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ObjectivesThe 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 methodsAn 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/β 10] 36.4 Gy [α/β 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

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.

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.

BackgroundGlioblastoma 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.Methods11 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.ResultsThe 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) for all of the non-brain OARs. Both the 4πPTVPD and 4π GTV100GYplans reduced the mean normal brain mean doses.Conclusions4π 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.

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.

Abstract Background Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. Methods 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Results Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Conclusions Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs.