Monday, July 22, 2019

Yup, Still There

What's still there, lurking in the dark recesses of my mind?


Two weeks ago I started to have a slight twinge in a front tooth. It got slowly worse over the next couple of days, to the point I called my dentist's office. They asked if I'm a grinder (sometimes) and whether I was wearing my night guard.

I wasn't. So I gave that a try. Seemed to help the first night.

But then over the weekend I developed a lot of tongue pain. It seemed to change a lot in character, but it definitely involved muscle pain that made it painful to eat. You don't realize how much you move your tongue while eating until it hurts to do so!

I probed a lot with my finger. Finally I probed waaaaay at the base of my tongue, between it and my jaw.


Yup, that's it.

Hmmm. Base of the tongue, you say?

Longtime readers may recall that the very first sentence I ever heard involving cancer contained the words "base of the tongue."

So, ya, I spent the weekend thinking I was having a recurrence of cancer.

And this is after years of telling people I'm cured.

I stewed.

I shared this theory with Wonderful Wife, who of course took it in stride. I planned in my head how I would contact the Head and Neck Cancer Center at Dana-Farber on Monday and try to get an appointment ASAP.

Monday I forgot. Hmmm.

Meanwhile, I had also developed a cold sore on my inner lip and two blemishes on my chin which are very unusual for me. Probing more, followed by a visual examination by Wonderful Wife, confirmed that at least part of the tongue pain was coming from a large sore on the side of my tongue.

Monday night I bolted awake with a different diagnosis: shingles. All on one side of the body, all in the same region, "tingliness" to the pain? Check, check and check.

I visited my doctor's office on Tuesday morning and it took the nurse practitioner about 60 seconds to confirm the diagnosis.

Whew. Not cancer.

This is what cancer survivorship is like. You move along in your life and everything seems normal, but that fear is just under the surface ready to pop out with the slightest opportunity.

You may remember that at one point in my journey I was elated to find out I had a sexually-transmitted disease (HPV). This time I was equally happy to have shingles.

I'm writing this on Monday two weeks after symptoms first appeared. It was quite painful all last week but managed pretty well with interspersed Tylenol and ibuprofen. Saturday it started to improve and today I am almost pain-free and the sores are healing. I'm glad that my course was brief.

I harp on readers incessantly about the HPV vaccine (and I'm about to do it some more). There's a vaccine for shingles, too. It's called Shingrix. The problem is that it is in short supply and hard to find. Every couple of months over the past two years I have thought about it and called a pharmacy or two to see if they have it available. I struck out every time. If you are over 50, I encourage you to obtain it.

Monday, June 17, 2019

HPV Vaccination is Paying Off - Scotland Edition

Several countries made HPV vaccination mandatory as long as a decade ago. That means the 12-13-year old young women who received it first (before it was approved for boys of the same age) are now in their early 20s are are receiving PAP smears. Scotland was one of those countries. The results are as very positive.

BBC News April 4, 2019:

HPV vaccine linked to 'dramatic' drop in cervical disease

The routine vaccination of girls with the HPV vaccine in Scotland has led to a "dramatic" drop in cervical disease in later life, new research suggests.
Human papilomavirus (HPV) is a sexually transmitted infection and some types are linked to cervical cancer.
Researchers said the vaccine has nearly wiped out cases of cervical pre-cancer in young women since an immunisation programme was introduced 10 years ago.
They found the vaccine had led to a 90% cut in pre-cancerous cells.
And they said the effects of the programme had "exceeded expectations".
The uptake of the vaccine in Scotland is about 90%.
A team of academics - from Strathclyde, Edinburgh, Aberdeen and Glasgow Caledonian universities - analysed vaccination and screening records for 140,000 women who went for their first cervical screen from 2008-2016.
Their study, published by the BMJ, concluded that Scotland's HPV vaccination programme has led to "a dramatic reduction in preinvasive cervical disease".
It adds that the vaccine is "highly effective" and should greatly reduce the incidence of cervical cancer in the future.

Sunday, June 16, 2019

Six Years

Wow, I can't believe I haven't posted since the five year mark a year ago!

Life goes on. Everything I said last year is even more true today.

The family is all well.

I am well.

Carry on!

Sunday, June 24, 2018

Five Years

So, I just passed a little milestone: five years since cancer diagnosis.

I’m an official cancer survival statistic!

