The ideal regimen of neoadjuvant chemotherapy and radiation in high risk extremity sarcomas is not known. We report our long-term (> 5 years) follow-up in high risk patients treated with neoadjuvant chemotherapy and preoperative hypofractionated radiation therapy. This was an IRB approved retrospective study of 122 high-risk extremity sarcoma patients treated at our institution. Patients typically received 2 cycles of ifosfamide-based chemotherapy with radiation delivered either concurrently with cycle 2 or sequentially to a dose of 3.5 Gy x 8 fractions. This was followed 4-6 weeks later by surgical resection. The patient cohort was 61.5% male and 38.5% female, with a median age of 46 years at diagnosis (range: 13 – 83). Tumors were located on an upper extremity in 20.5% and a lower extremity in 79.5% of patients. Median tumor size was 10 cm (range: 1.1 – 60 cm). Eighty percent of tumors were high grade. The most common histologies treated were pleomorphic sarcoma NOS in 30%, synovial sarcoma in 27%, liposarcoma in 17%, and other histologies in 25%. Planned oncologic resection was performed in 83% of cases, while 17% were initially excised outside of our center and referred for re-excision. The rates of local recurrence, distant metastasis, and overall survival were analyzed using the Kaplan-Meier method and the log-rank test was used for comparisons for each covariate. A Cox proportional hazards model was used for multivariate analysis. Median follow-up was 5.8 years (range 0.3 – 24) in all patients, and 9.1 years (range 0.5 – 24) in surviving patients. Pathologic complete response (necrosis ≥ 95%) was seen in 20.3% of 109 analyzable patients. Negative margins were achieved in 93% of patients. Limb sparing was achieved in 95% of patients. Six patients were treated with the intent of limb-sparing resection but were found to be unresectable and required amputation. Local control, distant metastasis-free survival, and overall survival at 6 years were: 84% (95% CI, 75% - 90%), 63% (95% CI, 53% - 72%), and 68% (95% CI, 59% – 76%). On univariate analysis, age > 60 years was the only factor significantly correlated with an increased risk of local failure (P < 0.01). On multivariate analysis, no factors evaluated were significantly correlated with an increased risk of local recurrence. For patients with high-risk extremity sarcoma, preoperative ifosfamide-based chemotherapy with hypofractionated radiation offers a treatment approach with excellent oncologic outcomes with long-term follow-up.

We report single-institution tumor control, rates of compression fracture, and pain control for patients treated with SBRT for spinal metastases treated to lesion only (LO) or full vertebral body (FVB). A total of 155 spinal metastases in 98 patients were treated with stereotactic body radiation therapy to doses of 8-45 Gy in 1-10 fractions (median dose 16 Gy in a single fraction) from January 2009 to February 2015. Fifty lesions (32%) were treated to the LO, and the remainder were treated to the FVB. Radiation plans were reviewed to determine whether the patient was treated to the LO or FVB. Rates of local control (LC) and compression fracture were estimated with Kaplan-Meier analysis. Patients' pain scores were recorded before and after treatment. The local control rate was 79% and 66% at 1 and 2 years in metastases treated to the FVB, and 85% and 75% in metastases treated to the LO. There was no difference in local control rates between the FVB group and the LO group. Pain scores were significantly lower before and after treatment in lesions in both groups. Pain reduction was significantly improved in lesions treated to FVB compared to LO. There were a total of 10 compression fractures within two years post-treatment, 6 in the FVB group and 4 in the LO group. Treating the FVB with SBRT in patients with spine metastatic disease results in improved pain reduction and higher rates of compression fracture compared to treatment to the LO. There was no difference in the rate of tumor control between the two treatment methods. Therefore, it may be reasonable to consider treating with SBRT to the LO in select patients if it is a small, anterior lesion and it would not interfere with reirradiation in the case of recurrence or presentation of another nearby metastasis.

The aim of this study was to establish if patients with multiple sclerosis (MS) who develop trigeminal neuralgia (TN) have worse outcomes with Linac-based stereotactic radiosurgery (SRS) compared to patients without MS. Between 1996 and 2014, 14 patients with TN treated with SRS had a diagnosis of MS. One patient had bilateral TN treated with SRS, thus there were 15 treatments evaluated. All patients underwent Linac-based SRS. Patients were followed and their pain scores were assessed using the Barrow Neurological Institute scale (BNI), scores I-V. We compared our findings with a literature review of 11 case series of Linac-based SRS for mostly typical TN (Varela-Lema, Pain Physician, 2015, 18:15-27), with response rate (range 75-96%, within mean 8.5 days – 3.8 months), pain recurrence rate (range 5-29%), and incidence of partial numbness (range 7.5-52%) reported as such. Mean follow-up time was 35.2 months (range 0-159.7). Five patients had rhizotomies, one of which had bilateral, before first SRS. All patients had failed medical management with pain scores BNI 4 or 5 at the time of SRS. Median time from surgery to first SRS was 19.5 months (range 1-63). Of the 15 TN SRS treatments, 13 received 90 Gy, 1 received 75 Gy, and 1 received 70 Gy. The BNI scores after SRS for 11/15 treatments ranged from I-IIIa, with median latency of 4 weeks (range 2-7). One patient had no relief and three were not scored. In 4/15 treatments (27%), patients experienced partial numbness on the treatment side, developing 1-7 months post SRS. In total, 8/15 (53%) treatments were successful without pain recurrence at time of last follow-up, 1 patient was lost to follow-up, and 5 (33%) had pain recurrence with a BNI of IV at a median of 12.5 months. The patient with bilateral TN only had recurrence on the right, which had received 70 Gy. Four out of 5 patients with recurrence underwent surgical procedures, 2 with complete relief. One patient underwent successful repeat SRS at 90 Gy, after failure of balloon compression and radiofrequency ablation, 32 months after the first SRS. The patient with bilateral TN with failure on the right received a repeat dose of 70 Gy 22 months after first SRS with pain relief for 8 months; however, this patient failed again on the right and underwent 3 additional rhizotomies without success. Linac-based SRS proved to be an effective, noninvasive treatment for MS patients with TN, with a 73% response rate and a median time to response of 4 weeks, comparable to treatment of patients without MS. Compared to findings in the literature, there was a comparable incidence of partial numbness on the treatment side and only a slightly higher pain recurrence rate in TN patients with MS compared to those without MS. There were no episodes of anesthesia dolorosa noted. Multiple sclerosis should not be considered a contraindication for SRS in patients with TN.

