Publications by our team

A. Dimitriadis, A. L. Palmer, R. A. S. Thomas, A. Nisbet, and C. H. Clark. “Adaptation and validation of a commercial head phantom for cranial radiosurgery dosimetry end-to-end audit.” Br. J. Radiol., p. 20170053, Apr. 2017. PMID: 28452563

Abstract

OBJECTIVE:

To adapt and validate an anthropomorphic head phantom for use in a cranial radiosurgery audit.

METHODS:

Two bespoke inserts were produced for the phantom: one for providing the target and organ at risk for delineation and the other for performing dose measurements. The inserts were tested to assess their positional accuracy. A basic treatment plan dose verification with an ionization chamber was performed to establish a baseline accuracy for the phantom and beam model. The phantom and inserts were then used to perform dose verification measurements of a radiosurgery plan. The dose was measured with alanine pellets, EBT extended dose film and a plastic scintillation detector (PSD).

RESULTS:

Both inserts showed reproducible positioning (±0.5 mm) and good positional agreement between them (±0.6 mm). The basic treatment plan measurements showed agreement to the treatment planning system (TPS) within 0.5%. Repeated film measurements showed consistent gamma passing rates with good agreement to the TPS. For 2%-2 mm global gamma, the mean passing rate was 96.7% and the variation in passing rates did not exceed 2.1%. The alanine pellets and PSD showed good agreement with the TPS (-0.1% and 0.3% dose difference in the target) and good agreement with each other (within 1%).

CONCLUSION:

The adaptations to the phantom showed acceptable accuracies. The presence of alanine and PSD do not affect film measurements significantly, enabling simultaneous measurements by all three detectors. Advances in knowledge: A novel method for thorough end-to-end test of radiosurgery, with capability to incorporate all steps of the clinical pathway in a time-efficient and reproducible manner, suitable for a national audit.

Cenzato M, Boccardi E, Beghi E, Vajkoczy P, Szikora I, Motti E, Regli L, Raabe A, Eliava S, Gruber A, Meling TR, Niemela M, Pasqualin A, Golanov A, Karlsson B, Kemeny A, Liscak R, Lippitz B, Radatz M, La Camera A, Chapot R, Islak C, Spelle L, Debernardi A, Agostoni E, Revay M, Morgan MK. European consensus conference on unruptured brain AVMs treatment (Supported by EANS, ESMINT, EGKS, and SINCH).   Acta Neurochir (Wien). 2017 Jun;159(6):1059-1064. PMID 28389875

Abstract

In December of 2016, a Consensus Conference on unruptured AVM treatment, involving 24 members of the three European societies dealing with the treatment of cerebral AVMs (EANS, ESMINT, and EGKS) was held in Milan, Italy. The panel made the following statements and general recommendations: (1) Brain arteriovenous malformation (AVM) is a complex disease associated with potentially severe natural history; (2) The results of a randomized trial (ARUBA) cannot be applied equally for all unruptured brain arteriovenous malformation (uBAVM) and for all treatment modalities; (3) Considering the multiple treatment modalities available, patients with uBAVMs should be evaluated by an interdisciplinary neurovascular team consisting of neurosurgeons, neurointerventionalists, radiosurgeons, and neurologists experienced in the diagnosis and treatment of brain AVM; (4) Balancing the risk of hemorrhage and the associated restrictions of everyday activities related to untreated unruptured AVMs against the risk of treatment, there are sufficient indications to treat unruptured AVMs grade 1 and 2 (Spetzler-Martin); (5) There may be indications for treating patients with higher grades, based on a case-to-case consensus decision of the experienced team; (6) If treatment is indicated, the primary strategy should be defined by the multidisciplinary team prior to the beginning of the treatment and should aim at complete eradication of the uBAVM; (7) After having considered the pros and cons of a randomized trial vs. a registry, the panel proposed a prospective European Multidisciplinary Registry.

Nagy G, Grainger A, Hodgson TJ, Rowe JG, Coley SC, Kemeny AA, Radatz MW. Staged-Volume Radiosurgery of Large Arteriovenous Malformations Improves Outcome by Reducing the Rate of Adverse Radiation Effects. Neurosurgery. 2016 Feb 15. [Epub ahead of print] Neurosurgery. 2017 Feb 1;80(2):180-192. PMID 28173493 

Abstract

BACKGROUND:

The treatment of large arteriovenous malformations (AVMs) remains challenging. Recently, staged-volume radiosurgery (SVRS) has become an option.

OBJECTIVE:

To compare the outcome of SVRS on large AVMs with our historical, single-stage radiosurgery (SSRS) series.

METHODS:

We have been prospectively collecting data of patients treated by SVRS since 2007. There were 84 patients who had a median age of 37 years (range, 9-62 years) who were treated until July 2013. The outcomes of 76 of those who had follow-ups available were analyzed and compared with the outcomes of 122 patients treated with the best SSRS technique.

RESULTS:

There were 21.5% of AVMs that were deep seated, and 44% presented with hemorrhage resulting in 45% fixed neurological deficit. There were 14% of patients who had undergone embolization before radiosurgery. The median nidus treatment volume was 19.7 cm3 (6.65-68.7) and 17.5 Gy (13-22.5) prescription isodose was given. Of the 44 lesions having radiological follow-up at 4 years, 61.4% were completely obliterated. Previous embolization (50% with and 63% without) and higher Spetzler-Martin grades appeared to be the negative factors in successful obliteration, but treatment volume was not. Within 3 years after radiosurgery, the annual bleed rates of unruptured and previously ruptured AVMs were 3.2% and 5.6%, respectively. Three bleeds were fatal and 2 resulted in significant modified Rankin scale 3 morbidity. These rates differ little from SSRS. Temporary adverse radiation effects (AREs) did not change significantly, but permanent AREs dropped from 15% to 6.5% (P = .03) compared with SSRS.

