January, 2016

The Year of Living Dangerously

By Michael J. Katin, MD

Suddenly, 2015 is over, unless your calendar is based on a non-Western-centric system, in which case December 31 doesn't mean much of anything. It was a memorable period, and while the average person might remember it for critical international events amazing accomplishments, and even the emergence of celebrity presidential candidates, and the release of the long-awaited sequel to a classic film series, we in the field of oncology will remember it for the multiple developments that affected and will continue to impact our practice and the future of cancer treatment. After a great deal of evaluation and retrospection, here are the selections for the top ten oncology-related (and, particularly, radiation oncology-related) events of 2015:

10. Sweet dreams are made of these: after years of having to argue against reports in the popular media that sugar needs to be avoided by cancer patients since cancer cells feed off sugar, and after we've dealt with patients complicating their diets with self-imposed restrictions, it turns out there may be something to this after all, if only obliquely. A study from Genoa, Italy, reported that women with metastatic breast cancer with high insulin levels (and, concomitantly, high blood sugar levels) had a worse prognosis than those with normal insulin levels. These women also tended to have a higher BMI, but, still, suspicious that having a higher circulating blood sugar level is detrimental to controlling the progression of cancer. Then, on New Year's Eve came a press release from the University of Texas MD Anderson Cancer Center that sucrose intake in mice, compared to a starch diet, led to an increased risk of cancer and metastatic disease. This was accompanied by a tabulation of the sugar content of various champagnes, and increased surveillance on the activities of mice during New Years' festivities.

9. Inbreeding: Kaiser Permanente announced that it would be separating itself from market forces by opening its own medical school. It expressed that concentration will be on teamwork and on its own style of "integrated diagnosis and treatment." Preliminary reports are that potential medical students will be selected and separated from their families at age 3 and imbued with the philosophies of Kaiser, with emphasis on cost containment and end-of-life care, followed by courses in basic science and physical diagnosis. Reportedly tuition will be reasonable, in exchange for a nominal commitment to work within the Kaiser system for the next 35 years. Presumably use of valuable resources f or cancer care will be determined judiciously.

8. Somewhere, beyond the sea: The Trans-Pacific Partnership agreement was presented in 2015 and awaits ratification. In its 30 chapters are extensive details about how the United States will interact with eleven other Pacific Rim countries. This includes some of our closest historical allies, such as Japan and Vietnam, and our current allies, such as Mexico. Despite the complexity of the material, content was able to be released for review (due to the efforts of WikiLeaks ). Although the goal is to help working families in the United States, there have been raised questions about provisions dealing with pharmaceuticals prompting inquiries from such ultra-conservative organizations as Breast Cancer Action and the Brookings Institution, about the inclusion of provisions that can keep pharmaceutical costs high as well as even raise prices of some current drugs. Maybe after it's been in effect for a while we'll find out what's in it.

7. Excecutive health: In 2015 it was reported (somewhat confusedly at first in some sources) that President Jimmy Carter had cancer of the liver spread to his brain. It turned out to be melanoma, and by the end of the year it was gratifying to hear that he was in complete remission following Keytruda (see #3, upcoming). And surgery. And radiation therapy. Although surgery and radiation therapy often weren't mentioned. Regardless, it showed that aggressive comprehensive treatment of a 90-year-old was worth it, and it is hoped this will remembered for the next elderly non-politician. Presumably he will be lecturing at the Kaiser Permanente Medical School. As for upcoming Presidential candidates, it is not as an oncology-oriented a group as previously (with John Kerry having had a radical prostatectomy and John McCain having been treated for melanoma) but a medical report on Donald Trump indicated he was in "exemplary" health, including having a PSA of 0.15. 0.15!!! This would be the lowest PSA ever recorded in a 69-year-old male with a prostate in place!

6. On my knees, looking for the answer After zillions of dollars have been spent on cancer research, it turns out the secret of preventing cancer might lie with the study of humans with Laron syndrome. A paper in Endocrine Practice: by Zvi Laron (who else) reviewed 50 years of data on persons with Laron syndrome, consisting of dwarfism, with signs of congenital growth hormone deficiency but with high levels of human growth hormone and low levels of human insulin-like growth-factor 1. These persons are essentially free of cancer despite having other problems, such as diabetes mellitus and cardiovascular disease. Interestingly, they also have a tendency to insulin resistance despite avoiding cancer, thus complicating the conclusions of #10 above. Presumably there would be enormous yield in abandoning most current research projects to concentrate on studying Laron syndrome persons to find out how they are immune to cancer. Is it just that they have a lot fewer cells than normal-sized humans? In that case, why is it that elephants have a much lower incidence of cancer than humans. A study published in JAMA in 2015 describes that cancer incidence does not increase with body size, with elephants having a 4.81% cancer mortality compared to 11-25% for humans (in their paper, anyway) and possibly because elephants have 40 allelles for the TP53 gene compared to 2 for humans. Also maybe because they're vegetarians (see #5).

