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European Questions About Vestibular Schwannomas In many countries now there are groups of patients who were treated at Staten Island University Hospital for acoustic neuromas or vestibular schwannomas who are forming social groups. Several recently asked a series of questions from a group in the United Kingdom about treatment options and results. An acoustic neuroma is a benign tumor of the 8th cranial nerve. This is a delicate nerve from the brainstem responsible for hearing and balance. The tumor seems to be increasing in its frequency of diagnosis. Yet, it is still an uncommon disease with an estimated 2000 Americans diagnosed each year. In some countries, there are very few patients diagnosed while in others the frequency seems great. This is likely due to access of patient care and the availability of contrast-enhanced MRI's. The most common early symptoms of acoustic neuromas or vestibular schwannomas are hearing loss, which is often unilateral. Often patients have ringing sounds or tinnitus in the ear. This is most often unilateral. Other symptoms include a full feeling in the ear and sometimes imbalance, dizziness or years of awkwardness. Many people aren't diagnosed for years after the development of symptoms. At the time of actual diagnosis, a great proportion recall having symptoms that have been a decade or two long. For many patients the typical route is to be seen by an ear specialist who subsequently orders an MRI or nuclear magnetic tests with contrast enhancement. Often a small lesion is seen in the intracanicular area, which leads to the internal portion of the ear. Another location that is common for acoustic neuromas is what is called the CP angle, or cerebellar pontine angle. This is a site near the brain stem where the delicate nerve leaves the brain to travel to the inner ear. Since approximately 1895, surgery had been a mainstay for this disease. From 1969, stereotactic radiation has been used. The success rate even in patients treated decades ago with stereotactic radiation remains high. In early years, this treatment remained a rarity. Recently, I was in Israel giving a lecture to a group of acoustic neuroma patients and their families and met a man who was treated with radiosurgery in the early 1970's. He has had good control of his tumor but because of the limited technology available then as well as a paucity of dose data, he had some damage to the facial nerve. In our hands, this is essentially never seen. What is so special about our approach at Staten Island University Hospital is that we perform fractionated radiosurgery, which means the dose is divided and also we use biologically the lowest dose worldwide. The questions brought forth from English patients and potential patients are interesting in their scope of knowledge about the disease and the treatment. Different treatment methods asked about include gamma knife (single fraction treatment), fractionated radiosurgery, single shot radiosurgery using Linear accelerator and proton beam. Of course there are surgical options and watchful waiting. Some people choose to have no treatment and this was especially true when surgery was the only option. Now as fractionated radiosurgery is gaining hold and the data is compelling, with in general a minimum of side effects and great benefits, many patients are selecting this method. There are other differences in that single fraction uses a screw on head frame. This is usually considered quite uncomfortable and most often patients get medicated with anesthetics or sedatives and sometimes even Decadron. Usually the patient says overnight in the hospital. Single fraction therapy doesn't allow for the benefits of fractionation - which are considerable. This is in marked distinction to fractionated radiosurgery where there is a non-invasive re-locatable head frame. Where patients come in, get treatment and go about their business. Many patients come here and say that our treatment is a" treat" and not a "treatment." Yet the success rate is very, very high with the vast majority never needing any further treatment and also maintaining hearing at the same level that they came in with or better. Currently, the overall control rate is 99% - meaning no further treatment is used. There are different approaches in different facilities. Each doctor may prescribe dose differently, at a different point and at a different isocenter and therefore what may seem to be similar doses may be markedly different doses. For example, gamma knife people often prescribe their dose at the fifty percent line which means the inside dose is very hot, double the dose in fact in the interior. With our program, there is a much more homogeneous dose. We believe that a homogeneous dose is more likely to lead to better results since the degree of hot spot is markedly less and therefore it is much less likely to harm the delicate eight nerve which is so crucial for balance and hearing and as well as for other nerves such as the fifth and seventh which are responsible for facial sensation and function. Their approach has been to lower the prescribed dose from what it was in the past. Also there are differences in head frame systems with invasive and non-invasive frames. There are a variety of non-invasive frames including those that use dental and occipital fixation and those that do not. Also there are systems that don't confirm the positioning of the re-locatable frame. We confirm in nearly two-dozen positions each time we use the frame. This allows us to be highly confident of the accuracy while maintaining the flexibility and the benefits of fractionation, which have been known for nearly eight decades. I am well aware of systems in many other facilities that don't perform daily measurement of the patient in treatment position. There are differences in fractionation programs. Our data shows if larger fraction size (500 rad fractions) is given the likelihood of hearing falls. There is statistical analysis confirming this fact. Furthermore, if we fractionate on alternate days versus consecutive days we have better hearing. For other centers that give higher doses on consecutive days with a higher total dose, the likelihood of hearing preservation will falter and the likelihood of harm to the surrounding nerves will increase. We are opposed to higher doses based on our high success rates - utilizing low dose treatment. With our high success rate we see no reason to give higher doses, in fact we see many reasons not to give higher does which may lead to serious adverse effects to the patient. In the treatment of tumors giving the correct dose leads to good outcome. Giving higher dose gives the patient risks without obvious benefits. Gamma knife system in general is markedly different because size of collimator is limited by the technology, whereas we have a vast array of collimator or beam sizes. In general the gamma knife people may use multiple overlapping fields, whereas we are very reluctant to use overlapping fields. Overlapping fields tend to create even higher hot spots than I discussed previously about isodose lines. If single fraction people cut the dose too closely it means there are cold spots and cold spots allow for tumor recurrence. If they treat too great an area, there is a likely increased risk to surrounding healthy tissues. Also in exchange for this great precision is the pain of the head frame, often medication and hospitalization associated with the head frame. We believe that we can properly and precisely treat the tumor, avoid harm to healthy tissues while giving the lowest actual dose to patients with acoustic neuromas and we have proof of hundreds of patients in this regard. Furthermore we have the flexibility of treating small as well as large tumors. Our group has the largest experience of treating larger acoustic neuromas - again with this fractionated approach. About radiation causing second malignancies - the only second malignancies that have been reported in the literature after radiosurgery that was single fraction. It is likely that the higher biological dose of radiation, the higher likelihood of malignant induction. We know that there is radiation repair with fractionation. The likelihood of repair falters precipitously with single fraction therapy. Fractionation likely helps avoid malignancies. Another possible factor that helps avoid malignancies is giving a lower dose. By giving the lowest dose feasible, fractionating and using radiosurgery techniques I believe that the likelihood of second malignancy will be kept to the lowest possible number. About gamma knife treatment in its present form - it is in fact not true that its dose has been around for a longer period of time. Gamma knife recently was treating patients at the 1800 and 2000 rad range - each center and physician is unique, of course. They have reduced the dose due to untoward side effects and because our low dose fractionation program has shown that we can give a lower dose, break up the dose, avoid the pain of the head frame and have a high degree of success and a higher degree of hearing preservation. If you look at hearing at any level with single fraction it is approximately fifty percent yet with our fractionated program hearing at the same or better level is approximately ninety percent. Thus the hearing appears better with our low dose fractionated program than with gamma knife. Also because we have continued to deliver the same dose for nearly ten years we have more data at the same dose for a longer period of time than most other centers. Furthermore, if one evaluates facial or trigeminal nerve damage, the likelihood of that occurring with single fraction technology is greater than with fractionated stereotactic radiosurgery in our hands. Again the reason is the low dose and the fractionation. If one simply looks at a major American clinic with single fraction experience from the early 90's, they had sixty percent facial nerve damage and sixty percent trigeminal nerve damage with overall eighty percent of their patients being treated for acoustic neuromas having facial and/or trigeminal nerve damage. This gives tremendous reassurance for patients undergoing fractionated stereotactic radiosurgery at Staten Island University Hospital. We have the largest experience worldwide for fractionated radiosurgery of acoustic tumors. We have more patients treated over a longer period of time than anyone else using fractionated technique. In conclusion, do I believe that there is a best method of treatment? Yes. Personally I believe that radiosurgery technique is very important. I believe that fractionation is important to maintain the best outcome for the facial, trigeminal and auditory nerve as well as the associated brain stem. I believe that the benefit is great both in terms of local comfort at the time of treatment and down the road hearing preservation. I, in fact, have doctors who perform single fraction therapy sending me their difficult patients or patients with only one hearing ear to have the highest likelihood of maintaining hearing. These doctors know that when hearing depends on one nerve the patient is much better served by fractionation. I extrapolate this argument to state that all patients should have as much hearing, whether one or two eared, as possible to maintain quality of life and avoid undesired adverse effects. Hearing Preservations In Patients With Acoustic Neuromas Acoustic neuromas are benign tumors that affect the crucial 8th cranial nerve responsible for hearing and balance. Patients with acoustic neuromas often, as a first symptom, detect change in hearing or balance. This often leads to doctors visits and, eventually, hearing tests and MRI's (nuclear magnetic scans) with gadolinium enhancement to evaluate this delicate 8th cranial nerve. It is 5th and 7th nerves off the brain stem, located adjacent to other delicate nerve that is responsible for movement and sensation in the face. Other names for most commonly affected adjacent nerves are the 5th (Trigeminal) and 7th (facial). While in the past surgery was often used today there are now competing and I believe much more appealing methods of treatment for those diagnosed with new or recurrent acoustic neuromas. These tumors are essentially always benign or non-cancerous. Hypo-fractionated stereotactic radiosurgery has been pioneered over this decade at Staten Island University Hospital. This is a method of giving low dose pinpointed radiation utilizing sophisticated radiosurgery techniques to the tumor in an attempt to avoid harm to healthy normal tissue while effectively testing the tumor. Other hospitals commonly use high or higher doses of radiation which are associated with a higher degree of harm to these delicate nerves. Our group start at a very low dose using a non-invasive headframe and divided dose into four or five treatments. The purpose of dividing the dose is to help maintain normal tissue function and to minimize toxicity of treatment. One great beauty of our program is that patients have received the same fractionated total radiosurgery dose. Radiation oncologists have known for 80 years that dividing radiation dose into fractions is likely to produce better results and less harm to healthy tissues than a large single fraction or even large multiple fractions. That's why radiation is routinely divided in dose for most all patients elsewhere in the body. Thus, the rationale of starting this unique program was to have effective yet safe control of the tumor while avoiding harm to healthy tissues. Our data has been presented at national and international meetings - most recently the German Acoustic Neuroma Association in Magdeburg. While our initial treatments were carried out on alternate or more days, there is some biological principles to suggest consecutive day treatment would be equivalent. Initially, patients with tumors greater than 3cm were treated with 400 rad times 5 treatments and patients with tumors 3cm or less were treated with 500 rad times 4 treatments on alternate or greater number of days. Thus, all patients received 2000 rad or centigray. Rad or centigray are equivalent measurements of radiation dose. Because of the success of the program and radio-biological principles that would suggest consecutive day treatment should be equivalent as well as in certain instances patients' preference, some patients were treated on sequential days. Now having the largest experience using fractionated radiosurgery world-wide for acoustic neuromas with over 300 patients treated, we have had years to follow the patients and have analyzed the hearing preservation rates based upon four groups. Those received 500 rad times 4 on consecutive days, those receiving 500 rad times 4 on alternate or more days, those receiving 400 rad times 5 on consecutive days and those receiving 400 rad times 5 on alternate or more days. Overall the vast majority of patients - 99% have had effective control of the tumor - meaning no further treatment for the tumor was needed or recommended. Of interest, however, is the difference in hearing preservation based upon treatment schedule. Those patients who receive 400 rad times 5 on alternate or more days had the best hearing preservation rate. Ninety-four percent (94%) of these patients maintained or improved the hearing based upon baseline hearing tests performed at the time of treatment. This is true regardless of tumor size. We are not speaking only about any hearing, but rather maintained level of hearing. When 500 rad times 4 was given on alternate or more days, 82% maintained hearing. In those patients being treated on consecutive days with 400 rad times 5, 75% maintained hearing. While in the group receiving 500 rad times 4 on consecutive days, 69% maintained hearing. Furthermore, the group that had the best hearing preservation rate (94%) treated with 400 rad times 5 also had the longest follow-up with a mean of 41 months. Hearing improvement also is an important issue. When 500 rad times 4 is given on consecutive days 6% had improvement; 500 rad times 4 on alternative days yields 9% improved hearing. 