Identifying radiation necrosis (RN) after radiation therapy (RT) of brain metastases (BM) remains challenging. The effect of RT dose, patient characteristics such as age, and intrinsic tumor characteristics such as receptor expression (RE) on the risk of RN remains unclear. In this study, we analyze a cohort of patients with breast cancer brain metastases (BCBM) to investigate characteristics of lesions that develop RN. Our single-institution retrospective analysis examines incidence of RN in 44 BCBM patients, who had a total of 373 BM treated with single or multiple courses of stereotactic radiosurgery, stereotactic RT, and whole brain RT. RN was identified by F-DOPA/PET, MRI, or surgical pathology. Patient age was reported at first treatment of RN lesion. Tumor RE was assessed as: Luminal A (LA, ER/PR+, HER2-), Luminal B (LB, ER/PR+, HER2+), HER2 (ER/PR-, HER2+), and Triple negative (TN, ER-/PR-/HER2-). Wilcoxon rank-sum test, Fisher exact test, and odds ratio were performed for statistical analysis. Of all BCBM lesions treated, 13/373 (3.5%) developed RN, accounting for 11/43 (26%) of patients. One patient (RE status LB, age 36) developed RN of three lesions. 10/13 lesions (77%) had received two courses of RT, mean BED 97.1. The remaining 3 cases of RN (23%) developed after only one course of SRS at 14-16 Gy (mean BED 56.4), a significantly lower dose (Z = -2.41, p = 0.016), although 1/3 of these patients had prior WBRT before developing that lesion. These patients' ages were 36, 40, and 41; two were LA, one was LB. In our BCBM cohort, 7/20 (35%) patients ≤ 50 years old developed RN, while only 4/24 (16.7%) patients >50 years old developed RN (OR = 2.7, CI 0.65-11.06). The distribution of RE in RN patients was 5/11 (45%) LA, 2/11 (18%) LB, 2/11 (18%) HER2, and 2/11 (18%) TN; this distribution did not significantly differ from the total BCBM cohort (Luminal A: p=0.73, Luminal B: p=1.0, HER2+: p=0.71, TN: p=1.0). Incidence of RN after single SRS suggests intrinsic tumor and/or patient factors likely played a role. Biological factors, such as younger age, that predispose patients to poorer prognosis may contribute to increase adverse events such as RN. Although the odds ratio for age did not reach significance, this may be due to limited sample size. While RE has prognostic significance in breast cancer, it did not appear to influence RN in BCBM. Thus, tumor aggressiveness does not necessarily translate into a risk factor for RN. BCBM that developed RN were more likely to have received multiple treatments and significantly higher BED.

Retrospective studies have shown that high dose radiation to neural stem cell niches in the subventricular zone (SVZ) increase progression-free and overall survival in glioblastoma multiforme (GB). A recent study showed that most GB recur adjacent to the SVZ. The purpose of this study was to determine if high dose radiation to the ipsilateral SVZ altered GB patterns of failure. Sixty-nine GB patients had resection (gross-total: n = 37; subtotal: n = 32) and adjuvant radiation (60 Gy/30 fractions) from 2005-2011. Median age and follow-up were 56 years and 18.3 months, respectively. All received systemic therapy, most commonly temozolomide. SVZ were contoured as 3 mm along the lateral wall of the lateral ventricle. Mean SVZ dose for the cohort was 49.1 ± 1.4 Gy, with seven patients receiving high doses (>60 Gy). Tumor recurrence was defined by clinical and radiographic consensus (neuro-oncologist, imaging). Recurrence was defined as in-field if within the planning target volume (gross tumor on T1 weighted MRI post gadolinium + T2 FLAIR + 1.5-2 cm margin). PFS and OS were calculated from date of surgery by Kaplan-Meier analysis. Odds ratios were used to analyze correlation between variables. The following covariates were tested for impact on PFS or OS on multivariate analysis (MVA): age > 60, gender, surgery, and ipsilateral SVZ dose > 60 Gy. The majority of primary tumors were SVZ-adjacent (48/69, 70%). Recurrences occurred both in-field (41/52, 79%) and adjacent to the SVZ (36/52, 69%). SVZ-adjacent primaries were more likely to contact the SVZ on recurrence than non-adjacent primaries (p = 0.0044, odds ratio 6.6, CI: 1.8-24.2). High SVZ dose did not effect SVZ relapse-free survival (RFS) (p = 0.072). There was a trend towards SVZ-adjacent primary tumors being more likely to recur distantly in the brain (p = 0.14, odds ratio 3.5). High SVZ dose had no impact on in-field RFS (p = 0.35). This study validated our prior findings of high SVZ dose leading to higher median PFS (20.0 vs, 9.1 months; P = 0.018) and OS (26.1 vs 17.6 months; P=0.051). On MVA, only ipsilateral SVZ dose > 60 Gy was a significant predictor of PFS (P=0.034). Similarly, ipsilateral CSC dose > 60 Gy trended towards impacting OS (P=0.062). Most GB arises adjacent to the SVZ. Tumors adjacent to the SVZ tended to fail adjacent to the SVZ and were also more likely to recur distantly than primaries that were not SVZ-adjacent. However, higher SVZ dose did not appear to alter the pattern of failure. Therefore, the mechanism by which high SVZ dose improves PFS and OS is not directly related to its impact on altering GB patterns of recurrence.

