You have been involved in and devoted to radiosurgery all your life. You have witnessed and made possible the evolution of radiosurgery: what is your take on the future challenges and opportunities in the current scenario?
 

Over the past five decades, and particularly during the last 30 years we have seen a consistent stable growth in the use of stereotactic radiosurgery for brain disorders. Although it started with the Gamma Knife alone for about 25 years, we have also seen competitive technologies emerge during the last quarter century. There are many centers for example that use adapted linac, proton beam and Cyberknife. This has not put a dent in the growth curve of Gamma Knife procedures in the world, quite the opposite in fact. Unfortunately, there has been no clearinghouse to track actual procedures done globally, regardless of technology used. Only the US CMS Medicare data base (patients generally are older than 65) maintains records. The Leksell Gamma Knife Society does track procedures that are voluntarily submitted by participating centers, and we know that more than 1.2 million patients across the world have had Gamma Knife surgery. If I limit myself to cerebral SRS, I think one major challenge for the future will be to investigate new or underused indications for which SRS can be applied. An important parameter in this context is cost versus clinical benefits. If the cost of technology remains high, which is most likely, it will be even more important to be able to apply the method to an expanding cohort of patients, i.e. to identify new indications. There are opportunities here!

An example of an indication that I think deserves to be explored are surgically or endovascularly high-risk arterial aneurysms. We know today that many aneurysms have an annual bleed risk that depending on size may be as low as <1 % per year. With the increasing use of MR and CTA an increasing number of unruptured aneurysms are incidentally discovered after trauma or headache complaints. These unruptured aneurysms are often found in young people with otherwise normal life expectancy. Radiosurgery should be explored as an option to microsurgery. Very interesting experimental work on this is currently underway at Hershey Medical Center in Pennsylvania under the leadership of James Connor and James McInerney.

Another indication that deserves exploring is treatment of medically resistant Major Depressive Disorder (MDD). According to the WHO this will be the number one cause of medical disability by 2030. Depression is increasingly prevalent, and it often afflicts young people. The targets for treating this disorder are often the same as those for Obsessive Compulsive Disorder (OCD). Much work on the use of SRS for the latter disease has been done by the group of Steve Rasmussen at Brown University on Rhode Island. Putting together a comprehensive team that includes psychiatry, neurosurgery, and radiation oncology is critical as these patients will still need ongoing counselling and medical management.

Other underused and underappreciated uses of radiosurgery include choroidal metastatic disease and uveal melanoma, for which many centers use Iodine 125 plaques, or refer their patients for proton radiation therapy.

Moving over to SBRT or body SRS I think the opportunities are manifold. Many applications for precise radiation delivery are currently explored for cancers in e.g. lung, liver, prostate etc. Like in other fields of medicine, including brain SRS, I do not think however that new approaches make existing ones obsolete, nor should they. The challenge is to identify when to use one method or another and not least when to use two methods in combination. Radiation, surgery, immunotherapy and other approaches can often enhance each other when diligently used in combination. The growing field of body SRS or SBRT is also affected by cost versus clinical benefits, maybe even more so since the disorders mostly are of a malignant nature and life expectancies are different from what they are when approaching benign conditions in the brain. An example of technology currently being marketed as a major improvement is MR guided radiation or so-called MR-Linacs. High field strength MR scanners combined with a linear accelerator are expensive systems often requiring an expense of 7-8 million dollars. The future will tell if such expense can be motivated by clinical outcomes. I’m not convinced that there will be a major difference in overall survival when doing MR and irradiation in separate rooms, as compared to using the combined MR-Linac system to compensate for organ movements. I believe that technology development should be guided by clinical needs, rather than new technology be on the outlook for clinical applications.

Have have you tackled these challenges you have been faced with?
 

Well, the first time I gave a talk about Gamma Knife surgery was in India in 1969. I talked to the Indian Neurosurgical Society about the first 6 cases we had treated with the prototype Gamma Knife in Stockholm. When I finished the audience was yelling “charlatan, throw him out”! The chairman led me out of the convention center and out of harm’s way. It was a sobering experience and it could of course have been rather demotivating for a young and inexperienced enthusiast. I did realize however, that the suggestion that you could do something in the brain without a craniotomy was provocative at the time. And it did indeed take another 18 years before people started thinking that maybe it was true, maybe you could treat some brain disorders non-invasively?

The experience in India had the opposite effect on me. I strongly felt that I needed to trust my instincts and beliefs, and as the years went by and we saw the results of what we were doing in Stockholm, this philosophy became a strong guiding force for me. Ragnar Granit, the 1967 Nobel laureate in Physiology or Medicine once said - “when you have seen something once you can believe it, when you’ve seen it twice you can publish it”.

So, to believe is a prerequisite but unfortunately often this is not enough. What you also need is to be able to withstand criticism and skepticism, sometimes even outright hostility from your own peers. You also need to be humble with your detractors and often swallow your pride. Finally, and importantly, you need to be tenacious and you need to persevere. 

