SIR Reporter’s Notebook
Vol. 12 No. 5 P. 32
Editor’s Note: This article is based on research presented during scientific press conferences at the Society of Interventional Radiology’s 36th Annual Scientific Meeting in Chicago in late March. All abstracts can be viewed at www.sirmeeting.org.
Higher Doses of Y-90 Liver Cancer Treatment Tolerated
Since its introduction in 2000, intra-arterial yttrium-90 (Y-90) radioembolization has been used to treat liver cancer in patients who are not candidates for surgery. New results from a large multi-institutional study presented by researchers at the Society of Interventional Radiology’s 36th Annual Scientific Meeting in Chicago showed that treating liver tumors with higher doses of Y-90 than previously tried is safe, provides results when chemotherapies have failed, preserves a patient’s quality of life, and can be done on an outpatient basis.
“We knew that this unique interventional radiology treatment, done on an outpatient basis, which combines the radioactive isotope Y-90 into microspheres that deliver radiation directly to a tumor, was one of the best ways to give patients a treatment that doesn’t harm healthy cells,” said Riad Salem, MD, MBA, FSIR, a professor of radiology, medicine, and surgery and director of interventional oncology at Northwestern University in Chicago. “Now we know that patients can actually tolerate much higher doses of radiation than previously thought, which provides results in patients progressing on standard chemotherapy.”
The four-year prospective study looked at 151 patients (the group was 55% male, with an average age of 64) with liver metastases from colorectal, neuroendocrine, and other cancers. In the study, several subgroups showed high rates of progression-free survival, such as 186 days for neuroendocrine patients compared with 95 days for colorectal cancer patients.
“These rates are an excellent indicator of the treatment’s effectiveness,” said Salem.
For example, a 60-year-old woman with advanced liver cancer that had metastasized from neuroendocrine tumors had lesions that were progressing as she continued standard chemotherapy treatments. “At the study’s higher dose, we were able to reverse the progression and achieve shrinkage of the tumors without any adverse events,” Salem noted.
In the United States, 20,000 cases of primary liver cancer are diagnosed each year; that number reaches 150,000 for metastatic colon cancer. While the surgical removal of liver tumors offers the best chance for a cure, Salem noted a majority of patients are not candidates for surgical resection for a variety of reasons. “Liver tumors are often inoperable because the tumors may be too large or numerous or have grown into major blood vessels or other vital structures. Historically, chemotherapy drugs become less effective as the disease progresses,” he said.
Radioembolization has been shown to benefit these patients. While it is a palliative, not a curative, treatment, patients can benefit by having their lives extended and experiencing fewer side effects, such as fatigue that can last for seven to 10 days after standard cancer therapy.
“While patients aren’t cured, their lives are being extended with less downtime, and their quality of life is improving,” said Salem.
The Y-90 embology therapy, which combines Y-90 into microspheres to deliver radiation directly to a tumor, allows for a higher local dose of radiation to be used, with no danger from radiation to the healthy tissue in the body, said Salem. And, he said, since Y-90 radiates from within and is administered in the hepatic artery, it can be viewed as “internal” radiation.
Salem said more research is planned, including combining Y-90 treatments with chemotherapy as well as increasing and fractioning the dose.
PAE for Postpartum Hemorrhage Preserves Uterus, Fertility
Pelvic arterial embolization (PAE) therapy is a safe and effective treatment for postpartum hemorrhage and preserves the uterus, according to researchers at the Society of Interventional Radiology’s recent annual scientific meeting.
“This large 225-patient study, in which 86% of the patients treated showed positive results, illustrated that pelvic arterial embolization has the advantages of being a safe, rapid, economic, and repeatable procedure, performed without general anesthesia,” said Ji Hoon Shin, MD, an associate professor in the radiology department at Asan Medical Center at the University of Ulsan College of Medicine in Seoul, South Korea. “Moreover, pelvic arterial embolization preserves the uterus, allowing resumption of menstruation and preserving fertility.”
Between January 2000 and June 2010, the outcomes on 225 patients (average age of 32) who underwent PAE for primary postpartum hemorrhage were analyzed, with researchers defining clinical success as the cessation of bleeding following an initial session without the need for additional therapy or surgery.
“Many case studies have reported on pelvic arterial embolization’s usefulness for the control of postpartum hemorrhage, yet most of them involved fewer than 100 patients. This study, based on the treatment of 225 patients in a single center, had an initial clinical success rate of 86%,” said Shin, adding that with repeat PAE, the clinical success rate increased to 89%.
The results also showed that some patients needed additional PAE sessions or surgeries; therefore, overall bleeding control was achieved in 97.8% of the patients studied.
“All women who carry a pregnancy beyond 20 weeks’ gestation are at risk for postpartum hemorrhage or PPH, which remains one of the major causes of maternal morbidity and mortality throughout the world,” said Shin.
Once a baby is delivered, the uterus normally continues to contract, expelling the placenta. After delivering the placenta, these contractions help compress the bleeding vessels in the area where the placenta was attached. The most common cause of PPH occurs if the uterus does not contract strongly enough and these blood vessels bleed freely, said Shin. Such excessive and rapid blood loss can cause a severe drop in a mother’s blood pressure and, if left untreated, may lead to shock and death.
For many years, hysterectomy has remained the only solution to controlling bleeding and arresting PPH that was unresponsive to conservative medical management. In surgery, to control the hemorrhage, a physician must open the lower abdomen and tie off bleeding arteries to the uterus, repair the uterus, or remove it entirely. Shin added that the traditional surgical methods to stem PPH, such as uterine artery ligation, uterine suturing, and hysterectomy, involve the loss of fertility and risks from general anesthesia.
