Cristina Ferrone, MD: Improving Care for Rare Cancers

Q: When Dr. Cristina Ferrone was a med student, the last thing she thought she would become was a surgeon. She was turned off by surgery because it was a male-dominated specialty that forced the few women in it to make hard lifestyle choices. She saw herself following more closely in her father’s footsteps towards medical oncology. However, when she entered surgical rotations during medical school she was surprised to find out how much she loved them. At Mass General she has built the Minimally Invasive Surgery Program for Liver and Pancreas from scratch, served as the Associate Program Director for the Residency Program since 2006, and become a leader in pancreatic cancer and bile duct cancer. By focusing on clinical and research work that excited her and honing in on a unique niche she has found her identity and built a balanced career in a field that is still largely male.

So, welcome, Cristina.

A: Thank you.

Q: I wanted to start out talking about the beginning of your career and I was wondering if you could talk a little more about how you ended up in surgery.

A: When I was a medical student I did my surgical rotation actually as one of my very last rotations, because I knew that that was something I definitely did not want to do, and I was surprised about how much I loved being in the operating room, I loved the fact that we worked as teams, and I had very inspiring resident mentors and faculty mentors, as well as the chair of the department who was also very inspirational.

You could see how patients came to them, they were able to address problems, they were able to fix problems, and they had an incredibly solid relationship and inspiring relationship with patients, and I think the stereotype is that surgeons come in, operate, and leave, and they don’t follow their patients and they don’t know their patients, and the beauty of cancer surgery is that you join a patient’s life in a very crucial moment, it’s an incredibly bonding experience, and especially when you’re doing high risk operations, because they’re truly putting their life in your hands and there has to be an enormous amount of trust between you and the patient in that they know you’re going to do everything you can to give them the best possible outcome.

And then you get the privilege of getting to know their family and their friends and following them over the course of the rest of their life.

Q: If you can go back to the beginning. Can you tell me a little bit more about what it feels like when you’re this young person going into the operating room, experiencing things for the first time?

A: It’s, it was incredibly exciting, and as a medical student I worked a lot with Dr. Tim Buckman who was one of the trauma surgeons, and I went to Washington University in St. Louis, and there was a lot of penetrating trauma in St. Louis, and so the students were really involved in the care of these patients, because many times there would be so many operating rooms running at the same time for big gang fights and gunshot wounds that you would be working as the first assistant as a medical student, and so you get an enormous amount of responsibility early on in assisting that faculty member.

Q: Was it ever scary to be in that situation?

A: Oh absolutely, but at least as a student you know that the faculty member knows what they’re doing and you, it’s very humbling, because you realize how much there is left to learn not only from the management standpoint but also the technical standpoint. And that is the great thing about surgery and cancer surgery, it’s not just the technical exercise of how do you do this operation, what are the steps of the operation, but when do you operate, which operation would be the best option for this patient. And thinking through all of that.

For cancer it’s really nice because we work with the medical oncologists and the radiation oncologists together, and we involve the patient very much in that discussion of these are the options that we have, we want to do what you the patient wants, and we want to give you the best outcome possible.

Q: Can you tell me a little more about how you ended up in this area of cancer?

A: Dr. Sam Wells who was the chair of the department in medical school, and Dr. Jeffrey Norton were big pancreatic surgeons, they did a lot of endocrine, but they did a lot of pancreas, so I got introduced to things like the Whipple Operation early in my student career.

And then I came to Mass General, and I was the last class that was admitted under Dr. Jerry Austin who was a former cardiac surgeon and Dr. Andy Warshaw became the chairman of the department, and Dr. Warshaw is probably one of the most famous pancreas surgeons in America, and he had always served as a mentor. So as an intern I was on his service and while you don’t really operate with him as an intern you take care of his patients. And it became sort of a passion to take care of pancreatic cancer patients and being able to accomplish an operation that is technically very challenging, probably one of the most challenging that you do in the abdominal cavity.

Q: So, coming in you’re joining the service of someone it sounds like is kind of a legend in the field. What was that like and how did you approach it as a young person?

A: Oh Dr. Warshaw was very intimidating. He was the chairman of the department and he is fairly serious and he was well-known as being very, very tough. He is incredibly smart, and so you know that he can almost, you felt like he could almost see into your head and figure out what you know and what you don’t know, and so you just worked as hard as you could, you tried to read as much as you could, and you tried to be as prepared as you could when he came around to talk about his patients.

So that was great.

