Saturday, January 28, 2012

Brachytherapy May Be An Effective Option For High-Risk Prostate Cancers


Brachytherapy for high-risk prostate cancers patients has historically been considered a less effective modality, but a new study from radiation oncologists at the Kimmel Cancer Center at Jefferson suggests otherwise. A population-based analysis looking at almost 13,000 cases revealed that men who received brachytherapy alone or in combination with external beam radiation therapy (EBRT) had significantly reduced mortality rates.

Their findings are reported online in the International Journal of Radiation Oncology,Biology,Physics.

Brachytherapy involves the precise placement of radiation sources directly at the site of a tumor and is typically used to treat low and intermediate risk prostate cancers. However, brachytherapy treatment for high-risk patients is less common and controversial, given in part to early retrospective studies that found it to be associated with lower cure rates compared to EBRT.

Many experts believe that these early series were limited by poor brachytherapy technique, and that high-quality contemporary brachytherapy may be an effective tool against high-risk prostate cancer.

"The study contradicts traditional policies of using brachytherapy in just low and intermediate risk patients by suggesting there may instead be an improvement in prostate cancer survival for high-risk patients," said co-author Timothy Showalter, M.D., assistant professor in the Department of Radiation Oncology at Thomas Jefferson University Hospital, and associate research member of Jefferson's Kimmel Cancer Center. "Although studies like this cannot prove an advantage for brachytherapy, our report does suggest that brachytherapy is no less effective than EBRT and should be considered for some men with high-risk prostate cancer."

Researchers identified 12,745 Surveillance, Epidemiology and End Results database patients diagnosed from 1988 to 2002 with high-grade prostate cancer of poorly differentiated grade and treated with brachytherapy (7.1 percent), EBRT alone (73.5 percent) or brachytherapy plus EBRT (19.1 percent). The team used multivariate models to examine patient and tumor characteristics associated with the likelihood of treatment with each radiation modality and the effect of radiation modality on prostate cancer-specific mortality.

Treatment with brachytherapy alone or brachytherapy in combination with EBRT, the researchers found, was associated with significant reduction in prostate cancer-specific mortality rates compared to EBRT alone.

Significant predictors of use of brachytherapy or brachytherapy plus EBRT were younger age, later year of diagnosis, urban residence and earlier T-stage.

According to the researchers, including lead author Xinglei Shen, M.D., a resident in Jefferson's Department of Radiation Oncology and a part-time master's degree student in the Jefferson School of Population Health, the study's findings provide ample evidence to further study brachytherapy as part of an effective treatment strategy for men with high-grade prostate cancer.

"Today, for the most part, brachytherapy is not being used for these high-risk patients or even recommended," Dr. Shen said. "But if you look at the biology and theory behind it, it makes sense: you can really give a lot more dose with brachytherapy than with EBRT alone to the prostate. And this presents an opportunity for high-risk patients."

Tuesday, January 24, 2012

Prostate Cancer Study Proves Drug Delays Disease Progression


For men diagnosed with low-risk, localized prostate cancer, being treated with the drug dutasteride (“Avodart”) delays disease progression and initiating active treatment, and also reduces anxiety, show the results of a three-year international clinical trial led by Dr. Neil Fleshner, Head of the Division of Urology, University Health Network (UHN).

The findings are published online today in The Lancet. “The results prove that using active surveillance plus dutasteride is a viable, safe and effective treatment option for men who often undergo aggressive local treatment despite low risk of dying from the disease,” says Dr. Fleshner, a surgical oncologist in UHN’s Princess Margaret Cancer Program and Professor of Surgery at the University of Toronto. Dr. Fleshner also holds the Love Chair in Prostate Cancer Prevention Research.

“This is very good news for men with low-risk disease because aggressive treatment can have a major impact on their quality of life, with risks of impotence and incontinence,” says Dr. Fleshner.

The three-year clinical trial enrolled 302 men between the ages of 48 and 82 diagnosed with low-risk localized prostate cancer and regularly monitored for clinical changes – a treatment option called “active surveillance”. In the trial – known as REDEEM (REduction by Dutasteride of clinical progression Events in Expectant Management of prostate cancer) – participants were randomized 1:1 to receive dutasteride or a matching placebo daily. The men also underwent biopsies at 1.5 and three years.

The study showed a significant delay in disease progression in the men treated with dutasteride – 38% compared with 48% who received the placebo. As well, the final biopsies showed the men treated with the drug were less likely to have cancer detected – 36% compared with 23%.

“This is the first study to show that a 5a-reductase inhibitor such as dutasteride reduces the need for aggressive treatment in low-risk disease,” says Dr. Fleshner. “The drug, currently commonly used to treat enlarged prostate, works by inhibiting the male sex hormone that causes the enlargement in the first place.”

