Seeking What's Possible

Friends,

A little more than a month ago, Elaine was in the kitchen, cooking and I was sitting at the counter, writing. She suddenly whirled around and said, “It’s a year today. It’s April 26th. The big surgery was a year ago today.” It was worth noting. It had been a difficult year, but we are both still here and happy together.

We’re in the flow of cancer now. It is a regular routine, as though everything’s alright, but with the nagging awareness that you’re under the Sword of Damocles. After her first round of conventional chemotherapy, Elaine entered remission, which means that most of the signs and symptoms had disappeared. But in all likelihood the cancer remains, with fewer cells present. For now.

Most women with primary peritoneal cancer have a similar experience. Their cancer is knocked back for 12-36 months and then it recurs, strengthened and more ferocious than ever. The problem is that, after the wrenching experience of chemotherapy - the hair loss, the intestinal roller-coaster, the bruising - nobody much wants to press on, and there’s the sense that you’re in a lull and can relax just a little.

That’s an illusion. Cancer is a stealthy, sneaky, relentless adversary, and it’s at it day and night. Or as my friend Tom Barr noted the other day, “the Emperor NEVER takes a day off.” This means that the ONLY path is vigilance, and pursuing every possible rational lead, independent of whether we feel like it or not. We’re after long term benefits for short term sacrifices, however difficult those may be.

With cancer, patients’ realistic options have been extremely limited in the past. But there’s one in front of us now that appears to be promising, and the very leading edge, not just of cancer care, but of medicine. A colleague at Harvard learned about Elaine, and put us in touch with a small Boston personalized medicine start-up. N-of-One (great name!) doesn’t provide care directly, but is really a personalized, cancer treatment, concierge ombudsman service. It is based on the understanding that cancer most often occurs from mistakes in the genetic code, and that individuals with the same kinds of cancer can have dramatically different error signatures.”

Here’s an excerpt of the explanation under the heading “Discovering the Molecular Signature of Cancer” on the N-of-One site.

...most cancers are associated with mistakes in the genetic code. Such mutations have been found in more than 120 genes. These genes control the synthesis of proteins that carry out the biochemical reactions (referred to as molecular signaling pathways) that regulate cell division, growth, and death. Mutations to one or more of these genes may cause a cell to produce too much or too little of a key protein or produce a defective protein that does not respond appropriately to the molecular signals. Carcinogenesis is initiated when these mutations are sufficiently severe to disrupt the molecular pathways that control cell division and other related cellular properties, resulting in the formation of a tumor, invasion of surrounding tissues, and metastasis.

Each cancer has its own unique genetic and molecular signature. This explains why individuals with the same type and stage of cancer may experience dramatic differences in their responses to chemotherapy. Researchers now have the means to rapidly analyze the unique signature of a patient's tumor based on the expression of the genes involved in its carcinogenesis. This capability has opened the door to more accurately predicting the outcome of a patient's cancer and individualizing his or her treatment to match the molecular characteristics of the tumor.

Think for a moment what a breathtaking, sweeping advance this is! It is now possible to conduct assays on tissues to evaluate mechanisms at the level of the gene. Then we can try to match the particular configuration of problems with therapies that exist or, alternatively, build a new therapy that can target that individual’s issues. This approach, still very much in its infancy, of course, moves medicine to a much deeper, more individual level of biology than ever before, and has immense promise.

So, in this approach, the N-of-One team would coordinate assays at labs around the country, each of which provide high expertise in different tests. As the results come in, a genomic profile would be assembled that reflects the patient’s - in this case, Elaine’s - molecular characteristics.

Then a search would be conducted to match Elaine’s genomic signature to an available genomic therapy. At the moment, there are nearly a thousand of them, though most aren’t germane to Elaine’s condition. Still, it is probably safe to say that there are more than any busy practicing oncologist can keep track of on his or her own. (Actually, it’s worth noting that Elaine’s current treatment regimen, a one-year course of Avastin, falls into one of the four categories of currently established genomic treatments.)

This is important. This approach is credible, yet few physicians I’ve spoken with have more than a passing knowledge of what’s available. Which means that many patients with serious conditions who might benefit from it, don’t, because their doctor is too immersed in the day-to-day to really understand it.

We’re now seriously assessing going down this path. Steve Buckley, our wonderful gynecologic oncologist, sat in on our call with Jennifer Levin-Carter, MD, the Founder of N-of-One, and is thinking through this with us. If we proceed, Dr. Buckley would still manage Elaine’s case, but presumably he’d have access to a great deal of new, better information.

