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.

We have had a few recent questions as to which patients are good candidates for SBRT for lung cancer.  The applications of SBRT for lung cancer grew out of the fact that patients with early stage yet medically inoperable lung cancer had fairly poor outcomes with conventional radiation therapy.  It is in these patients that SBRT trials have been conducted, and in these patients that great success has been shown.

For example, if a patient with an isolated lung cancer (T1, T2, N0) was not able to undergo surgery because of other medical conditions such as heart disease, historically success with conventional external beam radiation therapy  was limited.  With traditional techniques, the chance of locally controlling a cancer such as this was 50% at best.  With SBRT, probability of locally controlling  such a tumor  now exceeds 90%… indeed a dramatic improvement.

SBRT can be used for patients with clinically early stage, solitary, non-small cell lung cancers, measuring as large as 5 to 7 cm.  Size is not the only consideration - location of the primary tumor is important.  Cancers that are largely adherent or close to the chest wall can lead to chest wall pain after therapy.  Radiation oncologists also assess carefully when cancers may be too close to the central structures of the chest and the large airways for SBRT treatment  -  alternative dose and fractionation strategies may be employed to lessen the risk of obstruction of the large airways due to possible inflammation and scarring after treatment.

Is SBRT an option for patients that may otherwise be able to undergo surgery?  That has yet to be established, although clinical trials with medically operable lung cancer are underway and results are pending.

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First, radiation therapy is strongly considered in patients who undergo surgery, though for whom cancer is not totally removed (or “resected”).  We typically refer to this situation as surgery with “positive margins,” meaning one of two things: 1) The surgeon was visually unable to remove all of the tumor - referred to as a “gross positive margin.”  The term “gross” refers to the unresectable residual disease being readily seen without the assistance of a microscope - similar to the phrase “gross anatomy,” referring to the physical study of the body’s muscles, bones, and internal organs as viewed with the naked eye upon dissection.  2)  The surgeon was visually able to remove the entire tumor (”gross negative margin” or “gross total resection”), but upon microscopic analysis, the pathologist found cancer right up to the edge of the specimen.  This is referred to as a microscopically positive margin - indicating the very high likelihood that on the remaining edge of lung tissue adjacent to the area where the gross tumor was removed, there are cancer cells left behind.

In these two situations of positive margins, we often recommend postoperative radiation therapy, aimed at eradicating remaining cancer.  The area of a positive margin, whether it is gross or microscopic, may often be readily localized by the radiation oncologist, enabling focused radiation therapy to that area.  As well, for patients that were good candidates to have surgery, such patients typically are in good enough general health and have enough pulmonary reserve to withstand some inflammation or scarring of the lung related to radiation therapy.

The second key instance in which radiation therapy is considered after surgery is the circumstance of completed resected cancer with pathologic evidence of cancer spread to the mediastinal lymph nodes - the lymph nodes in the center of the chest.  Studies over the past few decades have suggested a cancer control benefit for patients with mediastinal lymph node positive disease if they undergo postoperative radiation therapy directed at the mediastinum (central chest lymph node region).  For patients with less extensive fully resected cancer at the time of surgery, postoperative radiation therapy is typically not recommended.   Among patients without positive lymph nodes in the mediastinum (thus earlier stage disease), retrospective studies have suggested that postoperative radiation therapy may be detrimental.  However, these cancer patients with potentially worse outcomes after radiation therapy for limited disease were treated in an era with inferior techniques and technology.

There are many other situations in which patients find themselves with questions about postoperative radiation therapy.  For example, after a “wedge” resection, the question often comes up about the potential benefit of postoperative radiation therapy.  Typically, a “lobectomy” is the preferred surgical procedure for patients with non-small cell lung cancer.  In a lobectomy, an entire “lobe” of the lung is removed - depending on whether it is the left or right lung, the lobectomy removes one-third to one-half of the lung volume on that side.  Studies have compared lobectomy to lesser procedures such as the wedge resection, in which only the known cancer and a small surrounding area around it are removed, though found higher rates of recurrence with the wedge resection.

Given the historic higher rates of recurrence with wedge resection, the question may arise as to whether postoperative radiation therapy directed at the surgical bed would reduce the risk of cancer recurrence.  Generally in this situation, postoperative radiation therapy is not recommended for a number of reasons.  First, with modern surgical techniques and intraoperative pathologic analysis, wedge resections likely carry a lower risk of recurrence than in years past.  The Japanese for example have published recent series of patients in which the rates of recurrence after wedge resection were quite low.  Second, for patients unable to medically tolerate a complete lobar resection, the additional side effects of lung directed radiation therapy may not be worth the further decrease in recurrence risk that radiation therapy affords.

