Treatment of patients with multiple brain metastases by isolated radiosurgery:Toxicity and survival

BACKGROUND Radiosurgery for multiple brain metastases has been more reported recently without using whole-brain radiotherapy.Nevertheless,the sparsity of the data still claims more information about toxicity and survival and their association with both dosimetric and geometric aspects of this treatment.AIM To assess the toxicity and survival outcome of radiosurgery in patients with multiple(four or more lesions)brain metastases.METHODS In a single institution,data were collected retrospectively from patients who underwent radiosurgery to treat brain metastases from diverse primary sites.Patients with 4-21 brain metastases were treated with a single fraction with a dose of 18 Gy or 20 Gy.The clinical variables collected were relevant to toxicity,survival,treatment response,planning,and dosimetric variables.The Spearman’s rank correlation coefficients,Mann-Whitney test,Kruskal-Wallis test,and Log-RESULTS From August 2017 to February 2020,55 patients were evaluated.Headache was the most common complaint(38.2%).The median overall survival(OS)for patients with karnofsky performance status(KPS)>70 was 8.9 mo,and this was 3.6 mo for those with KPS≤70(P=0.047).Patients with treated lesions had a median progression-free survival of 7.6 mo.There were no differences in OS(19.7 vs 9.5 mo)or progression-free survival(10.6 vs 6.3 mo)based on prior irradiation.There was no correlation found between reported toxicities and planning,dosimetric,and geometric variables,implying that no additional significant toxicity risks appear to be added to the treatment of multiple(four or more)lesions.CONCLUSION No associations were found between the evaluated toxicities and the planning dosimetric parameters,and no differences in survival rates were detected based on previous treatment status.

Therapeutic usability of two different fiducial gold markers for robotic stereotactic radiosurgery of liver malignancies:A pilot study

AIM: To assess how the application of different types of markers affects the tracking accuracy of Cyber Knife's.METHODS: Fifteen patients were recruited and subjected to the ultrasound-guided placement of markers. Two different type of needles 25 gauge(G) and 17 G containing two different fiducial marker, gold notched flexible anchor wire 0.28 mm × 10 mm(25 G needle) and gold cylindrical grain 1 mm × 4 mm(17 G), were used. Seven days after the procedure, a Cyber Knife planning computed tomography(CT) for the simulation of radiation treatment was performed on all patients.A binary CT score was assigned to the fiducial markers visualization. Also, the CT number was calculated for each fiducial and the values compared with a specific threshold.RESULTS: For each patient from 1 to 5, intra-hepatic markers were placed(one in 2 patients, three in 8 patients, four in 3 patients, and five in 2 patients). A total of 48 needles were used(thirty-two 17 G and sixteen 25 G) and 48 gold markers were placed(32 Grain shaped markers and 16 Gold Anchor). The result showed that the CT visualization of the grain markers was better than the anchor markers(P = 5 × 10^(-9)). Furthermore, the grain markers were shown to present minor late complications(P = 3 × 10^(-6)), and the best CT threshold number(P = 0.0005). CONCLUSION: The study revealed that the Gold Anchor fiducial marker is correlated with a greater number of late minor complications and low visualization by the CT.

Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma

Glioblastoma multiforme(GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM(r GBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery(GKRS) salvage therapy. Following a Pub Med search for studies usingGKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rG BM treatment. In this review, we compare overall survival following diagnosis, overall survival following salvage treatment, progression-free survival, time to recurrence, local tumor control, and adverse radiation effects. This report discusses results for rG BM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates(from diagnosis, range:16.7-33.2 mo; from salvage, range:9-17.9 mo). Three studies identified median progression-free survival(range:4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects(range:0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rG BM patient. However, there needs to be a randomized clinical trial to test GKRS for rG BM before the possibility of selection bias can be dismissed.

An Overview of CyberKnife Radiosurgery

Stereotactic radiosurgery is a non-invasive procedure that utilizes precisely targeted radiation as an ablative surgical tool. Conventional radiosurgery devices, such as the Gamma Knife, rely upon skeletally attached Stereotactic frames to immobilize the patient and precisely determine the 3D spatial position of a tumor. A relatively new instrument, the CyberKnife (Accuray, Inc., Sunnyvale, CA), makes it possible to administer radiosurgery without a frame. The CyberKnife localizes clinical targets using a very accurate image-to-image correlation algorithm, and precisely cross-fires high-energy radiation from a lightweight linear accelerator by means of a highly manipulable robotic arm. CyberKnife radiosurgery is an effective alternative to conventional surgery or radiation therapy for a range of tumors and some non-neoplastic disorders. This report will describe CyberKnife technology and oncologic applications in neurosurgery and throughout the body.