CONCLUSION:

Obliteration and hemorrhage rates of large AVMs treated by SVRS are similar to historical SSRS. However, SVRS offers a lower rate of AREs.

Kemeny AA. Tolosa-Hunt Syndrome: Another legitimate target for radiosurgery? Acta Neurochir (Wien). 2016 Jan;158(1):141.
PMID 26611688

A. Dimitriadis, I. Patallo Silvestre, I. Billas, S. Duane, A. Nisbet, and C. H. Clark. “Characterisation of a plastic scintillation detector to be used in a multicentre stereotactic radiosurgery audit.” Radiat. Phys. Chem., no. Special Issue: ICDA2 Conference Proceedings, Feb. 2017.

A. Dimitriadis, K. J. Kirkby, A. Nisbet, and C. H. Clark. “Current Status of Cranial Stereotactic Radiosurgery in the UK.” Br. J. Radiol., vol. 89, p. 20150452, Dec. 2016. PMID: 26689091

Abstract

OBJECTIVE:

To investigate and benchmark the current clinical and dosimetric practices in stereotactic radiosurgery (SRS) in the UK.

METHODS:

A detailed questionnaire was sent to 70 radiotherapy centres in the UK. 97% (68/70) of centres replied between June and December 2014.

RESULTS:

21 centres stated that they are practising SRS, and a further 12 centres plan to start SRS by the end of 2016. The most commonly treated indications are brain metastases and acoustic neuromas. A large range of prescription isodoses that range from 45% to 100% between different radiotherapy centres was seen. Ionization chambers and solid-water phantoms are used by the majority of centres for patient-specific quality assurance, and thermoplastic masks for patient immobilization are more commonly used than fixed stereotactic frames. The majority of centres perform orthogonal kilovoltage X-rays for localization before and during delivery. The acceptable setup accuracy reported ranges from 0.1 to 2 mm with a mean of 0.8 mm.

CONCLUSION:

SRS has been increasing in use in the UK and will continue to increase in the next 2 years. There is no current consensus between SRS centres as a whole, or even between SRS centres with the same equipment, on the practices followed. This indicates the need for benchmarking and standardization in SRS practices within the UK.

A. L. Palmer, A. Dimitriadis, A. Nisbet, and C. H. Clark. “Evaluation of Gafchromic EBT-XD film, with comparison to EBT3 film, and application in high dose radiotherapy verification.” Phys. Med. Biol., vol. 60, no. 22, pp. 8741–8752, 2015. PMID: 26512917

A. Rojas-Villabona , N. Kitchen and I. Paddick, “Investigation of dosimetric differences between the TMR 10 and convolution algorithm for Gamma Knife stereotactic radiosurgery.” J Appl Clin Med Phys.2016 Nov 8;17(6):6347. PMID:27929495

Abstract

Since its inception, doses applied using Gamma Knife Radiosurgery (GKR) have been calculated using a simple TMR algorithm, which assumes the patient’s head is of even density, the same as water. This results in a significant approximation of the dose delivered by the Gamma Knife. We investigated how GKR dose cal-culations varied when using a new convolution algorithm clinically available for GKR planning that takes into account density variations in the head compared with the established calculation algorithm. Fifty-five patients undergoing GKR and harboring 85 lesions were voluntarily and prospectively enrolled into the study. Their clinical treatment plans were created and delivered using TMR 10, but were then recalculated using the density correction algorithm. Dosimetric differences between the planning algorithms were noted. Beam on time (BOT), which is directly proportional to dose, was the main value investigated. Changes of mean and maximum dose to organs at risk (OAR) were also assessed. Phantom studies were performed to investigate the effect of frame and pin materials on dose calculation using the convolution algorithm. Convolution yielded a mean increase in BOT of 7.4% (3.6%-11.6%). However, approximately 1.5% of this amount was due to the head contour being derived from the CT scans, as opposed to measurements using the Skull Scaling Instrument with TMR. Dose to the cochlea calculated with the convolution algorithm was approximately 7% lower than with the TMR 10 algorithm. No significant difference in relative dose distribution was noted and CT artifact typically caused by the stereotactic frame, glue embolization material or different fixation pin materials did not systematically affect convolu-tion isodoses. Nonetheless, substantial error was introduced to the convolution calculation in one target located exactly in the area of major CT artifact caused by a fixation pin. Inhomogeneity correction using the convolution algorithm results in a considerable, but consistent, dose shift compared to the TMR 10 algorithm traditionally used for GKR. A reduction of the prescription dose may be neces-sary to obtain the same clinical effect with the convolution algorithm. Head shape definition using CT outlining can reduce treatment uncertainty from head shape approximations.

