Jane was too young to die. Jane was 56. I was 58. We were preparing to leave teaching to spend time with each other. We planned to write some books. We had dreams.
Things are better than they were in 2010…
We were not done living or learning or teaching or dreaming. Neither are most of the NET cancer patients I meet. They have careers that matter, children that matter, dreams that matter. Instead, most face a years-long struggle against an incurable disease that slowly strips them of their dignity, as well as their energy and purpose.
Dreams still nightmares
We are still in the dark ages when it comes to NET cancer, as Jill Watson so ably points out in her comment on yesterday’s post. We have made progress, but not enough to make a big enough difference,
We have no cure. We have few ways to slow the progress of the disease. We have few ways to improve patients’ quality of life. We still lack any reliable means of detecting the disease early enough to make a curative difference.
Dreams of greater awareness
Most primary care doctors still have never heard of NET cancer. Too many of those who have, think of it as, “a good cancer to get.” They see it as slow-moving and tout the idea you can live for years with it. They don’t experience what those years can be like.
Too many oncologists know too little about the disease as well. The things they know are what they heard in medical school. They’ve rarely actually seen a case and are equally rarely up on the latest research or new standards of care.
Changing reality
But 2010 really was a turning point in the treatment of NET cancer. In June of that year, the FDA approved two new drugs–everolimus and sunitinib–for pancreatic NET. Those were the first new drugs approved for NET cancer in nearly 20 years. Those drugs have since shown an impact on other forms of NET as well.
Sandostatin–the month-long form of octreotide–would soon be joined by lanreotide, reducing octreotide to a mid-month rescue shot for many patients. One of the worst parts of my day was watching Jane inject herself in the belly with octreotide. For many–though not all–patients, those days were drawing to a close.
Moving from dreams to reality
Based on a Phase 3 trial, telotristat etiprate should receive approval in the next few months. It also addresses NET cancer symptoms and seems to slow the progress of the disease for many patients.
While for patients in Europe–or those with the means to get there–PRRT had been an option for many years, trials of that radiation treatment had not yet begun in the US when Jane died. The successful completion of those trials in recent months should bring FDA approval shortly for an even better form of that therapy. Again, it doesn’t work for everyone–and is in no way a cure–but its impact on quality of life for many is significant.
Delaying tactics, not cures
Patients with other forms of cancer had tried liver embolization in 2010, but no NET patients had. Today, for those with liver mets, bland, chemo, and radiation embolization therapy have become fairly common–and fairly successful. But, again, not for everyone.
To patients and their families, none of those things is enough. Each improves quality of life. Each increases longterm survival. None of them represents a cure. Nor do the early returns on other therapies in the works.
Diagnostic dreams could fuel a cure
We do have one therapy that offers a chance of a cure: early surgery. But it is rare the tumors are found early enough for surgery to do anything more than what the other therapies do: extend life and improve the quality of that life. In 2010, we had no decent means of detecting the presence of the cancer before it reached an advanced stage.
Today, we are a little better. Jane’s tumors were invisible to every scan her doctors did before the tumors exploded into her liver. Within two years of her death, the PET octreoscan–using octreotide as a contrast agent–made many tumors more visible. Recently completed trials of the Gallium-68 scan are even better.
Dreams of a simple test
But for those tests to reveal the tumors, a primary care physician has to know enough about NET cancer to know to order those tests. What we really need is an inexpensive drug test that could become as routine as the test we use to check for prostate cancer. That kind of test would be a game-changer.
None of this offers any real solace to those fighting the disease at this moment. As Jill points out, the slow pace of getting an idea from the lab to every patient’s bedside is agonizing. But things are getting better. There is far more in the pipeline than there was in 2010. And every slowing of disease progression buys time for patients to get to that next treatment.
Tomorrow is coming
But there needs to be more. That can’t happen without more doctors, more researchers, more lab space, and more NET cancer centers–all of which requires more resources than we have now.
Tomorrow, we’ll look at what resources we had compared to what we have now. Things are better than they were in 2010–but not as good as they need to be.
One of my dreams is that some day no one will place a stone like this in their garden in memory of someone who died of NET cancer.
(Editor’s Note: My apologies for a long gap between posts here. I’ve been busy working with the people at Dana-Farber on a new fundraising campaign to raise money for NET cancer research there.)
Thanksgiving Eve
Thanksgiving five years ago was both the best and worst I’ve ever had. It was the best because, despite a life threatening coma that had ended two days before, Jane was alive and seemingly well. The night before had been difficult. My simple presence in the room seemed to be having a bad effect on Jane’s state of mind–and on her physical health as a result.
…it has to be done.
At about 10 p.m., the medical people sent me down the hall to sleep in another room. “If we need you, we’ll come get you–and if we do, you’ll need to be sharp.” The words were not comforting, but Jane and I had insisted they be brutally honest at all times about Jane’s condition and prognosis.
Thanksgiving sunrise
I slept very little that night. Mostly, I waited for sunrise. I knew, somehow, that if the sun came up and no one had come to get me, things would be all right. And they were.
The words were not comforting…
I called the front desk. They said to come over when I was ready–that things were better. I walked down the hall and turned into her room. Jane was sitting up in the bed. She turned to me and smiled. “I love you hubby.” And then I was in her arms–and we were happy.