400 rad times 5 on consecutive days gives 25% improvement compared to the 400 rad times 5 on alternative days who had 20% hearing improvement. This would suggest that not only did the group truly maintain (with many actually having documented improved hearing) their hearing to a greater degree, they also maintained it years after treatment suggesting that they most likely will continue to maintain hearing at a high degree. Also crucial is the follow-up. The 400 rad times 5 on alternative days or more treatment had the longest mean follow-up of 41 months. Four hundred rad times 5 on consecutive days had 26 months mean follow-up. 500 rad times 4 on alternative days had 38 months mean follow-up, while the 500 rad on consecutive days had 24 months mean follow-up. Additionally, statistical analysis was performed and showed that the patients who received 400 rad times 5 on alternate or more days compared to all other groups had statistically improved hearing than the other groups. When statistical analysis was performed, a P value of 0.03 was produced. This means that results truly were superior and not related to some other extraneous factor. This data is very important in guiding patients with acoustic neuromas. I personally recommend alternate or more day treatments for all patients seeking care at Staten Island University Hospital. I believe that consecutive day treatment or higher dose treatment is fraught with danger of decreased hearing rates. The danger being loss of hearing. All groups at Staten Island University Hospital have had high tumor control rate regardless of treatment schedule. Furthermore, the largest tumors were in the 400 rad times 5 on alternate days - measuring a median of 2.6cm. This compared to the group of 400 x5 on consecutive days measuring 2.55cm. 500 rad times 4 on consecutive day treatment measured 1.0cm and those getting 500 rad times 4 on alternative or more day measured 1.5cm. Thus, even people with larger tumors can benefit from this approach. Seeing hundreds of patients in follow-up having had acoustic neuroma treatment makes one sensitive to a variety of issues. A most important issue in addition to successful tumor control is quality of life most often meaning hearing preservation, balance and facial function. Currently 99+% maintained facial and trigeminal nerve function meaning the face moves normally and has normal sensation when starting out in that regard. Of interest, we have patients who have improved facial as well as hearing function after fractionated radiosurgery. Our data has been presented at national and international meetings. This hearing preservation data will continue to be updated. Based upon the significant follow-up of these groups, I believe that time will only show the increased importance of dose and fractionations schedule when delivering effective radiosurgery for those with acoustic neuromas. Those are crucial issues to those with acoustic neuroma and their loved ones to discuss prior to any treatment decision. Unfortunately most patients undergoing surgery for acoustic neuromas lose all hearing - a marked contrast. At this time high dose single shot radiosurgery or high dose fractionated radiosurgery over short periods of times may be placing the patients neurologic function in jeopardy. I see little reason for higher dose and faster treatment. Results years later suggest our fractionated low-dose approach has great appeal. We will continue to follow our data and patients to confirm these results over years to come. The Largest Series of FSR for AN Patients Worldwide In seven years of fractionated radiosurgery our data has been presented at national meetings, has been published and serves as an inspiration for many patients and other medical centers. Currently we have treated two hundred patients with acoustic neuromas. The beauty of fractionation is that it diminishes side affects while maintaining excellent control rates for these benign tumors affecting the eighth cranial nerve. Most patients with acoustic neuromas have symptoms such as decreased hearing, tinnitus or buzzing in the ears, as well as headaches and imbalance. Other patients have other symptoms that may indicate progression with adjacent delicate tissues being adversely afflicted. Recently the Johns Hopkins group has put out their data for treatment of thirty-two patients with a minimum six-month follow-up. They treated patients with 500 rad, times five on five consecutive days. Rad is a measurement of radiation dose. Tumors with more than 5.5cc (cubic centimeters) in volume received 300 rad daily, times 10 over two weeks. The mean tumor volume was 1.6cc in their report. Tumors ranged from 0.1 to 12.4cc. While twenty-eight patients had no prior treatment, four were prior surgical failures and subsequently underwent radiosurgery. One patient had neurofibromatosis and had treatment to both tumors. Whether the treatment was simultaneous or sequential was not defined. The follow-up was 17 months mean. All tumors were successfully controlled with ten smaller and twenty-three unchanged in size. One patient died of unrelated causes. No patient had facial weakness but two patients developed a new trigeminal neuropathy. This trigeminal neuropathy occurred three months after treatment in one patient and twenty-four months after treatment in the second patient. Seventy-five percent of patients were said to have useful hearing after radiosurgery. The authors concluded that "short course daily fractionated stereotactic radiotherapy for acoustic neuromas results in acceptable toxicity and may provide high control of tumors. Longer follow up is needed to assess outcomes." Since our Staten Island University Hospital group has been performing radiosurgery, now in its seventh year, we do indeed have longer follow-up. The beauty of our program is that we have used a lower dose. Our total dose for all tumors is 2000 rad compared to the Hopkins dose of 2500 rad for small tumors and 3000 rad for larger tumors. We believe it is not necessary to administer a higher dose - especially since our control rate is so favorable. Higher than necessary doses could increase the complication rate. Furthermore that two Johns Hopkins patients have developed trigeminal neuropathy at this short period of follow up would suggest that most likely other patients at Johns Hopkins will develop this neuropathy since the mean follow up is only seventeen months and one patient developed neuropathy twenty-four months after treatment. That six percent of patients have developed trigeminal neuropathy at such a short period of time would suggest that others will likely develop neuropathies. I personally believe this is due to the dose of radiation. The Hopkins group is giving at least a 25% higher dose than the Staten Island University Hospital group for small tumors and for larger tumors it is giving 50% greater dose albeit in ten fractions. That we have currently treated nearly two hundred patients and have had no treatment failures would suggest that the dose of 2000 rad is most likely adequate especially in terms of the longer follow up and less toxicity compared to Johns Hopkins. The trend of acoustic neuroma radiosurgery over the last decade has been in reducing treatment doses. Many centers using high doses have experienced marked toxicity. For example; the Foote et al described the Mayo Clinic experience where nearly 60% of patients had trigeminal neuropathy and 60% had facial neuropathy. We know that by cutting down the dose Gamma Knife radiation doctors can reduce the incidence of complications yet not to the low likelihood as seen with fractionation at Staten Island University Hospital. This is especially notable since we have treated tumors up to 32 cubic centimeters in volume. Personally I believe that excessive radiation dose especially in a greater number of patients treated over longer period of time will lead to little benefit to the patient compared to our work. At one point prior to instituting fractionated radiosurgery at Staten Island University Hospital I contemplated raising the dose slowly over time. The reason that it was not raised was that the treatment results were so good - very high control rates with minimal side effects. The vast majority of our patients have maintained or some actually have improved their hearing. My interpretation of the Johns Hopkins data is that the dose is too high. It should be cut down to maximize benefits. I would encourage them in following the Staten Island University Hospital footsteps which currently has the largest series of fractionated radiosurgery for acoustic neuroma patients worldwide.
G. Lederman, J.Lowry, S. Wertheim, M. Fine, M. Raden, P. Silverman, E. Lombardi, G. Qian , S. Pannullo, E. Arbit.
Radiation Onc. Dept., Radiology Dept., Neurosurgical Onc. Dept., Staten Island University Hospital, S.I., NY
Purpose: FSR offers the advantage of divided dose treatment with the precision of stereotactic radiosurgery for AN via the Gill-Thomas-Cosman relocatable head frame. FSR should result in superior outcome because of radiobiologic repair of normal surrounding structures while maintaining efficacy of treatment. Materials and Methods: Described are 195 patients (pts) aged 13-88 years (mean 54) with 201 AN ranging in volume from 0.1-33.0cc (mean 4.8). 151 AN had maximum diameters 3cms (range 0.1-2.8, mean 1.5) and 50 measured 3cms or greater (range 3.0-5.8, mean 3.7). 2000 Centigray (cGy) divided in 4 or 5 fractions was delivered utilizing stereotactic radiosurgery technique. Tumors larger than 3cm have 5 fraction FSR. Results: Clinical follow-up was 3-79 mos (median 25). AN less than 3cms had clinical follow up of 3-79 mos (median 24) with 41 AN (28%) decreasing in size, 106 (70%) showing cessation of growth and 4 (2%) increasing in size. Of 101 with pure tone audiometry, 10 (10%) improved, 70 (69%) remained stable and 21 (21%) worsened. One elderly pt with uncontrolled hypertension had transient facial weakness, which resolved. Of 77 pts, 43 (56%) had improved balance and 34 (44%) stable. Clinical follow-up for 50 AN 3cms or greater was 5-78 mos (median 30). 60% decreased in size. The remainder showed cessation of growth. Of 29 pts with follow-up audiometry 7 (24%) improved, 21 (73%) were stable and 1 (3%) worsened. Of 31 symptomatic pts, 21 (68%) had improved balance and 9 (29%) were stable and 1 (3%) worsened. No pt had surgery for treatment failure. Conclusion: FSR is an effective treatment for pts with AN either less than or greater than 3cms in maximum diameter. The vast majority of pts after FSR maintain hearing, avoid facial or trigeminal neuropathy and remain in remission years after treatment.
ACOUSTIC NEUROMA RISKS OF TREATMENT
by: Gil Lederman, M.D.
Surgery has been used since 1895 for treatment of a benign brain tumor called acoustic neuroma. This is a tumor that is nearly always benign arising from a delicate little nerve that runs to the ear from the brain stem. The nerve�s position and function make symptoms like hearing loss, imbalance and ringing especially frequent. Surgery has such a long track record that its risks and benefits are so well known.
Most patients undergoing surgery become deaf in the treated ear and many have facial paralysis. Many have other complications including spinal fluid leak, bleeding in the brain and other neurologic adverse events.
Competing treatment is radiosurgery - where beams of pinpoint radiation converge on the tumor. Usually, the tumors stop growing and then slowly shrink with time. Some surgeons like to remind acoustic neuroma patients that there will be a shadow remaining on MRI scans after successful radiosurgery. Often not spoken is the fact that this dormant or receding shadow is usually of no consequence and allows the patient to live quite normally and quite fully compared to surgery with after effects.
Some suggest possibility of cancers induced by radiosurgery although there have been no definitive reports after 150,000 patients with a variety of diseases - most with benign conditions - having been treated world-wide. Rumors of a few cases persist, yet in numbers to be considered, nearly zero. Some researchers in the field believe that eventually about 0.1% may develop a malignancy in the treated field although even this number hasn�t been manifested.
A seldom-discussed point is the mortality or death rate. Major centers report about one-half to 1% of acoustic neuroma patients undergoing surgery succumb to the effects of surgery. This number seems small and distant - however, at times it is quite palpable and painful.
This week a colleague came to me to describe a 42 year old Massachusetts Institute of Technology trained Ph.D. married father of three who traveled to a major American institution on the West Coast for acoustic neuroma surgery.
The man had neurofibromatosis II, a disease that had affected both nerves. His prior surgery had apparently left him deaf in one ear and the progressive opposite tumor left him nearly deaf in the second ear. Yet, he was very functional and worked at a high tech firm in New Jersey. Now several weeks after the Bas Mitzvah (a religious confirmation) of his child he returned to the scene of the prior surgery for a second acoustic neuroma resection. The man seemed to be active and fully involved at this happy event. By report, the patient had surgery and shortly thereafter began bleeding in the brain. He lost consciousness and became comatose dying about five days later.
The pain obviously is great even to an acquaintance who knew this man not closely since he had recently moved to the man�s neighborhood. The patient having lost nearly all his hearing had difficulty acquiring new friends.
