Small Target Volumes Research Articles

Dosimetric impact of the low-dose envelope of scanned proton beams at a ProBeam facility: comparison of measurements with TPS and MC calculations

Due to the low-dose envelope of scanned proton beams, the dose output depends on the size of the irradiated field or volume. While this field size dependence has already been extensively investigated by measurements and Monte Carlo (MC) simulations for single pencil beams or monoenergetic fields, reports on the relevance of this effect for analytical dose calculation models are limited. Previous studies on this topic only exist for specific beamline designs. However, the amount of large-angle scattered primary and long-range secondary particles and thus the relevance of the low-dose envelope can considerably be influenced by the particular design of the treatment nozzle.In this work, we therefore addressed the field size dependence of the dose output at the commercially available ProBeam® beamline, which is being built in several facilities worldwide. We compared treatment planning dose calculations with ionization chamber (IC) measurements and MC simulations, using an experimentally validated FLUKA MC model of the scanning beamline. To this aim, monoenergetic square fields of three energies, as well as spherical target volumes were studied, including the investigation on the influence of the lateral spot spacing on the field size dependence. For the spherical target volumes, MC as well as analytical dose calculation were found in excellent agreement with the measurements in the center of the spread-out Bragg peak. In the plateau region, the treatment planning system (TPS) tended to overestimate the dose compared to MC calculations and IC measurements by up to almost 5% for the smallest investigated sphere and for small monoenergetic square fields. Narrower spot spacing slightly enhanced the field size dependence of the dose output. The deviations in the plateau dose were found to go in the clinically safe direction, i.e. the actual deposited dose outside the target was found to be lower than predicted by the TPS. Thus, the moderate overestimation of dose to normal tissue by the TPS is likely to result in no severe consequences in clinical cases, even for the most critical cases of small target volumes.

Stereotactic radiosurgery (SRS) in high-grade glioma: judicious selection of small target volumes improves results.

We present a retrospective review of 55 Stereotactic Radiosurgery (SRS) procedures performed in 47 consecutive patients with high-grade glioma (HGG). Thirty-three (70.2%) patients were diagnosed with glioblastoma and 14 (29.8%) with grade III glioma. The indications for SRS were small (up to 30 mm in diameter) locally progressing lesions in 32/47 (68%) or new distant lesions in 15/47 (32%) patients. The median target volume was 2.2 cc (0.2-9.5 cc) and the median prescription dose was 18 Gy (14-24 Gy). Three patients (5.5% incidence in 55 treatments) developed radiation necrosis. In eight cases (17%) patients received a second salvage SRS treatment to nine new lesions detected during follow-up. In 22/55 SRS treatments (40.0%) patients received concurrent chemo- or biological therapy, including temozolamide (TMZ) (15 patients), bevacizumab (BVZ) (6 patients) and carboplatin in one patient. Median time to progression after SRS was 5.0 months (1.0-96.4). Median survival time after SRS was 15.9 months (2.3-109.3) overall median survival (since diagnosis) was 37.4 months (9.6-193.6 months). Long-lasting responses (>12 months) after SRS were observed in 25/46 (54.3%) patients. We compared a matched (histology, age, KPS) cohort of patients with recurrent HGG treated with BVZ alone with the current study group. Median survival was significantly longer for SRS treated patients compared to the BVZ only cohort (12.6 vs. 7.3 months, p = 0.0102). SRS may be considered an effective salvage procedure for selected patients with small volume, recurrent high-grade gliomas. Long-term radiological control was observed in more than 50% of the patients.

