I previously mentioned that some neuroendocrine tumors can be slow-growing and that is true, but they still are malignant tumors. My first patient did well for just over five years but then began to show rapid growth of the metastases in her liver. We treated her with several different regimens of chemotherapy but she survived for only an additional eighteen months before succumbing to liver failure. The second sister who also had malignant pancreatic tumors fared better and survived for almost fourteen years before she, too, developed a large burden of cancer within her liver that no longer responded to chemotherapy, and she, too, succumbed. The two sisters whose smaller tumors were removed have not developed any new tumors in their remaining pancreas tissue and have shown no evidence of development of renal-cell carcinoma or pheochromocytoma. The sister with the retinal angiomas has had vision problems but is being treated aggressively by her ophthalmologist and has been able to maintain her vision for many years now. The mother of these girls eventually developed worsening heart disease, including congestive heart failure related to her years of poorly controlled hypertension, and succumbed to heart and kidney failure.
Cancer is genetic in that malignant cells develop because of mutations or other abnormalities that occur in genes. However, the majority of cancers arise as spontaneous, nonhereditary events. We know that environmental causes, including cigarette smoking or exposure to certain chemicals or radiation; some types of infections, including hepatitis B or C or human papilloma viruses; or poorly understood and undefinable simple bad luck can lead to the genetic aberrations that produce a cancer in a patient. We are in a remarkable period in cancer research because we may one day in the foreseeable future be able to target more of the abnormal genes present in any given individual’s malignant cells. In the meantime, we closely watch our patients who are known to have a high familial risk to develop certain types of cancer, and we intervene early when possible to prevent the development of malignant disease.
It’s an important lesson: preventing cancer is far preferable to treating cancer.
8
Told You So
“Service to others is the rent you pay for your room here on earth.”
Muhammad Ali
Service: The action of helping or doing work for someone; an act of assistance
I love baseball. As a boy, in the 1960s, I played baseball every chance I got. My love of the game came from my father, who was a minor-league baseball player in west Texas when I was born. Like tens of thousands of other boys and men at the time, my baseball hero was New York Yankee centerfielder Mickey Mantle. In fact, the entire time I played high school ball I never went a game without my Mickey Mantle signature Louisville Slugger bat and Rawlings baseball glove.
Reading Jim Bouton’s book Ball Four revealed to me the occasionally unsavory behaviors of my baseball hero. While my image of him was slightly tarnished, I still admired Mantle and considered him one of the greatest ballplayers of all time. In the mid 1990s word came out that Mickey Mantle was suffering from alcohol- and hepatitis–induced cirrhosis. He entered a treatment program and confessed he had spent too many years abusing alcohol and causing damage to his liver. He also admitted that he drank heavily because he assumed that, like his father and other male relatives in his family, he would never live past age forty. Mutt Mantle, Mickey’s father, died from lymphoma shortly after Mantle’s rookie season in 1951. Ironically, when Mickey Mantle was diagnosed with hepatocellular cancer his CT scans were sent to me to assess whether he would be a candidate for surgical treatment. Due to the severity of his cirrhosis and extent of the cancer, he was not. He went on to receive a liver transplant but died only two months later when the cancer returned in his lungs and other sites. I mourned the passing of an American icon and my personal baseball hero. I still have the New York Times front page and sports section from the day he died.
I have encountered many patients with a similar sense of fatalism. They have a family history with relatives who died at unusually early ages of heart disease, stroke, cancer, or some other cause. Their concerns about early mortality are understandable based on their own experience.
In the late 1990s a patient from a major Texas university was referred to me. He was a fifty-nine-year-old man who had undergone removal of a malignant tumor of his colon the year before. He then developed liver metastases in the right lobe of his liver. He was a bright, well-read, thoughtful, and charming man. He was a full professor and accomplished in his area of education. We discussed treatment options, including a right hepatectomy, the removal of the entire right lobe of the liver—which involves taking out approximately two-thirds of the organ. He had totally normal liver function and had been in excellent health otherwise so I felt he would tolerate this operation well. I also knew that the remaining left lobe of the liver would regenerate over a six-to-eight-week period, and his overall liver volume would return to near normal.
I always take time to explain to patients the features of liver regeneration, which is a remarkable occurrence in human biology. I told the professor that his right liver lobe would not grow back, but rather his left lobe would grow in volume and size to take over the function for the portion of liver that was removed. Many people assume that if I take out the right lobe, a new right lobe will simply grow back. They ask me if their right lobe is going to be a “brand-new liver.” I invariably smile and clarify that the new liver cells will be mixed in with the old liver cells and that they will not reform as a normal-appearing liver.
