Linear accelerator-based radiosurgery for trigeminal neuralgia: comparative outcomes of frame-based and mask-based techniques.

OBJECTIVE: Precise and accurate targeting is critical to optimize outcomes after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). The aim of this study was to compare the outcomes after SRS for TN in which two different techniques were used: mask-based 4-mm cone versus frame-based 5-mm cone. METHODS: The authors performed a retrospective review of patients who underwent SRS for TN at their institution between 1996 and 2019. The Barrow Neurological Institute (BNI) pain score and facial hypesthesia scale were used to evaluate pain relief and facial numbness. RESULTS: A total of 234 patients were included in this study; the mean age was 67 years. In 97 patients (41.5%) radiation was collimated by a mask-based 4-mm cone, whereas a frame-based 5-mm cone was used in the remaining 137 patients (58.5%). The initial adequate pain control rate (BNI I-III) was 93.4% in the frame-based 5-mm group, compared to 87.6% in the mask-based 4-mm group. This difference between groups lasted, with an adequate pain control rate at ≥ 24 months of 89.9% and 77.8%, respectively. Pain relief was significantly different between groups from initial response until the last follow-up (≥ 24 months, p = 0.02). A new, permanent facial hypesthesia occurred in 30.3% of patients (33.6% in the frame-based 5-mm group vs 25.8% in the mask-based 4-mm group). However, no significant association between the BNI facial hypesthesia score and groups was found. Pain recurrence occurred earlier (median time to recurrence 12 months vs 29 months, p = 0.016) and more frequently (38.1% vs 20.4%, p = 0.003) in the mask-based 4-mm than in the frame-based 5-mm group. CONCLUSIONS: Frame-based 5-mm collimator SRS for TN resulted in a better long-term pain relief with similar toxicity profiles to that seen with mask-based 4-mm collimator SRS.

Comparison of Clinical Outcomes Stratified by Target Delineation for Patients Undergoing Stereotactic Body Radiotherapy for Spinal Metastases.

OBJECTIVE: Stereotactic body radiotherapy (SBRT) is an effective treatment of spinal metastases in the vertebral body. However, variation has existed between practitioners regarding the appropriate target delineation. As such, we compared the tumor control, rates of compression fractures, and pain control for patients who had undergone SBRT for spinal metastases to either the lesion only (LO) or the full vertebral body (FVB). METHODS: A total of 126 spinal metastases in 84 patients had received single-fraction SBRT from January 2009 to February 2015. Of the 126 lesions, 36 (29%) were in the FVB group and 90 were in the LO group. The SBRT plans were reviewed to determine the treatment volume. Odds ratios were used to compare the rates of compression fracture and local failure. Regression analysis was performed to identify the predictors of outcome. RESULTS: A total of 5 failures had occurred in the FVB group and 14 in the LO group; however, the difference was not statistically significant (P = 0.5). No difference was found in pain reduction between the 2 groups (P = 0.9). Seven post-treatment compression fractures occurred in the LO group and four in the FVB group; however, the difference was not statistically significant (P = 0.6). The minimum dose to the planning target volume, patient age, and planning target volume size were the only significant factors predicting for local failure, vertebral body fracture, and pain control, respectively. CONCLUSIONS: Given that we found no difference in tumor control, pain reduction, or fracture rate between patients treated to the FVB versus the. LO, it might be reasonable to consider SBRT to the LO for select patients.

Increased cochlear radiation dose predicts delayed hearing loss following both stereotactic radiosurgery and fractionated stereotactic radiotherapy for vestibular schwannoma.

