Archives for May 2017

GBM Treatment: One Small Step at a Time

GBM Treatment: One Small Step at a Time

Brain Cancer.

The term strikes fear in even the strongest of us and for good reason. In the past 5-10 years, treatment’s progressed by leaps and bounds in a great many cancers, while in others progress lags. Unfortunately  glioblastoma (GBM), the most common of adult brain cancers, is one of the latter. GBM remains an aggressive disease with a median survival of just over a year in the strongest of patients (and only half that in the more infirm).

In 2005, we took a baby step forward with glioblastoma. The EORTC / NCIC trial showed the addition of temozolomide to standard surgery and radiotherapy extended median survival from 12.1 months to 14.6 months, and improved patients’ chances of being alive at 2 years from 10.4% to 26.5%2.  While not a home run, it was good enough to become the standard of care for the next decade.  But there progress stalled, and would probably still be stalled if it hadn’t been for some unconventional thinking.

The conventional approach to cancer treatment is to eradicate every single cancer cell, achieving cure. But because GBM cells are extremely hard to kill, all of these approaches ultimately failed.

All right then, so we can’t kill it – but what if we could hold it to a stalemate?

Enter Tumor Treating Fields (TTF): a little bit science fiction, a little bit science fact. I have to admit I was very skeptical when I first heard of the technology, and was even less enthused when I saw what a nuisance it is for patients – but it works. In 2015, investigator Roger Stupp (who developed temozolomide treatment in the first place) showed that adding TTF to standard treatment improved median overall survival from 16.6 to 19.6 months, and improved a patients’ chances of surviving 2 years from 29% to 43%3 – that’s as big a step forward as adding temozolomide was in 2005.

What’s the magic? TTF subjects tumor cells to rapidly alternating electrical fields, disrupting cell division. And since it’s uncontrolled cell division that makes a cell cancerous in the first place, the TTF approach hits the cancer right where it hurts.

TTF doesn’t cause nausea, or fatigue, or infections, or low blood counts. It doesn’t even require patients come into the office for treatment– but there is a down side. Patients have to wear an electrode array affixed attached to their bare scalps (meaning they have to shave their heads), and powered by a backpack-sized battery pack. – and they have to wear it for 18 hours a day. Apart from the obvious inconvenience, the worst side effect most patients experience is some mild scalp irritation.

In America we like to imagine beating cancer all at once, a sudden stunning breakthrough that solves the problem once and for all. We’re a culture that prefers football to soccer – touchdowns, home runs, and blowout victories to gradual wins of 2-1 – but in reality cancer treatments have almost always improved gradually, one small step at a time. I’m not sure we will ever see a home run in GBM…but I do believe that slow and steady will eventually win the game.

  1. Stupp R, Mason W, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. NEJM, 2005 Mar 10; 352(10): 987-96.
  2. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomized phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009 May; 10(5): 450-66.
  3. Stupp R, Taillibert S, Kanner AA, et al. Maintenance therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA. 2015 Dec 15; 314(23): 2535-43.

Melanoma Deserves Your Attention

Melanoma Deserves Your Attention

Our skin is the body’s largest organ, so maybe it’s no coincidence that skin cancer is the most common type of cancer.

Though there are exceptions, they usually form on skin that had heavy sun exposure – so unlike most cancers that hide inside the body, we can actually see these cancers with our naked eyes.

Most types of skin cancer aren’t terribly dangerous, but malignant melanoma’s the exception. Though it’s the least common type of skin cancer, it’s by far the most aggressive. Melanoma’s easy to cure – but only if we can catch it before it starts to spread. It can invade nearby tissues and spread to other body sites much earlier in its lifespan than most other cancers – while it’s still just millimeters in size. That’s what makes it so dangerous, and why early detection is so crucial.

Recognizing melanoma’s signature features are the key to early diagnosis, treatment and cure.

Just remember “ABCDE”:

Asymmetry: One part of a mole or birthmark doesn’t match the other.

Border: The edges are irregular, ragged, notched, or blurred.

Color: the color is not the same all over and may include shades of brown or black, sometimes with patches of pink, red, white or blue.

Diameter: The spot is larger than ¼ inch across – about the size of a pencil eraser.

Evolving: The mole is changing in size, shape, or color over a few weeks or months.

If you’re in doubt about a spot on your own skin, please don’t hesitate and see your primary care provider. It might save your life.

FLT3 mutations in AML: From Trivia to Triumph

FLT3 mutations in AML: From Trivia to Triumph

Here’s an aggravating fact about medical education – a large chunk of what’s taught in medical school is useless trivia:

  • The muscle that elevates your palate is called the tensor veli palatini…
  • Here’s the best way to treat leprosy…
  • Adults whose acute leukemia cells carry an internal tandem mutation of the FLT3 surface tyrosine kinase have a worse prognosis…

I and other cancer specialists have known that last little nugget for about ten years, but haven’t been able to do squat with it:

“So should I use a different induction chemotherapy for FLT3-mutants?” (No)

“Should all FLT3 mutants get a stem cell transplant?” (Not necessarily)

“Is there anything I can do differently for these patients?” (Silence)

Thanks. Thanks a fricken’ lot.

It’s a little unfair to rant, I know. There’s a long lag time between discovery and new treatments for cancer -but the wait is hard, especially with new leukemia patients coming in the door every month.

But last week finally – finally – a drug targeting this specific molecular defect was approved by the FDA.

See, FLT3 is like an “on” switch for cell division. It’s supposed to only be on when it gets a particular environmental signal, and not every cell even carries the switch. But about 35% of acute myeloid leukemia patients have FLT3 abnormally expressed in their cancers – and the switch is stuck in the “on” position, driving cancer cell growth.

Happily, the new FLT3-inhibiting drug midostaurin (given as a twice-daily pill) markedly improved response and survival rates in AML when added to the standard chemotherapy cocktail. The benefits seemed most pronounced among people who ultimately went on to receive a stem cell transplant – but a higher percentage of patients were able to achieve the remission usually required as a first step before transplant.

So now I can re-categorize the FLT3 information from “trivia” to “critical information” in my brain, as I impatiently wait for more breakthroughs.

FDA Press Release 4/28/17: click here