In your opinion, what’s the best strategy to develop and advance SRS proficiency?
 

Across the world SRS is done with teams composed of different professional backgrounds, depending in part on what disorder is being treated. Multidisciplinary medicine has become routine, but the knowledgebase of surgeons, oncologists, and medical physicists are critical to ensure that patients get the best care. There is a risk that a “push button” procedure, such as SRS, erroneously is regarded as a low-risk procedure. It is indeed possible for relatively poorly trained or inexperienced physicians to start doing SRS. Because there is no loss of blood or other dramatic complications as in open surgery, there can be a false sense of security. When coupled with an incomplete commitment to long term study and analysis, the risks, regardless of them being relatively lower than with many conventional options, are not recognized. In my opinion the best way to become a skillful radiosurgery practitioner is to spend time at a high-volume academic center with recognized and well published long-term results. I often hear that a center or physician has been accredited after a 1- or 2-week course, often conducted by the manufacturer of the technology in question. This of course is wholly inadequate, in addition to being questionable on other grounds. A 6- to 12-month fellowship or observership at a center as mentioned above, will teach patient selection criteria for all indications. It will teach the tricks of the trade when it comes to treatment planning and above all it will teach the timing of follow-up and the importance of documentation. If you consider all the indications that can be addressed with SRS today, there is a lot to learn! In addition to such a fellowship, regular attendance at specialized teaching programs is necessary. These can be courses or meetings dedicated to a subset of indications or even to just one specific indication. It is the responsibility of each participating specialty, its professional societies, and the physicians themselves to commit to getting the best possible training and experience.

Do you see any risks for the future?
 

Reinventing the wheel can be a risk. Radiosurgery practitioners have spent more than 30 years proving that single session procedures can largely replace fractionated procedures. We should not invest in expensive evaluations to determine if single session outcomes with 90% tumor control and 1% risk can be improved by reverting to fractionation, to show a 90.5% tumor control rate and a 0.9% risk rate. An example of this that deeply concerns me is that some people fractionate small vestibular schwannomas (VS). I see two risks (assuming that they follow their patients properly) – first that tumor control rates go down (or at best remain the same) and second that 10-20 years down the road we will see secondary induced malignancies, something we today know is exceedingly rare. I know that Pittsburgh has published one case among 1900 cases treated for VS. Jeremy Rowe in Sheffield has published at least two papers on the subject, confirming that the incidence is insignificant.

Patients with VS’s too large for single session SRS should also not be fractionated. They should undergo microsurgical volume reduction followed by SRS to the remnant affecting the nerves in the inner acoustic canal. In Rio de Janeiro recently, I paraphrased Dolly Parton (who sang “don’t take my man just because you can”) by saying don’t fractionate just because you can! This should apply to all benign indications for which we have established excellent results, minimal risks and no secondary malignancies.

What has the Leksell Gamma Knife Society meant for you?
 

It was 1987, 18 years after my experience in India. The first US Gamma Knife had been installed in Pittsburgh and a couple more were on their way to Charlottesville, Chicago and a few other places. I then felt that there would be a need for a forum where to share experiences, good as well as bad, and to openly discuss potential research areas to be explored. At the first Leksell Society meeting in 1989 there were 10 or 12 participants. After two days of deliberations I asked them if they wanted to get together again in a years’ time. Their unanimous answer was yes. So, between 1989 and 2000 we met every year and the Society grew in parallel with the number of peer-reviewed publications and the number of patients treated. In 2000 John Jane, then editor in Chief of Journal of Neurosurgery finally accepted to publish the proceedings from the meeting. After that I felt that annual meetings were becoming problematic. It is difficult to produce meaningful new science to motivate long distance travel to destinations across the world once every year. So, the Society meeting became a biennial event. In 2014 we met in New York and there were close to 800 participants.

The last and final meeting was in Dubai in March of 2018. I then explained that I was discontinuing the meetings. The rationale for this was severalfold. 1) Radiosurgery has become very well ingrained in the daily practice of neurosurgery and radiation therapy. 2) The published science is overwhelming and very convincing. 3) The methodology has expanded to other parts of the body and ISRS has grown to become a meeting that truly covers both brain and body. 4) Travel allowances are increasingly reduced everywhere, making it ever harder to fly to the Leksell Society meeting and to the ISRS congress every other year and 5) If there is to be only one major dedicated international radiosurgery meeting, the ISRS, with its broader scope, should be that meeting. I also stated the opinion that the Leksell Society and the ISRS should continue to work together, to move the science forward and to educate the global communities about the benefits of being able to offer patients radiosurgery, in addition to other therapeutic modalities.

To me personally my work with the Leksell Society and its meetings has been hugely rewarding. I have witnessed the enormous changes that have transpired over the last 50 years. I have also been vindicated after having been summarily thrown out of the congress in India in 1969!

Finally, as I now have retired since a few weeks, I am comforted by having a huge number of friends all over the world. Long lasting friendships that I will honor and cherish for the remainder of my life.