Our Approach to Rare Cancers

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma Programs. Today I'm happy to be joined by Dr. Sudipto Mukherjee. Sudipto is a hematologist here at Cleveland Clinic and Director of our Taussig Rare Cancer Program. He's here today to talk to me about our approach to rare cancers.

Welcome, Sudipto. Maybe as we start, you can give us a little background on your role here at Cleveland Clinic?

Sudipto Mukherjee, MD, MPH: Thank you, Dale. Thank you for inviting me. As part of the Rare Disease Program, which sounds like a program. It is actually a multi-disciplinary team of clinicians, pathologists and specialists from different departments all across the enterprise. The main focus of this program is to make Cleveland Clinic a center of excellence for these rare diseases, because they tend not to get highlighted in most of the cancer programs in the country. We want to make this a one-stop shop for people who have concerns about rare diseases or have been diagnosed with rare diseases to come here, make sure that their diagnosis is unequivocally established, and have a good and thorough knowledge about their prognosis and the treatment options available, which at this point in time are not too many, in fact limited, and then give them an opportunity to participate in clinical trials.

I have been working with a fantastic team of dedicated clinicians, and pathologists, and surgeons, and radiologists who have volunteered and dedicated their time specifically to focus on these diseases. And this program started around the beginning of 2017. We have already made a lot of important strikes in these last few years, and we hope to continue to do so.

Dale Shepard, MD, PhD: So I guess I'm going to have us take a step back real quick. So rare cancers, rare blood diseases. What do we mean by that? How are we defining what that means to be rare?

Sudipto Mukherjee, MD, MPH: That actually is an excellent question. When you talk about rare, it means different things to different people, and it could be related. If you look at it from a big perspective, all cancers are rare compared to chronic diseases like diabetes, or heart attack, or stroke. In our terminology, we used a very restrictive definition where we defined a rare disease, or a rare blood disorder, or a rare cancer as less than two cases per 100,000 per year in the US. This does eliminate a lot of the common cancers of the cancer that are commonly seen, and only includes those that meets that definition criteria. But even applying this very restrictive criteria, we have identified a total of anywhere from 81 to 82 diseases that we now incorporate under our rare disease program, for which we have the resources and skilled physicians to take care of these patients.

Dale Shepard, MD, PhD: And as I recall, those are primarily based on things where we may have a clinical or surgical expertise or trial opportunities or things like that, is that correct?

Sudipto Mukherjee, MD, MPH: That is absolutely correct.

Dale Shepard, MD, PhD: Now, how do we get this into a multidisciplinary approach? How has that happened?

Sudipto Mukherjee, MD, MPH: So it is still a work in progress, and it's a very difficult task to tackle. You can imagine when a person who has a concern for a rare disease or has been told about a rare cancer, they call in for a second opinion or a new consultation, unless you have a system formalized and in place, it might take a long time to finally get to the diagnosis. What we try to do at the Cleveland Clinic is basically developed a dedicated physician disease matrix that includes all specialties that may have a role in managing that disease either directly or indirectly, such as somebody requiring a surgery of a special site. Dedicated pathologists might require radiation at some point. What we do is we follow this matrix that we have develop up in consultation with these different departments.

So when a person calls in here, we are able to initiate that workflow. And depending upon what steps needs to be done to get a diagnostic field as quickly as possible, that is what we enroll. So for example, we would try to cluster the consultations in as fewer days or even in the same day, if possible, and the workflow will go along the lines of, if somebody develops a mass somewhere, they see the surgeon, it gets biopsy, and they are automatically depending upon the pathologic result would be connected to whichever would be the most relevant specialty. So if it is a rare disease, per se, for which we have dedicated physicians, they will automatically be directed to that person. As you know, this is challenging because you have to streamline different departmental workflows, scheduling workflows, but we are committed to it.

We have a system that is up and running, of course, will require fine tuning over the years. But this has, I believe, made it very easy for the patients who come in to have a really quick turnaround in establishing what they have and what the next steps would be.

