Health-related quality of life after stereotactic radiosurgery in patients with brain metastases.

PURPOSE: This study aimed to assess health-related quality of life (HRQoL) in patients with brain metastases treated with stereotactic radiosurgery (SRS) and to identify factors associated with this. METHODS: HRQoL was measured pre-SRS, at 3- and 6-month follow-up. Physical functioning, cognitive functioning, role functioning, and fatigue were analyzed with the EORTC QLQ-C30 questionnaire. Motor dysfunction, future uncertainty, visual disorder, communication deficit, and headaches were analyzed with the EORTC QLQ-BN20. Clinically important symptom or functional impairment was assessed following set thresholds. Factors associated with impairment were identified through multivariable logistic regression analyses. RESULTS: At baseline, 178 patients were included; 54% (n=96) completed questionnaires at 3 months and 39% (n=70) at 6 months. Before SRS, 29% of linear accelerator (LINAC) patients reported physical and cognitive impairment, while 25% reported impairment for fatigue. At 6 months, 39%, 43%, and 57% of LINAC patients reported impairment respectively. Forty-five percent of Gamma Knife (GK) patients reported impairment pre-SRS for physical, cognitive functioning, and fatigue. At 6 months, 48%, 43%, and 33% of GK patients reported impairment respectively. Except for role functioning, pre-SRS symptom and functioning scores were associated with impairment at 3 months, whereas scores at 3 months were associated with impairment at 6 months. Age, gender, systemic therapy, and intracranial progression were not associated with clinically important impairment. CONCLUSION: As 33-57% of patients with brain metastases reported symptom burden and functional impairments that were of clinical importance, it is recommended to pay attention to the HRQoL outcomes of these patients during clinical encounters.

Neurocognitive functioning after Gamma Knife and LINAC stereotactic radiosurgery in patients with brain metastases.

PURPOSE: Brain metastases (BM) themselves and treatment with stereotactic radiosurgery (SRS) can influence neurocognitive functioning. This prospective study aimed to assess neurocognitive decline in patients with BM after SRS. METHODS: A neuropsychological test battery was assessed yielding ten test outcomes. Neurocognitive decline at 3 and 6 months post SRS was compared to measurement prior to Gamma Knife (GK) or linear accelerator (LINAC) SRS. Reliable change indices with correction for practice effects were calculated to determine the percentage of neurocognitive decline (defined as decline on ≥ 2 test outcomes). Risk factors of neurocognitive decline were analyzed with binary logistic regression. RESULTS: Of 194 patients pre-SRS, 40 GK and 29 LINAC patients had data accessible at 6 months. Compared to baseline, 38% of GK patients declined at 3 months, and 23% declined at 6 months. GK patients declined on attention, executive functioning, verbal memory, and fine motor skill. Of LINAC patients, 10% declined at 3 months, and 24% at 6 months. LINAC patients declined on executive functioning, verbal memory, and fine motor skills. Risk factors of neurocognitive decline at 3 months were high age, low education level and type of SRS (GK or LINAC). At 6 months, high age was a risk factor. Karnofsky Performance Scale, BM volume, number of BM, tumor progression and neurocognitive impairment pre-SRS were no risk factors. CONCLUSION: Neurocognitive decline occurs in a considerable proportion of patients with BM treated with GK or LINAC SRS. Overall, high age appears to be a risk factor for neurocognitive decline after SRS.

Stereotactic radiosurgery for limited brain metastasis using three different techniques: helical tomotherapy, volumetric modulated arc therapy, and cone-based LINAC radiosurgery.