The best of times, the worst of times
Friends brought her father and sister to visit that day. When they left, I went downstairs and found a cup of pumpkin soup. By the time I got back, Jane’s chicken broth had arrived. That was our last Thanksgiving dinner together. We watched the Patriots beat the Cowboys and Jane fell asleep. Jane thought this was the final brightening in her family’s tradition. I had hope it was more than that–but we had squeezed out one more Thanksgiving.
…and we were happy.
And that was why it was the worst Thanksgiving–because it was the last. It haunts me to this day. Twenty-four hours later, she had another carcinoid crisis and went into another coma. I spent Saturday morning agonizing over what to do: should I let her go? Was there still a fighting chance?
Decision point
A friend came up that morning and Jennifer Chan, her oncologist, came in a little later. They convinced me that there was one more card to play: a massive dose of octreotide that would run the hospital’s supply to zero and deplete supplies elsewhere in the city as well.
It haunts me to this day.
Six hours later, Jane was awake–and both surprised and delighted to be there. Thanksgiving was not a false renewal after all. She was going to go home–not for Christmas, she knew–but in time for us to spend February vacation in the room overlooking the lake we had spent the last night of our vacation at in August.
The dream–and the nightmare
We lived for that dream for almost two weeks. Doctors put in a pacemaker, friends visited, we watched television together. We even argued once or twice–the kind of arguments people who have been married and love each other have when things are going well.
…one more card to play…
Five years ago today, things started to go to hell. Jane wanted to get out of bed to use the bathroom, wanted me to carry her there. I couldn’t–she had a feeding tube and all kinds of monitors that limited that kind of thing. If she wanted to sit in a chair, she had to be lifted with a small crane.
Into the night
She wanted me too take her home. I told her I couldn’t–not yet. She needed to stay her and get stronger. “I want to go home,” she whispered.
…things started to go to hell.
She did not sleep that night. I should have known then something was wrong. But I was tired. I was cranky. I hadn’t slept in a real bed in nearly three weeks–hadn’t really slept well in months. At least, those are the things I tell myself.
The final crisis
In the morning, the nurses sent me to have breakfast. I brought it back to the room with me as I sometimes did when Jane seemed to want me close at hand. We moved her out of the bed and into a chair. We watched two episodes of Frasier and Jane started nodding off.
She did not sleep that night.
The nurse came in and asked her if she wanted to take a nap. Jane nodded. We put her back to bed and she fell asleep. I sat next to the bed, holding her hand while I read something. An hour went by. The nurse came in with a blood pressure cuff. She said the sensor didn’t seem to be working right. This was not abnormal. Jane’s arms were so thin things didn’t always work right.
The hospitalist
Nurses have great poker faces, but spend enough time with them and you can tell when something isn’t quite right–and we’d asked for honesty. She went to find the hospitalist. He came in and ran through Jane’s vitals. We all knew by the time he was finished that Jane was in a coma. And I knew what that meant.
An hour went by.
He left to call Jen. He came back a few minutes later. “There’s nothing left to try,” he said. ” We promised honesty. We can keep her alive–maybe even bring her out of the coma. But there will be another–and she’ll just keep getting weaker. She’ll never come off the machines again–and we both know she doesn’t want to live that way.”
Keeping promises
The fighting chance had turned into no chance just that quickly. And I knew he was right–this was not how Jane wanted to live. I had promised her I would let her go if–or when–the time came. And I would do it beautifully and with honor.
‘There’s nothing left to try.’
We would start taking her off the machines in the morning, he suggested. That would give me time to gather some friends together to be with us at the end. And if she woke up, I needed to tell her what was going on. It was the hardest thing I’ve ever done–and I don’t think I did it very well.
Building the future
I will give a speech tomorrow night as we launch a fundraising initiative with the people at the Dana-Farber Cancer Institute. I’ll talked about Jane’s final days and hours. I’m not sure I’ll get through it without a cascade of tears. But I’ll do it because, just like letting Jane go, it has to be done.
…I don’t think I did it very well.
It has to be done so that someday there won’t be a need to tell her story again; so that someday no one will have to suffer what she did; so that someday no husband or wife will suffer what I–and so many others–have suffered because of this disease.
May that day come soon.
On Thanksgiving, I gave thanks for what Jane and I had together. But one day I want to be thankful that no one else will die from the cancer she fought.
Dr. Matthew Kulke, who heads the Program in Neuroendocrine and Carcinoid Tumors at the Dana-Farber Cancer Institute, calls 2010-11 a watershed moment in NET cancer. Results on the trials of Everolimus and Sunitinib were released, leading to their approval by the FDA for pancreatic NETs; trials were gearing up in the US for PRRT, the radiation treatment long in use in Europe for alleviating NET cancer symptoms, but about which questions remained in the US; the first cell lines for NETs were in development both in vitro and in vivo.
…every day brings a greater understanding…
If 2010-11 was a watershed moment in NET cancer history, 2015-16 may prove a true turning of the tide moment. The announcements and events of the last few months create new hope for every NET cancer patient. They range from substantial new research grants to significant drug trial results to a potentially entirely new understanding of how neuroendocrine tumors grow and develop.