With PAE, a tiny nick is made in the skin in the groin and, using real-time imaging, a catheter is guided into the arteries supplying the uterus, and small particles are injected to block the blood flow to the uterus and stop the bleeding.
“Many obstetricians and gynecologists know the usefulness of pelvic arterial embolization over surgery, yet there is not always a connection between them and the interventional radiologist,” explained Shin. “Collaboration with these doctors is imperative with the hope that they will begin to refer patients to an interventional radiologist for treatment, making pelvic arterial embolization a more popular alternative to surgery.”
While these results are promising, Shin stressed the necessity to explore the impact of the treatment on future fertility. And, he noted, most patients referred for PAE had stable blood pressure, so other studies will be forthcoming on the treatment’s role in a clinical setting where the patient’s condition may be more unstable.
Embolization Helps Urinary Tract Problems Caused by Fibroids
In addition to shrinking fibroids, uterine fibroid embolization (UFE) can also improve several kinds of lower urinary tract problems in women that are specifically caused by those fibroids, said researchers at the Society of Interventional Radiology’s recent annual scientific meeting.
“Fibroids can cause a variety of unpleasant, life-disrupting urinary symptoms for women, such as bladder frequency, urgency, and the need to urinate during the night, and UFE can significantly improve these symptoms and daily life for women,” said James B. Spies, MD, MPH, FSIR, a professor and chair of the radiology department at Georgetown University Medical Center in Washington, D.C.
In UFE, imaging is used by interventional radiologists to guide a thin catheter to the uterine artery, and embolic particles the size of a grain of sand are released into blood vessels feeding the fibroid, cutting off its blood flow and causing it to shrink and its symptoms to subside.
With this study, researchers confirmed that UFE controlled and relieved many participants’ lower urinary tract problems, such as urinary frequency and/or urgency and urinary retention, using standardized measures of urinary symptoms, said Spies. The prospective study included 46 women (average age of 44) with symptomatic fibroids who had lower urinary tract symptoms and underwent UFE between March 2008 and May 2010. All subjects underwent a preprocedure pelvic MRI and completed validated questionnaires that measured urinary distress and impact, pelvic organ/urinary incontinence/sex, uterine fibroid symptoms, and quality of life. They also completed a standardized 48-hour bladder diary (preoperatively and three months after the treatment).
At three months after treatment, the women indicated an improvement in most urinary symptoms, and bladder diaries showed a significant reduction in the number of total voids at day and night. Uterine volume, dominant fibroid size, location, or bladder compression did not affect the degree of improvement in urinary distress scores. However, researchers found no difference in incontinence episodes, stress incontinence, or urge incontinence scores before and after the procedure, he said.
“This research shows that minimally invasive uterine fibroid embolization effectively reduces fibroid-related urinary symptoms in women and should therefore be offered as a treatment choice,” he added. Uterine fibroids are the most frequent indication for hysterectomy in premenopausal women, according to Spies, and they can cause prolonged, heavy menstrual bleeding severe enough to cause anemia or require transfusion, disabling pelvic pain and pressure, urinary frequency, pain during intercourse, miscarriage, and interference with fertility. Twenty to 40% of women aged 35 and older have uterine fibroids of a significant size, and black women are at a higher risk for fibroids as many as 50% have fibroids of a significant size.
Previous studies have shown UFE to be a safe and effective treatment compared with hysterectomy, and more than 300,000 women have this surgery performed annually in the United States to treat symptomatic uterine fibroids. UFE offers less risk, less pain, and a shorter recovery time compared to surgery, said Spies.
Antioxidants Before CT May Cut Radiation Cell Damage
Giving imaging patients a unique formulation of oral antioxidants before they undergo CT scans and other exams may minimize cell damage from ionizing radiation, according to researchers at the Society of Interventional Radiology’s 36th Annual Scientific Meeting in Chicago. The researchers reported that the preliminary clinical trial showed as much as a 50% reduction in DNA injury when administering the formula prior to CT scans.
“In our initial small study, we found that preadministering to patients a proprietary antioxidant formulation resulted in a notable dose-dependent reduction in DNA injury,” said Kieran J. Murphy, MD, FSIR, a professor and vice chair, director of research, and deputy chief of radiology at the University of Toronto and University Health Network. “This could play an important role in protecting adults and children who require imaging or a screening study.”
The human body is 70% water, and x-rays collide with water molecules to produce free radicals that can go on to do damage by direct ionization of DNA and other cellular targets, according to Murphy. The study sought to evaluate whether a specific combination of antioxidants have an ability to neutralize these free radicals before they can do damage. The researchers found that even though the body poorly absorbs many antioxidants, one particular mixture was effective in protecting against the specific type of injury caused by medical imaging exams.
“Our intent was to develop an effective proprietary formula of antioxidants to be taken orally prior to exposure that can protect a patient’s DNA against free radical-mediated radiation injury, and we have applied to patent this formulation and a specific dose strategy,” said Murphy.
The experiments measured DNA damage as a surrogate marker for DNA injury. Blood was drawn from two study volunteers in duplicate, creating four individual tests per data point. A big protein complex that binds to the site of the damage repairs DNA strand breaks. The researchers labeled one of the proteins with a fluorescent tag. Then, under a powerful 3D microscope, the DNA was examined for signs of repair. The more repair that was seen, the more DNA damage must have been done by the CT scan to initiate the repair. The experiments clearly showed a reduction of DNA repair in the treatment group, which means there was less DNA injury as a result of preadministering the antioxidant mixture, said Murphy.
The researchers noted that this is a small study and that more research needs to be done, but they are optimistic about the antioxidants’ potential.
“Preadministering this formula before a medical imaging exam may be one of the most important tools to provide radioprotection and is especially important for patients getting CT scans,” said Murphy. The group says the next step is a clinical trial, which the researchers are planning to begin in Toronto.