PURPOSE: Specific radiation delivered to tumors by stereotactic radiosurgery (SRS) has become widely used in the treatment of brain metastasis. This study aimed to compare radiation therapy planning and its parameters from SRS using three different modalities: helical tomotherapy (HT), volumetric modulated arc therapy (VMAT), and cone-based linac radiosurgery (Cone-based). MATERIALS AND METHODS: Each contouring dataset of patents who experienced one to four brain metastasis received SRS in our center was re-planned to create radiation therapy planning in all three treatment systems (HT, VMAT, and Cone-based). The parameters of conformity index (CI), homogeneity index (HI), CI50, and gradient index (CGI) were analyzed to compare the effects of the three techniques. Decision score analysis was used to evaluate the performance on dosimetric and organs-at-risk parameters among the different techniques by applying the Cone-based technique as a benchmark. RESULTS: A total of 21 patients with 39 lesions were included in this study. The results from the decision score analysis demonstrated statistically identical CI, CI50, and CGI values between Cone-based and VMAT for single lesions. For multiple lesions, VMAT also provided better CI when compared to Cone-based technique while HT exhibited the poorest dosimetric parameters. Moreover, VMAT exhibited the lowest BrainV5Gy value and displayed the shortest beam-on time calculation. CONCLUSION: We have conducted a comprehensive comparison of SRS planning approaches. The Cone-based technique revealed the highest HI value, while VMAT provided the best estimated beam-on time value. HT displayed a feasible SRS modality for single lesions, but not for multiple lesions.

Assessment of single isocenter linear accelerator radiosurgery for metastases and base of skull lesions.

BACKGROUND: Newer technology for stereotactic radiosurgery (SRS) should be assessed for different multi-leaf collimators (MLC). OBJECTIVE: Assess plan quality of an automated, frameless, linear accelerator based (linac) planning and delivery system (HyperArc) for SRS using both standard MLC (SMLC) and high definition MLC (HDMLC) compared to a cobalt-60 based SRS system (Gamma Knife, GK). METHODS: We re-planned twenty GK Perfexion-treated SRS patients (27 lesions) for HyperArc using SMLC and HDMLC. We assessed plan quality using the following metrics: gradient index (GI), Paddick and RTOG conformity indices (CIPaddick, CIRTOG), volume receiving half of prescription isodose (PIVhalf) and maximum dose to 0.03 cc for brainstem, optic chiasm and optic nerves, and V12Gy for brain-GTV. RESULTS: Linac plans had better conformity with HDMLC being most conformal. GK exhibited better GI. PIVhalf demonstrated no statistically significant difference between HDMLC and GK, and SMLC was nominally worse than GK. Mean PIVhalf was generally 0.85 cc larger for SMLC than HDMLC. For TV > 1.0 cc, the relative differences in CIRTOG, GI, and PIVhalf for SMLC vs. HDMLC were less than 21%. For TV less than < 1.0 cc, there were more obvious relative differences for SMLC vs. HDMLC in CIRTOG (mean 146%, max 700%), GI (mean 49%, max 162%), and PIVhalf (mean 77%, max 522%). Organ at risk doses were met in all plans. CONCLUSIONS: New linac-based plans positively compare to GK plans overall. HDMLC should be strongly considered for treatment of lesions < 1.0 cc given the significant improvements in conformity and PIVhalf over SMLC.

Linear Accelerator-Based Radiosurgery of Grade I Intracranial Meningiomas.

OBJECTIVE: To determine the local control rate and complication rate in the treatment of grade I intracranial meningiomas. METHODS: A retrospective study was performed of patients with grade I meningioma who received radiosurgery with a dedicated linear accelerator from January 2002 to August 2012 with a minimum follow-up of 2 years. We performed descriptive statistics, logistic regression, and progression-free survival analysis through a Kaplan-Meier curve. RESULTS: Seventy-five patients with 78 grade I meningiomas received radiosurgery, 39 underwent surgery plus adjuvant radiosurgery, and 36 only radiosurgery. The follow-up median time was 68 months (range, 35-120 months). The tumor control rate was 93%, the 5-year progression-free survival was 92% (95% confidence interval, 77%-98%). Acute toxicity was 2.6%, and grade 1-2 late toxicity was 26.6%. Postradiosurgery edema was the main late morbidity. Age >55 years was the only significant factor for attaining a response >75%. The background of surgery before radiosurgery was the only significant prognostic factor for showing edema (odds ratio 5.78 [95% confidence interval, 2.14-15.64]). CONCLUSIONS: The local control rate attained in our series is similar to that reported in other series worldwide; the acute toxicity rate was low and late toxicity was moderate.

Micro-Multileaf Collimator LINAC Radiosurgery for Vestibular Schwannomas.

