Cristiano Quintini, MD, Director of the Liver Transplant Program at the Cleveland Clinic, expert in liver surgery for cancer and benign tumors, discusses a new option for colorectal cancer patients.
Interview conducted by Ivanhoe Broadcast News in October 2018.
Colorectal cancer is the third leading cause of cancer related to death. Why is it so deadly?
Dr. Quintini: It is a very deadly cancer because often times when the cancer is discovered, the tumor has spread outside of the boundaries and has involved organs for which surgery is not possible.
Can you explain what liver metastasis is and why patients with colorectal cancer develop it?
Dr. Quintini: When a patient is diagnosed with liver metastasis, it means that the cancer has spread from its original place to the liver. For patients with colorectal cancer, the liver is the most common place where metastasis occurs. This happens because the blood naturally flows from the colon and rectum through the liver. Cancerous cells like to travel through the blood stream and deposit in the first organ encountered, which is represented by the liver in the case of colorectal cancer.
Why are only a third of patients candidates for a liver resection?
Dr. Quintini: Because in order to perform successful liver surgery for patients with cancer, you need to be able to preserve at least twenty five to thirty percent of the liver. Otherwise, the patient will not be able to recover. Often, when we discover that the cancer has metastasized to the liver, more than seventy-five or eighty percent of the liver is involved and therefore surgery would be too dangerous and therefore impossible.
What is the treatment plan if resection is not an option?
Dr. Quintini: If resection is not an option, chemotherapy remains the only treatment that we can offer to these patients. We know that the best outcomes for these types of cancers are achieved when chemotherapy and surgery can work together to render the patient cancer free. When one of the two, either chemotherapy or surgery, is not possible then the outcomes are worse. Definitely, long-term survival for patients who can only undergo chemotherapy is extremely low, about five to ten percent survival at 5 years if surgery is not an option.
What was your role in developing the new transplant protocol?
Dr. Quintini: We have a transplant protocol for colorectal cancer that has metastasized to the liver, and I consider this protocol as one of the most powerful examples of the multidisciplinary collaboration necessary to beat the most complex diseases. Dr. Aucejo, head of our liver cancer program, has been leading this effort and has worked very closely with transplant colleagues, oncologists, hepatologists, radiologists, radiation oncologists and colorectal surgeons to assemble a team of teams that has one ambitious goal: to beat advanced colon cancer.
This was based on a pilot study from a study in Norway, can you tell me about that study?
Dr. Quintini: Our protocol for transplant of patients with colorectal cancer liver metastasis has been developed by looking at data from the University of Oslo in Norway. In 2011, they published their experience about twenty-one patients who underwent liver transplant for unresectable liver metastasis from colorectal cancer and they reported a five-year survival of about sixty percent. Just to give you an idea about survival, in the context of chemotherapy alone, we know that the five-year survival is only about ten percent. Therefore, this study suggested that liver transplant is a potentially effective treatment option impacting tremendously the five-year survival rate of a patient population that has often exhausted all treatment options.
Tell me about the new protocol and how it is different.
Dr. Quintini: Patients have to be at least six months away from the resection of their primary colorectal cancer. The cancer has to be confined to the liver. We cannot transplant patients who present with cancer that has spread outside of the liver because the immunosuppression that is necessary to maintain liver transplant patients alive would actually increase the likelihood of tumor growing and spreading. The last thing that we always assess is that these patients are not candidates for liver resection. The cancer has to involve more than sixty, seventy, eighty percent of the liver and resection is not an option. These are in a nutshell the requirements. There are more technicalities involved, more details. And, our protocol is different from the Norway protocol because in their study, they only used cadaveric transplant as a way to transplant these patients. In our protocol, we are preferentially using living donor liver transplant. That’s something that we offer in our program, and we felt that it was a better option for these patients for many reasons. First and foremost, these organs are allocated directly to these persons and so there’s less waiting time involved. Furthermore, we are increasing the donor pool, which is important when dealing with an experimental protocol.
Walk me through the procedure of the liver transplant.
