Changing times and early debates

CHAPTER

Changing times and early debates

11

Abstract The machine was soon being called the Gamma Knife. Its spread led to increasing numbers of papers from different centers but particularly Pittsburgh. As mentioned in the preface, the introduction of new methods in medicine is seldom without problems. There were a number of squabbles about the treatment of various indications. It was suggested that for AVMs, the GKS was unnecessary. For meningiomas, there was marked skepticism within the milieu itself in the early days. Metastases were not treated in Stockholm because of Leksell’s opposition to the treatment of malignant disease, and indeed, these tumors became generally popular indications rather later. There was a thought that pituitary adenomas could be better treated with GKS but it proved too unreliable, and for these tumors, GKS remains an ancillary treatment method. The most marked disagreements were with respect of the vestibular schwannomas. This discussion continues to the present.

Keywords AVM, pituitary adenoma, vestibular schwannoma, meningiomas, metastases

1 INTRODUCTION Gamma Knife surgery (GKS) was invented in Stockholm. The world’s leading and indeed for 14 years, only Gamma Knife department was there. Nearly all the conditions that are treated today were treated during those early years. The exceptions are metastases and gliomas as Leksell wanted all patients followed for a long time. He was concerned that the treatment of patients with malignant disease with short term survival would make it harder to convince his peers about the long-term benefits of radiosurgery. He was also as stated earlier concerned that the results on a given patient should be followed before another case with the same diagnosis should be treated. In consequence, during those 14 years, roughly one patient a week was treated as outlined in Chapter 9. Peer-reviewed publication is the means by which new scientific ideas are tested and appraised. Also in medicine, peer-reviewed papers are accessible through the MEDLINE database. Nothing in this world is perfect, and while the creativity and Progress in Brain Research, Volume 215, ISSN 0079-6123, http://dx.doi.org/10.1016/B978-0-444-63520-4.00011-9 © 2014 Elsevier B.V. All rights reserved.

103

104

CHAPTER 11 Changing times and early debates

ingenuity that produced the Gamma Knife came from Stockholm and were of the highest quality, the publication of results did not meet the same standards. In those early days, consensus about the right dose for each diagnosis had not been reached. The Stockholm publications were the only publications at this stage, and they did not always spread clarity. When the method started to spread, the absence of systematic peer-reviewed publication became a problem. However, it will be seen that the group in Pittsburgh made a vital and unrepeatable contribution to Gamma Knife surgery with their honest reporting of their work in peer-reviewed publications available to all interested parties. Over and above high-quality reporting, as indicated in the preface, the introduction of a new treatment method into an always conservative medical milieu is difficult, and the quality of publication must have a considerable influence on the acceptance of a new technique. What follow are an outline of the debates in the early days that had an impact on the use of Gamma Knife surgery for different indications and the early work that helped in convincing the milieu of the value of the method. The remarks are limited to indications where there were a substantial number of patients.

2 AVMs This indication is probably one of the first to gain some measure of acceptance. However, apart from two papers, one case study (Kondziolka et al., 1991a,b) and one reporting five cases (Pollock et al., 1994), all the subsequent reports were in book chapters and thus not peer-reviewed and not easily available to others. The number of radiosurgery practitioners at this time was small enough to constitute a community, which could, even in those days without emails, keep in contact. Thus, the word got around that the margin dose to arteriovenous malformations (AVMs). AVMs was 25 Gy and permanent complications were seen in 3% of patients. The occlusion rate in AVMs, which had bled and had a maximum diameter of 2.5 cm or less, was said to be 80% (Steiner et al., 1972, 1974). However, there was considerable opposition to radiosurgery in the early days. It must be remembered that in the 1970s, management of AVMs was much more timid than is the case today. In 1979, there were reports on over 160 patients from Gothenburg and Canada. The first was a report on decision making about whether or not to operate (Pellettieri et al., 1979). The second was a report of microsurgery in 166 cases (Drake, 1979). Thus, one center is unclear about indications, whereas another is operating routinely. This was an evolving milieu with no consensus. The first focused radiation treatments were being done in Boston where Raymond Kjellberg at the HCL/MGH cyclotron treated his first patient using the Bragg Peak on May 25, 1961. His center treated by far the most patients in those early days and by 1993 had managed 1250 (Barker et al., 2003). However, his work had a serious weakness. Routine angiograms after treatment were never performed, so that the occlusion rate in this work is unknown. Dr. Kjellberg initiated two somewhat querulous correspondences with Steiner and Lunsford (Kjellberg, 1988) and subsequently with Dan Leksell (Kjellberg,

