The following transcript is from an interview between Dr. Marcela del Carmen (MDC), a leading GYN Oncologist from Mass General Cancer Center in Boston and Diane Redington (DR), a woman with a GYN Carcinosarcoma (also known as MMMT) who is seeking to motivate researchers to advance the science and uncover knowledge about carcinosarcoma and find a cure for this cancer. On January 5, 2017, Diane conducted a series of interviews with Dr. del Carmen on the topic of Carcinosarcoma. This interview discusses diagnosis and treatment of MMMT.

Marcela G. del Carmen, MD, MPH is a graduate of the Johns Hopkins School of Medicine. She completed a residency in gynecology and obstetrics at Johns Hopkins Hospital and a fellowship in gynecologic oncology at Massachusetts General Hospital. She graduated with a Masters in Public Health from the Harvard School of Public Health.

Dr. del Carmen was on the faculty at Johns Hopkins before returning to join the faculty at Massachusetts General Hospital. Dr. del Carmen is board certified in Obstetrics and Gynecology and Gynecologic Oncology. She is a Professor of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School. Dr. del Carmen is also Chief Medical Officer of the Massachusetts General Physicians Organization.

Dr. del Carmen is a fellow of the American College of Obstetricians and Gynecologists and also of the American College of Surgeons, and a full member of the Society of Gynecologic Oncology, the International Gynecologic Cancer Society, and the New England Society of Gynecologic Oncologists. Dr. del Carmen has been a member of the Ovarian Cancer Committee of the Gynecologic Oncology Group and currently serves on several committees in the Society of Gynecologic Oncologists.

Dr. del Carmen’s research interests include the surgical treatment of gynecologic malignancies, specifically ovarian cancer, the management of rare gynecologic tumors and improving access to health care services for underserved populations.  Dr. del Carmen has been a principal investigator of clinical trials evaluating novel therapies in the treatment of ovarian cancer, as well as the design of a novel device for delivery of intra-peritoneal catheter

1. What do I do if I am diagnosed with this cancer? (DR)

Dr. del Carmen, when a patient is diagnosed with a gynecological carcinosarcoma or MMMT, it’s pretty devastating. So, what we’d like for you to talk about is, “What do you do when you receive this diagnosis? How do you find a team to help you make a decision on which direction to go in? And then we’d like for you to talk a little bit about treatment based on the stage that you’re diagnosed at and the kind of things that you should consider when you’re trying to make treatment decisions.”

Find an Expert Team (MDC)

Sure, so first of all, I think the most important thing that a patient can do to advocate for her care is to really go to a place that has expertise in dealing with gynecological cancers. When you think of gynecological cancers, specifically cancer of the ovary, it is defined, irrespective of cell type, by the National Cancer Institute [NCI] as being a rare cancer. So already, you are beginning to see how you’re not going to have every hospital, every physician, is going to be able to offer the appropriate expertise around care. When it comes to cancer of the ovary treatment, again, irrespective of cell type, there are data, largely out of the United States, that show that your outcome, how long you live and how well you live during that time is really, really contingent on who takes care of you. So finding that expert team of doctors and clinicians who are going to take the lead in helping you make decisions about your care is probably the most critical piece to your care and to the ultimate outcome of your cancer treatment.

Carcinosarcoma is rare. (MDC)

With regards to carcinosarcoma, that is defined as being an exceedingly rare form or cell type of cancer of the ovary or cancer of the uterus. When you look at all women that develop ovarian cancer or uterine cancer, fewer than 5% of those patients will have this particular cell type. The cell type is tricky to treat because it is pretty aggressive based on its inherent biology. These tumors are basically comprised of a combination of what we call epithelial carcinoma – these are your regular “garden variety” serous ovarian and endometrial ovarian cancer, for example – and then the second component of the tumor is a sarcoma type. So this combination of epithelial carcinoma and sarcoma is what makes it “triple MT” [MMMT] or a carcinosarcoma, and these tumors tend to be aggressive in how quickly they spread and then how refractory [resistant] they can be sometimes to surgical and systemic treatment or chemotherapies.

Confirm the Diagnosis (MDC)

So, to address the first question, the first thing you need to say is you want to have an expert pathologist, somebody who does GYN pathology, day in and day out, look at the tissue slides to make sure that you have indeed been rendered the correct cell type and that your cancer is truly a carcinosarcoma, because many of these cancers are misclassified by pathology doctors who are not really experts. When you think about it, if you are talking about a cancer that occurs with a frequency of 5% of the time [of ovarian cancers], it’s going to take an expert pair of eyes to be able to make the accurate diagnosis.

