4 PROVIDENCE TOGETHER.

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1 4 PROVIDENCE TOGETHER

2 ancer entered Clara Harris life early. Her mother died When surgery is a risky option, cancer patients such as Clara Harris are benefiting from a new and novel form of radiation therapy. of the disease when Harris was just 15. Later, her uncle, sister and brothers would develop cancer. So it wasn t entirely unexpected when, in 1991, Harris was diagnosed with breast cancer. Given her family s history, she opted for a radical treatment: She had her left breast removed. With the immediate threat gone, Harris carried on with her life. She and her children followed her husband, Ralph, as his career with Union Pacific Railroad Co. took him to various towns throughout Oregon. Harris raised their children, sang in her church choir and worked in women s ministries. She didn t know at the time that the early-stage breast cancer was just the beginning of her cancer ordeals. Later battles would take her through countless tests, treatments and therapies, from doctor to doctor, and finally to Providence, to Steven Seung, M.D., Ph.D., and to a new form of radiation treatment that holds promise for those with medically inoperable tumors. > > > BY SHIRLEEN HOLT PHOTOS BY PETE STONE Now enjoying her garden in Woodburn, Clara Harris is reaping the benefit of advanced treatments for inoperable cancer. PROVIDENCE TOGETHER 5

3 Stereotactic body radiation therapy is changing the paradigm of the radiation oncology industry. Steven Seung, M.D., Ph.D. CHASING TUMORS All this was still ahead of Harris in 1999, when the family moved to Gladstone. I didn t know it at the time, says Harris, 64, but that was the best thing to happen because we were in the Portland area where it turned out I could get the best treatment for my cancer. Shortly after the move, Harris noticed blood in her urine. Tests revealed that she had cancer again, this time in her right kidney. With the hope of keeping the cancer contained, doctors removed the kidney. One year later, however, cancer appeared in her chest, bones and brain. By the time I found Dr. Seung at Providence, I could hardly walk from the cancer in my bones. It was extremely painful to put weight on my hip. Meeting Dr. Seung, medical director of the Gamma Knife Center of Oregon at Providence Cancer Center and a radiation oncologist with The Oregon Clinic, was the first step in a long journey of state-of-the-art therapies to chase Harris metastatic kidney cancer. She received radiation therapy for cancer in her bones and endured five weeks of immunotherapy at Providence for lung tumors. Dr. Seung eliminated the tumors in her brain with Gamma Knife therapy, a highly advanced radiation procedure. It was wonderful to receive the Gamma Knife therapy, says Harris, because it was too risky to have surgery to remove the tumors. It s just amazing what has been accomplished in cancer treatment and how it has helped me survive. The Gamma Knife treatment was so successful that Harris asked Dr. Seung if there was such a treatment for cancer in other parts of the body. He assured her that researchers were working on it. When I asked that question, says Harris, I never thought I would need to use the new treatment. THE EVOLUTION OF RADIATION THERAPY The goal of using radiation therapy to treat cancer has always been to deliver a lethal dose of radiation to a tumor while limiting damage to healthy tissue. In the early days, radiation oncologists had to be experts regarding the skeletal system as it appeared on X-rays. They used the bony landmarks to direct the beams because they couldn t see the tumor on plain X-rays, says Dr. Seung. We didn t want to miss the tumor, so we had to make the beams bigger than necessary. The technique, he says, was similar to using a showerhead spray to rinse a tiny piece of dirt. The problem was that the cone of radiation destroyed both the tumor and the healthy tissue around it. There needed to be a way to fine-tune the radiation. Many small beams of radiation from different angles would have to converge to a point to create a concentrated, more lethal dose to the tumor. This therapy is feasible only when the position of the tumor can be precisely defined by computer technology that creates a threedimensional image of the tumor and surrounding area. The 3-D image helps the radiation oncologist determine exactly where to target the radiation. Although much effort goes into accurately positioning the patient for each treatment (the skin is even marked with dots that are lined up with the machine), accurate positioning hasn t always been available. Humans breathe, and the movement creates an unstable boundary for high-dose radiation. How do you limit the motion created by breathing without suffocating a patient? The scanning process is too long for holding a breath, and holding a breath wouldn t be consistent from one scan to the next. Some patients are too ill to hold their breath anyway. SHRINK-WRAPPED Something additional a fourth dimension had to be developed in order to deliver the highest dose of therapy to the smallest area that includes the tumor. The fourth dimension was time. Enter stereotactic body radiation therapy, or SBRT, a new form of radiation treatment that Harris had asked about years earlier. The technology provides the precise, high-dose therapy of Gamma Knife to the chest, liver and spine. It combines 3-D scans of the tumor during the patient s breathing cycle. This allows the radiation oncologist to choreograph the radiation beams to the tumor while the patient breathes normally. Because the radiation oncologist no longer has to guess where the tumor will move, the accuracy can now be dialed in to within millimeters. Providence Cancer Center started treating patients with stereotactic body radiation therapy in January With support from Providence Portland Medical Foundation, the therapy has become a ray of hope for those with medically inoperable lung and liver tumors. Among the first patients: Clara Harris. To stabilize Harris for treatment, technicians shrink-wrapped her torso onto a customized foam mold on the machine table. At first, I was worried about being claustrophobic when they wrapped me to the foam mold, says Harris, but the treatment room is such a large, airy space with lovely photos on the ceiling and the therapy didn t take long, so it wasn t a problem. > > > 6 PROVIDENCE TOGETHER