OBJECTIVE: This study evaluates the efficacy of linear accelerator (LINAC) radiosurgery using micro multi-leaf collimator technique (µMLC) in the treatment of a consecutive series of patients with vestibular schwannomas. PATIENTS AND METHODS: In this retrospective study, we enrolled 50 patients with non-neurofibromatosis type 2 vestibular schwannoma who were treated with µMLC LINAC-based SRS at University Hospital of Cologne, Germany. A minimum clinical follow-up of 24 months was conducted. Thirty-nine out of the 50 tumors (78 %) were treated with µMLC LINAC as a primary treatment (a newly diagnosed tumor). The remaining 11 vestibular schwannomas (22%) were treated as a salvage treatment (5 patients with a residual tumor; and 6 patients with a recurrent tumor following a microsurgical resection). The median tumor volume was 1.4 ml. The median tumor surface dose, median maximal dose and median therapeutic isodose were 12 Gy, 16 Gy and 77% respectively. RESULTS: Follow-up MR images showed that a tumor progression-free status was achieved for 95.7% of patients. Partial tumor shrinkage was observed after µMLC LINAC SRS for 21.3% of patients. No change in tumor size (a stable tumor) was noted for 74.5% of patients. Tumor progression was observed for 4.3% of patients. At the end of follow-up, the actuarial 5- year and 10 year progression-free survival after radiosurgery were both 95.7%. CONCLUSIONS: LINAC radiosurgery using a micro multi-leaf collimator for vestibular schwannomas smaller than 3 cm is effective in yielding a high local tumor control, whereas the treatment-related morbidity remains low.

Prognostic factors for complete obliteration of arteriovenous malformations treated with LINAC-based stereotactic radiosurgery.

OBJECTIVES: Few series analyzing prognostic fac tors predicting for obliteration of arteriovenous malformations (AVMs) following linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) have been reported. We analyzed prognostic variables, outcomes, and toxicities in 88 patients undergoing LINAC-based SRS for AVMs. METHODS: Following IRB approval, patient records were retrospectively analyzed to identify independent predictors of complete response (obliteration) (CR) and time-to-CR. The majority of AVMs were treated using multiple isocenters and non-coplanar arcs. The median AVM volume was 2.67 cm3 (0.05 - 33.51). Median marginal and maximal doses were 17 (12-24) and 26.1 Gy (15-40), with a median prescription isodose surface of 65%. RESULTS: Spetzler-Martin (SM) grade was determined for 86 patients and was: I-3 pts (3%); II-23 pts (27%); III-45 pts (52%); IV-13 pts (15%); V-2 pts (2%).Of 80 patients with follow-up imaging, 44 (55%) had documented complete responses (CR). Kaplan-Meier estimate probability for CR at 4 years was 62% (95% CI: 0.50, 0.74). Median time to CR was 3 years (95% CI: 2.08, 3.17). Multivariate analysis demonstrated the Spetzler-Martin grade (OR=0.14 for grade III vs. grade I-II; p=0.004 and OR 0.07 for grade IV-V vs. grade I-II; p=0.002) and dichotomized marginal dose > 17 Gy (OR=4.19; p=0.01) to be significantly associated with CR. DISCUSSION: This report demonstrates that for LINAC-based SRS of AVM, marginal dose and Spetzler-Martin grade are strong predictors of complete AVM obliteration.

Radiosurgery with a linear accelerator in cerebral arteriovenous malformations / Radiocirurgia com acelerador linear em malformações arteriovenosas cerebrais

OBJECTIVE: To evaluate results achieved with radiosurgery and complications of the procedure when treating arteriovenous malformations with linear accelerator. METHODS: This retrospective study was conducted between October 1993 and December 1996. Sixty-one patients with arteriovenous malformations were treated with radiosurgery utilizing a 6MV energy linear accelerator. Ages of the 32 female and 29 male patients ranged from 6 to 54 years (mean: 28.3 years). The most frequent initial symptom was cephalea (45.9 percent), followed by neurological deficit (36.1 percent). Cerebral hemorrhage diagnosed by image was observed in 35 patients (57.3 percent). Most arteriovenous malformations (67.2 percent) were graded Spetzler III and IV. Venous stenosis (21.3 percent) and aneurysm (13.1 percent) were the most frequent angioarchitecture changes. The dose administered varied from 12 to 27.5Gy in the periphery of the lesion. RESULTS: Out of twenty-eight patients that underwent conclusive angiography control, complete obliteration was achieved in 18 (72 percent) and treatment failed in 7 (absence of occlusion with more than 3 years of follow-up). Four were submitted to a second radiosurgery, and one of these has shown obliteration after 18 months of follow-up. DISCUSSION: Several factors were analyzed regarding the occlusion rate (gender, age, volume, localization, Spetzler, flow, embolization, total of isocenters, prescribed dose and chosen isodose) and complications (total of isocenters, localization, volume, maximum dose, prescribed dose and chosen isodose). Analyzed variables showed no statistical significance for obliteration of the vessel, as well as for treatment complications. The largest diameter of the arteriovenous malformation, its volume and the dose administered did not influence time of obliteration. CONCLUSION: Radiosurgery is effective in the treatment of arteriovenous malformations and can be an alternative for patients with clinical...

OBJETIVO: Analisar os resultados obtidos com radiocirurgia e as suas complicações do procedimento, no tratamento das malformações arteriovenosas com acelerador linear. MÉTODOS: Este é um estudo retrospectivo. Entre Outubro de 93 e Dezembro de 96, sessenta e um pacientes com malformações arteriovenosas foram tratados, utilizando um acelerador linear com 6MV de energia. As idades variaram de 6 a 54 anos (média: 28,3 anos), 32 pacientes mulheres e 29 pacientes homens. O sintoma inicial mais freqüente foi cefaléia (45,9 por cento), seguido de déficit neurológico (36,1 por cento). Hemorragia cerebral diagnostica por exame de imagem foi observada em 35 pacientes (57,3 por cento). A maioria das malformações arteriovenosas (67,2 por cento) eram graus III e IV de Spetzler. Estenose venosa (21,3 por cento) e aneurisma (13,1 por cento) foram as mais freqüentes alterações da arquitetura vascular. A dose administrada variou de 12 a 27,5Gy na periferia da lesão. RESULTADOS: Dos vinte e oito pacientes que se submeteram a controle angiográfico conclusivo, 18 tiveram obliteração completa (72 por cento) e 7 falharam ao tratamento (ausência de oclusão com mais de três anos de seguimento). Quatro pacientes foram submetidos a uma segunda radiocirurgia, e um paciente deste grupo apresentou obliteração em 18 meses de seguimento. DISCUSSÃO: Vários fatores foram analisados em relação ao grau de oclusão (sexo, idade, volume, localização, Spetzler, fluxo, embolização, total de isocentros, dose prescrita e isodose escolhida) e complicações (total de isocentros, localização, volume, dose máxima, dose prescrita e isodose escolhida). As variáveis analisadas não mostraram significância estatística para a obliteração do vaso, bem como para as complicações de tratamento. O maior diâmetro da malformação arteriovenosa, seu volume e a dose administrada não influenciaram no tempo de obliteração. CONCLUSÃO: Radiocirurgia é eficiente no tratamento das malformações arteriovenosas...

LINAC Radiosurgery for Hemangioblastoma

The author performed radiosurgery with linear accelerator(LINAC) on two patients who were unable to receive surgical treatment. A 75-year-old-male patient(case 1) whose main complaints were gait disturbance and headache had undergone total resection of cerebellar hemangioblastoma five years before the admission and the lesion recurred. Because the patient's general condition was poor, radiosurgery with LINAC was performed and at 1 month after the radiosurgery, obstructive hydrocephalus developed, and ventriculoperitoneal shunt was done. After 11 months, follow-up brain magnetic resonance image findings showed the decrease of the size of the tumor, and the patient's consciousness returned to alertness. He could also walk using a cane. A 28-year-old male paient(case 2) whose main complaints were vertigo, ataxia refused to receive surgical resection due to his religious beliefs, and radiosurgery was performed, after cyst aspiration with ommaya reservoir insertion as an alternative. Eighteen months later, the tumor size has decreased and there were no radiosurgical complications. The patient has been followed-up at the outpatient without any notable symptoms. Through these two cases, the authors experienced tumor control by LINAC radiosurgery when surgical treatment is not acceptable. Radiosurgery seems safe and effective in the treatment of hemangioblastoma, but there is the need for further evaluation.