Dale Shepard, MD, PhD: So particularly rare tumors, people come in and they presumably have a rare tumor. Can you talk a little bit about the role of pathology and what we're doing to try to optimize those processes to really make sure the patient gets the right treatment for the right disease?

Sudipto Mukherjee, MD, MPH: Pathology is absolutely critical. The things that we do is pretty much completely reliant on having a very clear and very unambiguous pathologic diagnosis. We have a very specialized group of pathologists here, both on the HE malignancies side, as well as in the solid tumor side who have had experience in diagnosing these diseases. They do also have an interest in these diseases. Now, when a patient comes in, what we try to do initially for new consultations is, if they are new and have never had a biopsy done or never been diagnosed, but have a concern for it, then we arrange for the biopsies and get them evaluated. The tricky situation becomes when a person comes here as a second opinion, or even a third opinion with reported diagnosis of a rare disease at an outside institution. We always try to get all the outside slides as well as mutational results for our in-house review.

It is not surprising that a lot of times the diagnosis can be completely overturned, or we may come up with a new diagnosis that was not said in the initial report from the outside hospital. These things happen and they're more likely to happen in the rare disease domain. Because first of all, you need an expertise, certain degree of pathologic expertise to diagnose these conditions. They may require some additional immunohistochemical staining, some additional genomic mutation analysis will finally arrive at a diagnosis, which we are able to offer. The bottom line is, without the pathology, things are not going to move forward. Anytime when a patient comes down for a second or third opinion, we always make it an absolute important point to get the outside of the initial biopsy slides so that you get the diagnosis before they have had a chance to go through multiple lines of therapy, which may confound the diagnosis at some situations.

Dale Shepard, MD, PhD: So we're talking about rare cancers. Can you give us an example? What are some of the more common of the rare cancers that we're seeing come through the program?

Sudipto Mukherjee, MD, MPH: The breadth of the rare hematologic or solid tumor diseases is quite wide in our program, considering that we have now listed 81 to 83 diseases. But to give you a snapshot of what are the relatively more common among the rare hematologic diseases that we see here, are histiocytic disorders. And under them, we have several different specific entities, Langerhans cell histiocytosis, Erdheim-Chester disease, Rosai-Dorfman disease, and some mixed histiocytic variance. We also see a fair number of Castleman's disease, unicentric or multicentric, or the TAFRO variant. In addition, we see are very rare cancer, quite commonly about four or five late cases per year of blastic plasmacytoid dendritic cell neoplasm. A lot of hypereosinophilic syndromes, chronic eosinophilic leukemias, a typical chronic myeloid leukemias, to name a few.

Dale Shepard, MD, PhD: Very good. How would you describe our ability to work with the referring physicians? So this is a podcast that is aimed at physicians. How do we work with them and how can we help out management of some of the patients they might find challenging with these rare cancers?

Sudipto Mukherjee, MD, MPH: My message to our colleagues in the communities and in the referring places is, we are open. You can reach out anytime you want, either to the cancer line or through email or calling the office directly. We have a very strong commitment from the department as well as the Institute to see any new consultations within five business days of hearing about the consult. What we would do would be, we will work very closely with you. As mentioned earlier, we would like to obtain any previous biopsies or pathologic specimens that had been collected as part of the evaluation process for the disease. We will request them to send you here so that we can do an in-house review. We will offer any additional testing to clinch the diagnosis beyond dispute. And we will also help the patient understand and negotiate the different treatment strategies that are available, work with them and help them in choosing a treatment strategy.

We can work in coordination with you and the patients can continue to get treated locally, and we can be involved in mutual shared care of the patient. And times when we have any new clinical trials open, we will reach out to you to notify you about those trials so that the patients, if they are interested, they have another opportunity to look at the treatment options. So what we offer is a very comprehensive support, if I may say so, where in the initial part, the patient may have to make a few trips here just to make sure that we have everything that needs to be done taken care of. But subsequently, the idea would be to tell them to continue to get care closer to their home in close coordination with us, where we are mostly in a supportive and a consultancy home.