PURPOSE: Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are noninvasive therapies for vestibular schwannomas providing excellent tumor control. However, delayed hearing loss after radiation therapy remains an issue. One potential target to for improving hearing rates is limiting radiation exposure to the cochlea. METHODS: We retrospectively reviewed 100 patients undergoing either SRS with 12 Gy (n = 43) or fSRT with 50 Gy over 28 fractions (n = 57) for vestibular schwannoma. Univariate and multivariate analysis were carried out to identify predictors of hearing loss as measured by the Gardner Robertson scale after radiation therapy. RESULTS: Deterioration of hearing occurred in 30% of patients with SRS and 26% with fSRT. The overall long term (> 2 year) progression rates were 20% for SRS and 16% for fSRT. Patients with a decrease in their Gardner Robertson hearing score and those that loss serviceable hearing had significantly higher average minimal doses to the cochlea in both SRS and fSRT cohorts. ROC analysis showed that a cut off of 5 Gy and 35 Gy, for SRS and fSRT respectively, predicted hearing loss with high sensitivity/specificity. CONCLUSION: Our data suggests the minimal dose of radiation that the cochlear volume is exposed to is a predictor of delayed hearing loss after either SRS or fSRT. A threshold of 5 Gy/35 Gy may lead to improved hearing preservation after radiotherapy. Further prospective multi center studies can further elucidate this mechanism.

Immediate Pain Relief Elicited After Radiosurgery for Classical and Symptomatic Trigeminal Neuralgia.

Background Immediate relief following radiosurgery for trigeminal neuralgia (TN) has been observed in a minority of cases. Objective Our goals were to determine the occurrence of immediate pain relief as real vs. placebo effect and to search for factors associated with this desirable outcome. Methods Between January 2003 and June 2008, 150 patients were treated with radiosurgery for classical or symptomatic TN. A commercially available linear accelerator (Novalis®, BrainLab) device was used to deliver 90 Gy to the root-entry zone with a 4- or 5-mm collimator. Pain outcomes were graded using a four-point scale. Complications were recorded through standardized follow-up evaluations. Treatment plans were retrieved and brainstem/trigeminal nerves were retrospectively re-contoured using standard anatomical landmarks. Dose-volume histograms were used to calculate the volume of brainstem/trigeminal nerve receiving 20%, 30%, and 50% of the prescribed radiation doses. Results Twenty-five (19.84%) patients presented with immediate pain relief, defined as pain cessation within 48 hours post-radiosurgery. Kaplan-Meier analysis showed that good/excellent pain outcomes were sustained and significantly better in the immediate pain relief group (p = 0.006) compared to non-immediate relief. Univariate and multivariate logistic regression analyses failed to show the correlation between brainstem/trigeminal nerve volumes, trigeminal nerve-pontine angle, prior surgical procedures, TN etiology, age, gender, and immediate pain relief. Neither post-radiosurgery complications nor recurrence rates were different between groups. Conclusion Immediate pain relief leads to sustained relief and patients present significantly better pain outcomes in comparison to those without immediate relief. The mechanism triggering immediate relief is still unknown and did not correlate with the volume of brainstem/trigeminal nerve receiving pre-specified doses of radiation.

Dose Hypofractionated Stereotactic Radiotherapy for Intracranial Arteriovenous Malformations: A Case Series and Review of the Literature.

BACKGROUND: Brain arteriovenous malformations (AVMs) are pathologic tangles of intracerebral vessels. The treatment of AVMs aims to reduce the risk of devastating intracranial hemorrhage (ICH). Hypofractionated stereotactic radiotherapy (HSRT) can be used to treat large lesions and reduce the risk of radiation toxicity to the surrounding structures. We analyzed the data from our institutional experience of the past 15 years in treating large AVMs with both 5- and 6-fraction HSRT and evaluated the pretreatment characteristics that are most predictive of the radiographic response. METHODS: We included 37 patients and 42 treatments of intracranial AVMs measuring >3 cm in their largest dimension. Data were collected retrospectively by reviewing the electronic health records. The AVM volume was measured before HSRT and at the most recent follow-up appointment. Symptomatic outcomes, including treatment-related inflammation, were measured and defined categorically. RESULTS: Complete obliteration was achieved in 11.9% of the patients. The mean AVM volume had decreased significantly after HSRT (P = 8.7e-8). The percentage of volume reduction differed significantly between patients receiving 30-Gy fractions, (∂V = -48.7%) and those receiving 25-Gy fractions (∂V = -29.1%; P = 0.035). Patients with partial or complete obliteration were more likely to have received a total dose of 30 Gy rather than 25 Gy (P = 0.056) and showed a trend toward being treatment naive (P = 0.053). CONCLUSION: HSRT can be used as a method to manage large AVMs, with obliteration in some cases and sufficient volume reduction in most others for adjuvant treatment with other modalities. The 30-Gy total dose was generally superior to 25 Gy in achieving obliteration or volume reduction. Further studies focused on longer follow-up periods are warranted.