LINAC Radiosurgery for Metastatic Brain Tumors

OBJECTIVE: The authors take a group of patient who have undergone radiosurgery for the treatment of metastatic brain tumor, and conduct a retrospective analysis on the therapeutic response and prognotic factors which influenced the outcome. METHODS: The cases of metastatic brain tumor managed with radiosurgery at our hospital between January of 1996 and December of 2000 were 26. Second radiosurgery was performed for new metastasis in two patients. RESULTS: Average age of patients was 59.3 years. A single lesion was found in 17 cases while multiple lesions were found in 11 cases. Median survival period of the pateints who have undergone radiosurgery was 53 weeks, and survival rate at 6 months, 12 months, and 24 months was 84.6%, 53.9%, and 19.6% respectively. Overall tumor-control-rate was 92.9%. There was one case of radiation necrosis as a complication. Extracranial metastasis, controlled primary cancer and above 70 of Karnofsky performance scale score were statistically significant prognostic factors for survival. CONCLUSION: Radiosurgery is safe and effective in the treatment of metastatic brain tumor. And the control of primary malignant tumor, the presence of extracranial metastasis and above 70 of KPS have seen shown to influence the therapeutic response and prognosis.

Frameless Fractionated Stereotactic Radiotherapy Using Linear Accelerator in Large Brain Tumors

OBJECTIVE: The goals of this study are to introduce the method of fractionated stereotactic radiotherapy (FSRT), to make treatment plans and to evaluate the role of frameless FSRT in large brain tumors. METHODS: Between August 1997 and December 2000, FSRT was performed in 47 patients with brain lesion. Eighteen patients had brain tumor larger than 3cm. We used 'Point Reference System' of Northwest Medical Physics Center. Three gold markers were fixated at a given place instead of sticking the frame in the head. We used multiple-arc FSRT for round tumor and conformal FSRT for irregular tumor. RESULTS: There was no acute toxicity, except for transient headache and dizziness in two patients. Patients did not need to be hospitalized, and also did not suffer from being invasive with frames. In the radiological response of tumor volume, 2(11.1%) showed complete remission. 8(44.5%) were reduced. 4(22.2%) showed no change. 4(22.2%) were not followed up. In the clinical response of symptoms, 9(50%) were improved, 7(38.9%) were continued, and 2(11.1%) were aggravated. There were limitations that the clinical results of each patient were varied in diagnosis and underlying disease. CONCLUSION: We can apply FSRT for brain tumor larger than 3cm safely and effectively, regardless of shape irregularity and minimize the injury of normal brain tissue.

Result of Stereotactic LINAC Radiosurgery of AVM

There are several treatment modalities of cerebral arteriovenous malformation, among these, stereotactic radiosurgery is effective means of obliteration of AVM with minimal morbidity. Since July 1988 to May 1998, our institute have conducted 98 radiosurgery for arteriovenous malformations. During this period, there were 2 major changes in delivering radiation, the first one is introduction of compute r dose planning system at september 1996(CUMC normal mode), the next was CUMC Stereotactic mode using non-flat filter delivery system since september 1997. Authors report the results of the first generation LINAC(linear Accelerator) radiosurgery before introduction of computer dose planning system for radiosurgery. During the first generation period(July 1988 to september 1996), 70 patients have had stereotactic radiosurgery for vascular malformation. Among these, 49 patients could be followed at least for 2 year with angiography or MRA(magnetic resonance angiography). Hemorrhage was the most common presenting causes of undergoing radiosurgery, the parietal lobe was the most prevalent area undergoing radiosurgery for vascular malformations. With grouping of volumes, vascular malformations we re grouped as 1) volumes less than 1 ml(n= 14 ), 2) 1- 4ml (n=21), 3) 4-10ml (n=4 ), 4 ) 10-14ml(n=4 ), 5 ) volumes over 14ml (n=6). the results are as follows ' for group 1 ), total occlusion rate were 85.7 F, for group 2 ) total occlusion rate were 71.4 %, for group 3 ),4 ),5 ), total occlusion rate were 50%. As a gross result of 49 patients, total occlusion rate was 69.4%, partial occlusion was 22.4%, no response 14.3 %. 4 cases of 70 radiosurgery for vascular malformation rebleeded (5.7 %) and 2 of these patients died of bleeding (2.9%). There was no symptomatic radiation complication, but 6 patients showed increased signal intensity on T2 weighted image on follow up magnetic resonance imaging.