There’s nothing magic about five years with my particular cancer. But in order to measure progress overall, the CDC and other organizations track and publish five-year survival rates for all cancer types. You can see them here (on the Survival tab).

It feels both long ago, and like yesterday.

Wonderful Wife and I find that we use it as a life milestone. We’ll be trying to remember when some other event occurred, like having the house painted, and we’ll ask each other, “Was that before or after cancer?”

Long-time readers of this blog may recall that once I learned my cancer was highly survivable, I wanted to treat it like the flu with an unpleasant treatment. I didn’t feel like it would become a significant life event for me.

I was wrong.

I’ve written about scares I’ve had since treatment, where some other symptom or remark by a clinician unleashes an unexpected level of fear. It surprises me that it is right there under the surface.

I’ve always tried to be an empathetic and kind person but I think surviving cancer has helped me become even more so.

Two years ago I went to work in Informatics at Dana-Farber. That continues to be quite an honor. It gives me weekly opportunities to be helpful and kind to patients who are in the thick of it. And my personal experience gives me valuable insight in my work. I am working on projects that should have a direct impact on cancer research and new and improved treatments.

The Progeny both suffer from anxiety. They did to some extent before cancer (it’s disheartening how many adolescents suffer from anxiety today), but cancer definitely stepped it up, especially for Progeny the Younger who is now 12. Both have gone to therapy.

Wonderful Wife has a long history of depression, which fortunately is pretty well managed with medication. But after the heroic effort she put in taking care of me during treatment and recovery, she experienced a deep trough for several months. Luckily, with the help of her doctors, she was able to climb out and has done pretty well since.

The side effects of treatment persist but are just part of life now. I still cough a lot because of diminished and thick saliva that makes my throat "sticky". I think my sense of taste has improved, but it's such a subjective thing that it's not clear whether that is physical change or modified perception. My hearing is still affected, but I only have significant trouble in noisy environments like restaurants and bars where trying to focus on a conversation can be exhausting. Those are constant reminders of cancer, but they have a neutral sense to them - they are what they are.

The fact that I write so seldom here these days is evidence of the recession of cancer and its effects into the background of my life. Life is normal and busy, and even though I have a long list of topics I’d like to write about here writing never seems to rise to the top of the list.

I’m not even sure anyone is still listening here. If you are, please send a note to john at Just say “I’m still here, keep writing!”

Next week I visit Dr. Chemo for my follow-up visit.  Those are now just twice per year.

I’m going to bake brownies and make cards with a family photo, and deliver them to the Head and Neck Clinic, the Infusion Center, and Radiation Oncology. These are the places where I spent most of my time during treatment. The staff sees most people at their worst, and I know they like it when former patients come back healthy and happy and normal.

Happy Five Years to me!

Friday, April 13, 2018

A Strong Thread

Wow, it's been ten months since I've posted here. Way too long. Please leave a comment to let me know if anyone is still here!

I actually have a stack of topics I've collected to write about but I never seem to make it a priority in my time or energy budget.  But here I am. And I'll try to get to those topics soon.

This week my friend and neighbor, a health economics researcher and blogger and Twitter god, wrote about a health issue he is experiencing. Then he wrote about the experience of writing publicly about a personal health issue, including the positive feedback he received, the rapid widening of his knowledge of the topic via input from his circle, and the response from a few people asking if he worried about future ramifications. He also wrote that he found the experience cathartic.

I sent him praise for his openness, and I asked if he was familiar with Brené Brown. It turns out he is quite familiar with her and strives to learn her lessons.

Well, that brought to mind my friend and former coworker Yair (who has consented to being identified here). In the middle of cancer treatment Yair praised me for my honesty and vulnerability on this blog and told me about BrenĂ© Brown, whom I had never heard of. I watched her famous TED talk videos (2010 and 2012). She speaks my language. Through years of therapy and 12-step groups and other work, the most important accomplishment of my life was finally arriving at the sense of worthiness that she describes, accurately, from my experience,  as the core of happiness.

Having that brought to mind by my friend/neighbor's recent writing caused me to go watch those videos again. Powerful stuff.  I highly recommend you invest the 40 minutes to watch them. I want my teenage daughters to watch them.

That, in turn, caused me to go back and reread many posts from this blog. I do that from time to time to remind myself where I've been. I started with Why Am I Here?, the post that prompted Yair's comment, but then moved backward in time into the worst parts of treatment. Yair was mainly praising my willingness to show weakness and fear, like in A Crying Shame and Ultraviolence. That last post, especially its last two sentences, caused me to cry tonight!