Q: Now as a person who is in the prime of your career, how do you think about mentoring those who are coming up behind you?

A: I think of myself as very fortunate. When I finished my fellowship and took the faculty position in 2006 at MGH Dr. Warshaw said, “Why don’t you work with Dr. Charlie Ferguson” who was a longstanding program director for the residency, “Why don’t you help him as the associate program director?” So I consider myself incredibly fortunate to have been put into that position to work more intimately with the residents.

And I do think that I seek out and the female residents seek me out as their advocate, whether it’s for personal life advice, career advice, navigating certain situations, and I think of that as a real privilege.

Q: Is there particular advice that you give? I know the field has changed so much probably over the course of your career, but are there common advice that you give or common problems that younger people are facing?

A: I think it’s for every profession. You have so many different competing pressures, whether it’s your career aspirations, the career aspirations of your significant other, your children, all of this comes together. And I think that the only advice that I can give people is that you have to decide with your partner or spouse what is the best for your entity.

Because in the end if you’re not happy at home I think that that generates an enormous amount of stress and it’s hard to do a good job at work if you’re not happy at home. And there is so many different ways to do it and there are different times when some things have to come before other things, and accepting that maybe sometimes backing off on your career aspirations a little bit for a period of time is not the worst thing, because you will make that up at different times and in different ways.

Q: I imagine being a surgeon is stressful--

A: It can be very stressful.

Q: And I know you’re the mom of multiple children, which I imagine is also stressful. So, how do you, how do you manage that stress piece for yourself?

A: I think as you move along in your career, it used to be that the technical portion of the operations was the most stressful because of the worry of complications. And the one thing about liver and pancreas operations is that they’re very high risk and you can have people die on the OR table, and there is nothing worse than a patient who has a bad complication. No matter if you tried your best and you did everything you could and you didn’t make any mistakes and there were no errors, but they still didn’t do as well as you want them to do, there is no worse feeling, because you feel personally responsible.

But yet, there are so many days that you have where you get the cancer out and the patient says to you, “Thank you for saving my life. Thank you. Thank you.” And their whole family thanks you. And there is nothing that is more rewarding than feeling like, “Wow, I have really impacted this person, this family, and their community.”

Q: Yeah. How do you learn to live through those bad outcomes and to move forward?

A: They are a lot of sleepless nights. So, some of it is talking through things with your colleagues, and I am very fortunate I have Dr. Lillemoe who is our current chair and Dr. Fernandez who has been my teacher as a resident and then my colleague and partner for many years. And then we have a junior partner, Dr. Quadan, and they have always been very supportive and very helpful to talk through what can I do, how, how can we alter things, and they’re always offering to help or reaching out to colleagues around the country.

But still that sense of personal responsibility, it’s an emotional burden, it really is a huge emotional burden that you know that you have to work through so that you can do your best for the upcoming patients.

Q: Yeah, it seems to me that that would be one of the hardest parts of practicing medicine.

A: I would say it’s, that’s, that’s the worst part. And this is the thing, with these high risk operations the highs are really, really high, because I operate on a lot of people that have been sent away by other big centers, and so they come as sort of their last hope, and you’re able to get these cancers out and really prolong their life.

But when things go not perfectly and patients have problems and they suffer, you suffer with them. You really do suffer with them. And it’s a lot of nights and phone calls and arranging things and trying to minimize any kind of stress on the patient.

Q: Can you talk a little bit about your peer network? I know you have talked about having relationships with mentors but also your peers around the country.

A: Yeah, so I think my peer network in many ways is, yes, the surgeons but a lot of the medical oncologists and radiation oncologists, just because we work together for clinical trials and for research protocols. And they really become a good part of your friendship circle and and your life.

There are definitely many surgeons around the country. There are not many women. We’re about 7-8% of the liver and pancreas surgeons are women. We all know each other very well, and I have to say it’s a very collegiate group of women, and we really stick together and help each other. And that makes it super fun.

Q: And how do those women around the country, how do you support one another? What does that look like, that support network?

A: So it ends up being more support in terms of at the big national meeting we need somebody to speak about X and to volunteer one of your peers, or saying, “I just heard there is a job opening. They called me about it. Make sure you apply, because this might be perfect, because I know you were thinking about going back to whatever area of the country.” And trying to help each other in that way, writing letters of recommendation for their promotion, if you know their chair or their chief, putting in good words for them and saying, “I worked with this person and she did a fantastic job. And really supporting each other that way.

And sometimes we just text each other pictures of our kids or pictures of birthday parties or other social things to keep it light and fun.

