Tuesday, June 19, 2018

Infusion 48; CT scan showns stable disease

On Thursday, June 14, I had my labs done in advance of my next Opdivo infusion. My labs were unexceptional, with the exception of continued increases in my liver enzymes (alanine aminotransferase, or ALT, 84 U/L, and aspartate aminotransferase, or AST, 56 U/L). Both have been creeping upward as my new tumor has grown. The levels are not so high as to cause immediate concern, but it’s something to watch, like an inexorably rising river during high rains. My prior CT scans have shown small nodules in my liver, nothing large enough to be definitive, but something to be aware of. If I had to bet, I’d guess that my liver will be the first organ that will have metastatic activity. I’ll cross that bridge when I come to it.

On Friday (June 15) I had nivolumab infusion #48 at the Kaiser Tysons Corner office. It was the third since I’ve resumed my treatments with Opdivo, and was so routine that I fell asleep. The nurse reported that I was snoring. Clearly I’m not drinking enough Diet Coke.

On Monday (June 18) I had another CT scan. There were 20 people in the waiting room and I resigned myself for a long wait, but the advantage of being a frequent scanner is priority boarding. I was quickly called in by the tech who remembered me due to my generous tips and was rewarded with only one blown vein. Maybe 15% of nothing is not enough? As usual, after the scan I was told to drink lots of fluids to flush out the barium and iodine. As usual, I went to McDonalds for two sausage and egg McMuffins and four liters of Diet Coke. And as usual, Kaiser had the CD of my scans ready after my visit to the Golden Arches.

Today (June 19) I received the results of yesterday’s scans. The headline is that the primary tumor in my neck has not grown in size. Stable disease is better than active growth. The scan actually measured the tumor to be slightly smaller, but that is most likely due to how the tumor was sliced by the scanner. Here’s the relevant text from the neck scan:

The previous enlarged left level 3/4 junction lymph node somewhat more difficult to see because of beam hardening artifact from adjacent contrast bolus but appears to measure about 1.4 x 1 cm which is borderline enlarged, though smaller than the previous size of 1.7 x 1.4 cm. Otherwise no enlarged or pathologic-appearing lymph nodes are seen throughout the neck.”

For my chest, abdomen, and pelvis there was “no significant lymphadenopathy or evidence of metastatic disease.” So yay for no tumor growth.

Later in the day, I went to Johns Hopkins for my last visit in connection with my participation in the Bristol-Myers Squibb-sponsored clinical trial that led to the FDA approval of Opdivo for metastatic bladder cancer. Because of the FDA’s approval last year, I can get nivolumab from any oncologist without my being in a clinical trial. I expressed my deep appreciation to Dr. Noah Hahn, and to senior clinical trial nurse Brad Wilt, and to the entire Hopkins staff, for their profession, compassionate, and persistent work at prolonging my life.

I also discussed with Dr. Hahn his recommendations going forward. He said that I should probably continue with nivolumab until either all my tumors were gone, or they were actively growing. In the even that my tumors continue to grow, Dr. Hahn said that there were lots of new therapies being tested on patients who had disease progression following immunotherapy. He mentioned a number of them – some of which I’ve previously blogged about – and invited me to reach out to him to discuss if and when that time came. He also encouraged me to keep up with my blog, saying how many of his patients had mentioned to him how they were readers of my blog. More than a few had sought him out based upon my good experiences with him and Hopkins.  

Dr. Hahn knew that I was planning on moving to Utah at some point, and said that one of his fellows,Dr. Ben Maughan, now practices with the HuntsmanCancer Center in Utah. Dr. Maughan likely will become my new oncologist when I eventually transfer my care out there. 

Life, meanwhile, has taken an unexpected turn with my wife’s unexpected diagnosis of early onset dementia. Jennifer’s cognitive decline became pronounced last October, and for the past nine months we have struggled to determine the problem. Four hospitals, 11 doctors, and 13 different drug regimens later, she continues to suffer from daily confusion, uncertainty, disorientation, and wandering. This disease is horrible for anyone, but seems especially cruel to strike my faithful wife at age 54. After her last hospitalization, the doctors recommended that she be transferred to an assisted living facility that specializes in memory care. She’s currently residing at a memory care center in Northern Virginia. After consultations with doctors and family, we’ve made the decision to relocate Jennifer to another memory care facility in Northern Utah on July 2. There she will be closer to our oldest daughter, a practicing physician, and her extended family.

This decision was informed by the very real risk that my disease will progress and that I won’t be around that much longer to be Jennifer’s primary caregiver. There is no published data to inform me of what happens to people with metastatic bladder cancer who have had a partial or complete response to nivolumab. Looking at data for mets BC patients who have had other types of immunotherapy, an article published earlier this year examined long-term outcomes for people with metastatic urothelial cancer who were treated with atezolizumab.  A close reading of the data and review of the charts suggest that, once there is a recurrence, most patients die within a year.

