Evaluation of time, attendance of medical staff and resources for radiotherapy in pediatric and adolescent patients. The DEGRO-QUIRO trial.

BACKGROUND: The German Society of Radiation Oncology (DEGRO) initiated a multicenter trial to develop and evaluate adequate modules to assert core procedures in radiotherapy. The aim of this prospective evaluation was to methodical assess the required resources for radiotherapy in pediatric and adolescent patients. MATERIAL AND METHODS: At three radiotherapy centers of excellence (University Hospitals of Heidelberg and Münster, the Medical School of Hannover), the manpower and time required for radiotherapy in pediatric and adolescent patients was prospectively documented consistently over a 2-year period. The data were collected using specifically developed standard forms and were evaluated using specific process analysis tools. RESULTS: A total number of 1914 data sets were documented and carefully analyzed. The personnel time requirements for all occupational groups were calculated as total time needed for a specific procedure and mean time per person. Regarding radiotherapy in general anesthesia, the required manpower was higher. The personnel time requirements in these cases were also longer, mainly due to longer room occupancy. Overall, the required resources were remarkably similar between the three different departments and may, therefore, be considered as representative. CONCLUSION: For the first time, the personnel time requirements of a radiotherapy department for the maintenance, protection, and optimization of operational readiness for radiotherapy in pediatric and adolescent patients with and without general anesthesia were determined methodically.

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.

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.

Gene expression signatures in the peripheral blood after radiosurgery of human cerebral arteriovenous malformations.

PURPOSE: To unravel biological mechanisms potentially resulting in the obliteration process after radiosurgery (RS) of human cerebral arteriovenous malformations (AVMs) by investigating molecular signatures on the transcriptomic level in peripheral blood of patients. PATIENTS AND METHODS: Venous blood samples were obtained at definite points of time before and after RS. The samples were tested for radiation-induced changes regarding biological markers (mRNA) using cDNA and oligo-microarray technology. The corresponding expression profiles were correlated with clinical data and obliteration signs in radiologic imaging. RESULTS: The proof of principle that RS outcome can be successfully correlated with transcriptomics of cellular blood components as disease parameter was demonstrated. The authors identified 76 differentially regulated genes (p < 0.001) after RS. Interestingly, in particular genes with known roles in anti-angiogenic and pro-coagulative pathways were identified as potentially relevant. In particularly, the authors found a significant downregulation of neuropilin-2, protein C inhibitor and cyclin-dependent kinase 6. They also found that low pretreatment blood mRNA levels of TLR4 (toll-like receptor 4) and STAT3 (signal transducer and activator of transcription 3) correlated with fast obliteration of AVMs. CONCLUSION: The authors report on a novel technique for molecular biological analysis of blood from patients with cerebral AVM treated with RS. Differential regulation of genes in peripheral blood was successfully correlated with RS and time to obliteration of AVMs. The identified genes indicate a potential new methodology to monitor RS, which may result in an individualized therapy and optimized follow-up.

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.

Multidisciplinary pain management based on a computerized clinical decision support system in cancer pain patients.

A prospective controlled intervention cohort study in cancer pain patients (n=50 per group) admitted to radiation oncology wards (62 beds, 3 wards) was conducted in a 1621-bed university hospital. We investigated the effect of an intervention consisting of daily pain assessment using the numeric visual analog scale (NVAS) and pain therapy counseling to clinicians based on a computerized clinical decision support system (CDSS) to correct deviations from pain therapy guidelines. Effects on guideline adherence (primary outcome), pain relief (NVAS) at rest and during physical activity (both groups: cross-sectional assessment on day 5; intervention group: every day assessment), co-analgesic prescription, and acceptance rates of recommendations (secondary outcomes) were assessed. The number of patients with at least one deviation from guidelines at discharge was decreased by the intervention from 37 (74%) in controls to 7 (14%, p<0.001). In the intervention group, pain (NVAS) decreased during hospital stay at rest from 3.0 (Delta(0.5) (Q(75%)-Q(25%))=3.0) on admission to 1.5 (Delta(0.5)=1.0) at discharge (p<0.01) and during physical activity from 7.0 (Delta(0.5)=4.0) on admission to 2.5 (Delta(0.5)=3.8) at discharge (p<0.001). At discharge, the number of patients treated with co-analgesics increased from 23 (46%) in controls to 33 (66%) in the intervention group (p=0.04). From 279 recommendations issued in the intervention 85% were fully accepted by the physicians. Deviations from well-established guidelines are frequent in pain therapy. A multidisciplinary pain management increased adherence to pain management guidelines.

