Month: January 2013

I learned a lot today during our appointment with Dr. Lipson at Johns Hopkins – so much that I can’t absorb the information and turn it around into a day-one story. I’ll write more in the next week about melanoma, but for today I’ll write about the biopsy.
Dr. Lipson seemed pleased with the chunk of tissue he took out of Robert’s leg. To explain why, he started talking about apples. This one, he said, was “not this soft, mealy, mushy thing you bite into. It’s crispy and firm.” Sometimes, he said, “you get an apple that’s like a four-day-old pear.” This one was more like a Honey Crisp apple: when you bite into it, “it comes off in one satisfying bite – you get a bite that’s self-contained.”
The good thing about a crisp biopsy is that you only need one stitch to close the wound. So, that’s all Robert got – one stitch!
We also took note that Robert’s injection sites are less reactive this time than they have been after the previous GVAX injections. This is not out of the mainstream of other patients who have completed the cycle of four injections in the trial.
Dr. Lipson likened this vaccine therapy to getting a series of allergy shots. The first time the vaccine is injected, the immune system recognizes it as a foreign substance and reacts at the injection sites, making them red. The reaction creates an army of T-cells and antibodies to fight the foreign substance if it comes along again. With the second injections, the immune system goes nuts because it knows what it’s looking for now, and hence, the swelling and itching are much worse.
Over time, the immune system gets used to the foreign substance, and with each additional injection, it cares less and less. That’s what we want to bring about with allergy shots, which generally are given over a much longer period of time.
With the GVAX, now it’s time to stop. We hope those T-cells and antibodies have done a job on any micrometastases left in Robert’s body after the surgery. Now, it’s time to get on with our lives …
That doesn’t mean we’re done at Johns Hopkins, however. We have two more follow-up visits, and the one in April will include scans to make sure there are no active tumors in Robert’s body. After that, we will watch and wait – and hope.
All for now. Call or email if you have questions.