I like to use an analogy based on my childhood experiences. As boys growing up in the southwest, my brother and I would frequently catch lizards, horned toads, scorpions, tarantulas, and other desert creatures. Every kid in the neighborhood knew that when stalking a blue-tailed lizard you had to catch it by the sides of its body. If you grabbed it by the tail, the tail would come off, and the lizard would scamper away and subsequently grow a new tail. The kid would be left with a still-wriggling tail in his or her hand—not as much fun as an entire lizard, but still good for disgusting your mother or the squeamish girl next door. I point out to patients that while I have met some folks with reptilian tendencies, the liver is not like the tail of a lizard and it doesn’t grow back a new lobe. And I explain that after a major liver resection patients do experience significant fatigue for six to eight weeks while the liver is regenerating. That’s because the liver is a selfish organ and uses a large amount of protein and energy to rebuild itself after a surgical procedure.
After a lengthy discussion, I asked my patient if he was feeling all right because he appeared sullen and contemplative. He told me that his father and uncle had died before the age of sixty-one. Therefore, he was not sure it was worth going through the surgery because he felt he was destined to have the same fate. He believed he was within two years of his expiration date. We had a lively conversation about the matter, and he decided to proceed with the operation.
I performed the hepatectomy, and he did quite well. Once he recovered from the operation and liver regrowth, he returned to his university duties. However, during subsequent follow-up visits during the first year, he had a somewhat pessimistic point of view because he wasn’t sure the operation would make a difference.
As fate would have it, almost exactly one year after his surgery I saw him back in my clinic for a scheduled checkup and noted that one of his blood tests, a serum tumor marker called carcinoembryonic antigen, was elevated. His CT scan revealed a single new 1.2-centimeter tumor in the hypertrophied left liver. He was sixty years old. He looked at me and said, “I told you so.” He had already received chemotherapy, so I encouraged him to consider a second surgery to perform a small wedge resection of this new tumor near the edge of the liver. I also advised him that this was a much smaller area of liver to remove and that his recovery period would be shorter. He went home to consider it and two weeks later he agreed to the procedure. Once again, he underwent the operation without any difficulty and his recovery period was uneventful.
&n
bsp; One year later my patient went to the trouble of making an appointment on his sixty-first birthday. He informed me he did this to see if he had actually made it to sixty-one healthy. He was frankly giddy during the visit. He gushed repeatedly, “I can’t believe I’m still here.” We had a great visit and made plans to schedule routine checkups with blood tests and scans watching for any evidence of recurrent cancer.
I just saw the now-long-retired professor in my office last month. He is seventy-nine years old. He has moved with his wife to the site of his alma mater in the southeastern United States. He attends college classes in subjects that intrigue him and have nothing to do with his forty-five-year professional career. He enjoys playing golf and going to college baseball games. And several times a year he sends me handwritten letters and he includes newspaper and cartoon clippings he thinks I will find interesting. I immediately recognize his writing on the envelopes and I look forward to reading about his exploits and travels, and laughing at his well-selected cartoons and news stories. Every time I see him for a health checkup, we talk about baseball. I have shared with him my childhood fascination with Mickey Mantle and he admitted he was a fan of the Mick, too.
Each time my patient visits me in the clinic or sends a hand-scrawled letter, he thanks me for my care and for the additional years of life he didn’t believe he would have. My reply is invariably the same: Always happy to help; always a privilege to serve.
I am reminded daily that none of us know how many days we will have on this earth. Things happen that are unexpected or unexplained. There are certain family tendencies or genetic disorders that can limit the life expectancy of specific individuals. Nonetheless, with our increased understanding of genetics and biology, along with the practice of a healthy lifestyle, we can change the fate we believe will befall us.
Unfortunately, cancer is a condition that will continue to trouble mankind. And sadly, too many cancers are induced by smoking, excessive alcohol intake, poor dietary choices, lack of exercise, and a long list of toxins and carcinogens in our environment. My colleagues and I are not able to cure every patient. Thus, an important goal is to find more successful and less toxic treatments so cancer can simply become a chronic condition patients can endure. As a society, we need to spend far more time and resources studying prevention of cancer, and that includes taking better care of our own health and the world around us.
We doctors always work hard for every patient, because we never know who will beat the odds and become a long-term-success story.
Like Mickey Mantle, I like to swing for the fence and try to go yard with each patient I treat.
I told you so.
9
The Five-Year Cancer-Survival Mark
“Great works are performed not by strength but by perseverance.”
Samuel Johnson
Perseverance: Persistence in doing something despite difficulty or delay in achieving success
Reaching the five-year survival mark after a cancer diagnosis is a milestone deeply ingrained in medical literature and in the minds of cancer patients. Problematically, many patients assume or believe that if they survive for five years after completing all treatments for their cancer, they are home free and “cured.” The origin of the five-year metric dates back to the 1930s when surviving that long after developing most types of cancer was unusual. This predated the era of cytotoxic chemotherapy drugs, and radiation treatments were still neophytic. Back then, surgical removal of localized malignant cancer provided patients the best chance for long-term survival, but the lack of early-detection methods meant many people presented with advanced disease that could not be treated surgically.
