Articles about new radiotherapy drugs, treatment methods etc.

MIT Method Reveals How Radiation Damages The Body

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01 Mar 2006

Researchers at MIT have devised a new method for examining how radiation damages normal tissue in the body. The knowledge may make it possible to reduce side effects for cancer patients or to develop treatments for radiation exposure.

About 50 percent of all cancer patients are treated with radiation therapy, either alone or in combination with some other type of treatment. Radiation can be very effective in killing tumor cells, but it also kills normal tissues nearby. In the gastrointestinal (GI) tract, this killing of normal cells can cause such side effects as nausea or diarrhoea within days or weeks of treatment, and serious GI tissue damage can occur months or years later.

"The long-term effects that occur six months to a year or more after exposure aren't reversible like the short-term ones, and they are a big unknown," said Associate Professor Jeffrey A. Coderre of MIT's Department of Nuclear Science and Engineering. The damage is similar to scar tissue formation and can seriously affect tissue function in the GI tract.

"We've come up with a tool to selectively irradiate blood vessels to study how radiation damages normal tissue over both the short term and the long term," said Coderre, who is co-author of an article appearing online the week of Feb. 27 in the Proceedings of the National Academy of Sciences (PNAS). "This is the first time it has been possible to do this."

Conventional techniques using external radiation beams are not specific enough for this type of study. "We are selectively delivering a radiation dose to all of the cells that make up the microscopic blood vessels throughout the body," he said.

The method Coderre and his colleagues at MIT and UCLA came up with involves putting boron into a drug administered intravenously in mice, and then subjecting the animals to whole-body neutron radiation using the MIT research reactor. Individual boron atoms in the blood capture a neutron, become unstable, and immediately split in half, giving off two short-range radiations (an alpha particle and a lithium ion) in the process.

The boron is kept in the blood by trapping it inside a type of nanoparticle known as a liposome, which is only billionths of a meter in size. These particles are too big to move from the blood into normal tissues, so the short-range radiations from the boron-neutron reactions in the blood only reach the blood vessel walls and cannot damage the normal tissues outside the blood vessels.

By selectively irradiating the blood vessels, it is possible to see where the breakdown of tissue structure and function starts following radiation exposure. And that information could lead to more effective and less damaging treatments, Coderre said.

Coderre said the method can be applied to other tissues. It also has implications for the development of radioprotectors or treatments for radiation exposure. But perhaps the greatest potential is in understanding the sequence of steps that begin at the time of irradiation but take years to create damage.

For example, there will be approximately 240,000 new cases of Prostate Cancer diagnosed in the United States in 2006. Depending on the dose of radiation delivered to their tumor, anywhere from 20 percent to 40 percent of those patients could show some degree of late damage.

http://www.medilexicon.com/medicalnews.php?newsid=38580∞

Amifostine Makes Radiation More Effective, Eases Side Effects

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02 Mar 2006

Doctors in Brazil have concluded that the drug amifostine eases many of the most common side effects associated with patients receiving radiation therapy to treat their cancer while simultaneously making the cancer more susceptible to radiation. The study was published in the March 1, 2006, issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology.

The researchers set out to evaluate, via a clinical investigation of already published work, whether adding amifostine to radiation therapy would prevent common side effects, such as mouth dryness, difficulty swallowing, lung inflammation, bladder inflammation, problems with the esophagus and inflammation of the mucous membranes. In some cases, these side effects can be severe enough that the patients' treatment has to be suspended or stopped completely - potentially preventing their cancer from being completely cured. The other major purpose of the study was to discover if amifostine would inadvertently protect the tumor from radiation.

The investigators narrowed their research to 14 randomized, controlled trials in which 1,451 patients were split into two groups: one receiving radiation therapy alone and the second receiving radiation therapy in addition to amifostine. Patients taking amifostine were shown to have less radiation-related side effects. The research also showed that the drug did not protect the tumor from the radiation therapy and patients receiving the drug were more likely to have their cancer affected by the radiation than patients not given amifostine.

Taking amifostine does have some drawbacks, with nausea and vomiting being the most common side effects reported. However, the doctors generally were able to control the side effects with anti-nausea medicine.