Our trip to Baltimore yesterday was not routine because we threw in an appointment with Dr. Tim Wang, director of the Cutaneous Surgery & Oncology Unit at Johns Hopkins. What I learned was different from what I expected.
Robert’s oncologist, Dr. Evan Lipson, referred us to Dr. Wang in a previous visit when I complained that a dermatologist here in D.C. wouldn’t show me what he was seeing on Robert’s body during an exam. I understand that was an unusual request, but I want to know what to look for. Dr. Wang has a reputation for helping people learn about melanoma, so we decided to consult with him for one of Robert’s quarterly skin check-ups.
Dr. Wang might have chuckled when he read Robert’s response on the pre-appointment form to questions about why we were there. The form asked about the location on the patient’s body of any troublesome spots, and also how long they had been there. A bit frustrated, perhaps, Robert muttered, “they’ve got to be kidding,” before writing “Everywhere” and “Forever.” That about sums it up …
It also could give you an indication of how frustrated I have been trying to apply the ABCDE principles when I look at Robert’s spots, as suggested by a National Cancer Institute nurse earlier this month. How long do they think I could get him to lie still? Let someone else do that …
But that left me with, basically, nothing to go on, so I was looking forward to taking lessons from Dr. Wang. Here’s what I learned.
First, check out the local area where the primary melanoma was removed from. This is important because a melanoma that’s been resected is most likely to come back in that same area. First, Dr. Wang said, not only should I look at the graft but also run my finger over it. Look for bumps or lumps particularly along the margins of the graft and just outside the graft area. These don’t need to be colored – they could appear as flesh-colored bumps.
Next, we should check Robert’s lymph nodes regularly for enlarged nodes, the size of a marble or golf ball. There are still plenty of nodes left in his neck, and I will notice if any of them are enlarged. I’ll leave digging in his armpits and groins for him to do …
The third task is the one I had puzzled over – looking for another melanoma to pop up somewhere else on his body. Dr. Wang said about 5% of melanoma patients have a second primary, which might present as any other cutaneous melanoma – a dark, asymmetrical spot with uneven edges and uneven color. But how to find one? On people, like Robert, with lots of sun damage and freckles, “you would go crazy if you did the ABCD thing for all of them,” he said.
This is particularly true if you try to start out focusing on individual spots. The secret is, don’t stand too close! I pointed to one particular spot on Robert’s back and another on his forehead that appeared to be darker than the others. Dr. Wang suggested that I stand back and look again. I could still see those spots, but now I also noticed others that were just as dark.
A worrisome spot (“spooky,” as Dr. Wang put it) would be bigger than a freckle. It would be not only dark, but also rough and uneven, possibly bleeding. I think size is another factor – they generally are at least 6mm in diameter – though they have to start somewhere and perhaps just go unnoticed when they are smaller than ¼ inch. That’s why the docs recommend that you look once a month and take note of any spots that are evolving, or growing.
It was hard to learn what to look for when Dr. Wang didn’t see anything. But he did point out a spot on Robert’s lower leg, just above the ankle, where two freckles seem to have blended together. Seen together, they are not symmetrical and are bigger than the others. We’ll watch them, but he was pretty sure they were just that – two freckles too close to separate on sight.
GVAX – Cycle 4
We are old hats now at getting the GVAX injections. The blood is drawn first-thing – lots of it, but Patient Robert lies on a gurney now and Nurse Robert draws the blood slowly so it won’t come as such a shock to the patient’s system. While the regular lab levels are being measured to make sure there are no indications of infection or illness that would preclude continuing with the vaccine, we see Dr. Lipson and talk about Robert’s reaction to the injections while he does the physical exam and palpates lymph nodes.
Cycle 3 seems to have caused less of a reaction, and Dr. Lipson said there is no set pattern with it – some patients continue to have more severe swelling and itching, but others don’t. Robert mentioned that he believes there has been one point of consistency in his reactions – a “raging heartburn” that comes on even before we get onto I-95 to drive home. Dr. Lipson and Susan, the study nurse, seemed surprised – as though this was a new finding, if it is related. But then again, we don’t know – and probably won’t – whether it is related to the vaccine. It seems to Robert as though it’s related, and indeed it happened again yesterday, although the reaction was a bit delayed this time – just long enough for us to go to Bertha’s and eat some mussels.
Perhaps it is related to the “garlic breath,” which I found to be much more objectionable yesterday than after the first three cycles. That reaction was much more noticeable to me this time than in the past. It doesn’t seem to bother Robert at all.
Although the swelling was there this time, it seemed to be less bothersome. Robert did not complain of itching yesterday or today.
So, tomorrow morning we are off to Baltimore early for the post-Cycle 4 biopsy. Feel free to call or email if you have questions, but please don’t expect an answer until Friday.

Today we visited the front-of-the-eye ophthalmologist for a test to see if Robert can keep driving. (He can. Yay!) He hadn’t been to an eye doctor in a while because his retinal specialist retired and we didn’t get around to finding a new one yet. But Dr. Ladas did a thorough exam and looked in there for anything that didn’t belong. All is OK in the eye department!
When we were at Johns Hopkins four weeks ago, Dr. Lipson told us there was no known connection between ocular melanoma and cutaneous melanoma. Today Dr. Ladas explained that both kinds usually present as primaries, and it would be unusual to find a metastasis from one to the other (skin to eye or eye to skin). He explained further that ocular melanoma generally begins with spots in the pigmented portion of the eye, sort of like freckles. Not only did he not find melanoma, he also didn’t find anything to watch. So, no eye freckles. This is good!
Now, of course when I said “all is OK in the eye department,” that is a relative statement. Robert’s eyes have not gotten any better – but then again, we didn’t expect them to. He still has little vision in his left eye, and it’s not correctible. We’ll replace his two-year-old contact lens for his right eye with a slightly stronger one. He can see well enough to drive, and the form is ready to go to the DMV.
Tomorrow we go to Hopkins for GVAX Cycle 4. I’ll try to write again on Wednesday.