Value of serial magnetic resonance imaging in the assessment of brain metastases volume control during stereotactic radiosurgery

AIM To evaluate brain metastases volume control capabilities of stereotactic radiosurgery(SRS) through serial magnetic resonance(MR) imaging follow-up. METHODS MR examinations of 54 brain metastases in 31 patients before and after SRS were reviewed. Patients were included in this study if they had a pre-treatment MR examination and serial follow-up MR examinations at 6 wk, 9 wk, 12 wk, and 12 mo after SRS. The metastasis volume change was categorized at each follow-up as increased(> 20% of the initial volume), stable(± 20% of the initial volume) or decreased(< 20% of the initial volume). RESULTS A local tumor control with a significant(P < 0.05) volume decrease was observed in 25 metastases at 6-wk follow-up. Not significant volume change was observed in 23 metastases and a significant volume increase was observed in 6 metastases. At 9-wk followup, 15 out of 25 metastases that decreased in size at 6 wk had a transient tumor volume increase, followed by tumor regression at 12 wk. At 12-wk follow-up there was a significant reduction in volume in 45 metastases, and a significant volume increase in 4 metastases. At 12-mo follow-up, 19 metastases increased significantly in size(up to 41% of the initial volume). Volume tumor reduction was correlated to histopathologic subtype.CONCLUSION SRS provided an effective local brain metastases volume control that was demonstrated at follow-up MR imaging.

Microsurgery vs. radiosurgery for the treatment of multiple metastases in the brain: a retrospective cohort study

Objective:Multiple brain metastases are a severe condition for cancer patients.To date,no general consensus exists regarding the optimal treatment procedure for multiple brain metastases.Radiotherapy is the most commonly used treatment option.The role of surgical resection for multiple brain metastases is unclear.The aim of this study was to compare the outcomes of patients with multiple brain metastases treated with either surgery or stereotactic radiosurgery(SRS).Methods:The medical records of 279 consecutive adult patients with multiple brain metastases treated with either surgery(26 patients)or SRS(253 patients)were retrospectively reviewed.Propensity score matching was conducted to correct for discrepancies in the baseline characteristics,and 78 patients(26 receiving surgery and 52 receiving SRS)were chosen for comparison of outcomes,such as overall survival,local tumor control rate,and symptom improvement.Results:The tumor size in the surgery group was significantly greater than that in the SRS group after propensity score matching.However,the neurological recovery rate,incidence of leptomeningeal metastasis after surgery,1-year local tumor control rate,and overall survival were not significantly different between groups.Conclusions:Our data demonstrate that surgery and radiosurgery have identical overall survival and local tumor control rates in patients with 2 to 4 brain metastases.Although SRS remains the primary and standard option for patients with brain metastasis,surgery offers several distinct advantages,such as establishing a diagnosis or relieving mass effects,and may additionally be beneficial in carefully selected patients with 2–4 brain metastases.

PROGNOSTIC FACTORS FOR DEEP SITUATED MALIGNANT GLIOMAS TREATED WITH LINAC RADIOSURGERY

Objective To study the function of radiosurgery on malignant glioma by analyzing prognostic factors affecting malignant gliomas treated with linac radiosurgery. Method Fifty-eight patients with deep situated malignant gliomas, aged 7 to 70 years, 28 anaplastic astrocytomas and 30 glioblastomas multiforme were analyzed. The median volume of tumor was 10.67 cm3, and median prescription dose for linac radiosurgery was 20 Gy. Results were analyzed with Kaplan-Meier curve and Cox regression. Result In follow-up 44.8 percent tumors (26 patients) decreased in size. Median tumor local control interval was 10 months, 15 months for anaplastic astrocytomas, and 9 months for glioblastoma multiforme. Tumor local control probability was 37.9 percent for 1 year and 10.3 percent for 2 years. Median survival was 22.5 months for anaplastic astrocytoma, 13 months for glioblastoma multiforme, and 15 months for all patients. The survival probability was 79.3 percent at 1 year and 20.6 per-cent at 2 years. Isocenter numbers and tumor volume were the prognostic factors for tumor control, but conformity index was the prognostic factor for survival by Cox regression analysis. Considering pathology, only isocenter number and target volume significantly affected tumor control interval. Complications appeared in 44.8 percent patients and the median interval of com-plication onset was 8 months. Symptomatic cerebral edema was observed in 31.0 percent patients. Conclusion Linac radiosurgery can effectively improve tumor local control and prolong survival for deep situated mali-gnant gliomas.