Influence of intravenous contrast agent on dose calculation in 3-D treatment planning for radiosurgery of cerebral arteriovenous malformations.

PURPOSE: To investigate the influence of local density increase by i.v. contrast agent on dose calculation in linac-based radiosurgery (RS) of cerebral arteriovenous malformations (AVMs). MATERIAL AND METHODS: RS was performed after three-dimensional (3-D) treatment planning using a total number of nine to 14 beams. Mean target volume was 5.3 cm(3) (range, 0.1-41.2 cm(3)). Mean maximum diameter was 23.2 mm (range, 8-51 mm). Dose deviation was estimated and calculated from the enhanced and unenhanced datasets of 30 patients. Dose calculation was performed using the same RS treatment plan on both datasets. Both plans were standardized to 1 Gy at isocenter with the same dose weight for all beams. RESULTS: Mean difference of Hounsfield units (DeltaHU) between enhanced and unenhanced CT was 152 HU (range, 50-350 HU). The estimated dose deviation was

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.

SU11657 enhances radiosensitivity of human meningioma cells.

PURPOSE: To analyze the effect of the multireceptor tyrosine kinase inhibitor SU11657 (primarily vascular endothelial growth factor, platelet-derived growth factor) in combination with irradiation in freshly isolated primary human meningioma cells. METHODS AND MATERIALS: Tumor specimens were obtained from meningioma patients undergoing surgery at the Department of Neurosurgery, University of Heidelberg, Germany. For the present study only cells up to passage 6 were used. Benign and atypical meningioma cells and human umbilical vein endothelial cells (HUVEC) were treated with SU11657 alone and in combination with 6-MV photons (0-10 Gy). Clonogenic survival and cell proliferation were determined alone and in coculture assays to determine direct and paracrine effects. RESULTS: Radiation and SU11657 alone reduced cell proliferation in atypical and benign meningioma cells as well as in HUVEC in a dose-dependent manner. SU11657 alone also reduced clonogenic survival of benign and atypical meningioma cells. SU11657 increased radiosensitivity of human meningioma cells in clonogenic survival and cell number/proliferation assays. The anticlonogenic and antiproliferative effects alone and the radiosensitization effects of SU11657 were more pronounced in atypical meningioma cells compared with benign meningioma cells. CONCLUSION: Small-molecule tyrosine kinase inhibitors like SU11657 are capable of amplifying the growth inhibitory effects of irradiation in meningioma cells. These data provide a rationale for further clinical evaluation of this combination concept, especially in atypical and malignant meningioma patients.

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.

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.

Pediatric cerebral arteriovenous malformations: the role of stereotactic linac-based radiosurgery.