Five years of growing change
When Jane was diagnosed in August of 2010, I read everything I could find on the topic. A Google search turned up barely a page of references–and some of those were duplicates. The day before Jane died, her doctor told me Jane’s case alone had doubled our knowledge of the disease. We spent about as much on treating Jane over those four months as was spent on research in the US for that entire year.
…a true turning of the tide…
Last month, more than 25 presentations were made at ECCO in Vienna on NET cancer–including a pair of featured presentations. We will spend more than four times as much money on research into NET cancer in the US this year as we spent in 2010. There is reason to hope.
Funding matters
In September, the NET cancer group at Iowa University received a SPORE Grant from NIH to study the “genetic and molecular composition” of neuroendocrine tumors with an eye toward developing new diagnostic techniques and treatment of the disease.
Results of the international PRRT trials, which included a number of US sites, were released at ECCO last month and could lead to FDA approval of that technique within the next year. Among the findings was a method of determining who the therapy would work well on.
…working to increase private funding…
Meanwhile, everolimus, already approved for pancreatic NETs, moved closer to FDA approval for gastrointestinal NETs as a result of the RADIANT-4 Phase III trials; telotristat etiprate, as reported here and in August, also will likely win FDA approval next year based on its recently completed TELESTAR trial.
Future matters
And these are just the highlights of the last few months. There are whispers of even bigger things on the near-horizon. Nothing looks like a cure yet–but every day brings a greater understanding of the disease and how it works, as well as new ideas for treatments that will not merely extend patients’ lives, but improve the quality of those lives as well.
…could lead to FDA approval of that technique…
We’ll look at all of these things–and much more–in more detail during the November 10 Walking with Jane Social Mediathon, which I am trying to get ready for. Stay tuned.
There are lots of different hands working on NET cancer issues–and we are beginning to see an increase in knowledge as a result.
Carcinoid syndrome sucks. I know. I watched Jane wrestle with it for years: the flushing, the mood swings, the insomnia, the diarrhea. I watched her inject herself in the belly with octreotide every morning, waited with her for the monthly sandostatin injection to thaw out at the Dana-Farber Cancer Institute.
…patients will still have to face at least a monthly needle.
None of the palliative drugs worked very well for her. Part of that was her cancer was so advanced when it was diagnosed that it simply overwhelmed all efforts to ease her symptoms. Any relief she got didn’t last long. Part of it may also have been the standard treatment doesn’t help everyone.
A new hope–at least for symptoms
But there is new hope on the horizon. The recently finished Phase 3 trial of telotristat etiprate showed the drug has a positive impact for “patients with carcinoid syndrome that is not adequately controlled by the current standard of care” according to a release last week from the drug’s developer, .
None of the palliative drugs worked very well for her.
The TELESTAR Phase 3 trial of the oral treatment was directed by Dr. Matt Kulke’s group at DFCI. If and when the FDA approves telotristat etiprate, it will be the first new treatment for NET cancer patients suffering from carcinoid syndrome in 16 years.
Quick action possible
According to Kulke, that approval could come within a year of the drug’s officially being submitted to the FDA. Because NET cancer is considered an orphan disease, new drugs for it get expedited treatment at the FDA.
…there is new hope on the horizon.
The study added telotristat etiprate to the current standard of care for a group of carcinoid syndrome patients who were not getting much relief from that standard. With both 250 mg and 500 mg doses, the patients “experienced a statistically significant reduction…in the average daily number of bowel movements over the 12 week study period” compared to those on a placebo, according to the .
Professional reactions
Kulke, who directs the Program in Neuroendocrine and Carcinoid Tumors at DFCI, called the TELESTAR results “promising, and the community of patients and caregivers who live and deal with carcinoid syndrome are excited about the prospect of a new treatment becoming available.”
“…a statistically significant reduction…”
Lexicon president and CEO Lonnel Coats was “extremely pleased” with the results of the trial. “We are committed to working closely with the FDA to file our…new drug application and to bring this innovative new treatment to patients whose lives are already impacted by the challenges of cancer.”
By the numbers
The release does not go into many details about the results of the trial, however. Those will be released at a conference in Vienna in late September. But it does offer a few glimpses from which patients and caregivers can glean some idea of the drug’s potential impact.
“We are committed to working closely with the FDA…”
The study defined a durable response as “at least a 30 percent reduction in daily bowel movements over at least half the days of the study period. Forty-four percent of the patients on the 250 mg dose achieved that level of relief. Forty-two percent experienced that on the 500 mg dose. Those numbers compare to 20 percent of patients on the placebo.
Side effects
Patients in all three arms of the trial had similar numbers of and types of “adverse events.” The “tolerability profile” with the placebo and the 250 mg dose were similar–and both were somewhat better than the higher dose when it came to mood and gastrointestinal discomfort.
…a 30 percent reduction in daily bowel movements…
The company promises to do “further in-depth analysis of safety and tolerability data.” Patients in the 12 week study are all now on an open label extension for 36 weeks, receiving 500 mg of telotristat etiprate three times a day.
How it works
Telotristat etiprate works by targeting tryptophan hydroxylase (TPH). TPH is an enzyme “that triggers…excess serotonin production within mNET cells.” The excess serotonin is what causes carcinoid syndrome.
