Innovation in Cancer Treatment

It looked like a cluster of small translucent golf balls stuck to one another. Nothing was moving.

Could that be what causes so much trouble? I was in the giant laboratory complex at Memorial Sloan Kettering, staring into a microscope at living cancer cells.

These would later be inserted into human analog mice for further testing. I was a guest of a group of researchers who had recently published an amazing paper in the New England Journal of Medicine. They had tested a large number of cancer patients with a special compound designed to interfere with the growth of their colon cancers.

When the results came back, everyone was astonished. The rate of remission was 100 percent. Unheard of. I was shown the photographs. In patient after patient, the tumors had simply stopped growing, then decreased in size, then finally disappeared. And they didn’t come back. Every single patient in the test was cured.

This was real science.

Waves of Innovation

Cancer has been with us a long time, and its treatment slowly has evolved to where we are today. The earliest description of breast cancer is from 1500 B.C. in Egypt, with a note that it was not treatable. The Greek physician Hippocrates around 400 B.C. used the term karkinos to describe carcinoma tumors.

Surgery

The oldest treatment for cancer is surgery. There was surgery for surface tumors in Ancient Egypt. It is still widely practiced today. Sometimes, cancer surgery can have some very radical effects on the patient, all of them unpleasant.

One needs only mention the word “mastectomy.” But the problem is that the process of metastasis guarantees that the cancer spreads invisibly and comes back, and often eventually overwhelms the patient. Surgery alone ultimately is not very effective.

Nevertheless, going under the knife is a mainstay for cancer treatment even today, although it is used in conjunction with other treatments.

Radiation Oncology

In 1895, Wilhelm Röntgen discovered X-rays. When applied to cancer treatment, there were problems. Much healthy tissue would be burned, and bones would be weakened. For about 20 years, starting in 1898, γ-rays (gamma) from radium became a source of cancer treatment. Note that the art of radiation therapy was slow in developing. The treatment methodology changed from application of a few large doses to small daily doses over a few weeks. Practitioners developed better dosimetry – the calculation of how much radiation was being applied. About half a century later, by the 1970s, radio oncology was accepted as a separate discipline and standard clinical practice.

But putting aside the beneficial effects, anyone who has gone through these treatments knows of the long-term damage to most patients. The body never really recovers from sitting in front of the exhaust of a cyclotron for a few seconds, five times per week, for 2–3 months.

Radiation can cause leukemia, or lung fibrosis after radiotherapy of breast cancer, plus sterilization, mutations, and other problems. Bones become fragile, and for most, the skin turns to leather, and the cream prescribed to restore it doesn’t work very well, if at all. And like surgery, by itself, radiation oncology has problems.

Until the 1960s, radiation and surgery used in combination had dominated cancer therapy, but the cure rates had remained stuck at around 33 percent. In other words, treatment for cancer didn’t work very well. Cancer was considered to be a type of death sentence.

Chemotherapy

It was discovered that soldiers after the end of World War I exposed to an accidental spill of sulfur mustards in Italy had noticeably depleted bone marrow and lymph nodes. They had been exposed to mustard gas, one of the new weapons of mass destruction developed during the Great War. At Yale University, Gilman and Goodman exposed mice with lymphoid tumors to nitrogen mustard and observed marked regressions. In 1943, Lindskog administered it to a patient with non-Hodgkin’s lymphoma and also saw marked regression.

This was the beginning, but the research did not kick off in earnest until the War on Cancer. This determined effort by the United States was funded only after strong insistence by President Richard Nixon. Looking back, he considered this program to be the greatest achievement of his presidency.

There was much experimentation to do, so many compounds to test. According to one scientist closest to the research, the testing area at the National Institutes of Health (NIH) was nicknamed the “puke ward.”

It took such a long time to find the right compounds, the right dosages, and the right protocol and timing for effective treatment. It was only when the dosing was correlated to the growth rate of the cancer cells that progress was made in earnest. Anyone familiar with chemotherapy knows that the dosages today are carefully calibrated to body mass, and all are precisely timed.

