Transcript
At first, thank you, Reinhardt, for our invitation and I take it everyone in the audience knows that normally this is your special topic. The main goal should always be the complete obliteration of the AVM nidus. And we have some important lessons learned from one session radiosurgery. And we know something about the optimal dose, this is not only true for Gamma Knife radiosurgery but also for Linac radiosurgery, something between 18 and 20 Gy. We have some lessons learned about the ideal volume. If we treat small volume AVMs around 5 cubic centimeters, we see rarely complications like edema or blood-brain barrier breakdown. We have important lessons learned about the maximum volume. If we don't respect those volumes, then the rate of complication will rise, probably from around 12%, it will rise about 30%. We know we have a Gold Standard. Most of our data is derived from Gamma Knife series. Here you see the multicenter series from Starke et al. So on the left side, you see the ideal case for radiosurgery, for one-session radiosurgery, small, deep-seated.
On the right side, you see the large AVM. What can we do with it? We can make compromises with the dose. We can do combined treatments with embolization. We can do multi-staged radiosurgery, or we can do hypo-fractionated stereotactic radiosurgery. In this case, a male patient, 36 years old with a hemiparesis with seizures, we have done a reduced dose of radiosurgery after two embolizations. And it works, you can see there, initial MRIs on the left side, four months post and one year post. After one year, you see edema and something...contrast enhancement. And eight years post, you see complete obliteration in the MRI. The DSA was rejected from the patient. What can we do, else?
If the AVM not so large, about 10 cubic centimeters, a female patient, 16 years old, with the bleeding, we have done only radiosurgery with reduced dose and as you can see, in the MRIs and in the DSA follow-up, complete obliteration of this AVM. What about the Gamma Knife experience? Here's an experienced group of Pittsburgh with a multistaged volumetric staged radiosurgery and after two or four staged radiosurgeries, they achieved complete obliteration of 36%. If they used the normal dose of about 17 Gy, they achieved a higher obliteration rate of more than 60% but this is not without complications. There are some serious bleedings, and if they use an additional radiosurgery after staged radiosurgery, the obliteration rates are better. After 7 and 10 years, about 50% was achieved.
What about repeat radiosurgery? It's another option. Again, the Pittsburgh group with the Gamma Knife and yes, one can achieve a good obliteration rate after a second radiosurgery but again, the factors for a good obliteration rate are the small volume, and a good reduction after first radiosurgery. But again, we have some serious bleedings, some side effects. And interesting, after the first radiosurgery, the side effects were around 5% and after the second radiosurgery, they rise to nearly 10%.
So in this case, what can we do with the really large AVMs? Here's a case with an AVM of 25 cubic centimeters, a female, 14-year-old patient with a hemidysesthesia on the left side. And after two embolizations, we have used hypofractionated stereotactic radiotherapy with a 7x5 Gy. And in this case, it was successful. We have achieved a complete obliteration. And we have published our experience, it's a typical Novalis Linac series. It's a pooled series from Germany Erfurt and Bonn. We have enrolled 121 patients and we have around one quarter Spetzler-Martin I and II grade. If one combines the Spetzler-Martin grades I to III, we have nearly three quarters, so the rest are the large and complicated cases. We have a high rate of eloquent localization of around 45%.
And what about the volume? Most cases are the small volume AVMs. We have some intermediate cases, and we have 20 cases with large AVMs. What have we done? In radiosurgery, the mean volume was under 5 cubic centimeters. In hypofractionated stereotactic radiotherapy, the mean volume was around 11 cubic centimeters. And we have a clear volume relationship. Everybody knows that small ones are good candidates, with obliteration rates around 80% and 90%. On the large ones, we achieved an obliteration rate around 50%. So, here are the 20 cases. Most of them were symptomatic, with bleeding, with seizures, with neurologic deficit. Most of the patients were pre-treated with embolizations or microsurgery. The median AVM volume was around 15 cubic centimeters and in those large AVMs, we have used 13 times radiosurgery and 7 times hypofractionated stereotactic radiotherapy.
