The ASTRO (American Society of Therapeutic Radiation Oncologists) was held in early November in San Diego. Here’s a little info on one of the highlight presentations.

The group from William Beaumont Hospital in Detroit (Welsh and colleagues, Abstract #1088), presented a very interesting analysis comparing patients with early stage lung cancer in their own institution treated with the more extensive lung surgery of a lobectomy (removing one third of the right lung or half of the left lung), wedge resection (a much smaller surgery), and stereotactic body radiotherapy (SBRT). SBRT is a non-interventional form of radiation that delivers very high doses of radiation to small areas with a high degree of precision and accuracy. This was a retrospective report evaluating the results of these patients. The lobectomy patients performed the best, but this might be explained by these patients having better lung function, and fewer other co-existing medical problems. The patients that were treated with wedge resection and SBRT tended to be the more fragile than patients treated with a lobectomy. The patients treated with SBRT had significantly better local control (92%) than the patients treated with a wedge resection (75%). Overall, then, this suggests that among patients who aren’t optimal candidates for a full lung surgery, SBRT may be a very strong choice.

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Tomotherapy is a relatively new platform for the delivery of radiation therapy. The radiation is produced and delivered by a linear accelerator. This linear accelerator has been integrated into a CT scanner, a configuration that produces several potential advantages.

First, the patient can undergo a CT scan just prior to the delivery of radiotherapy. The CT scan obtained prior to the delivery of radiation is used to ensure that the internal targets or tissues that one is seeking to avoid have not changed their location between treatments. This is also called IGRT, or Image-Guided Radiotherapy. IGRT very cleary improves the accuracy and precision of the radiotherapy that is delivered. The potential benefits of this improvement are that less normal and healthy tissue will be exposed to radiation. While this is intuitively a very good thing, it has not been conclusively demonstrated (yet) to be of clinical benefit to each and every patient. Another advantage is that multiple remote areas can be targeted simultaneously. For some patients, this approach might be particularly useful. Finally, the treatment is delivered from a large number of angles (or helical arcs from a simplistic viewpoint), which allows for more honed deliver of radiation.

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Amifostine is the generic name for a drug that is marketed using the name Ethyol. This medicine is supposed to protect against the damaging effects of radiation. The medicine was originally developed by the military that was working on a medicine that would protect soldiers from exposure from a radioactive “dirty” bomb. It was ultimately licensed by the pharmaceutical industry for medical uses.

The drug is supposed to be a free radical scavenger. Since radiation creates free radicals that subsequently damage DNA, a free radical scavenger would theorectically mitigate some of this effect. The drug is believed to be preferentially taken up by normal tissues instead of the tumor, which is why amifostine shouldn’t protect the tumor.

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In some instances, patients present with growth of lung cancer on the inside of the airways (endobronchial). For example, a tumor is growing inside the wall of the trachea or the bronchi. When this occurs, patients often have symptoms like shortness of breath or persistent cough. This situation can occur when patients have disease in their lung or even when this is the only site of disease. The diagnosis is usually made by a pulmonologist who performs a direct visualization of the airways by bronchoscopy. These nodules are missed on CT scans frequently because even when the block most of the airway –they are actually still quite small. Here’s a representative view of an endobronchial lesion:

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This type of tumor position is perfectly suited for a treatment approach called endobronchial high dose rate (HDR) brachytherapy. This treatment approach utilizes a radioactive seed that is placed directly in contact with the tumor. The length of contact and time of contact are determined by the size of the tumor and its location. High dose rate refers to the use of a very hot radioactive seed that is usually made out of iridium. The seed is attached to the end of a wire. A very specialized machine houses the radioactive seed and wire. It can then be programmed to feed the wire out of the machine and into the catheter for a predetermined length and time. High dose rate procedures have basically replaced low dose rate procedures because the radiation dose can be delivered in a period of minutes rather than days if one used low dose radioactive sources.