Dale Shepard, MD, PhD: A lot of these rare diseases, rare blood cancers, there are foundations, for instance, that might support groups. How have we worked with those groups to help raise awareness and help support the activities that they're doing to help our patients?

Sudipto Mukherjee, MD, MPH: Especially for the rare diseases, where it is so much being driven by the patient advocacy groups and for this very specific disease societies. In general terms, unlike the more common cancers and diseases, these are rare diseases do get neglected in terms of funding or in terms of that research or infrastructure support in most of the cancer programs in the country. So we strongly believe that the way to get our word to the patients and to generate awareness about these diseases is to reach out and spread the message. And towards that goal, we have been working very vigorously over the last two, three years, with all the prominent disease societies in the US and internationally. We have very closely collaborated, and now we are a part of the Castleman Disease Consortium Network, which is the largest group of specialized centers in the US and abroad that are considered institutions that provide specialized care for these patients.

We are actively applying to be a part of the Erdheim-Chester Alliance, which is a global community of institutions that treat these conditions. We are now a part of a small select group of institutions that has found the QCML consortium and we will be opening. We will be participating in several of the trials when they do open. We have also become a part of the North America Histocyte organization that will identify us as a center of excellence for treating these diseases. Now, why we do these is because these are the disease societies of consortium's that have a long track record of patient advocacy and involving with the patients. And by collaborating with them, we are able to get our works to the patients. Second of all, it also gives patients tremendous opportunities in the sense that when these consortiums open clinical trials, we as part of those consortiums can open these trials for the patients.

So it is a two way traffic. And I think without this collaboration, it is very difficult to make progress and advances in the rare disease domain.

Dale Shepard, MD, PhD: You've also gotten pretty involved with the National Organization for Rare Disorders, is that correct?

Sudipto Mukherjee, MD, MPH: That's correct. And the National Organization for Rare Diseases is probably the largest organization that deals with a whole bunch of rare diseases, and not just limited to the cancers, they also deal with non-cancer diseases. Because of their strong advocacy, because of their extensive networking, they provide a perfect platform for increasing awareness, for highlighting the strengths of any particular institution in a particular disease. And by that, giving patients the opportunities and the knowledge where to go when they have a specific condition or which places to visit based on the availability of clinical trials for their particular condition. And our goals, our focus on how to treat and manage these rare diseases, perfectly aligns with NORD. And we have been very actively collaborating with them, and we hope to continue this partnership for a long, long time.

Dale Shepard, MD, PhD: What about our outreach to patients and interactions with them through social media?

Sudipto Mukherjee, MD, MPH: As you know, the reach of social media is immense. And it is also very personal way of teaching to the patients and their families who are going through these very difficult to treat diseases. Social media, I think, is something that because of its reach, because the messages can be tailor made to particular patients or particular disease groups. We definitely have tried to use this to expand and spread our message. I think this is a forum that gives you unbelievable opportunities in telling your stories, in telling patient stories, and highlighting clinical trial opportunities or highlighting any newer clinical trials that will be open to the patients and to the patient advocacy groups in real time.

The message is really quickly, and it is more tangy. Information is everything now in today's world. And the sooner you can deliver it, and the more accurate the information is, the more likely it is for the patient to get benefit from it. And that in turn also increases our reach among the patients that also makes us able to highlight our work. And hopefully, it's a symbiotic thing where not only we benefit in telling the patients what we can do for them, it also gives the patient the knowledge and the opportunity to come and visit us if they are going through a situation which has been hard to diagnose or treat.

Dale Shepard, MD, PhD: So speaking of that electronic outreach, we have certainly gotten more into an era of doing electronic consults and virtual visits. And certainly the ability to do that allows us to reach out to people in rural areas, for instance, that might not have had specialty care as easily available. So how have we been able to harness electronic consults and virtual visits to treat patients or provide recommendations for patients with rare diseases?