A. Rojas-Villabona , K. Miszkiel, N. Kitchen ,R. Jäger and I. Paddick. “Evaluation of the stability of the stereotactic Leksell Frame G in Gamma Knife radiosurgery.” J Appl Clin Med Phys. 2016 May 8;17(3):5944. PMID:27167264

Abstract

The purpose of this study was to evaluate the stability of the Leksell Frame G in Gamma Knife radiosurgery (GKR). Forty patients undergoing GKR underwent pretreatment stereotactic MRI for GKR planning and stereotactic CT immediately after GKR. The stereotactic coordinates of four anatomical landmarks (cochlear apertures and the summits of the anterior post of the superior semicircular canals, bilaterally) were measured by two evaluators on two separate occasions in the pre-treatment MRI and post-treatment CT scans and the absolute distance between the observations is reported. The measurement method was validated with an indepen-dent group of patients who underwent both stereotactic MRI and CT imaging before treatment (negative controls; n: 5). Patients undergoing GKR for arteriovenous malformations (AVM) also underwent digital subtraction angiography (DSA), which could result in extra stresses on the frame. The distance between landmark local-ization in the scans for the negative control group (0.63 mm; 95% CI: 0.57-0.70; SD: 0.29) represents the overall consistency of the evaluation method and provides an estimate of the minimum displacement that could be detected by the study. Two patients in the study group had the fiducial indicator box accidentally misplaced at post-treatment CT scanning. This simulated the scenario of a frame displacement, and these cases were used as positive controls to demonstrate that the evaluation method is capable of detecting a discrepancy between the MRI and CT scans, if there was one. The mean distance between the location of the landmarks in the pretreatment MRI and post-treatment CT scans for the study group was 0.71 mm (95% CI: 0.68-0.74; SD:0.32), which was not statistically different from the over-all uncertainty of the evaluation method observed in the negative control group (p = 0.06). The subgroup of patients with AVM (n: 9), who also underwent DSA, showed a statistically significant difference between the location of the landmarks compared to subjects with no additional imaging: 0.78 mm (95% CI: 0.72-0.84) vs. 0.69 mm (95% CI: 0.66-0.72), p = 0.016. This is however a minimal differ-ence (0.1 mm) and the mean difference in landmark location for each AVM patient remained submillimeter. This study demonstrates submillimeter stability of the Leksell Frame G in GKR throughout the treatment procedure.

W.T. Millar, J. W. Hopewell, I. Paddick,  C. Lindquist, H. Nordstron, P. Lidberg and J. Garding. “The role of the concept of biologically effective does (BED) in treamtment planning in radiosurgery.”  Phys Med. 2015 Sep:31(6): 627-33. PMID: 25982304

Abstract

Radiosurgery (RS) treatment times vary, even for the same prescription dose, due to variations in the collimator size, the number of iso-centres/beams/arcs used and the time gap between each of these exposures. The biologically effective dose (BED) concept, incorporating fast and slow components of repair, was used to show the likely influence of these variables for Gamma Knife patients with Vestibular Schwannomas. Two patients plans were selected, treated with the Model B Gamma Knife, these representing the widest range of treatment variables; iso-centre numbers 3 and 13, overall treatment times 25.4 and 129.6 min, prescription dose 14 Gy. These were compared with 3 cases treated with the Perfexion(®) Gamma Knife. The iso-centre number varied between 11 and 18, treatment time 35.7 – 74.4 min, prescription dose 13 Gy. In the longer Model B Gamma Knife treatment plan the 14 Gy iso-dose was best matched by the 58 Gy2.47 iso-BED line, although higher and lower BED values were associated with regions on the prescription iso-dose. The equivalent value for the shorter treatment was 85 Gy2.47. BED volume histograms showed that a BED of 85 Gy2.47 only covered ∼65% of the target in the plan with the longer overall treatment time. The corresponding BED values for the 3 cases, treated with the Perfexion(®) Gamma Knife, were 59.5, 68.5 and 71.5 Gy2.47. In conclusion BED calculations, taking account of the repair of sublethal damage, may indicate the importance of reporting overall time to reflect the biological effectiveness of the total physical dose applied.

C. Chung, M. Torrens, I. Paddick, S. Ryu, P. Hanssens and D. Jaffray. “Radiosurgery Nomenclature: A Confusion of Tongues.” Int J Radiat Oncol Biol Phys. 2015 Jul 1;92(3):512-3. PMID: 26068485

H. Benmakhlouf , J. Johansson, I. Paddick and P. Andreo. “Monte Carlo calculated and experimentally determined output correction factors for small field detectors in Leksell Gamma Knife Perfexion beams.” Phys Med Biol. 2015 May 21;60(10):3959-73. PMID: 25909660

Abstract

The measurement of output factors (OF) for the small photon beams generated by Leksell Gamma Knife® (LGK) radiotherapy units is a challenge for the physicist due to the under or over estimation of these factors by a vast majority of the detectors commercially available. Output correction factors, introduced in the international formalism published by Alfonso (2008 Med. Phys. 35 5179-86), standardize the determination of OFs for small photon beams by correcting detector-reading ratios to yield OFs in terms of absorbed-dose ratios. In this work output correction factors for a number of detectors have been determined for LGK Perfexion™ (60)Co γ-ray beams by Monte Carlo (MC) calculations and measurements. The calculations were made with the MC system PENELOPE, scoring the energy deposited in the active volume of the detectors and in a small volume of water; the detectors simulated were two silicon diodes, one liquid ionization chamber (LIC), alanine and TLD. The calculated LIC output correction factors were within ± 0.4%, and this was selected as the reference detector for experimental determinations where output correction factors for twelve detectors were measured, normalizing their readings to those of the LIC. The MC-calculated and measured output correction factors for silicon diodes yielded corrections of up to 5% for the smallest LGK collimator size of 4 mm diameter. The air ionization chamber measurements led to extremely large output correction factors, caused by the well-known effect of partial volume averaging. The corrections were up to 7% for the natural diamond detector in the 4 mm collimator, also due to partial volume averaging, and decreased to within about ± 0.6% for the smaller synthetic diamond detector. The LIC, showing the smallest corrections, was used to investigate machine-to-machine output factor differences by performing measurements in four LGK units with different dose rates. These resulted in OFs within ± 0.6% and ± 0.2% for the 4 mm and 8 mm collimators, respectively, providing evidence for the use of generic OFs for these LGK beams. Using the experimentally derived output correction factors, OFs can be measured using a wide range of commercially available detectors.