Magnetically Focused Proton Irradiation of Small Volume Targets

Magnetically Focused Proton Irradiation of Small Volume Targets

Effects on Scattered Radiation Through Flattening Filter Free (FFF) IMRT at 6 and 10 MV Beam Energy

Removal of the flattening-filter (FFF) in IMRT decreases matter in the therapeutic beam that contributes to formation of scattered radiation (SR). By this means, it is possible to reduce contamination with ionizing radiation distant from the treated volume. It is yet unclear, what effect various beam energies have on SR in fully modulated FFF-IMRT plans with identical dose distributions. We used a LINAC with 160-leaf MLC to irradiate IMRT plans with almost identical dose distributions and for each beam energy identical therapeutic efficacy for 6 and 10MV with and without flattening filter. Plan a) Emulation of large volume pelvic RT for lymphatic metastasized prostate cancer, single dose 2 Gy. Plan b) small volume plan to prostate/seminal vesicles, single dose 2 Gy. Plan c) Intensely modulated small volume plan to prostate/seminal vesicles with integrated prostate-boost, single doses 2.25/3 Gy. All plans were applied to a RW3-slate phantom. SR was measured with semiflex chamber and a reference- dosimeter in 40 cm distance cranial to the isocenter. With both energies, 6 and 10MV respectively, FFF-IMRT resulted in significantly reduced SR in comparison to conventional IMRT (FF-IMRT). The reduction was more prominent with 10MV FFF-IMRT than with 6MV FFF-IMRT. Comparing energies, FF-IMRT with 10MV led to more SR in comparison to 6MV FF-IMRT. In contrast, with FFF-IMRT less SR was measured with plans A) and B) when 10MV was used in comparison to 6MV, but not with plan C). FFF-IMRT removes effectively a relevant scatter body from the therapeutic beam. Small target volumes (with integrated boost volumes) require more intensive modulation, therefore leading to increased interaction of photons with the MLC. This omits the SR-saving effect of FFF-IMRT. Because of different depth dose curves, more monitor units (MU) are used for comparable efficacy between 6 and 10MV. This leads to more SR with 6MV in comparison to 10MV in lesser modulated FFF-IMRT. Again, this effect is obscured in small target volumes with several doses levels due to more MLC-modulation.

Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation

This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5–30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo® TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus® chamber. An EBT3® film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification.

A treatment planning study to assess the feasibility of laser-driven proton therapy using a compact gantry design.

Laser-driven proton acceleration is suggested as a cost- and space-efficient alternative for future radiation therapy centers, although the properties of these beams are fairly different compared to conventionally accelerated proton beams. The laser-driven proton beam is extremely pulsed containing a very high proton number within ultrashort bunches at low bunch repetition rates of few Hz and the energy spectrum of the protons per bunch is very broad. Moreover, these laser accelerated bunches are subject to shot-to-shot fluctuations. Therefore, the aim of this study was to investigate the feasibility of a compact gantry design for laser-driven proton therapy and to determine limitations to comply with. Based on a published gantry beam line design which can filter parabolic spectra from an exponentially decaying broad initial spectrum, a treatment planning study was performed on real patient data sets. All potential parabolic spectra were fed into a treatment planning system and numerous spot scanning proton plans were calculated. To investigate limitations in the fluence per bunch, the proton number of the initial spectrum and the beam width at patient entrance were varied. A scenario where only integer shots are delivered as well as an intensity modulation from shot to shot was studied. The resulting plans were evaluated depending on their dosimetric quality and in terms of required treatment time. In addition, the influence of random shot-to-shot fluctuations on the plan quality was analyzed. The study showed that clinically relevant dose distributions can be produced with the system under investigation even with integer shots. For small target volumes receiving high doses per fraction, the initial proton number per bunch must remain between 1.4 × 10(8) and 8.3 × 10(9) to achieve acceptable delivery times as well as plan qualities. For larger target volumes and standard doses per fraction, the initial proton number is even more restricted to stay between 1.4 × 10(9) and 2.9 × 10(9). The lowest delivery time that could be reached for such a case was 16 min for a 10 Hz system. When modulating the intensity from shot to shot, the delivery time can be reduced to 6 min for this scenario. Since the shot-to-shot fluctuations are of random nature, a compensation effect can be observed, especially for higher laser shot numbers. Therefore, a fluctuation of ± 30% within the proton number does not translate into a dosimetric deviation of the same size. However, for plans with short delivery times these fluctuations cannot cancel out sufficiently, even for ± 10% fluctuations. Under the analyzed terms, it is feasible to achieve clinically relevant dose distributions with laser-driven proton beams. However, to keep the delivery times of the proton plans comparable to conventional proton plans for typical target volumes, a device is required which can modulate the bunch intensity from shot to shot. From the laser acceleration point of view, the proton number per bunch must be kept under control as well as the reproducibility of the bunches.