To investigate the dosimetric impact of positioning errors on target coverage and spinal cord sparing for spinal radiosurgery patients. Additionally, to demonstrate feasibility of a planning tool to calculate how dosimetrically sensitive each individual plan is to misalignments. Data from 62 spinal radiosurgery patients were included in this study. The dosimetric effects of positioning uncertainties were investigated by simulating positioning errors in each treatment plan. For each treatment plan the direction of misalignments that minimize target and cord separation was geometrically determined. For each plan three additional plans were created, where the planning isocenter was shifted in that direction 1 mm, 2 mm and 3 mm, for a total of 248 plans. We evaluated the potential clinical relevance of these errors by measuring their dosimetric impact on target and cord. V100% and D95%, and Dmin were evaluated for the target volume, Dmax and and V12Gy were evaluated for the cord. In 51% of the patients, a 1 mm shift introduced a Dmax dose that exceeded the 12 Gy maximum dose planning criteria. A 2 mm and 3 mm shift resulted in 75% and 86% of patients exceeding the 12Gy maximum dose correspondingly. The maximum change in V12Gy to the cord among all patients was 17%, 26% and 36% respectively for 1 mm, 2 mm and 3 mm shifts, where the spinal cord was outlined 6 mm above and below the target volume. Correspondingly, the maximum variations in D95% were 5%, 9% and 15%. V100% decreased more than 5% in 8%, 25% and 51% of plans. We have shown that plans have great variability in terms of their dosimetric sensitivity to positioning errors and we have introduced the concept of a tool for determining how vulnerable each individual plan is to positioning errors prior to treatment. The spinal cord dose limits in clinical use are not only based on actual tissue tolerance but are also convolved with positioning inaccuracies. In the conception of these constraints, the actual spinal dose tolerances have been compromised to account for positioning uncertainties. Application of the presented tool can help identify which patient plans are more resilient to positioning uncertainties, for which less stringent cord dose limits can be applied, potentially allowing greater target coverage and increased tumor control probability.

For patients with high grade extremity sarcoma our institution utilizes an abbreviated pre-operative (pre-op) radiation regimen of 3.5 Gy x 8 fractions given with neoadjuvant ifosfamide-based chemotherapy. Patients with necrosis scores of < 50% are often treated with a post-operative (post-op) boost based on previous data suggesting higher local recurrence rates. We retrospectively reviewed patients treated with this pre-op regimen to determine whether local failure rates vary between those who did and did not receive a post-op boost. This was an IRB-approved study of patients treated in our Department with a pre-op regimen of 3.5 Gy x 8 fractions between 2002-2013. A total of 28 patients were identified. When post-operative RT was given, the median dose was 28 Gy. Charts were reviewed to assess for local failure, distant failure, and overall survival. Median follow-up for the entire cohort was 36 months. Median age of the entire cohort was 47 years old. The preoperative tumor size was: < 5 cm (4), 5-10 cm (13), and ≥10 cm (11). Tumor location was upper extremity (8) and lower extremity (20). The distribution of histologies treated was: high grade NOS (9), synovial (7), liposarcoma (3), myxofibrosarcoma (3), Chondrosarcoma (2), and other (4). Clinical outcomes are presented in Table 1. The local recurrence risk in the entire cohort of patients was 4%. These data do not demonstrate an increased risk of local recurrence in patients with ≤50% necrosis score. Whether a boost is necessary in this subset of patients is not obvious.Scientific Abstract 3409; TableEntire Cohort≤50% necrosis score + pre-op RT≤50% necrosis score + pre and post-op RT>50% necrosis score + pre-op RTNumber of patients288713Median follow-up (months)36254738Local Failure1 (4%)01 (14%)0Distant Failure12 (43%)4 (50%)1 (14%)7 (54%)Median time to any failure (months)10.810.213.611.4Overall Survival20 (71%)4 (50%)6 (86%)10 (77%) Open table in a new tab

The Monte Carlo (MC) dose calculation algorithm is considered a more accurate algorithm for treatment planning, particularly for tumors located in regions of inhomogeneous tissue densities, such as the lung. We compared the dose distribution calculated by MC and Pencil Beam (PB) with and without tissue density consideration in stereotactic body radiation therapy (SBRT) treatment planning for lung tumors. We reviewed treatment plans for six lung tumors in five patients treated with SBRT. The prescription dose was 54 Gy delivered in three fractions to the planning target volume (PTV) using the standard PB algorithm without tissue heterogeneity correction. Retrospectively, each treatment plan was re-calculated using MC and PB computational models keeping the original monitor units and beam orientations, with and without tissue heterogeneity correction (HC+/-). We compared the dosimetric coverage of the PTV as well as that of the normal surrounding tissue using these calculations. The average mean dose to the PTV calculated by each method (PB/HC-, PB/HC+, MC/HC- and MC/HC+) was 56.4 Gy, 65.0 Gy, 55.5 Gy, and 57.3 Gy, respectively. For each tumor, the plan calculated using the Monte Carlo algorithm with heterogeneity correction applied (MC/HC+) was considered the reference dose calculation. The most significant deviations from MC/HC+ calculations were seen in the plans calculated using PB with heterogeneity correction applied (PB/HC+), where the dose to 95% of the PTV (D95%) and 50% of the PTV (D50%) were on average 21% and 13% higher, respectively. In contrast, the D95% and D50% of plans calculated using PB without heterogeneity correction (PB/HC-) were within 5% and 2% of MC/HC+ calculations, respectively. For normal tissue calculations compared to MC/HC+, the average absolute difference in the maximal dose to the esophagus, spinal cord, heart and proximal bronchial tree was 1.2 Gy, and the average absolute difference in percent-volume of total lung receiving 20 Gy (V20Gy%) was 0.3%. Our current standard in SBRT treatment planning for lung tumors is to use the PB algorithm without heterogeneity correction (PB/HC-). Our results suggest that PB/HC- is most consistent with dosimetric calculations obtained using MC/HC+. Future SBRT lung protocols will likely incorporate heterogeneity-corrected Monte Carlo computations, and further understanding of the dosimetric relationships amongst these algorithms is necessary.