I. Paddick and E. Motti. “Targeting and Conformality in Arteriovenous Malformation Radiosurgery”:  Prog Neurol Surg. 2013;27:35-48. PMID: 23258507

Abstract

The struggle to achieve a high degree of conformity around targets of complex morphology has been one of the driving forces in the development of ever more sophisticated radiosurgical devices and intricate treatment delivery. Rarely are radiosurgical targets more complex in shape than those associated with arteriovenous malformations (AVMs). In this report we examine theoretical and practical issues of target delineation and creation of conformal AVM treatment plans, and comment on the concepts of gradient and homogeneity.

‘Targeting and Conformality in Arteriovenous Malformation Radiosurgery” is a paper co-authored by Ian Paddick included in the new publication by Karger, Gamma Knife Radiosurgery for Brain Vascular Malformations, edited by Aray Niranjan, Hieyuki Kano and L Dade Lunsford. The book which can be previewed here is available for purchase from Karger.

ISSN: 0079-6492
e-ISSN: 1662-3924
ISBN: 978-3-8055-9619-0

E.B. Dinca,P. de Lacy, J. Yianni, J. Rowe, M.W. Radatz, D. Preotiuc-Pietro and A. A. Kemeny. “Gamma Knife surgery for pediatric arteriovenous malformations: a 25-year retrospective study.” J Neurosurg Pediatr.  2012 Aug 31. PMID: 22938080

Abstract

Object The authors present their 25-year experience in treating pediatric arteriovenous malformations (AVMs) to allow comparisons with other historic studies and data in adults. Methods Data were collected from a prospectively maintained departmental database selected for age and supplemented by case note review and telephone interviews as appropriate. Results Three hundred sixty-three patients, ages 1-16 years (mean ± SD, 12 ± 3.2 years), underwent 410 treatments; 4 had planned 2-stage treatments and 43 were retreated subsequent to an initial partial response. Fifty-eight percent received general anesthesia for the procedure. Sixteen percent had previously undergone embolization. The most common presenting symptoms were as follows: hemorrhage (80.2%), epilepsy (8.3%; overall seizure prevalence 19.9%), and migrainous headaches (6.3%). Only 0.28% of the AVMs were incidental findings. The mean lesion volume was 3.75 ± 5.3 cm(3) (range 0.01-32.8 cm(3)), with a median Spetzler-Martin grade of III (range I-V). The mean peripheral (therapeutic) dose was 22.7 ± 2.3 Gy (range 15-25 Gy), corresponding to a mean maximum dose of 43.6 ± 6 Gy (range 25-51.4 Gy). The obliteration rate was 71.3% in patients who received one treatment and 62.5% for retreated patients, with a mean obliteration time of 32.4 and 79.6 months, respectively. The overall obliteration rate was 82.7%. No follow-up data are as yet available for the 4 patients who underwent the staged treatments. Only 4 patients received peripheral doses below 20 Gy, and the AVM was obliterated in 3 of these patients. The other patients received 20, 22.5, or 25 Gy and had obliteration rates of 82.6%, 77.7%, and 86.3%, respectively. The bleeding rate postradiosurgery was 2.2%, and the cumulative complication rate was 3.6%, with radionecrosis being the most common complication (1.1%). Conclusions Surprisingly, there was no correlation (p = 0.43) between outcome and radiosurgical dose when that dose was between 20 and 25 Gy, thus suggesting that the lower of these 2 doses may be effective. Radiosurgery for pediatric AVM is safe and effective.

E.B. Dinca, J. Yianni, J. Rowe, M.W. Radatz, D. Preotiuc-Pietro, P. Rundle, I. Rennie and A. A. Kemeny. “Survival and complications following Gamma Knife radiosurgery or enucleation for ocular melanoma: a 20-year experience.” Acta Neurochir (Wien). 2012 Apr;154(4):605-10. PMID: 22231777

Abstract

BACKGROUND:

We present our experience in treating ocular melanoma at the National Centre for Stereotactic Radiosurgery in Sheffield, UK over the last 20 years.

METHOD:

We analysed 170 patients treated with Gamma Knife radiosurgery, recorded the evolution of visual acuity and complication rates, and compared their survival with 620 patients treated with eye enucleation. Different peripheral doses (using the 50% therapeutic isodose) were employed: 50-70 Gy for 24 patients, 45 Gy for 71 patients, 35 Gy for 62 patients.