Q: And that balance of real life and professional life. I am curious to hear, you have said when you started doing a lot of this work, nobody else was really doing the work that you’re doing now. So, what made you go to this space that there wasn’t someone standing there necessarily that you could follow?

A: I think there was an opening. In many ways it was an opportunity and for pancreatic cancer we had always had a great reputation, but the chemotherapy had changed, and I was working Dave Ryan from medical oncology and Ted Hong from radiation oncology, and we had a common patient, a young woman, kids, she presented with a pancreatic cancer where the blood vessels you have to have to stay alive were involved.

And Dave said, “We’re going to give her the chemotherapy that we usually use for people who have metastatic disease, because we know that works.” And Ted said, “Okay, well she did well with the chemo. I’m going to give her radiation.”

Her tumor markers came down, but if you looked at the scans it looked like those blood vessels were still involved. And so we had a long conversation with the patient, and we said, “You know, we don’t know how much of this cancer is dead.”

And she said, “I want you to try.” And they said, “Cristina, are you willing to try?” And I said, “I’ll try.”

But there was, we present all of the patients who are going in the operating room in conference, and there was a lot of pushback from people who tend not to do as much pancreas, but they said, “You know, are you crazy? Are you out of your mind? The CAT scan shows that there is still blood vessel involvement. You’re never going to get that out. You’re going to put this poor woman through an operation.”

And we went in and we were very careful and it took nine hours to get it out. And she lived for almost five years with no cancer coming back and was able to enjoy her kids and was able to enjoy her family, and some people might say, “Oh well it’s only five years.” But when otherwise you would have died in five months five years is a long time.

Q: Yeah.

A: And that’s what started our whole program for locally advanced pancreas cancer, and that’s what was the basis of doing two clinical trials, and those two clinical trials then gave me the opportunity to now lead a national clinical trial looking at when we time chemotherapy for patients with pancreas cancer.

So it’s an exciting time, because a lot of it is changing and really none of this would have ever happened if I didn’t have Dave Ryan who is very forward thinking, Ted Hong who is forward thinking, and knowing that in the operating room I always have my colleagues as backup.

Q: I want to go back to that moment when you’re presenting this case, and everyone is saying you’re crazy. What gave you the confidence or the courage to go forward in the face of all of that?

A: I think it was one of those times where I said, “You know what, I’m going to do what I think is the right thing to do.” And I said to the group, “We had a very educated conversation with this patient. We explained everything.” I said, “I explained the risks in more detail than I think I have ever explained risks. And we have to give her a chance.” Because at some point the patient is allowed to make a choice about what they want to do and how aggressive they want to be.

And I think that people had some concerns about the technical approaches and how we were going to do that, and so I thoughtfully laid out the steps that I was going to undergo to be able to get it out. But also in the back of my mind, realizing this patient has any problems after the operation I’m going to be sitting in hot water. It’s a make it or break it moment, but I felt that we were doing the right thing and the patient was informed and the team was informed.

Q: It seems to me that patient component is a big part of it. I know working here I’ve learned a lot about how much of medicine is choices and tough choices, and often it falls on the person. And how do you guide a person through those kinds of decisions?

A: You know, it’s interesting, because patients really vary significantly. There are some patients who say, “I just need you to decide.” And I won’t let them get off the hook that easily. And there are others who want to know every step. And so it’s a wide spectrum.

Many ask, “What would you do?” But I don’t think it’s the right thing for me to tell them what would I do, because the reality is it’s, and this is what I say to every single one of them, “I am here to do what you want me to do. I can tell you what the two or three options are, and this is the risk associated with these options.”

And some people say, “Swing for the fences. I want to go for the home run. I realize that there is the most risk associated with that.” And others say, “You know what, I’m completely risk averse. I feel okay and that potential benefit is not worth it to me to take on the risk of a big operation.”

And I think both answers are correct, because it’s really what the person is comfortable with internally.

Q: So, as you’ve been doing this work and pioneering and changing the way things are done, what do you think has made you successful doing something that no one has done before?

A: I think honestly the team that I’ve worked with. We’ve made a huge effort to make a contribution to the field. And that includes some of the basic science and translational science researchers that I work with, because we have a common goal and the common goal is to impact the field. And we all think of our role as our job is to push the limit, our job is to make change, our job is to contribute. And that being the common goal makes us all really work well together.

Q: Can you talk a little more about how your clinical practice and your research work, how those fit together?

