D. Alezra

Linear accelerator radiosurgery for vestibular schwannoma

OBJECT The use of radiosurgery in the treatment of acoustic neuromas has increased substantially during the last decade. Most published experience relates to the use of the gamma knife. In this report, the authors review the methods and results of linear accelerator (LINAC) radiosurgery in 44 patients with acoustic neuromas who were treated between 1993 and 1997. METHODS Computerized tomography scanning was selected as the stereotactic imaging modality for target definition. A single, conformally shaped isocenter was used in the treatment of 40 patients; two or three isocenters were used in four patients who harbored very irregular tumors. The radiation dose directed to the tumor border was the only parameter that changed during the study period: in the first 24 patients who were treated the dose was 15 to 20 Gy, whereas in the last 20 patients the dose was reduced to 11 to 14 Gy. After a mean follow-up period of 32 months (range 12-60 months), 98% of the tumors were controlled. The actuarial hearing preservation rate was 71%. New transient facial neuropathy developed in 24% of the patients and persisted to a mild degree in 8%. Radiation dose correlated significantly with the incidence of cranial neuropathy, particularly in large tumors (> or = 4 cm3). CONCLUSIONS Single-isocenter LINAC radiosurgery proved to be an effective treatment for acoustic neuromas in this series, with results that were comparable with those reported for gamma knife radiosurgery and multiple isocenters.

Linear accelerator radiosurgery for meningiomas in and around the cavernous sinus.

OBJECTIVE A retrospective study to evaluate the efficacy and side effects of linear accelerator radiosurgery in the treatment of cavernous sinus meningiomas. METHODS Between 1993 and 2001, 42 patients with meningiomas involving the cavernous sinus underwent linear accelerator radiosurgery at our institution. A mean radiation dose of 14 Gy was delivered to the tumor margin. The median tumor volume was 8.2 cm3 (mean, 8.4 cm3). Median follow-up was 36 months (mean, 38 mo). RESULTS Control of tumor growth was achieved in 97.5% of the patients. There was no mortality or permanent extraocular motor or pituitary dysfunction. Treatment-related complications included new trigeminal neuropathy in 4.7% and a new visual field defect in 2.8%. Two patients required shunt placement after developing hydrocephalus. One patient with symptomatic temporal lobe edema underwent partial excision of the tumor. Improvement of existing cranial neuropathies was noted in 29% of affected trigeminal nerves, in 22% of oculomotor nerves, and in 13% of Cranial Nerves IV and VI. CONCLUSION This study indicates that linear accelerator radiosurgery can achieve a high control rate of meningiomas involving the cavernous sinus with no mortality and a low incidence of morbidity.

Assessing the quality of conformal treatment planning : a new tool for quantitative comparison

We develop a novel radiotherapy plan comparison index, critical organ scoring index (COSI), which is a measure of both target coverage and critical organ overdose. COSI is defined as COSI=1-(V(OAR)>tol/TC), where V(OAR)>tol is the fraction of volume of organ at risk receiving more than tolerance dose, and TC is the target coverage, VT,PI/VT, where VT,PI is the target volume receiving at a least prescription dose and VT is the total target volume. COSI approaches unity when the critical structure is completely spared and the target coverage is unity. We propose a two-dimensional, graphical representation of COSI versus conformity index (CI), where CI is a measure of a normal tissue overdose. We show that this 2D representation is a reliable, visual quantitative tool for evaluating competing plans. We generate COSI-CI plots for three sites: head and neck, cavernous sinus, and pancreas, and evaluate competing non-coplanar 3D and IMRT treatment plans. For all three sites this novel 2D representation assisted the physician in choosing the optimal plan, both in terms of target coverage and in terms of critical organ sparing. We verified each choice by analysing individual DVHs and isodose lines. Comparing our results to the widely used conformation number, we found that in all cases where there were discrepancies in the choice of the best treatment plan, the COSI-CI choice was considered the correct one, in several cases indicating that a non-coplanar 3D plan was superior to the IMRT plans. The choice of plan was quick, simple and accurate using the new graphical representation.

A murine model for the study of molecular pathogenesis of radiation proctitis.

PURPOSE To establish a novel mouse brachytherapy model with which to study the role of inflammation in the pathogenesis of radiation proctitis. METHODS AND MATERIALS The distal rectums of BALB/c and C57BL/6 mice were irradiated with three to five fractions of 5.5 to 8 Gy. Tissues were harvested and evaluated for histopathology, using the radiation injury score (RIS). Cytokine mRNA expression was assessed using real-time PCR. RESULTS Fifty percent of the mice treated with 22 Gy delivered in four fractions of 5.5 Gy died as a result of anorectal stenosis and distal bowel obstruction prior to the time of scheduled sacrifice, with a latency period of 4 to 10 weeks for the BALB/c and 3 to 4 weeks for the C57BL/6 mice. The RISs were 7, 12, and 8 at 2, 6, and 11 weeks, respectively, in the BALB/c mice and was 8.7 in the C57BL/6 mice on week 6. A 100- to 300-fold increase in interleukin-1beta (IL-1beta) (p = 0.04) and IL-6 mRNA (p = 0.07) and a 5- to 6-fold increase in transforming growth factor (TGF) and tumor necrosis factor-alpha mRNA expression levels (p < 0.001 and p = 0.01) were observed at 2 to 6 weeks after radiation. Cytokine mRNA tissue expression correlated positively with radiation dose (p < 0.0001). The RIS correlated well with IL-1beta and IL-6 mRNA levels in the BALB/c mice and with IL-1beta, IL-6, and TGF mRNA levels in C57BL/6 mice. Analysis of receiver operating characteristic curve showed that IL-1beta and IL-6 have the largest area under the curve and therefore are good markers of radiation proctitis (p < 0.001). CONCLUSIONS Radiation-induced proctitis was associated with a dose-dependent, characteristic proinflammatory cytokine response pattern in a novel mouse model suitable for interventional studies.

