Cancer Patients Take Heart: The Power of Public Opinion

A January 27, 2014, report on National Public Radio brought recent discussions into sharper focus. Though the story was unrelated to cancer, the lessons learned provide a road map for cancer patients in their pursuit of the most effective, least toxic treatments.

The condition known as “clubfoot” (talipes equinovarus) is a congenital deformity that afflicts one of every 1,000 births in the US. The abnormal internal rotation of the ankle is highly debilitating if not corrected shortly after birth. For decades, orthopedic surgeons used complex surgical procedures that disrupted the ankle structure and realigned the bones. Despite numerous surgeries, this rarely corrected the deformity resulting in chronic arthritis and gait disturbances. The costs were significant and the loss of productivity for those afflicted even greater, yet the dilemma remained unresolved.

PonsetiInto the fray came Dr. Ignacio Ponseti. Ponseti, the son of a Spanish watchmaker, had gained a unique perspective on structural integrity working in his father’s shop. Fleeing the Spanish Civil War he came to the US to practice orthopedic surgery at the University of Iowa. Recognizing the poor outcomes for clubfoot surgery, he took it upon himself to rethink the problem. After all, newborns have flexible ligaments. These ligaments, he reasoned, could be re-trained through a series of casts that were replaced serially over months after birth. Once the foot was in better alignment, the children were placed in a boot to retrain the joint into its normal alignment. Not surprisingly, this simple, noninvasive, inexpensive method was eschewed by the orthopedic professionals. Undaunted, he continued to practice his art, with excellent results year after year. Dr. John Herzenberg, a Baltimore-based practitioner of the Ponseti method was quoted: “People were falling over themselves to do fancy invasive surgery, and this one strange old guy, who speaks softly with a Spanish accent in Iowa, was getting sort of ignored by the drumbeat of people who were in favor of surgery.” Despite its obvious appeal and its manifest successes, this technique remained largely in Iowa for 50 years.

And then came the Internet. When a child born with clubfoot in 2000 was recommended for standard surgery, her mother went online to examine all the options and came across Dr. Ponseti. She traveled to Iowa for an opinion. Convinced that Dr. Ponseti’s approach was superior, this brave mother took the leap and undertook the Ponseti method. Dr. Ponseti completely corrected the child’s foot. Horrified that her daughter would have suffered a life of misery without this brilliant breakthrough, this young mother took it upon herself to get the word out. Using the Internet, she created a Yahoo Support Group called “No Surgery 4 Clubfoot.”  Families with afflicted children could now find out about this technique and identify practitioners who used it.

Voting with their feet, parents took their children to centers that applied this simple, relatively noninvasive approach. Over time, the academic community and their adherents to invasive surgery found themselves on the wrong side of patient referrals. Demanding better outcomes for their children, parents charted a new course for their medical care and forced their doctors to agree or be left behind. With a 97% success rate today, virtually every orthopedic surgeon in America practices the Ponseti method. Indeed, it is now recommended by the American Academy of Orthopedic Surgeons.

I relate this story to cancer patients as they confront similar resistance. While marginally effective therapies are promoted by many academic centers, simple, comparatively easy techniques are available that can empower patients in treatment selection. Just like the clubfoot parents, cancer patients must demand access to treatment options and explore every lead.

The Internet has offered an entirely new platform for cancer patients to communicate their experiences, recommend physicians, educate friends and family members and change referral patterns. The power to change the way cancer is treated in America today is within the grasp of the patients themselves. Just like Dr. Ponseti, who knew that his method worked and just like his patients who avoided the pain and suffering they would have otherwise endured, patients enlightened about better ways to treat cancer need to communicate and take charge of their disease.

Empowering Patients Towards Personalized Cancer Care

We have one more guest blogger to introduce during Dr. Nagourney’s absence: Patricia Merwin. Pat just celebrated her fourth anniversary of wellness after receiving a diagnosis of metastatic lung cancer.

In July of 2011, I attended a local TEDx conference in Long Beach, CA where Dr. Robert Nagourney gave a compelling talk about the nature of his work and the future of cancer care. TED is a global organization with a mission to “share ideas worth spreading,” a very appropriate forum for Dr. Nagourney to share his insights into cancer and how to defeat it.

Just three months earlier, at another TEDx event in the Netherlands, Dave deBronkart also gave a talk about the future of cancer care.  Dave deBronkart, better known as “E-patient Dave,” was diagnosed in January 2007 with a rare and terminal kidney cancer.  Given a dismal prognosis, Dave refused to cede his life to “standard care.”  Instead, he turned to a group of fellow patients online and found the information that eventually led to a treatment that saved his life. Dave deBronkart has since become a prolific online patient advocate and an internationally renowned speaker on the subject of patient empowerment and participatory medicine.