3 Pituitary region tumors

1989). Both correspondences are more polemic than didactic in tone. One is left with the impression of someone defending his practice not when it is under attack but when colleagues elsewhere relate different possibly competing treatment methods with excellent results. The controversy soon faded into oblivion as irrelevant. Another correspondence arose between Bennet Stein’s group in New York Ladislau and Steiner’s in Charlottesville. The paper describes the microsurgical treatment of 67 AVMs in awkward locations and the abstract concludes with the statement, “The authors’ surgical results compare favorably with those from radiosurgery centers which, in their opinion, supports the conclusion that microneurosurgery is superior to radiosurgery, except for a small percentage of lesions that are truly inoperable on the basis of inaccessibility” (Sisti et al., 1993). Steiner wrote an editorial about the paper pointing out some weaknesses (Steiner et al., 1993). Stein replied with a letter criticizing Steiner’s editorial. The details of this debate were strongly emotional but have also faded into oblivion as irrelevant. The Pittsburgh group was to produce a series of 227 patients treated in 3 years, where 143 patients (63%) had hemorrhages, 104 (46%) had headaches, and 70 (31%) had seizures (Lunsford et al., 1991). The lesions were classified according to the Spetzler grading system: 64 (28%) were grade VI (inoperable), 22 (10%) were grade IV, 90 (40%) were grade III, 43 (19%) were grade II, and 8 (4%) were grade I. Total cover of the AVM nidus was possible in 216 patients (95%). Dose depended on location and volume. The 2-year obliteration rates according to volume were <1 cm3 all 8 (100%), 1–4 cm3 22 (85%), and 7 (58%) of 12 AVMs greater than 4 cm3. Two patients developed permanent new neurological deficits believed to be treatment-related. Two patients died of repeat hemorrhage at 6 and 23 months after treatment during the latency interval prior to obliteration. The abstract contains nothing about dosage, but the paper reported the dose range and found no correlation between dose and complications. In the text, it states that 79.6% of patients received 20–27 Gy and 19.9% received 15–19 Gy. There was no clear statement of the relationship between dose and volume because with the KULA dose planning system in use at the time, target volume measurements were not possible. Nonetheless, the clarity and detail of this report provided the platform for expansion of the use of the method.

3 PITUITARY REGION TUMORS The only patients to be the subject of contemporary reporting were those with Cushing’s disease. It was as stated earlier at a time of evolving techniques, and the 76% control rate after repeated treatments was a lot better than that achieved by conventional fractionated radiotherapy. It was logical to treat the Cushing’s disease patients as their tumors were known to be largely small and thus intrasellar. Prior to the introduction of MR, there was much guesswork in the treatment of these lesions. Basically, a location in the sella turcica was accepted as the appropriate target. Computed tomography (CT) did not really help a lot as these tiny lesions are often not shown on CT. The author remembers a small series of four patients in Bergen in

