Stereotactic radiosurgery and fractionated stereotactic radiotherapy: comparison of efficacy and toxicity in 260 patients with brain metastases.

We retrospectively evaluated and compared the efficacy and the toxicity profile of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) for the treatment of patients with brain metastases (BM). Between 2000 and 2009, 260 patients with 1-3 BM were treated using either SRS (median dose 20 Gy; n = 138) or two different FSRT dose concepts: 7 × 5 Gy (n = 61) or 10 × 4 Gy (n = 61). The median survival for SRS, 7 × 5 Gy and 10 × 4 Gy was 8, 7 and 10 months (p = 0.575), respectively, and the overall survival (OS) was 9 months. Follow-up imaging data were available in 214 of the 260 patients. The 1-year local progression-free survival (LPFS) was 73, 75 and 71 %, respectively (p = 0.191). After a mean follow-up of 28 months (range: 2.1-77 months), the rate of complete remission, partial remission, stable disease and progressive disease were 29, 40, 21 and 10 %, respectively. On multivariate analysis, RPA class I was associated with better OS and regional progression-free survival (both p < 0.001). SRS was associated with a higher toxicity rate (grade I-III) compared to the 7 × 5 Gy and 10 × 4 Gy groups (14 vs. 6 vs. 2 %, respectively; p = 0.01). Although FSRT was used for large lesions and/or lesions near critical structures, the LPFS was comparable to SRS. Importantly, FSRT presented low toxicity and appears to be an effective and safe treatment for BM not amenable to SRS. The 10 × 4 Gy fractionation scheme warrants further investigation due to its efficacy and safe toxicity profile.

Multidisciplinary treatment of brain metastases derived from colorectal cancer incorporating stereotactic radiosurgery: analysis of 78 patients.

BACKGROUND: We investigated the role of radiotherapy, including whole brain radiotherapy and stereotactic radiosurgery (SRS), and prognostic factors in patients with colorectal cancer (CRC) who developed brain metastases. PATIENTS AND METHODS: The data of 78 patients who received multidisciplinary treatment from 1996 to 2007 were reviewed. Overall survival (OS), intracerebral control (ICC), and local control (LC) were retrospectively analyzed. Six potential prognostic factors were evaluated: age, gender, number of brain metastases, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to radiotherapy. RESULTS: The median OS and ICC for the entire cohort were 8 and 6 months, respectively. Surgical resection-incorporating treatment resulted in significant improvement in OS (P = .036). On multivariate analysis, OS and ICC were significantly correlated with lack of extracerebral metastases (P = .024 and P = .041, respectively), lower number of lesions (P < .001 and P = .007, respectively) and interval from primary CRC diagnosis (P < .001 and .005, respectively) whereas RPA class I-II demonstrated significance only for OS (P = .045). SRS-incorporating therapy revealed a 1-year LC probability of 85%. No association between LC and any of the potential prognostic factors was observed. CONCLUSION: Our data indicate that surgery can prolong survival in CRC patients with brain metastases. SRS-incorporating treatment provides excellent LC rates and should be considered for patients with 1-3 lesions. The strong association between survival and the prognostic factors identified in this study highlights a patient subset that may potentially benefit from new, more aggressive therapies.

Radiotherapy for brain metastases from renal cell cancer: should whole-brain radiotherapy be added to stereotactic radiosurgery?: analysis of 88 patients.

PURPOSE: To evaluate the role of stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) for the treatment of brain metastases in patients with renal cell cancer (RCC). PATIENTS AND METHODS: 88 patients were treated with either SRS (n = 51) or SRS + WBRT (n = 17) for one to three lesions, or with WBRT (n = 20) for more than three brain metastases. Overall survival (OS), intracerebral control (IC) and local control (LC) were retrospectively analyzed. Six potential prognostic factors were assessed: age, gender, number of brain metastases, extracerebral metastases, recursive partitioning analysis (RPA) class, and interval from tumor diagnosis to irradiation. RESULTS: The median times for OS, IC, and LC from the time of diagnosis were 11, 9, and 10 months. The median OS times for SRS, SRS + WBRT, and WBRT were 12, 16, and 2 months. Addition of WBRT to the SRS improved IC (p = 0.032) but not OS (p = 0.703). On multivariate analyses, improved OS was associated with the absence of extracerebral metastases (p < 0.001) and RPA class (p = 0.04), and IC with treatment (p = 0.019). SRS provided a 1-year, 2-year, and 3-year LC probability of 81%, 78%, and 55%, respectively. No association between LC and any of the potential prognostic factors was observed. The results of the subgroup analyses, regarding treatment modality, were similar to the entire cohort, particularly for RPA class I patients. CONCLUSION: Addition of WBRT to SRS offers better IC and should be considered for RCC patients with one to three brain metastases, especially in RPA class I group. SRS offers excellent LC rates, while WBRT should be reserved for patients with multiple metastases and poor prognosis.