Several years ago, another man called me up at home having heard about fractionated radiosurgery and the results. He said he was very intrigued but as the surgical resection was scheduled for the next day, he felt embarrassed to cancel the operation. He related that he had established a relationship with the surgeon and "couldn�t let the surgeon down."
About ten days later I found his name and phone number on my dresser and decided to call back to see how the surgery had gone. A woman answered the phone at home and identified herself as the patient�s wife. When asked about the outcome she replied that "he had died on the operating table."
These kinds of events to me drive home the revolution that is going on in the treatment of acoustic neuromas and indeed many brain tumors. Many with brain and indeed, tumors of other parts of the body that I see choose non-invasive approaches over older operations. One patient recently reminded me how he, about thirteen years ago, had undergone an open removal of his gallbladder when a neighbor shortly thereafter had a laparoscopic cholecystectomy - having the gallbladder removed through small incisions with high tech approach.
After convalescing for months he compared himself to his neighbor who went back to work the next day. Only then did he decide to approach his newly diagnosed brain tumor in a less invasive fashion than historically one might have predicted.
What is the basis for this confidence in non-invasive treatment of acoustic neuromas? Our group has now treated 177 people with acoustic neuromas. We have the largest series of fractionated radiosurgery worldwide and indeed the longest group continually treated at the same dose of radiation.
While many other centers are lowering their dose in an attempt to match our results, it is doubtful based upon current information they will get to that point. In the ultimate form of flattery, a major researcher using gamma knife is switching over to a similar method of fractionation that we pioneered at Staten Island University Hospital.
We have treated both small (less than 3cm) as well as larger than 3cm acoustic neuromas using fractionated or divided radiation dose. Small tumors have been treated using 500 rad daily for four days while larger tumors received a 400 rad dose over five treatment days. Rad is a dose of radiation absorbed.
Specially designed techniques at our institution are made to minimize the dose to brain stem. This fractionation schema from a biological point is quite low especially compared to single shot radiosurgery (for example Gamma knife style) which uses 1200 to 2000 rad - more commonly lower doses in this era.
Other centers are using a protracted fractionation scheme over about six weeks consisting of 5400 rad.
We see no reason for the extensive period or the higher dose of radiation exposure.
At this time no patient has required surgery or radiosurgery for failure. One patient had a transient facial weakness, which resolved. Several patients have improved facial function, having come to us with weakness prior to radiosurgery and regained strength after fractionated treatment.
Compared to surgery where about 85% of the patients are deaf after treatment, in our hands 85% have maintained or actually improved hearing. We have a documented improved hearing rate of 15%.
There are many reasons for us to be optimistic about treatment of patients with acoustic neuromas. Patients are followed diligently with hearing tests and gadolinium enhanced MRI�s. Data managers as well as physicians track the outcome of patients and compare results to other major centers.
Our data is presented at national and international meetings and as well published, most recently in letterform in the April 8, 1999 New England Journal of Medicine. There we compared our outcome to the Gamma knife experience where 31% of patients were unable to work after treatment. Nearly 20% of their patients had combined surgery and Gamma knife radiation as a combined initial treatment strategy compared to our approach avoiding invasive surgical resection in 100% of patients. We mean the avoidance of surgery both before radiosurgery as well as after. No patient has received invasive surgery for resection of the acoustic neuroma at any time.
Also, because there are no pins in the head, no patient receives medication, sedation or hospitalization for this fractionated out patient therapy. Each of the four or five treatments takes about 20 minutes and patients carry on their normal activities throughout this treatment course.
There can be fluctuation in symptoms, which are well known to patients with acoustic neuromas. Many report alteration in the level of hearing, tinnitus, balance, aches and pains. These symptoms, in general, subside after treatment. Most patients - about 75% - tell us their balance is subjectively better and many report similarly on other symptoms.
Fortunately for patients newly diagnosed with acoustic neuroma there is much work to evaluate. Options that just a decade ago was totally unknown today seem most appealing. We believe our strategy will be one that will be the standard of care in the next century based upon work and diligent follow-up of these fractional radiosurgery treated patients at Staten Island University Hospital. Other facilities worldwide are following our approach.
What makes our experience so remarkable? Fractionation allows normal healthy tissues like the brain stem, fifth or trigeminal in the seventh or facial nerve to repair the radiation effects. Single shot radiosurgery, which administers the entire dose in one maximal impact, doesn�t allow for radiation repair.
Fractionation has been well known throughout this century and is the reason that radiation elsewhere in the body, for example, tumors of the breast, lung, prostate and other sites receive divided dose treatment rather than the single knock out blow. The rationale is simply fractionation allows for normal tissue repair. The other pillar in our program is the low dose and the experience with great number of patients over a relatively long period. Technical expertise is crucial, as we have performed more than 15,000 radiosurgery.
Postscript: The surgeon responsible for the death of the 42 year old M.I.T. graduate just told another prospective acoustic neuroma patient - as related by the patient that the death did occur, but was due to the patient being blind and comatose at the time of surgery. Remarkable, since those who saw this man a few days before at his synagogue noted he was neither blind nor comatose. The most severe complication - death - at acoustic neuroma surgery and the surgeons� failure to recognize, minimize and inform subsequent patients, will ultimately condemn acoustic neuroma surgery to the footnotes of medical history. Surgery has had its day.
FRACTIONATED STREREOTACTIC RADIOSURGERY FOR ACOUSTIC NEUROMAS
The following was written by Dr. Lederman in response to a patient inquiry.
Thank you for the letters. There are many points that need to be clarified--there seems to be a great lack of information about fractionated strereotactic radiosurgery for acoustic neuromas. Indeed, our experience is the largest (170 plus patients) worldwide. And we have kept the same dose over the 7 years. Gamma knife professionals established the technique for acoustic neuromas 30 years ago. In recent years they have altered the dose especially to decrease the toxicity. The reported data shows control rates of 90 plus percent even years later. To the best of my knowledge we have the only dedicated study for large acoustic neuromas greater than 3 cms. We also have the identical results to the small acoustic neuroma group (less than 3 cms tumors). In fact, it is these people with larger tumors that suffer at greater rates. Regrettably known by post-operative acoustic neuroma patients are complications such as no hearing preservation, exceptionally high rates of facial damage as well as the other complications. There is a very strong basis for fractionation--so strong that nearly all radiation in the world is fractionated--whether for the breast, lung, pancreas, prostate, bladder and more. There is essentially no site excluded from fractionation. So what is different about the approach for treatment of acoustic neuromas? A screw on head frame was developed years ago. When placed it was accurate, but quite uncomfortable--to the point a person was feeling more concerned about getting the frame off rather than the benefit of fractionation. As expected the development of an accurate noninvasive head frame negated much of this old approach to radiosurgery. Suddenly, consideration of the critical surrounding tissues-like brainstem, fifth, seventh and eighth cranial nerve can be protected not only by the accuracy of radiosurgery, but also by the known benefits of fractionation. Fractionation is not new to radiation biologists--this data dates back to the turn of the century. In our experience, 85 percent have maintained or improved hearing and most coming with imbalance reporting improvement. A single transient facial weakness in an 80 year old patient with uncontrolled high blood pressure (the symptoms resolving spontaneously) not requiring surgery or repeat radiation or radiosurgery of any kind was reported. Patients are living their lives and doing what they want. This is in marked contrast to those going through surgery and at least in some degree to those having gamma knife treatment. The report from Pittsburgh noted that 31 percent of gamma knife patients could not work after gamma knife surgery. This would suggest a marked alteration in quality of life. Of course, one might say lowering the dose of gamma knife might help. Only time will tell. Our data appears to be superior, collected over a longer time than the current gamma knife data. Avoid the pain of the headframe and its associated medication, and frequently required hospital stays. Four or 5 treatments for small as well as large acoustic neuromas each just over 30 minutes as an outpatient without any medication is a small price to pay. Patients come here because of our data, the quality of life, and the chances of maintaining quality over the years to come. Randomized studies would not be done because the difference in outcome would preclude intelligent people from having their treatment based upon a roll of the dice. Penicillin did not require randomized studies in the 1940s. Must more be subjected to old treatment to prove a point? I doubt if any randomized study would gather patients. Honestly, informed people are able to evaluate the data if given the opportunity. Our data was published in letterform in the New England Journal of Medicine on April 8th, 1999. Some try to place fear rather than fact in the minds of those concerned about acoustic neuroma patients. If a shadow exists on an MRI scan, why would one be concerned? Many patients have been treated with radiosurgery for benign conditions over decades that have not produced a malignancy in the treated field. Clinical and radiographic evaluation have shown high success control. So, why do some continue these baseless tactics? An issue seldom discussed is treatment mortality, but I do since the pain is so fresh in my ears. Just today, I was told a 42 year old MIT trained Ph.D. married with 3 children underwent surgery for resection of an acoustic neuroma at an American institution known for its surgical skill who died after the resection. Apparently surgery was done 5 days ago; within hours bleeding within the brain started and couldn't be controlled. The man became comatose and died 4 days later. This man and others cannot speak, but we should learn the lesson. In my eyes, this was most probably a tragedy that could have been avoided like other deaths, and all the disabilities that have afflicted those with acoustic neuromas that died after the resection.
Sincerely yours,
New England Journal of Medicine, Vol 340, pgs 1119-1120, 1999 The following was written in response to Long Term Outcomes After Radiosurgery for Acoustic Neuromas, New England Journal of Medicine, Vol 339, pgs 1426-1433,1998 Dear Editor, While radiosurgery has made great strides, not discussed by Kondziolka et al1 was how single fraction Gamma Knife (GK) radiosurgery (radiation delivered in one dose) compares to fractionated treatment. Historically, radiation has been divided in dose to minimize normal tissue damage. Fractionated stereotactic radiosurgery for acoustic neuromas using the same dose since inception over five years ago, for all sized neuromas - 0.1 to 32cc in volume and up to 5cm in maximum diameter andincluding neurofibromatosis II (NFII) patients appears superior.2,3,4 Despite larger and NFII tumors, in 142 patients the facial and trigeminal preservation rate is 100% and 86% maintained hearing. One patient had a resolved facial weakness. None had worsening facial function. With fractionated radiosurgery a non-invasive head frame avoids the need for skull pins, anesthesia, sedation and hospitalization.5 In comparison, GK results in 49% of patients with hearing loss, 21% facial neuropathy and 27% trigeminal nerve damage.1 Thirty-one percent of GK patients became unemployed after radiosurgery. Not surprising is that those who developed facial or trigeminal neuropathy might indeed suffer. Kondziolka et al reports 18% of GK patients having craniotomy followed by radiosurgery for primary treatment. This two-step strategy will have greater morbidity but make subsequent single fraction radiosurgery appear safer since patients will likely have surgically-induced neurologic deficits like hearing loss and facial neuropathy prior to radiosurgery. Our group has never advocated nor performed debulking surgery prior to radiosurgery. This minimizes intervention, cost, morbidity and possibly mortality. Fractionated radiosurgery appears to offer superior tumor control and neurologic outcome including maintaining hearing, facial and trigeminal function and avoiding pre-or-post radiosurgery craniotomy. It can be economically implemented worldwide. Sincerely yours,
J. Lowry, MD
References: 1 Kondziolka, D., Lunsford, L.D., McLaughlin, M., Flickinger, J. Long-Term Outcomes after Radiosurgery for Acoustic Neuromas. N.Engl.J.Med. 339:1426-1433; 1998.2 Lederman, G., Lowry, J., Wertheim, S., Fine, M., Lombardi, E., Wronski, M., Arbit, E. Acoustic Neuroma: Potential Benefits of Fractionated Stereotactic Radiosurgery. Stereotactc Funct Neurosurg. 69; 175-182, 19973 Lederman, G., Wertheim, S., Lowry, J. Rashid, H., Silverman, P., Qian, G., Lombardi, E., Wronski, M., Arbit, E. Acoustic Neuromas Treated by Fractionated Stereotactic Radiotherapy. In Kondziolka, D., ed., Radiosurgery. Basel, Karger, 1998. 2: 25-30.4 Rashid, H., Lowry, J., Wertheim, S., Fine, M., Silverman, P., Lombardi, E., Qian, G., Arbit, E., Lederman, G. Improved Results for Acoustic Neuroma Treated with Fractioanted Stereotactic Radiosurgery. Int J. Radiat Oncol Biol Phys. 42;1 suppl, 1998.5 Gill S., Thomas, D., Warrington A., Brado, M. Relocatable frame from stereotactic external beam radiotherapy. Int J. Radiat Oncol Biol Phys.30;599-603; 1991.
