Adolf Ertl

Local tumor control and morbidity after one to three fractions of stereotactic external beam irradiation for uveal melanoma

BACKGROUND AND PURPOSE To evaluate prospectively local tumor control and morbidity after 1-3 fractions of stereotactic external beam irradiation (SEBI) in patients with uveal melanoma, unsuitable for ruthenium-106 brachytherapy or local resection. MATERIAL AND METHODS This phase I/II study includes 62 selected patients with uveal melanoma. The mean initial tumor height was 7.8+/-2.8 mm. With the Leskell gamma knife SEBI, 41 patients (66%) were irradiated with two equal fractions of 35, 30 or 25 Gy/fraction, 14 patients (22%) were treated with three fractions of 15 Gy each, and seven patients (11%) with small tumor volumes below 400 mm(3) were treated with one fraction of 45 Gy. The mean total dose was 54+/-8 Gy. The minimal follow-up period was 12 months, and the median follow-up was 28.3 months. Data on radiation-induced side-effects were analyzed with the Cox proportional hazards model for possible risk factors. RESULTS Local tumor control was achieved in 98% and tumor height reduction in 97%. The mean relative tumor volume reductions were 44, 60 and 72% after 12, 24 and 36 months, respectively. Seven patients developed metastases (11%). Secondary enucleation was performed in eight eyes (13%). Morbidity was significant in tumors exceeding 8 mm in initial height; it was comparable and acceptable in those smaller. In the stepwise multiple Cox model, tumor localization, height and volume, planning target volume (PTV), total dose and patient age were identified as the strongest risk factors for radiation-induced lens opacities, secondary glaucoma, uveitis, eyelash loss and exudative retinal detachment. In this model, the high-dose volume irradiated with more than 10 Gy/fraction was the strongest risk factor for radiation-induced uveitis. CONCLUSIONS Stereotactic external photon beam irradiation and a total dose of 45-70 Gy delivered in one to three fractions are highly effective at achieving local tumor control in uveal melanoma. Further clinical studies using smaller fraction doses, and consequent smaller high-dose volumes, are justified to optimize dose and fractionation. Fractionated stereotactic irradiation has a challenging potential as an eye-preserving treatment in uveal melanoma.

Gamma-Knife Radiosurgery for Brain Metastases of Renal Cell Carcinoma: Results in 23 Patients

Summary From Jan. 1993 to Sept. 1995 23 patients suffering from brain metastases from renal cell carcinoma were treated with the Leksell Gamma Knife at the University of Vienna. At the time of diagnosis 13 patients had single and 10 patients presented with multiple metastatic lesions with a total of 44 metastases in MRI scans. Median tumour volume was 5500 cmm (range 100–24000 cmm). Predominant neurological symptoms and signs were different forms of hemiparesis, focal and generalized seizures, cognitive deficit, headache, dizziness, ataxia and CN XII paresis. Fourteen patients received Gamma Knife Radiosurgery (GKRS) with a median dose of 22 Gy (range 8–30 Gy) at the tumour margin. Nine patients underwent a combined treatment of a radiosurgical boost with a median dose of 18 Gy (range 10–22 Gy) at the tumour margin followed by Whole Brain Radiotherapy (total dose 30 Gy/2 weeks). In 20 patients tumour volume reduction up to 30% of the primary tumour volume was found after 4 weeks, evaluated on CT or MRI. A total remission was seen in 4 cases 3 months after GKRS. We achieved a local tumour control of 96%. Rapid neurological improvement after GKRS was seen in 17 patients. The median survival time was 11 months; the one-year actual survival in this unselected group was 48%. Five long term survivors were still alive, 18 patients had subsequently died, 15 of them of general tumour progression. GKRS induces a significant tumour remission accompanied by rapid neurological improvement and therefore provides the opportunity for extended high quality survival. Neither local tumour control was improved nor CNS relapse free survival was prolonged significantly by additional WBRT.

Prognostic factor analysis for multiple brain metastases after gamma knife radiosurgery: results in 97 patients.

Stereotactic radiosurgery (SR) is being used with increasing frequency in the treatment of brain metastases. This study provides data from a clinical experience with radiosurgery in the treatment of cases with multiple metastases and identifies parameters that may be useful in the proper selection and therapy of these patients. From January 1993 to April 1997, 97 patients (43 women and 54 men; median age 58 years) suffering from multiple brain metastases (median 3; range 2–4) in MRI scans, received SR with the Gamma Knife. The median dose at the tumor margin was 20 Gy (range 17–30 Gy). Median tumor volume was 3900 cmm (range 100–10 000). Different forms of hemiparesis, focal and generalized seizures, cognitive deficit, headache, dizziness and ataxia had been the predominant neurological symptoms. Major histologies included lung carcinoma (44%), breast cancer (21%), renal cell carcinoma (10%), colorectal cancer (8%), and melanoma (7%).The median survival time was 6 months after SR. The actual one-year survival rate was 26%. In univariate and multivariate analysis, a higher Karnofsky performance rating and absence of extracranial metastases had a significantly positive effect on survival. Local tumor control was achieved in 94% of the patients. Complications included the onset of peritumoral edema (n=5) and necrosis (n=1).SR induces a significant tumor remission accompanied by neurological improvement and, therefore, provides the opportunity for prolonged high quality survival. We conclude that radiosurgical treatment of multiple brain metastases leads to an equivalent rate of survival when compared to the historic experience of patients treated with whole brain radiotherapy. Patients presenting initially with a higher Karnofsky performance rating and without extracranial metastases had a median survival time of nine months. Each such case should therefore be evaluated based on these factors to determine an optimal treatment regimen.