So to me, the first part of it is making sure that if you have been diagnosed with a carcinosarcoma of the uterus or of the ovary, make sure that that diagnosis has been rendered by an expert gynecologic pathologist. And those pathologists usually live in tertiary care centers or cancer care centers, mostly affiliated to big academic centers. So whether it is the MGH or the Brigham, Sloan-Kettering, Hopkins, the Mayo Clinic, MD Anderson, but places where all they do, day in and day out, is read gynecological cancers as opposed to what happens in a lot of other places where a general pathologist is reading prostate cancer today, they’re reading colon cancer tomorrow and then the next day they are going to read ovarian cancer. So because of the rarity associated with this diagnosis, I think the first step is to make sure that you have a solid diagnosis based on expert pathology review.

Team of Experts (MDC)

I think after that, if it is indeed a carcinosarcoma, you really need to put together a team of experts who have a lot of experience managing these cancers.

• Gynecologic Oncologist – A gynecologic oncologist, who is going to weigh in as to whether surgery is indicated and appropriate. If that’s the case, the timing of surgery becomes really relevant.
• Medical Oncologist – And then I think a medical oncologist is helpful in making some recommendations regarding what is the role of chemo and what kind of chemotherapy you should have. Part of that conversation oftentimes involves around the accessibility of a clinical trial.

Clinical trials can be tricky. They’re not for everyone. But for many patients they’re the right choice to make.

• Radiation Oncologist – And I think that having a team of doctors and included in that may be – depending on the stage and what else is going on – radiation oncologists to see if there is any role for radiation treatment in the therapy that’s going to be individualized for that patient.

2. What is the Treatment for Carcinosarcoma? (DR)

Could you describe the treatment for carcinosarcoma based on when you’re diagnosed with it? There seems to be such broad variation depending on what treatment center you go to. I think you alluded to that. I think the quality of your treatment team is going to define how long you live. It could be a huge factor in your treatment.

The Staging Process (MDC)

For this cancer because of the inherent aggressive biology of them… so they can come up either from the uterus or from the ovary. Irrespective of how early the stage is, and these cancers I want to highlight, they’re staged surgically, for the most part.

Sometimes if we are not going to operate, we stage them clinically by imaging studies – usually chest, abdomen and pelvic CT or a PET CT.

But for the most part, when you’re talking about early stage carcinosarcoma, you’re talking about a tumor that is either confined to the uterus, if it’s coming from the uterus, or confined to the ovary, if it’s arising from the ovary. The information about that confinement, meaning that we know with 100% certainty that the cancer has not spread, is based on surgical findings.

Let me kind of walk you through a sort of generic patient experience in early stage tumors:

• These patients come in either with a biopsy of the lining of the uterus or the endometrium that shows that they have a carcinosarcoma that began in the endometrium,
• Then they usually get imaging before they go to the operating room,
  And usually a PET CT to look for cancer outside of the [uterine] lining.
• If the PET CT does not show any evidence of metastases, then those patients are triaged to surgery
• They will have a full hysterectomy [removal of the uterus], they will have removal of their ovaries and fallopian tubes, and they will have a comprehensive lymph node dissection, where they have lymph nodes in the pelvic area and along the aorta removed
• All that tissue gets sent to pathology, it gets looked at under the microscope
• And based on what is shown under the microscope with regards to any microscopic metastases, we assign that person’s cancer a stage
• If the cancer is confined, let’s say in the example of uterine primary – if it’s confined to the uterus, even it’s really, really early, because these tumors have a very aggressive biology, almost all patients will get recommendations for chemotherapy
• We have one shot of curing it, and we want to be as aggressive as we can. If the cancer comes back, it’s a lot harder to treat it. And generally, it’s not curable if it recurs.
• Most patients, even if they have an early stage cancer, will go through surgery. The surgery is part of the treatment, but it’s also the staging portion of the management.
• Then even in early stage disease, these patients usually end up getting six cycles of chemotherapy, primarily Taxol [paclitaxel] and carboplatinum [Carboplatin]. There are emerging data that that doublet [Taxol-Carboplatin] is as good as the other chemotherapies that we had before with less toxicity.
• Depending on the finer details around the pathology report, they may end up needing a little bit of radiation therapy, something called brachytherapy to the top of the vagina.
• If the cancer has spread microscopically to the lymph nodes, then that changes the staging to a more advanced stage, meaning Stage 3. However, the likely outcome is probably better than if you present with big, bulky metastatic disease up front. So, I would say largely, patients that appear to have disease confined to the uterus will go through surgery for treatment. The surgery’s also part of the staging. Most of these patients will have 6 rounds of chemotherapy and maybe some radiation to the top of the vagina.

