Recent Treatment Advances in Radiation Oncology
About the Lecture
Radiation therapy is an effective tool in the arsenal of anti-cancer therapies and there are more options with greater precision and few side effects than were available a decade ago. Radiation therapy uses high energy ionized x-rays to cause damage to the DNA of cancer cells leading to their death, but also damages the DNA of normal cells causing short-term and long-term side effects. Recent advances, using 3-dimensional conformal radiation therapy, radiation oncologists use a CT scan to map out the tumor and the critical normal structures in 3-dimensions to optimally direct the radiation. More recently, intensity-modulated radiation therapy further improves the ability to conform the treatment volume to the exact shapes of the tumor that is wrapped around a vulnerable structure such as the spinal cord, heart, or the visual apparatus. Stereotactic radiosurgery (SRS) for brain tumors, and stereotactic body radiation therapy (SBRT) is even more sophisticated. These approaches uses multiple converging beams of radiation on smaller targets allowing high doses of radiation to be delivered focally to tumors and spare adjacent critical tissue. They are typically delivered in 1-5 treatments compared to conventional radiation which is often given over 4-6 weeks offering a non-invasive approach to eradicate tumors in that are not amenable to surgical removal, with success rates approaching that of surgery. Modern radiation therapy provides patients with more options compared to 10-15 years ago.
Percy Lee, MD, earned his medical degree from Harvard Medical School, where he graduated magna cum laude. At Harvard, he was also a Howard Hughes Medical Institute Research fellow. He interned at Massachusetts General Hospital and received specialty training in Radiation Oncology from Stanford University. Dr. Lee is an Assistant Professor in Radiation Oncology and Clinical Director of the Stereotactic Body Radiation Therapy (SBRT) program. His expertise includes intensity-modulated radiation therapy (IMRT), as well as SBRT and stereotactic radiosurgery (SRS) where highly focused radiation is concentrated on localized tumors. Dr. Lee is also focused on developing novel functional image-guided radiation therapy approaches and discovering new molecularly targeted anti-angiogenic drugs for cancer therapy. In addition, he is investigating combining molecular targeted therapy with SBRT in a rationale and innovative approach with the goal of improving treatment outcomes.
This is a summary of a lecture presented on July 13, 2010.
Recent advances in radiation therapy are making it possible for us to move from two dimensional to four dimensional imaging and to provide more targeted treatment. As a radiation oncologist, my goal is to provide more accurate, more precise physical and biological targeting. This will allow for escalations in the radiation dose, potentially treating the cancer more effectively, reducing the amount of time that it takes to receive radiation therapy and, thereby, reducing toxicity. The ultimate goal is to improve tumor cure rates.
What is therapeutic radiation?
Therapeutic radiation can be thought of as using x-rays of higher frequency (therefore more energetic and potent) along a spectrum of different wavelengths of visible and invisible light. For example, low frequency radiation comes from things like the radio, microwaves, infrared light, visible light, and ultra violet light. High frequency energy includes x-rays and gamma rays for treatment; the highest end of the spectrum appears at the cosmic level of the solar system. Therapeutic radiation kills cancer cells by either directly affecting the DNA or by indirectly oxidizing water (making free radicals) that diffuse towards the DNA and cause damage. If a critical double strand of the DNA breaks in the tumor cell, tumor cell death will occur. Cancer cells do not have the ability to repair themselves in the same way as normal cells. Radiation therapy has typically been given over longer periods of time with smaller amounts of radiation because traditional forms of radiation were less accurate and more normal tissue was in the radiation portals (fields). The slow daily doses of radiation are more likely to irreversibly damage cancer cells than normal cells because normal cells can repair sub-lethal damage. However, we now have better ways to completely exclude normal tissue in our radiation fields, and therefore, can now escalate the daily dose.
Stereotactic Body Radiation Therapy
Stereotactic body radiation therapy (SBRT) is a new approach that differs from more traditional therapies in a variety of ways. Previously, radiation would be mapped out as large areas around the tumor site because we did not have tools to verify if we were hitting the right target . The problem with this older approach with a large field is that a considerable amount of normal tissue may lie within the field while a portion of the actual tumor may still lie outside the field on any given day (due to lack of imaging daily to verify tumor location). SBRT differs from traditional therapy because it uses highly focused radiation concentrated on small tumors and only low doses to surrounding tissues. By using more focused, higher doses on the tumor site we can use fewer treatments. A single large dose or a few treatments is more biologically effective than 6 weeks of incremental doses of daily radiation, eliminating the longer period of radiation that has characterized more traditional approaches. In order for SBRT to be successful, it has to be done using very precise delivery techniques. This is accomplished by using image-guidance and using four-dimensional CT scanning prior to treatment. This technology allows the treatments to be mapped with very small margins around the tumor, thereby sparing the majority of normal tissue of high doses of radiation. A special belt is used to monitor a patient’s respiratory motion during the CT scan, so that the radiation oncologist can correlate internal tumor and organ motion with a patient’s breathing pattern. Once this is established it can be determined how the tumor moves with each breath. Potentially, we can use this information to turn the therapeutic radiation beams on and off as the tumor moves in and out of the field, to further reduce the field of radiation.
