Resection Cavity Contraction Effects in the Use of Radioactive Sources (1-25 versus Cs-131) for Intra-Operative Brain Implants.

Background and Objectives Intra-parenchymal brain surgical resection cavities usually contract in volume following low dose rate (LDR) brachytherapy implants. In this study, we systematically modeled and assessed dose variability resulting from such changes for I-125 versus Cs-131 radioactive sources. Methods Resection cavity contraction was modeled based on 95 consecutive patient cases, using surveillance magnetic resonance (MR) images. The model was derived for single point source geometry and then fully simulated in 3D where I-125 or Cs-131 seeds were placed on the surface of an ellipsoidal resection cavity. Dose distribution estimated via TG-43 calculations and biological effective dose (BED) calculations were compared for both I-125 and Cs-131, accounting for resection cavity contractions. Results Resection cavity volumes were found to contract with an effective half-life of approximately 3.4 months (time to reach 50% of maximum volume contraction). As a result, significant differences in dose distributions were noted between I-125 and Cs-131 radioactive sources. For example, when comparing with static volume, assuming no contraction effect, I-125 exhibited a 31.8% and 30.5% increase in D90 and D10 values (i.e., the minimal dose to 90% and 10% of the volume respectively) in the peripheral target areas over the follow-up period of 20.5 months. In contrast, Cs-131 seeds only exhibited a 1.44% and 0.64% increase in D90 and D10 values respectively. Such discrepancy is likewise similar for BED calculations. Conclusion Resection cavity contractions affects Cs-131 dose distribution significantly less than that of I-125 for permanent brain implants. Care must be taken to account for cavity contractions when prescribing accumulative doses of a radioactive source in performing the brain implant procedures

Patient-Specific Fetal Dose Determination for Multi-Target Gamma Knife Radiosurgery: Computational Model and Case Report.

A 42-year-old woman at 29 weeks gestation via in vitro fertilization who presented with eight metastatic brain lesions received Gamma Knife stereotactic radiosurgery (GKSRS) at our institution. In this study, we report our clinical experience and a general procedure of determining the fetal dose from patient-specific treatment plans and we describe quality assurance measurements to guide the safe practice of multi-target GKSRS of pregnant patients. To estimate fetal dose pre-treatment, peripheral dose-to-focal dose ratios (PFRs) were measured in a phantom at the distance approximating the fundus of uterus. Post-treatment, fetal dose was calculated from the actual patient treatment plan. Quality assurance measurements were carried out via the extrapolation dosimetry method in a head phantom at increasing distances along the longitudinal axis. The measurements were then empirically fitted and the fetal dose was extracted from the curve. The computed and measured fetal dose values were compared with each other and associated radiation risk was estimated. Based on low estimated fetal dose from preliminary phantom measurements, the patient was accepted for GKSRS. Eight brain metastases were treated with prescription doses of 15-19 Gy over 143 min involving all collimator sizes as well as composite sector mixed shots. Direct fetal dose computation based on the actual patient's treatment plan estimated a maximum fetal dose of 0.253 cGy, which was in agreement with surface dose measurements at the level of the patient's uterine fundus during the actual treatment. Later phantom measurements also estimated fetal dose to be in the range of 0.21-0.28 cGy (dose extrapolation curve R2 = 0.998). Using the National Council on Radiation Protection and Measurements (NCRP) population-based model, we estimate the fetal risk of secondary malignancy, which is the primary toxicity after 25 weeks gestation, to be less than 0.01%. Of note, the patient delivered the baby via scheduled cesarean section at 36 weeks without complications attributable to the GKSRS procedure. GKSRS of multiple brain metastases was demonstrated to be safe and feasible during pregnancy. The applicability of a general patient-specific fetal dose determination method was also demonstrated for the first time for such a treatment

Resection Cavity Contraction Effects in the Use of Radioactive Sources (1-25 versus Cs-131) for Intra-Operative Brain Implants.