Dr. Quintini: Liver transplant is a very well established surgical procedure. It’s very effective as shown by the one-year survival, which is about ninety-two, ninety-four percent. It consists very simply in removing the native liver and replacing it with a new one. In the vast majority of cases, the liver has been damaged by a disease process, such as autoimmune disease, alcohol, fatty liver disease or viral infections. In the case of a colorectal metastasis, the patient may have experienced severe damage to the liver because of the chemotherapy. The cancer may have grown to a point where the majority of the liver is involved. Therefore, a safe tumor resection surgery would not be possible. In the vast majority of cases, we transplant organs that come in from brain dead donors, so from a cadaveric donation as we define it. In about ten, fifteen percent of the time, we use a living donation as a means to give a transplant to patients who are on the waiting list. Living donor liver transplantation is a very powerful way to give options to patients who would have to wait too long on the waiting list. Basically, living donor liver transplantation consists in removing 40-60 percent of the native liver from a healthy person and transplanting that part to a person who is in need. That’s what living donor liver transplantation is. It’s technically much more challenging but the outcomes are great. More importantly, you give access to organs that patients would not have access to if they were on the waiting list. About twenty, twenty five percent of the patients who are placed on the liver transplant waiting list around the country die without ever being offered an organ.
Who is the best candidate for this treatment and who is not a good candidate?
Dr. Quintini: Obviously, the best candidate is a candidate who is in good health otherwise. For colorectal cancer, it is crucial to make sure that the patient does not have any extra hepatic disease, meaning that the cancer has not spread outside of the liver. Then, we assess potential donors. Donors have to be very healthy, they have to be willing to donate and they have to be willing to undergo a major operation that at times is quite involved.
Can you talk to me about Carol?
Dr. Quintini: Carol is what I consider one of the most beautiful examples of how our different teams worked together to achieve a common goal, which is treatment of Stage 4 colorectal cancer. Everything started with a diagnosis of colon cancer. She’s seen Dr. Pelley, oncologist, Dr. Hull, a colorectal surgeon, and she received chemotherapy. In her case, chemotherapy worked very well. She had already extensive liver metastasis and at that point, she was not a candidate for liver surgery. But because she had such a great response to chemotherapy, we decided to take her to the operating room to treat her colon cancer as well as her liver metastasis in what we call a two-stage procedure. In the first stage, we removed the primary colon cancer and all the liver metastasis located in the left side of her liver. Then, we sent her to our interventional radiologist for a procedure that allowed us to grow the left side of the liver (now cancer free) and to shrink the right side (still involved by cancer). After a month, we removed the right side of her liver. What’s quite unique about Carol is that we also incorporated a lot of innovative strategies in the treatment of her advanced colon cancer. First, we implanted at the time of the second liver surgery a pump to deliver chemotherapy directly into her liver. This is called Hepatic Artery Infusion (HAI) Pump. That was something that only a few places around the world can offer. She had a tremendous response from that. In fact, the cancer did not come back. However, her liver developed fibrosis because of the chemotherapy since this pump can kill the cancer but can also cause some damage to the biliary tree. As a result, Carol developed liver failure. Now, because she was disease free at that point, we were able to work her up for a living donor liver transplant, as part of the protocol we described earlier. She was lucky to have a person willing to donate part of their liver to her and she received a successful living donor liver transplant. This is the second major innovation that was used to treat Carol and fight the cancer.
Can you explain how an implantable chemotherapy fusion pump works?
Dr. Quintini: The hepatic artery chemotherapy infusion pump for the liver is a simple concept. We’re placing a catheter inside one of the arteries that supply the liver. The concept is to deliver a very high concentration of a chemotherapeutic agent that can only be absorbed by the liver. It’s a chemotherapy that does not affect the entire body or treat cancer in other organs. We can deliver higher concentrations of chemotherapy to the liver without the entire body experiencing the side effect of chemotherapy. Also, because we are able to deliver a much higher concentration of chemotherapy, it’s much more effective than the systemic therapy in preventing the cancer from coming back in the liver.