Kondziolka D (ed): Radiosurgery 1997 Radiosurgery, Basel, Karger, 1998, vol.2, pp 25-30
G. S. Lederman, S. Wertheim, J. Lowry, H. Rashid, P. Silverman, Guo-Xin Qian, E. Lombardi, M. Wronski, E. Arbit
Departments of Radiation Oncology, Radiology and Neuro-Oncological Surgery It is estimated that over five thousand patients with acoustic neuromas have been treated worldwide with stereotactic radiosurgery as of 1997. The majority have been treated by single fraction utilizing the Gamma knife. , The results and the follow up of patients indicate that treatment with stereotactic radiosurgery is an effective means to control acoustic neuroma growth and as such has established itself as a viable alternative to microsurgery. While serious morbidity for radiosurgery is exceptionally rare, cranial neuropathies affecting the facial nerve, trigeminal nerve and the cochleovestibular nerve were common. Treatment modifications including reduction in radiation dose and increase of isocenters for a better conformity between isodose and tumor have decreased the incidence of complications. Because at Staten Island University Hospital both LINAC based stereotactic radiosurgery and the relocatable head frame are used (which allow the use of fractionated stereotactic radiation), a study has been undertaken to define the role of fractionation on both tumor control and complications. Material and Methods: Thirty-three patients, with an age range of 35 to 89 years (mean 60), with thirty-four acoustic neuromas were treated between November, 1993 and December, 1995. Tumor volumes ranged from 0.1 to 32 cubic centimeters (cc) (mean, 7.8 cc). Treatment planning was carried out using GE-9800 Quick Scanner with contrast-enhanced CT fine cuts through the area of interest. The relocatable Gill-Thomas-Cosman head frame was fitted individually with custom dental and occipital plates. The head frame position was verified before each treatment with depth helmet measurements. Treatment regimen included the administration of 500 centigrays (cGy) weekly times four for small tumors (less than 3cm maximal diameter) or 400 cGy weekly time five for large tumors, for a total dose of 2000 cGy defined at the 90% isodose line. Number of isocenters used per tumor ranged from one to three (mean, 1.3). Patients were followed with enhanced MRIs, auditory evoked potentials and pure tone audiometry with speech discrimination examination at three months intervals as well as physical and neurological examination for the first two years and semiannually thereafter. Results: All treated acoustic neuromas were controlled. Median clinical follow-up was 24 months (range,12 to 42 mos) and median MRI follow-up was 18 months(range,10 to 38 mos). Twenty-five acoustic neuromas diminished in size (74%) and nine showed cessation of growth (26%). No acoustic tumor increased in size after fractionated radiosurgery. Pure tone audiometry testing and speech discrimination score were available in 28 of 33 patients after treatment. Four improved (15%), twenty-one had stable hearing (75%) and three worsened (10%). The remaining patients declined audiometry. Two patients who presented with facial weakness had improved facial strength and function. No patient had new facial or trigeminal neuropathy. All 33 patients subjectively reported on balance. Twenty-six of 33 improved (79%), six remained stable (18%) and one worsened (3%). The results of treatment are shown in Table 1. No patient in either group reported or was found to have new clinical signs of 5th or 7th cranial neuropathy. Discussion Acoustic neuromas are benign tumors that arise from the neurilemmal sheath of the superior division of the vestibular nerve at the junction of central and peripheral myelin Obersteiner-Redlich zone so other proper name of those tumors is vestibular schwannomas. These tumors comprise 8 to 10 percent of all intracranial tumors and their annual incidence is estimated at 0.78 to 1.27 cases per 100,000 population, resulting in approximately 2500 new cases per year in the United States. The growth rate of acoustic neuroma is unpredictable and variable with some tumors demonstrating minimal growth and others a growth rate of up to 20 mm per year. Clearly however, these tumors tend to enlarge, and if left untreated, will lead to cranial nerve damage, especially cochleovestibular nerve, later facial nerve and even trigeminal nerve damage. Large acoustic neuromas can cause significant cerebellar and brain stem compression and obstructive hydrocephalus with corresponding symptoms and signs. Table 1: Results of fractionation scheme for acoustic neuroma
Microneurosurgical resection is an established effective treatment modality for acoustic neuroma but it is fraught with mortality of more than 0.5% and serious morbidity occurring in the range from 5 to 45% of acoustic schwannomas surgeries. The surgical morbidity is to a degree due to the intricate anatomy of the cerebello-pontine angle, the internal auditory canal and the relation of the tumor to the cranial nerves in these locations. Moreover, the incidence of complications and in particular cranial nerve damage is directly related to the tumor size and experience of "center of excellence". Stereotactic radiosurgery established itself a place as an alternative treatment modality for acoustic neuroma as it became apparent that in over several thousands patients treated thus far, the tumor could be controlled, with no mortality and minimum morbidity. The main morbidity was the resulting temporary or permanent facial and trigeminal neuropathies that occurred in up to 87% and 92% of treated patients. Modification in the technique including reliance on MRI-based treatment planning, the use of more elaborate treatment plans, the use of more isocenters for a closer match between treatment isodose and tumor, and dose reduction has improved the results somewhat, without compromising the tumor control rate. In spite of these modifications, single fraction stereotactic radiosurgery still results in high incidence (21%) of facial and trigeminal neuropathies. The rationale for a fractionation scheme as used in this pilot study was to decrease damage to surrounding normal tissue. The scheme used in this study was the administration of 400 cGy five weekly or 500 cGy four weekly depending on tumor size to a total dose of 2000 cGy. A surprising observation emanating from this study was the relatively high percentage of tumors (73%) that have actually decreased in size after treatment. This observation is in variance to results reported by others using a single fraction where tumors generally remain stable and rarely decrease in size. This is perhaps the result of a slight increase in total dose administered to our patients afforded by fractionation. Moreover, the fractionation scheme utilized did not cause a single cranial neuropathy, either temporary or permanent. Our observations are in line with the theoretical treatise by Larson who contends that targets with low ratio of alpha/beta (3-5) in which complications are mainly caused by radiation damage to normal tissue, are better treated with fractionation. While it remains to be seen if any of these tumors will evolve for the long term, the occurrence of cranial neuropathies is highly unlikely at this late stage. In most reported series cranial neuropathies occurred within one year of treatment. The median follow up of our patients was 24.0 months with no cranial neuropathy developing during this time. Conclusion: Fractionation as compared to single dose stereotactic radiosurgery appears to minimize neurological toxicity to cranial nerves without compromising tumor growth control. Moreover, 73% of acoustic neuromas treated showed a decrease in size. Undoubtably, the technique of treating acoustic neuromas is still in a stage of evolution. Nevertheless, this pilot study demonstrates that fractionated stereotactic radiotherapy for acoustic schwannomas can avoid complications while not compromising tumor control and should stimulate further interest in this novel approach. REFERENCES:
Dr. Lederman: Briggs et al have recently published their data (in Neurosurgery Vol. 34, #5:785-791, 1994). They described 167 acoustic neuromas measuring 4 cms or greater between 1982 and 1990. Tumors were resected by a translabyrinthine approach. In 96%, the surgeon felt that the tumor was totally removed although post-operative CT scans or MRIs were not performed. Recurrence rates were not described and are apparently to be investigated in the future. Facial nerve function at follow up was classified. After surgery, it was Grade I or normal in 27.3% of patients. It was abnormal in the remainder. The Grade was II in 14.7%, Grade III in 17.5%, Grade IV in 16.1%, Grade V in 9.8% and Grade VI in 14.7% of patients. Dr. Kornhauser: Did their patients have facial weakness before surgery? Dr. Lederman: Facial nerve weakness was seen in only 9% of patients prior to surgery meaning 91% percent of patients had normal facial function before surgery. After surgery, 72.7% had abnormal facial function while only 27.3% had normal function post-operatively. Dr. Kornhauser: Were there other complications? Dr. Lederman: Briggs et al reported vascular complications in 4.8%. There were signs of infarction in the brainstem or cerebellum in four and hematoma in one. Three patients required repeat operations to remove hematoma or collection of blood within the head. Spinal fluid leak occurred in 9.6% of patients. Furthermore, 7.2% of patients had meningitis treated.
Dr. Kornhauser:Were other cranial nerves involved? Dr. Lederman: Glossopharyngeal or vegas nerve dysfunction was said to be infrequent. Tracheostomies were placed in three patients - one prophylactically at time of surgery and two after developing post-operative aspiration pneumonia. Dr. Kornhauser: It is unfortunate that they do not have recurrence or control rates available on their patients. Dr. Lederman: The good news is that they were able to perform this major operation without any operative mortality. Also hearing is lost in all patients with this approach, a "primary disadvantage of the translabyrinthine approach," the authors noted. Dr. Kornhauser: There is British data for surgical removal of acoustic neuromas as well. Dr. Lederman: Welch and Dawes published their results in the Journal of Otolaryngology and Otology (December 1985, Vol 99, 1217-1223). They described surgical removal in 37 of 47 patients with tumors greater than 3 cms. Thus, they were only able to remove tumors completely in 79% of patients. Furthermore, facial function was normal in 19% only of operated patients. Thus, the vast majority of patients had abnormal facial function after surgery. Other complications of surgery included damage to the trigeminal nerve which the authors noted in "all cases." Forty-five percent of patients underwent surgery (tarsorrhaphy) because of an inability to close the eyelid. Other cranial nerves affected post-operatively included 9, 10 and 11. Four patients required tracheostomies and two died of aspiration pneumonia. There was post-operative ataxia in 19% of patients with another 6% also having what the authors described "significant disability." Other complications reported included epilepsy, spinal fluid leak, brain hematoma, hemiplegia, meningitis, septicemia and brain stem infarction. Dr. Kornhauser: What follow-up protocol was followed after surgery in these patients? Dr. Lederman: Most surgical series did not perform either CT or MRI scanning to determine tumor control. Dr. Kornhauser: Harner et al from the Mayo Clinic recently reviewed their surgical experience with acoustic neuromas. Dr. Lederman: They reported 39 patients with pre-operative hearing and acoustic neuromas greater than 4 cms. in size. None were left post-operatively with hearing. Surgeons utilized a retrosigmoid approach. Dr. Kornhauser:What about a group of patients with smaller tumors? Dr. Lederman: There were 85 patients with pre-operative hearing and tumors measuring 2.1 to 3.0 cms. The post operative hearing rate was only 6%. The group of 37 acoustic neuroma patients with pre-operative hearing with measuring 3.1 to 4 cms. had a 97% rate of hearing loss post-operatively. Only one of 37 patients which all had pre-operative hearing, had post-operative hearing in this group. Dr. Kornhauser: And facial nerve function? Dr. Lederman: Similarly they had a high rate of facial nerve dysfunction after surgery. Dr. Kornhauser: Gardener and Robertson evaluated post-operative hearing preservation. What were their results? Dr. Lederman: Gardener & Robertson (Annals of Otolaryngology, Rhinology, Laryngology, 97: 55-66; 1988) evaluated hearing preservation in unilateral acoustic neuromas by reviewing the world's literature and made some pointed observations. The authors concluded that "Hearing preservation is a reasonable goal in unilateral acoustic neuroma surgery, although the number of available candidates is relatively small." They found only five cases of hearing preservation in medical literature with unilateral acoustic neuromas of 3 cms. or larger in size when supporting audiometry testing was available. Dr. Kornhauser: How many cases were reviewed? Dr. Lederman: They combined series with more than six hundred patients. Dr. Kornhauser: Did they comment on the number of surgical deaths? Dr. Lederman: Yes. There were eight. Dr. Kornhauser: Thus, surgery offers marked morbidity to patients and some mortality. Dr. Lederman: We have seen many patients previously treated with surgery who now come for evaluation. Many of these have gone through very prolonged periods of care after surgery. This further emphasizes to us the need of equally - if not more effective - therapy with elimination of the invasion and reduction of side effects associated with microsurgery.
