Ursula Matulonis, MD
Dana-Farber Cancer Institute partnered with CancerConnect so that patients could ask Ursula Matulonis, MD, their questions about uterine, ovarian, and cervical cancer. Dr. Matulonis is Medical Director and Program Leader of the Medical Gynecologic Oncology Program at the Susan F. Smith Center for Women's Cancers at Dana-Farber, and Associate Professor of Medicine at Harvard Medical School. You can find patients' questions and Dr. Matulonis' answers below.
Q: I have a question about Stage IV uterine cancer follow-up protocol. I had surgery, radiation, and chemo, completing treatment in August 2011. I'm currently NED [no evidence of disease]. I recently had to change oncologists due to insurance issues. My new oncologist is less aggressive on follow-up visits and testing than the oncologists who first treated me, preferring to wait until symptoms reappear. Would you please describe the best practices for follow-up of Stage IV uterine cancer five years after the conclusion of treatment?
A: The Society of Gynecologic Oncology published follow-up guidelines in 2011. If you look at Table 2 in the linked recommendation, there are details for follow-up for uterine cancer based on low, intermediate, or high risk for recurrence.
Q: I have Stage III uterine cancer. I was treated with three rounds of brachytherapy in the vagina followed by six months of Taxol and Carboplatin chemotherapy. I could not have full pelvic radiation because seven months prior I had finished chemotherapy to treat Waldenstrom's macroglobulinemia (WM), and therefore the bone marrow was not strong enough to withstand full pelvic radiation. My doctor is now recommending that I have the pelvic radiation. The radiologist is concerned because of my past history of ulcerative colitis, although it has not been active for many years. Do you think the treatment I did have is enough for my best chance of a non-recurrence, or do I have the pelvic radiation for 15 days and risk the possibility of having a major flare up of ulcerative colitis?
A: It sounds like you have two reasons why the pelvic radiation was put on hold: WM diagnosis and your history of uterine cancer. We don't know the importance of radiation therapy for Stage III uterine cancer, but our radiation oncologists will usually recommend pelvic radiation in addition to chemotherapy. On the other hand, because you have these two reasons why the radiation was put on hold, I would have a frank conversation with your radiation oncologist about the pros/cons of the radiation and definitely would seek a second opinion from a radiation oncologist who specializes in gynecologic cancers.
Q: What can we do to prevent ovarian cancer?
A: If someone is part of a high-risk ovarian cancer family and they test positive for a BRCA1 or -2 germline mutation, that woman can have her ovaries and fallopian tubes removed; doing that will definitely lower her risk.
Q: Is taking curcumin recommended for prevention of recurrent ovarian cancer? Is there anything you can recommend to help prevent recurrence?
A: Curcumin given to ovarian cancer cells growing in culture has been successful, but, unfortunately, one cannot ingest the amount of curcumin orally that could kill ovarian cancer cells. There are no medications thus far that have been shown to prevent recurrence, but several are being tested, including PARP inhibitors and ipilimumab, which is an immunotherapy; these are all on clinical trials.
Q: If I have had ovarian cancer, is there any genetic screening to determine whether my two daughters (ages 42, 35) have a hereditary cancer risk?
A: This depends on your age and your family history. However, if your ovarian cancer is called a “high-grade serous,” this is the type of ovarian cancer that can be transmitted from generation to generation via high risk gene. In addition, you would be the one who would be tested, not your daughters, since they don't have ovarian cancer. I would consult a genetics counselor so a better approximation can be determined for your family risk.
Q: I had ovarian cancer, type 1B and had a total hysterectomy and chemotherapy. My CA-125 has been less than 2 for two years. What are my chances of recurrence?
A: Congratulations! There is a still a chance of recurrence, but it gets lower every year. Five years will be an important milestone, too.
Q: Are there any new treatments that look promising for low-grade ovarian cancer that presented first as a borderline tumor and recurred as low grade?