Altogether, the recommendation for postoperative radiation hinges on its ability to significantly reduce the risk for cancer recurrence in situations where it is not likely to cause significant enough damage to remaining lung that a patient’s quality of life is hindered.  In situations of positive margins and cancer spread to the lymph nodes of the mediastinum, radiation therapy may confer a significant overall benefit to the patient.

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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.

On the cellular level, radiation induced fibrosis has been linked to abnormal fibroblast activity.  Fibroblasts are a class of immune type cells which normally help tissues repair after injury.  However, in situations of radiation induced fibrosis, these cells overreact, and produce excessive extracellular matrix around healthy cells.  This process is triggered by a free radicals incited by therapeutic ionizing radiation.

In cases of radiation induced fibrosis, the initial inflammation triggered by therapeutic ionizing radiation spirals out of control, and in the irradiated area, the inflammatory response turns chronic, with potentially significant resultant scarring.

What can be done?  Radiation damage acts through a free radical mechanism, and radiation scarring can often affect small blood vessels and result in decreased blood flow to irradiated tissue.  Due to these mechanistic underpinnings, a group in France has published some work on combination therapy with Vitamin E (an anti-oxidant, or free radical scavenger) and pentoxifylline (a vasodilator, marketed as “Trental”).  Together, these medications seemingly could target part of the mechanism (oxidative damage) and part of the complication (reduced blood flow).

The French group published a study in 2003 in the Journal of Clinical Oncology that examined the potential benefit to six months of treatment with a combination of Vitamin E and a vasodilating drug by the name of pentoxifylline.  In this study, 24 women with a history of breast cancer and radiation induced fibrosis of the skin and underlying tissues were randomly assigned to one of four treatment groups: 1) Vitamin E alone, 2) pentoxifylline alone, 3) combination therapy with Vitamin E and pentoxifylline, and 4) placebo.  The investigators reported that radiation induced fibrosis surface regression was significantly improved among women taking the combination of Vitamin E and pentoxifylline, such that the mean radiation induced fibrosis surface regression was reduced in comparison to placebo in 60% vs. 43% of patients.  The “p-value” for the comparative statistic was p=0.038 (for the non-statistician readers, that p-value suggests that the findings had only a 4 in 100 probability of being due to chance).

While many physicians employ vitamin E and pentoxifylline in cases of radiation fibrosis based on this data, I remain highly skeptical of its benefit.  First, it is shocking to me that in this study, there was a 43% improvement among patients taking placebo!  That is an extraordinary placebo effect!  Rarely in any study of medication are the benefits so great - and in this study, it appears that the majority of the benefit was realized by those taking nothing!  Second, as one carefully examines the data, it is clear that the patients taking placebo had the same benefit, or even a slightly increased benefit, compared with those patients that were taking Vitamin E only, or pentoxifylline only.  Thus, if the benefit of the combination drug therapy is real, there is a yet to be established synergistic phenomenon upon which the therapeutic benefit completely relies.  It is surprising to me that each drug alone yielded no benefit whatsoever over placebo.

While it makes some sense that these medications are directed at helping some of the problems in radiation induced fibrosis, I am not convinced of their benefit.  As well, in this study, the outcome measured was soft tissue fibrosis among patients treated for breast cancer.  I know of no comparable data among patients treated for other cancers or for fibrosis of other body sites or organs.

In my practice, I will offer to patients with radiation fibrosis a trial of therapy with Vitamin E and pentoxifylline, given that they are very safe medications, though I upfront explain my uncertainty that they will be of benefit.

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   “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.

   Smoking particularly inhibits the effectiveness of radiation therapy. Most types of therapeutic radiation depend on oxygen free radical mechanisms, that is, the effectiveness of the radiation to break the DNA of the cancer cells relies on the presence of oxygen in the target tumor. Smoking cigarettes and other forms of tobacco reduces the oxygen carrying capacity of blood, and leads to less oxygen availability for interaction with radiation.

   The effect of smoking while undergoing radiation treatment was recently examined by physicians at The Mayo Clinic in Scottsdale and a group from Luebeck Germany. Dr. Dirk Rades and colleagues published a 2008 analysis in the International Journal of Radiation Oncology, Biology, Physics, of 181 patients treated with radiation therapy for non-small cell lung cancer, and found that local control of lung cancer at one year was 46% among currently smoking patients versus 71% among patients that were not currently smoking. For the statisticians among you, this was statistically significant when all other factors where taken into account (i.e. multivariate analysis).