Purpose/Objective(s)We report retrospectively the response of melanoma brain metastases treated with stereotactic radiosurgery (SRS) in UCLA Radiosurgery Department, evaluating the volumetric changes from the day of treatment.Materials/MethodsWe evaluate 117 melanoma brain metastases in 39 patients (28 male, 11 female) treated with SRS. We use for SRS treatment a Novalis 6 MV, with micro multileaf collimator M3 and software iPlan3. The volumetric study of these patients was based on MRI images before and after SRS. Patients are selected with minimum follow up of 5 months and at least 2 MRI in this interval. Median follow up was 9.16 months (5.1 - 41.7). We introduce the terms: “speed of shrinkage” and “speed of growth” defined as the ratios of percentage of shrinkage and growth, respectively, to the interval. “Volumetric response” defined as decrease of the volume (shrinkage). Median prescribed peripheral dose was 18Gy (range: 10-25) to the 90% prescription isodose line. Median age was 52 years (range: 27-77), median grade of Karnofsky index was 90 (range: 60-100) and mean volume 2.25 cm3 (range:0.03-32.23). Overestimated increased contrast enhanced volume was found in 6 hemorrhagic metastases which was excluded from the study.ResultsVolumetric response reported in 95.3% of metastases with a mean delay to response 3.13 months (median 3.25). A subgroup of initially responding metastases (13.9%) finally relapsed with a mean delay of 7 months (median 6.69). According to Kaplan-Meier analyses, actuarial LC for 6-month, 1-year and 2-years was 91.6%, 82%, 77.6% respectively. For “LC group” median percentage of shrinkage was 80% (mean: 71%) and median speed of shrinkage 8%/month (mean: 9%). For “Relapsed group” median percentage of growth was 205% (mean: 191%) and median speed of growth 28.7%/month (mean: 98). Small initial volume and increased speed of shrinkage found to be statistical significant (p < 0.05) favorable predictor factors for complete response.ConclusionsAccording to the accurate volumetric evaluation of melanoma brain metastases, SRS found to be an efficient therapeutic approach, in terms of decreasing volume, with a median delay for response 3.13 months. Speed of shrinkage and initial tumor volume are favorable predicting factors for complete response. Purpose/Objective(s)We report retrospectively the response of melanoma brain metastases treated with stereotactic radiosurgery (SRS) in UCLA Radiosurgery Department, evaluating the volumetric changes from the day of treatment. We report retrospectively the response of melanoma brain metastases treated with stereotactic radiosurgery (SRS) in UCLA Radiosurgery Department, evaluating the volumetric changes from the day of treatment. Materials/MethodsWe evaluate 117 melanoma brain metastases in 39 patients (28 male, 11 female) treated with SRS. We use for SRS treatment a Novalis 6 MV, with micro multileaf collimator M3 and software iPlan3. The volumetric study of these patients was based on MRI images before and after SRS. Patients are selected with minimum follow up of 5 months and at least 2 MRI in this interval. Median follow up was 9.16 months (5.1 - 41.7). We introduce the terms: “speed of shrinkage” and “speed of growth” defined as the ratios of percentage of shrinkage and growth, respectively, to the interval. “Volumetric response” defined as decrease of the volume (shrinkage). Median prescribed peripheral dose was 18Gy (range: 10-25) to the 90% prescription isodose line. Median age was 52 years (range: 27-77), median grade of Karnofsky index was 90 (range: 60-100) and mean volume 2.25 cm3 (range:0.03-32.23). Overestimated increased contrast enhanced volume was found in 6 hemorrhagic metastases which was excluded from the study. We evaluate 117 melanoma brain metastases in 39 patients (28 male, 11 female) treated with SRS. We use for SRS treatment a Novalis 6 MV, with micro multileaf collimator M3 and software iPlan3. The volumetric study of these patients was based on MRI images before and after SRS. Patients are selected with minimum follow up of 5 months and at least 2 MRI in this interval. Median follow up was 9.16 months (5.1 - 41.7). We introduce the terms: “speed of shrinkage” and “speed of growth” defined as the ratios of percentage of shrinkage and growth, respectively, to the interval. “Volumetric response” defined as decrease of the volume (shrinkage). Median prescribed peripheral dose was 18Gy (range: 10-25) to the 90% prescription isodose line. Median age was 52 years (range: 27-77), median grade of Karnofsky index was 90 (range: 60-100) and mean volume 2.25 cm3 (range:0.03-32.23). Overestimated increased contrast enhanced volume was found in 6 hemorrhagic metastases which was excluded from the study. ResultsVolumetric response reported in 95.3% of metastases with a mean delay to response 3.13 months (median 3.25). A subgroup of initially responding metastases (13.9%) finally relapsed with a mean delay of 7 months (median 6.69). According to Kaplan-Meier analyses, actuarial LC for 6-month, 1-year and 2-years was 91.6%, 82%, 77.6% respectively. For “LC group” median percentage of shrinkage was 80% (mean: 71%) and median speed of shrinkage 8%/month (mean: 9%). For “Relapsed group” median percentage of growth was 205% (mean: 191%) and median speed of growth 28.7%/month (mean: 98). Small initial volume and increased speed of shrinkage found to be statistical significant (p < 0.05) favorable predictor factors for complete response. Volumetric response reported in 95.3% of metastases with a mean delay to response 3.13 months (median 3.25). A subgroup of initially responding metastases (13.9%) finally relapsed with a mean delay of 7 months (median 6.69). According to Kaplan-Meier analyses, actuarial LC for 6-month, 1-year and 2-years was 91.6%, 82%, 77.6% respectively. For “LC group” median percentage of shrinkage was 80% (mean: 71%) and median speed of shrinkage 8%/month (mean: 9%). For “Relapsed group” median percentage of growth was 205% (mean: 191%) and median speed of growth 28.7%/month (mean: 98). Small initial volume and increased speed of shrinkage found to be statistical significant (p < 0.05) favorable predictor factors for complete response. ConclusionsAccording to the accurate volumetric evaluation of melanoma brain metastases, SRS found to be an efficient therapeutic approach, in terms of decreasing volume, with a median delay for response 3.13 months. Speed of shrinkage and initial tumor volume are favorable predicting factors for complete response. According to the accurate volumetric evaluation of melanoma brain metastases, SRS found to be an efficient therapeutic approach, in terms of decreasing volume, with a median delay for response 3.13 months. Speed of shrinkage and initial tumor volume are favorable predicting factors for complete response.