Robert said in his initial email to family and friends about his melanoma that it was a risk factor for his blood relatives. I’ve done a little studying on the subject, and my assessment of that statement (whatever THAT’s worth!) is a little different now. But the bottom line remains the same: please have a complete scan of your body, if you haven’t already, and discuss your risk factors with a dermatologist.

I decided to look into this when I found out recently that my grandmother (“Lovey,” to those of you who knew her) had ocular melanoma. I knew  that she had had one eye removed – who could forget Lovey’s glass eye?! – and I knew she had cancer in it. However, I had not heard it described as melanoma until I reviewed some of my family’s medical history with my mother a couple of weeks ago. That information raised a question for me: are my children at increased risk of contracting melanoma because they have family history on both sides?
Dr. Evan Lipson, Robert’s oncologist at Johns Hopkins, suggested that I contact researchers at the National Institutes of Health who are studying melanoma in families, so I wrote to Dr. Margaret Tucker, the National Cancer Institute’s principal investigator on familial melanoma. Research study nurse Ginny Pilcher responded by sending me the latest information on the study as well as links that would help me learn more. The research is being conducted by the NCI’s Division of Cancer Epidemiology and Genetics (DCEG). Dr. Tucker is head of the division’s Human Genetics Program.
By studying families with numerous incidences of melanoma, Dr. Tucker’s and her colleagues’ work through the years has helped identify several melanoma susceptibility genes. The researchers continue to look for other genes that are associated with melanoma, and new information has been reported within the last year based on their work. We know that Robert doesn’t have mutations of the BRAF or KIT genes that have been associated with melanoma. As far as I know his tissue hasn’t been examined for other melanoma susceptibility genes.
Even with all the recent research findings, however, I think they still don’t know enough about what causes melanoma to predict whether Allison, Loren, and Gabriel are really at increased risk just because of Robert’s illness. Their risk factors are probably no less than his – fair skin and/or lots of moles, plus a history of heavy sun exposure, can’t help them in this department. And, I’m not sure sun screens were any better when they were little than in Robert’s childhood – though they certainly can help themselves from now on by using SPF 30 sun screen EVERY DAY. (Yes, the latest research bears this out – it is not an unfounded advertisement for the sunscreen industry.) In retrospect, I’m not sure how much good Robert’s slathering with SPF 8 has done through the years. Today, we know more.
As for my “double-dose” question about Lovey’s eye: Dr. Lipson said researchers don’t yet know whether the genetic defect that leads to ocular melanoma is the same as defects that lead to cutaneous melanoma. In any case, he said his recommendations for their care – presumably the same for other family members of melanoma patients – would be the same: thorough skin exams by a dermatologist every six to 12 months. If insurance doesn’t want to cover it, I suggest going for pre-approval and appeal if they say no. In the long run, they should prefer pay for examinations twice a year rather than for treatment after diagnosis.
Nurse Ginny at the National Cancer Institute sent suggestions, based on the DCEG melanoma research program’s guidelines. For families in their study, she said, they recommend:
Perform a self-examination of your skin every month. If you note any changes in size, shape, color or borders, please notify your dermatologist. Do the skin exam in a well-lit room with a full-length mirror so you can look at both the front and back of your body. Hand-held mirrors may also be useful.  Helpful Hint: Look at your moles for Asymmetry, Borders, Color and Diameter, Evolving. You may find it helpful to write down the date of your skin self-exam, noting new moles and any changes in existing moles you have observed. Be sure to notify your health care provider as soon as possible if you discover changes or new moles that concern you.
For all individuals with a family history of melanoma, they recommend:

Examining your skin every month. If you notice any changes in your moles, specifically, if any have enlarged, developed a black area, if any moles itch, crust or begin to bleed, or if you become more aware of a mole because it “feels different,” see your health care provider.

Having a thorough skin examination by a health care provider every 6  to 12 months or more often if you notice changes.

Having an excisional biopsy (not a shave biopsy) of any moles that are changing in a suspicious manner.