5. Grills will be grills: Maybe vegetarians live longer but maybe it just seems longer. In any event, specific links between evils of meat-eating and cancer have been irregular UNTIL a paper in Cancer, published on-line in November, It turns out that grilling can increase mutagenic compounds MelQx and PHlP, intake of which were found to be higher in persons who developed renal cell carcinoma, with the possibility of a genetic susceptibility factor. Other studies had also suggested a connection between charred meat and pancreatic cancer, colorectal cancer, and prostate cancer. As noted above, elephants don't grill.

4. Hit me with your best shot: 2015 was definitely the year that "targeted therapy" entered the pop oncology lexicon. Selection of treatment based on individual tumor characteristics has been around for years. Estrogen receptors were first identified by Elwood V. Jensen in the 1950's, molecular profiling was advertised at least as early as 2004, and by 2006 the human genome had been mapped out, but as of 2015 molecular profiling has become a status symbol. It seems to be down to which test has the best-sounding name –Oncotype, Symphony, CancerNext, RespoinseDx, Mammastrat, Blueprint, Previstage GCC< Run-D.M.C. -- to look through thousands of potential variants for which most do not have treatments.

3. All that glitters: Radiation oncologists have felt left in the lurch as publicity churns away about glitzy expensive targeted therapies and immune therapies. It seems that aiming a killer beam at the tumor is not very dramatic anymore. Fortunately, there are studies indicating that radiation therapy need not be abandoned, as long as we're happy to be one of several participants in the next generation of cancer treatment There have been multiple reports that disrupting tumors with radiation therapy seems to make immune checkpoint inhibitors work better (possibly similar to chumming.). Blowing all this away is the possibility of using radiation therapy in conjunction with nearly every overhyped word from the past several years: "Combination of Gold Nanoparticle-Conjugated Tumor Necrosis Factor-alpha and Radiation Therapy Results in a Synergistic Antitumor Response in Murine Carcinoma Models." Now just sort of overlook the words "murine" and "models" and you may really have something.

2. You're either on the bus or off the bus: The outlook wasn't brilliant for the Mudville Nine that day. CMS was about to impose another 6 to 9 per cent cut in the fee schedule for freestanding radiation oncology facilities, which would have made it improbable for the majority to be able to stay in operation. It appeared that we were thought to exist in an enchanted land in which expenses go down and technology constantly decreases in cost. Although it's an honor to be thought that we operate so much more efficiently than other enterprises that constantly increase their charges, it's an honor better to be declined. It was therefore a major triumph that the 2015 Omnibus Spending Bill included a freeze in the fee schedule for three years, even though a raise would have been nice. It also, incidentally, postponed the breast cancer screening recommendations of the U. S. Preventive Services Task Force (USPTF) for two years, possibly saving more lives than any other provision in the 2000-page bill.

1. I just don't feel like myself: Truly the most unexpected and disturbing oncology publication of the year 2015 has to be the report by Atis Muehlenbachs and 17 additional authors (it took 18 people to convince themselves this was happening) from the New England Journal of Medicine, November 5. Oncologists have always been overwhelmed by the number of malignancies and the fact that practically any part of one's body can go bad. Non-parasitologists are readily repulsed by the wonderful types of things that other species can do to humans. Now just combine the two concepts. An unfortunate dwarf tapeworm (Hymenolepsis nana) had probably been indulging in charred meat and excessively consuming sugar, resulting in its developing cancer, but it was generous enough to shed metastases to the lungs, liver, adrenals, and lymph nodes of an even more unfortunate 41-year-old gentleman in Colombia. Despite aggressive treatment, the patient eventually passed away, presumably therefore also resulting in the death of the dwarf tapeworm Does this mean that the field of oncology, as complicated as it is currently, is not even close to being comprehensive enough to handle all possibilities?


Emanuel Countdown: The Emanuel Countdown will be suspended for several months, to be replaced by a tribute to each of the 15 persons currently seeking the position of President of the United States. The Emanuel Countdown will resume after the nominees of both parties have been selected. The clock, however, will still be running.

Hey, Cruz (to the tune of Hey, Jude )

Hey Cruz, can you explain
How a Canadian can run for president
But maybe the papers that you've released
Show you're at least
A legal resident.

Hey Cruz, you've gone so far
Since you starred in Mission Impossible
Or maybe that was a different Cruse
Thinking it through,
That seems more plausible.

Just keep them out, don't let them in
Hey, Cruz, you'd win
If you can make sense of immigration
The border will be sealed up tight
But once each night
Will open long enough for deportations.
Nah nah nah nah nah nah nah nah nah.

Hey, Cruz, you've memorized
The entire Constitution
But no more space was left in your brain
For climate change
Or evolution.

Hey, Cruz, we think you must
Know you look just like Grandpa Munster
But you're the one the base would elect
If you protect
Their churches and gun stores.

And every time that you debate
You dominate
With logic, facts and style you are unbeatable
And in this nomination race
You'd have first place
If only you were not so disagreeable.
Nah nah nah nah nah nah nah nah nah

Hey, Cruz, we soon will tell
If the delegates will be selecting you
And you could become the nominee
But the RNC will never let you let you let you let you let you let you oh!
Nah nah nah nah nah nah nah
Nah nah nah nah, Not Cruz!
Nah nah nah nah nah nah nah
Nah nah nah nah, Not Cruz!
(Repeat 75 more times)