Purpose/Objective(s)Accuracy is essential in stereotactic body radiation therapy (SBRT) to maximize tumor control while minimizing toxicities. A fiducial-based approach offers higher tumor localization accuracy but requires an invasive procedure and delays therapy. We quantified the improvements in patient set-up using gold fiducial markers compared with using spine anatomy in linear accelerator-based SBRT.Materials/MethodsBetween August 2008 and March 2009, 16 consecutive patients were treated with 71 fractions (3-5 fractions per tumor, 5-18 Gy per fraction) of fiducial-guided SBRT. Internal tumor volume was defined for all patients based on a 4-Dimensional treatment planning CT. Additional margin (0-6 mm) was used to create a planning tumor volume. There were 30, 21, and 20 fractions treated for tumors of the thorax, abdomen, and pelvis, respectively. Paired oblique kV imaging of fiducial markers was used for initial set-up. Retrospectively, daily set-up was determined independently using either fiducial-to-fiducial matching (DRR to kV imaging) or matching of surrounding stable spine anatomy. Using fiducial-based matching as baseline, set-up error was defined as the absolute displacement for each fraction between fiducial-matching compared to spine-matching in the anterior-posterior (AP), lateral (LAT), and superior-inferior (SI) dimensions.ResultsTumors of the thorax had a mean set-up error in the AP, LAT, and SI dimensions of 4.7 +/- 2.8 mm, 3.2 +/- 3.0 mm, and 4.0 +/- 2.9 mm, respectively. Tumors in the abdomen had a mean set-up error of 5.2 +/- 4.5 mm, 3.0 +/- 2.3 mm, and 5.3 +/- 5.2 mm while tumors in the pelvis had an error of 2.5 +/- 1.6 mm, 2.5 +/- 1.6 mm, and 1.6 +/- 1.0 mm in the same dimensions, respectively. In the AP dimension, 23, 43, and 60% of the fractions in the thorax, abdomen, and pelvis had set-up errors < 3 mm. In the same sites, this range of error was seen in 60, 57, 75% and 40, 43, 90% in the LAT and SI dimensions, respectively. In the AP dimension, 50, 29, 40% of the fractions in the thorax, abdomen, and pelvis had set-up errors between 3-6 mm. This was seen in 27, 29, 25% and 13, 29, 10% in the LAT and SI dimensions, respectively. Finally, in the AP dimension, 27, 29, and 0% of the fractions in the thorax, abdomen, and pelvis had errors > 6 mm. This was seen in 13, 14, 0% and 13, 29, and 0% in the LAT and SI dimensions, respectively.ConclusionsIn the thorax and abdomen, where there is relatively larger motion due to respiration, fiducial markers significantly improve tumor localization during daily set-up. Less set-up errors were detected when tumors in the pelvis were localized using neighboring spine instead of fiducial markers, which may obviate their need in the pelvis. Due to limited sample size, additional data will be needed to confirm these results. Purpose/Objective(s)Accuracy is essential in stereotactic body radiation therapy (SBRT) to maximize tumor control while minimizing toxicities. A fiducial-based approach offers higher tumor localization accuracy but requires an invasive procedure and delays therapy. We quantified the improvements in patient set-up using gold fiducial markers compared with using spine anatomy in linear accelerator-based SBRT. Accuracy is essential in stereotactic body radiation therapy (SBRT) to maximize tumor control while minimizing toxicities. A fiducial-based approach offers higher tumor localization accuracy but requires an invasive procedure and delays therapy. We quantified the improvements in patient set-up using gold fiducial markers compared with using spine anatomy in linear accelerator-based SBRT. Materials/MethodsBetween August 2008 and March 2009, 16 consecutive patients were treated with 71 fractions (3-5 fractions per tumor, 5-18 Gy per fraction) of fiducial-guided SBRT. Internal tumor volume was defined for all patients based on a 4-Dimensional treatment planning CT. Additional margin (0-6 mm) was used to create a planning tumor volume. There were 30, 21, and 20 fractions treated for tumors of the thorax, abdomen, and pelvis, respectively. Paired oblique kV imaging of fiducial markers was used for initial set-up. Retrospectively, daily set-up was determined independently using either fiducial-to-fiducial matching (DRR to kV imaging) or matching of surrounding stable spine anatomy. Using fiducial-based matching as baseline, set-up error was defined as the absolute displacement for each fraction between fiducial-matching compared to spine-matching in the anterior-posterior (AP), lateral (LAT), and superior-inferior (SI) dimensions. Between August 2008 and March 2009, 16 consecutive patients were treated with 71 fractions (3-5 fractions per tumor, 5-18 Gy per fraction) of fiducial-guided SBRT. Internal tumor volume was defined for all patients based on a 4-Dimensional treatment planning CT. Additional margin (0-6 mm) was used to create a planning tumor volume. There were 30, 21, and 20 fractions treated for tumors of the thorax, abdomen, and pelvis, respectively. Paired oblique kV imaging of fiducial markers was used for initial set-up. Retrospectively, daily set-up was determined independently using either fiducial-to-fiducial matching (DRR to kV imaging) or matching of surrounding stable spine anatomy. Using fiducial-based matching as baseline, set-up error was defined as the absolute displacement for each fraction between fiducial-matching compared to spine-matching in the anterior-posterior (AP), lateral (LAT), and superior-inferior (SI) dimensions. ResultsTumors of the thorax had a mean set-up error in the AP, LAT, and SI dimensions of 4.7 +/- 2.8 mm, 3.2 +/- 3.0 mm, and 4.0 +/- 2.9 mm, respectively. Tumors in the abdomen had a mean set-up error of 5.2 +/- 4.5 mm, 3.0 +/- 2.3 mm, and 5.3 +/- 5.2 mm while tumors in the pelvis had an error of 2.5 +/- 1.6 mm, 2.5 +/- 1.6 mm, and 1.6 +/- 1.0 mm in the same dimensions, respectively. In the AP dimension, 23, 43, and 60% of the fractions in the thorax, abdomen, and pelvis had set-up errors < 3 mm. In the same sites, this range of error was seen in 60, 57, 75% and 40, 43, 90% in the LAT and SI dimensions, respectively. In the AP dimension, 50, 29, 40% of the fractions in the thorax, abdomen, and pelvis had set-up errors between 3-6 mm. This was seen in 27, 29, 25% and 13, 29, 10% in the LAT and SI dimensions, respectively. Finally, in the AP dimension, 27, 29, and 0% of the fractions in the thorax, abdomen, and pelvis had errors > 6 mm. This was seen in 13, 14, 0% and 13, 29, and 0% in the LAT and SI dimensions, respectively. Tumors of the thorax had a mean set-up error in the AP, LAT, and SI dimensions of 4.7 +/- 2.8 mm, 3.2 +/- 3.0 mm, and 4.0 +/- 2.9 mm, respectively. Tumors in the abdomen had a mean set-up error of 5.2 +/- 4.5 mm, 3.0 +/- 2.3 mm, and 5.3 +/- 5.2 mm while tumors in the pelvis had an error of 2.5 +/- 1.6 mm, 2.5 +/- 1.6 mm, and 1.6 +/- 1.0 mm in the same dimensions, respectively. In the AP dimension, 23, 43, and 60% of the fractions in the thorax, abdomen, and pelvis had set-up errors < 3 mm. In the same sites, this range of error was seen in 60, 57, 75% and 40, 43, 90% in the LAT and SI dimensions, respectively. In the AP dimension, 50, 29, 40% of the fractions in the thorax, abdomen, and pelvis had set-up errors between 3-6 mm. This was seen in 27, 29, 25% and 13, 29, 10% in the LAT and SI dimensions, respectively. Finally, in the AP dimension, 27, 29, and 0% of the fractions in the thorax, abdomen, and pelvis had errors > 6 mm. This was seen in 13, 14, 0% and 13, 29, and 0% in the LAT and SI dimensions, respectively. ConclusionsIn the thorax and abdomen, where there is relatively larger motion due to respiration, fiducial markers significantly improve tumor localization during daily set-up. Less set-up errors were detected when tumors in the pelvis were localized using neighboring spine instead of fiducial markers, which may obviate their need in the pelvis. Due to limited sample size, additional data will be needed to confirm these results. In the thorax and abdomen, where there is relatively larger motion due to respiration, fiducial markers significantly improve tumor localization during daily set-up. Less set-up errors were detected when tumors in the pelvis were localized using neighboring spine instead of fiducial markers, which may obviate their need in the pelvis. Due to limited sample size, additional data will be needed to confirm these results.

