Experimental determination of the photon-energy dependent dose-to-water response of TLD600 and TLD700 (LiF:Mg,Ti) thermoluminescence detectors.

The aim of this study has been the experimental determination of the energy dependent dose-to-water response of TLD600 and TLD700 thermoluminescent detectors (Harshaw) in X-ray beams with mean photon energies from about 20 to 200keV in comparison with 60Co gamma rays and 6MV X-rays. Experiments were carried out in collaboration with the German secondary standard laboratory PTW Freiburg. The energy dependent relative responses of TLD600 and TLD700 thermoluminescence detectors were determined at radiation qualities between 30kVp and 280kVp. The overall uncertainty of the measured values was characterized by standard deviations varying from 1.2 to 3%. The present results agree with previous studies on the energy dependent dose-to-water response of TLD100. As an application example, the results were used to measure doses associated with X-ray imaging in image-guided radiotherapy.

Development, physical properties and clinical applicability of a mechanical Multileaf Collimator for the use in Cobalt-60 radiotherapy.

According to the Directory of Radiotherapy Centres (DIRAC) there are 2348 Cobalt-60 (Co-60) teletherapy units worldwide, most of them in low and middle income countries, compared to 11046 clinical accelerators. To improve teletherapy with Co-60, a mechanical Multi-Leaf Collimator (MLC) was developed, working with pneumatic pressure and thus independent of electricity supply. Instead of tungsten, brass was used as leaf material to make the mechanical MLC more affordable. The physical properties and clinical applicability of this mechanical MLC are presented here. The leakage strongly depends on the fieldsize of the therapy unit due to scatter effects. The maximum transmission through the leaves measured 2.5 cm from the end-to-end gap, within a field size of 20 cm × 30 cm defined by jaws of the therapy unit at 80 cm SAD, amounts 4.2%, normalized to an open 10 cm × 10 cm field, created by the mechanical MLC. Within a precollimated field size of 12.5 cm × 12.5 cm, the end-to-end leakage is 6.5% normalized to an open 10 cm × 10 cm field as well. This characteristic is clinically acceptable considering the criteria for non-IMRT MLCs of the International Electrotechnical Commission (IEC 60601-2-1). The penumbra for a 10 cm × 10 cm field was measured to be 9.14 mm in plane and 8.38 mm cross plane. The clinical applicability of the designed mechanical MLC was affirmed by measurements relating to all relevant clinical properties such as penumbra, leakage, output factors and field widths. Hence this novel device presents an apt way forward to make radiotherapy with conformal fields possible in low-infrastructure environments, using gantry based Co-60 therapy units.

Dosimetric robustness against setup errors in charged particle radiotherapy of skull base tumors.

BACKGROUND: It is expected that physical dose deposition properties render charged particle dose distributions sensitive to targeting uncertainties. Purpose of this work was to investigate the robustness of scanned-beam particle therapy plans against setup errors for different optimization modalities, beam setups and ion species. MATERIAL AND METHODS: For 15 patients with skull base tumors, localized in regions of severe tissue density heterogeneity, scanned lateral-opposed-beam treatment plans were prepared with the treatment planning system TRiP98, employing different optimization settings (single- and multiple-field modulation) and ion species (carbon ions and protons). For 10 of the patients, additional plans were prepared with individually selected beam setups, aiming at avoiding severe tissue heterogeneities. Subsequently, multiple rigid positioning errors of magnitude 1-2 mm (i.e. within planning target expansion) were simulated by introducing a shift of the irradiation fields with respect to the computed tomography (CT) data and recomputing the plans. RESULTS: In presence of shifts, in carbon ion plans using a lateral-opposed beam setup and fulfilling clinical healthy tissue dose constraints, the median reduction in CTV V95% was up to 0.7 percentage points (pp) and 3.5 pp, for shifts of magnitude 1 mm and 2 mm respectively, however, in individual cases, the reduction reached 5.1 pp and 9.7 pp. In the corresponding proton plans similar median CTV V95% reductions of up to 0.9 pp (1 mm error) and 3.4 pp (2 mm error) were observed, with respective individual-case reductions of at most 3.2 pp and 11.7 pp. Unconstrained plans offered slightly higher coverage values, while no relevant differences were observed between different field modulation methods. Individually selected beam setups had a visible dosimetric advantage over lateral-opposed beams, for both particle species. While carbons provided more conformal plans and generally more advantageous absolute dose values, in presence of setup errors, protons showed greater dosimetric stability, in most of the investigated scenarios. CONCLUSION: Residual patient setup errors may lead to substantial dose perturbation in scanned-beam particle therapy of skull base tumors, which cannot be dealt with by planning target expansion alone. Choice of irradiation directions avoiding extreme density heterogeneities can improve plan stability against such delivery-time uncertainties.