Impact of Cochlear Dose on Hearing Preservation following Stereotactic Radiosurgery and Fractionated Stereotactic Radiotherapy for the Treatment of Vestibular Schwannoma.

Objective The objective of this study was to examine the effect of cochlear dose on hearing preservation in stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) for vestibular schwannoma (VS). Design This is a retrospective case-control study. Setting This study was completed at the Ronald Reagan UCLA Medical Center, a university-affiliated tertiary care center. Participants Patients who underwent SRS (marginal dose of 12 Gy) or fSRT (marginal dose of 50.4 Gy) procedures for VS were included in the study. Main Outcome Measures The main outcome measure was hearing preservation. Audiometric data, when available, were used to determine the level of hearing according to the Gardner Robertson scale. Results A total of 38 patients (14 SRS and 24 fSRT) were analyzed. SRS patients with decreased hearing received a significantly higher minimum cochlear dose (7.41 vs. 4.24 Gy, p = 0.02) as compared with those with stable hearing. In fSRT patients, there were no significant differences in cochlear dose for patients with decreased hearing as compared with those with stable hearing. For SRS patients, who received a minimum cochlear dose above 6 Gy, there was a significant risk of decreased hearing preservation (odds ratio: 32, p = 0.02). Conclusion Higher minimum cochlear dose was predictive of decreased hearing preservation following SRS. Though the study is low powered, the radiation dose to the cochlea should be a parameter that is considered when planning SRS or fSRT therapies for patients with VS.

Long-term Outcomes With Ifosfamide-based Hypofractionated Preoperative Chemoradiotherapy for Extremity Soft Tissue Sarcomas.

OBJECTIVES: The objective of this study was to analyze outcomes for patients with soft tissue sarcoma of the extremities using neoadjuvant ifosfamide-based chemotherapy and hypofractionated reduced dose radiotherapy, followed by limb-sparing surgery. MATERIALS AND METHODS: An Institutional Review Board (IRB)-approved retrospective review of patients treated at a single institution between 1990 and 2013 was performed. In total, 116 patients were identified who received neoadjuvant ifosfamide-based chemotherapy and 28 Gy in 8 fractions of preoperative radiation (equivalent dose in 2 Gray fractions, 31.5 Gy [α/ß 10] 36.4 Gy [α/ß 3]) followed by limb-sparing surgery. Local recurrence (LR), distant failure (DF), and overall survival (OS) were calculated. Univariate and multivariate analysis for LR, DF, and OS were performed using Cox analysis. Statistical significance was set at a P<0.05. RESULTS: Median follow-up was 5.9 years (range, 0.3 to 24 y). Actuarial LR at 3/6 years was 11%/17%, DF at 3/6 years was 25%/35%, and OS at 3/6 years was 82%/67%. On multivariate analysis, only a positive surgical margin was significantly correlated with worse local control (P=0.005; hazard ratio [HR], 18.33; 95% confidence interval (CI), 2.41-139.34). Age over 60 years (P=0.03; HR, 2.34; 95% CI, 1.10-4.98) and tumor size over 10 cm compared with tumor size ≤5 cm (P=0.03; HR, 3.32; 95% CI, 1.15-9.61) were associated with worse OS. CONCLUSIONS: Soft tissue extremity sarcoma patients treated using reduced dose hypofractionated preoperative radiotherapy in combination with ifosfamide-based chemotherapy shows acceptable local control and warrants further investigation.