105

106

CHAPTER 11 Changing times and early debates

which it was thought that CT showed tumor in two patients and did not in two. The two patients with identified tumor did not improve, and the two where no tumor could be seen with certainty were cured. Thus, the Stockholm Gamma Knife reporting of Cushing’s disease was helpful and for a while could compete with other treatment methods until microsurgery became the treatment of choice. At a later date, in Bergen, a pilot study concluded that radiosurgery could be used following failed microsurgery and in patients who for whatever reason could not or would not undergo microsurgery (Ganz et al., 1992). As a primary treatment, the Bergen group found GKS unreliable and inferior to microsurgery. The group continues to maintain microsurgery as the first treatment for this indication. In Pittsburgh, another early paper (Stephanian et al., 1992) recorded findings in 35 patients that were similar to those published from Stockholm and demonstrated a higher success rate with Cushing’s disease. This series used MR localization. There was a variable response with other endocrinopathies. It is also fair to mention that while hormonal normalization was registered in 3 of 10 patients with acromegaly, the criterion for normality was less than 5 ng/ml, which is rather high by modern standards. In ten patients with nonsecreting adenomas, growth was controlled in all. One patient who had previously two craniotomies and fractionated radiotherapy developed visual deterioration after radiosurgery and was the only patient to do so. The place of radiosurgery in pituitary adenomas remains a matter for debate due at least in part to the complexity and variability of the lesions being treated (Pollock et al., 1994).

4 MENINGIOMAS Relatively few of these were treated in the early stages because they could not be visualized. When CT came, this problem was largely overcome. However, the role of the Gamma Knife was not immediately determined in Stockholm even after the introduction of CT to visualize them. The first publication based on a Stockholm material was in 1991 by Ladislau Steiner. In it, Steiner remained skeptical to the use of the Gamma Knife in the primary treatment of these tumors (Steiner et al., 1991). The author recalls a meeting in Hong Kong in 1994 where he presented a material containing meningioma cases, and Steiner, who was also present at the meeting, was highly skeptical of the results. In contrast with Stockholm, in Pittsburgh, meningiomas were found to be good objects for the Gamma Knife surgery (Kondziolka et al., 1991a,b). Fifty patients were treated during the first 30 months. Most were in the skull base. In 16 (32%), it was a primary treatment, and in 36 (72%), it followed previous microsurgery. Dose selection reflected the proximity of cranial nerves and vascular, pituitary, and brainstem structures. The actuarial 2-year tumor control rate was 96%. Only two patients showed delayed tumor growth outside the radiosurgical treatment volume. It was concluded that to date, stereotactic radiosurgery proved to be a relatively safe and effective therapy for selected patients with symptomatic meningiomas, either as an adjuvant treatment to prior resection or as a primary treatment alternative for

6 Vestibular schwannomas

patients whose advanced age, medical condition, or high-risk tumor location militated against surgical resection. This simple presentation was greatly appreciated. The difference is probably more the result of the Stockholm patients being less systematically assessed. Moreover, imaging at the time of the Stockholm treatments was less sophisticated than that available to the Pittsburgh group.

5 METASTASES For the purposes of this text, metastases were not treated in Stockholm during the early years because of Leksell’s opposition to treating malignant tumors. He was convinced that the results would be poor because of the nature of the disease and thus could damage the reputation of the new technique of radiosurgery. He was very strict about this and he clearly had a point. The treatment of metastases started in earnest in 1986 after his death. Their treatment was also not among the early indications in Pittsburgh.