Dr. Kornhauser: Many have commented on incomplete surgical resection of acoustic neuromas and facial function. Are there current series that evaluate this? Dr. Lederman: Dr. Ojemann (Clinical Neurosurgery 1992; Vol. 40, pg. 498-535) found that of patients undergoing surgery with tumors 3.0 to 3.9 cms in greatest diameter, only 48% had normal facial function. Similarly, in patients having tumors greater than 4.0 cms, 49% had normal facial function, as defined by having a Grade I House-Brackmann grading. Only 2 to 3% of patients had pre-operative facial nerve paralysis. In fact, the majority of patients end up with abnormal function after surgery. It should be recalled that a large share of patients had incomplete surgical removal of the acoustic neuromas. That is a critical difference in procedure compared to Comey's report. Complete resections yield very high complication rates. Incomplete procedures have less high complication rates but leave tumor behind.
Dr. Kornhauser:Tell me about Ojemann's partial or incomplete resections. Dr. Lederman: In the 70 patients having acoustic neuromas 4 cms or greater, only 32 or less than half, had total removal with the majority actually having tumor left behind. For patients having tumors measuring 3.0 to 3.9 cms, there were 91 patients evaluated. Sixty-four percent had total removal with more than one-third having tumor left behind. Dr. Kornhauser: What were the reasons for incomplete removal of the acoustic neuroma? Dr. Lederman: It was reported that surgery was not completed because of tumor adherence to the facial nerve or brain stem. That was the predominant cause. Other causes included patient age, patient request, vascularity of tumor, history of cancer, the only hearing ear, intraoperative cardiogram change or bleeding during surgery. Dr. Kornhauser: With your radiosurgical technique at Staten Island University Hospital, the entire tumor is treated. Dr. Lederman: Yes, that is what we do. We see no point to perform an incomplete procedure. Why leave tumor untreated to grow back and cause problems? Dr. Kornhauser: Do other surgical series confirm each other as far as morbidity of surgical treatment in larger tumors? Dr. Lederman: Samii et al (Clinical Neurosurgery, 1984, vol. 32, pg. 242-272) reported that of 60 patients with acoustic neuromas larger than 3.0 cms, only 15% had hearing post-operatively. Dr. Kornhauser: Did Glasscock discuss the likelihood of hearing preservation? Dr. Lederman: Yes, in fact he observed that large tumors were most likely associated not to have hearing after treatment, stating "Preservation of hearing is unlikely when the tumor is larger than 2 cms." Dr. Kornhauser: Parving had looked at quality of life issues. How did he perform his analysis? Dr. Lederman: Parving et al (Archives of Otolaryngology Head & Neck Surgery, 1992) evaluated 293 patients who had surgery between 1976 and 1990 in Denmark. A questionnaire was mailed and 93% responded. Thus, it was a large surgery group evaluated for function after surgery. Tinnitus had occurred in 62% prior to surgery and was present in 49% after surgery. Fifty-six percent were dizzy six months after surgery and 64% reported damage to the facial nerve due to the surgery. Twelve percent had a total loss of facial nerve function. The authors concluded "This study showed that deafness, equilibrium and reduced facial nerve function were the most marked problems after surgery." Dr. Kornhauser: Did they make recommendations as a result of these observations? Dr. Lederman: Yes. They said, "improved information to patients before surgery may reduce the frequency of negative experiences." Parving et al ended their article by writing, "The verbal information concerning symptoms given before surgery was thought to be satisfactory by only 71%, while the information given by the different staff members concerning this surgery was thought to be satisfactory by 87% to 93%. This might be improved by giving written material, by the professionals providing more thorough information concerning the risks and complications, and by including information from subjects who have been operated on for acoustic neuroma previously." Dr. Kornhauser: Wiegand and Fickel performed a similar survey of American acoustic neuroma patients. Dr. Lederman: In Wiegand & Fickel's survey of 541 patients with acoustic neuromas (Laryngoscope 99: 179-187;Feb 1989), 80% "noted a deficit in facial movement post-operatively." The authors noted "only 38% can achieve eye closure on the affected side. This predisposes patients to significant eye related problems post-operatively." Dr. Kornhauser: What kind of eye problems did patients undergoing surgery for acoustic neuromas have post-operatively? Dr. Lederman: Eye related problems were noted in 84% of patients having undergone surgery. Fifty-one percent had dryness and corneal abrasions while 16% had infections. Additionally, 10% had double vision, 8% blurred vision, 8% eye pain, 5% tearing during meals and 2% photophobia.
Furthermore, the eye problems were worsened by any kind of exposure, especially wind, cold air or air conditioning or bright sunlight in a significant share of patients. Dr. Kornhauser: Were there psychological issues as well in the post-operative group? Dr. Lederman: Thirty-eight percent of people responding had depression including symptoms of depression, anxiety and sleep disturbance which were mentioned frequently (437 times by 541 patients). When asked about the most difficult aspect of the surgery, 30% commented on their change in appearance and facial weakness, 19% in hearing loss, 16% in loss of independence, 14% in eye problems, 14% in altered self-image, 10% in difficulty with balance and 95 in fatigue. Dr. Kornhauser: It appears that the results of surgery have tremendous impact on many aspects of the patient - both physical and psychological. Dr. Lederman: We believe it is important for patients to understand as much as possible about the outcome prior to commencing treatment. Our patients, in general, are exceedingly happy about the treatment and are able to continue on their activities. We do treat large tumors in patients having already been afflicted by their tumors. As we have discussed, there is a good chance of symptom improvement and an exceedingly high chance of tumor control now.
Dr. Kornhauser: Pollock compared outcome in acoustic neuroma patients having either surgery or radiosurgery. But what were the complication rates in the group of patients having microsurgery for tumors less than 3 cms in the very recent Pollock study? Dr. Lederman: Pollock compared microsurgical treatment to single fraction radiosurgery during the years 1990-1991. He found, "Fifteen patients (38%) had one or more post operative complications after microsurgical resection of their acoustic neuroma. Complications included rhinorrhea (18%), wound infection (5%), cerebellar contusion (5%), progressive hydrocephalus (3%), pseudomeningocele (3%) dysphagia (3%), diplopia (3%) and hemiparesis (3%). Nine patients (23%) underwent gold weight tarsoplasty and two patients (5%) had canthopasty for management of corneal exposure. Three patients (8%) required wound revision for persistent rhinorrhea and one patient had evacuation of a post operative cerebellar hematoma." Dr. Kornhauser: And in the radiosurgery group? Dr. Lederman: Facial nerve damage occurred in 22% after single fraction radiosurgery for acoustic neuromas measuring less than 3 cms. Dr. Kornhauser: There is, as well, a current report describing single fraction radiosurgery of acoustic neuromas from the Mayo Clinic. Dr. Lederman: Foote et al in 1995 described their experience of using the gamma knife for 36 patients with acoustic neuromas. Tumor size ranged from 0.6 to 3.2 mm The follow-up ranged from 2.5 to 36 months with a median of 16. Ten tumors were smaller and 26 (74%) were unchanged. Dr. Kornhauser: What about the complication rate in that series of single fraction radiosurgery? Dr. Lederman: The authors noted "The one and two year actuarial incidences of facial neuropathy were 52.2% and 66.5% respectively. The one and two year actuarial incidences of trigeminal neuropathy were 33.7% and 58.9% respectively. The one and two year actuarial incidences of facial or trigeminal neuropathy (or both) was 60.8% and 81.7% respectively." Dr. Kornhauser: That is dramatically different than the Staten Island University Hospital experience. To what would you attribute your favorable results? Dr. Lederman: A variety of factors - the most important is fractionation. Fractionation allows us to minimize the toxicity. That is an observation that is shown in our data. Furthermore, our linear accelerator-based system gives a more homogeneous dose of radiation because fewer isocenters or spheres of radiation are required. The majority of our patients were treated with a single isocenter whereas the median number of isocenters per tumor in the Mayo series was five with a range of one to twelve. Overlapping isocenters deliver much higher doses of radiation which is unfortunate. These create hot spots. We have been able to minimize hot spots by our system. Dr. Kornhauser: You just reported your results at the LINAC Radiosurgery meetings in Florida. Can you describe your findings? Dr. Lederman: The purpose of our report was to describe patient groups by tumor size - less than 3 cms. or 3 cms. or greater at maximum diameter of acoustic neuroma. Dr. Kornhauser: Why the emphasis on the size of acoustic neuromas? Dr. Lederman: Pollock et al (Neurosurgery Vol 36, 1; 215 - 229, 1995) wrote "Most patients with acoustic neuromas greater than 3 cms. in average diameter will require microsurgical resection of the tumor in order to reduce brain stem compression." We vehemently disagree. Surgery is an option. Similarly single fraction radiosurgery is one radiation option. These are not the only options. Based upon the presented data as well as others published, surgery is an exceedingly unappealing option. Complication rates are high for surgical patients and it is overwhelmingly high in patients with 3 cm. or greater-sized acoustic neuromas - especially when compared to our fractionated stereotactic radiosurgery experience. We believe fractionated radiosurgery merits strong consideration in light of the facts available. Radiosurgery for large acoustic neuromas has been little - if at all - studied until our recent report. Dr. Kornhauser: How was radiosurgery performed at Staten Island University Hospital? Dr. Lederman: We perform fractionated radiosurgery using a non-invasive head frame and linear accelerator-based treatment. Dr. Kornhauser: Is linear accelerator-based method of treatment critical? Dr. Lederman: I believe that while both methods are highly successful in controlling acoustic neuromas, linear accelerators have the advantage of creating a more homogenous of radiation distribution and as well, has a greater flexibility in collimator - or beam - size. It would seem very important to have collimators that measure more than 1.4 or 1.8 cms., especially in dealing with tumors that are 3 cms. or greater. We have 12 different collimator sizes available to best create a conformal fit for the tumor. How we prescribe our dose is also different, adding to the homogeneity of treatment here and furthermore, fractionation helps prevent normal tissue damage. I am strong believer that the "proof of the pudding is in the eating" and we have results that are highly favorable for those with acoustic neuromas - of all sizes. Dr. Kornhauser: Can you tell me about your data? Dr. Lederman: More than 100 patients with acoustic neuromas have been treated at Staten Island University Hospital with fractionated stereotactic radiosurgery. This is the world's largest fractionated radiosurgery series. We reported on 41 patients with 42 tumors with average follow-up of greater than 3 years. The age range was 35 to 88 years with a mean of 60. The greatest tumor diameter for any individual acoustic neuroma ranged from 0.3 to 5.0cc. The mean was 2.4 cc. Dr. Kornhauser: What were the results of the large acoustic neuroma group - those measuring 3 cms. or greater? Dr. Lederman: There were 16 acoustic neuromas in the group measuring 3 cms. or greater. The size ranged from 3.0 to 5.0 cms. in maximum diameter. The mean was 3.7 cms. Dr. Kornhauser: And the follow-up period? Dr. Lederman: It ranged from 12 to 49 months with a median of 38.3 at the time of the writing of the abstract. There are a good share of patients out more than three years. Up to two years is the period of greatest vulnerability to side effects, according to reports based upon single fraction radiosurgery. Of course, the data currently has longer follow-up. Dr. Kornhauser: What side effects did you see? Dr. Lederman: There was no patient treated at Staten Island University Hospital reporting signs or symptoms 5th (trigeminal) or 7th (facial) nerve damage - NONE. All patients maintained or improved their facial function. Dr. Kornhauser: I understand you have examples of facial nerve that improved in two patients who had multiple unsuccessful operations. Dr. Lederman: One woman with bilateral acoustic neuromas had three unsuccessful operations. She was left with progressive neurologic deterioration including marked facial dysfunction (House-Brackmann Grade V). After fractionated stereotactic radiosurgery at Staten Island University Hospital, she now can close her eye and close her mouth. Her face at rest is essentially symmetric. She and her family report that eating is much more feasible in that her mouth is stronger and holds food in. Dr. Kornhauser: That's amazing - zero facial nerve or trigeminal complications in those high risk patients!! How