To retrospectively review the safety and efficacy of image-guided linear accelerator-based radiosurgery for the treatment of patients with benign nerve sheath tumors. Between March 2003 and July 2007, 20 patients with 25 nerve sheath tumors were treated with spinal radiosurgery. Patient age varied from 17 to 78 years (median 61). Five patients had neurofibromatosis type-1 and 4 had neurofibromatosis type-2. Seven patients underwent subtotal tumor removal 2 to 36 months prior to radiosurgery. There were 8 neurofibromas, 8 schwannomas, and 9 lesions diagnosed on clinicoradiographic features. Eleven tumors were located in the cervical spine, 10 in the lumbar spine, and 4 in the thoracic spine. The largest tumor dimension varied from 0.9 to 4.1 cm (median 2.1). Tumor volume varied from 0.5 to 13.7 cc (median 2.6). Thirteen lesions caused sensory disturbance, 12 caused pain, and 9 motor weakness. Radiosurgery was performed in the outpatient setting with a 6 MV linear accelerator equipped with a micro-multileaf collimator (Novalis, BrainLAB, Feldkirchen, Germany). Forward dose planning was used for 20 lesions and inverse planning for 5 tumors. Forward planned targets were treated with 3 or 4 arc fields. Inverse planned targets were treated with 6 static beams. Median peripheral tumor dose and prescription isodose were 12 Gy and 90%, respectively. Image-guidance was performed using a combination of optical tracking with infrared reflectors, fusion of oblique amorphous silicon radiographs with a dynamically reconstructed digital radiograph and automatic patient positioning capable of 4 degrees of movement. Follow-up varied from 6 to 48 months (median 12). There have been no local failures detected on follow-up magnetic resonance imaging. Twenty-three tumors have remained stable and 2 lesions demonstrated at least 50% reduction in the greatest tumor dimension. Reduction in pain occurred in one site, reduction in numbness in two sites and an improvement in motor weakness in one site. There has been no clinical or imaging evidence of spinal cord injury following radiosurgery. One patient had a transient increase in pain and 1 a transient increase in numbness, both occurring 6 months after radiosurgery. The results of this limited experience indicate that linear-accelerator-based spinal radiosurgery is safe and effective for patients with benign nerve sheath tumors. Further follow-up with a larger group of patients is required but these results imply that spinal radiosurgery may represent a therapeutic alternative for patients with spinal nerve sheath tumors.