Comparison of stereotactic radiosurgery and fractionated stereotactic radiotherapy of acoustic neurinomas according to 3-D tumor volume shrinkage and quality of life.

BACKGROUND AND PURPOSE: Stereotactic radiosurgery (SRS) and also fractionated stereotactic radiotherapy (SRT) offer high local control (LC) rates (> 90%). This study aimed to evaluate three-dimensional (3-D) tumor volume (TV) shrinkage and to assess quality of life (QoL) after SRS/SRT. PATIENTS AND METHODS: From 1999 to 2005, 35/74 patients were treated with SRS, and 39/74 with SRT. Median age was 60 years. Treatment was delivered by a linear accelerator. Median single dose was 13 Gy (SRS) or 54 Gy (SRT). Patients were followed up > or = 12 months after SRS/SRT. LC and toxicity were evaluated by clinical examinations and magnetic resonance imaging. 3-D TV shrinkage was evaluated with the planning system. QoL was assessed using the questionnaire Short Form-36. RESULTS: Median follow-up was 50/36 months (SRS/SRT). Actuarial 5-year freedom from progression/overall survival was 88.1%/100% (SRS), and 87.5%/87.2% (SRT). TV shrinkage was 15.1%/40.7% (SRS/SRT; p = 0.01). Single dose (< 13 Gy) was the only determinant factor for TV shrinkage after SRS (p = 0.001). Age, gender, initial TV, and previous operations did not affect TV shrinkage. Acute or late toxicity (> or = grade 3) was never seen. Concerning QoL, no significant differences were observed after SRS/SRT. Previous operations and gender did not affect QoL (p > 0.05). Compared with the German normal population, patients had worse values for all domains except for mental health. CONCLUSION: TV shrinkage was significantly higher after SRT than after SRS. Main symptoms were not affected by SRS/SRT. Retrospectively, QoL was neither affected by SRS nor by SRT.

Stereotactic radiotherapy for the treatment of nonacoustic schwannomas.

OBJECTIVE: Nonacoustic schwannomas are rare tumors in contrast to the most common neuromas of Cranial Nerve VIII. The current treatment of choice in these cases is microsurgical resection, but the risk of postoperative complications is high, especially in cavernous sinus-invading tumors. In many of these cases, it is not possible to achieve complete tumor removal, resulting in the probability of recurrences. For those patients, radiosurgery (RS) or stereotactic radiotherapy (SRT) can offer an alternate treatment. METHODS: Within a 5-year period (2000-2005), 19 intracranial nonacoustic neuromas were treated with SRT-13 trigeminal neuromas, five neuromas of the lower cranial nerves (jugular foramen), and one located in the orbital region. Of these cases, there were nine women and 10 men who were, on average, 54 years of age (range, 33-83 yr). Eight patients had previously undergone surgery elsewhere and showed progressive tumor growth. All 19 patients were treated with SRT: 15 with normal fractions of 1.8-2 Gy single dose up to 54-59.4 Gy. Their irregular tumor volume ranged from 4.2 to 43.1 ccm (average: 14.1 ccm). Hypofractionation with 6 to 7 x 5 Gy was applied in four cases with an average tumor volume of 4.1 ccm (2.2-6.2 ccm). Clinical results and the efficacy for tumor control with an average follow-up of 35 months (11-63 mo) were evaluated. RESULTS: Local tumor control rate was 95% (18 of 19 cases): one patient previously operated on had a recurrence of tumor progression after SRT, followed by a second subtotal resection. A tumor regression was proved in 11 cases (one neuroma disappeared and four patients had tumor shrinkage of more than 50%, the other six experienced shrinkage between 20% and 40%). Within the first 6 months, two patients developed temporarily increased tumor volume as well as a confirmed reaction to irradiation. In one of these two cases, there were mild side effects according to CTC Grade I. No patient experienced a new or increased neurological deficit. Improvement of their cranial nerve disturbances was achieved in 11 of 19 patients and the other eight showed no clinical changes. The mostly moderate trigeminal pain decreased slowly. CONCLUSION: SRT is a low-risk and effective treatment option for intracranial neuromas. Particularly in cases of sinus cavernous-invading trigeminal and in jugular foramen tumors, SRT can be the treatment of choice. Concerning tumor regression, SRT is as effective as RS.