Mean follow-up was four years. As I have taught already, we have achieved an obliteration rate of 50%, mild clinical side effects. So, if you search in the literature, PubMed search with the search term hypofractionated stereotactic radiotherapy and AVM, you will get 21 hits. And in this year, Zhong et al have published a review about hypofractionated stereotactic radiotherapy not only concerning AVMs but also tumors. Here is a table of the series using hypofractionated stereotactic radiotherapy in large AVMs. And I have modified it a little bit, I have added a German study from last year and I have added some data from Reinhardt Wurm and if the results of all studies can be summarized as follows, 12 studies, a total case number of 352 patients, the mean nidus volume was around 18 cubic centimeters, the mean total dose was around 30 Gy, with a range of 12 to 55 Gy and the mean number of fractions were 5 fractions with a range of 2 to 13 fractions. And altogether, the obliteration rate was 50%, the bleeding rate was 10% and the rate of radiation necrosis was 9%.
Reinhard Wurm proposed for AVMs, a low alpha-beta ratio of 2 Gy and this means 35 Gy in 5 or 55 Gy in 11 fractions equal 18 Gy one session radiosurgery. And here is the data Reinhardt Wurm has presented last year in the German-speaking Novalis meeting and this one, 61 AVMs with a follow-up of about 60 months, a good obliteration rate in the MRI with a rate of 74%. And he sees a very early improvement of the AVMs after 6 months and also, the so-called side effects he sees very early after 6 months, but they were resolved mainly after 2 years with only 8% permanent, and 5% with a permanent deficit.
So, what can we do with hypofractionated stereotactic radiotherapy in AVMs? We can use it as definitive treatment or we can use it somewhat as pre-treatment for a second treatment like radiosurgery or like microsurgery. Some exemplary cases. Here is an 18-year-old female patient with a temporo-mesial left-sided AVM, Spetzler-Martin grade 4, with a bleeding, a symptomatic epilepsy, and an upper quadrant anopsia. The embolectomy was classified as too risky. Alternatively, we have done stereotactic radiotherapy and in this case, it was a somewhat reduced dose, 5x6 Gy. The volume was not so large, under 10 cubic centimeters, here in this case, 8 cubic centimeters. Because of the mild asymptomatic re-bleeding, we have done definitive treatment before three years and the reduced nidus was only 0.35 cubic centimeters and we have treated this remnant with 16 Gy. We show complete obliteration with MRI and DSA. The outcome was good, able to work, and modified ranking score of 1. The other MRIs, you see on the left side the MRI and T2 pictures. You see the follow-up, 2012 to 2015 with, in the MRI, complete obliteration. You see the DSA follow-up, this is complete obliteration.
Okay, the second case is an exemplary case for hypofractionated stereotactic radiotherapy as definitive treatment. Again, a female patient, 44 years old, temporo occipital left-sided AVM with a more diffuse nidus, Spetzler-Martin Grade 4, initial diagnosis already in 2009, symptomatic with seizures. Op resection was declined and alternatively we do hypofractionated stereotactic radiotherapy, also with a somewhat reduced dose, 11x4 Gy, the volume was about 20 cubic centimeters. The side effects were moderate, local alopecia, some radiogenic reaction, with a transient quadrant anopsia. We see in the MRI complete obliteration already in 2014, DSA was initially rejected but the patient agreed last year, and we can prove complete obliteration with DSA already. The outcome was again good, able to work and modified ranking score of 1. Here is the pictures again, MRI and T2 pictures, with the diffuse nidus. Here you see the angiography before treatment, and here you see the follow-up from the right side to the left side. After one year, we see the radiogenic reaction with a transient focal deficit in upper right-sided quadrant anopsia but is resolved. And on the left side, you see the complete nidus obliteration and again the MRI follow up with MRA and T2 pictures and also the DSA follow up before and after, and lateral and APU.