Clinical outcome of image-guided adaptive radiotherapy in the treatment of lung cancer patients

ABSTRACTBackground. Adaptive strategy with daily online tumour match is a treatment option when treating locally advanced lung cancer patients with curative intended radiotherapy (RT).Material and methods. Fifty-two consecutive lung cancer patients treated with soft tissue match, adaptive RT and small planning target volumes (PTV) margins were analysed. A control group of 52 consecutive patients treated with bone match, no adaptive strategy and larger margins was included. Patients were followed with computed tomography (CT) scans every third month. CT-images showing loco-regional recurrences were identified. The recurrence gross tumour volume was delineated and registered with the original radiation treatment plan to identify site of failure. All patients were toxicity-scored using CTCAE 4.03 grading scale. Data were analysed using the Kaplan-Meier analysis.Results. The median follow-up time was 16 months (3–35). Within a year, 35% of the patients in the adaptive group (ART-group) and 53% in the control group (No-ART-group) experienced loco-regional failure, showing improved loco-regional control in the ART group (p = 0.05). One patient in the ART-group and four patients in the No-ART-group showed marginal failure. Median overall progression-free survival time for the ART-group was 10 months (95% CI 8–12), and 8 months (95% CI 6–9) for the No-ART-group. Severe pneumonitis (grade 3–5) decreased from 22% in the No-ART-group to 18% in the ART-group (non-significant, p = 0.6). No significant difference in severe dysphagia was found between the two groups.Conclusion. In the first small cohort of patients investigated, implementation of soft-tissue tumour match and adaptive strategies for locally advanced lung cancer patients increased the loco-regional control rate without increasing treatment-related toxicity.

SU‐E‐T‐374: Evaluation and Verification of Dose Calculation Accuracy with Different Dose Grid Sizes for Intracranial Stereotactic Radiosurgery

Purpose:In this study, we aim to evaluate the effect of dose grid size on the accuracy of calculated dose for small lesions in intracranial stereotactic radiosurgery (SRS), and to verify dose calculation accuracy with radiochromic film dosimetry.Methods:15 intracranial lesions from previous SRS patients were retrospectively selected for this study. The planning target volume (PTV) ranged from 0.17 to 2.3 cm3. A commercial treatment planning system was used to generate SRS plans using the volumetric modulated arc therapy (VMAT) technique using two arc fields. Two convolution‐superposition‐based dose calculation algorithms (Anisotropic Analytical Algorithm and Acuros XB algorithm) were used to calculate volume dose distribution with dose grid size ranging from 1 mm to 3 mm with 0.5 mm step size. First, while the plan monitor units (MU) were kept constant, PTV dose variations were analyzed. Second, with 95% of the PTV covered by the prescription dose, variations of the plan MUs as a function of dose grid size were analyzed. Radiochomic films were used to compare the delivered dose and profile with the calculated dose distribution with different dose grid sizes.Results:The dose to the PTV, in terms of the mean dose, maximum, and minimum dose, showed steady decrease with increasing dose grid size using both algorithms. With 95% of the PTV covered by the prescription dose, the total MU increased with increasing dose grid size in most of the plans. Radiochromic film measurements showed better agreement with dose distributions calculated with 1‐mm dose grid size.Conclusion:Dose grid size has significant impact on calculated dose distribution in intracranial SRS treatment planning with small target volumes. Using the default dose grid size could lead to under‐estimation of delivered dose. A small dose grid size should be used to ensure calculation accuracy and agreement with QA measurements.

Image-Guided Radiotherapy Using a Modified Industrial Micro-CT for Preclinical Applications.