A: Low-grade serous cancers are much different from other ovarian cancers; I would suggest that you have your cancer genotyped, which you may be able to do at your hospital center. In addition to drugs, such as hormonal agents (aromatase inhibitors, tamoxifen), which can be active, clinical trials that test drugs called “MEK” inhibitors are showing real promise. There will be several studies that are focusing on different biologic agents, such as MEK inhibitors, in the near future. The website www.clinicaltrials.gov lists all available studies.
Q: What is the most likely prognosis with undifferentiated cancer in one ovary?
A: If the stage is really Stage I with a grade 3 cancer, you have an excellent chance of the cancer never returning, likely >75%. We don't know how much chemotherapy impacts those statistics, but chemotherapy is typically recommended.
Q: Any thoughts on the best clinical trial going for platinum-resistant ovarian cancer?
A: There is a lot going on ... I would peruse the www.clinicaltrials.gov website to see what studies are close to your home.
Q: Are any hospitals working on a vaccine against ovarian cancer in the New York area?
A: I believe Memorial Sloan-Kettering has one available; the University of Pennsylvania definitely does.
Q: I have Stage III 3c serous epithelial ovarian cancer. I enrolled in a clinical trial in which I received Taxol (IV), Carboplatin (IP), and Avastin (IV), which ended in March 2012. Now, I receive only Avastin (IV) for the remaining months. However, there is a possibility that my cancer has metastasized to my right iliac bone. I am awaiting the results of a bone biopsy and should know the results by the end of this month. If I have bone mets [metastasis], what general treatment options would you recommend? Is there a clinical trial I could enroll in?
A: Bone metastases from a high-grade serous ovarian cancer would be very unusual, and I agree with your oncologist that a biopsy should be done. If you do have a recurrence that is documented on a biopsy, another clinical trial is an option, re-use of Carboplatin, weekly Taxol, Doxil, etc. So there are many options for you.
Q: I had Stage III ovarian cancer and finished treatment about six months ago. I am so scared about a recurrence. What should I be looking for? Are there symptoms, or would I just have an elevated CA?
A: Often the CA-125 is able to pick up recurrence in the absence of symptoms. If symptoms do appear, they would include ones that you may have experienced at diagnosis and include abdominal bloating, shortness of breath, changes in bowel habits (such as diarrhea and/or constipation), pelvic or abdominal pain.
Q: I have Stage IV platinum-resistant ovarian cancer and have had gemcitabine. I have lesions on my liver and outside of my colon. Is there another treatment for me?
A: Absolutely. It depends on when you last received carboplatin, but re-use of that drug is a possibility, as are weekly Taxol or Taxotere, Doxil, and topotecan.
Q: How successful have PARP inhibitors been when used with patients with the BRCA1 and BRCA2 mutations? What is the future of PARP inhibitors for use in treating ovarian cancer?
A: PARP inhibitors have definitely shown activity in recurrent ovarian cancer, particularly in patients with a germline BRCA1 or BRCA2 mutation, as well as those who do not harbor a mutation but have a high-grade serous histology.
Q: When will olaparib be available?
A: Olaparib and other PARP inhibitors are available on clinical studies (www.clinicaltrials.gov). Several Phase III studies that test olaparib plus other PARP inhibitors should be underway later this year; if these studies are positive and the FDA accepts the data, a PARP inhibitor could be on the market in the next three years.
Q: I have PPC/ovarian cancer simultaneous primaries, Stage IIIC back in April 2010. After optimal debulking, I have never had a remission, and have been on consecutive chemo/treatment for over two years. I am BRCA-negative, and have also been in a dendritic immunotherapy trial (CVAC) for two months until I recurred. I am now on my seventh consecutive drug combination after having partial responses on all the others. I am clearly running out of options for next steps, if my current regimen proves either ineffective or intolerable. What types of things can I do next to ensure I can continue to battle this disease?