do you explain that successful outcome? Dr. Lederman: I believe it is due to the fractionation program as well as our equipment and importantly, our staff. We have an extensive medical, physics, dosimetrists and radiation therapists team. These people from one end to another are actively involved in quality assurance and all parts of the procedure are double-checked. - and often triple-checked for accuracy. Dr. Kornhauser: Different radiosurgery centers treat differently, don't they? Dr. Lederman: Yes. Just like no two painters or musicians are the same - no two radiosurgery techniques are the same. Just because radiosurgery is offered does not mean results like these can be recreated. Different methods of dose prescription or delivery can alter the outcome greatly. Dr. Kornhauser: How do you follow patients who have had radiosurgery? Dr. Lederman: We ask for every six month follow-up consisting of MRI with gadolinium-enhancement and auditory testing for the first two years. After that, the follow-up is extended to every six months and then, annually. Analysis of most surgical series are not able to give long term results because of inadequate follow-up. We are attempting to be meticulous in our follow-up as well as our treatment so that other physicians and patients can have an excellent understanding of the process prior to commencing. A share of our patients have recurrent tumors despite surgery and their tumors are controlled after fractionated stereotactic radiosurgery. . We believe follow-up is critical. Dr. Kornhauser: Tell me more about your group of patients with large acoustic neuromas? Dr. Lederman: Control of tumor means that the tumor has stopped growing or shrunk in size. All acoustic neuromas treated at Staten Island University Hospital were controlled. A shadow will exist on MRI scans. No shadow has shown any progressive signs - just the converse, in fact. Earlier radiosurgery series have shown the effectiveness and long-term control of acoustic neuromas by radiosurgery. Ours is special in that we have been able to diminish toxicity dramatically and, as well, successfully treat larger tumors. Dr. Kornhauser: And hearing in your group? Dr. Lederman: The majority of patients actually had stable or improved hearing. Eighteen percent of our patients with acoustic neuromas 3 cms. or greater had documented improvement in pure tone audiometry with 73% remaining stable. Similar improvement occurred in those having tumors less than 3 cms. Dr. Kornhauser: Why is that important? Dr. Lederman: It is a quality of life issue. If one has stereo hearing then one has bi-directional hearing. This means if a car honks, it is easier to tell the direction and in general, it improves the quality of life. Why lose something if it can be maintained? Dr. Kornhauser: These results must be very gratifying. Dr. Lederman: We continue to inform patients and physicians, analyze data and present our findings at national and international meetings. I strongly believe that fractionated stereotactic radiosurgery will be the treatment of choice for acoustic neuromas in the future. Today, it is considered vanguard or cutting edge treatment. There is a decades-long radiosurgery tradition. We intend to enhance it. Fractionated radiosurgery should be evaluated by all who have acoustic neuromas. It offers a great chance at tumor control, while avoiding surgery, anesthesia and the prolonged - and often multiple - hospital stays and convalescence associated with surgery.
By: Gil Lederman, M.D.
Those having attended Harvard Medical School keep in communication with colleagues and the school through the Harvard Medical Alumni Bulletin. My wife (Josiane trained at Massachusetts General Hospital in Dermatology) and I both receive it and I enjoy to read about my colleagues and where they have landed throughout the world as well as updating current activities at the medical school.
In the most recent edition, the Alumni Notes records a comment from Dr. Stephen F. Cooper, a graduate of the 1974 class of Harvard Medical School. His note is quite brief but to me quite poignant. He wrote, "Recovering from acoustic neuroma excision. Not yet back to work."
To me, this was quite devastating news. For this decade we have been developing innovative non-invasive treatments for acoustic neuromas and other benign and malignant brain tumors. In fact, our acoustic neuroma work has brought patients from around the world to Staten Island University Hospital. Our data appears in major medical meeting, medical journals and the current oncologic
medical text books.
The basic problem with surgical intervention of this disease is not the results of tumor treatment but rather the results on the patient. The vast majority of patients are hospitalized for prolonged periods of time and many suffer untoward effects. Almost all patients are left deaf in the operated ear and facial paralysis is very common. Other complications including spinal fluid leakage, bleeding into the brain and paralysis, are not uncommon even at the so-called largest surgical centers. A patient survey has evaluated these points. Often it takes months for the patient to attempt to return to normal activities.
Because toxicity of surgery is so great, often resulting in inability to return to normal function as described by that Harvard Alumnus or even worse, the possibility of death, non-invasive treatments have been sought.
At Staten Island University Hospital more than one hundred patients have been treated with CP angle tumors using fractionated technique. CP angle describes the location in the brain where acoustic neuromas most commonly are found. There are many aspects of great appeal compared to surgery or single shot radiosurgery.
Surgery results in hearing loss for the vast majority of the patients. That means deafness in the operated ear. Also, patients, when asked after surgery about facial function report in the majority have weakness or paralysis of the face on the involved side. This creates great social and physical problems as well as emotional and psychological distress. There are other negative aspects to surgery which include the possibility of bleeding in the brain, damage to the surrounding brain, paralysis, stroke or even worse.
Single shot radiosurgery minimizes many of these complications but still hearing is only about 50% preserved. Facial paralysis has been reported in up to 50% of the patients with trigeminal neuropathy in a similar proportion. Some institutions are dropping the dose of single shot radiosurgery in an attempt to get results equivalent to those with fractionation. But long-term data remains sparse from this lower dose. If dose is lowered too much, recurrence rates may rise.
Fractionated radiosurgery at Staten Island University Hospital has been ongoing and is the largest such series in the world. Our data is compelling in that the vast majority of patients have maintained and in some cases even improved hearing.
The likelihood of facial paralysis is minuscule as is trigeminal neuropathy which was not observed.
No patients have required surgery for treatment failure. The work is all done non-invasively with no pins in the head. The pin-on-head frame is quite unpleasant and we do everything we can to avoid it.
The greatest appeal of fractionation is the protection of the normal, healthy surrounding nerves and brain stem - the critical issue which fractionation can provide.
What happens to our patients undergoing fractionated radiosurgery at Staten Island University Hospital?
The typical patient will come for four or five treatments, with each treatment lasting approximately one half hour. Before and after treatment they have eaten, carried on their normal activities, worked, walked, and slept every night at their own home (or hotel if coming from afar).
I suspect if that same Harvard Medical School Graduate had had fractionated radiosurgery at Staten Island University Hospital he might comment in passing about all aspects of his life, noting additionally that he had fractionated radiosurgery for acoustic neuroma and that he continued to work and carry on normal functions throughout his few treatments.
Our efforts have been to educate patients and their physicians about the new treatment options. A recent patient from Wales, Great Britain, returned after a five day stay here committed to changing the course in her life to educate patients and physicians that new non-invasive treatment options are available. I certainly wish her, and in fact, all success.
The rationale of radiosurgery or pinpoint radiation has always been strong. A main issue has been that equipment developed for radiosurgery was initially developed by surgeons. I suspect surgical training and in fact lack of radiation training led to the concept of the single intervention is much like invasive surgery.
The problem with single fraction radiosurgery is, however, that it ignores the principles of radiation that have been developed over the past 100 years.
During those decades it has been shown that fractionation or dividing the radiation dose leads to a higher tolerance of the normal, healthy surrounding tissues. It is not only for cancer results that divided dose fractionation of the radiation is undertaken although that is, indeed, an issue. It is to protect the normal, healthy surrounding tissues.
Those principles are true throughout the body and they should be especially true in the brain where normal, delicate structures such as the brain stem and cranial nerves surround even benign tumors like the acoustic neuroma.
A recent study by Ito et al, from the University of Tokyo, has outlined their results of acoustic neuroma patients treated on the gamma knife. There were 46 patients who underwent radiosurgery between June 1990 and June 1994 and followed there. The patients ranged in age from 13 to 77 years with a median of 54. Tumor diameter ranged from 0 to 25 millimeters (mm) with a mean of 12.
Maximum tumor dose ranged from 20 to 40 Gray with peripheral doses of 12 to 20 Gray. One to 8 isocenters - or spheres of radiation - were used with a mean of 3.2 and median follow-up was 39 months.
All patients were treated using Gamma Knife at the center with a dose prescribed at the 50% isodose line and 30 patients in the 60% or 70% isodose line at six patients each. This is the point about the tumor where the curves of radiation fall off. Their results showed that in 2 patients or 4% the tumor increased by 2mm or more in diameter. Eighteen percent of the 38 patients with any hearing before treatment became totally deaf after single-shot radiosurgery within an average time of three months.
The risk factors for deafness after single-shot radiosurgery included the diagnosis of neurofibromatosis too and the number of isocenters. The authors noted that, "pre-treatment hearing level was not associated."
Pure-tone audiometry worsened in 61% of the patients with an onset of time of eight months. Low-tone average diminished in 53% of the patients and high-tone 46% of the patients.
Sixty-nine percent of the patients with a preserved caloric response (a test using altered temperature water injected into the ears) before treatment lost this after treatment with a time of eight months on average. The peripheral tumor radiation dose and the maximum tumor radiation dose were associated here.
Twenty-two percent of patients had facial palsy or weakness within six months. Risks of developing face weakness included the patient's age, tumor size, and the number of isocenters.
Fifty percent of the patients additionally had facial palsy or transient facial spasm after treatment with an average time of six months. Trigeminal nerve dysfunction occurred in 30% of patients.
Furthermore, authors noted that, "of the five patients who had undergone microsurgery prior to radiosurgery, three had already had facial palsy. In two of those three patients, exacerbation of facial palsy occurred after radiosurgery. All of the five patients had moderate to severe hearing loss before radiosurgery, which was exacerbated after treatment in three patients."
Why is the fractionated radiosurgery data from Staten Island University Hospital so different from this? A variety of answers but the main one is more versatile equipment and fractionation. We have not seen a permanent facial paralysis and, in fact, there has been no trigeminal neuropathy.
The vast majority of patients (over 80%) treated with fractionated radiosurgery have maintained their hearing with about 10% of patients actually improving their hearing as documented by pure-tone audiometry. Only about 10% have had diminished hearing.
Furthermore, the group at Staten Island University Hospital have been able to treat large as well as small tumors with tumors measuring up to 5 centimeters in diameter and 32 cubic centimeters in volume undergoing fractionation.
The follow-up of time is similar to the Tokyo study but the complications have not been seen.
While obviously both methods are superior to surgery, it is clear which method offers the opportunity of less hot-spots, dose homogeneity and fewer collimators therefore producing less hot-spots. That is clearly associated with fractionated stereotactic radiosurgery program.
Of course, years of follow-up will be necessary to determine the outcome but at this interval - an important milestone since most recurrences and complications occur within the first several years - fractionated radiosurgery offers the tremendous appeal of being a non-invasive procedure avoiding a head-frame with pins in the skull and as well the versatility of a greater number of collimators and protection of the normal, healthy surrounding crucial structures.
by Gil Lederman M.D.