Purpose/ObjectiveAlthough radiotherapy is a key component of cancer treatment, its implementation into pre-clinical in vivo models with relatively small target volumes is frequently omitted either due to technical complexity or expected side effects hampering long-term observational studies. We here demonstrate how an affordable industrial micro-CT can be converted into a small animal IGRT device at very low costs. We also demonstrate the proof of principle for the case of partial brain irradiation of mice carrying orthotopic glioblastoma implants.Methods/MaterialsA commercially available micro-CT originally designed for non-destructive material analysis was used. It consists of a CNC manipulator, a transmission X-ray tube (10–160 kV) and a flat-panel detector, which was used together with custom-made steel collimators (1–5 mm aperture size). For radiation field characterization, an ionization chamber, water-equivalent slab phantoms and radiochromic films were used. A treatment planning tool was implemented using a C++ application. For proof of principle, NOD/SCID/γc−/− mice were orthotopically implanted with U87MG high-grade glioma cells and irradiated using the novel setup.ResultsThe overall symmetry of the radiation field at 150 kV was 1.04±0.02%. The flatness was 4.99±0.63% and the penumbra widths were between 0.14 mm and 0.51 mm. The full width at half maximum (FWHM) ranged from 1.97 to 9.99 mm depending on the collimator aperture size. The dose depth curve along the central axis followed a typical shape of keV photons. Dose rates measured were 10.7 mGy/s in 1 mm and 7.6 mGy/s in 5 mm depth (5 mm collimator aperture size). Treatment of mice with a single dose of 10 Gy was tolerated well and resulted in central tumor necrosis consistent with therapeutic efficacy.ConclusionA conventional industrial micro-CT can be easily modified to allow effective small animal IGRT even of critical target volumes such as the brain.

Areas of high 18F-FDG uptake on preradiotherapy PET/CT identify preferential sites of local relapse after chemoradiotherapy for non-small cell lung cancer.

The high rates of failure in the radiotherapy target volume suggest that patients with stage II or III non-small cell lung cancer (NSCLC) should receive an increased total dose of radiotherapy. Areas of high (18)F-FDG uptake on preradiotherapy (18)F-FDG PET/CT have been reported to identify intratumor subvolumes at high risk of relapse after radiotherapy. We wanted to confirm these observations on a cohort of patients included in 3 sequential prospective studies. Our aim was to assess an appropriate threshold (percentage of maximum standardized uptake value [SUVmax]) to delineate subvolumes on staging (18)F-FDG PET/CT scans assuming that a smaller target volume would facilitate isotoxic radiotherapy dose escalation. Thirty-nine patients with inoperable stage II or III NSCLC, treated with chemoradiation or with radiotherapy alone, were extracted from 3 prospective studies (ClinicalTrials.gov identifiers NCT01261585, NCT01261598, and RECF0645). All patients underwent (18)F-FDG PET/CT at initial staging, before radiotherapy, during radiotherapy, and during systematic follow-up in a single institution. All (18)F-FDG PET/CT acquisitions were coregistered on the initial scan. Various subvolumes in the initial acquisition (30%, 40%, 50%, 60%, 70%, 80%, and 90% SUVmax thresholds) and in the 3 subsequent acquisitions (40% and 90% SUVmax thresholds) were pasted on the initial scan and compared. Seventeen patients had a local relapse. The SUVmax measured during radiotherapy was significantly higher in locally relapsed tumors than in locally controlled tumors (mean, 6.8 vs. 4.6; P = 0.02). The subvolumes delineated on initial PET/CT scans with 70%-90% SUVmax thresholds were in good agreement with the recurrent volume at a 40% SUVmax threshold (common volume/baseline volume, 0.60-0.80). The subvolumes delineated on initial PET/CT scans with 30%-60% SUVmax thresholds were in good to excellent agreement with the core volume of the relapse (90% SUVmax threshold) (common volume/recurrent volume and overlap fraction indices, 0.60-0.93). The agreement was moderate (>0.51) when a 70% SUVmax threshold was used to delineate on initial PET/CT scans. High (18)F-FDG uptake areas on pretreatment PET/CT scans identify tumor subvolumes at greater risk of relapse in patients with NSCLC treated by concomitant chemoradiation. We propose a 70% SUVmax threshold to delineate areas of high (18)F-FDG uptake on initial PET/CT scans as the target volumes for potential radiotherapy dose escalation.