So, I come to the summary and conclusions. Radiosurgery provides, with a known time delay in small AVMs, a high obliteration rate of around 80% to 90%. Hypofractionated stereotactic radiotherapy or repeat radiosurgery or staged radiosurgery provides, in large AVMs, a response, with an AVM reduction and an acceptable complete obliteration rate of approximately 50%. For those AVMs not totally obliterated, hypo-fractionated stereotactic radiotherapy maybe makes them smaller and turns some lesions manageable by single-dose radiosurgery or microsurgery. A second radiosurgery on smaller residual nidus promises a real chance for definitive AVM obliteration. And higher doses per fraction maybe seemed to exhibit better response, but however, patients receiving higher total dose may be at risk for a higher rate of complication. Fractionated regimens equal to 7 Gy five times or 5 Gy 11 times may be accepted compromises between obliteration and complication. Thank you very much for your attention.
On the right side, you see the large AVM. What can we do with it? We can make compromises with the dose. We can do combined treatments with embolization. We can do multi-staged radiosurgery, or we can do hypo-fractionated stereotactic radiosurgery. In this case, a male patient, 36 years old with a hemiparesis with seizures, we have done a reduced dose of radiosurgery after two embolizations. And it works, you can see there, initial MRIs on the left side, four months post and one year post. After one year, you see edema and something...contrast enhancement. And eight years post, you see complete obliteration in the MRI. The DSA was rejected from the patient. What can we do, else?
If the AVM not so large, about 10 cubic centimeters, a female patient, 16 years old, with the bleeding, we have done only radiosurgery with reduced dose and as you can see, in the MRIs and in the DSA follow-up, complete obliteration of this AVM. What about the Gamma Knife experience? Here's an experienced group of Pittsburgh with a multistaged volumetric staged radiosurgery and after two or four staged radiosurgeries, they achieved complete obliteration of 36%. If they used the normal dose of about 17 Gy, they achieved a higher obliteration rate of more than 60% but this is not without complications. There are some serious bleedings, and if they use an additional radiosurgery after staged radiosurgery, the obliteration rates are better. After 7 and 10 years, about 50% was achieved.
What about repeat radiosurgery? It's another option. Again, the Pittsburgh group with the Gamma Knife and yes, one can achieve a good obliteration rate after a second radiosurgery but again, the factors for a good obliteration rate are the small volume, and a good reduction after first radiosurgery. But again, we have some serious bleedings, some side effects. And interesting, after the first radiosurgery, the side effects were around 5% and after the second radiosurgery, they rise to nearly 10%.
So in this case, what can we do with the really large AVMs? Here's a case with an AVM of 25 cubic centimeters, a female, 14-year-old patient with a hemidysesthesia on the left side. And after two embolizations, we have used hypofractionated stereotactic radiotherapy with a 7x5 Gy. And in this case, it was successful. We have achieved a complete obliteration. And we have published our experience, it's a typical Novalis Linac series. It's a pooled series from Germany Erfurt and Bonn. We have enrolled 121 patients and we have around one quarter Spetzler-Martin I and II grade. If one combines the Spetzler-Martin grades I to III, we have nearly three quarters, so the rest are the large and complicated cases. We have a high rate of eloquent localization of around 45%.
And what about the volume? Most cases are the small volume AVMs. We have some intermediate cases, and we have 20 cases with large AVMs. What have we done? In radiosurgery, the mean volume was under 5 cubic centimeters. In hypofractionated stereotactic radiotherapy, the mean volume was around 11 cubic centimeters. And we have a clear volume relationship. Everybody knows that small ones are good candidates, with obliteration rates around 80% and 90%. On the large ones, we achieved an obliteration rate around 50%. So, here are the 20 cases. Most of them were symptomatic, with bleeding, with seizures, with neurologic deficit. Most of the patients were pre-treated with embolizations or microsurgery. The median AVM volume was around 15 cubic centimeters and in those large AVMs, we have used 13 times radiosurgery and 7 times hypofractionated stereotactic radiotherapy.
Mean follow-up was four years. As I have taught already, we have achieved an obliteration rate of 50%, mild clinical side effects. So, if you search in the literature, PubMed search with the search term hypofractionated stereotactic radiotherapy and AVM, you will get 21 hits. And in this year, Zhong et al have published a review about hypofractionated stereotactic radiotherapy not only concerning AVMs but also tumors. Here is a table of the series using hypofractionated stereotactic radiotherapy in large AVMs. And I have modified it a little bit, I have added a German study from last year and I have added some data from Reinhardt Wurm and if the results of all studies can be summarized as follows, 12 studies, a total case number of 352 patients, the mean nidus volume was around 18 cubic centimeters, the mean total dose was around 30 Gy, with a range of 12 to 55 Gy and the mean number of fractions were 5 fractions with a range of 2 to 13 fractions. And altogether, the obliteration rate was 50%, the bleeding rate was 10% and the rate of radiation necrosis was 9%.