Acoustic neuromas are unusual tumors that affect the nerve responsible for hearing and balance.
This eighth cranial nerve to come off the brain is named the auditory nerve. Cranial nerves come directly off the brain to control a variety of important functions such as sight, smell, hearing, eating and more. Because of the nerve's critical location adjacent to the ear and brain stem (the source of other cranial nerves), neurologic functional impairment of facial strength as well as hearing loss and headaches can be experienced.
Often the hearing loss is insidious so that the tumor may grow to fairly large proportions before being discovered.
Before the days of CT scans (computerized topography) and MRI's (magnetic resonance imaging),m tumors were more difficult to diagnose early. Now a relatively simple but sophisticated scan can produce an image allowing physicians to make a presumptive diagnosis painlessly and non-invasively.
Usual symptoms of the disease include loss of hearing, poor balance and facial weakness.
The standard of care has been surgical removal. Occasionally, patients will have bilateral tumors and therefore removal may result in significant neurologic damage.
Some refuse to undergo open surgery and others are felt to be in poor health and are unacceptable for surgery. Side effects of surgery include infections, leakage of spinal fluid and neurologic deterioration.
Hearing loss occurs in essentially all patients undergoing surgery, with complete hearing loss noted in nearly 95% of patients. It is the very unusual patient who retains hearing after surgery.
Furthermore, the vast majority of patients have weakness of the involved side of face after surgery with few actually having neurologic improvement.
Because of the deterioration after open surgery, plus the potential morbidity of the procedure, alternatives have been sought.
One obvious options in stereotactic radiosurgery. This is a method where pencil-thin radiation beams from thousands of angles attack the tumor while protecting the normal surrounding critical brain structures. Using this advanced technique, large doses of radiation can be administered to the acoustic neuroma while minimal effects are produced on the adjacent normal brain.
Stereotactic radiosurgery is performed after a sophisticated head frame is placed on the patient's head. A high resolution contrast CT scan is obtained to delineate the exact location of the tumor as distinct from the normal brain structures.
Intensive physics planning determines the exact radiation attack. After multiple quality assurance procedures, the patient is treated in what is usually a 30 to 60 minute painless, bloodless, anesthesia-less procedure.
Recently reported in the journal, Cancer," were 85 patients with acoustic neuromas who received radiosurgery by Flickinger and colleagues.
All patients were evaluated after radiosurgery. No patient died in the subsequent period of time.
Forty-one percent had decrease in size of the tumor while 56% of the patients have stabilization of f growth in the tumors. Only two of the 85 patients (3%) had enlargement in the size of the tumor during the subsequent period of observation.
None of the complications associated with open surgery was seen in the patients undergoing stereotactic radiosurgery. This eliminated infections, acute neurologic deterioration or meningitis as side effects of treatment.
Forty-six percent of the patients who had useful hearing prior to radiosurgery still had useful hearing at the time of evaluation. Most nerve damage after radiosurgery was felt to be temporary.
Hearing damage was greater in patients with larger tumors. The smaller tumor, the less likely neurologic function would occur.
Thus, radiosurgery appears to be a viable option for patients with acoustic neuromas. The patients tolerated the procedure exceedingly well with minimal side effects.
Other centers found long-term control rates of 86% in patients with acoustic neuromas treated with radiosurgery.
Furthermore, it appears hearing is more likely to be maintained in patients undergoing stereotactic radiosurgery than open surgery.
Linear accelerator-based stereotactic radiosurgery can treat larger tumors with more homogeneous distribution of radiation than can the older generation gamma knife. The gamma knife has a maximum pencil-thin beam of 1.8 centimeters, while stereotactic radiosurgery using a linear accelerator system can treat beyond 4 centimeter lesions.
Thus, for many reasons, stereotactic radiosurgery may be an appealing choice of patients with acoustic neuromas. It avoids open surgery and associated morbidity and mortality. It certainly does not preclude further surgery, should the patient desire than and it may offer dramatic and permanent shrinkage obviating the need for open brain surgery.
New developments have dramatically altered the care of those with acoustic neuromas. While early radiosurgery reports showed the success of the technique, our recent report shows a very high control rate with no damage to the facial or surrounding nerves. Furthermore, many patients have had improvement in their symptoms. Obviously when one develops nerve or brain damage from tumors, it is impossible to predict who will improve or who will not. The appeal of the technique, however, remains. It is totally non-invasive with no pins in the head and therefore no risks of complications from bleeding, skull fracture, tears in the skin or infection. Furthermore, by fractionating treatment surrounding healthy brains are best protected.
by: Gil Lederman, MD
New data from Staten Island University Hospital
and other radiosurgery centers are bringing very promising news
for those afflicted with acoustic neuroma - a benign tumor of
the brain's eighth nerve. Common symptoms of this tumor are hearing
loss, ringing in the ear and imbalance.
These tumors can enlarge and cause significant
and permanent neurologic damage - even death - if not successfully
treated. While surgery has been the mainstay of therapy for many
years, a new non-invasive method of treatment - stereotactic radiosurgery
- has made tremendous inroads. New data continues to support
its use.
A just-published retrospective study reported
by Pollock et al and published in Neurosurgery in 1995
compared surgery to stereotactic radiosurgery. One hundred forty-nine
patients had acoustic neuromas treated. Seventy-one patients
had open surgery and 78 patients had stereotactic radiosurgery.
Treatment option was determined by patient and physician.
Sixty patients were excluded because of
prior surgery and 27 of those patients had tumor recurrence despite
surgery. Eight patients had neurofibromatosis (a disease
predisposing to acoustic neuromas) and 25 patients were excluded
for arbitrary criterion of having a tumor larger than 3 centimeters.
Two patients were lost to follow up.
Of 87 remaining patients evaluated, 40 patients
underwent surgery and 47 patients had stereotactic radiosurgery.
The authors noted that the tumor sizes were
"somewhat larger in the stereotactic radiosurgery group."
It was also noted that "microsurgical resection was performed
by experienced acoustic neuroma surgeons."
Stereotactic radiosurgery was administered
using a Cobalt source, single fraction method with a dose of 13
to 18 Gray. Gray is a measurement of radiation. Median follow
up was three years.
The patients undergoing surgery had a greater
incidence of operative or delayed facial nerve dysfunction - occurring
in 52% - and a greater incidence of long term post operative
facial paresis (or weakness) occurring in 37% of patients. That
is particularly interesting in that surgeons operated on those
with smaller tumors - a group one would believe to have lesser
complications if all were equal.
Furthermore, open surgery resulted in diminished
"serviceable hearing." Serviceable hearing was maintained
in only 3 of 21 patients undergoing open surgery compared to 6
of 8 patients undergoing stereotactic radiosurgery.
Open surgery had a higher rate of new onset
post-operative headache. This occurred in 21% of patients having
surgery compared to 5% treated with single fraction stereotactic
radiosurgery.
Authors noted "patients resumed their
normal activities sooner after stereotactic radiosurgery."
This also was very markedly significant.
At time of follow up, one patient having
surgery had a recurrence and one had post operative hydrocephalus
(fluid build-up in the brain). Thirty eight percent of patients
having surgery had complications. These included rhinorrhea
(brain fluid leaking through the nose), wound infection, brain
contusion, progressive hydrocephalus, pseudomeningocele, dysphagia
(difficulty swallowing), double vision or unilateral body weakness.
Nine patients or 23% having had open surgery
for the acoustic neuroma underwent subsequent surgery to the eyelids
in an attempt to remedy facial nerve weakness. Eight percent
of surgical patients had a revision of the wound because of the
leakage of the spinal fluid through the nose and one patient had
removal of a blood clot on the brain post operatively.
This compares dramatically to the stereotactic
radiosurgery group. Of the patients undergoing stereotactic radiosurgery,
the control rate was 94%. Only 6 patients had complications including
ventricular enlargement. In these 6 patients, tumor volume was
6.9 cubic centimeters - more than twice the volume of others treated.
Six had a shunt placed, with four having marked improvement.
No patient required additional surgery.
In discussing the outcome, the authors noted
that the "goal of acoustic neuroma management is to provide
the best patient outcome possible. Management strategies that
maintain facial nerve function, reduce treatment associated morbidity
and allow the patient to resume a normal lifestyle as quickly
as possible after intervention are desirable. The results of
this study show that stereotactic radiosurgery was more effective
than microsurgical resection in preserving normal facial function.
Hearing preservation was associated with less morbidity. Patient
functional outcomes and patient satisfaction of the tumor management
were greater in the stereotactic radiosurgery group, though these
did not reach statistical significance due to the sample size
of the present study. Patients who had radiosurgery were able
to return to their pre-operative level of function sooner than
patients who underwent microsurgery. Moreover hospital length
of stay and total management charges were significantly less in
the radiosurgery group."
The authors of this retrospective study
concluded that "when compared to microsurgical resection
of acoustic neuromas, stereotactic radiosurgery is an effective
and less costly management strategy."
It should be noted that in data presented
by the radiosurgery group from Staten Island University Hospital
at the European Brain Tumor Meetings, a control rate of 100% with
no facial nerve damage was observed for acoustic neuromas using
fractionated radiosurgery.
The main difference in the Staten Island
University Hospital approach is fractionation of radiosurgery
using a pinless headframe technique. By dividing the
dose into four or five smaller portions (depending on tumor size),
surrounding vital brain tissues such as facial nerve and brain
stem are further protected from the radiation while the tumor
is vigorously attacked. The high control rate and lack of facial
nerve damage, makes this technique a very attractive non-invasive
treatment option.
Staten Island University Hospital's approach
using fractionation allows treatment of tumors both smaller than
- as well as greater than - 3 centimeters in diameter. Our experience
treating tumors from pinpoint size up to nearly 6 centimeters
in maximum diameter, has shown that fractionation maintains efficacy
of treatment while minimizing or avoiding the known toxicities
of open surgery or single fraction radiosurgery.
Currently, scores of patients have been
treated at Staten Island University Hospital. Results remain
impressive with patient requiring surgery for treatment failure.
There has been no incidence of trigeminal nerve neuropathy.
Fractionation continues to have great appeal
with patients around the world traveling to Staten Island University
Hospital for fractionated treatment of their acoustic neuroma.
In light of the beneficial outcome, the rationale of this approach
is clear - avoidance of open surgery and its convalescence as
well as morbidity and mortality associated with it. Fractionated
stereotactic radiosurgery will most probably the treatment of
choice in future when it is more widely available. This innovative
approach is used routinely at Staten Island University Hospital.
by: Gil Lederman, MD
There are great advances being made in non-invasive
treatment of acoustic neuromas. The most promising is fractionated
stereotactic radiosurgery.
While surgery has been used for 101 years
as treatment for acoustic neuromas, it has been marked by great
difficulty both for the surgeon attempting to resect a tumor in
such a delicate location as the cerebellopontine angle as well
as the patient who endures not only the operation but the post-operative
consequences. Since surgery is often so morbid, new treatment
techniques have been developed to maintain the successful outcome
while minimizing the complications.
Radiosurgery is precision radiation. In
the past 25 years, single-shot radiation, so-called stereotactic
radiosurgery, was implemented and has been successful in the treatment
of acoustic neuromas. However, the risk to surrounding tissues,
like when operated upon, is often high. Modern-day stereotactic
radiosurgery centers using Gamma Knife have reported combined
complications to the facial and trigeminal nerves up to 80% in
patients after single fraction stereotactic radiosurgery. The
outcome to patients who have facial paralysis is of course devastating
and overwhelming.
Radiation throughout the body is fractionated
or divided in dose to protect the normal, healthy tissues. That
is most crucial for tumors in the cerebellopontine angle - the
location of acoustic neuromas.
