In this edition:
- Jefferson Expands its Liquid Biopsy Capabilities
- Temple University Hospital Offering “Valve-in-Valve” Treatment Option for Aortic Valve Replacement
- Fox Chase Review: Evidence Points to Fallopian-Tube Origins of Ovarian Cancers; Ovary-sparing surgical approach could prevent surgical menopause in women at high risk for ovarian cancer
Editor’s note: Research, new techniques and improved facilities by Philadelphia International Medicine® hospitals and physicians may lead to new ways to treat some of our most challenging diseases. Below are just some examples from our hospitals.
Jefferson Expands its Liquid Biopsy Capabilities
Philadelphia — A new type of liquid biopsy for solid tumors based on analyzing exosomes from the blood is being tested at Thomas Jefferson University.
Thomas Jefferson University announces a partnership with Exosome Sciences Inc. to evaluate a novel liquid biopsy platform that might offer clinicians new and actionable information about a patient’s cancer as the disease progresses and changes via a simple blood test.
“The term ‘liquid biopsy’ describes the fact that a simple blood sample can contain many tumor-derived molecules and even tumor cells enabling molecular analyses similar to those possible in tumor tissue samples,” says Ulrich Rodeck, M.D., Ph.D., Professor of Dermatology, Cutaneous Biology and Radiation Oncology at Jefferson and co-lead investigator of the study.
Jefferson is a leader in liquid biopsies for cancer. Massimo Cristofanilli, M.D., Director of the Jefferson Breast Care Center at the Sidney Kimmel Cancer Center discovered in 2004 that a blood test could help to predict the prognosis of women with breast cancer. This study established that the number of circulating tumor cells in a blood sample can give doctors a quick and minimally invasive snapshot of whether a patient is likely to respond to treatment or not. In addition to circulating tumor cells, the blood also contains free-floating cancer DNA, providing researchers with an option to access treatment-relevant gene alterations in blood samples.
The new partnership between Exosome Sciences Inc. and a Jefferson team led by Dr. Rodeck, and Adam Luginbuhl, M.D., Assistant Professor of Otolaryngology Head and Neck Surgery, will focus on exosomes as a novel liquid biopsy platform. Exosomes represent a rapidly evolving frontier in liquid biopsy research. They consist of tiny bubbles or sacs pinched off the surface of cells that contain cellular contents such as RNA and proteins enclosed by the cell membrane. Recently, researchers discovered that cancer cells release large amounts of exosomes. Evidence is building that shedding these exosomes may allow a tumor to become more aggressive, to resist treatment more efficiently and, to suppress the body’s attempt to fight the cancer by dampening the cancer-specific immune response.
The team aims to collect blood samples from patients with head and neck cancer, specifically tumors in the oral cavity. Exosome Sciences will separate and characterize tumor-derived exosomes. Further molecular characterization of exosomes derived from both, tumor and normal cells will be carried out at Jefferson. The investigators will initially focus on exosome-associated RNA because RNA is abundant in exosomes and can give researchers a sampling of the genes that are currently ‘in-use’ by a cell. The inclusion of ‘normal’ exosome analysis will provide a look at the whole picture of treatment responses encompassing not just diseased but also normal tissues. The goal is to determine whether molecular signatures correlate with and predict patient responses. In future work, exosome protein content will be included in the analysis. It is expected that diverse liquid biopsy techniques will boost the ability to track cancer development and treatment responses in real time providing critical information to adjust treatment approaches.
“Head and neck cancer is an ideal disease entity to study. We’ll be able to look at how treatments affect not only tumor behavior, but also the normal tissue based on exosomes profiles, giving us a window into tolerability of treatment,” says Dr. Luginbuhl.
Exosome Sciences is a diagnostic subsidiary of Aethlon Medical, a developer of extracorporeal therapies that target the elimination of infectious viruses and tumor-secreted exosomes from the bloodstream.
Temple University Hospital Offering “Valve-in-Valve” Treatment Option
for Aortic Valve Replacement
Temple University Hospital is offering a first-of-its kind minimally invasive option for high risk patients in need of a second aortic valve replacement. The U.S. Food and Drug Administration (FDA) expanded the approved use of the CoreValve® System to treat these patients on March 30.
This treatment using the CoreValve® System is known as “valve-in-valve” replacement, and is designed for patients who previously underwent open-heart surgery to replace a faulty valve with an artificial heart valve made of animal tissue. As time goes by, these artificial heart valves wear out, making a second replacement necessary.