Independent calculation of dose distributions for helical tomotherapy using a conventional treatment planning system.

PURPOSE: The dosimetric verification of treatment plans in helical tomotherapy usually is carried out via verification measurements. In this study, a method for independent dose calculation of tomotherapy treatment plans is presented, that uses a conventional treatment planning system with a pencil kernel dose calculation algorithm for generation of verification dose distributions based on patient CT data. METHODS: A pencil beam algorithm that directly uses measured beam data was configured for dose calculation for a tomotherapy machine. Tomotherapy treatment plans were converted into a format readable by an in-house treatment planning system by assigning each projection to one static treatment field and shifting the calculation isocenter for each field in order to account for the couch movement. The modulation of the fluence for each projection is read out of the delivery sinogram, and with the kernel-based dose calculation, this information can directly be used for dose calculation without the need for decomposition of the sinogram. The sinogram values are only corrected for leaf output and leaf latency. Using the converted treatment plans, dose was recalculated with the independent treatment planning system. Multiple treatment plans ranging from simple static fields to real patient treatment plans were calculated using the new approach and either compared to actual measurements or the 3D dose distribution calculated by the tomotherapy treatment planning system. In addition, dose-volume histograms were calculated for the patient plans. RESULTS: Except for minor deviations at the maximum field size, the pencil beam dose calculation for static beams agreed with measurements in a water tank within 2%/2 mm. A mean deviation to point dose measurements in the cheese phantom of 0.89% ± 0.81% was found for unmodulated helical plans. A mean voxel-based deviation of -0.67% ± 1.11% for all voxels in the respective high dose region (dose values >80%), and a mean local voxel-based deviation of -2.41% ± 0.75% for all voxels with dose values >20% were found for 11 modulated plans in the cheese phantom. Averaged over nine patient plans, the deviations amounted to -0.14% ± 1.97% (voxels >80%) and -0.95% ± 2.27% (>20%, local deviations). For a lung case, mean voxel-based deviations of more than 4% were found, while for all other patient plans, all mean voxel-based deviations were within ± 2.4%. CONCLUSIONS: The presented method is suitable for independent dose calculation for helical tomotherapy within the known limitations of the pencil beam algorithm. It can serve as verification of the primary dose calculation and thereby reduce the need for time-consuming measurements. By using the patient anatomy and generating full 3D dose data, and combined with measurements of additional machine parameters, it can substantially contribute to overall patient safety.

Proposal for a new prognostic score for linac-based radiosurgery in cerebral arteriovenous malformations.

PURPOSE: We evaluate patient-, angioma-, and treatment-specific factors for successful obliteration of cerebral arteriovenous malformations (AVM) to develop a new appropriate score to predict patient outcome after linac-based radiosurgery (RS). METHODS AND MATERIALS: This analysis in based on 293 patients with cerebral AVM. Mean age at treatment was 38.8 years (4-73 years). AVM classification according Spetzler-Martin was 55 patients Grade I (20.5%), 114 Grade II (42.5%), 79 Grade III (29.5%), 19 Grade IV (7.1%), and 1 Grade V (0.4%). Median maximum AVM diameter was 3.0 cm (range, 0.3-10 cm). Median dose prescribed to the 80% isodose was 18 Gy (range, 12-22 Gy). Eighty-five patients (29.1%) had prior partial embolization; 141 patients (51.9%) experienced intracranial hemorrhage before RS. Median follow-up was 4.2 years. RESULTS: Age at treatment, maximum diameter, nidus volume, and applied dose were significant factors for successful obliteration. Under presumption of proportional hazard in the dose range between 12 and 22 Gy/80% isodose, an increase of obliteration rate of approximately 25% per Gy was seen. On the basis of multivariate analysis, a prediction score was calculated including AVM maximum diameter and age at treatment. The prediction error up to the time point 8 years was 0.173 for the Heidelberg score compared with the Kaplan-Meier value of 0.192. An increase of the score of 1 point results in a decrease of obliteration chance by a factor of 0.447. CONCLUSION: The proposed score is linac-based radiosurgery-specific and easy to handle to predict patient outcome. Further validation on an independent patient cohort is necessary.