Whole-brain radiation therapy alone vs. combined therapy with stereotactic radiosurgery for the treatment of limited brain metastases: A systematic review

Objective The aim of the study was to compare the efficacy and safety of whole brain radiotherapy(WBRT) used alone and combined with stereotactic radiosurgery(SRS) in the treatment of limited(1–4)brain metastases. Methods We searched for randomized controlled and matched-pair analysis trials comparing WBRT plus SRS versus WBRT alone for brain metastases. The primary outcomes were the overall survival(OS), intracranial control(IC), and localcontrol(LC). The secondary outcome was radiation toxicity. The log hazard ratios(lnHRs) and their variances were extracted from published Kaplan-Meier curves and pooled using the generic inverse variance method in the RevMan 5.3 software. The non-pooled outcome measures were evaluated using descriptive analysis. Results Three randomized controlled trials and two matched-pair analysis studies were included. There was no difference in the OS for limited brain metastases between the two groups [lnHR 0.91(95% CI 0.76–1.09, P = 0.32) vs. 0.72(95% CI 0.44–1.19, P = 0.20)]. The LC and IC were significantly higher in the combined treatment group [lnHR 0.69(95% CI 0.55–0.86, P = 0.001) vs. 0.41(95% CI 0.29–0.58, P < 0.0001)]. For patients with a single lesion, one trial showed a higher survival in the combined treatment group(median OS: 6.5 months vs. 4.9 months, P = 0.04). The combined treatment was not associated with significantly higher incidence of radiation toxicity. Conclusion Combined treatment with WBRT plus SRS should be recommended for patients with limited brain metastases based on the better LC and IC without increased toxicity. It should also be considered a routine treatment option for patients with solitary brain metastases based on the prolonged OS.

Concise review of radiosurgery for contemporary management of pilocytic astrocytomas in children and adults

Pilocytic astrocytoma(PA)may be seen in both adults and children as a distinct histologic and biologic subset of low-grade glioma.Surgery is the principal treatment for the management of PAs;however,selected patients may benefit from irradiation particularly in the setting of inoperability,incomplete resection,or recurrent disease.While conventionally fractionated radiation therapy has been traditionally utilized for radiotherapeutic management,stereotactic irradiation strategies have been introduced more recently to improve the toxicity profile of radiation delivery without compromising tumor control.PAs may be suitable for radiosurgical management due to their typical appearance as well circumscribed lesions.Focused and precise targeting of these well-defined lesions under stereotactic immobilization and image guidance may offer great potential for achieving an improved therapeutic ratio by virtue of radiosurgical techniques.Given the high conformality along with steep dose gradients around the target volume allowing for reduced normal tissue exposure,radiosurgery may be considered a viable modality of radiotherapeutic management.Another advantage of radiosurgery may be the completion of therapy in a usually shorter overall treatment time,which may be particularly well suited for children with requirement of anesthesia during irradiation.Several studies have addressed the utility of radiosurgery particularly as an adjuvant or salvage treatment modality for PA.Nevertheless,despite the growing body of evidence supporting the use of radiosurgery,there is need for a high level of evidence to dictate treatment decisions and establish its optimal role in the management of PA.Herein,we provide a concise review of radiosurgery for PA in light of the literature.

Robotic radiosurgery in pancreatic cancer: A systematic review

AIM: To present a systematic review of techniques and clinical results.METHODS: A systematic review of published literature was performed. Only studies reporting patient outcome after radiosurgery(single fraction) delivered with robotic devices [i.e.,robotic radiosurgery(RRS)] have been analyzed.RESULTS: A total of 96 patients from 5 studies were included. The studies are characterized by small series and different methods in terms of dose,target definition,combination with chemotherapy and/or standard fractionated radiotherapy and evaluation modalities. Preliminary results are positive in terms of tumor response(ORR = 56%) and local control of the tumor(crude rate of local progressions: 19.5%).Results for median overall survival(11.4 mo) seem comparable with the ones of prolonged chemoradiation(range: 8.6-13.0 mo). However,gastrointestinal toxicity seems to be the main limitation of RRS,especially at the duodenal level.CONCLUSION: RRS allows for local treatment in a shortened time(1 fraction) compared to traditional treatments(about 1 mo),providing the possibility for an easy integration with systemic therapies. Preliminary results did not show any outcome differences compared to standard chemoradiation. Thus,further efforts to reduce gastrointestinal toxicity are strongly needed.