High-resolution dose profile studies based on MR Imaging with polymer BANGTM gels in stereotactic radiation techniques

High-resolution dose profiles produced by the Leksell Gamma Knife were obtained in BANG(TM) polymer gel, using a 3 T whole-body scanner upgraded by a magnetic resonance microscopy unit. The gel was contained in 22.3 mm diameter flasks that were inserted into a solid, tissue-equivalent head phantom irradiated by fields of by 8 and 14 mm collimators. Dose profiles were obtained from a linear dose-response curve (R(2) vs. Dose). Excellent agreement was obtained when the gel data were compared to film dosimetry and calculated data.

Gamma Knife Radiosurgery of Acoustic Neurinomas

Summary The authors report on their series of 40 patients with 41 acoustic neurinomas (ACNs), including one patient with bilateral acoustic neurinomas suffering from neurofibromatosis type 2 (NF II) who were treated with the gamma knife unit at their institution between August 1992 and October 1995. Of these 41 tumours, 21 ACNs had been operated on before (1 to 4 times), 20 ACNs were exclusively treated by gamma knife radiosurgery (GKRS). The maximal axial tumour diameter ranged from 6 to 33 mm (median: 25 mm), the maximal transverse tumour diameter ranged from 7 mm to 36 mm (median: 16 mm). The dose distributed to the tumour margin was 10 to 17 Gy (median: 12 Gy) by enclosing the tumour with the 40% to 95% isodose line (median: 50% isodose line) and using 1 to 12 isocenters (median: 5 isocenters). Central loss of contrast enhancement was observed in 78% of the patients within six to 12 months after radiosurgery. Thirty-two patients were observed over a minimum follow up period of at least 36 months, 9 patients were lost to follow up as they died of unrelated causes or refused further check-ups. Within the follow up period of up to seven years, magnetic resonance imaging (MRI) control scans revealed the tumour diameter stable or decreased in 29 cases and increased in three tumours. Of 14 patients with useful hearing before treatment, 9 patients were examined in addition to pure tone audiogramm by measurement of brainstem auditory evoked potentials (BAEPs) one to four years after radiosurgery. None of these patients showed a postoperative loss of the cochlea function. According to slight alterations of the cochlea function (cochlea summating action potential), pure tone audiometry of those patients revealed only slight changes of the hearing level (HL) within a maximum range of ±15 Decibel (dB). The hearing threshold improved in two, was stable in four and deteriorated in three patients, respectively. We observed postradiosurgical aggravation of a pre-existing facial weakness in two out of 13 patients, a new occurrence of facial palsy was seen in two cases (four years after treatment), one of them was previously operated on and both suffered from cystic degeneration with mass effect. Tinnitus improved in six out of 13 patients, deteriorated in two and never appeared as a new permanent sequela. Trigeminal hypaesthesia did also not appear as a new permanent symptom, improved in three out of 9, and deteriorated in one out of 9 patients. Vertigo increased in six out of 23, was stable in 8 and decreased in nine out of 23 patients each. GKRS proves to be a safe and highly satisfactory therapeutical option or addition to open surgery, especially for radiologically verified regrowing residual ACNs, but also as primary treatment in selected patients. A high rate of tumour control can be achieved with an acceptable rate of neurological deficits.

High resolution polymer gel dosimetry by parameter selective MR‐microimaging on a whole body scanner at 3 T

High dose variations across small spatial distances, as present in brachytherapeutic applications or radiosurgery and especially gamma-knife therapy, are difficult to quantify by standard dosimetry. We demonstrate the possibility to obtain planar spatial resolutions for dose imaging at pixel sizes below 200 microm within multislice parameter selective MR imaging on polymer gels. The sensitivity of the transversal and longitudinal relaxation time as well as diffusivity on dose is shown. High spatial resolution is achieved by parameter selective microimaging of polymer gels on a high-field (3 T) whole-body MR system equipped with a dedicated strong gradient system and a small probe head matched to the sample size. In addition to the spin-spin relaxation rate R2 = 1/T2 we investigate the sensitivity of the longitudinal relaxation rate R1 = 1/T1 and the diffusivity Dapp in acrylic polymer gels on irradiation up to dose levels of about 20 Gy. Dose images are obtained after calibration of the corresponding MR parameters by known dose levels of gamma irradiation. Also the MR-parameter T1 may be used for dose imaging. The impact of all of the three parameters T1, T2, and diffusivity on obtained signal intensities in irradiated regions has to be taken into account in nonoptimized pulse sequences. Further, very high spatial resolution imposes several restrictions on the evaluation of R2, which have to be considered for quantitative dosimetry. These restrictions are discussed in detail. We also demonstrate the importance of such a high spatial resolution in case of a set of differently sized gamma-knife stereotactic irradiation schemes. Gel dosimetry based on MR parameter selective microimaging represents a potent alternative for the detection of dose distributions characterized by steep dose gradients, typical in brachytherapeutic and radiosurgical applications.

