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We had our last visit with Dr. Convit yesterday, and Robert no longer needs to keep his skin graft covered. There is still a scab over a small portion of the graft, but Dr. Convit said it should fall off naturally. It’s OK to wash his head in luke-warm water and to shampoo the entire site (hair or no hair …). No more bandages. No more Nurse Ratched! Yay for me! Progress for Roberet  indeed!
I will miss our periodic visits with the plastic surgeon because he has been the most encouraging and upbeat member of the team we have seen at Washington Hospital Center. But I’m glad we are moving on to what’s next …

As for what that is – Robert is on the list to begin a clinical trial at Johns Hopkins of the GVAX vaccine that is being tested in melanoma. This type of vaccine has been used safetly against other kinds of cancer. There’s actually now starting to be some evidence that the GVAX vaccine for pancreatic cancer improves patients’ lifespans, but for us the evidence is less important than the possibility that it will do some good. 
The study procedure is somewhat tedious in the beginning, and right now we’re in the “wait” stage. The folks at Hopkins are working with our insurance company to see how much of the treatment costs will be paid through insurance (thank you, BBNA) and how much Hopkins will pick up. Once that has been settled, we’ll go to Baltimore a few times for screening and testing. This will include the three-month full-body scan with a Wood’s lamp (for an explanation click here) to make sure no more melanomas have cropped up; PET, MRI, and brain scans to look for other active cancer sites in his body; a full set of blood tests and EKG; and a review of the pathology specimens at Hopkins. We expect all of this to take place in September/October and the series of four monthly vaccinations to begin in October or November.
It’s not been determined yet whether Robert will be in the second or third study group. The second group receives only the high dose of the vaccine and the third group also receives injections of cyclophosphamide one day before each vaccination. There is one more slot in the second group before the third group begins to be treated. If someone else moves along more quickly Robert would be in the group that receives the low-dose chemotherapy drug as well. (My July 24 post discussed cyclophosphamide and other factors we needed to consider before deciding whether to enter the trial.) If he ends up in the third group, it will mean two trips to Baltimore for each vaccination rather than one. On the other hand, it appears that the cyclophosphamide would be beneficial.
We might prefer to be in the third group, as long as it doesn’t delay starting the vaccines too long. There is a deadline – the vaccinations must begin within 4 months of when he was determined to be free of disease. There’s some question about whether that falls in October or November … we are awaiting word on the actual deadline.
We did take some time to consider a peptide vaccine trial that’s starting up at the University of Virginia. This clinical study is just beginning, and the procedures are much more involved – a big factor for us because Charlottesville is so much further away than Baltimore. I think the deciding factor for Robert was that the screening for the peptide vaccine trial includes a sentinel node biopsy of the vaccine site. (Robert explained this procedure in an email I copied here on June 12.) He’s not too keen on going through that again …
September is a busy month. I’ll be in Asheville for Gabriel’s birthday, and later in the month we take off for the Society of Professional Journalists’ annual convention. Mix in there the High Holidays and several work deadlines for Robert – plus whatever we have to do in Baltimore – and we’re looking forward to October! But we can always take time to talk with family and friends, so if you have any questions about any of this, just give us a call.

Our trip to the University of Pennsylvania was valuable in two ways. We got a good synopsis of Robert’s melanoma – what’s positive, what’s negative, what’s the bottom line. And, we got a run-down of all the options for treatment, including some we hadn’t heard about before. We have one more piece of information to put into the mix, and then we’ll be ready to decide what’s next.

The Stanford report added some details, and Dr. Schuchter explained them to us. On the plus side:

The pathologists saw tumor-infiltrating lymphocytes in the melanoma, meaning that Robert’s immune system was trying to eliminate it.

They called the patterning of the lymphocytes “brisk,” which is good – it means there were a lot of them.
On the downside:

The tumor had a high mitotic rate – five dividing cancer cells in a square millimeter of tissue (5/mm2). That means it was growing and adds to the risk.
The most important factor, as we’ve known, is that this tumor was thick – 9.5mm. Any melanoma bigger than 4mm is considered high-risk, and the size alone is enough to mean that the patient has Stage II disease. Dr. Schuchter said the thickness and high mitotic rate present in Robert’s case “trump” the other factors, including our old friend NED (no evidence of disease, or the absence of any sign that the cancer spread beyond the top of his head).
The worry is that this big, deep, mitotically active tumor may have given off some micrometastases before it was excised. We have no way of knowing whether it did.
Dr. Schuchter said many people with Stage II disease and melanomas this big choose the “watch and wait” option. For at least the first year or two they have skin examinations with a Wood’s lamp every three months and PET/CT scans every six months to a year to find any evidence of metastatic disease as early as possible. The biggest risk of recurrence is in the first three years, so the stretch between observations lengthens after that. After five years the examination frequency drops to annually.
For those who want to be more proactive, there are only a few options at Stage II. The chemotherapy agents now available, most notably forms of interferon, have not improved the outcomes enough to outweigh their nasty potential side effects. A promising new drug, ipilimumab, is not yet approved for Stage II, and while its side effects are not as bad as those seen with interferon, they are can be severe.
Researchers have been working on different types of cancer vaccines for a number of years. One is the GVAX vaccine being used in the trial at Johns Hopkins that we have been talking with Dr. Sharfman about (see Another perspective on the vaccine trials, 7/24/2012). Another ongoing trial, at the University of Virginia, is testing a melanoma peptide vaccine.
Dr. Schuchter said she prefers a vaccine trial for someone with Stage II melanoma rather than ipilimumab because of ipi’s side effects. She will find out whether the peptide vaccine trial includes Stage II melanoma patients, and if so, we will give that option full consideration.
Meanwhile, Robert is on the list to be screened for the Hopkins trial. Dr. Sharfman said it would be a few weeks before they are ready to begin, as they enter new subjects into the trial one-at-a-time. We’ll update you here when there’s more to say.