Continuous Positive Airway Pressure for Motion Management in Stereotactic Body Radiation Therapy to the Lung: A Controlled Pilot Study.

OBJECTIVE To determine the effect of continuous positive airway pressure (CPAP) on tumor motion, lung volume, and dose to critical organs in patients receiving stereotactic body radiation therapy (SBRT) for lung tumors. METHODS AND MATERIALS After institutional review board approval in December 2013, patients with primary or secondary lung tumors referred for SBRT underwent 4-dimensional computed tomographic simulation twice: with free breathing and with CPAP. Tumor excursion was calculated by subtracting the vector of the greatest dimension of the gross tumor volume (GTV) from the internal target volume (ITV). Volumetric and dosimetric determinations were compared with the Wilcoxon signed-rank test. CPAP was used during treatment if judged beneficial. RESULTS CPAP was tolerated well in 10 of the 11 patients enrolled. Ten patients with 18 lesions were evaluated. The use of CPAP decreased tumor excursion by 0.5 ± 0.8 cm, 0.4 ± 0.7 cm, and 0.6 ± 0.8 cm in the superior-inferior, right-left, and anterior-posterior planes, respectively (P ≤ .02). Relative to free breathing, the mean ITV reduction was 27% (95% confidence interval [CI] 16%-39%, P<.001). CPAP significantly augmented lung volume, with a mean absolute increase of 915 ± 432 cm(3) and a relative increase of 32% (95% CI 21%-42%, P=.003), contributing to a 22% relative reduction (95% CI 13%-32%, P=.001) in mean lung dose. The use of CPAP was also associated with a relative reduction in mean heart dose by 29% (95% CI 23%-36%, P=.001). CONCLUSION In this pilot study, CPAP significantly reduced lung tumor motion compared with free breathing. The smaller ITV, the planning target volume (PTV), and the increase in total lung volume associated with CPAP contributed to a reduction in lung and heart dose. CPAP was well tolerated, reproducible, and simple to implement in the treatment room and should be evaluated further as a novel strategy for motion management in radiation therapy.

IMRT vs. 3D Noncoplanar Treatment Plans for Maxillary Sinus Tumors: A New Tool for Quantitative Evaluation

We compared 9-field, equispaced intensity modulated radiation therapy (IMRT), 4- to 5-field, directionally optimized IMRT, and 3-dimensional (3D) noncoplanar planning approaches for tumors of the maxillary sinus. Ten patients were planned retrospectively to compare the different treatment techniques. Prescription doses were 60 to 70 Gy. Critical structures contoured included optic nerves and chiasm, lacrimal glands, lenses, and retinas. As an aid for plan assessment, we introduced a new tool: Critical Organ Scoring Index (COSI), which allows quantitative evaluation of the tradeoffs between target coverage and critical organ sparing. This index was compared with other, commonly used conformity indices. For a reliable assessment of both tumor coverage and dose to critical organs in the different planning techniques, we introduced a 2D, graphical representation of COSI vs. conformity index (CI). Dose-volume histograms and mean, maximum, and minimum organ doses were also compared. IMRT plans delivered lower doses to ipsilateral structures, but were unable to spare them. 3D plans delivered less dose to contralateral structures, and were more homogeneous, as well. Both IMRT approaches gave similar results. In cases where choice of optimal plan was difficult, the novel 2D COSI-CI representation gave an accurate picture of the tradeoffs between target coverage and organ sparing, even in cases where other conformity indices failed. Due to their unique anatomy, maxillary sinus tumors may benefit more from a noncoplanar approach than from IMRT. The new graphical representation proposed is a quick, visual, reliable tool, which may facilitate the physicians choice of best treatment plan for a given patient.

Feasibility and low toxicity of early radiotherapy after high‐dose chemotherapy and autologous stem cell transplantation for patients with high‐risk Stage II–III and locally advanced breast carcinoma

This prospective trial examined the feasibility, toxicity, and effectiveness of early locoregional radiotherapy after high‐dose chemotherapy and autologous stem cell transplantation in patients with high‐risk American Joint Committee on Cancer (AJCC) Stage II–III and locally advanced breast carcinoma.

Spine radiosurgery: lessons learned from the first 100 treatment sessions.