Like e-Patient Dave, I was given a “dismal prognosis” when I was diagnosed in 2008 with advanced metastatic lung cancer.  I too refused to cede my life to the standard protocol of the day. But it was not my health care providers who led me to Dr. Nagourney, it was a close friend.  Empowered with the knowledge that it was possible to improve my odds for survival, I chose functional profile testing (EVA-PCD®) to help determine my personalized treatment plan. It was a wise, informed decision resulting in the best possible outcome.  I have since become an online patient advocate, spreading the word to thousands of other patients so that they can become knowledgeable about this important test that could save their lives.

According to Dr. Nagourney, “Every system performs exactly as it was designed to perform. The current system of medical oncology provides adequate care for the average patient. There is little room for true, individualized care, for it disrupts the norm.”  But every patient with cancer has the same objective. To find the treatment that will work for “me.”  With a system skewed toward averages and away from the individual, the path to personalized medicine must be to empower the person with the most at stake – the patient. Dr. Nagourney says, “Today’s patient must become his or her own best advocate.”

More and more, patients are turning to online forums and other patient groups, not just for support, but to seek and share the latest news and information about treatments, side effects, tests, etc. If two heads are better than one, then thousands of engaged patients should, at the very least, provide good food for thought, “ideas worth spreading.”

Dr. Nagourney believes that “it’s in the online trenches where the real, personal war of cancer is being waged.  The old paradigm, that knowledge runs downhill from academics to practitioners to patients is being turned upside down as empowerment goes from the bottom up, not just from the top down.”  I’m sure e-Patient Dave would agree, along with countless other e-patients like him.

The Good, the Bad and the Good

Two years ago, almost to the day, I met a charming gentleman who had been diagnosed the preceding month with metastatic non small cell lung cancer.

The work-up that confirmed his diagnosis also identified an EGFR mutation. This mutation enabled him to receive the targeted agent erlotinib (Tarceva®) as first line therapy and it provided immediate benefit. An incidental finding in his work-up was a meningioma (a benign brain tumor that often arises in the midline of the brain, in an area known as the falx).

Follow up MRI showed no growth of the meningioma. The patient remained on the same therapy for three months at which time his treating physician decided to consolidate him with chemotherapy. The patient’s tolerance could not have been worse: nausea, malaise, fatigue and a 30 pound weight loss. He requested that I assume his care. After careful consideration, I put him right back on what worked in the first place – erlotinib.

With the exception of a few minor toxicities the patient did beautifully. As we approached his restaging with PET/CT and MRI of the brain, scheduled for August 2012 (his two-year point), he presented to a university medical center with disturbing neurological symptoms. An MRI revealed the meningioma to be much larger than originally found two years earlier. Surgery was scheduled for the following day.

The patient and I discussed his situation by phone as he sat in his hospital room awaiting the surgery. If this were a meningioma, it could be removed. However, if this was related to his lung cancer, then there was an opportunity at hand to determine (using the EVA-PCD® platform) whether the cancer was still responsive to erlotinib or had developed mutations that might confer resistance (e.g., T790M). On the one hand, high dose pulse erlotinib can be effective for CNS disease, so long as resistance has not developed. On the other hand, newer classes of drugs that target T7090M might be required.

We needed tissue for testing, so we could create a functional profile of the tumor, and the surgery was 12 hours away. The patient wanted us to do the study. I wanted to do the study. The problem was that I needed to arrange to get tissue to the lab and time was running short.

With an admirable degree of sleuth work, we identified the surgical resident on duty that evening. We explained our need and he proceeded to explain in great detail that this would never happen. Above and beyond the protocols and standards by which he delivered care, he had 45 other patients to cover, as well as consults to conduct. I hung up disappointed that this opportunity would be missed.

The next morning as I finished hospital rounds I noticed a 6:40 a.m missed call on my cell phone. It was from the hospital where the patient was undergoing surgery. I then received a second call from the same number. It was the attending senior surgeon. He was about to scrub in for the scheduled surgery and offered to assist me in any way he could. He explained that they hoped and believed that this was a benign meningioma. If it was, he would remove it and there would be no need for our involvement. An hour later, communicating via speakerphone in the OR, the surgeon explained that this was indeed adenocarcinoma consistent with the patient’s lung cancer diagnosis. He promised to process the tissue carefully, and then provided his cell phone number so we could communicate. I felt a sense of great relief.

While I cannot say what our laboratory tests will find, the story is both educational and inspirational. The patient is an example of a breakthrough in medical science that provided him an excellent and durable response with comparatively little toxicity. That was the good.

The bad reflected the overworked resident’s insouciance. He was busy, it was late and it appeared that we had confused him with someone who cared. After all, there is no payback to perform above-and-beyond-the-call-of-duty medicine. That was sad, for we are now training physicians who are technicians and not healers. They play by the rules and never extend themselves. No one can ding them for doing their job and no one applauds them for doing more.

