractice, we usually did a very good job taking care of our patients, and we learned to be responsible, obsessively detail-oriented, and independent in our medical reasoning and decision-making. And there was no doubt that the patients viewed us as their real doctors during that hospital stay, not the semi-anonymous old guy in the long white coat that came in 5 times a week parading in the room with a huge team of unknown people wearing scrubs and short white coats, all the while not saying much and deferring to the sleep-deprived young 'uns with the clipboards and pockets jammed with papers.

I like this perspective article because it was balanced and was not one of those "days of the giants" pieces romanticizing the old way of practicing medicine. In the modern era, attendings are usually young physicians themselves, often hospitalists physicians, who are not that many years out of training, but are typically much more involved in the day-to-day activities than 1980's attending. They are personally responsible for every major medical decision, as it should be. The hospital team structure these days is much more matrixed and redundant, and in my opinion much better for patient safety and continuity. Still, in the olden days before EHR's and discharge planners, the bedside teaching we received from the senior physicians, with a greater emphasis on interacting with the patient, listening to the patient story, and doing the physical exam, had plenty of merit, even in its brevity. Hope you enjoy the piece.

Monday, September 17, 2012

Duration of adjuvant chemotherapy: How much is enough?

(I've been away this week at the Epic Users's Group meeting in WI as part of my IT role at Hopkins, so I haven't been able to contribute to my blog. Here's another post continuing my series on recently published literature about breast cancer that patients and physicians might find relevant.)

How many cycles of chemo do you need? As a breast cancer oncologist, this question comes up in clinic a lot, particularly since I see a large number of women with early-stage disease who are being referred for my recommendations about adjuvant chemotherapy following lumpectomy or mastectomy. Since many of these patients are going to be cured even without chemo (especially if the cancer is estrogen receptor positive, meaning they will be receiving tamoxifen or an AI drug), minimizing the number of cycles of a toxic treatment like chemotherapy is critically important to achieve the optimal balance between benefits of therapy and side effects and risks. Unfortunately, we rarely have solid scientific evidence about how much is "enough," and I can appreciate how patients must think oncologists are incredibly arbitrary and vague when we advise six cycles of treatment not four, 20 weeks of therapy not 18, etc. And why do the recommendations always seem to be expressed as even numbers? Why not ever 3 or 7 cycles? (Don't ask me to try to answer that one…)

A recent trial published as an Early Release article in the Journal of Clinical Oncology came out online several weeks ago. This was a report of CALGB study 40101, entitled "Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles As Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes." If you are a JCO subscriber you can read the full article online. Also, there is a good summary article about the trial in the ASCO Post last week. I won't try to describe the study in detail except to say that early stage breast cancer patients who were either node-negative or had three or fewer positive nodes were randomly assigned to receive chemo with four cycles or six cycles of AC (Adriamycin/Cytoxan, a very widely used adjuvant regimen) or four cycles or six cycles of Taxol. The bottom line is that four-year relapse-free survival and overall survival was virtually identical when comparing the patients who received four cycles of either AC or Taxol with those who received six cycles of the same. Whether Taxol was superior or inferior to the AC was not reported yet, as further follow-up will be required before an answer can be determined. Having said that, the AC combination is a widely-used standard, and in very few situations would Taxol be given by itself as adjutant treatment. But clearly 6 cycles is almost always going to be more toxic than 4 cycles; now we know that it's not better, so in this population of patients (i.e., not necessarily applicable to all breast cancer patients), six cycles should NOT be used routinely.

So why can't we answer the question about duration of chemotherapy for all types of breast cancer patients and in other cancers as well?  Why is it so hard to get this information? Well, it just is, and that is very disappointing for oncologists and patients alike. These studies are very difficult to do, since they require large numbers of patients willing to be randomized and many years of follow-up. Remember that no more then 3-4% of all adult patients in the U.S. participate in cancer clinical trials. This trial enrolled 3171 women over a 6-year period of time, and it was performed in multiple institutions. That means that many thousands more treated in those same institutions either were offered the trial and declined it or were not eligible in the first place. And it took 10 years to get the results. That's because there was only a 1% difference in survival at 4 years for women treated with 6 cycles of chemo vs. 4 cycles - not statistically significant and practically not enough of a difference to justify the misery of increasing the length of the chemo by an additional 4-6 weeks. In a disease like early-stage breast cancer, where most patients do well - overall survival was > 95% - you only see differences in treatments when there is an "event," like a relapse, a death due to breast cancer or another cause, or a side effect so severe that it requires the patient to drop out of the study. In other words, only when something bad happens to a patient in the study do you really learn whether there are differences in treatment. And I should also say that it is not intuitive that four cycles of breast cancer chemo of this type are equivalent to six. It could have gone either way, and there are many other examples in oncology where shorter durations of treatment are definitely inferior to longer. So it requires a clinical trial of this magnitude to answer a question of this type.