?Our research shows that adding amifostine to radiation therapy helps reduce side effects while at the same time making the radiation treatments more effective at killing the cancer cells,? said Andre Deeke Sasse, M.D., a radiation oncologist at Nucleo Brasileiro de Oncologia Baseada em Evidencias in Sao Paolo, Brazil. ?We recommend that patients undergoing radiation therapy for cancer ask their doctor about adding amifostine to their treatment.?

For more information on radiation therapy for cancer, please visit http://www.rtanswers.org∞.

ASTRO is the largest radiation oncology society in the world, with more than 8,500 members who specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, biology and physics, the Society is dedicated to the advancement of the practice of radiation oncology by promoting excellence in patient care, providing opportunities for educational and professional development, promoting research and disseminating research results and representing radiation oncology in a rapidly evolving healthcare environment.

http://www.rtanswers.org∞

http://www.astro.org∞

http://www.medilexicon.com/medicalnews.php?newsid=38675∞

New Device Increases Survival Rates Of Women With Advanced Rectal Cancer By Providing Radiation During Surgery

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28 Feb 2006

Colorectal cancer is widely considered a man's disease, but actually affects an equal number of women and men. Detected early, it is highly curable in both genders, with survival rates approaching 90 percent. But if the cancer is detected at a more advanced stage, the outlook is often dismal.

The good news is that an FDA-approved mobile electron-beam system known as the Mobetron, developed by Intraop Medical Corporation of Sunnyvale, Calif., has proven clinically successful in extending survival rates and reducing tumor recurrence rates in patients with advanced rectal cancer.

The Mobetron delivers radiation directly to the tumor bed as part of colorectal cancer surgery. This is the ideal time to radiologically cleanse the area of any errant cancer cells that might have escaped removal. This technique is known as intraoperative radiation therapy or IORT.

About 130,000 new cases of colorectal cancer are diagnosed annually in the U.S. with more than 56,000 deaths each year, according to American Cancer Society statistics. This makes colorectal cancer the third most-common cancer in the U.S.

In the recent European clinical study, 651 women and men with locally advanced rectal cancer received IORT as part of their treatment. These patients showed substantial improvement in survival rates and tumor recurrences over those who did not.

After standard treatment for advanced rectal cancer, which consists of surgery, chemotherapy and radiation, about 25% of patients are expected to survive five years, and 50% of these patients have tumor recurrences that require additional surgery, treatment and hospitalization. In the recent European study, however, patients treated with IORT in addition to the standard treatments showed five-year survival rates of 67%, 10-year survival rates of 46%, and five- and 10-year tumor-control rates of 88% and 86%, respectively.

Dr. Harm Rutten, Chief of Surgery at Catharina Zeikenhuis in Eindhoven, Holland, the principal investigator of the study, commented: "These results are truly exceptional. As a surgeon who treats many patients with this advanced disease, it is gratifying to have a tool that can help these patients and save their lives."

This extensive study of patients with locally advanced rectal cancer was conducted by four major European referral centers, all members of the International Society of IORT-Europe (ISIORT-Europe). It is the largest such study ever reported in medical literature, as well as the largest ever that involved intraoperative radiation therapy.

"With clear evidence of such dramatic tumor control with IORT, this is a most important study," agrees Dr. Donald A. Goer, President and CEO of Intraop. "These results," he adds, "represent a triple-win - a win for the patients, a win for their doctors, and a major win for cost-effective healthcare. This study strengthens the evidence that IORT and the Mobetron present a major advance in cancer treatments for both women and men."

Intraop Medical Corporation
http://www.isiort.org∞
http://www.intraopmedical.com∞
http://www.medilexicon.com/medicalnews.php?newsid=38494∞

Timing Of Radiation Treatments For Colon Cancer May Need Adjusting

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11 Apr 2006

Scientists have unexpectedly discovered that mice with the gene defect that causes colon cancer in humans can differ from normal mice in how they respond to radiation treatments. The large intestine carrying the gene defect in mice that received staggered doses of radiation was three to four times more resistant to the radiation than in control mice.