A major limitation of this article is that the data set closed in December 2016, before many of the most recent combination drug therapies were even being tested. Also, the data set is small, the age of the patients skews much older than me, and they have more co-morbidities than do I. Plus, my recent scan tells me that, for now I have stable disease. But still. I am realistic about my poor prognosis. I have no use for rose-colored glasses, especially when planning for the care of my wife after I am dead.

We’ll get Jennifer settled into the Utah memory care facility in early July. Garrett will complete his two year mission for our church on July 10. Spencer and Kirsten will join us in Utah for a few days, and we’ll have a Brothers family reunion – the first time all of us will be together since March of 2016. Garrett will have only a few weeks to transition into normal life before he matriculates at Carnegie Mellon University in Pittsburgh, so at some point he and I will fly back to DC to prepare for school.

I’m scheduled for infusions through Kaiser on June 29, July 16, and July 30. I’ll ask to have a PET scan in late July or early August, which may give better insight into whether the nivolumab is working. Notwithstanding the results of yesterday’s scan, I have not been holding out hope that Opdivo will work as well this time, for three reasons. First, Dr. Hahn previously told me that, in theory, the nivolumab should have taught my immune system to kill every cell that had a PD-L1 enzyme, so any new tumor growth is probably another mutation of my mutation-rich metastatic bladder cancer. Second, my original mets lit up on CT scans a lot better than this tumor, leading me to wonder if it’s a different type of mutation. Third, projecting hope takes a lot of energy, and my energy has been directed elsewhere lately. Given that I have no control over my cancer, I have found that I expend far less emotional energy by accepting the facts of my prognosis as it is, rather than setting myself up for a dissonance between what may be false expectations and reality.  Plus, I’d rather be pleasantly surprised than bitterly disappointed.

If and when I find out that nivolumab isn’t working, I’ll look at my next options. That will be Plan F. I’ll reach out to Dr. Hahn and Dr. Apolo, among others. For some strange reason, there are more clinical trials available in the DC area than in Utah. Go figure. So maybe I’ll stay in DC longer, or commute back and forth between Utah and DC as needed. I knew there was a reason we hadn’t sold our house yet.

If, however, I learn in August that the Opdivo is causing my tumors to shrink, then I’ll likely relocate to Utah after I deliver Garrett to Carnegie Mellon. I’ll rent a place somewhere between Jennifer’s assisted living location and my grandchildren and look for goodness and joy every day.

Thursday, May 31, 2018

Infusion #47

Today's infusion was utterly routine. I'm glad that I'm getting my Opdivo at the local Kaiser Permanente facility. It's close by, and I'm in and out in the time that it took me to drive to Baltimore. It's the newest and nicest of any of the infusion centers I've been to so far (GW, NIH, Hopkins, and now KP Tysons). Plus the nurses bring me cold Diet Cokes so I don't even need to put down my recliner.

It looks likely that I'll be moving to Utah by the end of the summer. Jennifer has been suffering from some serious health issues. In light of my precarious health status, I thought it prudent that we get her reestablished closer to her family as well as our doctor daughter. So I've been looking into the availability of continuing by treatments at the Huntsman Cancer Center at the University of Utah. It appears that I should be able to do so. My greater concern is the availability of clinical trials in Utah if the nivolumab does not work. There are a lot more options in the DC area. But I'll cross that bridge when I come to it.

Monday, May 14, 2018

Opdivo infusion #46

After an 18 month hiatus, I'm back on immunotherapy. This time I'm at the Kaiser Permanente facility in Tyson's Corner Virginia, which is only a few miles from my home. It's newer and more spacious than either Hopkins or GW's chemo areas. At the appointed time, I was seated in the recliner and the nurse quickly placed an IV (since I was deported last year) and did a blood draw (I'd done my labs last Friday, but she didn't see a Hepatitis B test on my chart). While that test was running, she scheduled my next 3 infusions. Once the nivolumab arrived, she hooked it up to the infusion machine, and it was no different from my 45 prior infusions. Here's to hoping that the effect likewise is no different, and once more I'll slide into remission.