FINDINGS:

There was no significant difference in survival between the 35-Gy, 45-Gy and 50- to 70-Gy groups when compared between themselves (p = 0.168) and with the enucleation group (p = 0.454). The 5-year survival rates were: 64% for 35 Gy, 62.71% for 45 Gy, 63.6% for 50-70 Gy and 65.2% for enucleated patients. Clinical variables influencing survival for radiosurgery patients were tumour volume (p = 0.014) and location (median 66.4 vs 37.36 months for juxtapapillary vs peripheral tumours, respectively; p = 0.001), while age and gender did not prove significant. Regarding complications, using 35 Gy led to more than a 50% decrease, when compared with the 45-Gy dose, in the incidence of cataract, glaucoma and retinal detachment. Retinopathy, optic neuropathy and vitreous haemorrhage were not significantly influenced. Blindness decreased dramatically from 83.7% for 45 Gy to 31.4% for 35 Gy (p = 0.006), as well as post-radiosurgery enucleation: 23.9% for 45 Gy vs 6.45% for 35 Gy (p = 0.018). Visual acuity, recorded up to 5 years post-radiosurgery, was significantly better preserved for 35 Gy than for 45 Gy (p = 0.0003).

CONCLUSIONS:

Using 35 Gy led to a dramatic decrease in complications, vision loss and salvage enucleation, while not compromising patient survival.

G, Nagy, O. Major, J. G. Rowe, M. W. Radatz, T. J. Hodgson, S. C. Coley and A. A. Kemeny. “Stereotactic radiosurgery for arteriovenous malformations located in deep critical regions.” Neurosurgery. 2012 Jun;70(6):1458-69; discussion 1469-71. PMID: 22186841

Abstract

BACKGROUND

Radiosurgery is widely used to treat deep eloquent arteriovenous malformations (AVMs).

OBJECTIVE

To evaluate how anatomic location, AVM size, and treatment parameters define outcome.

METHODS

Retrospective analysis of 356 thalamic/basal ganglia and 160 brainstem AVMs treated with gamma knife radiosurgery.

RESULTS

Median volume was 2 cm (range, 0.02-50) for supratentorial and 0.5 cm (range, 0.01-40) for brainstem AVMs; the marginal treatment doses were 17.5 to 25 Gy. After single treatment, obliteration was achieved in 65% of the brainstem, in 69% of the supratentorial, and 40% of the peritectal AVMs. Obliteration of lesions <4 cm was better in the brainstem (70%) and in the supratentorium (80%), but not in the peritectal region (40%). Complications were rare (6%-15%) and mild (≤ modified Rankin scale [MRS] 2). Rebleed rate increased with size, but was not higher than before treatment. AVMs >4 cm in the brainstem were treated with unacceptable morbidity and low cure rate. Obliteration of large supratentorial AVMs was 65% to 47% with more complications ≥ MRS3. Repeat radiosurgical treatment led to obliteration in 66% of the cases with minor morbidity.

CONCLUSION

Deep eloquent AVMs <4 cm can be treated safely and effectively with radiosurgery. Obliteration of peritectal AVMs is significantly lower after a single treatment. However, morbidity is low, and repeat treatment leads to good obliteration. Radiosurgical treatment >4 cm in the brainstem is not recommended. Supratentorial deep AVMs >8 cm can be treated with radiosurgery with higher risk and lower obliteration rate. However, these lesions are difficult to treat with other treatment modalities, and a 50% success rate makes radiosurgery a good alternative even in this challenging group.

G. Nagy, J. G. Rowe, M.W. Radatz, T.J. Hodgson, S.C. Coley and A.A. Kemeny. “A historical analysis of single-stage gamma knife radiosurgical treatment for large arteriovenous malformations: evolution and outcomes.” Acta Neurochir (Wien). 2012 Mar;154(3):383-94. PMID: 22173687

Abstract

BACKGROUND

Large arteriovenous malformations (AVMs) remain challenging and difficult to treat, reflected by evolving strategies developed from simple radiosurgical plans, to encompass embolization and, recently, staged volume treatments. To establish a baseline for future practice, we reviewed our clinical experience.

METHOD

The outcomes for 492 patients (564 treatments) with AVMs >10 cm(3) treated by single-stage radiosurgery were retrospectively analysed in terms of planning, previous embolization and size.

RESULTS

Twenty-eight percent of the patients presented with haemorrhage at a median age of 29 years (range: 2-75). From 1986 to 1993 (157 patients) plans were simplistic, based on angiography using a median of 2 isocentres and a marginal dose of 23 Gy covering 45-70% of the AVM (median volume 15.7 cm(3)). From 1994 to 2000 (225 patients) plans became more sophisticated, a median of 5 isocentres was used, covering 64-95% of the AVM (14.6 cm(3)), with a marginal dose of 21 Gy. Since 2000, MRI has been used with angiography to plan for 182 patients. Median isocentres increased to 7 with similar coverage (62-94%) of the AVM (14.3 cm(3)) and marginal dose of 21 Gy. Twenty-seven percent, 30% and 52% of patients achieved obliteration at 4 years, respectively. The proportion of prior embolization increased from 9% to 44% during the study. Excluding the embolized patients, improvement in planning increased obliteration rates from 28% to 36% and finally 63%. Improving treatment plans did not significantly decrease the rate of persisting radiation-induced side effects (12-16.5%). Complication rate rose with increasing size. One hundred and twenty-three patients underwent a second radiosurgical treatment, with a 64% obliteration rate, and mild and rare complications (6%).