Special aspects of diagnostic imaging for radiosurgery of arteriovenous malformations.

OBJECTIVE: Radiosurgery can be considered a well-established option for the treatment of arteriovenous malformations (AVMs). The exact application of the therapeutic dose is based on the availability of imaging data sets with superior image quality that can be superimposed using an image fusion algorithm. For follow-up studies, the quantitative comparison of the respective image data sets also plays an important role. Until now, digital subtraction angiography (DSA) has been a mandatory tool for treatment planning and follow-up procedures. The aim of this study was to investigate whether a suitable computed tomographic (CT) and/or magnetic resonance (MR) angiography procedure can replace DSA and, if so, in which cases. METHODS: For 34 AVM patients, various MR data sets were used together with the stereotactically localized CT and DSA data sets for treatment planning. To define the AVM nidus precisely, all available MR data sets were fused onto the CT data set by the use of an automatic image fusion algorithm. The nidus was outlined in both localized DSA projections, resulting in the DSA target volume. Subsequently, the DSA target volume was adapted by inclusion of the available CT/MR data sets (localized and/or fused, slice by slice), resulting in the final target volume. Finally, both volumes were compared and analyzed. For precise comparison purposes, all available digital follow-up studies were fused. RESULTS: In all cases, the thin-slice MR data sets (1-mm slice width) that included T1-weighted series and time of flight angiographies have been precisely fused onto the stereotactically localized treatment planning CT. The final target volume was compared with the DSA target volume as follows. In 19 cases, the final target volume was larger than the DSA target volume; in six cases, it was smaller; and in five cases, it was approximately equal. The difference was significant (Wilcoxon test, difference <0.0001; t test, t = 3.01; P > 0.005). In four cases, outlining the AVM was not possible without DSA. In five patients, a two- or three-vessel DSA was needed because there were different AVM compartments. In cases in which a previous partial embolization had been undergone by the patient, the use of superimposed CT sets with and without contrast medium was important to define the completely embolized partial volumes that were not subject to treatment. The inclusion of the DSA images enabled a better identification of those arterialized veins that did not belong to the nidus. In six cases, the follow-up MR studies showed contrast enhancements overlapping the AVM nidus as a result of brain-blood barrier disturbances (T1-weighted series with contrast). In seven cases, perifocal reactions were primarily observed (T2-weighted series) 12 months after treatment with rather low clinical relevance. CONCLUSION: By integrating all available imaging modalities, the exact three-dimensional definition of the AVM nidus was safely realized for all patients. Stereotactic DSA data acquisition remains a crucial tool for safe nidus definition in radiosurgery treatment planning and cannot, therefore, be discarded at present. It is recommended that a quantitative comparison of all MR follow-up studies be established.

Hypofractionated stereotactic radiotherapy for brain metastases--results from three different dose concepts.

PURPOSE: To evaluate efficacy and toxicity of hypofractionated stereotactic radiotherapy (hfSRT) with three different dose concepts for irresectable brain metastases not amenable to radiosurgery (SRS) using non-invasive fixation of the skull. PATIENTS AND METHODS: From 6/2000 to 6/2005, 150 patients with 228 brain metastases were treated at the dedicated stereotactic radiosurgery system Novalis (BrainLAB, Feldkirchen, Germany) in two German treatment centers. Three different dose concepts were applied: 5 x 6-7 Gy (A: 72 brain metastases), 10 x 4 Gy (B: 59 brain metastases) and 7 x 5 Gy (C: 97 brain metastases). Median planning target volume (PTV) was 6.1 cm(3) (range, 0.02-95.97). RESULTS: Rates of complete remission (CR), partial remission (PR), no change (NC) and progressive disease (PD) were 42%, 30%, 21% and 7%, respectively (median follow-up 28 months). Median survival was 16 months. Survival at 6 and 12 months was 83% and 66%, respectively. Side effects were dependent on the PTV and on dose concept (median PTV in case of increasing edema or necrosis: 17 cm3, A: 22%, C: 7%). HfSRT with 10 x 4 Gy (B) was well tolerated without side effects. CONCLUSION: Hypofractionated stereotactic radiotherapy is an effective and safe treatment. In case of brain metastases >15 cm(3) (diameter >3 cm) and concerning toxicity, 10 x 4 Gy seem to be more advantageous than shorter fractionation with higher doses while 5 x 6-7 Gy and 7 x 5 Gy were followed by higher response rates. Further specification of tolerance doses and tolerance according to the different brain regions has to be done.