Entrapment of the temporal horn secondary to postoperative gamma-knife radiosurgery in intraventricular meningioma: A case report

BACKGROUND Entrapment of the temporal horn (ETH) is a rare pathologic condition. It is a kind of focal hydrocephalus caused by obstruction of flow pathway of cerebrospinal fluid. It is caused by various conditions, but ETH secondary to postoperative gamma-knife radiosurgery (GKS) is extremely rare. CASE SUMMARY A 52-year old previously healthy woman underwent resection of a large intraventricular meningioma. A small fragment of residual tumor with no obvious enlargement of the temporal horn was observed 3 mo after surgery, and she was referred for GKS. Two months after GKS, she complained of headache and progressive paralysis of the left limb. Magnetic resonance imaging revealed enlargement of the temporal horn. There was a second procedure to resect the residual tumor 8 mo after GKS. After the second procedure, she recovered smoothly. As of the date of this writing, she has remained in good condition. CONCLUSION This case reminds us that ETH should be considered in the treatment of intraventricular meningiomas, especially before GKS.

Arteriovenous Malformation (AVM) Treated with Robotic Radiosurgery: Impact of Beam Reduction in 12 Gy Normal Brain Volume and It’s Clinical Implication

Purpose: Dosimetric study to evaluate impact of “beam” reduction in AVM radiosurgery on normal brain dose parameters and it’s clinical implications. Materials and Methods: Five small volume AVMs (nidus volume 0.31 - 1.94 cc) planned for single fraction SRS with robotic radiosurgery system. Planning scans done with CT scan brain, CT & MR angiography, then nidus volume and organ at risk (OARs) were contoured. Planning was done with multiplan planning system. Plan evaluated as per Flickenger model parameters of 12 Gy nomal brain vol & marginal dose. 7.5 mm and 10 mm cons used, optimization done with seqential algorithm. 20 Gy was prescribed to isodose with appropriate nidus coverage (>98%). Total beams of five plans were 85 - 250, monitor unit 17,259 - 24,602 MU. 12 Gy normal brain volume is 0.9 - 7.6 cc. Then beam reduction is done by reducing beams with minimum MU in steps of 50, 100, 150, 200, 250 MU and after beam reduction, re-optimization done. Prescription isodose was changed to keep the nidus coverage > 98%. Impacts of beam reduction on 12 Gy normal brain vol and conformity/homogeniety index were analyzed. Results: Optimal plans of five patients with 20 Gy prescribed to 88% - 90% isodose, nidus coverage more than 98%. In dosimetric parameters, mean CI was 1.36 - 1.51, nCI 1.41 - 1.51, HI 1.1 - 1.4 and mean 12 Gy normal brain volume 0.17, 1.44, 5.3, 5.5 and 7.6cc respectively. After beam reduction of less than 50 MU contribution (in case#1), prescibing at suitable isodose (85%) beam reduces to 79 and 12 Gy volume marginally increases to 26.4 cc. Beam reduction of less than 100 MU reduces to 53 - 92 beamlets. Reduction of beams with less than 150 MU contribution did not significantly change the 12Gy normal brain volume. However, reduction of beamlets with more than 200 MU, 250 MU, 300 MU, 450 MU and 550 MU significantly affects the 12 Gy normal brain volume. Prescription-isodose modified from 83% to 50% to have >98% coverage. CI and HI increased from 1.36 - 1.51 to 2.51 - 2.63 and 1.1 - 1.4 to 1.52 - 1.54 respectively. There was exponential increase in 12 Gy volume with reduction of beams with higher proportion in larger nidus. Conclusions: In robotic radiosurgery system, beam reduction even after re-optimization impairs the conformity index and increase 12 Gy normal brain volume, hence long-term toxicity. Optimal beam numbers are required for optimal plan generation.

