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On Target - Using Clinical Studies

The Data Quest
Issue No. 4

Using Clinical Studies

Date: April 18, 2012


Using clinical studies, not marketing, to determine the most effective radiation therapies New therapies can be driven as much by marketing as medical results, and it is important for consumers to be able to distinguish which one is in play when they are making treatment decisions.

Radiation oncologist Joseph Herman says this is particularly true in his field, which delivers treatment through technologically advanced pieces of equipment. “Often claims are made about the usefulness of new techniques in the absence of information to support them,” says Herman.

Stereotactic body radiotherapy (SBRT) or cyber knife (CK) are both forms of focused
radiation used successfully to treat brain and lung cancers. More recently focused radiation has been touted as a promising new treatment for pancreas cancer, causing confusion among patients and concern among physicians. Why the concern? Herman says currently there is little evidence to show that stereotactic radiotherapy can shrink pancreas tumors or improve survival. “We need to gather evidence to scientifically determine which approaches are the best and safest for patients,” says Herman. “We must validate what we say or believe is happening in patients with real data.”

Stereotactic radiotherapy and CK use high doses of precisely targeted beams of radiation instead of scalpels to cut through tumors and kill cancer cells. It can be a valuable tool in treating cancer as these targeted beams can reach tumors that are inaccessible by traditional surgical means, but it is not for every cancer, according to experts. Higher doses of radiation can mean greater toxic side effects to normal tissue.

Herman says Johns Hopkins is among the leading innovators of new technologies, so he believes its scientists can lead the way in collecting and analyzing data from Hopkins and other institutions to determine the safety and effectiveness of these new medical technologies.

Less is More: A Closer Look at Stereotactic Body Radiotherapy for Pancreas
Cancer

More is not always better, particularly in radiation oncology, Herman says. Higher doses of radiation can cause serious side effects to normal cells.

Herman, Daniel Laheru, Chris Wolfgang, and a team of Kimmel Cancer Center clinician
scientists are collaborating with investigators at Memorial Sloan Kettering Cancer Center and Stanford University to study stereotactic radiotherapy approaches for pancreas cancer.

They want to find out if a high dose of stereotactic radiation therapy delivered over one to five days could lead to fewer side effects and be as effective as the standard radiation treatment, which is delivered over a five-week period along with chemotherapy.

In early studies, patients were treated with one day of radiation therapy to the pancreas
and a small amount of surrounding tissue. The high-dose approach can cause unpleasant
and sometimes dangerous bowel toxicities and other side effects in 30 to 40 percent of patients treated. Herman believes lowering the dose of radiation each day, but extending the treatment to five days, will maintain the therapeutic benefits for pancreas cancer patients but decrease side effects and improve quality of life.

So far, he appears to be right. To date, almost 25 patients have been treated with the
new stereotactic radiation delivered over only five days. Patients feel better after therapy, and aside from some mild fatigue, they do not experience any side effects,” Herman says. Among the success stories is an 87-year-old patient with inoperable pancreas cancer who underwent the new treatment and suffered none of the toxicities to the bowel seen with the higher-dose treatments. He is a year out from treatment and doing well, according to Herman. He has gained 20 pounds and is no longer taking chemotherapy.

These outcomes are exciting, but Herman warns that further studies and longer term
followup are needed to confirm these early results. The next step will be to combine novel drugs and vaccines with stereotactic radiotherapy to try and augment its ability to kill cancer cells.

A New Approach for Rectal Cancer

Brachytherapy is a type of radiation treatment that is given internally in the rectum, directly to the tumor. Herman and surgeon Susan Gearhart are currently conducting the first U.S. study to look at its effectiveness in low rectal cancers, those less than 12 centimeters from the rectum.

Treatment for rectal cancer includes a surgical procedure called a total mesorectum
excision to remove lymph nodes and blood vessels in the tissue adjacent to the rectum
that could contain cancer cells and lead to a cancer recurrence. With surgery alone, about 10 to 15 percent of patients will have their cancers come back, usually within just a few centimeters of the original tumor, so patients typically receive chemotherapy and radiation therapy to the pelvis in an attempt to stave off the cancer’s return.