It is unusual even now to read a clinical cancer paper that does not include five-year real or actuarial (predicted) survival rates. Every clinician involved in cancer care has seen thousands of graphs demonstrating the declining survival curve from the time of diagnosis until the five-year mark. Clinical trials for any given type of cancer are designed to compare a novel therapeutic approach to the standard therapy for that type and stage of cancer—with a goal of demonstrating that a significant percentage of patients live longer using the new treatment. There are many anticancer agents that have been approved for use because survival in the group of patients receiving the new agent was improved by a few percentage points (statistically significant when compared with the older therapy). For some aggressive types of cancer where five-year survival is still the exception, other so-called surrogate end points are now accepted in clinical trials. This includes measurement of “time to progression,” meaning patients are assessed to see if a new treatment keeps their cancer at bay for a longer period of time, even if only a few weeks or months, compared to standard therapy.
I emphasize to all my patients that being alive five years after completing treatment for cancer is not a guarantee they’re cured. Cancer does not read the textbooks and it can lurk in the shadows of various and—occasionally—unusual sites in the body. Still, cancer clinicians celebrate and love success stories. Eighteen years ago a woman in her mid-thirties presented to me with a nonobstructing rectal cancer and an eighteen-centimeter right lobe liver metastasis. The tumor in her rectum was bleeding and the large mass in her liver was abutting the right and middle hepatic veins, and was causing her considerable pain. When the medical and radiation oncologists and I finished her evaluation, we created a treatment plan that started with intravenous, multiple-drug chemotherapy for three months. At the end of that time, CT scans showed that the liver tumor and her rectal cancer were slightly smaller, and the patient reported her rectum was no longer bleeding. While unconventional at the time, I decided to proceed with an operation called an extended right hepatectomy, removal of the entire right lobe and a portion of the left lobe of the liver. The accepted sequence of surgical treatment at the time was to remove the primary (rectal) cancer first, then deal with the liver metastasis later. But, this lady still had a very large liver tumor involving two of the three hepatic veins, and if it grew just a few centimeters while she recovered from the rectal cancer operation, the tumor would become unresectable. So I attacked the liver metastasis first and removed the tumor completely, with negative margins. While recovering from this operation, she received a combination of low-dose chemotherapy and pelvic radiation therapy to treat the tumor in her rectum. This combination approach is used to treat many types of cancer, with the low-dose chemotherapy acting as a so-called radiation sensitizer, to enhance the killing of the cancer cells during the radiation treatments. After she completed five weeks of chemoradiation and recuperated for an additional four weeks, I operated to remove her rectal cancer and all of the surrounding lymph nodes. She recovered from this procedure and received an additional three months of systemic chemotherapy.
When I first met this young woman in my office, she tearfully showed me a picture of her two-year-old daughter. She stated unequivocally, “I want to see my daughter graduate from high school.” I cringed internally but was circumspect in my response to her remark. I informed her that I would certainly do my best to treat her but I could provide no promises regarding how long she would live with stage IV rectal cancer. In May two years ago, I received a high school graduation announcement from my patient as she celebrated the graduation of her daughter. I rejoiced that my patient had done so well and was alive without any evidence of recurrence of her cancer. For the next two days after I received that announcement I was energized and excited. Yes! A major victory!
Not every win can be considered an unqualified success, however. The treatments used for cancer can be dangerous and are associated with both short- and long-term side effects and toxicities. Consider one of my patients who has survived almost a decade after I removed the right lobe of his liver for colorectal-cancer liver metastases. His chemotherapy treatments included a drug called oxaliplatin because clinical trials showed that use of this agent combined with additional anticancer drugs improved the probability of survival. A common side effect of this
drug is neuropathy. It can manifest as pain and tingling or numbness and loss of sensation in the hands and feet. This man is a cancer survivor who has never had evidence of recurrent or new metastatic disease. Yet he is extremely unhappy because he has suffered almost complete loss of feeling in his fingers and feet. Before treatment, he played a stringed instrument and was an accomplished member of a major American symphony orchestra. Now he is no longer able to perform because he does not have the sensation needed for the fine fingering work necessary to play in the orchestra.
Another, often-unspoken reality for patients who survive more than five years after cancer therapy is that the treatments themselves are carcinogenic. Many chemotherapy drugs and ionizing-radiation applications are mutagenic, meaning they cause defects in the DNA of normal cells. Cancer can arise in previously healthy cells decades after completing chemotherapy or radiation. For this reason, patients who have cancer as children or young adults must be followed their entire lives as they can develop second or even third malignancies.
In My Hands Page 6