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Last Updated 6/4/03.

Stereotactic Radioablation at Indiana University

by Keith Altman
(dx Stage IV March 2001)

In this article, I will briefly discuss my experience with Stereotactic Radioablation (SR) at Indiana University. IU is one of several United States sites which does SR for cancer metastases both inside and outside the liver. The University of Colorado and U Penn have similar programs as IU from what I have been told. Other cancer centers have entirely different versions of SR, and of these I have no personal experience. I am assuming the reader has a basic familiarity with SR as described in the Conformal Radiation Discussion/References Here . Some BB posts with further information (posted while I was undergoing SR myself) may be found Here (also see Main Page ).

The primary problem patients exploring SR will face is that there is no standardization - each cancer center offering this technique does it in a different way and there are no clinical trials comparing the multitude of approaches. There are several main factors which can be varied in the way SR is done, which are

(1) The amount of radiation delivered to the tumor
(2) The "fractionation" of that radiation (number of radiation sessions)
(3) How to deal with the "breathing problem" - patient motion during therapy which will cause the tumor to move out of the narrow radiation field unless something is done to compensate for it.

Introduction

Indiana University has followed the approach pioneered at the Karolinska Hospital in Stockholm, Sweden a number of years ago. The patient is placed in a styrofoam "body frame" which is custom fit to his/her body. A clamping device is placed over the patient's diaphragm in order to reduce the "up and down" motion of breathing. And then the patient is placed in a standard linear accelerator, but custom milled lead "beam compensators" are placed in front of the radiation beam (to modify its intensity) for each beam position. This beam position is changed 7 times so that the tumor is hit from 7 different angles. That way, the volume of radiation healthy tissue ends up absorbing is only 1/7th of what the tumor gets, reducing the "collateral damage". There are only 3 treatments which take place over the course of a week, and this is called a HYPOfractionated (low number of sessions) radiation scheme. According to the physicist I spoke to at IU, HYPOfractionation of high dose (3600 cGy in 3 fractions or sessions of 1200 cGy each) radiation will result in better "tumor kill" than HYPERfractionated (high number of sessions) radiation (usually 30+ sessions of low dose radiation, one each day for a few minutes, over the course of a month or more), even if the total dose of radiation delivered by each scheme is the same.

Pictures of Body Frame

Limitations of Stereotactic Radiation at IU

As noted before, it is hard to nail down a precise definition of "Stereotactic Radioablation" because each institution which offers this therapy has its own version and its own definition of patients eligible for therapy. I can only tell you about my experience at IU, other versions of SR may be different and they may accept patients with different characteristics/types of disease. However, the same considerations probably apply to all versions of SR, and the experience I had at IU is somewhat generalizable.

First, there appears to be a limit on the total number of metastases which IU will treat with SR - they told me that they would not accept patients with more than 4 tumors. Of course, it's hard to tell how rigid they are with this policy, and it is very possible that they would consider patients having an extra met or two. Some of the reason for this upper limit may be that there is a lifetime limit of radiation which "can" or "should" be delivered to the body, and I guess they don't want to do too much. Another big part of the reason has to do with what is called "curative intent", which is explained in the following,

Theoretically, if a patient with say one or two liver metastases had IU's version of SR, then that patient could be "cured" with SR, just as he/she could with liver resection. This of course assumes the patient did not have "cancer seeding" elswhere in the liver/body. IU seems to view SR as a "potentially curative" therapy, somewhat similar to surgery. I think that deep down the rad oncs at IU know that most patients receiving SR will not be cured because their disease is systemic rather than local, hence they cannot be cured by any local therapy. But they realize too that a patient with limited metastasis (i.e. with 4 or fewer mets according to their definition) might have added survival time from the procedure, assuming their tumor biology is such that disease recurrence is slow. They think a patient with more widespread disease probably would not benefit from ANY local therapy, and there is thus no point in trying SR (whether that is correct or not is another discussion, but I feel sure from talking to them that that is their belief). So they try to limit the patients they treat to the the ones they believe will have the best chance of benefit from the therapy. After all, there is apparently quite a bit of work that goes into the radiation planning, it has to be done manually as there is no automatic computer generated plan. Plus, a dedicated physicist has to spend a week on each patient's treatment, creating custom lead beam compensators for the linear accelerator. They don't want to do this work for nothing.

EXAMPLE: Consider Abstract 1500 (ASCO 2003) which says

Forty-six patients with a total of 107 metastases from colo-rectal carcinoma were treated with extracranial stereotactic radiotherapy. Thirty-eight patients were treated for liver metastases, 6 patients for lung metastases, 1 for a retroperitoneal lymph node metastasis and 1 for a suprarenal gland metastasis. All patients were considered inoperable...Stereotactic radiotherapy was given by use of 5-8 MLC-shaped fields with a central dose of 45 Gy in 3 fractions over 5-8 days...Local control was observed in 89 metastases (83%). However, due to recurrence outside the irradiated volume, the median time to progression was only 6 months. Seven patients (15%) were without progression at 24 months after treatment. Median survival was 13 months

Now, besides the issue of how many mets you could have treated and still benefit from SR, there is the additional issue of whether or not SR is even possible for a given met. There are certain locations for mets, even within the liver, which IU will refuse to treat. For example, following my first (successful) SR in Feb 2002 to a solitary liver met, I experienced another recurrence of 2 additional mets in the liver. This time, instead of both being deep in the center of the liver, one was right on the surface, next to the small intestine. Since I had a prior liver resection, the small intestine was probably adhered to the liver (they said), and IU would not touch this. According to them, they had treated similar cases in the past which resulted in intestinal perforation. This is entirely consistent with what I have heard regarding radiation beams hitting the small intestine - you don't want to do it. SR is delivered to the tumor at a very high concentrated dose - if that tumor adjoins or is on intestinal tissue, you do not know what the effects might be.