Reirradiation with intensity-modulated radiotherapy in recurrent head and neck cancer.

BACKGROUND: In this retrospective investigation we analyzed outcome and toxicity after intensity-modulated reirradiation of recurrent head and neck cancer. METHODS: Thirty-eight patients with local recurrent head and neck cancer were evaluated. The median dose of initial radiotherapy was 61 Gy. Reirradiation was carried out with step-and-shoot intensity-modulated radiotherapy (median dose: 49 Gy). RESULTS: Median overall survival was 17 months, and the 1- and 2-year overall survival rates were 63% and 34%. The 1- and 2-year local control rates were 57% and 53%. Distant spread occurred in 34%, and reirradiation induced considerable late toxicity in 21% of the patients. Thirty-two percent showed increased xerostomia after reirradiation. The risk for xerostomia was significantly higher for cumulative mean doses of ≥45 Gy to parotid glands. Considering median cumulative maximum doses of 53 Gy to the spinal cord and 63 Gy to the brainstem, no late toxicities were observed. CONCLUSIONS: Reirradiation with intensity-modulated radiotherapy in recurrent head and neck cancer is feasible with acceptable toxicity and yields encouraging rates of local control and overall survival.

Repeated linac-based radiosurgery in high-grade cerebral arteriovenous-malformations (AVM) Spetzler-Martin grade III to IV previously treated with radiosurgery.

BACKGROUND: Aim was to access outcome and toxicity of repeated linac-based radiosurgery in incompletely obliterated cerebral AVM. PATIENTS AND METHODS: Between 1998 and 2008, 11 patients were treated with repeated radiosurgery. The median dose to the 80%-isodose was 15 Gy (range, 12-18 Gy). During initial radiosurgery the median dose was 18 Gy (range, 9-22 Gy). RESULTS: The median time interval between initial radiosurgery and re-treatment was 9 years (range, 4-16 years). The median follow-up was 26 months (range, 2-115 months). Treatment response was seen in 8 patients (89%). Complete (partial) obliteration was achieved in 5 (3) patients (56%, 33%, respectively).The median time to complete obliteration was 26 months (range, 5-45 months). Pre-existing neurological symptoms improved in 2 patients (18%), were stable in 7 patients (64%) and worsened in 2 patients (18%). Prevalence of intracranial hemorrhage was 9% (1/11). Post-re-treatment intracranial hemorrhage rate was 2.7% (1/38 years at risk). During follow-up, no secondary malignancies or toxicity>grade III were observed. CONCLUSION: Repeated linac-based radiosurgery in incompletely obliterated cerebral AVM is an effective treatment option with a high rate of treatment response and an acceptable risk for side effects. Marginal doses above 15 Gy might further improve the rate of complete obliterations.

Intensity modulated radiotherapy in the management of sacral chordoma in primary versus recurrent disease.

PURPOSE: To investigate treatment outcome in patients suffering from sacral chordoma after intensity modulated radiotherapy (IMRT) for primary versus recurrent disease. MATERIAL/METHODS: We report on 34 patients with histologically proven sacral chordoma. Seventeen patients were treated at time of initial diagnosis with post-operative IMRT (n=13) or with IMRT alone (n=4). Seventeen patients were treated in recurrent disease after surgery (n=11) or with radiotherapy alone (n=6). Median total dose to the boost volume (PTV2) was 66 Gy (range, 72-54) with 2 Gy per fraction using an integrated boost concept. Median dose to target volume (PTV1) was 54 Gy in 1.8 Gy. RESULTS: Local control was 35% (12/34) and overall survival 74% (25/34) after a median follow-up of 4.5 years. Actuarial local control was 79%, 55% and 27% after 1, 2 and 5 years, respectively. Local control was significantly higher in patients treated for primary tumors (p<0.03) and in total doses >60 Gy (p<0.01). Actuarial overall survival was 97%, 91% and 70% after 1, 2 and 5 years, respectively. CONCLUSION: These data demonstrate that local control after IMRT is higher in patients treated for primary tumors and using higher radiation doses. Therefore, we recommend radiotherapy as part of initial treatment in sacral chordoma.