PURPOSE: To evaluate retrospectively clinical outcome and obliteration rates after linac-based radiosurgery (RS) in children with cerebral arteriovenous malformations (AVM). METHODS AND MATERIALS: Between 1996 and 2002, 22 children with cerebral AVM were treated at our institution. Mean age at treatment was 11.8 years (range, 4.4-16.4 years). Classification according to Spetzler-Martin was 1 child grade I (4%), 7 grade II (32%), 12 grade III (56%), 1 grade IV (4%), and 1 grade V (4%). Median single dose was 18 Gy/80%-isodose. Median AVM volume was 4.2 mL (range, 0.4-26.5 mL). Median RS-based AVM-score was 1.07 (range, 0.61-3.55). Fifty-nine percent of children experienced intracranial hemorrhage before RS. Median follow-up was 3.1 years (range, 1.7-7.3 years). RESULTS: Actuarial complete obliteration rate (CO) was 54% after 3 years and 65% after 4 years, respectively. Median time interval to CO was 27.1 months. Intracranial hemorrhage after RS was seen in five children after median 13.9 months. Annual bleeding risk was 9.1% after 1 year and 13.6% after 2 years. Maximum diameter>or=3 cm and AVM-volume>or=6 mL were significant predictors for intracranial hemorrhage. Neurologic deficits were improved/completely dissolved in 58% of children and remained stable in 42%. No new onset of neurologic dysfunction was seen after RS. CONCLUSIONS: RS is safe and effective in pediatric cerebral AVM with high obliteration rates. Size and volume of AVM are significant predictors for intracranial bleeding. The same treatment guidelines as in adults should be applied. Careful long-term follow-up observation is required after RS from long life expectation.

Improved target volume definition for fractionated stereotactic radiotherapy in patients with intracranial meningiomas by correlation of CT, MRI, and [68Ga]-DOTATOC-PET.

PURPOSE: To evaluate the influence of 68-Ga-labeled DOTA (0)-D-Phe (1)-Tyr (3)-Octreotide positron emission tomography ([68Ga]-DOTATOC-PET) for target definition for fractionated stereotactic radiotherapy (FSRT) as a complementary modality to computed tomography (CT) and magnetic resonance imaging (MRI). Because meningiomas show a high expression of somatostatin receptor subtype 2, somatostatin analogs such as DOTATOC offer the possibility of receptor-targeted imaging. PATIENTS AND METHODS: Twenty-six patients received stereotactic CT, MRI, and [68Ga]-DOTATOC-PET as part of their treatment planning. Histology was: World Health Organization (WHO) Grade 1 61.5%, WHO Grade 2 7.7%, WHO Grade 3 3.9%, and undetermined 26.9%. Six patients received radiotherapy as primary treatment, 2 after subtotal resection; 17 patients were treated for recurrent disease. Dynamic PET scans were acquired before radiotherapy over 60 min after intravenous injection of 156 +/- 29 MBq [68Ga]-DOTATOC. These PET images were imported in the planning software for FSRT. Planning target volume (PTV)-I outlined on CT and contrast-enhanced MRI was compared with PTV-II outlined on PET. PTV-III was defined with CT, MRI, and PET and was actually used for radiotherapy treatment. RESULTS: PTV-III was smaller than PTV-I in 9 patients, the same size in 7 patients, and larger in 10 patients. Median PTV-I was 49.6 cc, median PTV-III was 57.2 cc. In all patients [68Ga]-DOTATOC-PET delivered additional information concerning tumor extension. PTV-III was significantly modified based on DOTATOC-PET data in 19 patients. In 1 patient no tumor was exactly identified on CT/MRI but was visible on PET. CONCLUSION: These data demonstrate that [68Ga]-DOTATOC-PET improves target definition for FSRT in patients with intracranial meningiomas. Radiation targeting with fused DOTATOC-PET, CT, and MRI resulted in significant alterations in target definition in 73%.

Linac-based radiosurgery or hypofractionated stereotactic radiotherapy in the treatment of large cerebral arteriovenous malformations.

PURPOSE: We investigate retrospectively clinical outcome after radiosurgery (RS) or hypofractionated stereotactic radiotherapy (HSRT) in patients with large cerebral arteriovenous malformations (AVMs). METHODS AND MATERIALS: This analysis is based on 48 patients with cerebral AVM greater than 4 cm treated with HSRT or RS at our institution. Fifteen patients received HSRT, with 26 Gy median total dose in 4 to 5 fractions, and 33 patients received RS with 17 Gy median total dose in 4 to 5 fractions. Median target volume was 27 cc in HSRT and 7 cc in RS; median maximum diameter was 6 cm and 5 cm, respectively. Seventeen patients experienced intracranial hemorrhage before treatment. Median follow-up was 2.6 years. RESULTS: The 3-year and 4-year actuarial complete obliteration (CO) after HSRT was 17% and 33% and after RS was 47% and 60%, respectively. Actuarial CO was higher in AVMs less than 5 cm (66% vs. 37% after 4 years). Intracranial hemorrhage after HSRT occurred in 3 of 15 patients after 18 months median, and after RS in 7 of 33 patients after 17 months median. Bleeding risk was significantly higher in patients with prior hemorrhage (p < 0.04). Preexisting neurologic dysfunction improved/dissolved in 50% and remained stable in 45%. CONCLUSIONS: Large AVMs need a long time period to obliterate and show a high bleeding risk. Multimodal treatment strategies are required to reduce treatment volume before radiotherapy.