…similar numbers of and types of “adverse events.”
It is different from somatostatin analogs, which work to reduce the release of serotonin outside the cells, because it works to inhibit the creation of excess serotonin to begin with. In a nutshell, control the TPH and you control the production of the serotonin that is causing the problem.
What the study doesn’t tell us
But before we get ready to throw away the syringes, we need to be aware the study didn’t try telotristat etiprate on its own. Patients continued with their somatostatin analogs throughout the study. There is no evidence here to suggest how the new drug would do on its own.
…works by targeting tryptophan hydroxylase…
It is possible the combination of the two methods is what caused the results–and it is equally possible only the telotristat etiprate was involved. We won’t know that until–and unless–someone studies telotristat etiprate as a stand-alone treatment.
The monthly needle remains
We also know that octreotide and lanreotide do slow tumor growth–something we don’t know about the new drug. For the foreseeable future, carcinoid patients will still have to face at least a monthly needle.
We won’t know that…
And nothing we have yet offers patients a cure. We can ease the symptoms. We can slow the progress of the disease. We can buy more time together–and more time to find a cure. This seems likely to help accomplish each of those ends.
I gave Matt Kulke a Walking with Jane Walking Stick on the day the results of the TELESTAR study were released. Telotristat etiprate seems likely to help many NET cancer patients with carcinoid syndrome have a better quality of life.
(Editor’s note: This is Part 2 of Beth R. McGivern‘s piece on her experience with NET cancer. In Part 1, she talked about her experience with the initial diagnosis of her disease and her decision to take part in the Gallium-68 PET scan trials. She detailed her experiences with that scanning method, as well. In Part 2, she talks about her decision to have surgery, and her recent discovery that her disease is progressing again.)
DFCI weighs in
I went to Dana-Farber (DFCI) in early 2013 for a consult. Dr. Jennifer Chan was very clear and honest about my situation– it was the first time that I felt I was hearing the whole situation and potential consequences of my decisions. She said that the large tumor was already pressing in on my small intestine–she showed it to me on a CT scan slice–and that there was near certainty that I would have a bowel obstruction due to that tumor at some point in the future.
Hopefully, the progression will be slow.
This was quite similar to Dr. Liu’s opinion, except she was an oncologist, not a surgeon. She set me up to meet with a surgeon and said that Dana-Farber was not going to do a huge, long surgery to get most of the extensive tumors out. They would take out the large tumor and the part of my small intestine that was causing the problem and whatever was nearby, but would not take out the smaller, more widely spread tumors. The surgery would be 3-4 hours.
Moving forward
At that point I had three opinions for surgery and two for watch and wait. I met with the surgeon, was convinced that this was a necessary step, and moved my care to DFCI. I was still nervous about the surgery and waited until after the summer because I wanted to be healthy for my niece’s wedding in August.
They would take out the large tumor…
I had the surgery in September, 2013 and they removed about 90 percent of my tumor load. During the surgery they removed two large tumors (the one hanging from my liver and a pelvic tumor that was about 6.6 cm) plus about 100 cm of my small intestine.
Surgery impact
Also removed was a 1 cm tumor in my right ovary and the corresponding fallopian tube. The doctor did not remove my gallbladder which is ok with me because I’m not having any trouble with it. The surgeon said that he got more than 90 percent of the tumors out, which is excellent.
I was still nervous about the surgery…
The surgery was large; I had tubes coming out of every orifice and I was in the hospital for six nights. The recovery took a long time. Long term effects of the surgery have been difficulty with nutrition absorption, frequent bowel movements and some loss of bowel control.
Post-surgery, I continued on Sandostatin LAR with semi-annual scans–and things remained status quo until this March. Then it finally happened: the dreaded news of cancer progression. After 4+ years on Sandostatin LAR and the debulking surgery, my remaining tumors have started to grow and progress. The good news is that there are no new visible tumors.
Progression
This March, my MRI showed tumor progression in my liver and one of my lymph nodes. We increased my dose of Sandostatin LAR from 20 mg to 30 mg in March, hoping that might slow down any further progression. My doctor wants to do another MRI in July to see if the tumors are still progressing. In July, if the tumors are stable, we’ll just continue with the 30 mg Sandostatin LAR.
…my remaining tumors have started to grow…
Since there are no approved drugs for mid-gut NET patients who have progressed on Sandostatin LAR, Dr. Chan mentioned some clinical trials that I might be well suited for that are going on at Dana-Farber:
Immunotherapy Phase 1B trial of MK-3475 for patients with advanced solid tumors
Angiogenesis inhibitors (a new form of chemotherapy)–there are a few choices for me in this category
Immunotherapy?
The immunotherapy trial sounded interesting. MK-3475 is the immunotherapy drug that has been used in advanced melanoma patients that has put some of them into remission. It works by targeting a protein called PD-L1 that allows the cancer cells to live and multiply without disturbance from the immune system.
We increased my dose of Sandostatin LAR…
MK-3475 is a drug that blocks the PD-L1 protein so that your own immune system can attack the tumor. Basically, if my tumor tested positive for PD-L1 then I would be eligible to try this clinical trial to see if the drug would work for my NETs.