Fractionated stereotactic radiotherapy of glomus jugulare tumors. Local control, toxicity, symptomatology, and quality of life.

BACKGROUND AND PURPOSE: For glomus jugulare tumors, the goal of treatment is microsurgical excision. To minimize postoperative neurologic deficits, stereotactic radiosurgery (SRS) was performed as an alternative treatment option. Stereotactic fractionated radiotherapy (SRT) could be a further alternative. This study aims at the assessment of local control, side effects, and quality of life (QoL). PATIENTS AND METHODS: Between 1999-2005, 17 patients were treated with SRT. 11/17 underwent previous operations. 6/17 received primary SRT. Treatment was delivered by a linear accelerator with 6-MV photons. Median cumulative dose was 57.0 Gy. Local control, radiologic regression, toxicity, and symptomatology were evaluated half-yearly by clinical examination and MRI scans. QoL was assessed by Short Form-36 (SF-36). RESULTS: Median follow-up was 40 months. Freedom from progression and overall survival for 5 years were 100% and 93.8%. Radiologic regression was seen in 5/16 cases, 11/16 patients were stable. Median tumor shrinkage was 17.9% (p=0.14). Severe acute toxicity (grade 3-4) or any late toxicity was never seen. Main symptoms improved in 9/16 patients, 7/16 were stable. QoL was not affected in patients receiving primary SRT. CONCLUSION: SRT offers an additional treatment option of high efficacy with less side effects, especially in cases of large tumors, morbidity, or recurrences after incomplete resections.

Stereotactic radiotherapy of meningiomas: symptomatology, acute and late toxicity.

BACKGROUND AND PURPOSE: Stereotactic radiosurgery (SRS) is well established in the treatment of skull base meningiomas, but this therapy approach is limited to small tumors only. The fractionated stereotactic radiotherapy (SRT) offers an alternative treatment option. This study aims at local control, symptomatology, and toxicity. PATIENTS AND METHODS: Between 1997-2003, 224 patients were treated with SRT (n = 183), hypofractionated SRT (n = 30), and SRS (n = 11). 95/224 were treated with SRT/SRS alone. 129/224 patients underwent previous operations. Freedom from progression and overall survival, toxicity, and symptomatology were evaluated systematically. Additionally, tumor volume (TV) shrinkage was analyzed three-dimensionally within the planning system. RESULTS: The median follow-up was 36 months (range, 12-100 months). Overall survival and freedom from progression for 5 years were 92.9% and 96.9%. Quantitative TV reduction was 26.2% and 30.3% 12 and 18 months after SRT/SRS (p < 0.0001). 95.9% of the patients improved their symptoms or were stable. Clinically significant acute toxicity (CTC III degrees ) was rarely seen (2.5%). Clinically significant late morbidity (III degrees -IV degrees ) or new cranial nerve palsies did not occur. CONCLUSION: SRT offers an additional treatment option of high efficacy with only few side effects. In the case of large tumor size (> 4 ml) and adjacent critical structures (< 2 mm), SRT is highly recommended.

Significant tumor volume reduction of meningiomas after stereotactic radiotherapy: results of a prospective multicenter study.

OBJECTIVE: Stereotactic radiosurgery (SRS) is well established in the treatment of cranial base meningiomas. Fractionated stereotactic radiotherapy (SRT) offers an additional treatment option. Data for radiological regression differ, ranging from 13 to 61%. Therefore, the aims of this prospective study were to quantitatively analyze tumor volume (TV) shrinkage and to calculate determining factors. METHODS: Eighty-four patients were examined under equal conditions before and after SRT. Fat-saturated axial T1-weighted contrast-enhanced magnetic resonance imaging scans with 1- to 3-mm slice thickness were used. After image fusion, TV was drawn in each slice to analyze TV shrinkage three-dimensionally by the planning system. RESULTS: Mean TV had shrunk by 33% at 24 months (P = 0.02) and by 36% at 36 months (P = 0.0007) after SRT. With regard to half-year intervals, TV reduction decreased continuously towards a steady state (P < 0.0001). Younger age (P = 0.001) and smaller TV (P = 0.01) are determining factors. There was no correlation between TV reduction, prescribed dose, histological classification, sex, or previous operations. CONCLUSION: Meningiomas shrink significantly after SRT. TV shrinkage declines towards a steady state, which is not yet defined. Younger age and smaller TV are determining factors. Previous operations, sex, prescribed dose, or histological subtypes do not affect TV shrinkage. Eighteen to 24 months after irradiation, when symptoms are clinically stable, is the best time for the first magnetic resonance imaging scans evaluating tumor control and shrinkage.