Stereotactic linac-based radiosurgery in the treatment of cerebral arteriovenous malformations located deep, involving corpus callosum, motor cortex, or brainstem.

PURPOSE: To evaluate patient outcome and obliteration rates after radiosurgery (RS) for cerebral arteriovenous malformations (AVM) located deep, in the motor cortex or brainstem and those involving corpus callosum. METHODS AND MATERIALS: This analysis is based on 65 patients. AVM classification according to Spetzler-Martin was 13 patients Grade 2, 39 Grade 3, 12 Grade 4, and 1 Grade 5. Median RS-based AVM score was 1.69. Median single dose was 18 Gy. Mean treatment volume was 5.2 cc (range, 0.2-26.5 cc). Forty patients (62%) experienced intracranial hemorrhage before RS. Median follow-up was 3.0 years. RESULTS: Actuarial complete obliteration rate (CO) was 50% and 65% after 3 and 5 years, respectively. CO was significantly higher in AVM <3 cm (p < 0.02) and after doses >18 Gy (p < 0.009). Annual bleeding risk after RS was 4.7%, 3.4%, and 2.7% after 1, 2, and 3 years, respectively. AVM >3 cm (p < 0.01), AVM volume >4 cc (p < 0.009), and AVM score >1.5 (p < 0.02) showed a significant higher bleeding risk. Neurologic dysfunction improved, completely dissolved, or remained stable in 94% of patients. CONCLUSIONS: Surgically inaccessible AVM can be successfully treated using RS with acceptable obliteration rates and low risk for late morbidity. The risk of intracranial hemorrhage is reduced after RS and depends on RS-based AVM score.

External beam radiotherapy in the treatment of male breast carcinoma: patterns of failure in a single institute experience.

AIMS AND BACKGROUND: We analyzed our own results in the treatment of male breast cancer patients with respect to local control, overall survival and possible prognostic factors for local and distant control. METHODS: Thirty-one patients with 32 carcinomas of the male breast were treated with radiotherapy. Twenty-five patients received radiotherapy to the chest wall including or not regional lymphatics after initial mastectomy (n = 23) or after surgery for local recurrence (n = 2). Median total dose was 60 Gy to the chest wall and 46 Gy to regional lymphatics. Seven patients with metastatic disease were referred for palliative radiotherapy. RESULTS: Overall survival after postoperative radiotherapy was 40% after a median follow-up of 4.3 years. Actuarial 3-, 5- and 10-year survival was 82.6%, 56.5% and 43.5%, respectively. Five-year progression-free survival was 62.5%. Survival was significantly affected by the presence of lymph node metastases (P <0.001). Local recurrence was seen in one patient after 29 months. CONCLUSIONS: Postoperative radiotherapy is important in the management of male breast cancer to improve local control and progression-free survival, resulting in one local failure in our analysis. The presence of lymph node metastases significantly impairs survival.

Characterization of 68Ga-DOTA-D-Phe1-Tyr3-octreotide kinetics in patients with meningiomas.