Other options
Unfortunately, my tumor was not positive–and from what I understand, none of the NET tumor samples tested positive. I guess it means that this particular pathway to immunotherapy does not work for NETs – and from what I’ve heard, most other gastrointestinal cancers. So if the tumors progress further, it’s on to angiogenesis inhibitors for me.
The immunotherapy trial sounded interesting.
These drugs have dissimilar side effects from most conventional chemotherapy medications because they work very differently. Rather than killing healthy cells along with cancer cells, as many chemotherapy drugs do, angiogenesis inhibitors only prevent new blood vessels from forming.
Fighting angiogenesis
At this point, there are no FDA approved angiogenesis inhibitors for mid-gut NETS. For pancreatic NETs, Sunitinib (Sutent) and Everolimus (Afinitor) are approved. The clinical trials that my doctor presented to me are for two drugs:
Cabozantinib: This is a phase 2 trial of a drug that is already approved for thyroid cancer.
Aflibercept: This is also a phase 2 trial of a drug that is already that is approved for colorectal cancer.
…angiogenesis inhibitors only prevent new blood vessels from forming.
Both these drugs, like all cancer drugs, have multiple side effects associated with them. All things being equal–and I don’t know if they are–I’d take the Cabozantinib because it is available in pill form rather than as an infusion. Neither of these clinical trials is randomized, meaning that there is no placebo arm, so if I do one of them, I will definitely be getting the real drug.
Considering options
My issue with angiogenesis inhibitors is that they seem to work better for pancreatic NETs than for mid-gut NETs. My feeling is based on some articles I have read and the fact that they are only FDA approved for pancreatic NETs. My doctor generally agrees with me, but believes that the inhibitors may still work for mid-guts, just not as well as they do for pancreatic NETs.
…I will definitely be getting the real drug.
She also suggested taking Afinitor on an off label basis, meaning that it is not approved for my specific condition. It is already approved for pancreatic NETs, so if I took Afinitor, at least I would not be subject to the rigorous rules of a clinical trial. Novartis released information last week about a phase III trial called Radiant-4 that showed Afinitor met the trial goals for gastrointestinal and lung NETs. This study might be enough for the FDA to approve Afinitor for other NET types than pancreatic.
Into the future
I asked her if we should consider peptide receptor radionuclide therapy (PRRT). She said that this could be a possibility at a later stage. At this point my tumor load is light and I don’t have too much carcinoid syndrome. The angiogenesis inhibitors make sense to see if that helps slow progression.
She also suggested taking Afinitor…
My doctor thinks that there may be PRRT trials available for mid-gut NETs in the US in the next year. It may make sense to partake in that treatment. I could also go to Europe for PRRT, where they are much farther along in the development of this therapy. I have some time to think about this as I wait for my disease to progress. Hopefully, the progression will be slow.
(Editor’s Note: This is the first of two parts of a piece Beth R. McGivern has written about her NET cancer experience. In this section, she talks about her diagnosis and her experience with the new Gallium-68 scan that is nearing the end of trials in the US. In the second part, she talks about her surgery and the drug trials she is now considering. That piece will run here the end of next week.)
by Beth R. McGivern
Discovery and questions
In 2010, I was diagnosed with widely metastatic disease with tumors all over my abdominal and pelvic area, the largest being a 12x10x8 cm tumor hanging from my liver. Surprisingly, there were only a few very small tumors in my liver.
…the expert opinions were so divided as to what I should do.
My first specialist started me on monthly Sandostatin injections but did not believe I should have surgery. I then had another specialist review my case through a second opinion service sponsored by my employer. This doctor also did not believe I should have surgery.
Scanning options
I was quite dissatisfied with my first specialist so I changed to another doctor and they suggested that I have an octreoscan, which I had never done. I had heard that there was a better scan called a Gallium 68 PET (68-GA) that was much better at detecting tumors than the octreoscan. This doctor thought I should have a de-bulking surgery and the octreoscan would help define my tumor load and surgical plan.
My first specialist started me on monthly Sandostatin...
The FDA has not approved the 68-GA PET as a diagnostic test in the US at this point. At the time of my investigation, the closest place to get into a clinical trial for a 68-GA PET was at Vanderbilt University in Nashville, TN. The problem with the clinical trial was that it would not be covered by standard medical insurance.
Goals and fears
The goals of this test were 1) to get an accurate idea of my tumor load, 2) to see if I had the receptors that would make some of the radiopeptide therapies available in Europe a treatment option for me and 3) to get another opinion about how I should treat my disease.
The FDA has not approved the 68-GA PET as a diagnostic test…
In July 2012, I had my appointment with Dr. Eric Liu, followed by my scheduled 68GA PET scan. This was my first scan other than a CT. I was nervous about being injected with a radioactive tracer–it just sounds a bit scary.
Last in line
Dr. Liu was very articulate and professional and spent a lot of time with me. I was very impressed with my experience at Vanderbilt-Ingram Cancer Center. Dr. Liu talked about my experience to date to gather some history. He said the 68GA PET scan would answer two questions: 1) Do I have appropriate receptors for the scan to work? 2) What is the extent and location of my disease?
…it just sounds a bit scary.