Or does it? Maybe I'll save this discussion for another blog post, but researchers have been realizing that the days of these mega-trials, with thousands of patients randomized to different treatments that themselves represent only tiny variations in therapy, are numbered. In this era where more and more of our cancer treatments are becoming more personalized to the individual patient, taking into account the genomic make-up of their cancer and other individual variables, designing more trials like CALGB 40101 will not serve our patients well or give us the important answers we need. Furthermore, the cost of doing such mega-trials is already prohibitive, and our clinical cancer research infrastructure can barely support trials that are much more modest in scope as it is. Unfortunately, we still have few "personalized" treatments for early stage breast cancer, so adjuvant chemotherapy will continue to be used, but stay tuned. I'm confident that in a few years, I will have options to offer my early stage breast cancer patients much more attractive than AC X 4. At least it's not 6.

Sunday, September 9, 2012

Surgical margins in lumpectomy: How much is enough?

When it comes to the "surgical margin" required in a breast cancer lumpectomy - the amount of normal tissue surrounding the tumor that must be removed along with the cancer to ensure that there are no residual cancer cells left in the breast - the answer is surprisingly unclear. Dr. Monica Morrow, Chief of Breast Surgery at Memorial Sloan-Kettering Cancer Center in New York, addresses this is a commentary in the New England Journal of Medicine from the July 5, 2012 issue. (Unfortunately, the full text is available only to NEJM subscribers and institutions; however, I covered many of Dr. Morrow's points in my free podcast from Cancer.Net where I summarized her talk on the same subject at the ASCO Annual Meeting June 2012.) Interestingly, published surveys have shown that even surgeons and radiation oncologists themselves cannot agree more than 50% of the time. At Johns Hopkins we tend to prefer 2 mm margins, but at our tumor boards we are always agreeing and disagreeing with that figure, mostly when discussing whether a particular patient should have additional surgery to try to achieve a larger negative margin. And that's the main issue. Should a "negative margin" be defined only as one where the tumor does not cross the inked border of the surgical specimen? Or should an additional amount of normal tissue also be taken out to achieve a wider "negative" margin? What if that requires the patient to undergo a second or even third surgical procedure and compromises the cosmetic outcome of the lumpectomy, an important goal for many patients? Studies have not uniformly shown larger negative margins are associated with a lower risk of local recurrence than a margin in which tumor simply is not touching the inked edge of the surgical specimen. For example, when MRI imaging is used in addition to mammography and ultrasound, additional tumor is frequently found, often resulting in the decision to move to mastectomy rather than lumpectomy; however, even then local recurrence rates and certainly long term outcomes are not uniformly improved.

This is not to say that lumpectomy margins are unimportant or that meticulous surgical technique should somehow not be practiced. Morrow gives some examples of clinical situations where re-excision of a close margin is highly appropriate (e.g., extensive DCIS). It is devastating when a patient undergoing a lumpectomy and radiation told upfront that she has a "good" prognosis breast cancer then goes on to experience a recurrence in the same breast months or years later, usually necessitating mastectomy.

Finally, Morrow points out that surgery and radiation are not the only treatments that reduce local recurrence. Hormonal therapy such as tamoxifen, chemotherapy, and trastuzumab (Herceptin) in HER2 positive patients, have all decreased the rate of recurrence in the breast in the modern era, compared to the 1980's and before (3-6% now vs. 10-15% prior to the wider use of drug therapy post lumpectomy, especially tamoxifen or AI's). When counseling patients it is important to emphasize these up-to-date statistics to counter a common misconception that mastectomy is always a "safer" choice.