The researchers, led by Bruce Boman, M.D., Ph.D., director of the Division of Genetic and Preventive Medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia and at Jefferson's Kimmel Cancer Center and Dennis Leeper, Ph.D., professor of radiation oncology at Jefferson Medical College, say these results may have implications for treating patients with colon cancer, which is a tumor that frequently has mutations in a gene called APC.

They reported their findings this week at the 2006 annual meeting of the American Association for Cancer Research in Washington, D.C. (Stem Cell Number and Radiation Resistance During Repair in Colonic Crypts of APC Mice: Abstract no. LB-311).

Scientists have known that patients' colon tumors with APC mutations have an increased amount of survivin, a protein that halts the process of programmed cell death. This increase also appears to be associated with a rise in the number of stem cells that sit at the bottom of colonic crypts, tube-like structures that make up the lining of the intestine. Drs. Leeper and Boman wanted to see if there was a difference in stem cell number between normal mice and mice that carry a mutation in APC. To do this, they exposed both normal and mutant mice to radiation, testing their ability to repair the resulting DNA damage. They speculated that increased survivin in the mutant mice might enable more stem cells to survive and affect the response to radiation. The researchers asked if mice with an APC mutation, making them prone to develop colon cancer, are different from normal mice in radiation sensitivity and their ability to repair the damage. Normal cells can repair DNA damage from radiation, Dr. Leeper explains.

They measured the survival of colon crypts in the small and large intestines in normal and mutant mice following radiation exposure, looking at the responses to both single doses of radiation and to staggered or "fractionated" doses of radiation, where the second dose is given five hours after the first dose, again causing the DNA repair to kick in.

"In the normal mouse the radiation-induced damage in the intestine is repaired, just as we expected," Dr. Boman explains. In fact, intestinal cells in both the mutant mouse and normal mouse reacted the same to the single dose of radiation.

But the mutant mice responded differently to the staggered radiation. "When we irradiate five hours later when repair has begun, and damage is being repaired, and then a second dose of radiation is given, the mutant mice are resistant," says Dr. Leeper. More specifically, the Jefferson team found that in the large intestine in the mutant mice, the colon crypt cells were more resistant to radiation by a factor of three to four.

"This has never been observed before to my knowledge," Dr. Leeper says. "This is a novel finding." He notes that the results could have important implications as to how radiation is given to colon cancer patients. "If you are giving radiation once a day, it shouldn't be a problem. But if you are fractionating treatments, given it two or three times a day, this finding could have implications. We would want to make sure that repair processes and signaling receptors come back to baseline before a second dose of chemotherapy is given."
http://www.medilexicon.com/medicalnews.php?newsid=41317∞

Jefferson Radiation Oncologists Among First To Use Cone Beam CT To Improve Treatment Accuracy

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01 Sep 2006

While one of the Holy Grails in radiation oncology is to spare as much healthy tissue as possible during therapy, patients undergoing treatment for weeks at a time physically change. Patients can lose weight during a period of therapy. They might lose or gain fluid. Tumors may shrink or unfortunately, continue to grow. As a result, radiation target sites change, which can be problematic for treatment.

Thomas Jefferson University Hospital in Philadelphia and the Kimmel Cancer Center at Jefferson are among the first centers in the nation to study the effect of incorporating a new technology - cone beam CT - into a source of radiation, namely a linear accelerator, in an attempt to find an answer to this vexing problem.

The technology creates three-dimensional axial CT slices of a patient's tumor, enabling therapists and doctors to compare these images with initial treatment planning images to determine how precisely focused the radiation set-up is. They can then make position adjustments if necessary to deliver a more targeted therapy to the patient. The hope is that this technology will lead to more highly customized radiation treatments, where higher doses are directed at the tumor while sparing the patient's normal body structures.

"Right now, cone beam is used as one additional means of verifying the accuracy of the radiation treatments that we deliver," says Mitchell Machtay, M.D., the Walter J. Curran Jr., M.D., associate professor of radiation oncology at Jefferson Medical College of Thomas Jefferson University and vice chair of the Department of Radiation Oncology. Traditionally, patients are positioned for their daily radiation treatment by making marks on their skin, based on earlier tests, Dr. Machtay explains. "Once that is done, unless dramatic changes are seen, it's hoped that those marks will hold up for two or three or six weeks of radiation and that the treatment will be given accurately.