Dr. Fleshner says a small percentage of men reported drug-related side effects including sexual difficulty with either desire or erections (5%), or breast tenderness or enlargement (3%). “It’s important to realize that these drugs have been around for almost 20 years in clinical practice to treat enlarged prostates and so we have a wealth of knowledge about their side effects, which are reversible if the drug is stopped.”

Participants were also assessed for cancer-related anxiety and the men on dutasteride reported feeling much less anxious because their biopsies and PSA values improved, adds Dr. Fleshner. (PSA – or prostate-specific antigen – is a blood test used to help diagnose prostate cancer.)

Tuesday, January 10, 2012

Cutting-edge gene therapy for bladder cancer


Bladder cancer, most frequently caused by smoking and exposure to carcinogens in the workplace, is one of the top 10 most common forms of cancer in men and women in the U.S. More than 70 percent of bladder cancers are diagnosed in stage T1 or less and have not invaded the muscle layer. At these early stages, standard treatment is surgery (transurethral resection) and the burning away of tumors with high energy electricity (fulguration). Many patients also may receive subsequent intravesical chemotherapy because there is often a high-risk for cancer recurrence.

The prognosis for recurrent cancer is poor, which drives clinician-scientists like William Larchian, MD, Urologic Oncologist, University Hospitals Urology Institute at University Hospitals Case Medical Center, and Associate Professor of Surgery, Case Western Reserve University School of Medicine, and his colleagues to develop an immunotherapy for bladder cancer that will stimulate the body's own natural defense mechanisms to cure the disease and prevent recurrence.

"What is interesting is that our bodies are capable of identifying, responding to and killing tumor cells naturally," explained Dr. Larchian. "We are developing a vaccination system to enhance this response and drive an effective immune response against existing and future bladder tumor cells in patients diagnosed with bladder cancer."

IL-2, a cytokine-signaling molecule, stimulates the T-cell immune response to cancer cells in the bladder. Dr. Larchian and his colleagues have developed a system that reliably introduces multiple copies of IL-2 DNA into bladder cancer cells.

"This method allows for more gene copies to enter the cells," he said, "and we are able to see higher rates of transfection compared to retroviral methods."

The enhanced IL-2 protein expression has been shown to successfully stimulate T-cell response and eliminate bladder tumors in a mouse model, particularly when followed by transfection with B7.1 gene. The addition of the B7.1 gene, which encodes an immune co-stimulatory molecule, enhanced T-cell production logarithmically and produced a 70 percent cure rate. Rechallenge with new cancer cells was also prevented. Clinical translation of this research has been submitted for Institutional Review Board approval at UH Case Medical Center.

Other research by Dr. Larchian and his colleagues aims to leverage this work to develop a gene-therapy system that can be utilized to deliver other key defense genes.

"Our future pursuits," he said, "will include using this system with very specific biological response modifiers, including anti-angiogenesis factors, and with the tumor suppressor gene, MCP3." Dr. Larchian also is developing a targeted drug delivery system using nanoparticles for bladder cancer treatment.

Thursday, January 5, 2012

Proton therapy effective prostate cancer treatment

Proton therapy, a type of external beam radiation therapy, is a safe and effective treatment for prostate cancer, according to two new studies published in the January issue of the International Journal of Radiation Oncology•Biology•Physics (Red Journal), the American Society for Radiation Oncology's (ASTRO) official scientific journal.

In the first study, researchers at the University of Florida in Jacksonville, Fla., prospectively studied 211 men with low-, intermediate-, and high-risk prostate cancer. The men were treated with proton therapy, a specialized type of external beam radiation therapy that uses protons instead of X-rays. After a two year follow-up, the research team led by Nancy Mendenhall, MD, of the University of Florida Proton Therapy Institute, reported that the treatment was effective and that the gastrointestinal and genitourinary side effects were generally minimal.

"This study is important because it will help set normal tissue guidelines in future trials," Dr. Mendenhall, said.

In the second study, researchers from Massachusetts General Hospital in Boston, Loma Linda University Medical Center in Loma Linda, Calif., and the Radiation Therapy Oncology Group in Philadelphia performed a case-matched analysis comparing high-dose external beam radiation therapy using a combination of photons (X-rays) and protons with brachytherapy (radioactive seed implants).

Over three years, 196 patients received the external beam treatments. Their data was compared to 203 men of similar stages who received brachytherapy over the same time period. Researchers then compared the biochemical failure rates (a statistical measure of whether the cancer relapses) and determined that men who received the proton/photon therapy had the same rate of recurrence as the men who received brachytherapy.

"For men with prostate cancer, brachytherapy and external beam radiation therapy using photons and protons are both highly effective treatments with similar relapse rates," John J. Coen, MD, a radiation oncologist at Massachusetts General Hospital in Boston, said. "Based on this data, it is our belief that men with prostate cancer can reasonably choose either treatment for localized prostate cancer based on their own concerns about quality of life without fearing they are compromising their chance for a cure."