Hypofractionated vs Hyperfractionated Radiation

The above discussion (limitations of SR) assumes a HYPOfractionated radiaton scheme (3 high dose sessions in about a week). There are other cancer centers besides IU which do HYPER fractionated radiation (30+ low dose sessions in over a month). I have heard that some of the centers offering hyperfractionated SR will treat more tumors (maybe up to 9 mets), and/or will treat tumors in locations IU might balk at (such as in the stomach or intestinal area). Hyperfractionated radiation is "easier" on the patient (causes fewer side effects), so this is entirely reasonable. What is not know is the difference in efficacy between hypo and hyper fractionated schemes. If one believes in the general principle of "no pain, no gain", then perhaps hyperfractionation is not as efficacious. The rad oncs at IU strongly believe that - they think both the biological theory and the experience gained in the clinic support hypofractionation (even though there are no clinical trials directly comparing the two). They may be right.

If a patient has abdominal mets, and is offered the opportunity to undergo surgical resection followed by Intraperitoneal Chemotherapy (such as done by Dr. Sugarbaker), they should consider that route as it is probably more efficacious (more likely to result in "cure", but a difficult therapy to recover from). If the surgeons refused to operate, and a hyperfractionated radiation scheme was offered, it might be a good way to at least temporarily halt tumor progression at not too terrible a cost in side effects. And, depending on the tumor location, even if outside the liver or lungs there is always a chance that a center such as IU would still be able to treat the patient with a "more effective" hypofractionated scheme (don't ASSUME anything based on what you read here, ask them yourself!). Of course, each patient must thouroughly discuss each of these options with the appropriate doctors before making any decisions.

Hypofractionated Stereotactic Radioablation vs Radiofrequency Ablation

So, we see a limitation in number of metastases which can be treated with SR, and a further limitation that only mets in the right location can be treated. Similar limitations apply to Radiofrequency Ablation , especially percutaneous RFA. See the link for definitions/different types of RFA, but I'll simply note here that percutaneous RFA is the "easiest" kind of RFA, where they stick the probe directly through the skin into the liver using ultrasound guidence. The other types of RFA are laproscopic and "open surgery" RFA, where they make an incision and "see" the organ before inserting the probe directly into it. Percutaneous RFA, like SR, cannot be done if the met in question is too close to the intestines or other organs, because they will be burnt in the process. Thus, with mets in the liver adjoining the intestine, you would have to use either surgery (wedge resection of liver met) or open surgery RFA (RFA performed during surgery, mets are manually isolated from other tissue before RFA is done). Of course, given that the efficacy of RFA compared to surgery is not known (probably is not as good), in such a situation the surgical approach would likely be preferred.

So - when would one PREFER SR over RFA or surgery (wedge resection)? Well, if you had a small number of mets located deep within the liver, and the patient had already undergone liver resection, then it may be quite difficult for the patient to undergo a second resection. If one or more of these mets are located near a major blood vessel in the liver, then RFA frequently will not work because of something called the Heat Sink Phenomenon, where the blood vessel draws heat from the RFA probe away from the met so that the temperature needed for successful RFA cannot be obtained. SR on the other hand does not have this limitation - it CAN be successfully done on mets regardless of blood vessel location. Therefore, this would be the ideal situation where SR might have a clear advantage over RFA (even open surgery RFA).

An Intelligent Approach - Liver Mets

Trial on Hypofractionated SR for Liver Mets at IU

Taking the above into consideration, it would seem to me that the smartest approach for a patient with a few small liver mets would be to explore whether a surgical approach would be feasable first (either wedge resection of surface mets, or lobe resection for deeper ones). If surgery is not a good idea, next explore if RFA is possible and likely to work (e.g. tumor is not close to blood vessels). Finally, if RFA is unlikely to work explore SR. Because there is a limit to the total amount of radiation you can get, you don't want to use it up unnecessarily (because you might have recurrence in the future which really needs SR!).

An Intelligent Approach - Lung Mets

Simple Things on a Summer Day
Radiotherapy Targets Tumors
Revolutionary Treatment for Inoperable Lung Cancer
Dr. Timmerman's Presentation

At IU, they actually began their SR program by treating lung metastasis (or primary tumors) before they tried it on liver mets - and it appeared to work quite well. But the development of RFA has been exactly the opposite - it was first used on liver mets, and only recently has expanded its application to the lung and other organs (bone, kidney, etc). So, there is much less data on RFA efficacy for lung than for liver tumors, and there are important differences between these two organs. Lung tissue does not regenerate as does liver - so when tissue is cut out or burned, there is always some loss of lung capacity (even if small). It is also possible to have complications such as a lung collapsing during the RFA procedure (especially if the surgeon does not have a lot of experience). Therefore, if surgery is not desired for lung mets (for whatever reason), I personally would probably choose SR over RFA because it is so much easier (less invasive, less complications), and may even be more effective.