Patterns of failure after stereotactic radiotherapy of intracranial meningioma.

The aim of this work is to evaluate patterns of failure in patients with recurrent meningioma after stereotactic radiotherapy. Of 411 patients with intracranial meningioma treated with radiotherapy at our institution, 22 patients with local tumor progression diagnosed by magnetic resonance imaging (MRI) after radiotherapy (RT) were identified and further investigated. The histologic grade of the meningiomas was World Health Organization (WHO) grade I in 54.5%, WHO grade II in 27.3%, and WHO grade III in 9.1% of cases. Fourteen patients had received fractionated stereotactic RT; five patients underwent intensity-modulated RT. The median total dose was 57.6 Gy at 1.8 Gy/fraction, five times weekly. Local recurrences were divided into the dosimetric categories "central" ("in-field") and "marginal" ("out-field"). Median follow-up was 59.5 months. Eleven local failures were found to be central, and 11 were marginal. Recurrence-free survival (P < 0.05) and site of local recurrence (P < 0.05) depended statistically significantly on histology. Median recurrence-free survival was 46 months for patients with benign meningioma (WHO grade I) and 31.5 months for patients with higher-grade meningioma (WHO grade II/III). In the WHO grade I group, three recurrences were central and nine were marginal, whereas in the WHO grade II/III group seven recurrences were central and one was marginal. Median time to local tumor progression and site of local recurrence significantly depended on histological grade of meningioma. Regarding site of failure, improvement of dose coverage for benign meningiomas and dose escalation for high-grade tumors might further improve therapy outcome.

Fractionated stereotactic radiation therapy in the management of primary optic nerve sheath meningiomas.

We analysed our long-term results after fractionated stereotactic radiotherapy (FSRT) in patients with primary optic nerve sheath (pONSM) meningioma, as a rare subtype of meningiomas. Between 01/1995 and 12/2007, 32 patients with pONSM were treated with FSRT. Fifteen patients received radiotherapy as primary treatment, four after biopsy, and six patients after surgical resection. Seven patients were irradiated for recurrent disease. Seventeen lesions were histologically proven and determined as WHO grade I pONSM. Median target volume was 15.7 cc, median total dose 54.9 Gy. Twenty-nine patients showed clinical symptoms before radiotherapy like reduced vision, unilateral loss of vision, or an exophthalmia. Median follow-up was 4.5 years. Overall local tumor control was 100%. Twenty-six patients had stable disease based on CT/MRI, while 6/32 had a partial remission of tumor volume. 97% of our patients showed stable vision or an improvement of visual acuity. Eleven patients (38%) showed an improvement of pre-existing clinical symptoms like double vision, exophthalmia and visual acuity. Only one patient showed an impairment of vision with progressive concentric decreasing of the visual field on the side of the irradiated ONSM. These data demonstrate that FSRT is an effective and safe treatment modality for local control in patients with pONSM with minimal risk of significant late toxicity.

4D-Imaging of the lung: reproducibility of lesion size and displacement on helical CT, MRI, and cone beam CT in a ventilated ex vivo system.