PURPOSE:The aim of this study was to retrospectively review local control and morbidity following stereotactic radiotherapy (SRT) for pituitary adenoma.METHODS:Between 1997 and 2004, 39 patients with pituitary adenomas received SRT. Median age was 56 years (range: 13 to 90 years). Thirty-three patients underwent incomplete transsphenoidal surgery prior to SRT and six had unresectable tumors. The largest tumor dimension varied from 1.7 to 6 cm (median: 3 cm). Tumor volume varied from 1.2 to 56 mL (median 10.5 mL). Thirty-five tumors were < or = 1 mm from the optic chiasm/nerve. Thirty-three tumors were non-functional. SRT was delivered by a dedicated linear accelerator (Novalis, Heimstetten, Germany). Beam collimation was achieved by a fixed circular collimator (five patients) or a micro-multileaf collimator (34 patients). Total dose varied from 4500 to 5040 cGy (median: 4860 cGy) and was prescribed at the 90 % isodose line.RESULTS:After a median follow-up of 32 months (range: 12 to 94 months), the local control rate was 100 %. Tumor size was stable in 26 patients and decreased in 13 patients. Hormone normalization did not occur following SRT. New endocrine deficiency occurred in six patients. No patient developed cranial nerve injury or second malignancy following treatment.CONCLUSIONS:SRT achieves a high rate of local control and a low rate of treatment-induced morbidity. SRT is applicable to pituitary adenomas in close proximity to the optic apparatus and tumors in excess of three centimeters in the greatest dimension. Further follow-up is necessary to establish the long-term outcome following SRT for pituitary adenomas.

Purpose: There are reports of successful gamma-knife stereotactic radiosurgery (SRS) for the treatment of gelastic seizures associated with a hypothalamic hamartoma. The authors reviewed the results of linear accelerator (LINAC) radiosurgery for patients with medically refractory gelastic seizures due to a sessile hypothalamic hamartoma. Methods: Three patients with gelastic seizures received SRS between 2003 and 2004. All patients had associated partial complex and/or generalized seizures. One patient demonstrated aggressive behavior. Sessile hamartomas varying in diameter from 6 to 14 mm were identified by MRI. SRS was delivered to a single isocenter by a dedicated LINAC equipped with either a circular beam collimator or a micromultileaf collimator. Patients received 1500 to 1800 cGy prescribed at the 90 to 95 % isodose line. Seizure outcome was scored according to Engel's classification. Results: Two patients became free of gelastic and partial complex/generalized seizures seven and nine months after radiosurgery. These patients remain free of seizures at 17 and 15 months, respectively, after treatment (Engle Class IA). One patient experienced a decline in gelastic seizure frequency nine months after treatment (Engle Class II) without significant reduction in aggressive behavior. Follow-up MRI demonstrated no change in the size or signal characteristics of any tumor. No patient developed post-treatment cranial neuropathy or hypothalamic-pituitary suppression. Conclusions: LINAC SRS represents a safe and effective therapeutic alternative for patients with medically refractory gelastic seizures due to unresectable hypothalamic hamartomas. Radiosurgery is associated with a latency of several months from treatment to reduction in seizure frequency. Further follow-up is required to establish the duration of seizure control following radiosurgery.

Object. The authors sought to assess the safety and efficacy of stereotactic radiotherapy when using a linear accelerator equipped with a micromultileaf collimator for the treatment of patients with acoustic neuromas. Methods. Fifty patients harboring acoustic neuromas were treated with stereotactic radiotherapy between September 1997 and June 2003. Two patients were lost to follow-up review. Patient age ranged from 20 to 76 years (median 59 years), and none had neurofibromatosis. Forty-two patients had useful hearing prior to stereotactic radiotherapy. The fifth and seventh cranial nerve functions were normal in 44 and 46 patients, respectively. Tumor volume ranged from 0.3 to 19.25 ml (median 2.51 ml). The largest tumor dimension varied from 0.6 to 4 cm (median 2.2 cm). Treatment planning in all patients included computerized tomography and magnetic resonance image fusion and beam shaping by using a micromultileaf collimator. The planning target volume included the contrast-enhancing tumor mass and a margin of normal tissue varying from 1 to 3 mm (median 2 mm). All tumors were treated with 6-MV photons and received 54 Gy prescribed at the 90% isodose line encompassing the planning target volume. A sustained increase greater than 2 mm in any tumor dimension was defined as local relapse. The follow-up duration varied from 6 to 74 months (median 36 months). The local tumor control rate in the 48 patients available for follow up was 100%. Central tumor hypodensity occurred in 32 patients (67%) at a median of 6 months following stereotactic radiotherapy. In 12 patients (25%), tumor size increased 1 to 2 mm at a median of 6 months following stereotactic radiotherapy. Increased tumor size in six of these patients was transient. In 13 patients (27%), tumor size decreased 1 to 14 mm at a median of 6 months after treatment. Useful hearing was preserved in 39 patients (93%). New facial numbness occurred in one patient (2.2%) with normal fifth cranial nerve function prior to stereotactic radiotherapy. New facial palsy occurred in one patient (2.1%) with normal seventh cranial nerve function prior to treatment. No patient's pretreatment dysfunction of the fifth or seventh cranial nerve worsened after stereotactic radiotherapy. Tinnitus improved in six patients and worsened in two. Conclusions. Stereotactic radiotherapy using field shaping for the treatment of acoustic neuromas achieves high rates of tumor control and preservation of useful hearing. The technique produces low rates of damage to the fifth and seventh cranial nerves. Long-term follow-up studies are necessary to confirm these findings.

Object. The authors studied outcomes and complications in patients who harbored arteriovenous malformations (AVMs) and underwent stereotactic radiosurgery involving the Novalis shaped beam unit. Methods. Between January 1998 and January 2002, 83 patients were treated with radiosurgery at University of California, Los Angeles. The mean patient age was 37.8 years. Forty-four patients completed follow up. There were 24 women. Sixteen patients underwent repeated radiosurgery. Embolization was performed in 13 patients and radiosurgery alone in 31. The mean follow-up period after embolization was 54.4 ± 21.9 months and 37.4 ± 14.6 months for radiosurgery alone. The mean peripheral dose was 15 Gy (range 12–18 Gy). The mean preradiosurgery lesion volume was 9.7 ± 11.9 ml for radiosurgery alone and 16.2 ± 11.3 ml for embolization. The AVMs in 13 patients (29.8%) were Spetzler—Martin Grade II, 12 (27.5%) were Grade III, eight (18.2%) Grade IV, and five (11.3%) were Grade V and VI each. Spetzler—Martin grade, volume, and peripheral dose were analyzed in consideration to outcome. A positive trend (p = 0.086) was observed between Spetzler—Martin grade and obliteration rate. Volume per se did not predict obliteration (p = 0.48). A peripheral dose of 18 Gy was shown to be the most important predictor for occlusion (p = 0.007). The overall obliteration rate was 52.5%. A transient complication was noticed in one case (2.3%) and but no permanent deficits due to radiosurgery have been detected so far. Three patients (6.8%) bled after radiosurgery. Conclusions. The range of the prescribed peripheral dose was narrow. An association between the mean peripheral dose of 15 Gy, high conformality, and homogeneous dose distribution permitted no permanent complications. Volume per se did not correlate with outcome. The next step will be to increase the peripheral dose shaping the beam and to achieve higher obliteration rates without increasing complications.