Disadvantage of Percutaneous RFA and Hypofractionated SR compared to open surgery

When making decisions between the treatments discussed here, you should always keep in mind that there is a definite disadvantage efficacywise between surgery and SR/percutaneous RFA, which is this:

Diagnostic scans performed prior to any procedure are not always accurate - just because they show nothing does not mean cancer is not there. The absolute best way to know what is going on (in the liver or elsewhere) is for a surgeon to visually inspect the organ in question, and use touch to "feel around" in the abdominal cavity for mets. CT scans are notorious for not picking up disease (especially extrahepatic or extralung), PET scans cannot pick up mets either if they are too small. It is possible that by choosing SR or percutaneous RFA over surgery, that disease will be missed which would have been picked up and resected during the surgical procedure. This could well be a fatal error, as once tumors have grown large enough to detect by scan, the surgeons may refuse to operate. I'm not saying I would ALWAYS choose surgery over SR or RFA (depends on other factors such as location of tumors, difficulty of operation, etc.), but I would always think carefully about the implications before making a decision.

Cancer Politics - Staten Island vs "Other" Cancer Centers

Oncology is one of the most politically charged areas of medicine, and as I noted previously there are many different versions of SR performed by different cancer centers. Of course each one of these claim THEIR way is "the way", and its a bit difficult to sort out who is right among the competing claims.

One of the first cancer centers to perform a version of SR in the United States was Staten Island Hospital , under Dr. Gil Lederman. There has been somewhat of a controversy surrouding Lederman, with accusations of misleading advertising and other "inappropriate" behavior along those lines. For an example of this, consider stories such as Harrison's Mysterious Last Days which appeared following the death of former Beatle George Harrison, who was treated at Staten Island in 2001.

Questions have also been raised by those close to Harrison about the conduct of Staten Island University Hospital's Dr. Gil Lederman, who treated the ex-Beatle last fall. Following Harrison's death, Lederman gave a number of television interviews commenting on Harrison's religious beliefs, personal values and whether he was in pain at the end. "George actually spoke with Dr. Lederman very little," says family friend Gavin de Becker. "But Dr. Lederman mounted a press tour exploiting George in the most shameless way." Lederman did not return calls for comment, but a representative of the New York State Department of Health confirmed that the doctor's statements to the press could be considered misconduct.

Other complaints had been made about the hospital's advertised "success rate" - for example in the following News Article , they say

According to Gil Lederman, M.D., director of radiation oncology at Staten Island University Hospital, "We're now able to attack tumors in the body with precision, divided high dose radiation which we could not get to before. For a variety of tumors, both primary and metastatic, small and large, control rates in excess of 90 percent have been presented and published. In contrast, the success rate of chemotherapy to control these tumors is no greater than 30 percent." The studies had been performed at Karolinska Hospital in Stockholm

Note the studies referred to were performed at Karolinska Hospital - NOT Staten Island. A Radiation Oncologist told me that Lederman has a different form of SR than is performed at Karolinska, which does a HYPOfractionated procedure like IU. I couldn't find any details about that on the SI website, but according to Steve Dunn , "The treatment is usually given as a series of five outpatient sessions spaced anywhere from a day to a week apart depending on the situation". This is apparently not the EXACT same procedure as done at IU (or Karolinska), so is it fair to quote Karolinska efficacy statistics? I dunno. Also, as noted in Abstract 1500 (ASCO 2003) (see above), if progression usually occurs anyway following SR (in a median of 6 months), is it fair to compare "success rate" in controlling a particular met to chemotherapy (i.e. shouldn't you really be comparing the survival times for SR vs chemo?). Just little details here and there which some viewed as "misleading".

Anyway, there do not appear to be any papers by Lederman in a Medline search of Staten and Lederman to indicate efficacy of Body Stereotactic Radiosurgery as used for metastatic cancer (there are some papers about stereotactic radiosurgery for brain tumors and localized prostate cancer, but not use for metastases of other cancers to organs outside their origins). I have no personal experience with Lederman, so I know nothing beyond what is said here. The radiation oncologists of whom I have tried to ask further details would not provide any (cancer politics!), but they did not appear to like him.

Conclusion

As with many things associated with cancer, there is no "right" or "wrong" answer as to which direction a patient should go. Ofentimes, one goes in the direction that one is able to find a doctor who will help! There are advantages and disadvantages to all of the therapies considered here. In a perfect world, you would be able to ask your current doctor to help you make a good decision. Unfortunately, the typical oncologist may not even be aware of what is possible with some of these treatment modalities such as SR. In such cases, the patient/caregiver must themselves explore the treatments, and based on imput from multiple doctors make their own decisions. I hope that this page gives you a starting point for that exploration.

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