6 VESTIBULAR SCHWANNOMAS 6.1 BACKGROUND The first standardized method of treatment was intracapsular removal as promoted by Cushing (Cushing, 1917). The recurrence rate and late mortality following intracapsular removal led to the increasing use of radical surgery as performed by Dandy (1925). The price for this policy was a total facial palsy in many patients. Thus, the practice developed of operating patients who had just some unilateral deafness and maybe quite mild unsteadiness, and in the process producing a total facial palsy. This was accepted as the necessary price for saving life and permitting long-term survival. Saving hearing was seldom an issue. The mortality of surgery in Olivecrona’ time and in his hands had fallen to 19%. During the early days of Gamma Knife treatments for vestibular schwannoma (VS), there were a number of anomalous reports, some published and some not. One such report from Stockholm, mentioned in Chapter 9 (Nore´n et al., 1983), detailed the delivery of much higher doses than are currently accepted both to the tumors and to the facial nerves, with no noteworthy ill effects. This was not commented upon at the time because the correct prescription doses were still being determined. The explanation remains undetermined. The Pittsburgh group with characteristic honesty reported high rates of facial and trigeminal nerve dysfunction in the early cases (Flickinger et al., 1993). These complications were over time gradually eradicated by means of improving knowledge of the appropriate prescription dose and improvements in dose planning. Opposition to radiosurgery was expressed in an article from the celebrated VS surgeon D.E. Brackmann who in a leading article detailed what he considered the weaknesses of radiosurgery and stressed the advantages of microsurgery

107

108

CHAPTER 11 Changing times and early debates

(Brackmann and Kwartler, 1990). In another paper, it was claimed that when radiosurgery did not control a tumor, subsequent surgery was more dangerous (Slattery and Brackmann, 1995). However, this paper reports five cases with very poor clinical function prior to surgery. Similar tumors were reported anecdotally in southern Sweden and Denmark in the early 1990s. Unfortunately, there is no publication on this topic. Nonetheless, it was stated that while surgery was more difficult, it was not claimed that this had any practical consequence for the patient. Thus, the introduction of the Gamma Knife was met with a degree of opposition from both neurosurgeons and otolaryngologists. This opposition has continued until the present day. Samii published the results of facial nerve function in his most recent 200 cases in 2006 (Samii et al., 2006). Among the 200 patients, there were 19% without good facial function. The actual distribution by Brackmann House grade is not tabulated in the paper. These results prompted a letter to the Journal of Neurosurgery (Ganz, 2007) where it was questioned that radical removal of such tumors is still appropriate. In view of Samii’s technical excellence and vast experience, these results have to be seen as the best possible. Since the facial palsy rate had remained high, an alternative treatment involving an intracapsular operation followed by radiosurgery was suggested. Samii in a reply took issue with the suggestion but agreed that if top-class surgery were not available, the suggestion might have merit.

6.2 SMALLER VESTIBULAR SCHWANNOMAS Tumor control following GKS is reported as 100% at 2 years in a series of 132 patients (Ganz et al., 2009). In another one, tumor control was 98.6% at 6 years (Flickinger et al., 2004). In both series, there was no permanent loss of facial nerve function. The mean tumor volume was 1.6 cm3 in the first series and not registered in the second. In a meta-analysis of 2204 patients, the facial nerve preservation rate was 95.5% if the tumor volume was 1.5 cm3 or less and 95.5% if it was more than 1.5 cm3. Moreover, the usual modern prescription dose is 12–13 Gy. For doses of 13 Gy or less, the facial nerve preservation rate was 98.5% irrespective of volume (Yang et al., 2009). No microsurgical series has ever matched these results. Gamma Knife users remain convinced that for tumors of 10 cm3 or less, GKS is not a treatment option but the treatment of choice.

6.3 LARGER VESTIBULAR SCHWANNOMAS After the introduction of the Gamma Knife, there was a convention that its use should be limited to smaller VSs. However, in 1991, a paper was published questioning the continued practice of radical removal of larger acoustic tumors (Lownie and Drake, 1991). Charles Drake had performed an intracapsular removal in 11 of his 124 VSs on whom he operated personally. This was done at the request of the patients who for different reasons could not accept a facial palsy. There was a postoperative facial palsy in two patients, and in both cases, it was the result of the sucker penetrating the