It’s important to keep this in perspective. When it’s all said and done, this approach, at this time, may provide no benefit for Elaine. But maybe it will. And that what makes it seem worth it.

In the meantime, Elaine is as beautiful, happy and busy now as I can remember. Our kitchen is doubling as a painting studio. There’s yoga and reading and some discussion of new ventures. Strange to say, but it’s a remarkable, productive time.

More as events unfold. Thanks again for going through this with us. Keep reading for Elaine’s take on where we are now.

B

The Breather

Elaine's 6-month long, first line chemo-therapy treatment finished 4 months ago, in October, and she's looking positively radiant. Now that she can taste again, she's put on a little much needed weight. Her hair has grown back into a very short but very attractive style, and people who don't know her or about the cancer spontaneously tell her how cute it is. (She's said, "My oncologist did it for me.") The bruising, the digestion problems, the numbness in her feet and hands, the relentless fatigue all have improved as we've entered the honeymoon period that is remission. 

Book Review: The Emperor of All Maladies: A Biography of Cancer

BRIAN KLEPPER

The opening page of Siddhartha Mukherjee’s The Emperor of All Maladies begins with a quote by Susan Sontag that is so on-point, yet so rare and fresh, that one can’t help being excited by the prospect of what’s to come.

Illness is the night-side of life, a more onerous citizenship. Everyone who is born holds dual citizenship in the kingdom of the well and in the kingdom of the sick.Although we all prefer to use only the good passport, sooner or later each of us is obliged, at least for a spell, to identify ourselves as citizens of that other place.

Joy, With Reservations

A very quick update. Today was 3 weeks exactly since Elaine’s final chemo infusion, and we had an appointment with the terrific Dr. Buckley, who would give us an update. Last Friday she had a PET scan, which shows the progress of the tumors and provides a basis for evaluating the status of her cancer. Needless to say, we’ve been on pins and needles for the past few days, hoping the report would be good. We are not superstitious, but somehow we found ourselves not wanting to hope too much, for fear of jinxing the result.

The Moment

At 11AM Wednesday, Elaine called to say that she was done and on the way home. She had just finished her 8th and last chemo infusion. It seems like yesterday to Elaine and an eon ago to me that Dr. Buckley told us she needed six months of treatment and we steeled ourselves for the long haul. Now we're finished, except for periodic checks, at least unless the cancer returns and we need to go through another round of chemo therapies.

Who We Are

Receive news of cancer, and it immediately becomes all consuming. But at some point, day-to-day life returns, although slightly askew. Now that we’re face-to-face with the gravity of our circumstance, it has become Life, With Cancer. But as my close friend Jerry Reeves, a pediatric oncologist in his first career, observed, “You don’t stop being who you are, just because you have cancer.”

Elaine has been as positive and uncomplaining as is possible to be. We’re simply working our way through it. But we try to not become morbid either. Playing the cancer card is a way to poke fun at how crazy our situation is, and to remind each other that life goes on.

So, in the snappy repartee that dominates a fair portion of our dialogue at home, the tumor humor plays out something like the following:

Early Morning. I’m up and am doing emails in the living room. Elaine calls out from the bedroom.

“Where’s my coffee! I have cancer, you know. I can’t be getting up to make my own coffee!”

There are variations on this theme.

Her: Boy, I could really go for a hamburger with fries and a shake.

Me: You’re shameless. Don’t you have any standards?

Her: No. I have cancer.

Exhausted

Eight years ago, when I was recovering from open heart surgery, I wrote that it was difficult at times to stay focused on recovery and feeling better. That was a big surgery, yes, but within two weeks my prospects were good again. There was no protracted treatment or life impact, except of course for focusing on living a healthier life. That experience proved to me that a positive attitude is both a discipline - a constantly cultivated perspective - as well as key to a healthy outcome.

But Elaine’s experience is showing us that maintaining a sunny disposition becomes far more difficult as the challenge drags on, and the prospects for getting better become more uncertain. The most difficult part of a long disease could be the exhaustion that ultimately can overwhelm, or at least shake the resolve of, even the best efforts to remain positive and clear. After 6 months that have included 5 hospitalizations, 4 surgeries, an emergency visit and 5 cycles of having poisons infused into her body, Elaine and I are having our resolve tested. And we know we have a very long road ahead.