Mets Day 898: Further consultations on my treatment options

Yesterday afternoon I sent the following email to Dr. Jeanny Aragon-Ching, my primary clinical oncologist at GW University:

Dr. Aragon-Ching:

Following up on my visit with you on Monday, September 8 regarding my PET-MRI scan results from NIH: Last week I was advised by Corrine Keen, Dr. Apolo's clinical nurse, that I was required to sign a consent form before NIH could send you copies of my scans. I have since signed and returned the form, so hopefully you should be receiving those scans soon. I would be most interested to hear of your thoughts once you have reviewed my most recent scan.

I had understood from our conversation on September 8 that you were going to check on the following:

1. What is the status of tissue from my cancer being sequenced? Has either GW or NIH sequenced my cancer, and if so, what are the results?  If not, is there sufficient tissue available to perform a genetic sequencing? The four sources of tumor available for biopsy would be as follows: 1) the fine needle aspiration at NIH on 9/5/13; 2) the bladder and nodes removed during my radical cystectomy at the University of Chicago on 5/2/12; 3) the TURBT performed by Dr. Fred Hendricks (GW MFA) at GW Hospital on 1/5/12; and 4) TURBT performed by Dr. Hendricks at GW Hospital on 12/1/11. FYI, I have checked with my insurer (United Health Care), and am advised that the cost of genetic sequencing is covered, provided that you obtain a preauthorization, and either send it to an in-network lab, or obtain preapproval to send it to another lab. According to UHC, the following labs are considered to be within the UHC network:

Myriad Genetics
Bioreference Labs
Integrated Genetics
Integrated Oncology

2. Regardless of whether there is tissue available from one of the older biopsies, does it make sense to have the tumor in the enlarged node biopsied and the tissue analyzed? Or is it sufficient to assume that the mets cancer in that node is identical to or sufficiently similar to the material that was biopsied at NIH on Sept. 5, 2013?

3. I understand that there is no definitive data on effect of lymphadenectomy [removal of the cancerous lymph node] and its contribution to survival on patients who continue to have nodal positive disease after chemotherapy. I have reviewed the articles with the following links, and wonder if I should further explore the possibility of lymphadenectomy.

EAU 2014 - The curative potential of lymphadenectomy after response to chemotherapy in patients with urothelial carcinoma presenting with regional or distant nodal metastases: Analysis of a series from a tertiary cancer centre

Postchemotherapy Lymphadenectomy in Patients With Metastatic Urothelial Carcinoma: Long-Term Efficacy and Implications for Trial Design.

Could a salvage lymphadenectomy after chemotherapy have clinical impact on cancer survival in patients with metastatic urothelial carcinoma

I understood your thoughts were that the data did not expressly support lymphadenectomy in my case, and that the risks likely outweighed the benefits. Is that correct? On the other hand, I have a hard time understanding why cutting out a growing tumor is a bad idea. If I wanted to further consider lymphadenectomy, with whom your you recommend that I speak?

4. You recommended that I relax and wait until my next scan (currently scheduled for 11/18/14 at NIH), and if that showed that the node was over 1.5 cm on the short axis, that I should consider one of immunotherapy clinical trials. Do you think that course gives me the greatest chance for increasing my overall survival?

Thank you for your ongoing care.

 Last night she responded with the following:

I have not received the scans from NIH yet but I've attached the genetic findings from your tumor from what Dr. Apolo has sent. [chart follows]

MRN	SoftPath ID	DNA#	Gene Sym	Gene Accession #	coding seq change	protein change	Interpretation
4993238	SB-13-5207	TCC-15	TP53	NM_000546.5	c.839G>C	p.Arg280Thr	Deleterious

The mutation is p53 which is not (as of yet) an actionable target per se. I don't think there's enough cells from the FNA [fine needle aspiration] to do more testing and the molecular testing that best fits our needs (if we are to do more testing) would be Foundation One Medicine or Caris Life Science testing, which are testing for drug targets (as opposed to the genetic tests run by Integrated Genetics or Myriad, etc which is used more for hereditary testing or diagnosis, for example).