References

anterior wall of the tumor capsule. Four of the 11 patients died 10–19 years after the operation from unrelated causes. Five have had no recurrence. There have been two recent series publishing the effects of combining intracapsular surgery with radiosurgery for cases that recur or regrow in one series of 383 patients, 151 patients had tumors large enough to require surgery (maximum diameter >2.2 cm) (Haque et al., 2011). The surgery was performed with intraoperative electrophysiological monitoring, and if strict monitoring criteria were not met, the surgery was discontinued. Of these 151 patients, 55 had a gross total resection and 96 a subtotal resection. The patients were followed up, and of these, 20 suffered regrowth and were treated with GKS. These findings lend support to Drake’s notion that by no means, all tumors grow after subtotal resection. In another paper, 50 patients underwent subtotal resection, with surgery stopped when adequate brain stem decompression had been achieved and the tumor was of a size considered appropriate for GKS (van de Langenberg et al., 2011). Good facial nerve function (House Brackmann grades 1 and 2) was achieved in 94% of patients. Thus, it would seem that there is a growing body of evidence to support the practice of subtotal removal followed by GKS for larger tumors.

REFERENCES Barker, F.G., Butler, W.E., Lyons, S., Cascio, E., Ogilvy, C.S., Loeffler, J.S., Chapman, P.H., 2003. Dose-volume prediction of radiation-related complications after proton beam radiosurgery for cerebral arteriovenous malformations. J. Neurosurg. 99 (2), 254–263. Brackmann, D.E., Kwartler, J.A., 1990. Treatment of acoustic tumors with radiotherapy. Arch. Otolaryngol. Head Neck Surg. 116 (2), 161–162. Cushing, H., 1917. Tumors of the Nervus Acusticus. Saunders, Philadelphia. Dandy, W.E., 1925. An operation for the total removal of cerebellopontile (acoustic) tumors. Surg. Gynecol. Obstet. 41, 129–148. Drake, C.G., 1979. Cerebral arteriovenous malformations: considerations for and experience with surgical treatment in 166 cases. Clin. Neurosurg. 26, 145–208. Flickinger, J.C., Lunsford, L.D., Linskey, M.E., Duma, C.M., Kondziolka, D., 1993. Gamma knife radiosurgery for acoustic tumors: multivariate analysis of four year results. Radiother. Oncol. 27 (2), 91–98. Flickinger, J.C., Kondziolka, D., Niranjan, A., Maitz, A., Voynov, G., Lunsford, L.D., 2004. Acoustic neuroma radiosurgery with marginal tumor doses of 12 to 13 Gy. Int. J. Radiat. Oncol. Biol. Phys. 60 (1), 225–230. Ganz, J.C., 2007. Surgery or Gamma Knife. J. Neurosurg. 106 (5), 937–938. Ganz, J.C., Mathisen, J.R., Thorsen, F., Backlund, E.-O., 1992. Acoustic neuroma: early results related to radiobiological variables. In: Lunsford, L.D. (Ed.), Stereotactic Radiosurgery Update. Elsevier Science Publishing Co., New York, pp. 359–364. Ganz, J.C., Reda, W.A., Abdelkarim, K., 2009. Adverse radiation effects after Gamma Knife Surgery in relation to dose and volume. Acta Neurochir. 151 (1), 9–19. Haque, R., Wojtasiewicz, T.J., Gigante, P.R., Attiah, M.A., Huang, B., Isaacson, S.R., Sisti, M.B., 2011. Efficacy of facial nerve-sparing approach in patients with vestibular schwannomas. J. Neurosurg. 115, 917–992. Kjellberg, R.N., 1988. The Gamma Knife. JAMA 260 (7), 2505.