A: Yeah, so my clinical practice is basically about 50 to 60% liver and 50 to 60% pancreas, and when I first came on faculty, I started to work with Nabeel Bardeesy on bile duct cancer. And the bile duct cancer is interesting because it involves the liver if it’s the bile ducts in the liver, it involves the tube that connects the liver into the intestine, which goes through the head of the pancreas, and so it really combines those two fields. And it was something that, with 10,000 cases a year in the United States, nobody cared about. And Nabeel Bardeesy and I really had a Great synergism to work on this disease. And we established the first mouse model together, we established the first cell lines together, we are looking at different options for treatment, and that has been incredibly stimulating.

David Ting, is one of the medical oncologists, has helped us an enormous amount with this and joining that with all of our pancreas research as well. And then the third component is I get to work with my father, which is fantastic. He is a medical oncologist too. He is an immunologist and spent most of his career on melanoma, but has really helped develop some of the things that they learned and techniques that they learned in melanoma for bile duct and pancreas cancer, including CAR T-Cell therapy and different antibody therapies that might open different avenues and different doors for treatment options for patients.

Q: How does that translate?

A: You know, some of it is is that if you look at prostate, breast, colon, melanoma, there is so many more cases a year, and there is a lot more research funding for those diseases than there is for pancreas or bile duct, just because they are much rarer. There is about 55,000 cases of pancreatic cancer and about 10,000 cases of bile duct cancer a year, when you compare to a couple hundred thousand for those other tumor types.

And so different ways of analyzing cancers and the methodology of evaluating the immune response to a different kind of answer can be translated to look at these rarer cancers and say, “Okay, do some of the same mechanisms apply? Can we use some of the same techniques to better understand why or why not one of these cancers would be susceptible to this type of therapy and how we could manipulate the immune microenvironment to get it to be more effective?”

Q: Yeah. What is it about pancreatic cancer that makes it so dire?

A: Most of the pancreatic cancer patients are like Pavarotti, Michael Landon, now Alex Trebeck, Aretha Franklin, so pancreatic adenocarcinoma, which is the one that tends to grow very quickly, it tends to be a very fibrotic and dense tumor, so we think chemotherapy has a harder time penetrating the cancer. But the cancer tends to infiltrate nerves, so what you can see under the microscope is you can actually see tumor cells inside the nerve sheath. Nerve sheaths look like cables, and you can actually see the cancer cells inside. And so we think that that is one of the reasons it’s able to be so aggressive, but also why patients tend to have pain. And oftentimes it shows up fairly late, where it has already progressed significantly before the patient realizes it.

Q: Is that because there aren’t symptoms, so people just don’t go looking for it?

A: Many of the patients complain of back pain, but the problem with the complaint of back pain is that common things being common, people get sent to physical therapy and different options to deal with musculoskeletal pain. So, I always say whenever I give a lecture to physicians who are screening large populations of patients is that the pancreatic cancer back pain is up where a woman’s bra strap in the back would be. So, it’s much, much higher than musculoskeletal back pain which tends to be much lower, sort of where your hips are.

And any time somebody has new onset diabetes it’s a red flag, and people who have unintentional weight loss.

Q: I am wondering, as you’re talking about no one really cared about this cancer, you started doing it, are other people, have other people picked this up now in other parts of the country or at other hospitals?

A: Bile duct cancer was really the orphan and we worked fairly heavily with Stacie Lindsey and the Cholangiocarcinoma Foundation, and I have to say this was a family from Utah where a young member passed away from bile duct cancer, and the entire family rallied around creating this foundation and they have done an unbelievable job. I have been on their Advisory Board now for seven or eight years, and the first meeting they had it was 40 of us sort of talking about bile duct cancer. And last year’s meeting, I think it was 600 people.

So, they have done a tremendous amount of work to bring light onto this rare cancer. And we have had some progress understanding the biology. It has some mutations that are what we call “actionable’” where we have medications that can treat it, as well as some immunotherapy approaches that have made incredible strides for a subset of patients.

Q: And when you think forward, you’re doing all this research, you’re learning about these cancers, and when you think forward? What is your future vision with your research? What do you hope you accomplish?

A: I have to say the thing that I am most excited about is we’re trying to set up a CAR T-Cell model that gets injected through the hepatic artery, which is a blood vessel that supplies the liver, but cancers in the liver preferentially get blood supply from the artery versus the portal vein, and so taking advantage of that blood supply and allowing us to manipulate that is what we’re working on now, and I’m very hopeful for that.