Friday, September 7, 2012

Diabetes, metformin, and breast cancer

A number of interesting connections between obesity, diabetes,  the diabetes drug metformin, and breast cancer have been discovered in recent years. It has been known for some time that obesity is an adverse prognostic factor for breast cancer. For example, obese women have a higher risk of developing breast cancer compared to normal-weight woman, and women who have been treated for breast cancer who gain a lot of weight after treatment have a higher risk of recurrence than those that do not. The exact mechanism is not known, but it is thought that naturally-occurring insulin may play a role, since obese women tend to have higher levels of insulin and have relative insulin resistance. Additionally, women with diabetes who take metformin, a widely used agent to control blood sugar, may have a lower risk of cancer. This was shown in a recently published study in the Journal of Clinical Oncology. A large population-based clinical study called the Women's Health Initiative (WHI) looked at 68,019 women between 50-79 who did not have breast cancer at baseline. Of these 3,401 had diabetes at study entry. Women with diabetes treated with medications other than metformin had a slightly higher chance of developing breast cancer. By contrast women with diabetes treated with metformin had about a 25% lower breast cancer incidence. It is possible that metformin produced this finding by diminishing some of the effects that insulin-related cellular pathways had on cancer cells.

So does this mean that we are ready to prescribe metformin in women without diabetes as a treatment to lower the risk of breast cancer? No. However, this question is being studied in a large international clinical trial called MA.32 in which women without diabetes who have been curatively treated for breast cancer with surgery, with or without radiation, chemo, or hormonal therapy, are randomly assigned either to the drug metformin orally twice a day for 5 years or a placebo for 5 years. Interestingly, in non-diabetic women, metformin does not seem to cause much hypoglycemia (low blood sugar) as you might expect, and thankfully there are not a lot of other side effects. We won't know the results of this important study for a number of years, but if it does show a benefit to metformin in reducing breast cancer recurrence risk further, this old, widely-used, and inexpensive medication may be added to standard cancer therapies. This trial is available at Johns Hopkins for eligible patients.

Thursday, September 6, 2012

Neuropathy from taxane-based adjuvant chemo does not correlate with breast cancer outcomes

So I wanted to try something a little different with the blog this week and try to write some brief posts about recently published breast cancer articles that I thought would be of interest to many. The links are to full text versions, and I realize that those without an individual subscription or institutional access may only be able to read the abstract which is less desirable (for many journals, full text can be accessed a number of months after publication, e.g., for JCO after 12 months).

Peripheral neuropathy is a common and often difficult side effect of breast cancer chemotherapy, particularly regimens that include the taxane drugs paclitaxel (Taxol) or docetaxel (Taxotere). In my practice, the majority patients who receive our current institutional standard 3rd generation adjuvant regimen of dose-dense Adria/Cytoxan every 2 weeks x 4 cycles followed by Taxol weekly x 12 develop at least a little bit of sensory neuropathy in their hands and/or feet by week 8-12 of the Taxol portion. For many patients it is only a minor annoyance and unpleasantness which resolves within a few months after end of chemo, but for a significant minority it can greatly affect quality of life by limiting mobility or dexterity and in some cases requiring pain medicines or other treatments. In a small number of patients, it takes many months to improve and occasionally there are residual symptoms at the 12 and 24 month post-treatment point. A recent article from Journal of Clinical Oncology looked at a previously reported (in 2008) clinical trial of adjuvant chemotherapy called E1199 and tried to determine if the women who developed neuropathy from the chemo were more or less likely to develop breast cancer recurrence and/or premature death. Other research had previously suggested that women who received taxanes as adjuvant treatment who then went on to develop neuropathy had a lower chance of recurrence than those that did not develop neuropathy, perhaps because whatever toxic effect the chemo had correlated in some way with great breast cancer cell kill. But this trial failed to show any connection at all with the incidence or severity of neuropathy and breast cancer outcome. In a multivariate analysis, the authors found that there was NO correlation between the development of Grade 2-4 neuropathy (which was as high as 22% in some treatment groups) and disease-free survival or overall survival.

The results are reassuring…sort of. Patients sometimes ask me, "If I did not get as much nausea or hair loss as expected, does that means the chemo didn't work?" Here, it is logical to conclude that women who get taxane-based chemo and who are lucky enough not to get neuropathy are just that - lucky, but not more prone to recurrence than women who have more side effects. In reality it's probably not a matter of luck but rather genes, as other research has shown that some women may have a special genetic predisposition to develop chemotherapy-induced neuropathy. Hopefully we can soon have a commercially-available, validated test which can be performed on all patients for whom taxane-based chemo is being considered, which can be used to predict which patients are more neuropathy prone. And even more importantly, we need to identify what alternatives that group has. Right now, we are not there yet, and it is important to recall that taxane drugs are a critical component of many modern adjuvant breast cancer regimens and cannot easily be dropped without compromising curability.

