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Not Black or White…
It is Gray – after L.H. Gray (known as “Hal” Gray), a British radiation scientist and researcher (1905-1965), after whom contemporary radiation dose measurement was named in his honor in 1975. The radiation dose in Gray refers to the amount of absorbed radiation energy per unit of mass in the body – one Gray is specifically one joule per kilogram.
Cancers have known dose thresholds at which elimination of the tumor is likely. Normal tissues have thresholds at which toxicity of radiation therapy may ensue. These dose values vary across different organs in the body, and depend on factors such as the absolute and relative volume of the organ under irradiation as well as the orientation of the radiation dose regions to the organ structure. In this discussion we will focus on dose limits of normal tissues as they relate to the treatment of lung cancer.
In and around the lungs are a myriad of critical normal tissues. First of all, there is the lung itself, and the major airways which feed its air supply: the trachea and bronchi. In the middle of the chest between the lungs (this area is known as the “mediastinum”) are found the esophagus (swallowing tube that connects the mouth and stomach), the vertebral column (bones of the spine) and spinal cord (nerves of the spine), and the great blood vessels of the chest: the aorta and vena cava. Adjacent to all of these is the heart (somewhat to the left side as we all know). Wrapping around the outside are the ribs, muscles of the chest wall, skin and breast tissue.
Potential Improvements in Whole Brain Radiation Therapy
We have often discussed on the GRACE forum the pros and cons of various approaches to address brain metastases from non-small cell lung cancer, such as whole brain radiation therapy and stereotactic radiosurgery. One concern with regard to whole brain radiation therapy is the potential long term impact on cognitive function, in particular potential reduction in skills related to short term memory, learning and multi-tasking.
Multiple lines of research evidence point towards one particular area of the brain as very important for learning and memory – the hippocampus. The hippocampus is located in the medial aspect of the temporal lobe of the brain. In the human brain, there is a right and a left hippocampus. Nearly all right handed people are left brain dominant, and the majority of left handed people are also left brain dominant – thus the left hippocampus frequently may play a stronger contributive role in cognitive function.
V20: What is it, and why do we care?
Radiation Oncologists are highly cognizant and careful with regard to the potential side effects of radiation therapy on the normal tissues and organs of the body. In the care of patients with lung cancer, the Radiation Oncologist must carefully examine potential radiation doses (depending on specific clinical situations) to the heart, chest wall (ribs and musculature), spinal cord, esophagus, and to the lung itself.
With regard to the healthy, normal lung tissue surrounding a lung cancer, it has been long known that radiation therapy can cause an inflammatory reaction in the lungs with a potentially significant negative impact on the patient’s health and respiratory function. When significant enough volume of the lung is exposed to significant enough radiation doses, the risk for causing a radiation induced lung problem is real. As a result of radiation exposure, a condition known as radiation pneumonitis can develop.
What is SBRT, and which patients are good SBRT candidates?
SBRT stands for Stereotactic Body Radiation Therapy, a radiation therapy approach which delivers high dose radiation to a target within the body, in either a single treatment session or up to approximately five treatment sessions (each session is typically referred to as a “fraction”).
The first term in the acronym, “stereotactic” refers to precise three dimensional localization of a tumor target. The incorporation of the second term in the acronym, “body,” is of historical derivation. Stereotactic radiation therapy was first invented for the treatment of brain tumors with tools like the Gamma Knife – which has been in practice for a half century. Extension of stereotactic high-dose radiotherapy techniques to tumor targets outside of the brain and cranium is relatively novel, an advent of the past decade. Thus the use of the term “body” delineates that the technique is being applied to extracranial (non-brain) tumors. Continue reading
Postoperative Radiation Therapy after Surgery for Lung Cancer
When technically and medically possible, surgery is often the best upfront therapy for non-small cell lung cancer (NSCLC). In some circumstances, radiation therapy after surgery can increase the chance of controlling cancer at its primary site and in regional lymph nodes. Let’s discuss some of those settings.
Vitamin E, Pentoxifylline, and Radiation Fibrosis
Radiation therapy is often a component of care for patients with cancer. While radiation has great capability to kill cancer, side effects are possible. Fortunately, dramatic strides have been made in improving radiation treatment over the last few decades – modern computing and technology allow focused delivery of high radiation doses to tumors with four dimensional image guidance, dramatically limiting radiation dose to normal, healthy structures in the body. (For those of you wondering – the “fourth dimension” is that of time – for example, localizing a tumor in three dimensions, but also tracking through space as it moves over time.)