Stereotactic radiation treatment planning and follow-up studies involving fused multimodality imaging.

OBJECT: Innovative new software solutions may enable image fusion to produce the desired data superposition for precise target definition and follow-up studies in radiosurgery/stereotactic radiotherapy in patients with intracranial lesions. The aim is to integrate the anatomical and functional information completely into the radiation treatment planning and to achieve an exact comparison for follow-up examinations. Special conditions and advantages of BrainLAB's fully automatic image fusion system are evaluated and described for this purpose. METHODS: In 458 patients, the radiation treatment planning and some follow-up studies were performed using an automatic image fusion technique involving the use of different imaging modalities. Each fusion was visually checked and corrected as necessary. The computerized tomography (CT) scans for radiation treatment planning (slice thickness 1.25 mm), as well as stereotactic angiography for arteriovenous malformations, were acquired using head fixation with stereotactic arc or, in the case of stereotactic radiotherapy, with a relocatable stereotactic mask. Different magnetic resonance (MR) imaging sequences (T1, T2, and fluid-attenuated inversion-recovery images) and positron emission tomography (PET) scans were obtained without head fixation. Fusion results and the effects on radiation treatment planning and follow-up studies were analyzed. The precision level of the results of the automatic fusion depended primarily on the image quality, especially the slice thickness and the field homogeneity when using MR images, as well as on patient movement during data acquisition. Fully automated image fusion of different MR, CT, and PET studies was performed for each patient. Only in a few cases was it necessary to correct the fusion manually after visual evaluation. These corrections were minor and did not materially affect treatment planning. High-quality fusion of thin slices of a region of interest with a complete head data set could be performed easily. The target volume for radiation treatment planning could be accurately delineated using multimodal information provided by CT, MR, angiography, and PET studies. The fusion of follow-up image data sets yielded results that could be successfully compared and quantitatively evaluated. CONCLUSIONS: Depending on the quality of the originally acquired image, automated image fusion can be a very valuable tool, allowing for fast (approximately 1-2 minute) and precise fusion of all relevant data sets. Fused multimodality imaging improves the target volume definition for radiation treatment planning. High-quality follow-up image data sets should be acquired for image fusion to provide exactly comparable slices and volumetric results that will contribute to quality contol.

Significance of different conformity indices for evaluation of radiosurgery treatment plans for vestibular schwannomas.

OBJECT: There are various kinds of conformity parameters currently in use, although several of them are limited and reflect only target volume coverage or normal tissue overdosage. Indices are reviewed with the goal of determining those that are most significant for the evaluation of radiosurgery treatment plans for patients with vestibular schwannoma, based on the authors' experience at the Novalis Shaped Beam Surgery Center. METHODS: Fifty-five radiosurgery plans for patients with vestibular schwannomas (VSs) have been evaluated. In this paper the conformation number (CN) and dose-related CN (dCN) are evaluated, and a penalty for underdosed target volumes and overdosed normal tissue is incorporated. A strategy is discussed to apply these indices (CN and dCN) to define the optimal prescription isodose (PI). For a given radiosurgery treatment plan, permitting partial target underdosage may offer an improvement of the CN. Variations of different conformation indices have been calculated for varying prescription levels--for example, an isodose plan. The resulting graph for the CN is discussed in detail to illustrate its use in defining the optimal PI level. For the 55 cases of VSs reported on, the median CNmax result was 0.78. CONCLUSIONS: It is possible to achieve highly conformal dose distributions with Novalis radiosurgical system. The CN is the parameter of choice when evaluating radiosurgery treatment plans and scoring possible treatment plans. It takes into account both target underdosage and normal tissue overdosage and offers a valuable scoring parameter while avoiding false-perfect scores.