The core of Dr. Brown's message is the title of that 2010 TED Talk: "The Value of Vulnerability". Vulnerability is what enables connection, and connection is what we all crave. She says, "it's what we're wired for."

With this post I thank Yair for connecting years ago, and for the thread that runs through a growing connection with my neighbor today.

Go forth and be seen!

Wednesday, June 7, 2017

A Big Advance in Cancer Care

One May 23 a very significant event took place in the history of cancer treatment. The FDA approved use of an existing drug for first line treatment of cancers based purely on specific DNA changes in the tumor, regardless of the body site of the tumor.

This is a first for the FDA. All previous cancer drug approvals have been for cancer originating in specific body site such as colon, breast, lung, etc.

This is a long post, but I want to describe the context so you can understand the significance of this event.

After the human genome was sequenced at the beginning of the 21st century, cancer researchers began to discover that some DNA changes were common in cancers originating in the same site: for example, a particular DNA mutation in the gene called BRAF is common in colon cancers. Drugs - called targeted therapies - were developed to kill cells with that specific mutation. Similar targeted therapies were developed for other mutations, which had common occurrence in other tumor sites.

Targeted therapies were a great advance and they are still being developed. But most of them produce drug resistance. The drug kills the cells at which it is aimed, but the tumor evolves. Yes, just like Darwin described: other cells in the tumor do not carry the targeted mutation and are thus more adapted to their environment and outcompete the targeted cells. The drug stops working and the tumor grows again: cancer recurrence.

In a separate thread, cancer researchers have wondered since the 1960s why the immune system doesn't attack tumors. One core answer to that question is provided by Siddhartha Mukherjee in "The Emperor of All Maladies": cancer is us. It is not a foreign substance or organism in the body, it is our own cells that have sustained DNA damage and lost control over their growth and division. Thus the immune system does not generally recognize cancer cells as foreign.

The immune system is incredibly complex. But knowing the human genome and being able to use that knowledge as a scaffold has allowed researchers to gain much more understanding of adaptive immune cell function; specifically the proteins on the surface of T cells and B cells, the core components of the adaptive immune system.

The most significant discovery in this realm so far was that some tumors could "hide" from the immune system by manufacturing a specific protein (PD-L1). Drug companies were able to make drugs that target that protein, unmasking the tumor cells and "releasing the brakes" on the immune system so that it would attack the tumor.

Results have been spectacular. It is not an exaggeration to say that this has been the single most significant impact on cancer care in decades. Cancers that were death sentences before these drugs, such as the first approved cancer type, metastatic melanoma, suddenly were treatable and some patients cancers disappeared completely (e.g. Jimmy Carter).

This class of drug is called immunotherapy for obvious reasons.

Unfortunately, these drugs don't work for all tumors. They currently produce a partial or complete response in about 30-40% of the cancers in which they are most used. So the obvious question is: why? And can we tell ahead of time which patients will benefit?

One of the drugs (pembrolizumab, marketed by Merck in the US as Keytruda) uses a biomarker to try to determine a patient's likely response. A biomarker is just a biological factor you can measure. Simple examples are weight or blood type. A more complex one (to measure) is amount of PD-L1 produced by a tumor. Pembrolizumab was believed to work in patients with "high" PD-L1 expression and was approved by the FDA for patients with that biomarker - in specific cancers.

[Full disclosure: I used to be employed by Merck but I have no current financial interest]

But more recent research has shown that what might really tell us which patients will respond to immunotherapies is how many mutations they have in their tumor cells' DNA. DNA is the template for proteins; DNA mutations can result in changes in the proteins produced. The theory is that the more mutations a cell has, the more changes are likely to occur in the proteins the cell has on its surface. And the more protein changes on the cell surface, the more likely the immune system will recognize the cell as "bad" and kill it.

As I've described in previous posts and above, cancer is a disease of the DNA. Accumulated mutations eventually activate an oncogene, causing cells to lose control over growth and division, or mutations disable a tumor suppressor gene, leading to the same problem.

Cells have multiple mechanisms to repair DNA damage and do so on a regular basis. But if you end up with mutations in the repair mechanisms, you're in trouble. One of these mechanism is mismatch repair. Loss of the mismatch repair mechanism can lead to one specific type of hypermutation called microsatellite instability.