However, the risk for side effects to normal tissue remains, even when limited by the most sophisticated radiation technology. One common late or long term side effect following radiation therapy is “radiation fibrosis.” The term fibrosis describes a process of scarring which can develop in the soft tissues of the body, such as skin, muscle, healthy lung, or breast tissue. Radiation fibrosis refers to a transformation from soft, supple, and pliable soft tissue to one that is more stiff, less flexible, and less able to normally withstand and repair after other minor injuries.
Smoking Cessation and Radiation Outcomes: Does it make a difference?
Last year, while I was in line to check out at my local warehouse grocery store, I noticed that the gentleman standing in line behind me did not have a shopping cart. I glanced over my shoulder a second time and since he appeared fairly approachable, I half-jokingly said, “It appears you are missing your cart, sir.” He looked down, sighed, and then looked at me, “No,” he said, “I am just here for cigarettes.”
“Have you ever tried to quit?” I asked.
“Oh yes, many times,” he said, with a bit of a chuckle.
“I bet you have smoked for many years,” I said.
“Oh, fifty years… You don’t understand – my quitting smoking is like you trying to stop drinking water.”
“I understand.” I said.
I see many patients that have been lifetime smokers, and for whom quitting seems an impossibility. Sometimes when faced with a smoking related cancer, such patients are able to find a way to quit. Often, patients that have been smokers all their life want to know: “will it really make a difference at this point… after a lifetime of smoking… to quit?”
The answer is a resounding YES… it makes a difference. In fact, it is one of the most proactive, cancer fighting actions that a patient can take. Quitting smoking also rapidly reduces the risk of heart attack and stroke, as well as reduces the risk of second cancers. There is a similar benefit in lung cancer, head and neck cancer, bladder cancer, and gynecologic cancers.
Treatment for “solitary” brain metastases: What is best?
A great challenge posed to many lung cancer patients is spread of lung cancer to the brain. Indeed this is a scary event, for which no one can be adequately prepared. Fortunately however, many treatment options do exist which can effectively control brain metastases in many cases. In general, surgery and radiation are the key tools to address cancer when it has spread to the brain. Chemotherapy and other systemic therapies typically do not penetrate the brain region very well, and hence are not particularly active against brain metastases.
For solitary brain metastasis, surgery is often employed upfront for both diagnosis and therapy. The term solitary (as opposed to “single”) is often used to connote the presence of no additional cancer metastases elsewhere in the body. In the case of a solitary brain metastasis, there is sometimes doubt as to whether a brain lesion is in fact a metastasis. In this case, surgical biopsy or resection of the suspect lesion can confidently rule out other possibilities such as infection or a primary brain tumor. Surgery also can decompress swelling and help reduce any associated symptoms that a lesion may be causing. Of course, surgery also can carry risks, though in most cases the neurosurgeon can accurately assess risks prior to surgery based on the location of the lesion within the brain. Neurosurgeons also have a wide variety of techniques available to them in order to be sure that the surgical procedure is not causing injury. Often part of the surgery may be done while the patient is awake – achieving the ultimate careful assessment of neurological function during surgery.
Repeating Chest Radiation Therapy: Feasible or Foolhardy?
Very often when cancer patients consult with me regarding radiation therapy, they inquire, “Is it true that after a full course of radiation therapy that a second course cannot be repeated?” My answer is similar to that for many questions about radiation: “It depends.”
The key concern regarding repeat radiation therapy is that it could potentially do more harm than good. Various structures and organs in the body have differing tolerances to radiation therapy – if these are exceeded there is a possibility that significant damage could be done.
However, radiation therapy, even in the setting of recurrent cancer can at times be effective in controlling disease or in helping to reduce a symptom, such as pain or bleeding. In three general scenarios, repeating radiation therapy is considered:
1) Prior radiation therapy was well below normal tissue tolerance. This scenario is possible among patients that initially undergo stereotactic body radiation therapy (SBRT) for an initial early stage lung cancer (e.g., T1N0 or T2N0), but then have a recurrence or cancer progression in the chest. SBRT delivers a highly focused, high radiation dose to the tumor only and may largely spare the critical organs of the chest, including the majority of the lungs, the esophagus, the spine, and the heart. This scenario is also possible among patients treated with traditional external beam irradiation to a lower dose – perhaps the initial course of therapy was delivered to a specific area to try to alleviate a specific symptom.