Three Dimensional Expansion of Margins for Single-fraction Treatments: Stereotactic Radiosurgery Brain Cases

Purpose: To derive a clinically-practical margin formula between clinical target volume (CTV) and planning target volume (PTV) for single-fraction stereotactic radiosurgery (SRS). Methods: In previous publications on the margin between the CTV and the PTV, a Gaussian function with zero mean was assumed for the systematic error and the machine systematic error was completely ignored. In this work we adopted a Dirac delta function for the machine systematic error for a given machine with nonzero mean systematic error. Mathematical formulas for calculating the CTV-PTV margin for single-fraction SRS treatments were proposed. Results: Margins for single fraction treatments were derived such that the CTVs received the prescribed dose in 95% of the SRS patients. The margin defined in this study was machine specific and accounted for nonzero mean systematic error. The differences between our formulas and a previously published formula were discussed. Conclusion: Clinical margin formulas were proposed for determining the margin between the CTV and the PTV in SRS treatments. Previous margin’s recipes, being derived specifically for conventional treatments, may be inappropriate for single-fraction SRS and could result in geometric miss of the target and even treatment failure for machines possessing of large systematic errors.

Evaluation of therapeutic effects of radiosurgery using ^(99)Tc^m-MIBI brain SPECT in patients with brain tumor

Objective: To evaluate the therapeutic effects of radiosurgery on brain tumor using 99Tcm-MIBI brain single-photon emission computed tomography (SPECT). Methods: Fifteen normal volunteers and 49 patients with brain tumor underwent 99Tcm-MIBI brain SPECT, and the tumor to non-tumor ratio (T/N) was calculated and compared before and after radiosurgery. The patients were regrouped according to different schedules for postoperative reexamination, and diagnostic sensitivity and specificity of 99Tcm-MIBI SPECT evaluated against that of conventional CT and magnetic resonance imaging. Results: After radiosurgery, the lesions were reduced or even disappeared in 22 cases, and tumor remnants or recurrence were found in 27 cases. The sensitivity, specificity and accuracy of 'Tc''-MIBI brain SPECT were 85. 2%, 68. 2% and 77. 6% , respectively. The sensitivity of postoperative 99Tcm-MIBI brain SPECT at 5. 8 months was 92% , significantly higher than that at 3. 1 months (89% , u = 2. 2545, P<0. 05) , and its accuracy was also higher than those at 3. 1 months (a = 2. 5927, P<0. 05) and at 9. 4 months (u = 2. 1760, P<0. 05). The preoperative T/N ratio averaged 9. 5?. 6, significantly lowered to 2. 9?. 1 postoperatively (t = 4. 4373, P<0. 001). T/N ratio of recurrence group was remarkably higher than those of tumor remnants group (t = 2. 1496, P<0. 05), edema group (t=9. 2186, P<0. 001) and cicatrization group (t = 6. 3906, P<0. 001). Conclusion; 99Tcm-MIBI brain SPECT is more accurate than CT in distinguishing tumor residuals from benign lesions such as edema and cicatrization. At about 6 months after radiosurgery, 99Tcm-MIBI SPECT can obtain optimal diagnostic effects.

Use of stereotactic radiosurgery in the treatment of gynecologic malignancies:A review

Recent retrospective studies have reported the use ofstereotactic radiosurgery(SRS) in the treatment of gy-necologic cancers. SRS uses real-time imaging and highdose radiation beams attached to precise robotic armsto target malignant lesions while sparing normal tissue.The purpose of this review is to examine the indicationsfor SRS in gynecologic oncology, review the currentliterature regarding the use of SRS in gynecologic can-cers, and identify future directions for research in thisarea. Literature on stereotactic radiosurgery was re-viewed using the PubMed search engine. Articles writ-ten in English from 1993-2013 were reviewed, and 20 case series and clinical trials were included. The safetyand efficacy SRS has been demonstrated in all gyne-cologic disease sites including cervical, endometrial,vulvar, vaginal, and ovarian cancers. Indications for itsuse include non-central pelvic recurrences in previouslyirradiated patients, complex or non-resectable diseaserecurrence, and solitary brain metastases. Toxicitiesare usually mild, though grade 3-4 toxicities have been reported. SRS is a promising second line treatment modality for patients with primary or recurrent disease who cannot undergo standard surgical or radiation therapy. Further research is required to determine optimal dosing and fractionation schedules, delineate appropriate patient populations, and assess longterm morbidity and survival.