Minimizing sun exposure to avoid sunburns, minimizing sun-tanning, avoiding tanning parlors, and using sunscreens with SPF 30 or greater liberally and frequently. Also, please consider the use of sun-protective clothing and sun-protective eyewear.
Since we have no knowledge of other melanomas in the family, I don’t know whether Robert’s siblings and cousins share his risk. Presumably, at least Sandy and Judy do – fair skin, red hair, lots of sailing as a kid. I know they will make their own decisions and do whatever’s right for themselves. I’m also sure they share my hope that we don’t get to the point of entering Dr. Tucker’s study.
To learn more, here are some links:
Unraveling Genetic Susceptibility to Melanomahttp://dceg.cancer.gov/newsletter/Linkage/0312_melanoma.shtml#fig1
The Genetics of Familial Melanoma: What Are We Learning?http://dceg.cancer.gov/files/Familial_Melanoma_Study_Newsletter_Fall_2011_%2810_17%29.pdf
Photos showing the ABCDE factors of melanomahttp://www.skincancer.org/skin-cancer-information/melanoma#panel1-1

Up early – easy drive, no traffic. Everything went as expected. Three down, one to go!
Robert’s appointment at Johns Hopkins for the third set of injections of the melanoma GVAX vaccine was scheduled at 8:30, so we were up and out by 7 a.m. – way too early for a retired person like me. But perhaps that’s why the traffic was so light and we ought to ask for early appointments from now on!

The rest of the visit was a breeze, too. Weight stable, temp on the low side, blood pressure 120/89 – only slightly elevated from Robert’s norm. There were no problems with the blood draw (if you want a refresher on the potential, click here), and soon we were in the exam room answering questions from Dr. Lipson. Routine questions, same old answers – the same medications, no physical complaints, no systemic reaction to the last cycle of vaccine. Robert reported that the itching at the vaccine sites came on much more quickly after the December injections than in November, when the hard and red patches at the vaccine sites developed over a few days and stuck around for a few weeks. Last month the itching was furious by the time we returned home from Hopkins.
 Apparently this reaction is normal. Dr. Lipson said, “We see changes in both the severity and  rapidity of the symptoms over time, so cycle one is just minor, cycle two is more vigorous, and cycles three and four are more variable.” Robert noted also that although the reaction at the vaccine sites was slower in the first cycle, those sites were still detectable when he had the second set of injections. The sites from the second cycle have disappeared already – only the biopsy site is still evident, and he accepts that as a “scar for life.”
To which I say: “Maybe. Maybe not.” The vaccines are part of our effort to see to it that he lives long enough for us to find out!
While the study nurse, Susan Sartorius-Mergenthaler, was injecting the vaccines, Robert had a chance to ask her some crystal-ball questions about the vaccine. He wondered what researchers thought would be the future course of therapy, assuming the vaccine receives FDA approval. One possibility, Susan said, is that patients would get an annual “booster” injection – or at some other interval.
Robert also was curious whether researchers foresee giving the initial vaccination in a single set of injections rather than over four months. Susan said she thought the therapy required too much vaccine to be administered in one session. But who knows what mechanism they might eventually devise? I’m sure they would have started out with oral polio vaccine rather than shots, if only they knew how in the beginning …
Susan also told us a little more about the study procedure – particularly the huge vials of blood they take from participants before each set of injections. She said the lab researchers save the samples and perform tests in batches rather than running all the tests on a single participant’s blood at the same time. They are collecting data over time and hope eventually to see patterns that help them understand how the body reacts to the vaccine. Also, she said, eventually Dr. Lipson will be able to share Robert’s data with us – to say whether they saw the particular immune reaction they are trying to induce.
We don’t know now whether the vaccine will be enough to prevent a recurrence of melanoma, and if Robert never has a recurrence, we won’t know for sure whether the vaccine prevented one that would have happened. All we know is that this is all we can do.
When we know more, we’ll let you know. Meanwhile, call or write if you have questions.