Sudipto Mukherjee, MD, MPH: That part is our work in progress. We have done things in bits and pieces, but we are actively working with our distance visit colleagues to formalize it. What eventually ended up happening is, if anybody has any specific condition about, or a concern about a rare disease, either they are going through it, or one of their loved family members are going through it, they can easily go to the website, find the number or the page and gives us a call, and then our distance health visit people take over. They average for all the calls to be delivered to the concerned physician who will be doing the consult. We do make it a point if we can, in a timely manner to get outside biopsy slides. Because as I've said before, pathology is the key. But that is not typically whole lot. We try for that in parallel.

And then we set up, it could be a video consultation, or it could be a telephone consultation, where we review all the records from before, and we talk to the patient and formalize our recommendations. Now, sometimes these are things that can be done in coordination with their local docs or the local hospitals. Sometimes they may have to come down here for a one-time visit just to make sure that all the diagnostic evaluations are complete and the treatment recommendations are finalized. This will become more and more a growing part of our practice, because the diseases are rare. So it is highly unlikely that you will see a huge burden of rare diseases in and around Ohio. So this gives us an opportunity for any patient to reach out to us. And this also gives us an opportunity to counsel and manage those patients, even though they may be far away.

And it establishes a line of communication, which may lead to future visits care, depending upon how well they are doing or upon availability of the clinical trials. And it also helps us spread our expertise, making it easier for people living far away to tap into and benefit from it.

Dale Shepard, MD, PhD: Lots of great work that's happened so far. What's the biggest gap, do you think? What's the next big step you'd like to take, to take this program as far as we can?

Sudipto Mukherjee, MD, MPH: I think the growth of the program is always an ongoing work. The program never stops growing. It's all about how hard you work to get your message to the patients, how hard you work to make it accessible to the patients. I think access is a huge deal in these patients with rare disease, with so many fears and concerns and limited therapies. Just a simple chat with the patient can make them really at ease. So we have done very well on the access front. We are working very hard to increase accessibility, not just in-person accessibility, but also electronically as we just discussed. I think the biggest area where we are focusing our work on would be, number one, trying to get all the pathology specimens in time to have a very comprehensive and fruitful consultation. That is a very challenging task to do because sometimes the biopsies can be spread over several institutions.

Outside diagnosis have been overturned on our in-house review on a fair number of patients. So that is always a challenge, to get all the tissue specimens in before the final consultation happens. So we know exactly what are we dealing with. And finally is a push to open more clinical trials in the rare disease domain. Because at the end of it all, once the diagnosis is said and done, we would like to offer them treatments. And the more treatment options you have, the better it is for the patient. And that is something which is on everyone's mind. Like, "I have this disease, what can I do about it?" So these are the areas we are focusing on heavily right now.

Dale Shepard, MD, PhD: Well, thank you very much for a great insight on this very important topic. Any additional comments?

Sudipto Mukherjee, MD, MPH: The only thing I would say to wrap this up is, we are open 24, seven. We have a strong commitment to see rare disease patient at the shortest possible notice. We have the expertise. We have physicians interested in these diseases, the expertise in these diseases. We have a multidisciplinary team that includes several departments across the enterprise, including pathology, oncologists, surgeons, radiologists from the department of cardiology, endocrinology. You will get a world-class multi-disciplinary team approach in establishing your diagnosis and coming up with a treatment plan. And we have a strong commitment to a very quick access and a strong commitment to a lifelong supportive care. So any questions you have, do not hesitate to reach out to us and we will do our best in taking care of you.

Dale Shepard, MD, PhD: Well, thank you very much for being with us today.

Sudipto Mukherjee, MD, MPH: Thank you very much for inviting me.

Dale Shepard, MD, PhD: This concludes this episode of cancer advances. You will find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google play, Spotify, SoundCloud, or wherever you listen to podcasts. And don't forget, you can access real-time updates from Cleveland Clinics Cancer Center experts on our Consult QD website, at consultqd.clevelandclinic.org/cancer. Thank you for listening. Please join us again soon.