Predictors of Local Recurrence in Patients With Myxofibrosarcoma.

OBJECTIVES: Myxofibrosarcoma (MFS) is reported to have a higher risk of local recurrence (LR) following definitive surgical excision relative to other soft tissue sarcomas. We reviewed our clinical experience treating MFS to investigate predictors of LR. MATERIALS AND METHODS: We retrospectively reviewed treatment outcomes for MFS patients treated at our institution between 1999 and 2015. A total of 52 patients were identified. Median age was 65 years (range, 21 to 86 y). Site of disease was: upper extremity (27%), lower extremity (46%), trunk (15%), pelvic (8%), and head and neck (4%). Patients had low, intermediate, high-grade, and unknown grade in: 23%, 8%, 67%, and 2% of tumors, respectively. Tumors were categorized as ≤5 cm (35%), >5 cm (56%), or unknown size (9%). In total, 71% received radiotherapy: 19% preoperative, 50% postoperative, and 2% both. All patients underwent surgery. Margins were negative in 71%, close/positive in 21%, and unknown in 8%. In total, 27% of patients received chemotherapy. Univariate Cox regression analysis was utilized to determine associations between clinical and treatment factors with LR. RESULTS: Median follow-up time was 2.9 years (range, 0.4 to 14.3 y). The 3-year actuarial LR, distant metastasis, and overall survival were: 31%, 15%, and 87%, respectively. Predictors of LR were patient age greater than or equal to the median of 65 years (hazard ratio, 13.46, 95% confidence interval, 1.71-106.18, P=0.013), and having close/positive tumor margins (hazard ratio, 3.4, 95% confidence interval, 1-11.53, P=0.049). CONCLUSIONS: In this institutional series of MFS older age and positive/close margins were significantly associated with a higher risk of LR.

Adjuvant Radiosurgery Versus Serial Surveillance Following Subtotal Resection of Atypical Meningioma: A Systematic Analysis.

BACKGROUND: Atypical meningioma (AM) is an aggressive subtype of meningioma associated with a high recurrence rates (RR) following surgical resection. Recent studies have compared outcomes of various treatment strategies, but advantages of adjuvant radiosurgery (ARS) over serial surveillance (SS) following subtotal resection (STR) remain unclear. To further elucidate this issue, we systematically analyzed the current literature on AM and compared outcomes of ARS versus SS after STR. METHODS: Embase, PubMed, and Cochrane databases were queried using relevant search terms. Retrospective case series that described patients with AM treated with ARS and SS after STR were included. Tests of proportions were performed to detect significant variations in RR, 5-year progression-free survival (PFS), and 5-year overall survival (OS) between the treatment strategies (ARS vs. SS) and among individual studies. RESULTS: A total of 619 patients (263 in the ARS group and 356 in the SS group) were identified. Mean RR, 5-year PFS, and 5-year OS were 53.5%, 50.3%, and 74.9%, respectively, for ARS versus 89.8%, 19.1%, and 89.8% for SS. RR differed between treatment strategies and ARS studies (P < 0.001), and 5-year PFS differed among treatment strategies, ARS, and SS studies (P < 0.001, P = 0.007, and P < 0.001, respectively). CONCLUSIONS: The data presented here show significant differences in RR and 5-year PFS between ARS and SS, suggesting a potential benefit of ARS. As our understanding of the clinical outcomes of various treatment strategies for AM increases, we also move closer to integrating modalities, such as radiosurgery, into management guidelines.

Adjuvant Stereotactic Radiosurgery and Radiation Therapy for the Treatment of Intracranial Chordomas.