Friday, May 11, 2018

Niolumab 3, Biopsy 0

Less than an hour after I sent my emails yesterday to my dream team of oncologists, I received a call from Dr. Apolo. She said that in the past week she had reviewed by current CT and PET scans, compared them to my CT scans of the past 4 years, consulted with NIH's interventional radiologists, and had just spoken with Dr. Hahn. She concluded that my new tumor was in a different location that my first supraclavicular node mets tumor that was first observed in mid 2013, biopsied by NIH in September 2014, and which disappeared as a result of my nivolumab therapy in 2015. The new tumor is deeper in my chest, near my trachea, and nestled in between the internal and external jugular veins and aorta. The new tumor shares the same lymphatic drainage as my first supraclavicular tumor. She said that it is 98% likely to be metastatic bladder cancer; the other 2% is that it is a different type of cancer. Her interventional radiologists confirm that it is too risky to biopsy with a guided needle. She and Dr. Hahn both agree that the risks of performing a surgical biopsy outweigh the diagnostic benefits. She and Dr. Hahn agree that I should immediately restart immunotherapy, preferably nivolumab, and see if the tumor responds. If not, then I can investigate my clinical trial options. I asked her whether I should stick with Hopkins, or get immunotherapy closer to home. She said she'd recommend keeping it as simple as possible. I thanked her for comprehensive review and advice. 

Later in the evening, Dr. Hahn emailed, "Given what you have described from your physicians at Kaiser, I would recommend foregoing the biopsy and restarting nivolumab. If we can do that through the study, then great.  If not, then treating you with any of the now FDA approved PD-L1/PD-1 agents would be ok too." The Hopkins clinical trial nurse is in the process of verifying whether I can resume treatment as part of the ongoing study by Bristol Myers Squibb of the drug. Now that nivolumab has been approved by FDA for metastatic bladder cancer as a result of the data from the clinical trial in which I participated, however, I don't have to be in a clinical trial to get the drug.

Today I received a note from Dr. Ferrera, who also agreed that the biopsy was too risky. She has put in orders for me to resume nivolumab therapy starting on Monday May 14 at the local Kaiser Permanente office six miles away from home. No copay, no extra costs, no commuting to Charm City. That's convenient!

Based the unanimous vote of my doctors, my Plan E is that I'm going to resume my infusions with Opdivo after an 18 month break. I'm not sure how long I'll go, but expect it will be for at least 6 months. I hope that the drug works as well this time as it did before.

Thursday, May 10, 2018

To biopsy or not to biopsy? That is the question.

This afternoon I met with Dr. Nyen Chong, a Kaiser Permanente thoracic surgeon, about performing a biopsy of my tumor. (Kaiser's Interventional Radiologists have said that a guided FNA not an option for this new tumor location.) We reviewed the location of the tumor, its proximity to 4 different veins, some lymphatic ducts, and nerve bundles. Dr. Chong explained that the tumor location would be very difficult although not impossible to access. He believed he could successfully perform a robotic-assisted biopsy, but that the risks of serious complications (serious bleeding or nerve damage causing paralysis) were about 10%. Regarding scheduling, he would not be able to perform the biopsy until mid-June. I understood him to opine that that he would recommend proceeding with the biopsy only if the odds of it providing information that would change the course of therapy exceeded the odds of the risks.

As I understand it, the odds that this new tumor is anything other than mets BC are very low, i.e., the low single digits. I have sent the following three questions to my three oncologists (Dr. Ferrera at Kaiser, Dr. Apolo at NIH, and Dr. Hahn at Hopkins):

1. Do you agree with Dr. Chong's assessment?

2. In view of the biopsy risks, would you recommend proceeding with the immediate resumption of nivolumab without having a biopsy? 

3. Or, would you insist on having the biopsy prior to my resuming therapy?

I'm leaning away from having the biopsy due to both the risks and the passage of time, but want to hear hear how oncologists answer my questions. Of course, either Dr. Ferrera or Dr. Hahn will have to agree to resume treatment without a biopsy, and for me to enter Dr. Apolo's cabo/nivo/ipi trial, I'll have to first resume nivolumab, then have tumor progression. I'll likely follow their consensus.

Monday, April 30, 2018

Mets confirmed by PET; NIH consult

Last Tuesday, Dr. Hahn suggested that I get a PET scan to try to confirm if my enlarged nodes really were metastatic cancer, and if it was, to see if I could get it biopsied. My Kaiser doctor agreed, put in the order, and it was promptly scheduled for Thursday at Kaiser's Capitol Hill location. As I drove into town, I was reminded at how little I miss driving in DC. I had an IV placed and received an injection of fluorodeoxyglucose, or FDG, which is a radioactive tracer that cancer cells love. After the injection, the tech said I needed to wait an hour for the FDG to drawn to any cancer cells, so he covered me with a warm blanket, reclined my chair, and turned off the light. I promptly fell asleep. Eventually the tech woke me up, took me to the next room, laid me on the table and rolled me into the scanner. I would have fallen asleep again except I had to hold my arms over my head. I could feel the magnets pulsing the cells of each section of my body, and marveled in our technology.The next day I picked up a copy of my scan on CD, and saw that my tumor was FDG avid, confirming that it's metastatic cancer.