"Ultimately, we believe that cone beam will lead to more highly customized radiation treatments, such as higher doses to the gross tumor and lower doses to normal structures within the body," explains Dr. Machtay, who specializes in treating head and neck cancers. He notes that this is particularly important for tumors of the head and neck, "where tumors and critical normal structures are tightly packed next to one another."

Richard Valicenti, M.D., associate professor of radiation oncology at Jefferson Medical College, uses cone beam CT for treatment planning for prostate cancer patients. "We've never had a way to directly visualize a target for radiation therapy before," he notes.

"Cone beam is a potential paradigm shift in checking the accuracy of a treatment," adds Dr. Machtay.

Jefferson is the most experienced center in the Delaware Valley in using the technology, notes Walter J. Curran Jr., M.D., professor and chair of radiation oncology at Jefferson Medical College and clinical director of Jefferson's Kimmel Cancer Center.

In cone beam, the CT scanner is attached to a radiation delivery machine. Prior to the actual treatment, a set of 3-dimensional CT scan images is obtained. This is compared to the conventional CT scan that was used for planning the patient's radiation treatment. If there are any differences in the patient's current position, this is corrected before treatment is actually given

"Positioning no longer depends on the road map marks on the skin," says Dr. Machtay. "With cone beam, we are actually looking at a CT scan of the inside of the patient to see if he or she is lined up properly and if there's been a change in the size or shape of the individual.

"We're using it to collect quality assurance data, to see how much movement there is from the first day of treatment to every other day of treatment. We're making the measurements and the adjustments necessary to hit the tumor.

"What we haven't done yet is actually change the number of radiation treatments, the dosages of treatment or the size of the beams based on the CT scans," he notes. In theory, cone beam is more accurate and the radiation beams can be more pinpointed, meaning less radiation exposure to the rest of the patient. That can mean fewer side effects, and perhaps a higher dose of radiation.

In treatment planning for head and neck cancer radiation therapy, Dr. Machtay explains that at least a 5 millimeter safety margin around the cancer is typical. "If this margin is reduced to 2.5 mm, and we think of it three-dimensionally, that's a lot less area of radiation exposure."

Cone beam can be applied to any cancer type. And while clinical trials using cone beam radiation are in the planning stages, says Dr. Machtay, "it's something that we would consider state of the art but not yet standard of care." The device is not yet approved by the FDA and currently is used on only about 25 percent of the patients receiving radiation therapy at Jefferson.
http://www.medilexicon.com/medicalnews.php?newsid=50840∞

Advanced Cancer Patients Could Benefit From Personalized Healthy Diets

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14 Mar 2007

It is well known that cancer patients undergoing chemotherapy and radiation therapy often experience nausea and loss of appetite. But until now, few researchers have looked into why this happens and what can be done to ensure that cancer patients maintain a healthy diet during treatment.

Researchers at the University of Alberta studying the effects of chemotherapy and radiation therapy on the senses report that most advanced cancer patients experience unique and persistent taste and smell abnormalities, believed to be a key factor in malnutrition and poor quality of life. The condition, known as chemosensory dysfunction, is believed to last long after patients have finished active chemotherapy or radiation therapy.

Taste distortion, heightened sensitivity to odours and a persistent bad taste in the mouth were the most common symptoms described by participants in the recent study conducted by Dr. Wendy Wismer and Dr. Vickie Baracos. However, Wismer says that every patient with chemosensory dysfunction has unique symptoms, and a diet tailored to her needs would likely improve quality of life.

"With taste and smell, and even with food consumption, we tend to draw broad conclusions and make sweeping recommendations," she says. For example, individuals with severe chemosensory dysfunction will often end up on a diet of soup or oral nutritional supplements such as Boost because their heightened or distorted senses make it difficult to eat much else.

"We're looking at how an altered sense of taste and smell affects the food you select. We argue that altered chemosensory perception is unique to the individual. In the same way that people need unique corrective lenses for their eyesight, patients need unique solutions for chemosensory distortion," Wismer explains.