Objective Chordomas are locally aggressive, highly recurrent tumors requiring adjuvant radiotherapy following resection for successful management. We retrospectively reviewed patients treated for intracranial chordomas with adjuvant stereotactic radiosurgery (SRS) and stereotactic radiation therapy (SRT). Methods A total of 57 patients underwent 83 treatments at the UCLA Medical Center between February 1990 and August 2011. Mean follow-up was 57.8 months. Mean tumor diameter was 3.36 cm. Overall, 8 and 34 patients received adjuvant SRS and SRT, and the mean maximal dose of radiation therapy was 1783.3 cGy and 6339 cGy, respectively. Results Overall rate of recurrence was 51.8%, and 1- and 5-year progression-free survival (PFS) was 88.2% and 35.2%, respectively. Gross total resection was achieved in 30.9% of patients. Adjuvant radiotherapy improved outcomes following subtotal resection (5-year PFS 62.5% versus 20.1%; p = 0.036). SRS and SRT produced comparable rates of tumor control (p = 0.28). Higher dose SRT (> 6,000 cGy) (p = 0.013) and younger age (< 45 years) (p = 0.03) was associated with improved rates of tumor control. Conclusion Adjuvant radiotherapy is critical following subtotal resection of intracranial chordomas. Adjuvant SRT and SRS were safe and improved PFS following subtotal resection. Higher total doses of SRT and younger patient age were associated with improved rates of tumor control.

Tomotherapy improves local control and changes failure patterns in locally advanced malignant pleural mesothelioma.

PURPOSE: The purpose of the study was to determine whether intensity modulated radiation therapy delivered via helical tomotherapy improves local control (LC) after pleurectomy/decortication (P/D) for malignant pleural mesothelioma compared with 3-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: Forty-five consecutive patients were treated with adjuvant radiation to 45 Gy in 1.8 Gy fractions after P/D between 2006 and 2014; 23 received 3D-CRT, and 22 received tomotherapy. Kaplan-Meier analysis was used to calculate overall survival, time to in-field or local failure (LF), and time to out-of-field failure. The Student t test and Fisher exact test were used to detect between-group differences. RESULTS: Median follow-up time was 19.4 months and 12.7 months for the 3D-CRT and tomotherapy groups, respectively. Eighty-two percent of patients had T3/T4 disease, and 64% had positive nodes; 17.4% and 41% of patients in the 3D-CRT and tomotherapy groups had nonepithelioid histology, respectively. Mean planning target volume dose, percentage of planning target volume receiving 100% of the prescription dose, and lung doses were significantly greater with tomotherapy (P < .05), but toxicity rates (including radiation pneumonitis rates) were equivalent. LC was significantly improved with tomotherapy on Kaplan-Meier analysis with outcomes censored at 2 years (P < .05); uncensored, this became a trend (P = .06). Median time to LF was 19 months with tomotherapy and 10.9 months in 3D-CRT (the latter interval being less than the median follow-up in the tomotherapy group). On univariate analysis, treatment modality was the only significant predictor of LC (P < .05). Isolated LF was significantly more frequent with 3D-CRT (P < .05). Conversely, isolated out-of-field failure was significantly more frequent with tomotherapy (P < .05). Overall survival and out-of-field control were not significantly different. CONCLUSION: Tomotherapy after P/D for malignant pleural mesothelioma is associated with improved target coverage that translates into improved LC compared with 3D-CRT. This is related to a change in failure patterns, with isolated LF being more common in the 3D-CRT group and isolated out-of-field failures predominating in the tomotherapy group.

Predictors of recurrence following resection of intracranial chordomas.