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There some patients with early stage lung cancer that are not good candidates for standard lung surgery because of their underlying poor lung function. A standard lung surgery typically involves removing the entire lobe of the lung that contains the cancer. Unfortunately, for some patients with underlying COPD or emphysema – they can’t afford to lose a complete lobe of the their lung. In this situation, some surgeons have performed more limited surgery including doing a “sub-lobar” resection. The results for patients who have this limited surgical resection are not nearly as good as patients that have a complete lobectomy. In some series, the incidence of local recurrence can be as high as 20-40% if only a limited surgery is performed. The problem with these limited surgeries is that the surgeon often leaves microscopic disease behind along the edges of the surgical specimen. In other tumor types, the surgical margins are evaluated carefully and more tissue is often resected if the margins are involved. In lung cancer, evaluation the margins from the surgery specimen is more difficult, and the incidence of additional microscopic cells left in the area around the resection is probably quite high. This probably explains while the recurrence rate for small tumors is quite low with a conventional lobectomy, and much higher when less tissue is removed in a sub-lobar resection.

Brachytherapy means the use of locally placed radiation. In this case, radioactive seeds are placed in and around the surgical suture line after the surgery is complete. These seeds are sewed into the lung tissue or sewed into a mesh fabric that is then placed on the lung in the area that is at highest risk.

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As I described in my last post, stereotactic body radiotherapy (SBRT) is a technique of treating lesions in the lung with a high dose of radiotherapy. Usually the treatment is administered in 3-5 fractions. Several institutions have reported very good results using this technique.

Recently, some centers have started reporting the long term follow up of these patients. As an example, Usematsu and colleagues from Japan reported at this year’s ASTRO that 131 patients with biopsy proven stage I NSCLC were treated with SBRT using between 5-10 fractions. Only 5 of the 131 patients demonstrated local progression. The 5 and 10 year overall survival rate was 54% and 48%., with a 5 and 10 year cancer-specific survival rate was 78% of 74%, respectively. Remember, the significant difference between the overall survival and cancer-specific survival in this setting is because many patients treated with SBRT are medially inoperable because of competing medical problems. Illustrating this factor, the 5 and 10 year overall survival rate of medically operable patients (who had refused surgery) was 72% and 65%, respectively.

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Stereotactic Body Radiation Therapy is a technique designed to deliver a very high dose of radiation to a target lesion in the lung. There are a variety of platforms that are used to deliver this type of treatment including Imaged Guided Linear Accelerators and the Cyberknife.

Increasing evidence suggests that this technique might be very effective at eradicating the disease in the areas treated.

Recently, however, there have been reports of complications associated with this treatment approach. Unfortunately, complications associated with treatment are often underreported because it is more interesting to report positive data then negative data.

At the recent meeting at the American Society for Therapeutic Radiation and Oncology (ASTRO, the main US-based radiation oncology professional society), the incidence of severe pain and rib fracture were reported in a combined series from the University of Virginia and the University of Colorado. Dunlap and colleagues (abstract here) reported that 13 of the 31 patients with lesions that were with 1.5 cm of the chest wall underwent high dose stereotactic radiotherapy either experienced chest wall pain or rib fracture. Most patients who experienced rib fracture or chest wall pain experienced it around 7 months. When they evaluated the plans after the fact, they identified the risk of rib fracture or chest wall pain to be associated with high dose radiation in the region of the rib. This series suggested that if the volume of the chest wall that received over 30 Gy was greater than 40 cc the risk of complications approached 50%. Although this series is somewhat small, there is the suggestion that if one can use techniques to limit the high dose region that overlaps the rib/chest wall region the risk of rib fracture or chest wall pain will be less.

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Dr. West previously wrote an introductory post (here) about radiation pneumonitis, but this is a common enough problem that it merits further discussion, including input from a radiation oncologist. The other issue is that Dr. West was using a review article of mine (abstract here) as a crib sheet, so now I can give you a bit of perspective directly from the source.