CONCLUSIONS

Better visualization of the nidus with multimodality imaging improved obliteration rates without changing morbidity. Our results support the view that prior embolization can make interpretation of the nidus more difficult, reducing obliteration rate. It will be important to see how results of staged volume radiosurgery compare with this historical material.

Kemeny AA. Long-term outcomes of microvascular decompression and Gamma Knife surgery for trigeminal neuralgia: a retrospective comparison study. Invited Editorial.  Acta Neurochir (Wien). 2017 Sep 18. PMID 28920139

Loescher AR, Radatz MW, Kemeny AA, Rowe JG. Stereotactic radiosurgery for trigeminal neuralgia: outcomes and complications. British Journal of Neurosurgery 08/2011; 26(1):45-52. PMID: 21815736 

Abstract

Stereotactic radiosurgery is one of a number of recognised treatments for the management of trigeminal neuralgia refractory to drug therapy. The reported success of stereotactic radiosurgery in managing patients with trigeminal neuralgia varies in different units from 22 to 75%. This paper reports the outcomes of patients with trigeminal neuralgia who were treated at the National Centre for Stereotactic Radiosurgery in Sheffield, UK. The study reports the outcome of 72 patients treated consecutively between October 2004 and May 2008. Data were collected prospectively by a postal questionnaire sent to patients at 6, 12 and 24 months after treatment. The median age was 65.6 years (39 males: 33 females). Fourteen patients had secondary trigeminal neuralgia (eight multiple sclerosis). Fifteen of the patients included in the study were receiving a second treatment (an initial treatment having improved their pain significantly for at least 6 months). All radiosurgical procedures were performed using a single 4 mm collimator isocenter covering the region of the dorsal root entry zone with a maximal radiation dose of 80 Gy. The percentage of patients defined as having an excellent outcome (pain free without medication) was 39% after 6 months, 36% after 12 months and 64% after 24 months. The percentage of patients who reported being very satisfied with treatment was 71% after 6 months, 57% after 12 months and 53% after 24 months. Half the patients with secondary trigeminal neuralgia were pain free without medication after treatment, and 60% of patients who underwent a second treatment were pain free. A new trigeminal sensory deficit was reported by 31% of patients after radiosurgical treatment.

Nagy G, Razak A, Rowe JG, Hodgson TJ, Coley SC, Radatz MW, Patel UJ, Kemeny AA. Stereotactic radiosurgery for deep-seated cavernous malformations: a move toward more active, early intervention. Clinical article. Journal of Neurosurgery 10/2010; 113(4):691-9. PMID: 20433275

Abstract

OBJECT

The role of radiosurgery in the treatment of cavernous malformations (CMs) remains controversial. It is frequently recommended only for inoperable lesions that have bled at least twice. Rehemorrhage can carry a substantial risk of morbidity, however. The authors reviewed their practice of treating deep-seated inoperable CMs to assess the complication rate of radiosurgery, the impact that radiosurgery might have on rebleeding, and whether a more active, earlier intervention is justified in managing this condition.

METHODS

The authors performed a retrospective analysis of 113 patients with 79 brainstem and 39 thalamic/basal ganglia CMs treated with Gamma Knife surgery. Lesions were stratified into 2 groups: those that might be lower risk with no more than 1 symptomatic bleed before radiosurgical treatment and those deemed high risk with multiple symptomatic hemorrhages before treatment.

RESULTS

Forty-one CMs had multiple symptomatic hemorrhages before radiosurgery with a first-ever bleed rate of 2.9% per lesion per year, a rebleed rate of 30.5% per lesion per year, and a median time of 1.5 years between the first and second bleeds. In this group the rebleed rate decreased to 15% for the first 2 years after radiosurgery and declined further to 2.4% thereafter. Pretreatment multiple bleeds led to persistent deficits in 72% of the patients. Seventy-seven CMs had no more than 1 symptomatic bleed before radiosurgery, making for a lifetime bleed rate of 2.2% per lesion per year. The short period between the presenting bleed and treatment (median 1 year) makes the natural history in this group uncertain. The rate of hemorrhage in the first 2 years after treatment was 5.1%, and 1.3% thereafter. Pretreatment hemorrhages resulted in permanent deficits in 43% of the patients in this group, a rate significantly lower than in the multiple-bleeds group (p < 0.001). Posttreatment hemorrhages led to persistent deficits in only 7.3% of the patients. Permanent adverse radiation effects were rare (7.3%) and minor in both groups.

CONCLUSIONS

Stereotactic radiosurgery is a safe management strategy for CMs in eloquent sites with the marked advantage of reducing rebleed risks in patients with repeated pretreatment hemorrhages. The benefit in treating CMs with a single bleed is less clear. Note, however, that repeated hemorrhage carries a significant risk of increased morbidity far in excess of any radiosurgery-related morbidity, and the authors assert that this finding justifies the early active management of deep-seated CMs.