Monday, September 3, 2012

Perspicacity Blog et #Springsteen

This post has nothing to do with medical oncology, biomedical informatics, patient-centered care, or anything remotely health-related - except perhaps the effects of humidity on the human body - but if you were following me on Twitter you figured out that I went to the Springsteen concert at Citizens Bank Park in Philly last night with my two sons. Speaking as a lifelong fan, adjectives fail, but epic, exuberant, and electrifying come close. Here's a quick review including the 33-song setlist. Over 3 1/2 hours with 8 encores. Unbelievable. Third time I've seen him live in the past 27 years. If you are of a certain age and have a pulse, try to catch one of his shows on this tour.

Sunday, September 2, 2012

The advice I gave the housestaff and fellows

I just finished one of my two 2-week rotations on the Solid Tumor Inpatient Service for this academic year at Hopkins, and I spent some time with the fellow and each of the residents at the beginning of their rotation and then on my last day on service discussing my expectations for them and a review of their performance, respectively. Having spent most of my professional life in a non-academic setting, I haven't had much previous experience with students and trainees, so I can't say I am particularly skilled at medical education or the best techniques for assessment and review, even though I find the teaching opportunities of my job at Hopkins one of my favorite parts. So instead of giving them a detailed list of recommenations about how they can be smarter and more effective physicians, I simply told them things that I wish I had been told at that point in my training that would have really broadened my perspectives at the time - in other words things that took me far too long to learn on my own and came only as I matured during 20+ years as an oncologist.

Here's what I told them:
  1. You can't possibly spend enough time listening to the patient. Hospital rounds are admittedly a highly artificial and inefficient construct from both the learner's perspective and the patient's, but from the perspective of the person in the bed or the family sitting in the room, both highly anxiety-producing and often unsatisfying. I tried to tell them that even though our time in each room was short, we had to try harder to let the patient and family talk and not spend the time talking AT them ("Today you are getting a PICC line, then we start your chemo, then PT will see you and if you can walk we'll send you home and if not maybe to rehab, and we'll give you something for nausea if you have it which most people don't, and then the discharge planner will give you a list of your meds for home and follow-up appointments, and call us for any fever since it could be a sign of a serious infection, OK?" Usually not ok.) Pause, listen, ask if they understand or have more questions.
  2. Always try to solve one problem for the patient every hospital day or every encounter in the office. As physicians we often fail to understand how important it is for the patient lying in the bed to get the TV remote fixed or the disability form filled out, even when (to us) that seems far less important than treatment of their cancer.
  3. Remember that for most if not all patients with a cancer diagnosis in the hospital or at a visit with the oncologist in the office, they are having the worst moment of their lives. A community-acquired pneumonia while on FOLFOX or a first visit to discuss adjuvant treatment of a T1 breast cancer is routine for us, but it is most often an unspeakable horror for the patient in front of us. So give them a break if they are irritable, slow to understand, or "non-compliant."
  4. You can't possibly be detail-oriented enough. True of course in all of medicine particularly so in a data-intensive specialty like internal medicine or medical oncology. Most residents seem to get this, but occasionally I see lapses that are easily prevented.
  5. Do your part to creat a medical record that allows another person to see the story of the patient and his/her illness. I am trying to teach my trainees that while our electronic tools allow us to include all sorts of data and details in the daily progress note, too much cut-and-paste and mindlessly repetitive problem lists confuse the narrative, so they need to start learning the discipline of effective documentation now. I don't think very many of my colleagues spend much time talking with the housestaff about this, but I believe as attendings, mentors, and role models, teaching this is nearly as important as teaching pathophysiology.
  6. Even if you're tired, burned out, or overwhelmed, or even if this specialty doesn't interest you long term, always appear interested, enthusiastic, and eager to learn. I think residents forget that it is so easy for the senior people to identify the complainers and whiners, and those trying to get out of doing work.
  7. People judge your character by how you behave when you are under stress, short of time, conflicted, etc. Pretty true for all of us don't you think?
I must say that I have been pretty happy with the trainees I have worked with in the past few years at Hopkins. One of the most positive aspects is that largely they DO have a collaborative working relationship with the nurses and staff, and there does seem to be mutual respect. I don't think that really was the case in the 1980's when I trained, and it is with no small sense of regret and shame that I remember that I didn't often view the non-physician staff as partners in care. Here's to hoping today's young physicians figure out how to do the other things above a lot sooner than I did.