2) Re-irradiation will employ techniques which limit additional radiation exposure to vital organs to a level not expected to cause vital organ injury. Radiation planning and delivery have become increasing sophisticated, such that it may be feasible to target recurrent or progressive lung cancer guided by 3-dimensional imaging, while avoiding the delivery of significantly high dose radiation to nearby critical anatomic structures. Modern imaging also is able to better characterize the extent of recurrent cancer after an initial course of radiation therapy – which helps determine if repeat treatment is likely to be of benefit.
3) The benefits outweigh the risks. Unfortunately, lung cancer is a difficult diagnosis. Recurrent lung cancer is even more difficult. In general, patients with recurrent lung cancer may expect to live in measures of months, or sometimes weeks. Typically, with sufficiently high doses the most dreaded radiation related vital organ toxicities such as spinal cord damage take over a year after re-irradiation to develop. For patients with symptoms from recurrent or progressive lung cancer that do not have effective alternative therapies, the short term benefits may often outweigh the long terms risks. In my experience, I have seen repeat radiation therapy dramatically help a patient that was repeated coughing up large amounts of blood – the treatment stopped the bleeding and despite the long term risks, in the short term, dramatically improved quality of life.
A recent article written by Drs. Branislav Jeremic and Gregory Videtic in the International Journal of Radiation Oncology, Biology, and Physics (generally referred to as the “red journal”, because who would want to say the full name?) reviews studies published over the last three decades in the medical literature with regard to chest re-irradiation for lung cancer. Their article summarizes the reported responses to treatment across multiple studies.
On average, 50% to 80% of patient undergoing repeat chest irradiation had decreased symptoms of cough, coughing blood, chest pain or shortness of breath. Side effects experienced by patients were in largest part related to the esophagus or to the lungs. Although rates of side effects varied widely across studies, irritation of the esophagus occurred in approximately 20% of patients undergoing re-irradiation to the chest, and irritation of lungs in about 8% of patients. By and large, these side effects tended to be mild to moderate. Severe side effects were less common, although at least one study reports a 5% rate of spinal cord damage, and it appears that at least one of the approximately 250 patients may have died related to radiation re-treatment.
The study also identifies a number of factors that may predict for longer patient survival after repeat chest radiotherapy. These factors are radiation dose, time interval to recurrence and re-irradiation, and the patients overall health status and level of activity (overall health status and level of activity are often referred to as performance status). While some of the data are conflicting, in general, patients with better performance status, longer time interval to recurrence and re-irradiation, and those treated to higher repeat radiation dose tended to live longer. These factors are highly inter-related.
Overall, in some circumstances of lung cancer recurrence or progression, repeat chest irradiation may be the best available treatment option. I hope this commentary highlights some of the key factors are involved in assessing potential risks and benefits.
Radiation-Based Treatment Options for Brain Mets: A Case-Based Approach
Unfortunately, patients with lung cancer often develop brain metastases. Once discovered, brain metastases are most often treated with radiation therapy, sometimes preceded by surgery.
For non-small cell lung cancer (NSCLC) patients with a solitary brain metastasis, that is, only one identifiable “spot” in the brain, surgery is often used in combination with radiation therapy. For NSCLC patients with multiple brain metastases, surgery offers less benefit. However, if the diagnosis is not clear, or if one of multiple lesions in particular is causing symptoms, surgery can helpful for both diagnosis and relief of symptoms. Relieving symptoms with surgery depends on the location of the lesion in regard to accessibility and function. If the lesion is in a non-critical brain area, it often may be surgically removed; however, if it is in a critical area (for example, the brain area that controls motor function of the right leg), surgery can lead to even worse function (of the right leg).
After surgery for NSCLC brain metastasis, radiation therapy is used to decrease the risk of brain metastases reoccurring or causing symptoms. Multiple options for radiotherapy treatment exist – mainly, whole brain irradiation and stereotactic radiosurgery. They can be used alone or together. For decades, standard treatment for lung cancer brain metastases has been whole brain irradiation. In more recent years, stereotactic radiosurgery has increased in availability and has been used increasingly.
Choosing the right treatment depends dramatically on patient circumstances. Let me describe a few situations:
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