Pneumonitis is one of the risk factors associated with radiation treatment to the lung. Radiation pneumonitis is an inflammatory reaction that resembles a pneumonia that typically occurs in patients 6-24 weeks after they have completed radiation treatment. The symptoms of radiation pneumonitis are often similar to the symptoms one experiences when one has a pneumonia or the bad flu. Patients can complain of a cough, shortness of breath, or even chest fullness. Most patients who develop these symptoms after radiation report that the symptoms resolve by themselves in 7-10 days. A few of the patients have really severe symptoms and come in to be evaluated by a physician. If the diagnosis of radiation pneumonitis is made, then patients can be treated quite effectively with a short course of steroids.

One of the important things to keep in mind is that radiation pneumonitis is a “diagnosis of exclusion.” What this means is that a very thorough and careful evaluation must be undertaken to make sure that the symptoms the patient is experiencing is not caused by something else. Only after the other possible explanations have been ruled out can one say that they have a diagnosis of radiation pneumonitis. I have noticed that there has been increasing awareness of this complication more recently. A really interesting analysis was recently reported in the literature. The physicians went back through the charts of patients diagnosed with severe radiation pneumonitis to evaluate the outcomes of these patients. They discovered to their surprise that many of the patients didn’t in fact have radiation pneumonitis but other serious conditions that had been initially “missed.” For example, one of the patients was ultimately diagnosed with a heart attack. Other patients were ultimately diagnosed with exacerbations of their COPD/emphysema. And some of these patients had infections that were ultimately treated with appropriate antibiotics. This report is a caution that should remind everyone to look elsewhere first before assuming that the symptoms are radiation pneunonitis.

Another thing to keep in mind is that some patients will have evidence of “radiation pneumonitis” on a CT scan but not have any symptoms. I think that most of us agree that these patients don’t need any treatment as long as they remain asymptomatic.

The causes of radiation pneunonitis are still being worked out. There are a number of possible suspects. The most obvious is the radiation dose, the daily fraction, and the amount of lung exposed to certain doses of radiation. Certain chemotherapy or targeted agents may make the lung more sensitive to radiation pneumonitis or may actually cause it independently. Although people with compromised lungs may do poorly if they develop radiation pneumonitis, I’m not sure that there is good evidence indicating that they are any more sensitive to this side effect than a person with healthy lungs.

Esophagitis is a symptom that occurs in patients undergoing radiation for lung cancer. It is not uncommon for patients to blame the radiation for this side effect. Radiation esophagitis if often described as a “sunburn on the inside of the esophagus.” The esophagus it the long swallowing tube that sits in the middle of the chest usually right next to the trachea (the windpipe). The tube connects the mouth to the stomach. Unfortunately, it is very difficult to avoid this structure when delivering radiation because it is intimately associated with the lung, central lymph nodes, and the trachea. Avoiding the esophagus would mean undertreating the tumor in many instances.

Patients who develop esophagitis will often complain of some heartburn like discomfort or pain with swallowing. These symptoms come on gradually and get worse as they complete treatment. They typically peak sometime after the radiation ends. In the most severe form, an ulceration can form in the esophageal wall (this happens very rarely).

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Despite the acute side effects, it is important to try and deliver the radiation treatment without any interruptions or delays in treatment. Experiments in the laboratory with cancer cell lines demonstrate quite convincingly that interrupting the radiation treatment even for a few days allows the cancer cells to grow back. A large retrospective study has demonstrated that the survival is significantly worse if patients had an interruption in their treatment of longer than 5 days. These results have also demonstrated that patients that go through the treatment without an interruption have a statistically higher chance of beating the disease than patients that experience an interruption in their treatment. Sometimes the interruption in treatment is simply unavoidable (i.e., because a patient is simply too sick), but treatment interruptions scheduled out of convenience should be avoided if at all possible.

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