The doctor said I was the last of the 50 patients that were in this clinical trial. He also mentioned, that he would appreciate it if I made a $2,000 contribution to Vanderbilt. The money would allow him to continue this important work to secure FDA approval for this scan in the US. This cost was explained to me up front before my appointment, so there was no surprise here.
Pre-test procedure
Dr. Liu said the injection should not hurt or cause any side effects–but an EKG was required before and after the scan. He assured me the radioactive tracer has a very short half-life and that I would be fine going through airport security the next day. We also discussed my doctor experiences in NYC, some of which had been “suboptimal”, and how it might work if I were to use him to treat my disease since I live so far away.
…I was the last of the 50 patients…
The prep for the scan included the EKG and the 68GA injection. Then I drank the same large container of barium contrast that I have had for all my CT scans. This process took about an hour. The injection did not sting, burn or cause any adverse consequences.
The scan experience
The PET scanner is similar to a long CT scan machine. The drill is that you have to lie on your back with your arms above your head and not move for about 30 minutes. The machine does not tell you to breathe in and out like the CT scanner does.
The injection did not sting…
Some people have issues being put into the enclosed tunnel-like machine but I just kept my eyes closed and tried not to move. Dr. Liu came into the room while the scan was going on. This surprised me as I had my eyes closed. He encouraged me to stay still and that I was doing a great job. It was a nice pep talk.
Scan results
After the scan was over I went for the second EKG and then to lunch.
It was a nice pep talk.
Later in the afternoon, we met again with Dr. Liu. He said he did not have the report yet but that I was positive for the receptors and although I have extensive disease there is no evidence of metastatic disease outside of the abdomen/pelvis.
Surgical questions
With the help of a radiologist, Dr. Walker, we reviewed the scans. The CT scan was right beside the 68GA scan on the computer screen. It was quite amazing, though I had no idea what we were looking at. The doctors said I had very low liver involvement with one definite liver metastasis to the right lobe and a possible metastasis to the left lobe.
…I was positive for the receptors…
The largest tumor hanging from my liver would most probably cause a bowel obstruction should it grow. There was also, they said, multifocal small bowel disease. That is where the primary tumor is located.
More surgical questions
Dr Liu said that he definitely thought that this was resectible because all of the tumors are in the abdomen and pelvis, i.e., not bone, brain or other mets. Surgery, although not curative, would mean that I would most likely die of something else other than carcinoid cancer. He described the surgery as major– probably six hours in the operating room with a 6-8 week recovery period.
…I had very low liver involvement…
Dr. Liu was the third carcinoid specialist that I had seen. Two had recommended taking Sandostatin and “watch and wait.” I took Dr. Liu’s surgical recommendation lightly as he is a surgeon and they usually recommend surgery.
Looking for answers
I was seeing another specialist in New York who was also recommending surgery and putting some pressure on me to do this, but I was uncomfortable because the doctor was not being clear as to what the surgery would entail or the rationale for it. Also, I was not comfortable with a giant abdominal surgery when I had no symptoms and the expert opinions were so divided as to what I should do.
He described the surgery as major…
At this point, I had two opinions for surgery and two for watch-and-wait. Later in 2012, I went to a conference sponsored by the New England Carcinoid Connection support group in Boston and heard some of the doctors from the Dana-Farber Cancer Institute speak. I thought they were more conservative and concerned with quality of life issues than most of the other doctors I had been to. I decided to get my fifth opinion there and that would break the surgery-or-watch-and-wait tie that I was in.
Editor’s Note: Carcinoid/NETs patients often have to make decisions about how to deal with their disease. With this piece, we launch a new series in which patients will talk about their individual experiences with specific procedures. Jillian Emmons was diagnosed with carcinoid/NETs in 2008. She had chemoembolization of her liver in February and March of 2015.
My surgeon told me in 2009 that one deals with carcinoid tumors with the four S’s: Surgery, Surgery, Surgery, and Sandostatin. However, there will likely come a time when the tumors in a patient’s liver are no longer considered operable and another route, such as transarterial chemoembolization (TACE), must be considered.
My situation
There are two reasons a neuroendocrine cancer patient might consider an embolization. The first is that the tumors, despite conventional treatments (Sandostatin or, more recently, Lanreotide), are still growing. The second is uncontrolled carcinoid syndrome.
The goal was to decrease the symptoms of carcinoid syndrome…
I found myself in the latter situation. Carcinoid syndrome varies from patient to patient, but I had uncontrolled flushing and occasionally experienced near fainting episodes. In addition to being uncomfortable and frustrating–symptoms arise when the carcinoid tumors release a large amount of hormones, and that will eventually lead to carcinoid heart disease if left unchecked.
Three ways to go
There are three types of embolization available to patients: bland embolization, radioembolization, and chemoembolization. Therapies must be tailored to each individual patient as we all have different profiles and needs.
…I had uncontrolled flushing and occasionally experienced near fainting episodes.
It was determined that radioembolization was not a good choice for me because 1.) I’m a small person and with repeated treatments would be at risk for hitting my lifetime max of radiation pretty quickly 2.) Radiation exposure is known to contribute to the incidence of cancer. If I were an older patient, this would not be a major concern, but at 35 it is something I consider greatly throughout dealing with my condition.