Knowing that fractionation can protect the
critical surrounding tissues such as the 5th and 7th cranial nerves
as well as the brain stem and cerebellum, Staten Island University
Hospital developed a program using divided dose pinpoint radiation
for treatment of acoustic neuromas. The techniques of radiosurgery
are similar, but what is different is the dose is divided to protect
the normal tissues.
We recently reported on 33 patients with
34 acoustic neuromas ranging in age from 35 to 89 years. Patients
were treated weekly for four or five weeks depending on the size
of the tumor. Tumor sizes ranged form 0.6 centimeters to 5.0
centimeters. All tumors were successfully treated. There was
cessation of growth or shrinkage in all patients.
Furthermore, the vast majority of patients
had either stable hearing or improved hearing as confirmed by
pure tone audiometry. This is in marked difference to patients
undergoing surgery where the vast majority of patients will lose
all hearing.
Additionally, a majority of patients had
improved balance. These statistics are true both for the group
having tumors less than 3 centimeters as well as those having
tumors 3 centimeters or greater undergoing fractionated stereotactic
radiosurgery.
Follow-up is now at a point beyond which
in other studies, recurrences or complications have occurred.
This technique is very well tolerated. For example, no patient
has had trigeminal neuropathy - a marked difference to surgical
or single fraction radiosurgery approaches.
In addition, fractionated stereotactic radiosurgery
uses a non-invasive head frame pioneered at Staten Island University
Hospital which is much more comfortable and convenient to the
patient. It does not require pins in the head like the head frames
administering single dose treatment. There is no risk of bleeding
or harm to the underlying bone.
In summary, the fractionated stereotactic
radiosurgery program developed at Staten Island University Hospital
offers great appeal for those with acoustic neuromas. The vast
majority of patients maintain hearing, avoid neurologic compromise,
avoid hospitalization and associated convalescence.
by Gil Lederman
Acoustic neuromas are being more frequently
diagnosed as those with hearing loss and sometimes other symptoms
are obtaining MRIs (Magnetic Resonance Imaging scans) which can
show small tumors at an early stage.
The several names used for this benign tumor
include acoustic neuroma, acoustic neuronoma and vestibular schwannoma.
It involves the 8th cranial nerve which has two branches - acoustic
and vestibular and under the microscope resembles schwann cells.
For that reason, vestibular schwannoma is a synonym.
The phrase "benign" generally
implies a course unmarked by progression or death. Unfortunately,
in the brain, this is not necessarily the situation. Because
the brain is so delicate and encased in bone, there is little
extra space for unusual growths of any type.
The incidence of acoustic neuromas is modest
- approximately 1 per 100,000 people per year. It's equivalent
to approximately 2,500 people being diagnosed each year in the
United States. That is of little relief to those diagnosed.
Because MRI can detect lesions which were previously not visible
by other means, it is likely that the true incidence is higher.
Symptoms include decreased hearing, ringing
in the ears and a change in balance. While acoustic neuromas
can affect either ear and sometimes both ears, most often it is
unilateral.
The vast majority have asymmetric loss in
hearing. Most commonly it is a high frequency hearing loss but
some will have normal hearing - or symmetric hearing with modest
diminishment or distortion. An early sign is avoiding one ear
while using a telephone.
As the tumor grows, it can encroach on the
adjacent brainstem. This may create headaches, difficulty walking
and damage to cranial nerves. Cranial nerves are neurologic structures
that originate from the brain performing certain motor or sensory
functions.
Late symptoms are pain, numbness or weakness
in the face. With increasing size, progressive symptoms include
nausea, vomiting and even coma, respiratory depression and death.
People with bilateral acoustic neuromas
commonly have an inherited disease called neurofibromatosis.
By radiographic appearance there is no difference between the
sporadically occurring unilateral acoustic neuromas and the bilaterally
occurring disease. The bilateral type is usually more aggressive
in its invasion, however.
Much acoustic neuroma data was presented
at a National Institute of Health Consensus Development Conference.
In a subsequent report, it was noted that "tumors tend to
enlarge unpredictably. Some do not change size for many years,
while other may grow at the rate of up to 20 millimeters in diameter
per year."
The Consensus report stated "all cases of vestibular schwannomas are thought to result from the functional loss of a tumor suppressor gene which has been localized to the long arm of chromosome 22. In at least 95% of patients, however, the disease is unilateral and the majority of these cases are sporadic, resulting from somatic mutation that are not associated with an increased risk for other tumors in either the individual or close relatives."
The Consensus report addressed the who and when of treatment. It was felt that since most at diagnosis have a symptomatic tumor, treatment should be carried out quickly. Especially included in this group were the young with progressive
neurologic deficits or evidence of tumor growth.
With MRI detecting small lesions, the natural history is unknown. An option is follow-up scans to determine the growth rate. The consensus panel alludes to "the risk of neurologic deterioration in conservatively managed patients."
Traditionally, radiation has been used in those who refuse to undergo invasive surgery. The National Institute of Health's panel writes that, "the greatest experience to date has been with stereotactic radiosurgery." They wrote that "early reports indicate the retardation of tumor growth as observed in the majority of patients."
Peri-operative surgical complications can
include air embolism, intracranial hemorrhage and stroke. "Cerebral
spinal fluid leak and meningitis can occur in a delayed fashion
and also can require immediate therapy."
"Loss of hearing in the operated ear
is the most common adverse consequence and can be a serious handicap.
These patients have difficulty in even modestly noisy environments
and do not have directional hearing", the NIH panel reported.
Also reported by the panel was the fact that "abnormal vestibular function occurs in almost all patients." Additionally noted was "one distressing complication of surgery is disfiguring facial nerve weakness or paralysis with consequent physical, emotional, psychosocial and possibly professional dysfunction." The panel reported treatment approaches to
"reanimation" of the face includes surgery and physical occupational therapy. "As yet, none of these can restore normal function appearance." Also discussed were other cranial nerves being damaged by surgery including the fifth, seventh, ninth, tenth and twelfth. The panel describes recurrence after surgery where the tumor was apparently either totally or partially removed; thus all cases need to be followed by imaging. Those that have recurred may be managed by re-operation, fractionated stereotactic or standard radiation.
Stereotactic radiosurgery avoids all cutting, bleeding and anesthesia. The panel reported that "stereotactic radiosurgery, a newer modality has benefit of a low early complication rate, but unknown long term complications." New approaches developed since the National Institute of Health Consensus meeting are lower radiation dose for stereotactic radiosurgery as well as fractionated radiosurgery.
Traditionally, fractionated radiation divides the total dose into smaller segments in an attempt to protect vital surrounding tissues. Normal tissues may repair radiation changes while tumors accumulate the radiation damage.
Our recently submitted data that has been accepted by the European Neuro-Oncology meeting in Holland shows a very high control rate. All patients having received radiation have had cessation of growth or shrinkage of the tumor. Furthermore, a significant share of patients with symptoms have had an improvement. There have been no patients who have suffered facial nerve damage
unlike single fraction radiosurgery.
Fractionated stereotactic radiation is an alternative to invasive surgery. After radiosurgery, people return to their normal activities essentially immediately with no recuperatory period. The vast majority undergoing stereotactic radiosurgery for acoustic neuromas have cessation of growth or more commonly, dramatic shrinkage in the size of the tumor.
The goals of stereotactic radiosurgery in the treatment of acoustic neuromas as well as metastases, meningiomas, arteriovenous malformations and brain tumors are obviously to stop tumor growth, avoid invasive surgery and eliminate the need for any surgical intervention as best as possible.
Stereotactic radiosurgery is a viable option for those who seek successful treatment without invasive surgery.
Staten Island University Hospital's data using fractionated stereotactic radiosurgery is the largest such experience in the world. Our data has been presented at national and international meetings and shows a very high success rate in controlling this benign tumor while in general avoiding the toxicity associated with open surgery. The appeal is a non-invasive head frame avoiding the pins in the head associated with the BRW head frame as well as the morbidity and potential mortality of open surgery. The fractionated approach minimizes the toxicity associated with single fraction radiosurgery while maintaining radiosurgery's efficacy.
by: Gil Lederman, MD
Radiosurgery has been used since the 1970s for treatment of acoustic neuromas - a benign tumor affecting the 8th cranial nerve. This tumor often causes decreased hearing, imbalance and other symptoms as it progresses in size.
While surgery has been traditionally performed, the majority of patients undergoing surgery will lose hearing and many will have facial weakness as well as other complications. Thus, the appeal for non-invasive treatment is great.
Recently, Flickinger et al in the International Journal of Radiation Oncology, Biology and Physics published evolving techniques for tumor treatment.
That group treated 273 patients with radiosurgery between 1987 and 1994 with a median follow up of 24 months. Patients evaluated who had pre-existing facial paralysis or deafness were felt not to be at risk for neuropathy of the 7th and 8th nerve and, therefore, were not included in the analysis of complications.
The authors reported a seven-year actuarial control rate of the tumor of 96.4%. The seven-year radiographic control rate was 91%. Three patients had tumor progression requiring surgical resection for a seven-year actuarial failure rate of 3.6% - or a crude rate of 1.1%. The authors noted that six other patients had a small amount of tumor growth (about 1 to 2 millimeters) on follow-up scans but had no further tumor growth or subsequent shrinkage.
Risk of damage to facial, trigeminal or auditory nerves was within the first 28 months after radiosurgery treatment. Facial neuropathy developed in 36 of 260 patients for an actuarial incidence of 17.2% at three years. Thirteen other patients had complete facial paralysis prior to radiosurgery and were excluded.
Trigeminal neuropathy developed in 49 patients for a three-year actuarial incidence of 22.6%. Later patients had a lower incidence.
Decreased speech discrimination developed in 38 of 146 patients for a three-year actuarial rate of 31%. The authors noted the relationship between the minimum tumor dose and facial neuropathy as well as trigeminal neuropathy was significant. Furthermore, the authors previously used CT scan as a basis of comparison but now believe that MRI is more accurate in following up small changes in the size of an acoustic neuroma.
The authors changed treatment technique by increasing isocenters. Treatment in the early era had only 2 or 3 isocenters. The number of isocenters, or spheres of radiation, in early years was 3.4 and more recently, it is 5.8.
The authors noted, "The desire to decrease the risk of post-radiosurgery hearing loss, and facial and trigeminal neuropathies by using lower doses needs to be balanced by the concern that the trade-off would result in a decrease in long-term tumor control."
Doses over the years have fallen. The minimum dose was 1700 Centigray in the early era and 1400 Centigray in the later era. Similarly the maximum dose was 3400 Centigray in the early era and 2800 Centigray in the later era. This minimum and maximum dose reflects radiation dose heterogeneity using multiple, small isocenters.
Most acoustic neuromas were treated with a minimum tumor dose of 1300 to 1500 Centigray where no trigeminal or facial neuropathy developed. The authors stated that despite the changes in technique, there has been "no detectable decrease in tumor control with follow-up so far."
The authors noted that 27% of patients had facial neuropathy in the earlier era compared to 8% in the current era. In the current era, 8% developed trigeminal neuropathy compared to 36% with the higher doses administered. Furthermore, hearing is improved at the lower doses and 56% of patients have serviceable hearing currently compared to only 40% at the higher doses. It appears that administering lower doses and using MRI scanning results in lesser complications.
A group at Staten Island University Hospital has taken this one step further by only using MRI scanning, historically, for purposes of comparison and by fractionating or dividing the dose of radiation.
Fractionated radiation is the mainstay for delivered radiation throughout the body. Why should radiation to this critical site be different? It seems that because of the surrounding sensitive nerves that fractionation should help protect these critical nerves including the 5th, 7th and 8th. In fact, our data shows a similar-to-higher control rate while avoiding trigeminal neuropathy. No cases, whatsoever, of trigeminal neuropathy and no permanent cases of facial neuropathy were experienced.
This ongoing work will produce results that give effective and safe treatment options for those with acoustic neuromas.
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