Management of intracranial chordomas remains challenging, despite improvements in microsurgical techniques and radiotherapy. Here, we analyzed the prognostic factors associated with improved rates of tumor control in patients with intracranial chordomas, who received either gross (GTR) or subtotal resections (STR). A retrospective review was performed to identify all patients who were undergoing resection of their intracranial chordomas at the Ronald Reagan University of California Los Angeles Medical Center from 1990 to 2011. In total, 57 patients undergoing 81 resections were included. There were 24 females and 33 males with a mean age of 44.6 years, and the mean tumor diameter was 3.36 cm. The extent of resection was not associated with recurrence. For all 81 operations, the 1 and 5 year progression free survival (PFS) was 87.5 and 40.4%, and 88.0 and 33.6% for STR and GTR, respectively (p=0.90). Adjuvant radiotherapy was associated with improved rates of PFS (hazard ratio [HR] 0.20; p=0.009). Additionally, age >45 years (HR 5.88; p=0.01) and the presence of visual deficits (HR 7.59; p=0.03) were associated with worse rates of tumor control. Tumor size, sex, tumor histology, and recurrent tumors were not predictors of recurrence. Younger age, lack of visual symptoms on presentation and adjuvant radiotherapy were associated with improved rates of tumor control following surgery. However, GTR and STR produced comparable rates of tumor control. The surgical management of intracranial chordomas should take a conservative approach, with the aim of maximal but safe cytoreductive resection with adjuvant radiation therapy, and a major focus on quality of life.

Incorporating cancer stem cells in radiation therapy treatment response modeling and the implication in glioblastoma multiforme treatment resistance.

PURPOSE: To perform a preliminary exploration with a simplistic mathematical cancer stem cell (CSC) interaction model to determine whether the tumor-intrinsic heterogeneity and dynamic equilibrium between CSCs and differentiated cancer cells (DCCs) can better explain radiation therapy treatment response with a dual-compartment linear-quadratic (DLQ) model. METHODS AND MATERIALS: The radiosensitivity parameters of CSCs and DCCs for cancer cell lines including glioblastoma multiforme (GBM), non-small cell lung cancer, melanoma, osteosarcoma, and prostate, cervical, and breast cancer were determined by performing robust least-square fitting using the DLQ model on published clonogenic survival data. Fitting performance was compared with the single-compartment LQ (SLQ) and universal survival curve models. The fitting results were then used in an ordinary differential equation describing the kinetics of DCCs and CSCs in response to 2- to 14.3-Gy fractionated treatments. The total dose to achieve tumor control and the fraction size that achieved the least normal biological equivalent dose were calculated. RESULTS: Smaller cell survival fitting errors were observed using DLQ, with the exception of melanoma, which had a low α/ß = 0.16 in SLQ. Ordinary differential equation simulation indicated lower normal tissue biological equivalent dose to achieve the same tumor control with a hypofractionated approach for 4 cell lines for the DLQ model, in contrast to SLQ, which favored 2 Gy per fraction for all cells except melanoma. The DLQ model indicated greater tumor radioresistance than SLQ, but the radioresistance was overcome by hypofractionation, other than the GBM cells, which responded poorly to all fractionations. CONCLUSION: The distinct radiosensitivity and dynamics between CSCs and DCCs in radiation therapy response could perhaps be one possible explanation for the heterogeneous intertumor response to hypofractionation and in some cases superior outcome from stereotactic ablative radiation therapy. The DLQ model also predicted the remarkable GBM radioresistance, a result that is highly consistent with clinical observations. The radioresistance putatively stemmed from accelerated DCC regrowth that rapidly restored compartmental equilibrium between CSCs and DCCs.

Feasibility of extreme dose escalation for glioblastoma multiforme using 4π radiotherapy.

