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.

Into 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.

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.”

Cancer Gets Personal

Early in the morning of Nov 21, I suffered the loss of my father. However prepared one might be for this eventuality, there is nothing that can really prepare you.

At 95 years of age, he had lived longer than many. I had cared for my father as a patient since 1974, when he was first diagnosed with inoperable prostate cancer. I remember the day I received notification of the diagnosis. I felt a sense of deep sorrow that my father at 74 would soon die of high-grade locally advanced prostate carcinoma. As a member of the generation that forgot to have children, I was saddened that my father would not live to see grandchildren.

I remember traveling to Connecticut for his initial evaluation and then scouring the literature for the best possible options. Fortunately, despite the aggressiveness of the disease it had not metastasized.

I arranged for my father to travel to California where I then oversaw his care in collaboration with Dr. A.M. Nisar Syed in radiation oncology. There is a well-known dictum in medicine that only doctors and their families suffer unexpected complications. In my father’s case it certainly rang true. First, the radiation implants did not penetrate the tumor and needed to be removed and replaced. As a result of this double procedure, he then developed bleeding that required emergency hospitalization several days later.

Despite these hiccups, the combination of implant and external beam radiation provided excellent control. With a full recovery my father returned to his normal activities.

As so often happens in medicine a personal experience provides a focused interest. I delved into the prostate cancer literature and became increasingly interested in the biology of this disease. One area of particular interest was the role of hormonal therapy. When? How much? How long?

When my father’s PSA began to rise the second year, I had a unique opportunity to examine these questions at a very personal level. Would the early institution of androgen blockade induce the hormone refractory state? Was there a “trigger” value of the PSA that dictated the institution of the therapy? I remember discussing these questions with a prostate cancer expert and chairman of the ECOG committee, Dr. Basil Kasimis, whom I had had the pleasure of working with several years earlier. I agonized over starting hormonal therapy as my father’s PSA rose from 4 to 10, to 25, to 54, and up to 150. Despite these frightening PSA values, there was no evidence of metastatic disease on serial bone scans, which I performed religiously every six to 12 months.

Almost a decade passed but there was still no metastatic disease. And then my father developed severe coronary artery disease in his early 80s. Coronary artery bypass graft was the only option. To avoid the possibility of seeding the sternal wound, I bit the bullet and treated him with hormonal suppression – immediately driving the PSA to nearly 0.

With his coronary artery bypass surgery a success, he came off hormonal therapy and I let his PSA drift upward again.

As he had returned to Connecticut, his urologist became increasingly concerned by the rising PSA, and, without my knowledge, decided to rechallenge him with hormonal ablation. While I understood the motivation for this intervention, I didn’t agree and took him off all hormones for a prolonged period of time. Over the subsequent years, I would intervene occasionally to shepherd my father through pneumonia, a broken hip, a bleeding ulcer, and a variety of other maladies so common in patients who transition from their 80s to their 90s. On several occasions, we gave brief courses of hormonal ablation to suppress the PSA, when the steepness of the rise gave concern. Twenty-one years after his diagnosis my father died of natural causes, with no evidence of metastatic prostate cancer.

The experience was instructive on many levels. First, I realized how important it is to treat all patients as if they are a member of your own family. Second, it takes a lot of guts to step outside the normal guidelines and to do what you believe to be best. Third, I realize that in medical oncology it is the most “aggressive” physician who has the courage not to treat.

So often in this field doctors institute treatment, not because it is needed, nor because it will work, but because by doing so they have “done their job,” the rest is no longer their responsibility.

But “doing your job” as a physician, particularly in medical oncology may demand that you step outside of the NCCN guidelines, however uncomfortable it may make you, to do the right thing. Virtually every urologist or oncologist in America would have treated my father for his rising PSA 20 years ago. While I cannot say with certainty, I feel fairly confident that he lived the past 21 years in part because I didn’t treat him. Every patient needs an advocate. I feel a sense of personal satisfaction that I was there to be my father’s. He lived a long and productive life, I hope and believe that I helped him to do so.

Every experience, even traumatic ones, can have a silver lining. My father’s diagnosis lead me to develop a combined modality approach for locally advanced prostate cancer that has provided among the best biochemical relapse-free survival rates ever observed in this disease. Had I known then what I know today, I would have certainly treated my father with this approach.

Secondly, my interest in prostate cancer lead me to examine the lifestyle, nutritional, and micro-nutritional aspects of this disease – knowledge that I apply to this day. This lead to my analysis of an herbal remedy for prostate cancer that unfortunately uncovered the adulteration of an herbal mixture as we reported. (Herbal Composition PC-SPES for Management of Prostate Cancer: Identification of Active Principles: Journal of National Center Institute, Vol. 94, No. 17, September 4, 2002.) Despite our disappointment at the discovery, it lead me to reexamine the use of estrogenic substances as therapies in this disease, insights that have provided benefit to many of my patients ever since.

In retrospect, it may have been my father’s natural inquisitiveness (that he imparted to me) that leads to my pursuit of these lines of investigation. And for that I will always be grateful.

To read more about Alphonse Nagourney, click here.