eCancer Consult, February 2013

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On Target with SBRT

Stereotactic body radiation therapy provides a low toxicity rate and precise control. SBRT’s stronger, less frequent doses of radiation could result in better outcomes for prostate cancer patients.

It’s more intense, focused, efficient and could result in better outcomes for patients with prostate cancer. Stereotactic body radiation therapy (SBRT) uses technology to aim high doses of radiation directly to the target. “If you can hit just the prostate and not the surrounding tissue, you can give the radiation faster,” explains Kevin Stephans, MD, a radiation oncologist at Cleveland Clinic’s Taussig Cancer Institute. “With SBRT, you can administer a couple of really big, really well-targeted doses with less radiation to surrounding tissue.”

Traditionally, external beam radiation has been the gold standard for treating intermediate and advanced prostate cancer. Generally, patients would require 39 to 42 treatment sessions every day during a 7½- to 9-week period. The treatment schedule is rigorous. “SBRT simplifies the treatment process,” Dr. Stephans points out. SBRT provides a low toxicity rate without reducing tumor control.

Hitting the Target

SBRT uses higher doses per fraction and fewer fractions than conventional radiation. And, SBRT provides more beam angles, Dr. Stephans says. Beams can be calibrated at different radiation doses. This is particularly beneficial for prostate cancer patients because often, cancer is concentrated in the periphery.

“With SBRT, we can target certain parts of the prostate with a higher dose of radiation,” he says. Entry and exit beam doses can be customized. “With SBRT, the beams only cross over the prostate, so that is the only area where the dose is really high.”

Tracking Performance

Setting up SBRT requires a CAT Scan to define the target treatment area. Markers placed prior to the scan help track the prostate during treatment. At-risk tissue along with the bladder, urethra, and normal surrounding tissue are identified and a physicist calculates the appropriate radiation.

The SBRT machine includes a robotic table top. “We can set up the prostate perfectly within millimeters so it is always within target,” Dr. Stephans says. Because the prostate moves significantly, even during treatment, the SBRT machine can be shut off and the beams realigned to increase the precision of radiation delivery.

Meanwhile, continuous real-time tracking based on the markers placed in the prostate allow physicians to clearly view the treatment area and radiation status at all times.

Improving Outcomes

There are other minimally invasive treatment options available for low-risk prostate cancer patients—one is a radioactive seed implant—SBRT outcomes may be more appropriate for intermediate- and high-risk patients.

While SBRT for prostate cancer is still relatively new, studies in patients with lung cancer who were treated with this high-dose radiation method have shown an improved overall survival rate and control compared to standard radiation.

Dr. Stephans says similar parallels can be drawn for treating prostate cancer with SBRT. “There is biological evidence that suggests that prostate cancer may respond better to bigger doses of radiation and that high-risk patients might have better outcomes with larger doses per session,” he says.

Mantle Cell Lymphoma Research Tests New Therapies

Is there a better way to treat Mantle Cell Lymphoma in older patients from the onset? And, can a different combination of therapies used during “maintenance” postpone remission? That’s what researchers hope to learn in a series of trials underway. Mantle Cell Lymphoma (MCL) is a rare non-Hodgkin’s lymphoma, and a challenging cancer to treat because it is aggressive. It is often discovered in more advanced stages, being widespread. MCL is rarely cured and, quite often, patients will slip out of remission quickly after therapy.

The good news: Promising clinical trials could shed light on a combination of therapies that are less intensive than chemotherapy and stem cell treatment, which is reserved for young, healthy individuals diagnosed with MCL. (The median age of diagnosis is mid- to late- sixties.)

“Some of today’s less intensive treatments look as good if not better than rituximab + our standard chemotherapy called CHOP,” says Mitchell Smith, MD, PhD, an oncologist specializing in MCL at Cleveland Clinic’s Taussig Cancer Institute. Dr. Smith is Study Chair of an intergroup randomized four-arm study in patients age 60 and older with previously untreated MCL.

The goals of the study are to determine whether adding a well-tolerated drug to initial therapy will improve treatment; and to see whether remission can be prolonged by adding a drug (rituximab) to the standard maintenance. “And, what if we do both?” says Dr. Smith. “The only way we’ll make headway with MCL treatment is to do these sorts of studies.”

Introducing Different Drugs

Ultimately, Dr. Smith and colleagues hope to determine whether adding bortezomib (Velcade ®, V) to induction rituximab-bendamustine (RB) therapy improves progression-free survival compared to RB alone. RB is the first-line treatment for older patients with MCL. The trial will also test maintenance therapies, after initial treatment.

Does adding lenalidomide to consolidation rituximab, following the RB or RBV treatment, improve progression-free survival compared to rituximab alone? It sounds more complicated than it is, Dr. Smith says. Basically, all participants are getting the induction rituximab-bendamustine therapy. Some will get bortezomib added to that initial treatment, while others will take lenalidomide as part of their maintenance therapy to see whether the combination delays remission, and some will get both.

“We are moving pretty rapidly in getting new drugs available and figuring out how to best use them,” Dr. Smith says, relating how the future treatment of MCL looks promising because of drugs on the horizon.

Gauging Treatment Success

“Previous studies in MCL were relatively small trials, often with age restrictions,” Dr. Smith says. “The intergroup strategy will increase enrollment and result in a greater population of MCL patients of different ages with various co-morbidities.”

Results of these trials will not be available for several years, but the study has some built-in checkpoints that should shed light on the efficacy of treatment protocols. For one, PET scans will be reviewed. “We don’t know how effective PET scans are in MCL because this has never been studied, but we do know with Hodgkin’s if your PET scan turns negative early, that’s a good sign,” Dr. smith says.

Also, researchers conduct molecular studies to analyze blood for disease. “We’ll see if we can find out after the six months of induction therapy who is predicted at that point to do well, and who will not do well so we can take a different treatment course,” Dr. Smith says.

We don’t have answers today about whether these new therapeutic combinations will initially treat and prolong the remission of MCL in older patients, or how the drugs will impact patients’ quality of life. But, Dr. Smith emphasizes, that’s exactly why these trials are so important.

“We do have new drugs available, and this [trial] introduces two of the new drugs,” Dr. Smith says. “We need to conduct the research so we can figure out how to best use them.”

Taussig Cancer Institute Clinical Trials

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