Arriving at my best route
Bland embolization uses beads alone to cut off the blood source to the tumors. My doctor felt that since more beads are used in bland embolization compared to the two other treatments, clogged bile ducts were more likely to occur–something that is best avoided.
Therapies must be tailored to each individual patient…
This left me with chemoembolization as the best option. As I mentioned before, I’m small. As a result, my doctor decided to use half the chemotherapeutic agent (epirubicin was the drug of choice for me, as it is more gentle on the heart than other options) that he normally would. He called this TACE-light.
Looking at the risks
As with any procedure, there are risks, which I read about in the scientific literature. Abstracts of such papers are readily available to the public. To get a complete copy of a desired paper, all one has to do is write to the author with the request.
He called this TACE-light.
To me, the risks that seemed particularly concerning were liver abscesses, liver failure, kidney failure, and death. I spoke with my physician at length about these risks and came to the conclusion I was unlikely to experience these–and the risk was worth it.
Personal situation
When papers report mortality levels, they include end stage patients whose livers are not doing well at the time of the procedure. The procedure can tip them over the edge and result in liver failure. My liver function tests were perfectly normal and, as such, I was unlikely to be in this group. I had also never had a reaction to contrast, and so was unlikely to experience issues with my kidneys from the procedure.
…the risk was worth it.
Finally, the likelihood of a liver abscess increases with tumor size. This meant the longer I waited to undergo TACE, the more likely it was that my tumors would grow–and the more likely that a liver abscess would form. In other words–if I were going to undergo this procedure, my risks were lowest right then.
So, I leaped.
First procedure prep
I arrived at the hospital about two hours prior to the TACE procedure. I was gowned up and had two IVs placed–one for Sandostatin, and one for the administration of sedatives, etc.
…my risks were lowest right then.
They offered me an Ativan pill to ease anxiety prior to the procedure. The procedure is under conscious sedation and given that anxiety can lead to carcinoid syndrome flare ups, I chose to take the Ativan to, hopefully, lower my risk for any syndrome related issues.
The insertion procedure
I remember the first procedure very vaguely. I remember the placement of the foley catheter. I remember struggling against them, so they had to try three times to place it, which is probably why I remember it. I also remember struggling against the catheter in my groin. I don’t remember any pain associated with either of these two catheters, just that they happened and I wasn’t happy about it at the time.
The procedure is under conscious sedation…
During the procedure, the patient is periodically asked to take a deep breath and hold it. This is the only other thing I remember from round one of the procedure itself.
Initial aftermath
The first night was better than expected. I used my pain pump occasionally, but this was really just for groin pain where the incision had been made. This area continued to be sore for about a week.
I remember the first procedure very vaguely.
At my facility, the required hospital stay is one night. Before I was released, I had to demonstrate a good appetite, ability to urinate, walk around, and of course the doctors checked me over multiple times throughout my stay.
On the home front
For me, recovery from TACE round one felt like a planned bout with the flu. I experienced fatigue, nausea, vomiting, and a low-grade fever over the course of about eight days after the procedure.
The first night was better than expected.
I experienced quite a bit of discomfort in my abdomen. It was hard to get comfortable without using a lot of pillows to support my body. The only way I can describe the feeling is to imagine your liver has been replaced with a large rock. It felt heavy and I was very much aware of it, though I wouldn’t qualify the feeling as pain.
Carcinoid symptoms decline
After about eight days, I felt pretty much back to normal. I continued to limit the amount of weight I lifted to about twenty pounds for the first couple of weeks post-TACE procedure.
…imagine your liver has been replaced with a large rock.
I noticed pretty much immediately that my flushing episodes had decreased in number and intensity. They were visibly less red and most of them were simply a visual occurrence and did not cause me to feel hot.
Follow-up tests
Three weeks after my procedure I returned to the interventional radiologist for a follow-up exam and blood work. I was shown images from my procedure demonstrating that it had gone technically well. Images of blood flow prior to the placement of the beads showed tumors throughout my liver.
…my flushing episodes had decreased in number and intensity.
After the beads had been placed, the tumors were no longer visible on the images as the blood supply to the tumors had been successfully blocked off. Blood tests showed that my liver function tests were perfectly normal–they are often elevated for a bit following the procedure–and my chromogranin A levels which had been hovering in the 1000-1100 ng/ml range for the past year were at 373 ng/ml. The normal range is <93 ng/ml.
Round #2
Round two took place about five weeks after the first round. This time, the left side of my liver was treated. I spoke with the nurses prior to the procedure about the Foley catheter issue and they went above and beyond to make me comfortable the second time around.
… my liver function tests were perfectly normal…
The set-up was the same, but my experience the second time was vastly different. I remember flushing during the procedure. I also remember a lot of pain surrounding the placement of the groin catheter and also when they removed it. Thankfully I had a wonderful nurse who held my hand when I needed it and got me through.
Recovery #2
Recovery the second time was much harder. I had been warned that the proximity of the stomach to the left side of the liver would likely result in acid reflux. I experienced intense burning upon lying down–and once it started, I could not get the burning to go away for a long time. I slept upright to combat that and it did the trick.
