The National Cancer Institute, part of the National Institutes of Health in Bethesda, Maryland, is working toward developing new protocols for improved treatment for peritoneal mesothelioma patients. In this interview, Mary Hesdorffer, NP, speaks with Andrew Blakely, MD (National Cancer Institute), a surgical oncologist specializing in peritoneal surface malignancies.
Diagnosis
Dr. Blakely details the difficulty in the initial diagnosis of peritoneal mesothelioma. Many women are first diagnosed with ovarian cancer before doctors accurately find that their cancer is peritoneal mesothelioma. A correct diagnosis is dependent on a pathology review, the quality of cell tissue being evaluated, and the expertise of the doctor obtaining the tissue. One way to accurately diagnose the patient is identifying the ideal areas to biopsy and providing a good sample of tissue.
Ovarian cancer and mesothelioma
Some women with ovarian cancer experience higher levels of CA 125 in their blood, which is an approved marker for ovarian cancer, but is not an approved marker for mesothelioma. Tumor markers are very patient specific and can be misleading when they are at elevated levels. Similar to mesothelioma, ovarian cancer tends to have a sensitivity to the immune system. These similarities between the two different types of cancer can lead to misdiagnosis.
HIPEC
Dr. Blakely said when it comes to treatment for peritoneal mesothelioma, centers around the country offer cisplatin monotherapy. He believes there is no evidence to say this treatment is inferior to anything else. There is retrospective data, not done in a clinical trial, that suggests a second treatment drug in addition to cisplatin could lead to additional benefit for the patient. Dr. Blakely’s preferred prescribed treatment for peritoneal mesothelioma is a combination of cisplatin with doxorubicin. There is an upcoming HIPEC trial, Dr. Blakely is involved in, where ovarian cancer patients and peritoneal cancer patients will be randomized. One set of patients will be treated with cisplatin and doxorubicin. The other set of patients will be treated with cisplatin and mitomycin. Dr. Blakely believes for peritoneal mesothelioma treatment, cisplatin is the standard of care.
TRIAL
This is a phase 1 trial studying standard of care and chemotherapy, to which Dr. Blakely said, will not sacrifice the quality of HIPEC or cytoreduction for scientific goals. Researchers will be looking at four types of histology: ovarian cancer, peritoneal mesothelioma, appendiceal cancer and colorectal cancer that have spread to the peritoneal cavity. 40 patients will be part of this trial, including 10 people in the peritoneal mesothelioma arm which will be split in half for each form of treatment.
The trial will be a lab-based platform where researchers will harvest peritoneal tumors and keep them alive for several days to study how the tumors react to changes in environment or exposure to chemotherapy. As part of the study, surgeons will take tumor nodules via surgery and simulate HIPEC treatment at the same temperature and dose of chemotherapy that the patient would receive. During this trial, patients will have HIPEC and cytoreductive surgery. Dr. Blakely and his colleagues will be looking to see if this line of treatment can demonstrate similar effects on the cell tissue with exposure to chemotherapy. If the trial is successful, researchers believe this will be a step toward personalizing HIPEC treatment to a patient’s individual tumor.
To qualify for this trial, the patient’s cancer must be in the abdomen and able to achieve the full benefit of cytoreduction and HIPEC.
National Institutes of Health and National Cancer Institute
At NIH/NCI multiple physicians study different diseases from different aspects. There is a long-standing multidisciplinary approach to mesothelioma. Patients that have a bicompartmental or tricompartmental disease can be evaluated and treated in sequence at this center. Novel investigations are also prioritized at NIH/NCI, where there is a big interest in learning more about BAP1 mutations. The institution is studying active surveillance of BAP1 patients 30 and older, by following them with serial thoracoscopy on each side and laparoscopy to detect cancer at an early stage and better refine guidelines as far as interventions and recommended decortication, cytoreduction and HIPEC. Dr. Blakely said it’s important for peritoneal mesothelioma patients to be checked for a germline mutation, because gene mutations can be found that have been studied more over the years.
The laparoscopy, as part of the study, is an outpatient procedure where surgeons will use two or three small incisions to get in the abdomen of the patient to focus on certain areas. Doctors know where mesothelioma and peritoneal malignancies can collect in the body. These areas are the right diaphragm over the liver, the pelvis and along the small intestine and omentum. This will give doctors an idea of how much disease the patient may have which can help determine if the patient should under-go cytoreduction and HIPEC.
The thoracoscopy procedure uses a special breathing tube with two chambers which are for each lung. Surgeons will make two or three small incisions between the ribs and survey the pleural cavity and lining around the lung on each side.
Both the laparoscopy and thoracoscopy can be done in around two hours.
Care while undergoing trial at NIH/NCI is provided free of charge except for travel and some extra expenses.
Young women, peritoneal and fertility
Understanding a woman’s fertility concerns and questions is a critical component of caring for a patient. NIH/NCI collaborates with Walter Reed Medical Centre on egg cell preservation and storage. This topic is something that will be brought up in a consultation at NIH/NCI. The reason why a woman’s fertility comes into question is because female peritoneal patients’ ovaries sit in the pelvis. This means the ovaries are secondarily involved in the area of the cancer. Removal of the ovaries is a component of cytoreduction surgery that is very common. To clear the pelvis of disease, not only the ovaries will be removed, but the uterus as well. This MesoTV video addresses fertility and mesothelioma.
HIPEC relapse
At NIH/NCI there is an interest in using an immunotoxin for treatment, which targets tumors that express a protein called mesothelin. Mesothelin is expressed in mesothelioma, as well as other tumors. A protocol in the works is using an immunotoxins to profuse a patient’s chest after surgery for recurrent pleural mesothelioma. This protocol is in the design stages and investigators are considering two methods: initial cytoreduction and hipec HIPEC patients undergo standard treatment, but leave a catheter to infuse the immunotoxinc into the peritoneal cavity in the early days following surgery, before leaving the hospital. The second option is to use the immunotoxin instead of the HIPEC procedure following a repeated cytoreduction. Researchers at NIH/NCI believe immunotoxin’s greatest benefit is following cytoreduction, when the amount of disease is as low as possible. The treatment primes the immune system to target cells that express mesothelin.
Our sponsors
MesoTV is a program by the Mesothelioma Applied Research Foundation. This program is made possible by our generous sponsors: Maune Raichle Hartley French & Mudd, LLC (MRHFM); Belluck & Fox; Bristol Myers Squibb; Novocure; Merck; The Gori Law Firm; Early Lucarelli Sweeney & Meisenkothen.