   Also of key importance and relevance in that study is the fact that the amount patients smoked prior to undergoing radiation therapy did not impact the effectiveness of the treatment.  Thus, for those patients that have smoked their entire life, and now face lung cancer, there is data to support that quitting during treatment can impact the outcome of treatment significantly, if one is able to stop smoking during treatment.

   As the man at the grocery store highlighted with his analogy to water deprivation, I do understand that it can be extraordinarily difficult to quit. But it can make a big difference in the treatment outcome.

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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.

Following surgery for a solitary brain metastasis, the greatest area at risk for metastatic progression in the brain is the very site from which the initially detected metastasis was surgically resected. This area is at very high risk – there is approximately a 70-80% risk of metastatic progression at this initial site following surgery alone. Elsewhere in the brain following surgery for a solitary brain metastasis, the risk of detecting additional metastases over the next year is approximately 50% - still a very high-risk, but not quite as high as the site of the initial metastatic lesion. In order to address the risks of cancer relapse at the initial site of disease or elsewhere in the brain, we consider whole brain radiotherapy, and often as an alternative to whole brain radiotherapy, stereotactic radiosurgery to the surgical resection cavity alone. Surgery followed by whole brain irradiation is a more traditional approach. As well, surgery + whole brain irradiation (in comparison to surgery alone) has been shown to be superior at preventing neurologic death, though not overall survival in a randomized trial. Whereas, surgery followed by stereotactic radiosurgery to the resection cavity (without whole brain irradiation) is an evolving paradigm, without the support of a randomized trial, though with good reported outcomes in non-randomized studies.

The pivotal question is: for which patients with a solitary brain metastasis, is surgery followed by radiosurgery to the resection cavity enough, obviating the need for immediate whole brain radiotherapy? This is a question which many patients face, and one for which there is no standard answer. It really depends on many factors surrounding the patient, his or her disease, goals, and greatest concerns. In general, surgery followed by stereotactic radiosurgery to the surgical resection cavity is safe and effective, addressing the brain area at the highest risk of recurrence and diminishing that risk significantly. Stereotactic radiosurgery “boost” to the resection cavity does not carry the side effect profile of whole brain irradiation, though does not decrease the risk of developing other areas of metastasis within the brain. While whole brain irradiation addresses both the initial site of resected metastasis as well as the rest of the brain, there is potential for greater side effects, though sometimes the true risks associated with whole brain radiation are exaggerated.

If whole brain irradiation is deferred in favor of stereotactic radiosurgery, close followup is very important – repeat brain MRIs on a regular interval are necessary. That being said, close followup is important even if whole brain irradiation is performed as well. Though the risk of other brain metastases drops with whole brain irradiation down from 50%, it does not drop to zero. Even after whole brain irradiation, there is a risk of 10-30% of developing additional brain metastases.

What about radiation therapy alone for a solitary brain metastasis? It has been shown that surgery + whole brain irradiation is better than whole brain irradiation alone – in fact, a study comparing these two treatments showed that surgery preceding whole brain irradiation led to significantly improved overall survival (Patchell et al., New England Journal of Medicine, 1990). However, for some patients that are not good candidates for surgery or surgery is not considered to be of benefit, stereotactic radiosurgery may offer excellent local control of a solitary lesion, by itself or in combination with whole brain irradiation. As well, in some situations, simple whole brain radiation, all by itself, may be the best therapy. Again, the best path of treatment is very specific to a patient’s individual circumstances. There are a multitude of options.

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   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.

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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:

Case #1:  Mr. W is a 70 year old gentleman diagnosed with locally advanced squamous cell carcinoma of the lung, stage IIIB.   He undergoes treatment with chemotherapy and radiation and the cancer generally responds well.  Two months later, he develops a headache and brain imaging demonstrates three lesions in the brain, consistent with brain metastasis, with some associated swelling.

For Mr. W, proceeding to whole brain irradiation would be my general recommendation.  Given the multiple brain metastases and short interval in which they developed, he is at high risk for development of additional brain metastases.

Case #2: Ms. X is a 36 year old woman with early stage adenocarcinoma of the right lung (T1N0).  She underwent a surgery for removal of the right upper lobe of the lung containing the cancer and has no evidence of disease for 2 years.  Then, she develops some very subtle weakness in the right leg.  Her physician obtains a brain MRI which identifies a 2 cm mass in the region of the brain controlling the right leg, with some swelling.  Restaging scans of the chest, abdomen, and pelvis identify no other areas of disease recurrence.  She continues to work full time.