UNLABELLED: Because biopsy has a high risk of hemorrhage and the findings of CT and MRI are often ambiguous, especially at the base of the skull, additional methods for the characterization of intracranial tumors are needed. Meningiomas show high expression of the somatostatin receptor subtype 2 and thus offer the possibility of receptor-targeted imaging. We used the somatostatin analog (68)Ga-DOTA-d-Phe(1)-Tyr(3)-octreotide (DOTA-TOC) labeled with the positron emitter (68)Ga (half-life, 68 min), obtained from a (68)Ge/(68)Ga generator, for PET of these tumors. In contrast to (18)F-FDG, this ligand shows high meningioma-to-background ratios. The aim was to evaluate kinetic parameters in meningiomas before radiotherapy. METHODS: Dynamic PET scans (3-dimensional mode; 28 frames; ordered-subsets expectation maximization reconstruction) were acquired for 21 patients (mean age +/- SD, 51 +/- 13 y) before radiotherapy during the 60 min after intravenous injection of 156 +/- 29 MBq of (68)Ga-DOTA-TOC. We analyzed 28 meningiomas (median grade [I] according to the system of the World Health Organization) with volumes of at least 0.5 mL (mean volume, 13.1 mL) and nasal mucosa as reference tissue, showing a slight to moderate physiologic uptake. For evaluation of the (68)Ga-DOTA-TOC kinetics, the vascular fraction (vB) and the rate constants (k1, k2, k3, and k4 [1/min]) were computed using a 2-tissue-compartment model. Furthermore, receptor binding (RB) (k1 - k1 x k2) and the ratios k1/k2 and k3/k4 were calculated. RESULTS: Significant differences (P < 0.05; t test) between meningiomas and the reference tissue were found for the mean standardized uptake value (10.5 vs.1.3), vB (0.42 vs. 0.11), k2 (0.12 vs. 0.56), k3 (0.024 vs. 0.060), k4 (0.004 vs. 0.080), and RB (0.49 vs. 0.13). Although there was no significant difference for k1 (0.54 vs. 0.40), the ratios k1/k2 (4.50 vs. 0.71) and k3/k4 (6.00 vs. 0.75) were markedly greater in meningiomas than in reference tissue. CONCLUSION: The high uptake of (68)Ga-DOTA-TOC in meningiomas can be explained by the high values for vB and by the remarkably low values for k2 and k4, leading to significantly greater k1/k2 and k3/k4 ratios and RB in meningiomas than in reference tissue. Thus, pharmacokinetic modeling offers a more detailed analysis of biologic properties of meningiomas. In further studies, these data might serve as a basis for monitoring the somatostatin receptors of meningiomas after radiotherapy.

Treatment outcome after linac-based radiosurgery in cerebral arteriovenous malformations: retrospective analysis of factors affecting obliteration.

PURPOSE: We investigated patient outcome and factors affecting obliteration rate after radiosurgery in cerebral arteriovenous malformations (AVM). MATERIAL AND METHODS: We have treated 110 patients with cerebral AVM with linac-based radiosurgery (RS). AVM classification according Spetzler-Martin was 17 patients grade I (15%), 39 grade II (36%), 41 grade III (37%), 12 grade IV (11%) and 1 grade V (1%). Median single dose was 18 Gy. Mean treatment volume was 4.7 cc (range, 0.1-24.0 cc). Fifty-two patients experienced hemorrhage prior to RS. Median follow-up was 2.5 years. RESULTS: Actuarial complete obliteration rate (CO) was 51% after 3 years and 67% after 4 years. CO rate was significantly higher in AVM <3 cm (64% vs. 43%, P<0.04) and in patients with grade I/II vs. III-V (71% vs. 33%, P<0.001). CO was significantly improved after doses >18 Gy (P<0.02) and in male gender (P<0.04). In multivariate analysis Spetzler-Martin grade remained significant. Intracranial hemorrhage after RS occurred in 9 patients 13.9 months median after RS. Neurological dysfunction improved/completely dissolved or remained stable in 95% of patients. No new onset of neurological dysfunction was seen. No significant adverse effects after RS were seen. CONCLUSIONS: The rate of obliteration after RS in AVM depends on applied single dose as well as size and Spetzler-Martin grade. RS is an alternative to neurosurgery, especially in patients with small or surgically inaccesible AVM.