Lymphocytic hypophysitis is a rare inflammatory disorder of the pituitary gland. Standard therapy consists of transsphenoidal resection or oral administration of corticosteroid medications. Two patients with symptomatic lymphocytic hypophysitis, which recurred after standard therapy, were treated with low-dose stereotactic radiotherapy. On imaging studies both lesions demonstrated a response to radiation and each patient experienced relief of symptoms. There has been no adverse sequela of the radiation treatment. The authors conclude that stereotactic radiotherapy represents an effective, noninvasive treatment option for patients with lymphocytic hypophysitis, particularly if the disease is recurrent after surgery or resistant to corticosteroid medications.

Purpose/Objective: Age Related Macular Degeneration(ARMD) is the leading cause of blindness in the world. The only proven treatment is laser photocoagulation. Despite this therapy, 70% of patients recur within 5 years. It is also known that patients with ARMD have a 10% risk per year of developing disease in the uninvolved eye.Because of the known effects of radiation on microvasculature, its use has been implemented in this disease. However,conflicting data exists regarding the use of EBRT in treating the involved eye. To date, no institution has studied whether EBRT may be preventative to the uninvolved eye. Therefore, we began a prospective study to evaluate the effects of EBRT on both eyes using a cohort of patients treated with protons to the involved eye only, as controls.Materials/Methods: Between 1997–2000 167 patients with "wet" ARMD were treated in the UCLA Department of Radiation Oncology. All patients had a visual acuity examination by an Ophthamologist and Flouroscein Angiography prior to treatment. Patients were treated with 6MV photons using a lens sparring technique to 15Gy in 3 fractions. Visual acuity assessments were performed at 3, 6, 9, and 12 month intervals. One hundred twelve patients were analyzable. Patients with bilateral "wet" disease, less than 1-year follow-up, or incomplete documentation were excluded. Thirty-seven patients treated with protons to the involved eye only were used to compare visual acuity with bilateral photon irradiation. Each patient received 14GyE in 1 fraction to the involved eye only, using a lens sparring technique. Thirty-two of 37 patients in the proton group were analyzable. Patients were excluded for bilateral proton treatment, or incomplete follow-up.Analysis was performed to determine the relative risk of visual deterioration in the involved and uninvolved eyes in both groups. Visual deterioration was defined as a greater than or equal to 2 lines lost on the Snelling chart or 1 line loss with documented progression of disease.Results: Our results revealed that visual deterioration is reduced by 18% and 20% in the involved and uninvolved eyes respectively, favoring bilateral irradiation. However, these results were not statistically significant using χ2 testing (p=.16 involved eye) (p=.39 uninvolved eye).Conclusions: Bilateral ocular radiation does not reduce the risk of visual acuity deterioration in the involved eye when compared to protons, and in the uinvolved eye when compared to observation at 1 year. As the dose in our series was low compared to other series, an increase in dose may prolong the interval to visual deterioration. Longer follow-up will be required to determine the risks and ultimate benefits of this novel treatment approach. Purpose/Objective: Age Related Macular Degeneration(ARMD) is the leading cause of blindness in the world. The only proven treatment is laser photocoagulation. Despite this therapy, 70% of patients recur within 5 years. It is also known that patients with ARMD have a 10% risk per year of developing disease in the uninvolved eye. Because of the known effects of radiation on microvasculature, its use has been implemented in this disease. However,conflicting data exists regarding the use of EBRT in treating the involved eye. To date, no institution has studied whether EBRT may be preventative to the uninvolved eye. Therefore, we began a prospective study to evaluate the effects of EBRT on both eyes using a cohort of patients treated with protons to the involved eye only, as controls. Materials/Methods: Between 1997–2000 167 patients with "wet" ARMD were treated in the UCLA Department of Radiation Oncology. All patients had a visual acuity examination by an Ophthamologist and Flouroscein Angiography prior to treatment. Patients were treated with 6MV photons using a lens sparring technique to 15Gy in 3 fractions. Visual acuity assessments were performed at 3, 6, 9, and 12 month intervals. One hundred twelve patients were analyzable. Patients with bilateral "wet" disease, less than 1-year follow-up, or incomplete documentation were excluded. Thirty-seven patients treated with protons to the involved eye only were used to compare visual acuity with bilateral photon irradiation. Each patient received 14GyE in 1 fraction to the involved eye only, using a lens sparring technique. Thirty-two of 37 patients in the proton group were analyzable. Patients were excluded for bilateral proton treatment, or incomplete follow-up. Analysis was performed to determine the relative risk of visual deterioration in the involved and uninvolved eyes in both groups. Visual deterioration was defined as a greater than or equal to 2 lines lost on the Snelling chart or 1 line loss with documented progression of disease. Results: Our results revealed that visual deterioration is reduced by 18% and 20% in the involved and uninvolved eyes respectively, favoring bilateral irradiation. However, these results were not statistically significant using χ2 testing (p=.16 involved eye) (p=.39 uninvolved eye). Conclusions: Bilateral ocular radiation does not reduce the risk of visual acuity deterioration in the involved eye when compared to protons, and in the uinvolved eye when compared to observation at 1 year. As the dose in our series was low compared to other series, an increase in dose may prolong the interval to visual deterioration. Longer follow-up will be required to determine the risks and ultimate benefits of this novel treatment approach.