…I had a wonderful nurse who held my hand when I needed it…
There was a lot more nausea and vomiting the second time as well. I lost about five pounds after each procedure–though I was able to pretty quickly gain it back. The biggest obstacle to recovery, though, was intense back pain which left me without much sleep. I relied on the prescribed oxycodone to get me through. Back massages also helped take my mind someplace else.
Symptom relief
The second procedure once again left me with decreased flushing. Two weeks out from the procedure my blood work showed elevated liver enzymes. These levels were watched closely and quickly returned to normal. My chromogranin A level was 247 ng/ml.
I lost about five pounds after each procedure…
I will have imaging done in May to show the progress of the tumors, but I feel as though the procedure was a successful one. The goal was to decrease the symptoms of carcinoid syndrome and we accomplished just that.
Editor’s Note: None of the above constitutes medical advice. It is a story about one person’s experience with this particular procedure. Your experience and situation may be very different from what is described here. If you think you are a potential candidate for this procedure, you need to discuss it thoroughly with your doctor. Neither the author nor the editor have medical degrees.
Liver embolization therapy is a directed therapy that takes advantage of the unique vascular supply of the liver to go after inoperable cancers that form in the liver. The method is seeing increasing use in NET cancer patients because they are often not diagnosed until the metastases in the liver are well along in their development and have colonized the liver to the point surgery is not a good option.
Not everyone is a good candidate…
Unlike the other organs in the body, the liver is not primarily fed by an artery. Rather, it gets 80-90 percent of the nutrients it needs through the hepatic portal vein system before shipping that blood onto the heart to be sent to the lungs for oxygen. The oxygenated blood then returns to the heart to be distributed to the rest of the body.
Tumor weakness
The hepatic artery does carry some nutrients to the liver, but the liver is not very dependent on those supplies. Blocking it or its downstream capillaries doesn’t seem to do the liver any longterm harm. But it can do the tumors significant harm. They get all their food and oxygen coming in on that arterial pathway. They even create their own vasculature to steal supplies to help them grow.
The method is seeing increasing use in NET cancer patients…
Regardless of where a tumor forms in the body, that desire for blood flow creates a weakness in any tumor. If we can prevent blood vessels from forming, the tumor will starve to death in short order. Several different drugs are designed to try to do this (angiogenesis inhibitors)–they may be the only option for affecting the vasculature of tumors growing in most places in the body. You can’t easily block an artery that is feeding both cancerous and healthy tissue.
Enter embolization
But the peculiar way the liver works means blocking arteries is not entirely–or necessarily–a bad thing, and that opens up another avenue of attack. If we can block the small arteries leading to a tumor, then the tumor will starve to death the same way a city under siege does. There may be some damage to surrounding tissue, but that damage is comparatively minor–and the liver is very good at repairing itself.
But it can do the tumors significant harm.
Researchers have developed three methods of liver embolization: bland (TAE), chemo (TACE), and radiation (TARE). All three use small beads to block the blood supply to the tumors, but the beads are treated with drugs before being inserted in chemoembolization, and impregnated with radiation in radioembolization. The bland embolization beads are sterile, but not treated with anything. They simply block the blood supply to the tumor.
Embolization fundamentals
The chemo and radiation treated beads deliver their payloads directly to the tumor, which means less chance of damage to surrounding healthy tissue and fewer side effects than regular chemo or external radiation treatments can entail. For NET cancer, TACE beads can be treated with a number of different chemical agents, either singly or in combination; Y90 is used with the irradiated beads used in TARE for NET cancer: SIR-spheres or TheraSpheres, the primary difference being how big a dose of radiation each sphere carries.
…the tumor will starve to death…
The basic procedure is the same for all three forms of liver embolization. A small tube is inserted into the femoral artery and threaded up to the liver. That tube is then used to place the tiny beads into the arteries leading to the tumors. The doctors only do one lobe at a time. The second lobe is done about a month after the first, if necessary.
Embolization impact
Liver embolization can be repeated later if the tumors return or begin to grow again if the first round of embolization is successful. The procedure may improve the quality of a patient’s life and extend that life. But it does not work for everyone, and none of these treatments offers a cure for the disease. It can only reduce the size and number of the tumors in the liver and may provide some relief from the symptoms of the disease for a time.
The basic procedure is the same for all three forms…
There is a wide range of side effects–ranging from minor to severe, including–among the most negative–liver failure, kidney failure and death. But the more severe side effects are rare–death occurs in less than five percent of all cases, and is less frequent the more experience the doctor has with the procedure.
Good news–bad news
At least one of the side-effects, postembolization syndrome (fever, nausea, vomiting, abdominal pain, and elevated liver enzymes), occurs in most patients. Strangely, the severity of that one side-effect may be an indicator of the success of the procedure rather than an indication of failure, as those with more severe versions of it seem to have had a better reduction in tumor size than those with milder reactions.
The procedure may improve the quality of a patient’s life…
Not everyone is a good candidate for this procedure and it should not be used if the tumors can be dealt with surgically in any event. And even for those who are not good candidates for surgery, it is not always possible. The greater the tumor burden, the less likely it is to be an option. Where exactly the tumors are in the liver also makes a difference.
A final point
The purpose of this article is not to give medical advice. Rather, it is designed to provide basic information about liver embolization for a non-medical audience. As with any medical procedure or treatment, you need to discuss your particular case with your doctor.