Dosimetric Advantages of Volumetric Modulated Arc Therapy Based Coronal Arc Delivery Technique in Brain Stereotactic Radiosurgery: A Feasibility Study

The feasibility of a volumetric modulated arc therapy (VMAT) based coronal arc (cARC) technique for treating a single brain metastasis or lesion proximal to the brainstem or optic chiasm was evaluated. Coplanar (CP) and non-coplanar (NCP) treatment plans to an anthropomorphic head/neck phantom scanned head-first supine were compared to a cARC plan with the phantom rotated vertically. A set of planning target volumes (PTVs) were contoured centrally between the brainstem and optic chiasm (“Ant PTVs”) and posterior to brainstem (“Post PTVs”). Dosimetric indices such as conformity index (C.I.), gradient measure (G.M.), and dose volume histograms (DVHs) were compared for CP, NCP and cARC techniques. The TG101 guidelines for organs-at-risk (OARs), and 95% of PTV receiving at least 100% of the prescription dose (D95 = 100%) were used as plan objectives. Reductions in D50 and D30 to the brainstem of 85.1% ± 3.9% and 87.6% ± 3.2%, respectively were seen for “Post PTVs”, and 51.1% ± 17.8% and 85.6% ± 6.0% respectively for “Ant PTVs” using cARC versus CP (p ≤ 0.01). For chiasm, reductions of D50 and D30 were 61.7% ± 3.2% and 44.2% ± 8.9% for “Ant PTVs”, by 69.3% ± 8.0% and 74.3% ± 8.2% for “Post PTVs” (p ≤ 0.01). Comparing cARC to NCP led to similar dosimetric improvements. The conformity index (C.I.) was measured to be 1.101 ± 0.038, 1.088 ± 0.054, and 1.060 ± 0.040 for cARC, CP and NCP respectively (p ≤ 0.01). The overall GM in cm was 0.581 ± 0.097, 0.708 ± 0.064, and 0.476 ± 0.050 for cARC, CP and NCP respectively (p ≤ 0.01). The mean distance gradient fall-off (in cm) was 0.249 ± 0.038 (cARC), 0.749 ± 0.107 (CP), and 0.621 ± 0.068 (NCP) at the center slice in anterior-posterior direction of the target volume (p ≤ 0.01). The objective of this study is to compare the dosimetric indices of cARC with CP and NCP techniques. In conclusion, cARC can provide improved dosimetry as compared to CP and NCP for lesion proximal to the brainstem or optic chiasm.

Gold Nanoparticles in Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations

Objective of the study: To explore the potential for therapeutic gain with gold nanoparticles in arteriovenous malformation radiosurgery based on their interaction with photons and protons. Study methods: Radiation dose enhancement resulting from the interaction of gold nanoparticles with irradiation ranging from kilovoltage to megavoltage photons and protons was researched in the literature. The role of angiogenesis and its regulation via vascular endothelial growth factors and cell membrane receptors, especially for endothelial cells in arteriovenous malformations, was investigated as a way for selective arteriovenous malformation deposition. Results: Radiation dose enhancement with gold nanoparticles is described in the literature but has so far only been investigated for its potential in treating malignancies. Because of the high atomic number of gold (Z = 79), dose enhancement occurs with photons mainly based on secondary photon and Auger electron production and the dose enhancement factor is the highest for irradiation with kilo voltage photons. Dose enhancement happens with megavoltage photons also but to a lesser extend and is mainly due to the ionization of gold by secondary photons and electrons generated by the megavoltage photons passing through tissue. The range of the secondary photo electrons emitted by gold is sufficient to cover the entire endothelial cell content. Protons interact with the production of Auger electrons which have a very short range, insufficient to cover the entire contents of endothelial cells, but sufficient to cause a high cell membrane dose for membrane located gold nanoparticles (AuNPs). Arteriovenous malformations are dynamic entities with angiogenesis taking place. This is reflected by a different expression of angiogenic receptors on the membrane of arteriovenous malformation endothelial cells compared to normal brain blood vessels, thereby opening the opportunity for selective deposition of such particles. For the use in proton therapy a new definition for the dose enhancement factor describing the local effect of nanoparticles is proposed. Conclusion: The concept of nanoparticle enhanced radiosurgery for arteriovenous malfor-mations by selective deposition of gold nanoparticles is a novel approach. The local dose enhancement opens the way for therapeutic gain which in turn could lead to improved obliteration rates and/or a shorter latent period.