A: I would suggest you have your cancer genetically tested for something called “somatic mutations,” which may be done at your hospital. I would also have you consult with a hospital that has a Phase I clinical trial program, since those are the types of clinical trials you are eligible for. A good website that describes all clinical trials being conducted is www.clinicaltrials.gov, and you can search for studies.
Q: What is your opinion of the use of Metformin to treat ovarian cancer for patients who do not have diabetes?
A: I don't recommend it off a clinical trial.
Q: I have Stage IV ovarian cancer. I had weekly Taxol for four weeks with rising CA-125, then GemCarbo, which seemed to help, but now one of the remaining tumors has grown. What kind of chemo could I have next?
A: There are a number of off-study drugs that are available, such as Doxil, topotecan, and Avastin, and I would also consider clinical trials.
Q: Is maintenance therapy recommended for Stage IV if the patient is NED [no evidence of disease] after frontline treatment? And, can 12 additional treatments of Taxol (full dose spaced 21 days apart) cause cancer to be resistant to chemo?
A: There is no FDA-recommended treatment after six cycles of Carboplatin and Taxol; I don't offer women additional Taxol after completing their initial Carboplatin and Taxol.
Q: I was diagnosed five years ago with Stage IIIC ovarian cancer. I had the debulking surgery and six treatments of Carbo/Taxol. Four weeks after my last treatment, my CA-125 began to climb quickly. I've taken all the usual second line drugs. My tumor sites are not operable — spleen, liver, curvature of stomach. What is the best suited trial for me? Or the next best drug out there?
A: I would suggest you have your cancer genetically tested for something called "somatic mutations." I would also have you consult with a hospital that has a Phase I clinical trial program, since those are the types of clinical trials you are eligible for. A good website that describes all clinical trials being conducted is www.clinicaltrials.gov, and you can search for studies.
Q: My doctors are talking about HIPEC. Can you tell me what that means exactly?
A: HIPEC stands for heated intra-peritoneal chemotherapy; our center doesn't use it, and there have been no studies supporting its use in ovarian cancer.
Q: Why for two years following treatment for cervical cancer would the doctors be watching the CA-125 marker? I have just gotten a second opinion from a gynecologic oncologist who says the CA-125 marker should never have been used for a guide after my external and internal radiation treatments and chemotherapy. There is no way to do biopsies due to fibroid tumors blocking my uterus, and insurance will not cover a PET scan, unless cancer is detected. So, please explain how a patient is told they will be watched for five years fairly closely if there is no way to detect what is going on internally. Many of my symptoms that would fit return of cancer also fit side effects after cancer.
A: I agree with you that following cervical cancer after treatment is difficult, and your doctors have to take into account your symptoms (if they are changing or worsening, which would be more suspicious for recurrent cancer), physical exam, scans (CT, PET, etc.) and then blood work. Many times, in the absence of a scan showing definitive recurrence, a biopsy has to be done to confirm a diagnosis of recurrence. The CA-125 blood test is not specific for ovarian cancer and can become elevated with other gynecologic cancers, lung cancer, breast cancer, etc. For that reason, I also sometimes follow it after someone has been treated, but it should never solely be used to detect or determine a recurrence of the cancer.
Q: I was diagnosed with cervical cancer in 2011. I had chemo, external radiation, and internal radiation. I have been cancer-free for the last 18 months. My stage was IIb, and I have fibroid tumors. I still have issues, including lower abdominal pain, bowel issues, some rectal and vaginal bleeding, and fatigue, and I wonder if this is typical after all this time? I have been through many tests: PET, CT scans, angiogram, etc., and have let my doctors know how I feel, but nothing is showing up. Any thoughts as to what direction I might take?
A: If all your tests don't show cancer (which is great), then these symptoms are likely from the radiation.
Note: This Ask the Expert Q & A is not intended to be a substitute for healthcare professional medical advice, diagnosis, or treatment. Speak to your healthcare provider about any questions you may have regarding your health.