A recent post on the Melanoma Research Foundation’s community list made me sad, mad, and – very thankful for you all. The writer, a newcomer to the community, was venting her frustration at her siblings’ lack of understanding that she is facing a very serious situation – newly diagnosed, recurring melanoma. She wrote: “It is so defeating to know that there will always be a ‘next time’ for surgery, and stitches, and co-pays. And there will always be another social expectation of a sunny beach get together.”
The understanding from our families and friends – the outpouring of concern, favors small and large, visits, cards, and phone calls – has been so important to us!

In particular:

Some of you have come from afar to visit, and one of you gave up all her vacation to be here.

All of you have been so restrained about calling us or expecting us to call you with every bit of news. We really appreciate not having to go over everything one more time when you can read the details here. That also leaves the phone time for important questions we didn’t think of – and just for keeping us in the loop about what’s going on with you.

Some of you have plied us with comfort food and sweets – so sweet!

One of you has spent many hours with me/us when I’m sure you had other things you would rather do.

Some of you don’t believe in this, but I do: I feel positive energy coming our way.
I can’t imagine dealing  with insensitivity from any of you while also going through this stressful time. Thank you all, from the bottom of my heart!
[Drumroll …]
And now, the biggest understanding is yet to come!
We are going to the beach …
This should not be a big surprise to those of you who know Robert well. He will not be held down. He will, for sure, slather with sunscreen of adequate SPF; wear a hat; cover up as much as possible and still enjoy himself; and limit the time we spend in the sun.
I understand completely why some – perhaps most – melanoma patients become sun-shy. We have considered all the factors at play here, and unless someone tells us not to, we will not stay indoors. We will hike and walk (and Robert will bike) to enjoy the beauties of the natural world. We will work our bodies and strengthen our muscles. We will breathe fresh air and suck in the smell of the ocean.
And we will be careful! That’s a promise …

As more people in our wider circle of friends find out about Robert’s melanoma, I’m getting questions about the disease that our inner circle (family and closest friends) didn’t need to ask. That’s because we told them from the beginning that Robert’s diagnosis in the first pathology report was metastatic melanoma. Since we know now that as of June 18 his status was “no evidence of disease” (NED), a factor some newcomers know when they first learn of his illness, I am frequently encountering this reaction: “That’s really good, right? So he can just go on with his life and it’s not likely to come back?”
I can’t find fault with anyone whose initial reaction is just that. Most melanoma patients (about 70%) have superficial spreading cutaneous melanoma, and the long-term prognosis for that type is very good if caught before it has a chance to spread beyond its primary site. Five- and 10-year survival rates are sometimes cited as high as 100% for “melanoma in situ.” Although many people know that the prevalence of skin cancer has been growing at an alarming rate, many also understand that skin cancer is most often curable. As one patient put it, “I thought … they would cut it out and that would be the end of it.”

