Lung cancer—which claims more American lives than any other cancer—can be difficult to detect, which makes it tricky to treat. In patients with chronic breathing problems, such as emphysema, the symptoms are very similar to those of a tumor, which means cancer can go unnoticed in the early stages. When lung cancer is caught early enough, surgery is often successful. But in patients with comorbidities, surgery might not be an option.

An estimated $9.6 billion is spent on lung-cancer treatment each year. Traditionally, medically inoperable patients are treated for several weeks with standard radiation—a treatment that often challenges their stamina and puts them at risk for further damage to the lungs. But this is no longer their only option. Today, these patients are candidates for lung radiosurgery, a noninvasive technique that allows radiation oncologists to target the tumor with higher radiation doses in fewer treatments—without damaging the surrounding healthy tissue.

The Cleveland Clinic Taussig Cancer Institute has employed this technique to treat lung cancer patients for a little more than 3 years. “It does extremely well at controlling the cancer, and even more importantly, it does extremely well at limiting and minimizing the potential lung injury to these patients,” said Gregory Videtic, MD, of the radiation oncology department at Cleveland Clinic. “That’s been the most remarkable.”

The Technique

Radiosurgery was originally developed to treat intracranial conditions, such as arteriovenous malformations and brain tumors. John Suh, MD, chair of radiation oncology at the Cleveland Clinic Taussig Cancer Institute, specializes in adult and pediatric brain tumors as well as stereotactic radiosurgery. “Given the excellent results with brain radiosurgery, there has been growing interest in using this form of radiation to other parts of the body, such as the lung and spine tumors,” he said. “In the case of lung cancer, the goal is to deliver high doses of radiation (stereotactic body radiation therapy) to small lung tumors.”

Using radiosurgery to treat lung tumors avoids two problems that arise with standard radiation treatment. Standard radiation usually requires therapy 5 days per week for up to 7 weeks—a regimen that can prove intolerable for more fragile patients. It also is less precise. “Inevitably, in the process of trying to get rid of the cancer, you’ve treated a lot of the lung, which can lead to a lot of problems for those patients, since they already had underlying lung dysfunction,” Videtic said.

Radiosurgery, by contrast, allows radiation oncologists to more precisely deliver higher radiation doses to the target. When describing the technique to patients, Videtic uses the analogy of burning a hole in a piece of paper with a magnifying glass. “The magnifying glass focuses all the energy into a point,” he said. “Around it, nothing burns, but only at that point.”

This precision not only preserves unaffected areas of the lung, but it also significantly shortens treatment time. “Essentially, a 3- to 5-day treatment with radiosurgery—if you compare it to once a day for weeks at a time—is almost equivalent to 10 to 12 weeks of therapy,” Videtic said. “You’re packing so much radiation into a very short period of time.”

When Videtic joined the Cleveland Clinic 4 years ago, the hospital had just invested in the Novalis radiosurgery system. There are several approaches to handling the motion-control issue when targeting the lung tumor. Videtic’s team uses a compression device, which tightly surrounds the patient to restrict his or her breathing. When the patient breathes shallowly, the tumor does not move as much. While the patient wears the device, many CT images are taken to create what Videtic calls a “virtual tumor.”

“If there’s even a little bit of motion, we plot out all of the motions of the tumor and merge them together,” he said. “That creates a virtual tumor, and that will become the target, which will be aimed at by the radiation machine.”

Other hospitals use different techniques, such as respiratory gating or the Accuray CyberKnife system, which targets the tumor in motion through the use of biomarkers. Videtic said his department may look into gating methods down the line, but currently, he is satisfied with his team’s approach. “I call it patient-friendly, because it limits the amount of potential injury that we might do to some of these patients because of having to implant markers,” he said.

Success Story

The Accuray CyberKnife system targets the tumor in motion through the use of biomarkers.

Videtic has found that radiosurgery eases patient fears about sustaining permanent damage to their healthy lung tissue. “People who tend to come to us have such bad emphysema or lung disease that they’re quite scared about being disabled from the therapy, even more so than the cancer,” he said.

Three years ago, Videtic met a 72-year-old patient who suspected that she had a lung tumor. She had had two previous lung cancers over the past 10 years and had lost one of her lungs to the disease. Although she wore oxygen 24 hours per day, she was otherwise functional and independent. Her surgeon, who referred her to Videtic, feared that biopsying the tissue in the remaining lung could be fatal. So, Videtic was presented with two challenges. “One is how do we treat somebody without a formal biopsy?” he said. “Secondly, can we treat her?”