The next part of the treatment plan is to “map the tumor,” e.g., how and where the radiation will be entering the patient. The preferred mapping method is called 4D-conformal radiation therapy and uses multiple imaging modalities to characterize the treatment target such as PET-CT and MRI images. This method provides detailed information to define the specific target from multiple angles, thus making delivery even more precise and enabling the maximum amount of radiation to be aimed at the most active portion of the tumor. In addition, the beams come from multiple angles and the intensity can be modulated (called intensity modulated radiation therapy or IMRT) which allows the primary area of the tumor to receive the most treatment while surrounding tissues receive less radiation, creating fewer side effects and less damage to normal tissue. The skin is also less damaged because the radiation treatments are coming from multiple angles.
Stage 1 lung cancer is, potentially, an operable and curable disease; however, many patients are not able to undergo a surgical procedure due to a variety of factors such as low pulmonary function, illness or other age-related variables. Here at UCLA, SBRT is being used for Stage 1 lung cancer patients ineligible for surgery because it allows for an increase in dosage with a lower side effect profile. In an article recently published in the Journal of the American Medical Association, data was presented from the first North American cooperative group trial of SBRT. In this trial 55 patients with medically inoperable peripheral tumors (non-small cell lung cancer stages 1A and 1B) were given three treatments of SBRT. They had tumor control in 98% of the patients, 72% survival at two years and a median overall survival of 48 months. The question has been raised whether the SBRT treatments in these lung patients is equivalent to doing a non-surgical wedge resection; however, SBRT appears to have better local control and regional control at 4 years. We are continuing to follow these patients. This type of treatment has raised the control rates from 30% with traditional radiation therapy to 90% in lung cancer patients who receive SBRT. Likely, this is because the biological dosage of radiation has been significantly increased.
This type of treatment is also being used in certain types of liver cancers as well. While surgery is possible in less than 15% of patients with hepatobiliary cancer, SBRT appears to be an effective non-surgical alternative. Further, it can be used to treat the tumor without creating some of the side effects that traditional radiation therapy creates in the liver such as radiation-induced hepatitis. SBRT is also being used to help control the cancer so that patients are able to get on the liver transplant list. Some patients who are not surgical candidates may become surgical candidates after such treatment. There is preliminary evidence to suggest that patients treated before liver transplant have a lower rate of recurrence and potentially some patients are cured, whereas this disease was previously thought to be highly incurable.
While lung and liver are only two examples of cancers where SBRT seems to be improving treatment strategies, there are other cancers that are also being considered and will likely be addressed in this manner in the future.
Patients sometimes hear about these treatments through advertisement by treatment centers indicating that they have a particular state of the art machine. There are many manufacturers of these machines that offer this type of treatment, such as the Novalis TX and Cyberknife. They have different names, like luxury cars such as BMW and Mercedes Benz. UCLA has the Novalis TX machine. The most important consideration is, as with driving a car, having someone who really knows how to use the machine. Just because a treatment center has a special machine does not insure that they have well-trained and experienced physicians using them. It is an important part of the equation to have improved technology but the human variable is critical. Mistakes often happen when technology is not being appropriately used by individuals and human judgment is not emphasized.
Safety is an important consideration in any radiation environment. Just as airline pilots go through a safety checklist with another pilot before take-off, similarly safety checklists are needed when using advanced radiation procedures. Data suggests that the use of these checklists helps reduce the number of mistakes that happen that are sometimes reported in the news.
We are making significant advances in radiation oncology and are now able to use increasingly more precise and safe treatments to map and treat cancer. And, we are expanding our understanding and application of SBRT and other radiation therapy approaches in radiation oncology every day. As Atul Gawande, MD, from Brigham and Women’s Hospital – Harvard Medical School has written in his books, “Better is possible. It does not take genius. It takes diligence. It takes moral clarity. It takes ingenuity. And above all, it takes a willingness to try.”
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