While I do find merit in lymphadenectomy for localized disease, your area of lymph node involvement is truly difficult to resect out, and this would be the field of cardiothoracic surgery (because of where it is located) and because these are underneath the clavicular (collar bone) area, it would be very difficult to traverse (unlike say in the abdomen - usually a retroperitoneal lymph node dissection is done) because of the collar bone (which connects your shoulder to the breast bone, important nerves/blood vessels in a cramped space in that area that can leave your brachial plexus vulnerable).  We generally follow the rules of thoracic surgery (for instance, for lung cancer) where involvement of these upper level supraclavicular nodes would generally preclude surgery as an option. 

I acknowledge that it is very hard to "relax and wait" in the face of these circumstances and I am painfully aware of the uncertainty that this entails.  If we did not have the immunotherapy option and the burden of disease is much more (meaning the size is way bigger and more disease is seen in your next scan), then I would favor chemotherapy still (therein lies the next question of which chemo).  However, if the adenopathy has just ever so slightly increased but to the point where you are eligible for the trial, then I think it's well worth considering it because of toxicity reasons (potentially less toxic perhaps).

Take care, JBA

This morning I'm still mulling over this information. I don't understand the information from the genetic findings, and will be doing some further readings about understanding genetic information generally, and the p53 mutation specifically. Also, I'm somewhat confused because I was previously told by several of my doctors that my bladder cancer had a large number of mutations; whereas this genetic finding identifies only one mutation. Maybe it was because the genetic screening did not test for all mutations, or because it stopped after finding the first mutation, or maybe it's because my metastatic bladder cancer has only a single identifiable mutation.

I'm also mulling over the information regarding lymphadenectomy. I understand Dr. Aragon-Ching to be saying that, if the node were somewhere else, lymphadenectomy might be a better option, but given it's current location, the risks outweigh the benefits.

I have no problem waiting and seeing, provided that is the best option. Heck, I've been doing that for more than two years; waiting and seeing for 15 months after my RC surgery, until the distant nodes popped up; get nuked with ddMVAC chemo; then wait and see for another year. If waiting and seeing is truly the best course, then I'm all for it. It's just that I'm not fully persuaded at this point.

Mets Day 895 - Visiting my granddaughter

I spent the past week in Utah, staying with my oldest daughter and son-in-law.  The occasion was the first birthday of my (only) grandchild. I had a wonderful time, spending hours each day reading books with Rose, watching her toddle around, and just enjoying the moment. Chelsea had the week off from the hospital -- her first break since starting her residency -- so I was able to spend time with her (and Josh) also. We went to the zoo, the dinosaur park, and a hike around Causey Reservoir. We did a few projects around their house, and hung up a swing for Rose on the branch of an apple tree in their back yard. It also was good to visit with extended family who attended the birthday party. There is much joy and rejoicing that can be found in the simple pleasures of spending time with those you love.

I have spent very little time thinking about the consequences of the latest scan. About the only thing that is different is that I was spurred to finish compiling a chart of our various accounts and obligations, consisting of all of the URLs, account numbers, user names, passwords, payment information, and comments. It takes a surprisingly long time to pull all of that information together into a single document. Other than that, my mind is untroubled, and I simply live in the moment.

Mets Day 880 - Second opinion on my treatment options

Today I met with Dr. Aragon-Ching, my clinical oncologist at GW. She is the doctor who has overseen all of my chemotherapy, and I respect and trust her options. Last week, I had sent her the following email:

I assume that Dr. Apolo has advised you of the results of my PET-MRI scan that I had on 9/2/14, which showed an increase in size in the supraclavicular lymph node (1.5 cm x 1.35 cm), with active uptake of the F18 flouride glucose, as well as enlargement of adjacent nodes.  I'd like to meet with you to discuss my treatment options.  My questions include the following:

1. Last November, when we suspended my dose dense MVAC after 3 rounds, we discussed the option of going back to it if the scans showed further growth.  In light of the 9/2/14 scan results, does it make sense to consider any further chemotherapy, and if so, what type?
2. Is it worth considering adding a taxene into a cisplatin-based therapy? If so, is that possible outside of a clinical trial?
3. What clinical trials, if any, would you recommend that I consider?
4. What would you do if you were me?