Background and Objectives Intra-parenchymal brain surgical resection cavities usually contract in volume following low dose rate (LDR) brachytherapy implants. In this study, we systematically modeled and assessed dose variability resulting from such changes for I-125 versus Cs-131 radioactive sources. Methods Resection cavity contraction was modeled based on 95 consecutive patient cases, using surveillance magnetic resonance (MR) images. The model was derived for single point source geometry and then fully simulated in 3D where I-125 or Cs-131 seeds were placed on the surface of an ellipsoidal resection cavity. Dose distribution estimated via TG-43 calculations and biological effective dose (BED) calculations were compared for both I-125 and Cs-131, accounting for resection cavity contractions. Results Resection cavity volumes were found to contract with an effective half-life of approximately 3.4 months (time to reach 50% of maximum volume contraction). As a result, significant differences in dose distributions were noted between I-125 and Cs-131 radioactive sources. For example, when comparing with static volume, assuming no contraction effect, I-125 exhibited a 31.8% and 30.5% increase in D90 and D10 values (i.e., the minimal dose to 90% and 10% of the volume respectively) in the peripheral target areas over the follow-up period of 20.5 months. In contrast, Cs-131 seeds only exhibited a 1.44% and 0.64% increase in D90 and D10 values respectively. Such discrepancy is likewise similar for BED calculations. Conclusion Resection cavity contractions affects Cs-131 dose distribution significantly less than that of I-125 for permanent brain implants. Care must be taken to account for cavity contractions when prescribing accumulative doses of a radioactive source in performing the brain implant procedures

Patient-Specific Fetal Dose Determination for Multi-Target Gamma Knife Radiosurgery: Computational Model and Case Report.

A 42-year-old woman at 29 weeks gestation via in vitro fertilization who presented with eight metastatic brain lesions received Gamma Knife stereotactic radiosurgery (GKSRS) at our institution. In this study, we report our clinical experience and a general procedure of determining the fetal dose from patient-specific treatment plans and we describe quality assurance measurements to guide the safe practice of multi-target GKSRS of pregnant patients. To estimate fetal dose pre-treatment, peripheral dose-to-focal dose ratios (PFRs) were measured in a phantom at the distance approximating the fundus of uterus. Post-treatment, fetal dose was calculated from the actual patient treatment plan. Quality assurance measurements were carried out via the extrapolation dosimetry method in a head phantom at increasing distances along the longitudinal axis. The measurements were then empirically fitted and the fetal dose was extracted from the curve. The computed and measured fetal dose values were compared with each other and associated radiation risk was estimated. Based on low estimated fetal dose from preliminary phantom measurements, the patient was accepted for GKSRS. Eight brain metastases were treated with prescription doses of 15-19 Gy over 143 min involving all collimator sizes as well as composite sector mixed shots. Direct fetal dose computation based on the actual patient's treatment plan estimated a maximum fetal dose of 0.253 cGy, which was in agreement with surface dose measurements at the level of the patient's uterine fundus during the actual treatment. Later phantom measurements also estimated fetal dose to be in the range of 0.21-0.28 cGy (dose extrapolation curve R2 = 0.998). Using the National Council on Radiation Protection and Measurements (NCRP) population-based model, we estimate the fetal risk of secondary malignancy, which is the primary toxicity after 25 weeks gestation, to be less than 0.01%. Of note, the patient delivered the baby via scheduled cesarean section at 36 weeks without complications attributable to the GKSRS procedure. GKSRS of multiple brain metastases was demonstrated to be safe and feasible during pregnancy. The applicability of a general patient-specific fetal dose determination method was also demonstrated for the first time for such a treatment

Pain experience using conventional versus angled anterior posts during stereotactic head frame placement for radiosurgery

Stereotactic frame placement for radiosurgery is assumed to be an uncomfortable experience. We developed angled anterior posts for the Leksell frame to avoid pin penetration of the temporalis muscle. This study aimed to determine the frequency of angled post requirement and quantify the patient pain experience from frame placement. We prospectively enrolled 63 patients undergoing radiosurgery. Angled posts were used when conventional post trajectory was posterior or within 3mm of the superior temporal line to avoid temporalis muscle penetration. Pain scores (0 to 10) were collected prior to frame placement, immediately after frame placement, before radiosurgery, after radiosurgery, and a day after radiosurgery. A total of 63 patients were enrolled: 33 (48%) patients required angled posts. Women were significantly more likely to require angled posts than men (60.0% versus 33.3%, respectively; p=0.034). Mean pain scores were very low, ranging from 0.33 to 2.23. There were no significant differences in pain outcomes between both groups at all time points. Stereotactic frame placement is not perceived to be a painful procedure. This information may be useful when counseling patients about the pain experience with frame application and the option of using angled anterior posts

Radiation-induced Cavernous Malformation as a Late Sequelae of Stereotactic Radiosurgery for Epilepsy