For Ms. X, I would recommend focused, single session, stereotactic radiosurgery treatment.  Surgical resection is likely not a good option given the location of the metastasis.  Whole brain irradiation is an option in this case; however, given the early stage of lung cancer initially and long interval before development of the brain metastasis, I would favor stereotactic radiosurgery, as Ms. X likely has less than the traditional 50% risk of developing additional brain metastasis.  As well, in the short term, she will be able to obviate 2 to 3 weeks of daily whole brain treatment, and avoid the possible short term side effects of fatigue, nausea, vomiting, hair loss, and sore throat.  She also will be able to keep working, with minimal interruption.  In the long term, while whole brain radiation is generally safe, she may avoid the potential long term side effects of whole brain irradiation, such has some decrease in short term memory or ability to multi-task, which may also interfere with her job.   If she opts for focused stereotactic treatment, she will particularly need close neurological follow-up and scheduled repeat surveillance brain MRIs.

Case #3:  Mr. Y is a 49 year old gentleman diagnosed with stage IV lung cancer, with a large mass in the chest, liver, bone, and brain metastases.  He has lost 60 pounds and getting out of bed is difficult.

For Mr. Y, I would recommend no aggressive directed therapy of brain metastases.  I would encourage comfort and quality of life related care, with consideration of steroid medications to ease any symptoms related to brain metastases.

Case #4:  Ms. Z is a 64 year old woman treated two years ago for a T2N2M0, Stage IIIA non-small cell lung cancer.  She underwent surgery, then chemotherapy, then radiation therapy.  Three months later, she was restaged with a brain MRI which detected a solitary 1cm brain lesion in the cerebellum (the lower, back part of the brain).  She has no other sites of active disease.

Patients like Ms. Z face multiple reasonable choices regarding brain metastasis treatment.  First, surgery is not an unreasonable option, given the lesion is likely surgically accessible.  Second, whole brain irradiation, alone or in combination with surgery, is also good treatment - Ms.  Z is at high risk of developing additional brain metastases, and will likely benefit from whole brain irradiation.  Finally, stereotactic radiosurgery is also an option - the important thing to realize however is stereotactic radiosurgery that may only be prolonging an inevitable need for whole brain irradiation, although may cause less in terms of side effects.

In general, whole brain irradiation is safe and effective in suppressing known brain metastases as well as subclinical (no symptoms) and subradiographic (not visible on scans) disease.  Stereotactic radiosurgery offers some benefits as a high dose focused treatment which is often only a single day of treatment, with potentially little to no time required for recovery.  Altogether, it is important for patients and physicians to discuss these various options for treatment, their effectiveness, their limitations, and their optimal selection given individual circumstances.

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Descriptions of second cancers date far back in the medical literature. Dr. Cahan and colleagues reported their clinical observation of “Sarcoma Arising in Irradiated Bone” in 1948, and articulated the following three criteria characteristic of cancers caused by radiation therapy: 1) histologic features of first cancer and secondary cancer are different, 2) secondary cancer is within the area previously treated with radiation, and 3) the secondary cancer has a latency period of 5 years – that is, the secondary cancer develops five years or later after the first. These criteria are not set in stone, but stand as a good general reference when trying to deduce whether a cancer was likely secondary to radiation.

Secondary cancers are caused by injury to the DNA of irradiated cells in such a way that genetic programming is altered to favor abnormal cellular growth and proliferation. In general it takes many years for secondary caners to develop. Many factors contribute to the risk for radiation carcinogenesis – some are specific to the patient and some are specific to radiotherapy treatment. Patients that are younger and smokers tend to be at higher risk for secondary cancers. Three important contributing factors specific to radiation therapy include the total radiation dose, the volume of irradiated tissue, and the type of tissue irradiated.

With regard to radiation dose, the probability of carcinogenesis increases with increasing radiation dose within a certain range, however the severity of the induced malignancy is not influenced by dose – known as a stochastic phenomenon. At very high dose, stereotactic radiosurgery data supports that there may be a lower risk for induction of a secondary malignancy, because of a very high probability of complete cellular kill in the high dose radiation field – that is, no damaged cells with a potential for malignant transformation survive, and fewer cells are exposed to an intermediate dose exposure. A completely safe minimum dose threshold, below which there is zero risk for radiation carcinogenesis does not appear to exist. However, at some threshold as described in the last commentary entitled “Radiation 101 – Background,” the risk of developing a cancer from radiation drops to the very low risk associated with the level of natural background radiation to which we are exposed every day. Thus we generally consider a safe level of radiation to be on the order of a few multiples of background radiation dose.