Long-Term Follow-Up of 82 Cavernous Sinus Meningiomas Treated with Radiosurgery

The cases of 82 patients with cavernous sinus meningioma (CSM) treated with Stereotactic Radiosurgery (SRS) at our institution from 1992 to 2005 were retrospectively reviewed. The mean follow-up time was 8.38 years. Patients’?age ranged between 16 and 78 years (mean 51). There were 35 patients who had been operated before, and two of them had been treated with fractionated radiotherapy. Twenty-three from 35 patients were surgically intervened?(65.7%)?and?presented post-surgical morbidity. Only in 3 cases the surgery was considered complete. The patients were referred for SRS treatment due to having tumour remains or a tumour growth. The mean volume of the tumour was 17.96 (+/?13.67) cm3.?All the patients had been treated with a Linear Accelerator (LINAC) using a high precision positioning and radiation system (SRS 2000) University of Florida. The clinical progress of the patients was assessed using preand post-SRS radiological imaging, post-surgical and pre-post-SRS morbidity and mortality. Tumour volume decreased significantly with RS in 61 of 82 patients (74.4%). The tumour volume remained stable 12 patients (14.6%) and only in 9 patients (11%) was there tumour growth after SRS. Of these, 5 required surgical intervention, and 7 of the 82 underwent SRS or another fractionated stereotactic radiotherapy after the RS. Morbidity due to the SRS was only seen in 14 out of the 82 patients treated with SRS, five of them recovered completely. SRS is a high precise and effective treatment with low morbidity, becoming more and more the option of choices?in the treatment of cavernous sinus meningioma.

EDGE non-invasive radiosurgery for gastric neuroendocrine hepatic portal lymph node metastases:a case report

Treating metastatic gastric neuroendocrine neoplasms （gNENs） is challenging, especially for those with progressive disease during somatostatin analog processing. In this report, we present a case of a welldifferentiated grade 2, type 3 gNEN with metastatic hepatic portal lymph nodes. EDGE non-invasive radiosurgery （800 cGy x 5 F） was performed to radiate the metastatic hepatic portal lymph nodes. Three months after the hyperfractionated radiotherapy, no signs of metastatic hepatic portal lymph nodes were observed using 8Ga-dotatate positron emission tomography-computed tomography or magnetic resonance imaging. Therefore, EDGE non-invasive radiosurgery could be a potential option for treating local metastatic nodes.

A Statistical Index for Evaluating the CTV Coverage Loss of Brain Stereotactic Radiosurgery When the PTV Margin Is Zero

Purpose: To develop a new statistical index “percent CTV (clinical target vo-lume) coverage probability” (%CCP), defined as the probability that a specific percent (e.g., 95%) of the CTV can be reliably covered by the prescription dose, for evaluating the coverage loss of brain (fractionated) stereotactic radiosurgery (SRS/fSRS) when the PTV (planning target volume) margin is zero. Methods: The random variable Q for CTV percent coverage was derived using a previously developed model for CTV random motion that follows a three-dimensional (3D) independent normal distribution with a zero mean and a standard deviation of 𝜎𝑆(for translation) or 𝜎𝛿(for rotation). Assuming both CTV and PTV are spherical with the same diameter dCTV, the cumulative distribution function of Q could be obtained analytically using the relation of sphere-sphere intersection. The %CCP was then derived as the reliability function of Q and was used to quantify the coverage loss for selected dCTV. Results: The 95%-95% clinical goal (95% of the times, at least 95% of the CTV is covered) is not achievable with dCTV mm. For common CTVs (dCTV mm) encountered in SRS/fSRS, only 60%-90% of the CTV could be reliably covered by the prescription dose 95% of the time. For 𝜎𝑆=0.5mm and 𝜎𝛿 =0.4˚, the 95% CCP was the highest when the distance between the CTV and the isocenter 𝑑𝐼⇔𝑇=0 and gradually decreased with the increasing 𝑑𝐼⇔𝑇. Conclusions: The %CCP was successfully derived for evaluating the CTV coverage loss for brain SRS/fSRS. When the PTV margin is zero, the 95%-95% clinical goal cannot be achieved for most targets (dCTV mm).