Stereotactic radiosurgery (SRS) is a promising treatment for medically intractable mesial temporal lobe epilepsy. SRS for epilepsy has had an acceptable safety profile with reports of radiation-induced vascular malformations confined to central nervous system pathologies with prominent angiogenesis - namely, primary brain tumors, metastases, and arteriovenous malformations. Theoretical risks for radiation-induced lesions following radiosurgery for epilepsy have yet to be established. Of 13 patients treated in a pilot trial for medial temporal lobe epilepsy, one developed multiple delayed radiation-induced cavernous malformations following radiosurgery. This patient received a prescription dose of 20 Gy delivered to the amygdala, anterior hippocampus, and parahippocampal gyrus. Eight years following treatment, computed tomography imaging demonstrated an evolving hyperdensity in the mesial temporal lobe. Magnetic resonance imaging confirmed multiple T2 hypointense lesions with a mixed-signal intensity core in the left parahippocampal gyrus and anterior temporal lobe. The patient was initially managed conservatively. However, recurrent hemorrhage ultimately caused an acute deterioration in mental status, aphasia, and hemiparesis, necessitating surgical resection. Pathology confirmed radiation-induced cavernous malformations. This represents the first case of a radiation-induced vascular lesion as a long-term sequela of radiosurgery for epilepsy and illustrates the potential for this complication even when low doses are used in patients without angiogenic lesions. Optimal timing and indications for surgical resection of radiation-induced cavernous malformations prior to the development of neurologic symptoms warrant further refinement. Long-term vigilance and clinical monitoring are required

Radiation-induced Cavernous Malformation as a Late Sequelae of Stereotactic Radiosurgery for Epilepsy.

Stereotactic radiosurgery (SRS) is a promising treatment for medically intractable mesial temporal lobe epilepsy. SRS for epilepsy has had an acceptable safety profile with reports of radiation-induced vascular malformations confined to central nervous system pathologies with prominent angiogenesis - namely, primary brain tumors, metastases, and arteriovenous malformations. Theoretical risks for radiation-induced lesions following radiosurgery for epilepsy have yet to be established. Of 13 patients treated in a pilot trial for medial temporal lobe epilepsy, one developed multiple delayed radiation-induced cavernous malformations following radiosurgery. This patient received a prescription dose of 20 Gy delivered to the amygdala, anterior hippocampus, and parahippocampal gyrus. Eight years following treatment, computed tomography imaging demonstrated an evolving hyperdensity in the mesial temporal lobe. Magnetic resonance imaging confirmed multiple T2 hypointense lesions with a mixed-signal intensity core in the left parahippocampal gyrus and anterior temporal lobe. The patient was initially managed conservatively. However, recurrent hemorrhage ultimately caused an acute deterioration in mental status, aphasia, and hemiparesis, necessitating surgical resection. Pathology confirmed radiation-induced cavernous malformations. This represents the first case of a radiation-induced vascular lesion as a long-term sequela of radiosurgery for epilepsy and illustrates the potential for this complication even when low doses are used in patients without angiogenic lesions. Optimal timing and indications for surgical resection of radiation-induced cavernous malformations prior to the development of neurologic symptoms warrant further refinement. Long-term vigilance and clinical monitoring are required

Proof-of-concept single-arm trial of bevacizumab therapy for brain arteriovenous malformation

Brain arteriovenous malformations (bAVMs) are relatively rare, although their potential for secondary intracranial haemorrhage (ICH) makes their diagnosis and management essential to the community. Currently, invasive therapies (surgical resection, stereotactic radiosurgery and endovascular embolisation) are the only interventions that offer a reduction in ICH risk. There is no designated medical therapy for bAVM, although there is growing animal and human evidence supporting a role for bevacizumab to reduce the size of AVMs. In this single-arm pilot study, two patients with large bAVMs (deemed unresectable by an interdisciplinary team) received bevacizumab 5 mg/kg every 2 weeks for 12 weeks. Due to limitations of external funding, the intended sample size of 10 participants was not reached. Primary outcome measure was change in bAVM volume from baseline at 26 and 52 weeks. No change in bAVM volume was observed 26 or 52 weeks after bevacizumab treatment. No clinically important adverse events were observed during the 52-week study period. There were no observed instances of ICH. Sera vascular endothelial growth factor levels were reduced at 26 weeks and returned to baseline at 52 weeks. This pilot study is the first to test bevacizumab for patients with bAVMs. Bevacizumab therapy was well tolerated in both subjects. No radiographic changes were observed over the 52-week study period. Subsequent larger clinical trials are in order to assess for dose-dependent efficacy and rarer adverse drug effects.Trial registration number: NCT02314377