The really good news was the response of the attending physician. This individual whom I have never met, evidenced an admirable degree of patient advocacy, commitment and compassion. This patient’s good outcome mattered to him and if there was something that I could bring to the table to help this person in need, then he was all there.

We are at a crossroads in medicine. Will we sponsor the healers or promote the technicians? In our laboratory we do everything in our power to provide all the science that we can bring to bear for every patient. The one component that we cannot offer as a service is the art of medicine. That is up to each individual physician.

Chemosensitivity Testing – What It Is and What It Isn’t

Several weeks ago I was consulted by a young man regarding the management of his heavily pre-treated, widely metastatic rectal carcinoma. Upon review of his records, it was evident that under the care of both community and academic oncologists he had already received most of the active drugs for his diagnosis. Although his liver involvement could easily provide tissue for analysis, I discouraged his pursuit of an assay. Despite this, he and his wife continued to pursue the option.

As I sat across from the patient, with his complicated treatment history in hand, I was forced to admit that he looked the picture of health. Wearing a pork pie hat rakishly tilted over his forehead, I could see few outward signs of the disease that ravaged his body. After a lengthy give and take, I offered to submit his CT scans to our gastrointestinal surgeon for his opinion on the ease with which a biopsy could be obtained. I then dropped a note to the patient’s local oncologist, an accomplished physician who I respected and admired for his practicality and patient advocacy.

A week later, I received a call from the patient’s physician. Though cordial, he was puzzled by my willingness to pursue a biopsy on this heavily treated individual. I explained to him that I was actually not highly motivated to pursue this biopsy, but instead had responded to the patient’s urging me to consider the option. I agreed with the physician that the conventional therapy options were limited but noted that several available drugs might yet have a role in his management including signal transduction inhibitors.

I further explained that some patients develop a process of collateral sensitivity, whereby resistance to one class of drugs (platins, for example) can enhance the efficacy of other class of drugs (such as, antimetabolite) Furthermore, patients may fail a drug, then be treated with several other classes of agents, only then a year of two later, manifest sensitivity to the original drug.

Our conversation then took a surprising turn. First, he told me of his attendance at a dinner meeting, some 25 years earlier, where Dan Von Hoff, MD, had described his experiences with the clonogenic assay. He went on to tell me how that technique had been proven unsuccessful finding a very limited role in the elimination of “inactive” drugs with no capacity to identify “active “drugs. He finished by explaining that these shortcomings were the reason why our studies would be unlikely to provide useful information.

I found myself grasping for a handle on the moment. Here was a colleague, and collaborator, who had heard me speak on the topic a dozen times. I had personally intervened and identified active treatments for several of his patients, treatments that he would have never considered without me. He had invited me to speak at his medical center and spoke glowingly of my skills. And yet, he had no real understanding of what I do. It made me pause and wonder whether the patients and physicians with whom I interact on a daily basis understand the principles of our work. For clarity, in particular for those who may be new to my work, I provide a brief overview.

1.    Cancer patients are highly individual in their response to chemotherapies. This is why each patient must be tested to select the most effective drug regimen.

2.    Today we realize that cancer doesn’t grow too much it dies too little. This is why older growth-based assays didn’t work and why cell-death-based assays do.

3.    Cancer must be tested in their native state with the stromal, vascular and inflammatory elements intact. This is why we use microspheroids isolated directly from patients and do not grow or subculture our specimens.

4.    Predictions of response are not based on arbitrary drug concentrations but instead reflect the careful calibration of in vitro findings against patient outcomes – the all-important clinical database.

5.    We do not conduct drug resistance assays. We conduct drug sensitivity assays. These drug sensitivity assays have been shown statistically significantly to correlate with response, time to progression and survival.

6.    We do not conduct genomic analyses for there are no genomic platforms available today that are capable of reproducing the complexity, cross-talk, redundancy or promiscuity of human tumor biology.

7.    Tumors manifest plasticity that requires iterative studies. Large biopsies and sometimes multiple biopsies must be done to construct effective treatment programs.

8.    With chemotherapy, very often more is not better.

9.    New drugs are not always better drugs.

10.   And finally, cancer drugs do not know what diseases they were invented for.
While we could continue to enumerate the principles that guide our practice, one of the more important principles is humility. Medicine is a humbling experience and cancer medicine even more so. Patients often know more than their doctors give them credit for. Failing to incorporate a patient’s input, experience and wishes into the treatment programs that we design, limits our capacity to provide them the best outcome.

With regard to my colleague who seemed so utterly unfamiliar with these concepts, indeed for a large swath of the oncologic community as a whole, I am reminded of the saying “There’s none so blind as those who will not see.”