The overall risk for developing a radiation related malignancy has historically been best described among breast cancer patients. As noted above, it often takes many years for development of secondary malignancies – breast cancer is a disease in which many patients undergo treatment with radiation, and fortunately, most breast cancer patients are cured of their disease and live for many years after treatment. It is late during this survivorship that a small fraction of patients may develop a secondary malignancy – because the risk is so small, thousands of patients must be studied in order to detect any increase in risk.

After radiation therapy for breast cancer, the risk of sarcoma, lung cancer, and other breast cancers have been described in the medical literature. From France, we have reports on thousands of women treated with radiation therapy for breast cancer over the last few decades. The French have reported a risk of developing sarcoma in the range from 0.28% to 0.48%. With regard to lung cancer, data from the United States and Sweden indicates that patients treated before the mid 1980’s were noted to have approximately a 0.5% increase in the risk of developing lung cancer - almost all secondary lung cancers appear to be in smokers. However, among patients treated in the last 30 years, this increased risk of lung cancer has disappeared. With regard to whether women are at increased risk for secondary breast cancers, data is too conflicting to draw firm conclusions. It appears that with older techniques, younger women may have been at a slightly elevated risk of developing a second breast cancer.

Considering secondary malignancy risks across all cancer sites, a recent review in the journal Lancet Oncology examines the secondary malignancy risk among 647,672 patients age 20 and older with cancers originating at 15 anatomic sites throughout the body. Both patients treated without and with radiation therapy were included in the analysis. Among all patients, 60,271 (9%) developed a second solid cancer, of which 3,266 were estimated to be related to radiotherapy, corresponding to a risk of five excess cancers per 1,000 patients treated with radiotherapy at 15 years after diagnosis. The authors appropriately concluded that a relatively small proportion of second cancers are related to radiotherapy in adults, suggesting that most are due to other factors such as lifestyle, carcinogenic exposures, and genetics. Highlighting the differences in risk across cancer sites, only 4% of second cancers originating in or around the eye were related to radiation therapy, yet 24% of second cancers following treatment of primary testicular cancer in men were related to radiation therapy. Of note, it is relatively uncommon nowadays to undergo radiation therapy for testicular cancer – surgery and chemotherapy are the most common forms of current treatment.

Generally, the risk of developing a radiation induced malignancy after treatment of cancer is very small, though certainly a scary thought. Remarkably though, radiotherapy related cancers account for a small minority of second cancers which develop in patients after treatment for a first cancer. In the Lancet study above, nearly 10% of cancer patients developed second cancers, but only 0.5% of patients developed cancers which seemed likely to be radiotherapy related. In discussion with cancer patients, radiation oncologists strive to balance the often highly effective cancer controlling benefit of radiation with the risk of secondary malignancy, as well as other possible side effects of treatment. Thankfully, with modern radiation techniques, the risk of causing a secondary malignancy is less than that demonstrated in historical studies, due to higher precision radiation targeting.

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Here’s the audio and video versions of the podcast (not really much video here, just in this format to have it go to the people subscribed to the video channel on iTunes, YouTube, etc.), as well as the transcript.

dr-mehta-brain-mets-qa-session-audio-podcast

dr-mehta-brain-mets-qa-session-transcript

Apologies for the echo and overall less than ideal sound quality of this one — there are some real limitations and compromises with the teleconference format.  Though our sound editor does the best he can, he still has to work with what he’s given.  Fortunately, everything is understandable even if it isn’t the New York Philharmonic here.  And the price is right.

Thanks to those who joined us, thanks to LUNGevity Foundation for partnering with us on this, and big thanks again to Dr. Mehta for his commanding presentation and generosity with his time in answering so many good questions for us.

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Here is the podcast of his presentation in both audio and video form.  Along with them, you’ll find below the transcript and figures associated with this program.

dr-minesh-mehta-prevention-and-treatment-of-brain-mets-audio-podcast

dr-minesh-mehta-prevention-and-treatment-of-brain-mets-transcript

dr-minesh-mehta-prevention-and-treatment-of-brain-mets-figs

We had a great Q&A session after this webinar, which we’ll post as a separate podcast in the next week or so.

I wanted to again express sincere thanks to LUNGevity Foundation for partnering with us and making this webinar possible.  I hope you find it helpful.

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