She arranged for an appointment today, and spoke with Dr. Apolo about my scans. I also did a considerable amount of research on pubmed.org to review the most recent literature on treatment of metastatic bladder cancer, and read about a dozen articles. A particularly useful article was Chemotherapeutic and targeted biologic agents for metastatic bladder cancer: A comprehensive review, published in January 2014 in the International Journal of Urology. It summarized the latest best practices, recent research, and many current clinical trials. Also of note was Optimal treatment for metastatic bladder cancer, just published (September 2014) in Current Oncology Reports.

I also researched articles regarding the possibility of having my metastatic lymph nodes removed. A June 2014 article in Clinical Geritouintology Cancer, Postchemotherapy lymphadenectomy in patients with metastatic urothelial carcinoma: long-term efficacy and implications for trial design, suggested that there might be a survival advantage for the removal of diseased nodes. Another article, Lymph node metastases in patients with urothelial carcinoma variants: influence of the specific variant on nodal history,from the June 2014 edition of Urologic Oncology, confirmed that micropapillary bladder cancer (the type I have) is the most common to have node positivity.

Thus prepared, I met with Dr. Aragon-Ching for more than an hour. She is one of the best types of clinicians -- when you meet with her, all of her attention is focused upon you, the patient. She is not rushing to the next appointment, or terse and abrupt in her communications. Instead, she willingly explored all of my questions, as well as the information from the articles that I brought.

She started by stating that, while she had spoken and traded emails with Dr. Apolo, she had not yet received a copy of my most recent scan. She cautioned me that the PET-MRI imaging is a new technology, and the fact that it measured my node to be larger than my prior CT scans did not necessarily mean that it had suddenly surged 30% in size in 6 weeks. Instead, she said it was possible that the clearer resolution of the new scan was just a better picture of what had been going on in that node for some time. (She also acknowledged that it was possible that, in fact my node had taken off in growth, although she said that would be atypical for a distant bladder cancer metastases.)

She also said that, when viewed in the big picture of metastatic bladder cancer that she sees every day, the results of this scan were no big deal. Her purpose was not to brush off my concerns, but instead to put into context what was happening to me compared to other Stage 4 bladder cancer patients. They may have multiple tumors of 3 cm or larger in their liver, or lungs, or other organs, and yet they are still being actively treated. I appreciated her message and reminder that it could be a lot worse.

Building on that, she said that she was looking into the future of the likely course of my disease, and that was strongly influencing her views on what I should do now. Dr. Aragon-Ching felt that my mets bladder cancer still was chemo-sensitive -- she believed that the reason why my mets BC was quiescent for the past year was because of the ddMVAC treatment that I had last fall -- and that my body could handle at least one more set of platinum-based chemotherapy treatments. That being the case, the question she was asking herself was, when was the best time to give me that course of chemotherapy. She said that other patients who had tumors in their organs could have their lives extended by having more chemo to slow the growth of those tumors. She said that it was highly likely that, at some point in the future, I also would have those type of distant tumors. She would rather keep the option of more chemotherapy in reserve for when I really need it. As far as what type of chemotherapy she would consider, she said that we'd cross that bridge when we came to it. She said that there were a number of options available, including carboplatin (instead of cisplatin), adding a taxene, and perhaps other drugs that could target the specific variants within my cancer.