Nagy G, Kemeny AA, Major O, Erőss L, Várady P, Mezey G, Fedorcsák I, Bognár L. [Radiosurgery of intracerebral cavernomas–current international trends]. Ideggyogy Sz. 2015 Jul 30;68(7-8):229-42. Review. Hungarian.
PMID: 26380417

Abstract

Although still a controversial management option, radio-surgery of intracranial cavernomas has become increasingly popular world-wide during the last decade. Microsurgery is a safe and effective treatment for symptomatic hemispheric cavernomas. However, the indication for microsurgical resection of deep eloquent cavernomas is relatively limited even in experienced hands. The importance of radiosurgery has recently been appreciated in parallel with increasing positive experiences both in terms of effectiveness and safety, especially for cases high risk for surgical resection, in the brainstem, thalamus and basal ganglia. While radiosurgery was earlier indicated mainly for surgically inaccessible lesions that had bled multiple times, a more proactive policy has recently become more accepted. In our opinion preventive treatment with the low morbidity radiosurgery serves the patients’ interest especially for deep eloquent lesions that had bled not more than once, due to the cumulative morbidity of repeated hemorrhages. Despite our increasing knowledge on natural history, there is currently no available treatment algorithm for cavernomas. Arguments for all three treatment modalities (observation, microsurgery and radiosurgery) are established, but their indication criteria are yet to be defined. It is time to organize a prospective population based data collection in Hungary, which appears to be the most realistic way to clarify indication criteria.

Nagy G, Kemeny AA Radiosurgery for cerebral cavernomas.J Neurosurg Sci. 2015 Sep;59(3):295-306. Epub 2015 May 13.
PMID: 25968927

Abstract

The role of stereotactic radiosurgery (SRS) in the management of cerebral cavernomas (CCMs) remains controversial. However, during the last decade the increasing knowledge on natural history and numerous publications from SRS centers using modern treatment protocols has been changing the initial resistance of the neurosurgical community. Unfortunately, the quality of publications on CCM SRS remains heterogeneous. Controversies arise from the lack of control groups, the different definition of hemorrhage, heterogeneous patient populations, and poor definition of treatment protocols. The key for proper interpretation of results is the understanding of the natural history of CCMs, which is varied both according to anatomical location and the presence or absence of previous hemorrhage. Hemispheric lesions appear to be more benign with lower annual bleed rate and risk of persisting disability, whereas those found in the thalamus, basal ganglia and brainstem typically have higher rebleed risk resulting in higher cumulative morbidity following subsequent hemorrhages. However, we are still unable at presentation to predict the future behavior of an individual lesion. In the present paper we critically review and analyze the modern SRS literature on CCMs. The expanding number of available data with current treatment protocols strongly supports the initial intuition that SRS is an effective treatment alternative for deep-seated CCMs with multiple hemorrhages reducing pretreatment annual rebleed rates from 32% pre-treatment to 1.5% within 2 years after treatment (N.=197). Moreover, it appears to stabilize lesions with no more than one bleed, and it is also effective for CCMs causing therapy resistant epilepsy especially if applied within 3 years after presentation. In modern SRS series the rate of persisting adverse radiation effects is low, resulting only in mild morbidity even in deep-seated lesions (4.16%, N.=376), and morbidity caused by post-treatment hemorrhages is also low (5.3%, N.=132). Admittedly, there is no high quality evidence to define the relative roles of microsurgery, SRS and wait-and-see policy in the management of detected CCMs at present. However, based on increasing positive experience, we recommend early SRS soon after presentation in neurologically intact or minimally disabled patients harboring deep-seated CCMs, because waiting for the cumulative morbidity of the natural history to justify an otherwise low-risk intervention does not serve the patient well.

Torrens M, Chung C, Chung HT, Hanssens P, Jaffray D, Kemeny A, Larson D, Levivier M, Lindquist C, Lippitz B, Novotny J Jr, Paddick I, Prasad D, Yu CP. Standardization of terminology in stereotactic radiosurgery: Report from the Standardization Committee of the International Leksell Gamma Knife Society: special topic. J Neurosurg. 2014 Dec;121 Suppl:2-15.
PMID: 25587587

Abstract

OBJECT:

This report has been prepared to ensure more uniform reporting of Gamma Knife radiosurgery treatment parameters by identifying areas of controversy, confusion, or imprecision in terminology and recommending standards.

METHODS:

Several working group discussions supplemented by clarification via email allowed the elaboration of a series of provisional recommendations. These were also discussed in open session at the 16th International Leksell Gamma Knife Society Meeting in Sydney, Australia, in March 2012 and approved subject to certain revisions and the performance of an Internet vote for approval from the whole Society. This ballot was undertaken in September 2012.

RESULTS:

The recommendations in relation to volumes are that Gross Target Volume (GTV) should replace Target Volume (TV); Prescription Isodose Volume (PIV) should generally be used; the term Treated Target Volume (TTV) should replace TVPIV, GTV in PIV, and so forth; and the Volume of Accepted Tolerance Dose (VATD) should be used in place of irradiated volume. For dose prescription and measurement, the prescription dose should be supplemented by the Absorbed Dose, or DV% (for example, D95%), the maximum and minimum dose should be related to a specific tissue volume (for example, D2% or preferably D1 mm3), and the median dose (D50%) should be recorded routinely. The Integral Dose becomes the Total Absorbed Energy (TAE). In the assessment of planning quality, the use of the Target Coverage Ratio (TTV/ GTV), Paddick Conformity Index (PCI = TTV2/[GTV · PIV]), New Conformity Index (NCI = [GTV · PIV]/TTV2), Selectivity Index (TTV/PIV), Homogeneity Index (HI = [D2% –D98%]/D50%), and Gradient Index (GI = PIV0.5/PIV) are reemphasized. In relation to the dose to Organs at Risk (OARs), the emphasis is on dose volume recording of the VATD or the dose/volume limit (for example, V10) in most cases, with the additional use of a Maximum Dose to a small volume (such as 1 mm3) and/or a Point Dose and Mean Point Dose in certain circumstances, particularly when referring to serial organs. The recommendations were accepted by the International Leksell Gamma Knife Society by a vote of 92% to 8%.