PURPOSE: Four-dimensional (4D) imaging is a key to motion-adapted radiotherapy of lung tumors. We evaluated in a ventilated ex vivo system how size and displacement of artificial pulmonary nodules are reproduced with helical 4D-CT, 4D-MRI, and linac-integrated cone beam CT (CBCT). METHODS AND MATERIALS: Four porcine lungs with 18 agarose nodules (mean diameters 1.3-1.9 cm), were ventilated inside a chest phantom at 8/min and subject to 4D-CT (collimation 24 x 1.2 mm, pitch 0.1, slice/increment 24 x 10(2)/1.5/0.8 mm, pitch 0.1, temporal resolution 0.5 s), 4D-MRI (echo-shared dynamic three-dimensional-flash; repetition/echo time 2.13/0.72 ms, voxel size 2.7 x 2.7 x 4.0 mm, temporal resolution 1.4 s) and linac-integrated 4D-CBCT (720 projections, 3-min rotation, temporal resolution approximately 1 s). Static CT without respiration served as control. Three observers recorded lesion size (RECIST-diameters x/y/z) and axial displacement. Interobserver- and interphase-variation coefficients (IO/IP VC) of measurements indicated reproducibility. RESULTS: Mean x/y/z lesion diameters in cm were equal on static and dynamic CT (1.88/1.87; 1.30/1.39; 1.71/1.73; p > 0.05), but appeared larger on MRI and CBCT (2.06/1.95 [p < 0.05 vs. CT]; 1.47/1.28 [MRI vs. CT/CBCT p < 0.05]; 1.86/1.83 [CT vs. CBCT p < 0.05]). Interobserver-VC for lesion sizes were 2.54-4.47% (CT), 2.29-4.48% (4D-CT); 5.44-6.22% (MRI) and 4.86-6.97% (CBCT). Interphase-VC for lesion sizes ranged from 2.28% (4D-CT) to 10.0% (CBCT). Mean displacement in cm decreased from static CT (1.65) to 4D-CT (1.40), CBCT (1.23) and MRI (1.16). CONCLUSIONS: Lesion sizes are exactly reproduced with 4D-CT but overestimated on 4D-MRI and CBCT with a larger variability due to limited temporal and spatial resolution. All 4D-modalities underestimate lesion displacement.

Accuracy of a commercial optical 3D surface imaging system for realignment of patients for radiotherapy of the thorax.

Accurate and reproducible patient setup is a prerequisite to fractionated radiotherapy. To evaluate the applicability and technical performance of a commercial 3D surface imaging system for repositioning of breast cancer patients, measurements were performed in a rigid anthropomorphic phantom as well as in healthy volunteers. The camera system records a respiration-gated surface model of the imaged object, which may be registered to a previously recorded reference model. A transformation is provided, which may be applied to the treatment couch to correct the setup of the patient. The system showed a high stability and detected pre-defined shifts of phantoms and healthy volunteers with an accuracy of 0.40 +/- 0.26 mm and 1.02 +/- 0.51 mm, respectively (spatial deviation between pre-defined shift and suggested correction). The accuracy of the suggested rotational correction around the vertical axis was always better than 0.3 degrees in phantom measurements and 0.8 degrees in volunteers, respectively. Comparison of the suggested setup correction with that detected by a second and independently operated marker-based optical system provided consistent results. The results demonstrate that the camera system provides highly accurate setup corrections in a phantom and healthy volunteers. The most efficient use of the system for improving the setup accuracy in breast cancer patients has to be investigated in routine patient treatments.

Risk of hemorrhage and obliteration rates of LINAC-based radiosurgery for cerebral arteriovenous malformations treated after prior partial embolization.

PURPOSE: We investigate patient outcome, risk of hemorrhage, and factors affecting obliteration after LINAC-based radiosurgery (RS) for cerebral arteriovenous malformations (AVM) treated after partial embolization. METHODS AND MATERIALS: This analysis is based on 50 patients treated after prior embolization. According to the Spetzler-Martin criteria the AVM classification was as follows: 9 patients, Grade I (18%); 19, Grade II (38%); 18, Grade III (36%); and 4, Grade IV (8%). Median RS-based AVM score was 1.41. Median single dose was 18 Gy/ 80% isodose (range, 15-22 Gy) and median AVM volume was 4.0 cc (range, 0.2-22.6 cc). In all, 34 patients (68%) experienced hemorrhage before RS. Median follow-up was 3.1 year (range, 8.5 months to 15 years). RESULTS: Actuarial complete obliteration rate was 67% after 3 years and 78% after 4 years. The complete obliteration rate was significantly higher in AVM <3 cm (92% vs. 60%, p < 0.01) and in AVM Spetzler-Martin Grade I/II (90% vs. 59%, p < 0,01). Intracranial hemorrhage after RS was seen in 6 patients (12%) after 8.5 months median. Annual bleeding risk was 7.9% after 1 year and 2.2% after 2 years. It was found that AVM diameter > or =3 cm (p < 0.006), AVM volume > or =4 cc (p < 0.01), AVM score > or =1.5 (p < 0.03), and single dose <18 Gy (p < 0.03) were associated with a significant higher bleeding risk. CONCLUSIONS: The rate of obliteration after RS in AVM treated after prior partial embolization depends on size as well as Spetzler-Martin grade. The risk of intracranial hemorrhage is not increased after RS and depends on AVM score, size, and volume, as well as on applied single dose.