However, with such low recurrence rates, Herman wonders if doctors may be overtreating the cancer, and whether a type of brachytherapy might achieve the same or better results. The technique is called endorectal brachytherapy, and it uses a cylinder-shaped applicator probe inserted into the patient’s rectum. After the probe is placed in the rectum, a wire with a radiation source at the tip is slowly inserted into the applicator. As it moves through the applicator, it delivers very focused radiation to the surface of the tumor. This highly focused radiation targets the tumor, and lesser amounts reach the nearby tissue surrounding the tumor that could contain cancer cells. Normal tissue, including the bladder, small intestine, and reproductive organs, are farther away from the probe and almost completely spared from radiation. The treatment takes only 15 minutes and the radiation is completely removed from the body afterwards.

In this new study, patients received four days of endorectal brachytherapy before having
surgery (without concurrent chemotherapy), as opposed to 28 days of external (X-ray) beam radiation therapy in standard treatment. Among the benefits, Herman says, is that endocrectal brachytherapy is significantly less expensive and likely decreases the risk of bowel complications and secondary cancers. It also delivers less radiation to the bladder and reproductive organs. Moreover, Herman says the shortened duration of treatment gets patients to surgery five to six weeks sooner and, for the most part,with fewer complications afterwards.

“In about half of patients, the tumor spreads after surgery. With fewer problems after surgery, we can get them to chemotherapy more quickly and, hopefully, stop some of these cancers from spreading,” he says. With standard therapy, treatment is longer and some patients have a further lag time as they wait for tissue damaged during treatment to heal. The standard therapy also treats lymph nodes in the pelvis, and, Herman says, with recurrences rates under five percent in the pelvic region, likely unnecessary.

When compared to standard X-ray or external beam radiation, Herman says endorectal brachytherapy may be more effective and less toxic. “With endorectal brachytherapy, 30 percent of patients have a complete response—their tumors are eradicated and there are fewer effects to normal tissue. In external beam radiation, only 10 to 15 percent
of patients have a complete response, and there is more toxicity to normal tissue,” he says. Although early studies are promising, Herman says he needs to evaluate the treatment in more patients. In addition, he cautions that endorectal brachytherapy is not for all rectal cancer patients. Of the approximate 80,000 new cases of rectal cancer diagnosed each year, Herman estimates that about half of these people would be good candidates for endocrectal brachytherapy. Ideal candidates have tumors that the endorectal probe can reach and pass by and have not spread to pelvic lymph nodes or other tissue and organs beyond the rectum. “Even if we find endrorectal brachytherapy only works as well as standard therapy, there is still a benefit,” says Herman. “It reduces toxicities, gets patients to surgery sooner, and costs less.”

Contributing to Personalized Cancer Medicine

Patients participating in Herman’s trials also are advancing personalized cancer medicine—therapies that are tailored specifically to the unique characteristics of each individual patient’s cancer. Blood and tumor samples provided by patients are allowing our laboratory scientists to search for cellular alterations that lead a cancer to spread to the pelvic lymph nodes and other changes that cause these cancers to be more aggressive.

This science is shedding more light on combined drugs and radiation therapy approaches that can improve the effectiveness of radiation therapy. Radiotherapy kills cells by irreparably damaging their DNA.

Drugs known as PARP inhibitors block an enzyme that helps cells repair DNA damage. Herman and Richard Tuli are combining radiation therapy with PARP inhibitors to see if it may augment therapies, allowing more cancer cells to be killed. Perhaps, Herman says, using these new drugs, clinicians could scale back the doses of radiation and potentially reduce side effects.

“We need to start thinking of radiation therapy like we do targeted drug therapies,” says Herman. “We are moving away from giving the same drugs to all patients and toward giving drugs that specifically target the cellular characteristics of each patient’s tumor. We need to begin to look at radiation therapy in the same way and determine what type
of radiation therapy is the best for which patients.”

Note:
For more information on the endorectal brachytherapy trial, contact Beth Griffith at 410-502-9243. Dr. Herman can be contacted at 410-502-3823.

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Focus on Translational Medicine

Using Clinical Studies

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