That segued to the question of what actionable information could be obtained from the specific type of mets MC floating around in my body. Dr. Aragon-Ching said that we were still years away from personalized medicine, where each cancer could be run through a DNA scan and a specific therapy designed for the disease. Knowing the mutations or specific characteristics of my cancer was not particularly helpful, because we simply do not have enough knowledge of how to treat each such variant. Researchers are testing different associations and hypotheses, but doctors are still treating cancers on a trial and error basis, she said. She agreed to follow-up on checking into the results of my cancer being sequenced, as well as samples being stained, to determine with types of drugs might have a better chance of working on my cancer.

We also discussed whether it made any sense to have my enlarged node or group of nodes surgically removed. She said that there was very little evidence that such surgery had a beneficial effect. The one study that I showed her referred not to enlarged nodes, but to residual cancer after chemotherapy. In addition, the location of my enlarged nodes -- under my clavicle, next to the brachial plexus nerve bundle -- presented substantial risks to any surgeon who went probing around in that area. She acknowledged that she was not a surgeon, but strongly recommended that I not do that. However, she did agree that it might make sense to do another fine needle aspiration of that node, if more material was needed for DNA sequencing or staining.  She said she would look into that and get back to me.

Dr. Aragon-Ching said that, in her opinion, the best treatment available for me in my position was one of the clinical trials using immunotherapy with PD-1 or PD-L1 expression. She gave me a set of powerpoint slides on PD-1 and PD-L1 immunotherapy that she just presented at the last meeting of ASCO (American Society of Clinical Oncologists), which reported up to 50% response among patients who had mets BC, prior chemo exposure, and distant tumors. There are four different drug companies aggressively trying to prove the efficacy of that class of drugs on metastatic bladder cancer. She said that it would make no difference if I waited a couple of months, because if the immunotherapy worked, it would shrink the tumor. Plus, she said that, as a price of being in a clinical trial, a patient needs to meet the standards for the study.  

We left it with my doctor having three items to follow up on, and she would get back to me. I noted how NIH had already scheduled a follow-up CT scan for me on November 18, with the assumption that it would show the node having grown to sufficient size that I met the requirements of the clinical trials. In the meantime, if we receive further information which indicates another course is better, we'll pursue that. 

Mets Day 875 - My cancer is slowly growing

This afternoon I received a call from Dr. Apolo with the results of yesterday's PET-MRI scan. She reported that the scan provided excellent images. The good news is that the scan did not reveal any tumors in my organs. The bad news is that the scan showed that the cancer is slowly growing in the same group of lymph nodes near the base of my neck, where the distant metastases was first detected in August of last year. She reported that the scan showed that the size of the largest node was 1.5 cm in the long axis, and 1.35 cm in the short axis. She said that the scan showed that there was a cancer tumor growing within that node, since the scan showed uptake of the 18F-flouride glucose. She added that other nodes in the area were also slightly larger in size than was reflected in prior scans. This means that my metastatic cancer was not sterilized by the dose dense MVAC chemotherapy that I had last fall, and has resumed its growth in my lymphatic system.

Dr Apolo said that there was no standard therapy that she would recommend at this point. I've already had two rounds of cisplatin-based chemotherapies, and my cancer had been shown to be cisplatin-resistant. She said that the most promising therapy would be an experimental immunotherapy, which is available only through a clinical trial. The standards for entering such trials, however, are that the tumor has to be at least 1.5 cm in size on its shortest axis, and mine is just under that size, at 1.35 cm. She recommended waiting for a couple of months, then having another scan. In the meantime, she would review the various clinical trials available, and we can discuss the pros and cons after my next scan.

Although I already knew the answer, I asked whether removing the nodes would have any beneficial effect. Dr. Apolo replied that studies had shown that there was no therapeutic benefit to removing metastatic nodes, because the cancer was spread throughout my lymphatic system.  Removing the nodes would not slow the spread of cancer to other parts of my body.