Wismer and Baracos studied 66 patients with advanced cancer receiving palliative care and asked them to evaluate their own taste and smell functions using a validated questionnaire and three-day food diaries to assess their dietary intake. The vast majority - 86 per cent of participants - reported some level of chemosensory abnormality. While this study focused on advanced cancer patients, Wismer believes the findings are relevant to any patient who has received chemotherapy or radiation therapy.

Further research will look at appropriate strategies to alleviate chemosensory dysfunction and explore how matching foods to an individual's unique chemosensory profile might help to prevent high rates of weight loss and malnutrition and improve quality of life.
http://www.medilexicon.com/medicalnews.php?newsid=64940∞

Correct Patient Positioning Can Decrease CT Radiation Dose

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15 Mar 2007

Simply centering the patient appropriately on the CT gantry can reduce radiation dose by as much as 56%, yet nearly all patients are incorrectly positioned for their examinations, a new study shows.

Nearly all, (42 out of 45) patients undergoing abdominal CT examinations were off-center. All 18 patients in the study undergoing chest CT were off-center too, said Mannudeep Kalra, MD, currently at Massachusetts General Hospital in Boston. Dr. Kalra is one of the authors of the study.

As part of the study, the 63 patients were positioned on the scanner gantry table by a radiology technologist according to standard department protocol. An x-ray was taken to show the initial patient location. The CT scanner's laser guidance system for patient positioning estimated the point where the patient would be centered on the CT gantry. "We then used an automatic centering technique (that isn't commercially available yet) to determine the true center point," Dr. Kalra said. Patients were off-center by anywhere from 5.5 mm to 64 mm for chest CT examinations and 5.5 mm to 56 mm for abdominal CT examinations, he said.

When patients were centered appropriately (i.e. based on the automatic centering technique) radiation dose was reduced anywhere from 7% to 29.9% in chest CT examinations, Dr. Kalra said. Radiation dose was reduced between 5.5% and 56% for abdominal CT examinations, he said.

"This study emphasizes that radiologists and technologists must pay close attention to patient centering. In addition, vendors are encouraged to develop and assess techniques that aid the technologist in accurate patient centering," Dr.Kalra said.

The study appeared in the February issue of the American Journal of Roentgenology, which is published by the American Roentgen Ray Society.

American Roentgen Ray Society (ARRS)
44211 Slatestone Ct.
Leesburg, VA 20176-5109
United States
http://www.arrs.org∞

http://www.medilexicon.com/medicalnews.php?newsid=65263∞

One Small Step For Deinococcus Or One Giant Leap For Radiation Biology?

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22 Mar 2007

In a new study published online in the open access journal PLoS Biology, Michael J. Daly, Ph.D., associate professor at the Uniformed Services University of the Health Sciences (USU), and colleagues show that the ability of the bacterium Deinococcus radiodurans to endure and survive enormous levels of ionizing radiation (X-rays and gamma-rays) relies on a powerful mechanism that protects proteins from oxidative damage during irradiation.

The field of radiobiology is built on the premise that radiation is dangerous because of its damaging effects on DNA. Contrary to that view, Daly et al. report that the ability of cells to survive radiation is highly dependent on the amount of protein damage caused during irradiation. Surprisingly, a dose of radiation that is sufficient to cause only minor DNA damage in radiation-sensitive cells will cause high levels of protein damage compared to resistant cells exposed to the same dose. This new model of radiation toxicity shifts the emphasis away from DNA damage toward protein damage, where DNA repair-related proteins in sensitive cells are devastated by radiation long before DNA is significantly damaged. In contrast, repair enzymes in extremely resistant cells survive and function with great efficiency after irradiation because they are protected, specifically by a chemical mechanism involving manganese (II) ions.

The new model of extreme radiation resistance reconciles many seemingly conflicting results published over the last two decades, and points directly at the existence of potent manganese-based radioprotectors that prevent protein damage. Daly expects that delivery of purified radioprotective Mn-complexes into sensitive cell-types will make them temporarily radiation resistant. This possibility opens up new avenues for radioprotection, including approaches to facilitate recovery from short- or long-term exposures to radiation such as cancer therapies, accident- or terror-related nuclear events, and astronauts exposed to cosmic radiation.
http://www.medilexicon.com/medicalnews.php?newsid=65600∞

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