Reinhard Wurm proposed for AVMs, a low alpha-beta ratio of 2 Gy and this means 35 Gy in 5 or 55 Gy in 11 fractions equal 18 Gy one session radiosurgery. And here is the data Reinhardt Wurm has presented last year in the German-speaking Novalis meeting and this one, 61 AVMs with a follow-up of about 60 months, a good obliteration rate in the MRI with a rate of 74%. And he sees a very early improvement of the AVMs after 6 months and also, the so-called side effects he sees very early after 6 months, but they were resolved mainly after 2 years with only 8% permanent, and 5% with a permanent deficit.
So, what can we do with hypofractionated stereotactic radiotherapy in AVMs? We can use it as definitive treatment or we can use it somewhat as pre-treatment for a second treatment like radiosurgery or like microsurgery. Some exemplary cases. Here is an 18-year-old female patient with a temporo-mesial left-sided AVM, Spetzler-Martin grade 4, with a bleeding, a symptomatic epilepsy, and an upper quadrant anopsia. The embolectomy was classified as too risky. Alternatively, we have done stereotactic radiotherapy and in this case, it was a somewhat reduced dose, 5x6 Gy. The volume was not so large, under 10 cubic centimeters, here in this case, 8 cubic centimeters. Because of the mild asymptomatic re-bleeding, we have done definitive treatment before three years and the reduced nidus was only 0.35 cubic centimeters and we have treated this remnant with 16 Gy. We show complete obliteration with MRI and DSA. The outcome was good, able to work, and modified ranking score of 1. The other MRIs, you see on the left side the MRI and T2 pictures. You see the follow-up, 2012 to 2015 with, in the MRI, complete obliteration. You see the DSA follow-up, this is complete obliteration.
Okay, the second case is an exemplary case for hypofractionated stereotactic radiotherapy as definitive treatment. Again, a female patient, 44 years old, temporo occipital left-sided AVM with a more diffuse nidus, Spetzler-Martin Grade 4, initial diagnosis already in 2009, symptomatic with seizures. Op resection was declined and alternatively we do hypofractionated stereotactic radiotherapy, also with a somewhat reduced dose, 11x4 Gy, the volume was about 20 cubic centimeters. The side effects were moderate, local alopecia, some radiogenic reaction, with a transient quadrant anopsia. We see in the MRI complete obliteration already in 2014, DSA was initially rejected but the patient agreed last year, and we can prove complete obliteration with DSA already. The outcome was again good, able to work and modified ranking score of 1. Here is the pictures again, MRI and T2 pictures, with the diffuse nidus. Here you see the angiography before treatment, and here you see the follow-up from the right side to the left side. After one year, we see the radiogenic reaction with a transient focal deficit in upper right-sided quadrant anopsia but is resolved. And on the left side, you see the complete nidus obliteration and again the MRI follow up with MRA and T2 pictures and also the DSA follow up before and after, and lateral and APU.
So, I come to the summary and conclusions. Radiosurgery provides, with a known time delay in small AVMs, a high obliteration rate of around 80% to 90%. Hypofractionated stereotactic radiotherapy or repeat radiosurgery or staged radiosurgery provides, in large AVMs, a response, with an AVM reduction and an acceptable complete obliteration rate of approximately 50%. For those AVMs not totally obliterated, hypo-fractionated stereotactic radiotherapy maybe makes them smaller and turns some lesions manageable by single-dose radiosurgery or microsurgery. A second radiosurgery on smaller residual nidus promises a real chance for definitive AVM obliteration. And higher doses per fraction maybe seemed to exhibit better response, but however, patients receiving higher total dose may be at risk for a higher rate of complication. Fractionated regimens equal to 7 Gy five times or 5 Gy 11 times may be accepted compromises between obliteration and complication. Thank you very much for your attention.