This news is disappointing but not unexpected. If anything, the surprise has been how slowly my mets has moved. Maybe it will continue to grow slowly. Maybe we'll find an experimental therapy that can slow or even reverse it (although that's a long shot). The most likely outcome is that it will spread like, well, a cancer, and eventually overwhelm my body. My hope is tempered with reality, but my faith remains unshaken:

Oh that my words were now written! oh that they were printed in a book!
That they were graven with an iron pen and lead in the rock for ever!
For I know that my redeemer liveth, and that he shall stand at the latter day upon the earth:
And though after my skin worms destroy this body, yet in my flesh shall I see God:
Whom I shall see for myself, and mine eyes shall behold, and not another; though my reins be consumed within me.

Mets Day 874 - PET-MRI Scan

Today I went to NIH for a combined PET-MRI scan. I was the first patient of the morning, and arrived at 6:15 am. In advance of the scan, a tech placed an IV in my arm (no nurse was available at the time to access my port), and was injected with 18F-fluoride. That's a type of glucose with a positron-emitting isotope that likes to accumulate in many types of cancer cells. After I was injected, the tech told me that I needed to wait for 45 minutes for the stuff to be absorbed into whatever cancer cells I have in my body. She added that the glucose liked to go into muscles that were used post-injection, so I should relax, close my eyes, and rest. I set aside my biography of C.S. Lewis and reclined my chair, while the tech turned out the light and shut the door.

Exactly 45 minutes later, the tech woke me up, escorted me to the machine, and turned me over to another tech.  He told me that NIH got the machine just  a few months ago, and that there were fewer than 20 in operation throughout the United States. It's a traditional closed MRI design, meaning that the patient lays on a moving table that is slid into a long tube surrounded by large spinning magnets and radiation-spewing beams. I've had both PET and MRI scans before; apparently what makes this machine special is that, instead of conventional photomultiplier tubes used on prior PET machines, this machine has avalanche photodiodes which are not affected by the strong magnetic field of the MRI system, so it can do a PET and MRI at the same time. 

The tech told me that the scan would be a bit over an hour long. After I got on the table, he placed a brace around me neck to limit my head movement, He strapped me onto the table, carefully placing my arms at my sides, then cinched the straps so I could not move. He put a bulb in my hand and told me to squeeze it if I started to feel claustrophobic or otherwise uncomfortable. He then stuffed earplugs into my ears, then put headphones over the earplugs. I remembered my MRI scan in April 2012 (which confirmed that my cancer had metastasized), when I wrote:

As I felt the noisy thumping of the machine, like a badly unbalanced washer during a vigorous spin cycle, I sensed the fluid in my cells jostling back and forth, and I felt my pelvis getting uncomfortably warm.  I thought of the scene from Gremlins where one of the evil critters was lured into the microwave, soon followed by a green explosion.  I remembered that the floor and walls of the MRI room was all tile, and that there was a mop and bucket in the corner.  That realization did not comfort me.  MRI, I realized, was an acronym for Microwave Roasted Individual.

 Today's scan was not quite as bad as that one, but it was close. I spent 90 minutes in that metal tube and the machine growled and hummed like a cheesy sci-fi movie. I felt my spine heat up as it was irradiated. An hour into the scan, I had beads of sweat forming on my face. I couldn't wipe my face, and the more I tried to ignore my perspiration, the greater was my desire to squeeze the bulb so I could just mop my brow. I then consciously relaxed, accepted the fact that I was hot and sweaty, and embraced my current state. Calmed, I rode out the scan for the last 30 minutes.

When the tech unstrapped me from the table, he saw how I had sweated through my the front and back of my shirt, and commented how it could get warm inside that tube. I briefly wondered how what percentage of patients have problems in completing their scans, then offered a prayer of gratitude that this scan was made available to me, and that I got through it ok.

I'll get my results in a few days. I have already accepted the results, whatever they may be. I don't control my cancer, and that acceptance gives me strength to embrace my current state: living one day at a time, enjoying one moment at a time, accepting hardship as the pathway to peace.