OBJECTIVE Local therapy to spine tumors has been shown to be effective in selected cases. Spinal radiosurgery (SRS) is an evolving radiotherapy regimen allowing for noninvasive, highly efficacious local treatment. The learning curve can compromise the results of any newly employed technology and should be studied to minimize its effects. In this paper the first 100 SRSs performed at several medical centers are presented and analyzed for the effects of the learning curve on outcome. METHODS A retrospective analysis was undertaken to evaluate data from patients treated with SRS at Sheba Medical Center and Assuta Medical Centers in the period from September 2011 to February 2016. Medical history, clinical and neurological findings, pathological diagnoses, SRS variables, complications, and follow-up data were collected and analyzed. Local control rates were calculated, and local treatment failure cases were qualitatively studied. RESULTS One hundred treatment sessions were performed for 118 lesions at 179 spinal levels in 80 patients. The complication rate was low and did not correlate with a learning curve. Mean follow-up time was 302 days, and the overall local control rate was 95%. The local control rate was dose dependent and increased from 87% (among 35 patients receiving a dose of 16 Gy) to 97% (among 65 patients receiving a dose of 18 Gy). The 6 treatment failure cases are discussed in detail. CONCLUSIONS Spinal radiosurgery is a safe and effective treatment. Comprehensive education of the treating team and continuous communication are essential to limit the effects of the learning curve on outcome.

SU‐FF‐J‐48: Localization Accuracy of a Gantry‐Mounted Radioactive Tracking System in the Clinical Radiation Therapy Environment

Purpose: The submillimeter accuracy of a novel gantry‐mounted radioactive fiducial tracking system has been reported previously in a number of semi‐clinical scenarios. These have included tissue equivalent phantoms without bones, and antomical phantoms including bones, but with measurements being made from a single gantry angle that does not include potential interference from the bones and the patient couch and potential tracking system alignment inaccuracy due to gantry and collimator rotation. In this study the gantry‐mounted tracking system is tested in a more realistic clinical scenario. This study used an anatomical phantom with bones placed at multiple positions about the isocenter and made localization measurements with the gantry and collimator at various angles. Method and Materials: The tracking device was installed on a Varian Trilogy® linac gantry. The radioactive marker was located at the approximate position of the prostate in an anatomical tissue equivalent phantom on the patient couch. Actual marker location was measured using a Microscribe MLX coordinate measuring machine (CMM) arm (certified spatial accuracy of 0.08 mm). The marker was attached to the tip of the CMM arm, which was inserted into a hole in the phantom, and its location was measured simultaneously by the CMM and the tracking system. 102 localization accuracy measurements were made at locations covering a 10cm diameter sphere centered at the linac iso‐center with varying gantry and collimator angles including those that would potentially induce interference due to bones and the patient couch. Results: The mean localization error for all measured positions and gantry and collimator angles was less than 1mm. Conclusion: The gantry‐mounted radioactive tracking system maintains sufficient accuracy for radiation therapy patient localization and monitoring in a real clinical environment even in the presence of bones and patient couch interference. Conflict of Interest: Research sponsored by Navotek Medical Ltd.

A Retrospective Feasibility Study of Salvage Pelvic Nodal Radiation in 6 Patients With Biochemical Failure Following Prostate Fossa Radiation: An Alternative to Androgen Deprivation Therapy (ADT).

Purpose:To evaluate salvage pelvic nodal radiation as an alternative to androgen deprivation therapy (ADT) in patients with biochemical failure and lymph node recurrence following salvage prostate fossa radiation. Methods:Six patients with biochemical failure and lymph node recurrence following prostate fossa radiation were treated with salvage pelvic nodal radiation therapy. A gross target volume was contoured using Choline PET/CT, CT, or MRI imaging. The clinical target volume included pelvic nodes. Avoidance structures were created using isodose lines from previous prostate fossa radiation plans. Radiation was delivered using IMRT or VMAT techniques. Failure was defined as a confirmed rise of prostate-specific antigen (PSA) over 0.2 ng/mL. Results:Four patients had presalvage PSA values <1 and 2 patients had PSAs >1. Dose to the clinical target volume was 54 to 60 Gy. The gross target volume dose was 60 to 73.6 Gy. One of the 2 patients with a high PSA received 6 months of concomitant ADT. Mean follow-up after RT for all patients was 24.9 months (range, 18.1 to 33.0 mo). All 5 patients with no ADT had significant PSA responses. PSA reduction was 80% (62% to 100%) of pre-RT PSA. At last follow-up, 2 patients with initial PSA<1 ng/mL remain free of biochemical progression at 33 and 20 months. Four patients have had PSA rise and meet criteria for failure. This included both patients with initial PSA values > 1. Duration of response before failure was 18.1 to 30.7 months. ADT for failure has been started in 1 patient. There was no grade ≥2 GI or GU toxicity. Conclusions:Salvage lymph node irradiation for patients with early biochemical recurrence and radiologic evidence of pelvic nodal metastases is well tolerated and associated with a durable biochemical response and may be an alternative to or may delay the need for ADT in some patients.