BACKGROUND: Glioblastoma multiforme (GBM) frequently recurs at the same location after radiotherapy. Further dose escalation using conventional methods is limited by normal tissue tolerance. 4π non-coplanar radiotherapy has recently emerged as a new potential method to deliver highly conformal radiation dose using the C-arm linacs. We aim to study the feasibility of very substantial GBM dose escalation while maintaining normal tissue tolerance using 4π. METHODS: 11 GBM patients previously treated with volumetric modulated arc therapy (VMAT/RapidArc) on the NovalisTx™ platform to a prescription dose of either 59.4 Gy or 60 Gy were included. All patients were replanned with 30 non-coplanar beams using a 4π radiotherapy platform, which inverse optimizes both beam angles and fluence maps. Four different prescriptions were used including original prescription dose and PTV (4πPTVPD), 100 Gy to the PTV and GTV (4πPTV100Gy), 100 Gy to the GTV only while maintaining prescription dose to the rest of the PTV (4πGTV100Gy), and a 5 mm margin expansion plan (4πPTVPD+5mm). OARs included in the study are the normal brain (brain - PTV), brainstem, chiasm, spinal cord, eyes, lenses, optical nerves, and cochleae. RESULTS: The 4π plans resulted in superior dose gradient indices, as indicated by >20% reduction in the R50, compared to the clinical plans. Among all of the 4π cases, when compared to the clinical plans, the maximum and mean doses were significantly reduced (p < 0.05) by a range of 47.01-98.82% and 51.87-99.47%, respectively, or unchanged (p > 0.05) for all of the non-brain OARs. Both the 4πPTVPD and 4π GTV100GYplans reduced the mean normal brain mean doses. CONCLUSIONS: 4π non-coplanar radiotherapy substantially increases the dose gradient outside of the PTV and better spares critical organs. Dose escalation to 100 Gy to the GTV or additional margin expansion while meeting clinical critical organ dose constraints is feasible. 100 Gy to the PTV result in higher normal brain doses but may be tolerated when delivered in proportionally increased treatment fractions. Therefore, 4π non-coplanar radiotherapy on C-arm gantry may provide an accessible tool to improve the outcome of GBM radiotherapy through extreme dose escalation.

Safety and efficacy of stereotactic body radiation therapy in the treatment of pulmonary metastases from high grade sarcoma.

Introduction. Patients with high-grade sarcoma (HGS) frequently develop metastatic disease thus limiting their long-term survival. Lung metastases (LM) have historically been treated with surgical resection (metastasectomy). A potential alternative for controlling LM could be stereotactic body radiation therapy (SBRT). We evaluated the outcomes from our institutional experience utilizing SBRT. Methods. Sixteen consecutive patients with LM from HGS were treated with SBRT between 2009 and 2011. Routine radiographic and clinical follow-up was performed. Local failure was defined as CT progression on 2 consecutive scans or growth after initial shrinkage. Radiation pneumonitis and radiation esophagitis were scored using Common Toxicity Criteria (CTC) version 3.0. Results. All 16 patients received chemotherapy, and a subset (38%) also underwent prior pulmonary metastasectomy. Median patient age was 56 (12-85), and median follow-up time was 20 months (range 3-43). A total of 25 lesions were treated and evaluable for this analysis. Most common histologies were leiomyosarcoma (28%), synovial sarcoma (20%), and osteosarcoma (16%). Median SBRT prescription dose was 54 Gy (36-54) in 3-4 fractions. At 43 months, local control was 94%. No patient experienced G2-4 radiation pneumonitis, and no patient experienced radiation esophagitis. Conclusions. Our retrospective experience suggests that SBRT for LM from HGS provides excellent local control and minimal toxicity.

Evaluation of high ipsilateral subventricular zone radiation therapy dose in glioblastoma: a pooled analysis.