Intensity-modulated radiotherapy for complex-shaped meningioma of the skull base: long-term experience of a single institution.

PURPOSE: We analyzed our long-term experience with intensity-modulated radiotherapy (IMRT) in patients with complex-shaped meningioma of the skull base. PATIENTS AND METHODS: Between January 1998 and December 2004, 94 patients with complex-shaped meningioma were treated using IMRT at our institution. Tumor distribution was: World Health Organization (WHO) Grade 1 in 54.3%, WHO Grade 2 in 9.6%, and WHO Grade 3 in 4.2%. In 31.9% of patients, the clinical and radiologic characteristics of the tumor were consistent with the diagnosis of meningioma. Twenty-six patients received radiotherapy as primary treatment and 14 patients postoperative for residual disease. Fifty-four patients were treated after local recurrence. Median target volume was 81.4 mL, median total dose was 57.6 Gy given in 32 fractions. RESULTS: Median follow-up was 4.4 years. Overall local control was 93.6%. Sixty-nine patients had stable disease based on computed tomography/magnetic resonance imaging (MRI), whereas 19 had a tumor volume reduction after IMRT. Six patients showed local tumor progression on MRI 22.3 months' median after IMRT. Three patients died from non-treatment-related conditions after IMRT. In 39.8% of the patients, preexisting neurologic deficits improved. Worsening of preexisting neurologic symptoms was seen in 4 patients and 2 patients developed new clinical symptoms from local tumor progression. Transient side effects such as headache were seen in 7 patients. Treatment-induced loss of vision was seen in 1 of 53 reirradiated patients with a Grade 3 meningioma 9 months after retreatment with IMRT. CONCLUSION: These data demonstrate that IMRT is an effective and safe treatment modality for long-term local control of complex-shaped and otherwise difficult to treat meningioma.

Prediction of radiation-induced changes in the lung after stereotactic body radiation therapy of non-small-cell lung cancer.

PURPOSE: To estimate the risk of radiation-induced changes in the lung before single-dose treatment (stereotactic body radiation therapy [SBRT]) of lung cancer, the quantitative dose-response and volume-response relations must be known. METHODS AND MATERIALS: A total of 64 patients treated for non-small-cell lung cancer with single doses of 20-30 Gy were classified according to the occurrence or nonoccurrence of perifocal changes in the lung detected by CT. Patients without toxic events in the lung were required to have >or=6 months of follow-up. The mean dose (D(mean)) in the ipsilateral lung and the volume receiving >7 or 10 Gy (V7 and V10, respectively) were used to calculate the dose-response and volume-response curves. The predictive value of additional variables was also investigated. RESULTS: Of the 64 patients, 83% exhibited the selected endpoint. The tolerance values at a 50% probability of toxic events were 1.2 +/- 0.7 Gy for the D(mean) and 5.8 +/- 3.0% and 3.1 +/- 2.0% for V7 and V10, respectively. A nonsignificant shift to higher doses was seen for the dose-response curve for the upper compared with the lower part of the lung. CONCLUSION: The D(mean), V7, and V10 can be used to predict the risk of lung toxicity after SBRT treatment of non-small-cell lung cancer. Because of the lack of patients with low prescribed doses, however, the related uncertainty of this prediction is still relatively large. The D(mean), V7, and V10 are equally well suited. The additional investigated variables did not provide significant advantages. The lower part of the lung appears to be more radiosensitive than the upper.