These two characteristics of tumor DNA lead to high tumor mutational load. Remember that a high number of mutations seems to increase the likelihood that a tumor will respond to immunotherapy.

And now we're back at the the recent FDA approval. It says:

Keytruda (pembrolizumab) is indicated for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This indication covers patients with solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and patients with colorectal cancer that has progressed following treatment with certain chemotherapy drugs.

The most important part is that it is approved for any solid tumor that has these DNA characteristics, regardless of the body site in which the tumor arose.

[You may not be used to the term solid tumor. It means what it sounds like: a cohesive mass of cancer cells in a mass. Liquid tumors includes such cancers as leukemias and lymphomas in which the cancer cells are distributed through the body in blood, bone marrow or the lymphatic system.]

People like myself who work in cancer genomics have long "known" that a day would come when we would treat cancers by their molecular (DNA) characteristics instead of their site of origin.

This FDA approval represents the first milestone in that transition.

Friday, May 5, 2017

Four Years

May 6, 2013 was the day I first visited my doctor about a sensation in my throat. She noticed a lump on my neck.

Thus, today is the fourth anniversary of my cancer diagnosis.

I'm doing just fine, thank you. I go in for surveillance follow-ups every six months now with my next appointment in July.

Cancer survival statistics are based on "5-year survival", which is pretty simple: is the patient alive or dead five years from diagnosis? If a particular cancer is going to kill you, it usually does so by then.

So, a year from today I'll (hopefully) be an official survival statistic!

Since we're on the topic of cancer survival, I thought I'd take the opportunity to give you the big picture.

One thing I've learned in my new job is where cancer statistics come from: cancer registries.

Every hospital that treats cancer must report cancer incidence to their state registry. The process is designed so that a particular patient is only reported once (even though they may be treated at multiple hospitals) to avoid double counting.

These registries are staffed by Certified Tumor Registrars. These are specially trained people, many with medical backgrounds, who carefully curate each cancer case to accurately record data such as patient demographics (age, gender, zip code, etc.) date of diagnosis (important for survival statistics), actual diagnosis, site of the tumor, initial treatment and response to initial treatment, and a whole bunch of other data.

That data is collected at the state or regional level and then reported onward to the federal government through two programs: the National Cancer Institute's SEER program (Surveillance, Epidemiology, and End Results, covering about 28% of the US population in 15 regions) or the CDC's National Program of Cancer Registries (covering 45 states and D.C.).

Here's a diagram I made for a talk I'm giving soon that illustrates the process (click to embiggen):

All that careful data collection enables us to see trends in cancer over long periods of time.

Here are the stats on new cancer incidence and death rates as of 2013:

The long-term trends are encouraging. Here are graphs showing changes in cancer survival for the most common forms of cancer, comparing survival in the 1975-1977 period to the 2006-2012 period:

Some highlights:

  • In the 1970s you had 75% chance of surviving breast cancer. Now you're chances are above 90%.
  • Prostate cancer 5-year survival was 67.8% and is now above 99%.

There are still too many cancer types in which we haven't made much progress: lung and pancreatic cancer are still very bad news, for example.

Many of the cancer types with poor survival, especially those two, are due to the fact they tend to be asymptomatic and therefore are not discovered until they are at an advanced stage.

Researchers are hard at work on that. Tumors, including nascent ones, shed both complete cells and also contents of dead cells into the bloodstream. There is hope that "liquid biopsies", which aim to detect cancer cells or cancer cell DNA in the bloodstream, will be able to detect these and other cancers much earlier. That approach is still a ways from routine use. As you can imagine, the number of tumor cells or amount of tumor DNA in the bloodstream is very low; identifying them reliably is like trying to tune in a very weak radio signal.

One advance that doesn't yet show up in the survival statistics above, since they currently cover the period through 2013, are the "immunotherapy" drugs Opdivo (nivolumab) and Keytruda (pembrolizumab). These are among the first approved drugs that leverage the immune system to attack cancer - they essentially "decloak" the cancer so the immune system can see it. These drugs were approved by the FDA in 2014 and have had a dramatic effect in some cancers, especially metastatic melanoma (melanoma that has spread). About a third of these patients, for whom the prognosis was previously less than one year of survival, have experienced complete remission.

Anyway, I'm glad to still be here four years after my own diagnosis. And I look forward to becoming a statistical survivor a year from now.