Metastatic Disease

For women that have metastatic disease up front, meaning that there is already a recognition by the clinician that the cancer has left its site of origin and it has spread at other places, the presentation of the patient can be different. They can present with something else and then as part of that something else, they have a workup [testing] that includes:

• CT scan of the abdomen and pelvis that shows that they have implants that look like cancer implants.
• We first need to figure out where the cancer is coming from. So, many of these patients will have a radiology-guided biopsy. So they have tissue that is procured by radiologists either through an ultrasound guidance or CT-guided procedure, and then that tissue gets looked at under the microscope, and we confirm a diagnosis.
• If that is the case, then the next question that we have to ask – we already know it is cancer, we already know that it has spread – then the next question is, “What is the role of surgery?” Can surgery be done and remove all cancer so that at the end of the surgical procedure there is no cancer left to the eyes of the surgeon? If that is the case, then surgery is the first line of treatment, followed by the same chemotherapy that you would get if you had early stage disease.
• If the operation would not lead to a complete resection, then surgery has no role, because it doesn’t add any value. It just delays the institution of systemic treatment. So, if the surgeon looks at the scans and says there’s tumor in areas that are not resectable [removal by surgery] because of the anatomy or the location, then we give chemotherapy.
• Again, the general standard is Taxol-carboplatinum [paclitaxel-Carboplatin], usually 6 cycles, and then we start to think about – is the chemotherapy working to shrink everything and then surgery may be an option? Now, that paradigm, where you would give chemo and then do surgery after the chemo, is completely “outside of the box.” We don’t have any data from any randomized trials that that is an effective way to treat these cancers. But sometimes we have to think creatively, and we think outside of the box not infrequently in medicine because not every patient is going to have a tumor that has read the textbook.
• So, I think that’s why, getting back full circle to the initial part of our conversation, that it is so critical that you have a multidisciplinary group of doctors who are experts in the management of gynecological cancers looking in as to what is the best treatment strategy individualized to your cancer, both to the stage of your cancer, your age, your medical co-morbidities, what else you bring to the table that should factor in into how best to treat your cancer.

3. What’s the role of radiation? (DR)

Very Localized Therapy (MDC)
So, you have to think of radiation therapy in the management of cancers of the gynecological tract as very localized therapy. Surgery and radiation are similar in that they treat only an area that you are going to remove surgically or that you are going to irradiate specifically. So they are not meant to treat the entire body.

Side Effects

• The difference between surgery and radiation is that when you go in and you remove something surgically, you are giving the patient surgical risks, meaning injury that can happen or a consequence of the surgery that is generally very acute. And once you recover from the surgery, you are rarely left with long-term side effects from that.
• When you give radiation therapy, you are radiating a local area of the body, but there are normal structures that are basically innocent bystanders that get exposed to the side effects of the radiation treatment, and you can end up with long-term side effects from radiation therapy, like bowel obstructions, injury to the bladder, injury to the ureters that are nothing other than you had radiation in an area where there were normal structures that also were exposed to the same dose of radiation therapy.

Benefit of Radiation

• And radiation can control tumor growth in a localized area. So, if you have tumor that really came only in the pelvis but had spread nowhere else, and you want to basically get microscopic cells that you may not have killed with chemotherapy or that you may not have removed surgically, then you want to locally irradiate that area to try to sterilize that part of the anatomy or that part of the field.
• So, it’s basically local control with the expense that you pay the price of having some long-term side effects from radiation therapy. So, the other point is that radiation therapy does not change overall survival. It changes the risk of a local recurrence. It decreases the chances if you are radiated in an area where the tumor came from but had not spread out of. By giving radiation, you basically decrease the chance that the tumor will come back in the same spot, but you don’t decrease the chance that the tumor is going to come back in a different location in the body.

Other Considerations

• Once you have cancer that has spread outside of an area of origin, then radiation therapy doesn’t make much sense, because these cancers are at risk of showing up other places, like your liver, your lung, your brain and so really, radiation wouldn’t control anything beyond the control that you would get with chemotherapy.

4. So, if you have more extensive disease, radiation is probably not a good method. (DR)

MDC
That’s correct. As a general statement, that is right. There are always exceptions to any rule. And I think that if a patient comes in and they had an area that looks like a metastases but there was really nothing above that, and that you think you would get better local control by giving some radiation therapy, sometimes we tailor the radiation to only be in that particular specific spot of the body and try to shield more normal anatomy away from the radiation beam. But in general, I would say radiation is local treatment, it decreases the risk of a cancer coming back in that specific area of the body, but it doesn’t change the risk that the cancer would show up in another place outside of the area that you irradiated.

DR
Thank you so much for sharing your time and expertise with us.

Watch the video of the transcript