Fractionated stereotactic radiation therapy in the management of benign cavernous sinus meningiomas : long-term experience and review of the literature.

PURPOSE: To analyze own long-term results with fractionated stereotactic radiotherapy (FSRT) in patients with benign meningiomas of the cavernous sinus and to review the literature on these rare lesions. PATIENTS AND METHODS: 57 patients were treated with FSRT for benign meningiomas of the cavernous sinus between 01/1990 and 12/2003 at the authors' institution. Histology was WHO grade I in 28/57 lesions, and undetermined in 29/57 lesions. 29 patients received radiotherapy as primary treatment, ten following surgery, and 18 patients were irradiated for recurrent disease. Median target volume was 35.2 cm3. Median total dose was 57.6 Gy with 1.8 Gy per fraction. 51/57 patients showed clinical symptoms before radiotherapy like reduced vision (n = 19), diplopia (n = 25), or trigeminal hyp-/dysesthesia (n = 17). RESULTS: Median follow-up period was 6.5 years. 50/57 patients were followed for > 36 months. Overall local tumor control was 100%. 39/57 patients had stable disease based on CT/MRI, while 18/57 had a partial remission of tumor volume. Overall survival for patients with WHO grade I meningiomas was 95.5% after 5 and 10 years. Two patients died 2.8 and 4.1 years after radiotherapy due to cardiac failure. In 11/57 patients, preexisting neurologic deficits improved. There was one patient with recurrent hyperlacrimation of one eye on the side of the irradiated meningioma. Three patients complained about subjective visual deterioration after FSRT without any objective findings in an ophthalmologic examination. No late toxicity RTOG >/= degrees III was seen. CONCLUSION: These data demonstrate that FSRT is an effective and safe treatment modality for local control of benign cavernous sinus meningiomas with a minimal risk of significant late toxicity.

Radiation therapy with charged particles.

Charged particle beams can offer an improved dose conformation to the target volume as compared with photon radiotherapy, with better sparing of normal tissue structures close to the target. In addition, beams of ions heavier than (4)He exhibit a strong increase of the linear energy transfer in the Bragg peak as compared with the entrance region. These physical and biological properties are much more favorable than in photon radiotherapy. As a consequence, particle therapy with protons and heavy ions has gained increasing interest worldwide, and many clinical centers are considering introducing radiation therapy with charged particles. This contribution summarizes the physical and technical principles of charged particle therapy with protons and heavy ions. It briefly reviews the clinical experience gathered so far with proton therapy and gives a more detailed summary of the recent results in carbon ion therapy of skull base tumors, head and neck tumors, non-small-cell lung cancer, hepatocellular carcinomas, bone and soft-tissue sarcomas, and prostate cancer.

Enhanced isoproterenol-induced cardiac hypertrophy in transgenic rats with low brain angiotensinogen.

We have previously shown that a permanent deficiency in the brain renin-angiotensin system (RAS) may increase the sensitivity of the baroreflex control of heart rate. In this study we aimed at studying the involvement of the brain RAS in the cardiac reactivity to the beta-adrenoceptor (beta-AR) agonist isoproterenol (Iso). Transgenic rats with low brain angiotensinogen (TGR) were used. In isolated hearts, Iso induced a significantly greater increase in left ventricular (LV) pressure and maximal contraction (+dP/dt(max)) in the TGR than in the Sprague-Dawley (SD) rats. LV hypertrophy induced by Iso treatment was significantly higher in TGR than in SD rats (in g LV wt/100 g body wt, 0.28 +/- 0.004 vs. 0.24 +/- 0.004, respectively). The greater LV hypertrophy in TGR rats was associated with more pronounced downregulation of beta-AR and upregulation of LV beta-AR kinase-1 mRNA levels compared with those in SD rats. The decrease in the heart rate (HR) induced by the beta-AR antagonist metoprolol in conscious rats was significantly attenuated in TGR compared with SD rats (-9.9 +/- 1.7% vs. -18.1 +/- 1.5%), whereas the effect of parasympathetic blockade by atropine on HR was similar in both strains. These results indicate that TGR are more sensitive to beta-AR agonist-induced cardiac inotropic response and hypertrophy, possibly due to chronically low sympathetic outflow directed to the heart.