4 Stereotactic body radiation therapy allows Steven Seung, M.D., Ph.D., to target tumors with high doses of radiation while preserving the healthy tissue that surrounds them. PROVIDENCE TOGETHER 7

5 To me, the word providence means divine guidance or care. The care I ve received has been given to me by God. I will always be living with cancer, but I know that Providence will be there for me for the rest of my life. Clara Harris Currently, it takes about a week of computerized planning to determine a patient s stereotactic body radiation therapy plan. Once the planning is complete, the patient will have one to five treatments over the course of one to two and a half weeks. Treatments range from 30 minutes to two hours, depending on the intricacy and number of areas being targeted. That s amazing considering standard radiation therapy is given five days a week for up to two months. The therapy is currently limited to lung, liver and spinal tumors. The side effects are well tolerated, and most patients don t notice a significant negative difference after treatment. It s very easy, Harris says. You can avoid surgery and a hospital stay, and it doesn t make you sick. I M A FIGHTER Radiation therapists have found that stereotactic body radiation therapy s precision reduces collateral damage to other tissue and dramatically affects cancer cells. Budding research even suggests that using the therapy to treat a tumor at one site in the body may cause tumors in other sites to shrink as well. Besides its leading-edge work in radiation oncology, Providence Cancer Center also is known for its research in cancer immunotherapy, the process of prompting the immune system to reject and extinguish tumors. Two Providence immunotherapy researchers are helping lead an investigation into the use of stereotactic body radiation therapy in conjunction with immunotherapy drugs to create a very unwelcome environment for cancer. Having expert radiation oncologists who happen to be immunologists is vital to the pairing of stereotactic body radiation therapy and immunotherapy in cancer treatment. The technology s precision saves precious T cells, and the high doses it can deliver can alter the tumor cells so that the tumor becomes a better target for immune cells. Researchers have found drugs that encourage T cells to destroy cancer cells affected by high-dose radiation. The potential for more efficiently controlling cancer is getting closer to reality. Five years ago, Providence Cancer Center enticed Marka Crittenden, M.D., Ph.D., and her husband, Michael Gough, Ph.D., from their jobs at the Mayo Clinic. At the time, Dr. Crittenden was searching for a location for her radiation oncology residency, and Dr. Gough needed to find an appropriate laboratory for his work as an immunologist. Impressed by the prominence of Providence Cancer Center researchers, Dr. Gough joined the team while Dr. Crittenden completed her residency in Oregon. Now Dr. Gough has his own Providence lab, and Dr. Crittenden is beginning her work at Providence as a radiation oncologist. She also is a lab partner to Dr. Gough and a clinical partner to Dr. Seung, who has a Ph.D. in immunology. There are very few immunologists in the radiation oncology field, and Dr. Seung is one of the best, says Dr. Gough. To have two in one place is remarkable. If we can change the way cancer cells appear to the immune system by using high-dose stereotactic body radiation therapy, we have an opportunity to increase the body s immune response with drugs aimed at empowering T cells to kill any surviving cancer cells, says Dr. Gough. Basically, we re changing the tumor environment to help the therapies work better. Drs. Crittenden and Seung already have collaborated on promising research that uses similar radiation and immunotherapy in mice. Because stereotactic body radiation therapy allows for higher doses of radiation than standard therapies, it more closely mirrors the levels given to mice in lab studies. As a result, researchers can draw better comparisons on the treatment s therapeutic benefits for humans. Radiation oncologists have excellent therapies that we can tweak to increase an endogenous [internal] response in the body, says Dr. Gough. With stereotactic body radiation therapy we could make a remarkable impact. 8 PROVIDENCE TOGETHER

6 Stereotactic body radiation therapy is changing the paradigm of the radiation oncology industry, says Dr. Seung. Who knows what treatment will look like a few years down the road? We are anxiously awaiting a volumetric modulated arc therapy software upgrade, which will decrease treatment times to 15 minutes or less. After her past decade of treatment, time is something Harris greatly appreciates. Time to spend with family and friends. Time to speak as a patient advocate for cancer. Time to work in her garden and to camp with her husband. And time to reflect on the fortuitous points when she needed the most advanced cancer care and received it at Providence Cancer Center. I think it s amazing that when I developed brain tumors Providence had Gamma Knife to treat them, says Harris. Providence had immunotherapy to treat my lung metastases. Providence got stereotactic body radiation therapy in January and I developed an inoperable chest metastasis right after that, so I was able to get that treatment. What do you think about that timing? In July, Harris discovered that the three treatments for her golf-ball-size chest tumor had already shrunk the cancer by 70 percent. She will have further scans to monitor the progress. I m a fighter, Harris says, and I appreciate being on the edge of new therapies. Anytime a patient can have a successful, noninvasive therapy, it s wonderful. And anytime you meet a person like Harris, it s a gift. Through the multiple treatments for her cancers, she has maintained her strength and serenity. She continues to volunteer and knits lap robes and scarves for charity while watching television. To me, the word providence means divine guidance or care, says Harris. The care I ve received has been given to me by God. I will always be living with cancer, but I know that Providence will be there for me for the rest of my life. n Cancer s one-two punch: Marka Crittenden, M.D., Ph.D., and Michael Gough, Ph.D., are researching how stereotactic body radiation therapy can work with the body s natural immune defenses to kill tumors. PROVIDENCE TOGETHER 9