Cancer prognosis is often discussed in relation to the stage of the disease, and as our family and close friends know, Robert’s case has been difficult to stage. At one point we understood the doctors at Washington Hospital Center to say that they were treating his case as melanoma in situ because there was no evidence of spread – the sentinel node biopsies and PET/CT scans showed no evidence of disease. That’s where you see the 100% survival rates. But that’s not the end of our story.
In staging melanoma to come up with treatment options and prognosis, melanoma experts also consider two measures of invasion into the immediate area – one called a “Clark level” and the other known as “Breslow thickness.” The Clark level measures the level of the skin that the melanoma has invaded – how deep did it go? The Breslow thickness is measured from the top of the tumor to its lowest point. Under the most recent cancer staging guidelines, the Clark level is only considered when staging tumors up to 1 mm thick. Generally, the thickness is a more accurate measure to consider when trying to come up with a prognosis for bigger tumors.
Because the lesion removed by the dermatologist in April was thought to be a sebaceous cyst, the skin was not removed at that time, making the depth and thickness difficult to measure. The original pathology report had no measurements – in fact, it included almost no information, other than the dreaded diagnosis of metastatic melanoma, and one of our doctors called it “pathetic.” After the tissues were sent to the dermatopathology lab at Boston University, we got our first indication of how thick the lesion was – 9.5mm. The recent report from Stanford University added one more piece of information – the tumor was centered in the “mid reticular dermis,” and the Clark level is IV or V.
Among the questions we will ask tomorrow is one about the depth. With a tumor this thick it’s not surprising that it was in the deepest level, the reticular dermis. My question is, how much of the thickness was on the outside? The cyst itself was raised, perhaps 1/8 to 1/4 inch, and then there was a dome extending upward from part of it. If that is the section they measured, it’s possible that most of the 9.5mm were on the outside.
More from the Stanford report
The Stanford report did not have the diagnosis I was hoping for – primary dermal melanoma. The dermatopathologists there believe their immunohistochemistry rules out PDM. Instead, they favor a diagnosis of primary nodular melanoma with regression. Nodular melanoma is not the best possible diagnosis – it is the most aggressive type of melanoma.
There is much more detail in the Stanford report, including lots that my superficial research doesn’t help me understand. We’ll ask Dr. Schuchter (at University of Pennsylvania) about them tomorrow, and when I can provide a reasonable explanation, I’ll write about anything important.
Meanwhile, we’re sticking with the most important positive factor: NED! The sentinel node biopsies and PET/CT scan done in June found no evidence of cancer. Patients with nodular melanoma who have no lymph node involvement have a much better prognosis than those whose cancer has spread. It’s not the 100% you hear about, but we’ll take what we can get!

Before 2000, melanoma cases like Robert’s – those that didn’t show up on the outside of the skin – generally were considered to be metastatic melanomas of unknown primary origin. Now, melanoma specialists recognize a subtype they call “primary dermal melanoma” (PDM). There’s not much recent information available on  the web about PDM – here’s my synopsis of what’s there.

Primary dermal melanoma cases have some common threads:
·        there was no evidence of melanoma or abnormal pigmentation on the outer layer of the skin;
·        clinical tests, including skin examinations with ultraviolet light, PET/CT scans, and sentinel node biopsies, found no evidence of melanoma elsewhere on/in the body;
·        the lesions tended to be very deep; and
·        patients whose cancers were characterized as PDM had “remarkably prolonged survival” compared with metastatic or nodular melanomas of similar thickness.
That last bit sounds good to me! But apparently, not all melanoma cases with the first three characteristics noted above fall into that category.
The first report I found on a group of patients with melanomas not evident on the outer skin layer that did not appear to come from another site (i.e., metastasize) covered 11 patients. University of Michigan researchers reporting on this group in 2000 postulated that these cases were not metastases of melanomas of unknown primary origin, dubbed them “primary dermal melanoma,” and noted that they had an unusually high survival rate.
Another group, seven patients, classified as having PDM was reported in 2004 in an article by Dr. Susan Swetter (et al.) of Stanford University. This article noted that, under staging guidelines then in use, these cases would be considered Stage IV, metastatic melanomas of unknown primary origin. Other patients at that stage had a five-year survival rate of 19%, but the seven PDM patients then being followed at Stanford were all alive after up to five years of follow-up (mean, 41 months), which the report characterized as “markedly better than what would be expected” for a primary melanoma that deep or for a metastatic melanoma of unknown primary origin.
By 2008, the Stanford study cohort had grown to 13 cases. In these cases the mean thickness of the melanoma was 9.6 mm – about the same as Robert’s, 9.5 mm, which Dr. Sharfman has told us makes Robert’s case “high-risk.” Although the survival rate for PDM had begun to come down by then, it was still unusually high at 92% after a mean follow-up duration of 44 months.
The Stanford researchers’ 2008 report noted that they had found lower levels of staining for some proteins than they found in metastatic and nodular melanoma. This shows that the body of information about PDM had grown by 2008 to the point where some researchers believed they had found some markers for it in their immunohistochemistry studies. That’s why we were happy to hear that the team at Washington Hospital Center had Robert’s slides sent to Stanford for comparison with their identified cases. No answer yet – but we will follow up with Drs. Jang and Venna soon.
Even without knowing those results, we have reason for optimism. The importance of measuring the thickness (depth) of melanomas was highlighted in a 2009 World Journal of Surgery article reporting that 65% of patients with melanomas that were thicker than 4 mm had lymph node involvement. The researchers, from the Netherlands, said that finding a positive sentinel node was the only predictor of overall survival in patients with thick melanomas. Since Robert’s very thick melanoma was not accompanied by lymph node involvement, we hope that bodes well for his longer-term prognosis. 
We are taking what we can get right now – but continue to look for more information. We will consult with another top melanoma researcher, Dr. Lynn Schuchter, at the University of Pennsylvania next week. Stay tuned … we’ll keep you updated here!