Suction Attachment for Stereotactic Radiosurgery of Intraocular Malignancies

We designed a suction attachment for the radiosurgical treatment of intraocular malignancies with the Leksell gamma unit (Gamma Knife). Our device consists of a circular suction chamber and an adjustable unit to be fixed to the Leksell stereotactic head frame. All components are made of plastic materials in order to avoid artifacts in CT or MRT imaging. A permanent suction of 600-800 mbar is provided by a standard vacuum pump, powered by a portable battery. Suction times up to 40 min were well tolerated in all cases. We successfully used this device, performing 17 radiosurgical treatments in 8 patients with large or extra-large uveal melanomas and one patient suffering from a choroidal metastasis.

Shuttle dose at the Vienna Leksell Gamma Knife

The aim of this study was to determine the shuttle dose for all collimator helmets (4, 8, 14 and 18 mm) of the Gamma Knife, model B, in Vienna, Austria. The additional dose accumulated during the transport of the patient in and out of the treatment position should be considered in the dose planning procedure of multicentre treatment regimens and in fractionated stereotactic Gamma Knife radiotherapy. The GafChromic film study was basically used to determine the shuttle dose of all four collimator helmets. In addition, measurements with an ionization chamber (18 and 14 mm collimator--and, for the 18 mm collimator helmet, TLD dosimetry--were performed in order to confirm the GafChromic film data. The shuttle dose ranged between 99.6 and 183.5 mGy, depending mainly on the size of the collimator and the irradiated isocentres at the half-life activity of Co-60 in a brand new Gamma unit. Our film-generated data were in good correlation with the dose levels obtained with the ionization chamber and the TLD dosimetry, showing a dose difference of less than 0.8%. Since it was possible to verify the shuttle dose even for the 4 and 8 mm collimator helmets, we consider it a non-negligible factor and would advocate the inclusion of the shuttle dose in radiosurgical dose planning.

A new method of readout in radiochromic film dosimetry

Radiochromic film as a dosimetry medium offers several advantages in high-resolution radiography. A new technique of readout was developed to measure the optical density distributions of the film in purely directed light. This technique implements radiochromic film dosimetry near the films absorption maximum by using a single-mode top-surface emitting laser diode (675.2 nm). The effective sensitivity of the film, compared with a helium-neon laser densitometer (632.8 nm), is increased approximately threefold. Good accuracy, high spatial resolution and simple assembly of the readout system is achieved. Beam profiles of the four final collimator helmets of a Leksell Gamma Knife (Elekta Inc., Sweden) were experimentally determined. Measured profiles and full-widths at half maximum are consistent with the computer generated data of the dose planning system (Kula 4.4, Elekta Inc., Sweden). The output factor of the 4 mm collimator (the smallest collimator with the steepest dose gradient), essential for the application of well defined doses, was checked. The measurements established an output factor of 826 +/- 9 that lies 9 +/- 1% lower than the adjusted one.

Dosimetry studies with TLDs for stereotactic radiation techniques for intraocular tumours

Between March 1993 and January 1997, stereotactic radiation techniques were used to irradiate 66 intraocular tumour patients with the Gamma Knife (Leksell Gamma Knife, model B unit) at the University of Vienna, Austria. This study investigates the dosimetry for stereotactic irradiation of ocular structures. For the dosimetry program KULA 4.4, Gamma Knife stereotactic irradiation of the eye represents an extreme frontal skull position. In addition, irradiation of the eye may be performed in the usual supine position in exceptional cases only. With the patient in the prone position, the dose planning program has to calculate with a significantly large number of single-beam extrapolations. In our first experiment we measured the isocentre dose for eight different gamma-angle positions, both in prone and supine positions, using TLD measurements in an Alderson head phantom. We found a maximum deviation of +/- 1.6% using these individually calibrated TLDs. In the second experiment we examined the dose cross profiles for the two most frequently used treatment positions (supine position, gamma = 65 degrees, and prone position, gamma = 140 degrees). For this purpose we implanted a specially designed TLD array into the orbit of a human cadaver head. We found excellent agreement of the dose values measured for the isocentre as well as the posterior part of the eye with orbit with deviations of less than -2.7%. However, for the anterior part of the eye, deviations between computer-generated calculations and the TLD measurements were found to range up to -30%. These differences were noticed both for supine and prone positions. For the Gamma Knife stereotactic irradiation of ocular tumours or pathologies, precautions should be taken to avoid significant underdosage in the anterior part of the radiation field.