The FDA approval means health insurance companies and Medicare will now cover this procedure for patients in need of the replacement who are also at high risk for complications associated with traditional open-heart surgery. Until now, these high risk patients were not able to obtain coverage for the procedure and had limited treatment options for this life-threatening condition.
“Many patients have been eagerly waiting for this and now that it is here, they can get the treatment they need,” says Grayson H. Wheatley III, MD, FACS, director of Aortic and Endovascular Surgery at Temple University Hospital, and associate professor of surgery at Temple University School of Medicine. “This is a huge opportunity for patients because it avoids the need for a second high risk surgery.”
During the “valve-in-valve” procedure, a cardiologist, cardiovascular surgeon and the rest of the clinical team work together to implant the CoreValve®. Initially the valve is compressed into a catheter and then inserted through an artery in the groin. With X-ray guidance, the catheter is guided to the heart and the failing artificial valve. The valve is then deployed from the end of the catheter, at which point it expands on its own and anchors to the old failed valve. Once the valve is in place, it restores the function of the aortic valve.
“The ‘valve-in-valve’ replacement is a very straight-forward procedure that I believe a lot of patients will prefer to a second open heart surgery,” says Howard A. Cohen, MD, director of Interventional Cardiology and the Cardiac Catheterization Laboratories at Temple University Hospital, and professor of medicine at Temple University School of Medicine. “This is a great option for older patients and others deemed high risk for traditional open surgery.”
Fox Chase Review: Evidence Points to Fallopian-Tube Origins of Ovarian Cancers;
Ovary-sparing surgical approach could prevent surgical menopause in women at high risk for ovarian cancer
A new surgical approach that removes the fallopian tubes while sparing the ovaries may provide premenopausal women at high risk for ovarian cancer, particularly those with BRCA1/2 mutations, with a cancer risk–minimizing surgical option that also reduces some negative effects of ovary removal at a young age, according to a review published in the May issue of Cancer Prevention Research, a journal of the American Association for Cancer Research.
Recent clinical evidence suggests that premalignant cells associated with ovarian cancer may, in fact, arise in the fallopian tubes and not the ovaries. Therefore, it may be possible to reduce ovarian cancer risk and mortality among women at high risk through the removal of just the fallopian tubes.
“Angelina Jolie’s recent announcement about undergoing preventive removal of her ovaries and fallopian tubes has really put this issue into the national media and has made it easier to talk about this once taboo topic,” said lead study author Mary B. Daly, MD, of the department of clinical genetics at Fox Chase Cancer Center. “With this discovery, we have made a real breakthrough in the understanding of ovarian cancer risk, but it is still too early for this surgical option to become standard practice.”
Ovarian cancer is relatively rare in the United States. However, when diagnosed in late stages, it has a five-year survival of only 43.8 percent, and early screening methods are limited. Among women with familial risk for ovarian cancer due to mutations in the BRCA1/2 genes, prophylactic removal of the ovaries and fallopian tubes—a bilateral salpingo-ooporectomy—has become the standard of care for risk reduction.
“For years, it was common thinking that ovarian cancer arose out of the single layer of cells that surrounds the outside of the ovary—the ovarian surface epithelium,” Dr. Daly said. “The problem with this theory was that researchers could never find premalignant lesions in these cells the way they could with most other solid tumors.”
In their review, Dr. Daly and colleagues discussed the discovery that 10 to 15 percent of the fallopian tubes in women with BRCA1/2 mutations who underwent preventive bilateral salpingo-ooporectomy had premalignant or invasive cancer cells. Subsequent studies showed that as much as 60 percent of women with sporadic ovarian cancer also had premalignant cells in their fallopian tubes.
“Removal of the ovaries and fallopian tubes in women any time before menopause puts women into immediate surgical menopause and results in short-term side effects including night sweats, hot flashes, and mood swings, and long-term side effects including an increased risk for heart and bone disease,” Dr. Daly said. “By undergoing fallopian tube removal alone, women would still have functioning ovaries and may not lose the protection that female hormones provide the heart and bones, but they may risk the possibility that ovarian cancer could still arise out of the ovaries.”
Dr. Daly and colleagues also discussed this approach in the approximately 600,000 women at average risk for ovarian cancer who undergo hysterectomies each year in the United States. Although these women are undergoing a procedure for a benign gynecologic condition, preventive removal of the fallopian tubes may be another compelling opportunity for ovarian cancer prevention.
”We suggest the initiation of a national cohort study where women would not be randomized to one procedure or another, but instead would be entered into a national registry so that over time we could answer some of the questions about this procedure,” Dr. Daly said.
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