Chemotherapy was highly controversial. There were a number of incidents when researchers presenting their findings at scientific conferences would be accosted by doctors in the audience standing up and screaming “you are administering poison to your patients; you are killing them; this is madness.” Newly graduated doctors entering the medical profession were told not to go into chemotherapy because it “would be a career-killer.”

And even some of the first trials at Memorial Sloan Kettering were a failure because the doctors initially were sloppy with the timing of the doses (something that was critical). They had not read the scientific papers carefully enough. But that changed.

As we know, although it was not at all easy, chemotherapy continued to make advances, and now is the mainstay of much treatment. A lot of today’s work involves searching the world for effective compounds. They come from some strange places, including mushrooms and the yew tree. One of the most popular cancer treatments today is called the “Red Devil” because it can cause red liquid to drip out of your feet. It was discovered in a bacteria found, of all places, in the basement of an abandoned castle in Southern Italy. It is highly effective.

And much progress has been made in testing multiple combinations of chemo drugs to find the right so-called “cocktail” that will best help a particular patient. This is known as “personalized medicine” and it is remarkable, at least when employed.

Insurance Coverage

Someone has to pay for all of this treatment, and insurance can be a barrier. For example, in testing for the BRCA1 or 2 gene, an indicator of susceptibility to breast cancer, a number of women have been frightened that although not sick, should they have the gene, they will be discriminated against.

Putting aside the COVID vaccine, which had no significant field trials, it takes around $2.6 billion and more than 10 years of research to investigate a new drug. So, cancer treatment is expensive. Surgery and the recovery from it is expensive. Also, the cost for chemotherapy varies, depending on the stage. For early-stage chemo, it might be around $5,000, but for a stage 4 patient, more than $34,000. Chemo without insurance can be around $50,000 for four sessions.

Insurance denials are commonplace. First of all, if any drug is being used even slightly off-label, it generally will not be approved. Even if their use is approved by the Food and Drug Administration (FDA), not all treatments will be considered to be medically necessary, even if “on label,” although insurance companies still claim they are not in the business of “practicing medicine” (although that is exactly what they are doing).

For Medicare patients with cancer, most find the appeals process overly complex, and the timing of the appeals process, even if expedited (if that is what we call it) can interfere with a sensitive cancer treatment regime. Most preauthorization and payment denials are never appealed. Medicare Advantage plans appear to deny claims by default. But by their own data, there is a 75-percent error rate, because all but a quarter of denied claims are reversed when appealed, and these reversals are by the Medicare Advantage plans themselves. Yet they are seemingly not embarrassed by this dismal and revealing record of carelessness.

Some pay out of pocket. Of course, there is no liability or consequences for damage inflicted on the vast majority of patients who never bother appealing – and as a result, never receive treatment.

The New Cancer Treatments

So, what will we expect for these compounds engineered at the molecular, and biological level that promise to create a new and exciting revolution in cancer treatment? After all, a 100-percent remission rate is remarkable. But will the well-heeled insurance establishment pay its bills?

My guess is that it all depends on cost. If these drugs are super-expensive, then there will be reluctance. After all, medicine is a business, at least for many. Will effective cancer treatment be available only to the rich? Will we continue to have the debate about economic inequality and the downstream disparities in healthcare? On the other hand, perhaps we can look at the bright side.

I was speaking with the lead researcher at Memorial Sloan Kettering. He is a surgeon. This remarkable man uses robotic surgery to treat cancers in the lower intestines and colon. These surgeries are very tough on the patient, and the recovery is uncomfortable. Ask any patient with a colostomy bag.

I asked him: “Why would you be interested in this new type of treatment? Won’t it make the type of work you do obsolete? It will ruin your career.”

He smiled and answered: “No, it is the other way around. Imagine cancer treatment without surgery, and without radiation. The patients will be lined up at the door.”

And perhaps we can imagine that the insurance companies will for once be happy to pay, because, after all, the ultimate costs for cancer treatment will greatly diminish, at least they should. Just think of it. No surgery, no radiation. Let’s say that again: “No surgery; no radiation.” A new world for all of us. In medicine, science is what is important; all else is secondary.