And I think the other thing is the big national trial for pancreas cancer, I’m incredibly excited about it, because it’s going to be a surgeon-led clinical trial, which is exciting, but it’s also that we’re combining efforts with Canada and the United States to try to make progress quickly.

Q: So with this national trial that you mentioned, can you tell me a little more what that looks like?

A: So, it is a trial that will be run through the Alliance, which is the cooperative group of many different institutions around the United States, and now we’re going to have the Canadian cohort join us as well. And it’s for patients with what we call resectable pancreatic cancer, as in you could operate right away. And it’s looking at the timing of the chemotherapy: should we give chemotherapy right when they are diagnosed and then go to the operating room or should we operate and then give chemotherapy.

And there are many nuances, because some of the chemotherapy is very strong, and the operation is very big and has significant risks. And so balancing those and really understanding how we can best serve patients and how we can improve their overall survival most significantly will be what the primary outcome is of this trial.

Q: I wanted to talk a little bit about building your career in surgery, which when you began was very male-dominated, certain fields, as you said, still are. There was a study done recently by Brigham and Women’s Hospital that found that one-third of women when they’re in training consider leaving training, a quarter of female surgeons end up leaving. So, how have you built a career and a life that is sustainable in this field that can obviously be difficult?

A: So I think it goes back to are you passionate about what you do, but I think that the reality is that I’ve always had an incredibly supportive family. And my husband is, I can’t ask for a more supportive husband. And so I think with that support and stability that helps you when things maybe are a little bit more tumultuous and rocky where you say, “Oh I’m so exhausted. Can I really fight the fight anymore?”

But I think when you think back of when the students are deciding on what field they want to go into, I always say the same thing to them, I said, “You know, don’t make a choice for lifestyle reasons, because if you’re doing something that you don’t like six to eight hours is really, really long, but if you do something that you love, even if you’re there eight to 10 hours or 12 hours, you’re going to feel invigorated and you’re going to feel like you’re making a contribution and you have purpose and you’ll really be good at what you do.”

Q: Do you think there are ways institutions can better support surgeon parents or professional parents?

A: I think a lot of institutions are trying to address this, because there are more women in medicine and there are more women who are in their childbearing years who want to have families, and so I think that the ACGME has made a lot of progress not only in limiting the work hours per week, but also building in maternity leave for women who do have children.

I think institutions are trying to work on daycare options in the hospital, because the reality is most surgical residents get to work by 6:00 AM and we hope that they leave by 6:00 PM, but sometimes they’re there later and needing that extra backup is incredibly important, because there is nothing more stressful than being at work and thinking there is nobody to pick up your child from the daycare, the soccer field.

I think the other part is I think that the institutions are trying to make some of the training programs maybe a little bit more flexible so that people can build things in that suits their needs. And it’s not only having a family. I mean, people have to take care of sick parents or sick siblings, and we have to be a little bit nicer to ourselves. The way that we want to treat our patients we also need to treat each other and our colleagues, because again if you are so stressed because of what is going on and you feel like you can’t manage that burden there is just a lot higher chance that you’re going to walk away, and we’ll lose somebody who would have most likely made a great contribution to the field. And it’s a big loss if we lose them.

Q: So if we can’t let people take care of themselves they can’t take care of other people.

A: And they can’t love what they do if they’re resentful because they can’t do what they need to do to keep their head above water.

Q: Well, thank you so much, Cristina.

A: Thank you, Amy.

Q: It’s been such a pleasure. Before I let you go I have my final five.

Q: What rituals help you have a successful day?

A: Thinking about a schedule that is as efficient as possible so that you can really take advantage of every minute, because we all only have 24 hours in a day. I always look at my schedule a week in advance and I figure out what holes there are and what places we could make things more efficient, and that includes things like who is going to drop off, who is going to pick up, who is where.

Q: If you weren’t a doctor what would you be?

A: An architect.

Q: Why?

A: I think it’s sort of the combination of art and structure and engineering that I love. It’s that manipulative portion and the spatial resolution that I find fascinating.

Q: What is the best decision you ever made?

A: To marry my husband.

Q: Do you have any guilty pleasures?

A: I work out every day at 5:00 in the morning, because that’s the only time that nobody bothers me, and the residents know that if they need me they better call my cell phone between before 5:00 AM or after 5:45.

Q: And what are you curious about right now?

A: Who is going to be our next President.

Q: Thank you so much, Cristina. It’s been wonderful talking with you today.

A: Thank you, Amy. Thank you for taking the time.
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