CONCLUSIONS:

An agreed-upon and uniform terminology and subsequent standardization of certain methods and procedures will advance the clinical science of stereotactic radiosurgery.

Fussey JM, Kemeny AA, Sankar S, Rejali D. Successful management of a catecholamine-secreting glomus jugulare tumor with radiosurgery alone. J Neurol Surg B Skull Base. 2013 Dec;74(6):399-402. doi: 10.1055/s-0033-1347375. Epub 2013 May 22.
PMID: 24436943 

Abstract

Secretory glomus jugulare tumors are often resected surgically to control the systemic effects of the catecholamines they produce. This involves complex skull base surgery, which carries significant risks and frequent morbidity. Stereotactic radiosurgery (SRS) is a recently recognized treatment for glomus jugulare tumors, though little is known about its use in secretory tumors. Case Report A young fit patient with a catecholamine-secreting glomus jugulare tumor was treated with SRS alone and over the following 37 months her urinary catecholamine excretion fell to near normal levels, and serial magnetic resonance imaging (MRI) confirmed a reduction in tumor volume. Discussion Radiosurgery is an accepted treatment for glomus jugulare tumors and is now readily available to skull base surgeons. In this case a catecholamine-secreting tumor was successfully controlled with radiosurgery alone. Further research and long-term follow-up will determine the role of this treatment in the nonsurgical management of secreting glomus jugulare tumors.

Nagy G, Kemeny AA Stereotactic radiosurgery of intracranial cavernous malformations. Neurosurg Clin N Am. 2013 Oct;24(4):575-89. doi: 10.1016/j.nec.2013.05.004. Epub 2013 Aug 2.
PMID: 24093575 

 

Abstract
Despite increasing worldwide experience, the role of stereotactic radiosurgery (SRS) in the management of cerebral cavernous malformations (CMs) remains controversial. Microsurgical excision of easily accessible CMs is typically safe; therefore, removal remains the gold standard for most of the symptomatic hemispheric lesions. However, there is now sufficient evidence supporting the use of SRS for the difficult cases. Waiting for the cumulative morbidity of the natural history to justify intervention does not serve the patient’s interest, therefore, we argue for early radiosurgical intervention. Carefully designed randomized controlled trials might resolve controversies concerning the role of SRS in treating cerebral CMs.

O’Connor L, Curl-Roper T, Reeves N, Kemeny AA, Josan VA. Image-defined resolution following radiosurgery for hypothalamic hamartoma. J Neurosurg Pediatr. 2013 Apr;11(4):464-8. doi: 10.3171/2013.1.PEDS12290. Epub 2013 Feb 1.
PMID: 23373624

 

 

Abstract
The authors present the rare case of complete image-defined resolution of a hypothalamic hamartoma (HH) following Gamma Knife surgery (GKS). A 9-month-old girl presented with an episode of generalized tonic-clonic seizures. Magnetic resonance imaging revealed a left-sided HH, which remained radiologically stable. By 3 years of age the patient had a development delay of 12 months, and experienced 8 gelastic seizures per day while on 2 antiepileptic medications. Thirty-one months after presentation, the patient underwent elective GKS to treat the HH. She has since been seizure free for 22 months, while receiving 3 antiepileptic medications. Twelve months after radiosurgery, MRI revealed complete radiological resolution of the lesion. The authors discuss alternative management options for HH, including microsurgical resection, endoscopic disconnection, stereotactic radiofrequency thermocoagulation, and interstitial radiosurgery. Gamma Knife surgery is a minimally invasive procedure associated with a lower morbidity rate than that of published surgical results. The present case demonstrates the potential for complete image-defined resolution of an HH post-GKS, without long-term neurological sequelae, emphasizing the safety and efficacy of this therapeutic option for the control of epileptic seizures produced by small-volume, surgically inaccessible HHs.

Szeifert GT, Levivier M, Lorenzoni J, Nyáry I, Major O, Kemeny AA. Morphological observations in brain arteriovenous malformations after gamma knife radiosurgery. Prog Neurol Surg. 2013;27:119-29. doi: 10.1159/000341772. Epub 2012 Dec 11.
PMID: 23258516 

 

 

Abstract

Morphological studies after Gamma Knife radiosurgery (GKRS) revealed endothelial destruction followed by spindle-shaped cell proliferation in the subendothelial region and in the connective tissue stroma of arteriovenous malformation (AVM) vessels. Histological, immunohistochemical and ultrastructural characteristics of this spindle-shaped cell population in the irradiated AVMs were reminiscent of those described as myofibroblasts in wound healing processes and pathological fibromatoses. These modified fibroblasts have contractile capacity, therefore this might contribute to the vessel occlusion, shrinking process and final volume reduction of AVMs after GKRS. Similar histopathological changes were observed in a cavernous malformation following high-dose irradiation.

Kemeny A, Reulen HJ, Cunha É Sa M, Trojanowski T. Additional competence training in neurosurgical (Stereotactic) radiosurgery. Acta Neurochir (Wien). 2012 May;154(5):941-5.
PMID: 22527573