109

110

CHAPTER 11 Changing times and early debates

Kjellberg, R.N., 1989. Radiosurgery. Neurosurgery 25 (4), 670–671. Kondziolka, D., Lunsford, L.D., Coffey, R.J., Flickinger, J.C., 1991a. Stereotactic radiosurgery of meningiomas. J. Neurosurg. 74 (4), 552–559. Kondziolka, D., Lunsford, L.D., Coffey, R.J., Flickinger, J.C., 1991b. Gamma knife radiosurgery of meningiomas. Stereotact Funct. Neurosurg. 57 (1–2), 11–21. Lownie, S.P., Drake, C.G., 1991. Radical intracapsular removal of acoustic neurinomas: longterm follow-up review of 11 patients. J. Neurosurg. 74, 422–425. Lunsford, L.D., Kondziolka, D., Flickinger, J.C., Bissonette, D.J., Jungreis, C.A., Maitz, A.H., Horton, J.A., Coffey, R.J., 1991. Stereotactic radiosurgery for arteriovenous malformations of the brain. J. Neurosurg. 75 (4), 512–524. Nore´n, G., Arndt, J., Hindmarsh, T., 1983. Stereotactic radiosurgery in cases of acoustic neurinoma: further experiences. Neurosurgery 13 (1), 12–22. Pellettieri, L., Carlsson, C.A., Grevsten, S., Norle´n, G., Uhlemann, C., 1979. Surgical versus conservative treatment of intracranial arteriovenous malformations: a study in surgical decision-making. Acta Neurochir. Suppl. (Wien) 29, 1–86. Pollock, B.E., Kondziolka, D., Lunsford, L.D., Flickinger, J.C., 1994. Stereotactic radiosurgery for pituitary adenomas: imaging, visual and endocrine results. Acta Neurochir. Suppl. 62, 33–38. Samii, M., Gerganov, V., Samii, A., 2006. Improved preservation of hearing and facial nerve function in vestibular schwannoma surgery via the retrosigmoid approach in a series of 200 patients. J. Neurosurg. 105, 527–535. Sisti, M.B., Kader, A., Stein, B.M., 1993. Microsurgery for 67 intracranial arteriovenous malformations less than 3 cm in diameter. J. Neurosurg. 79 (5), 653–660. Slattery 3rd, W.H., Brackmann, D.E., 1995. Results of surgery following stereotactic irradiation for acoustic neuromas. Am. J. Otol. 16 (3), 315–319. Steiner, L., Leksell, L., Greitz, T., Forster, D.M., Backlund, E.O., 1972. Stereotaxic radiosurgery for cerebral arteriovenous malformations. Report of a case. Acta Chir. Scand. 138 (5), 459–464. Steiner, L., Leksell, L., Forster, D.M., Greitz, T., Backlund, E.O., 1974. Stereotactic radiosurgery in intracranial arteriovenous malformations. Acta Neurochir. Suppl. 21, 195–209. Steiner, L., Lindquist, Ch., Steiner, M., 1991. Meningiomas and gamma knife radiosurgery. In: AI-Mefty, O. (Ed.), Meningiomas. Raven Press, New York, pp. 263–272. Steiner, L., Lindquist, C., Cail, W., Karlsson, B., Steiner, M., 1993. Guest editorial: microsurgery and radiosurgery in brain arteriovenous malformations. J. Neurosurg. 79 (5), 647–652. Stephanian, E., Lunsford, L.D., Coffey, R.J., Bissonette, D.J., Flickinger, J.C., 1992. Gamma knife surgery for sellar and suprasellar tumors. Neurosurg. Clin. N. Am. 3 (1), 207–218. van de Langenberg, R., Hanssens, P.E., van Overbeeke, J.J., Verheul, J.B., Nelemans, P.J., de Bondt, B.J., Stokroos, R.J., 2011. Management of large vestibular schwannoma. Part I. Planned subtotal resection followed by Gamma Knife surgery: radiological and clinical aspects. J. Neurosurg. 115, 875–884. Yang, I., Aranda, D., Han, S.J., Chennupati, S., Sughrue, M.E., Cheung, S.W., Pitts, L.H., Parsa, A.T., 2009. Hearing preservation after stereotactic radiosurgery for vestibular schwannoma: a systematic review. J. Clin. Neurosci. 16 (6), 742–747.