PURPOSE: Cancer stem cells (CSCs) may play a role in the recurrence of glioblastoma. They are believed to originate from neural stem cells in the subventricular zone (SVZ). Because of their radioresistance, we hypothesized that high doses of radiation (>59.4 Gy) to the SVZ are necessary to control CSCs and improve progression-free survival (PFS) or overall survival (OS) in glioblastoma. METHODS AND MATERIALS: 173 patients with glioblastoma pooled from 2 academic centers were treated with resection followed by chemoradiation therapy. The SVZ was segmented on computed tomography to calculate radiation doses delivered to the presumptive CSC niches. The relationships between high SVZ doses and PFS and OS were examined using Cox proportional hazards models. Five covariates were included to estimate their impact on PFS or OS: ipsilateral and contralateral SVZ doses, clinical target volume dose, age, and extent of resection. RESULTS: Median PFS and OS were 10.4 and 19.6 months for the cohort. The mean ipsilateral SVZ, contralateral SVZ, and clinical target volume doses were 49.2, 35.2, and 60.1 Gy, respectively. Twenty-one patients who received high ipsilateral SVZ dose (>59.4 Gy) had significantly longer median PFS (12.6 vs 9.9 months, P=.042) and longer OS (25.8 vs 19.2 months, P=.173). On multivariate analysis, high radiation therapy doses to ipsilateral SVZ remained a statistically significant independent predictor of improved PFS but not of OS. The extent of surgery affected both PFS and OS on multivariate analysis. CONCLUSION: High radiation therapy doses to ipsilateral CSC niches are associated with improved PFS in glioblastoma.

A child with gemcitabine-induced severe radiation recall myositis resulting in a compartment syndrome.

Chemotherapeutic induction of radiation recall (RR) is a rare event in which a chemotherapeutic agent given days to years after radiation therapy causes an inflammation reaction of the tissues within the irradiated area-"recalling" increased radiation effects to that area. In this unique case, a 14-year-old girl with a synovial sarcoma of the forearm was treated with neoadjuvant chemotherapy and radiation therapy. Gemcitabine was administered in an adjuvant setting inducing a RR reaction. The severity of the inflammation resulted in a forearm myositis secondarily causing a compartment syndrome that was treated with several prolonged courses of corticosteroids. The symptoms of RR and compartment syndrome have resolved 1 year postonset, although magnetic resonance imaging continues to show myositis and soft-tissue edema. This case highlights the need to maintain a heightened awareness to recognizing the signs and symptoms of RR and the potential severity of RR in pediatric cancer patients in conjunction with chemotherapeutic agents used more frequently in adults.

Image-guided linear accelerator-based spinal radiosurgery for hemangioblastoma.

PURPOSE: To retrospectively review the efficacy and safety of image-guided linear accelerator-based radiosurgery for spinal hemangioblastomas. METHODS: Between August 2004 and September 2010, nine patients with 20 hemangioblastomas underwent spinal radiosurgery. Five patients had von Hipple-Lindau disease. Four patients had multiple tumors. Ten tumors were located in the thoracic spine, eight in the cervical spine, and two in the lumbar spine. Tumor volume varied from 0.08 to 14.4 cc (median 0.72 cc). Maximum tumor dimension varied from 2.5 to 24 mm (median 10.5 mm). Radiosurgery was performed with a dedicated 6 MV linear accelerator equipped with a micro-multileaf collimator. Median peripheral tumor dose and prescription isodose were 12 Gy and 90%, respectively. Image guidance was performed by optical tracking of infrared reflectors, fusion of oblique radiographs with dynamically reconstructed digital radiographs, and automatic patient positioning. Follow-up varied from 14 to 86 months (median 51 months). RESULTS: Kaplan-Meier estimated 4-year overall and solid tumor local control rates were 90% and 95%, respectively. One tumor progressed 12 months after treatment and a new cyst developed 10 months after treatment in another tumor. There has been no clinical or imaging evidence for spinal cord injury. CONCLUSIONS: Results of this limited experience indicate linear accelerator-based radiosurgery is safe and effective for spinal cord hemangioblastomas. Longer follow-up is necessary to confirm the durability of tumor control, but these initial results imply linear accelerator-based radiosurgery may represent a therapeutic alternative to surgery for selected patients with spinal hemangioblastomas.