Are there any side effects or precautions for donors?
Dr. Quintini: Living liver donation is a big operation. About 40-70 percent of the liver is removed from a healthy person. So the first step is to make sure that the surgery and the recovery process occur without any complications. Complications are always taken into account as a part of this operation, but we put in place a lot of strategies to try to mitigate those risks and reduce them as much as possible. The patients are undergoing intensive monitoring for a couple of days after the surgery, then we watch them very closely for about 5-7 days. Most of the patients are able to go home after that time. We continue to follow them up very closely and watch very closely for potential complications and act very aggressively in trying to resolve complications if they arise.
And is this possible because the liver can grow back?
Dr. Quintini: Yes, the liver is an amazing organ. You can remove about seventy, seventy five percent of somebody’s healthy liver and expect regeneration between four and six weeks. That’s one thing we’re taking advantage of: the ability of the liver to regenerate on both sides, the donor and the recipient, so that we can ensure donor safety from one end and save the recipient who may not have access to organs on the other.
Is using cadaver donors standard and if not why?
Dr. Quintini: The most common type of transplant in the country and in the world is a liver transplant from a cadaveric donor – from somebody who has been declared brain dead. That’s the most common type of organs available and also that allows us to perform transplant on critically ill patients. Now living donor is a complimentary type of transplant that we use to transplant those patients who are not critically ill so they may get on the transplant waiting list and wait for a long time. Living donor liver transplant allows us to give organs to patients who would have not had access to a cadaveric organ transplant in a timely manner. Organ allocation and transplant occur by means of priority. Patients who are the sickest get the highest priority on the waiting list. About twenty, twenty five percent of the patients die on the waiting list waiting for an organ. Therefore, living donation allows us to intervene at a stage when the patient is not as sick and give those patients an additional chance to receive an organ.
And going back to the protocol, what is the ultimate goal by using this new protocol?
Dr. Quintini: The ultimate goal is to give hope for a treatment to patients who have been deemed not treatable. Patients who are sent to hospice or sent to other treatments may qualify for this protocol. That’s exactly why we think it’s important to promote this kind of treatment on these patients, because there’s a patient population that has exhausted all the options, including chemotherapy, for which this protocol may be an option.
To follow up how will this protocol help future patients, was there anything else you wanted to add there?
Dr. Quintini: This transplant protocol is an additional tool for a very selective patient population. Not all patients qualify for this procedure, not all patients should have access to transplants. But there is a selective patient population in which we believe the transplantation could have an impact in the long term.
Is there anything I didn’t ask you that you want people to know?
Dr. Quintini: I think it’s important to know that the vast majority of the patients receiving a liver transplant for colorectal metastasis will develop a recurrence of their cancer. But, what we know is that amazingly their survival is much better compared to the standard of care (chemotherapy only). So the idea is to prolong their life and bridge them to more innovative and effective treatment options that may be available in five years, six years, ten years. That’s the goal and the strategy that we use with our protocol.
If this protocol would not have been available to Carol what would her situation have been?
Dr. Quintini: Carol had already been deemed un-curable and un-resectable when she was referred to us. She was referred to us to explore different chemotherapy trials. What happened with Carol is that her case was discussed, as we do for all these cases, in a multidisciplinary conference. There were colorectal surgeons, liver surgeons, oncologists, hepatologists and radiation oncologists who specialize in this type of cancer. We were all in one room and all the options were explored for Carol. The first step was acknowledging that she had a great response to chemotherapy. That gave us hope to be very aggressive with her treatment. She’s also very young and very motivated. Once chemotherapy proved to be very effective, we then were able to transform Carol from an un-resectable patient to a resectable patient. That was also achieved with implementation of the hepatic artery chemotherapy infusion pump and other innovative surgical strategies. Transplant was the ultimate treatment, and she did extremely well. All the data we have from the literature suggests that the five-year survival for Carol would have been extremely low if she didn’t have access to these surgical and transplant options.
END OF INTERVIEW
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