Videtic used a PET scan to help understand the tumor, and the results convinced him that it was behaving like a cancer. “Even though we didn’t have proof, I talked about it with the patient,” he said. The patient told him she believed it was cancer and gave permission for him to treat it. He let her know about the radiosurgery option, and after he addressed her fears about sustaining additional lung damage, she agreed to the treatment. Videtic performed the stereotactic radiosurgery, and the cancer disappeared after about 6 months.

“What has been very instructive is that she’s remained essentially the same,” he said. “She’s obviously still the same person with one lung on oxygen, but her needs haven’t changed. She’s still independent.”

Of course, radiosurgery is not ideal for every patient. Patients who have distant metastases, have had previous radiation therapy, have an active infection, or are pregnant are not candidates.

Much also depends on the size and position of the tumor. Suboptimal candidates include those with tumors that are larger than 5 cm or that are positioned within 2 cm of the carina. “Any time the tumor is larger than 5 cm, the dose fall-off of the radiation dose becomes suboptimal,” Suh said. “The ideal radiosurgery target is a small, discrete target that is easily identifiable. Treatment of larger lesions can lead to side effects.”

Ideal radiosurgery candidates present with the early stages of lung cancer, and Suh hopes that advances in imaging will help detect lung cancers earlier. “If you can detect lung cancer earlier, the use of stereotactic body radiation therapy or radiosurgery becomes possible,” he said. “Unfortunately, the majority of the patients that we see today actually have advanced lung cancer.”

Future Applications

Even though lung radiosurgery has been in use for several years, there is still a lot of potential for growth, which will likely be inspired by improving education efforts and public awareness. “The use of lung radiosurgery or stereotactic body radiation therapy is not common at many centers,” Suh said.

As the recognition grows, areas for improvement will likely be addressed. “In the future, I think the combination of a biologic agent or chemotherapy with high-dose precision radiation may help improve outcomes for these patients,” Suh said.

While the nuances of the available technology continue to improve, Videtic said that the latest strides in lung radiosurgery are in finding new applications. For example, there are several efforts to study the effects of lung radiosurgery on medically operable patients, to see if the noninvasive procedure is as effective as surgery. In Japan, there has been some research into this area with encouraging preliminary results.

Videtic’s team belongs to the Radiation Therapy Oncology Group study group, and he hopes to participate in the group’s future studies in this area. While it is still too early to determine whether radiosurgery has comparable results to surgery, there is a strong suggestion that the success rate will be similar. “With radiosurgery, the control rates are 80% to 90%, which is equivalent to surgery,” Videtic said. “So, as far as controlling the cancer where it started, it’s extremely good, and it’s comparable with surgery, as far as we can see.”

If radiosurgery does prove to be as effective as surgery for operable lung cancer patients, it will have tremendous implications. The noninvasive treatment option would allow patients to have faster treatments with minimal recovery time and without the risks associated with surgical procedures. “I think there are a lot of exciting avenues to explore with radiosurgery,” Suh said. “Cancer patients are asking for greater convenience when they undergo treatment. I believe the future is bright for this form of radiation treatment.”

MD Anderson and Accuray to Launch CyberKnife Trial

The study will examine surgery versus radiosurgery results in lung cancer patients.

A study set to launch this spring will test the effectiveness of lung radiosurgery when compared with surgery for medically operable lung cancer patients. The trial, led by the Texas MD Anderson Cancer Center in Houston, is sponsored by Accuray, Sunnyvale, Calif, makers of the CyberKnife Robotic Radiosurgery system.

Traditionally, lung radiosurgery candidates are medically inoperable, while surgery has been the option of choice for most patients who present with early-stage disease. This randomized trial will involve accruing approximately 1,200 patients with early-stage, operable lung cancer through 20 to 40 CyberKnife institutions worldwide. The patients will be divided between two arms of the study—600 will undergo surgery, and 600 will undergo radiosurgery.

Patient accrual will begin this spring, and the trial will take approximately 5 years to complete. “This will be a landmark study,” said Eric Lindquist, senior vice president and chief marketing officer for Accuray. “It will look at the survival rate of patients who are treated with either surgery or CyberKnife for early-stage, operable lung cancer.”

If the survival rates for the two methods prove to be comparable, the noninvasive radiosurgery option could become a common treatment for early-stage lung cancer patients. This would allow treatment with higher doses in fewer sessions, involving little to no patient-recovery time. “This could dramatically change how lung cancer is treated—not just in the United States, but worldwide,” Lindquist said.

—A. Carlson

Ann H. Carlson is a contributing writer for Medical Imaging. For more information, contact .