On Friday, Kaiser's interventional radiology department called and said that an IR had reviewed my CT and PET scans, and didn't think that my tumor could be biopsied with a fine needle aspiration (FNA) without risking damage to the either the surrounding nerve bundles, or the nearby cluster of veins and arteries. IR instead referred me to one of Kaiser's general surgeons to attempt a biopsy the old fashioned way -- cutting me open and trying to slice out a chunk of the tumor. How very 1950's, I thought. Maybe I'll see if the IR's at NIH or Hopkins are up to the challenge. (NIH did a FNA biopsy in a nearly location back in September 2014.)

Today I met with Dr. Andrea Apolo and her team at the National Cancer Institute at NIH's Bethesda campus. (living in the DC area does have its benefits.) I am fortunate that I met Dr. Apolo at a BCAN event in April 2012, just weeks after my cancer first went metastatic. She has been a valuable source of information, second opinions, and comfort ever since. She has steered me into two clinical trials while always looking out for my best interests. She is an example of the best type of public servant.

Here is the list of questions and notes that I prepared for our meeting:

Data re recurrence of mBC after immuntherapy-induced response?
How likely is it that this mBC is the same mutation as before?
Will sequencing tumor tissue for neoantigens assist in therapy selection? (PD ligand, CTLA-4 expression, HER2, inflamed TME, TSC1/2, other immune cytolytic gene signatures)
Kaiser IR is apprehensive of FNA. Can NIH do another FNA? Or Betsy Plimack at Fox Chase https://clinicaltrials.gov/ct2/show/NCT03291028
Does NIH’s analysis of my old sample (9/5/14) give any insight? (high mutation burden, HER2+, PDL expression)
What are my best therapy options?
  Resume Nivolumab
  Cabo/nivo/ipi https://clinicaltrials.gov/ct2/show/NCT02496208
  Enfortumab Vedotin (Nectin-4 expression; Trial EV-201) https://clinicaltrials.gov/ct2/show/NCT03219333
  PCV+Atezolizumab https://clinicaltrials.gov/ct2/show/NCT03289962

Dr. Apolo said that getting a tissue sample via biopsy, then getting it sequenced, was the best way to understand what was going on. They could compare it to my earlier biopsy and determine whether it was the same mutation or something new. She'll have the NIH IR's look at my scans and see if they are willing to try to do the biopsy. (She seemed horrified that Kaiser wanted to try to get to the tumor by cutting me open.) She observed that the mets grew while I was off therapy -- I have not had any nivolumab for nearly 18 months -- and that there was a chance that I would again respond to nivolumab. She also said that her cabo/nivo/ipi trial was designed for patients who had progressed while on immunotherapy, so I did not qualify for that trial. (Plus, the chances of side effects were greater than just nivolumab alone.) She noted how some patients who had gone off immunotherapy, then had a relapse, had again responded when they went back on therapy (although the data are still limited.) Her recommendation was that, unless the biopsy showed something unexpected, I should resume nivolumab. She also said that it was not urgent that I do so immediately, as my mets appeared to be growing relatively slowly.We parted with her promising to get back to me in a week or so. It was a great consult.

I've had some time to reflect on the news of the return of my cancer. I'm a bit surprised on how nonplussed I am. I've expected this shoe to drop for some time and now that it has, I've determined that nothing has changed. I had not changed my assumptions on how long I would live: I do not have to deal with altered expectations, because long ago I learned to let go of any expectations. I continue to live one day at a time, giving thanks to God each morning, and gratitude each evening.

Tuesday, April 24, 2018

My mets are back

This morning, Johns Hopkins MyChart posted the interpretation by their radiologists of my CT scans at Kaiser of March 19. In my neck, the radiologists said that a "left supraclavicular lymph node demonstrates loss of normal reniform shape, and is suspicious for metastasis." In my chest, "increased size of the enlarged left upper paratracheal lymph node, which may represent metastatic disease. Given the location between several vessels, this would be difficult for percutaneous biopsy." It looks like my remission is over, and my mets are back. 

I tend to be proactive and would prefer not to wait for my doctors, so I sent the following questions to my doctors at Hopkins, Kaiser, and NIH:

1. What would you recommend my next steps to be?
2. Does it make sense to do a biopsy of the left supraclavicular lymph node? If so, should that be a JHUH, Kaiser, or NIH? 
3. What is the best type of genetic testing that can be done on the tissue to inform the next therapy?
4. Should I go back on nivolumab immediately (either through the clincial trial or, since it's been approved, outside of the trial protocol), or await testing, or consider a different therapy such as Dr. Apolo's cabo/nivo/ipi trial?
It looks like I'll have a period of uncertainty ahead.