Multifunctional gold nanorods for selective plasmonic photothermal therapy in pancreatic cancer cells using ultra-short pulse near-infrared laser irradiation.

Gold nanorods (AuNRs) have attracted considerable attention in plasmonic photothermal therapy for cancer treatment by exploiting their selective and localized heating effect due to their unique photophysical properties. Here we describe a strategy to design a novel multifunctional platform based on AuNRs to: (i) specifically target the adenocarcinoma MUC-1 marker through the use of the EPPT-1 peptide, (ii) enhance cellular uptake through a myristoylated polyarginine peptide (MPAP) and (iii) selectively induce cell death by ultra-short near infrared laser pulses. We used a biotin-avidin based approach to conjugate EPPT-1 and MPAP to AuNRs. Dual-peptide (EPPT-1+MPAP) labelled AuNRs showed a significantly higher uptake by pancreatic ductal adenocarcinoma cells when compared to their single peptide or avidin conjugated counterparts. In addition, we selectively induced cell death by ultra-short near infrared laser pulses in small target volumes (∼1 μm3), through the creation of plasmonic nanobubbles that lead to the destruction of a local cell environment. Our approach opens new avenues for conjugation of multiple ligands on AuNRs targeting cancer cells and tumors and it is relevant for plasmonic photothermal therapy.

Neuro-Oncology Practice: Time Flies When You Are Having Fun!

Neuro-Oncology Practice: Time Flies When You Are Having Fun!

Cancer imaging in the era of precision treatment: present and future

Cancer imaging in the era of precision treatment: present and future

Simultaneous Integrated Boost (SIB) for Advanced Head and Neck (H&N) Cancer May Accelerate Muscle Loss in Concurrent Chemoradiation as Assessed by a Validated CT-Based Tool

transverse, coronal and sagittal plane. In a patient with ACC of the parotid gland, thickening of the facial nerve was observed, suggestive for perineural growth. Conclusions: For HN RT, T2-FFE provides an excellent high resolution imaging technique for lymph node and cranial nerve localization. This technique with endogenous T2 and diffusion contrast performs better than conventional T1w MRI and DW-MRI. Therefore, it allows delineation of verified fields for elective radiation treatment of lymph nodes and cranial nerves. This might result in smaller target volumes and sparing of normal tissues. Author Disclosure: M. Philippens: None. J.J. Bluemink: None. H. Dehnad: None. J.J.M. Zwanenburg: None. C.H.J. Terhaard: None.

Sci-Fri PM: Dosimetry - 03: Delta4 diode absolute dose response for large and small target volume IMRT QA

The goal of this project was to quantify the over-response/under-response of the Delta4 diodes for Helical Tomotherapy plans on extreme target volume sizes. A custom Delta4 phantom quarter with a hole to insert an ionisation chamber (IC) close to the center of the phantom have been used to acquire simultaneous IC and diodes absolute dose measurements. Eight plans for different target volumes were created from 20cm to 1cm diameter. Diodes dose measurements in the target were compared with IC measurement, to quantify absolute dose accuracy. IC measurements show a good agreement with planned dose (±2%). Diode measurements demonstrate a good agreement with IC for regular target size of 5 and 10cm (0 to 1%). For larger targets, an over-response is observed for FW 25mm and 10mm (2 to 3%). for small target of 1cm diameter, a major under-response is observed for FW 25mm and 10mm (−8 and −36%). The over-response could to be due to the extra amount of scattered radiation and the opposite for under-response. Although this scatter hypothesis still has to be proven, early testing demonstrates an over-response of 40%/20% of the central diodes compare to IC when an open helical rotational beam is delivered 75mm/25mm away frommore » the center of the phantom. These results are in agreement with the real patient Delta4 DQA results at our center.« less

Treating patients with real-time tumor tracking using the Vero gimbaled linac system: Implementation and first review

PurposeTo report on the first clinical application of a real-time tumor tracking (RTTT) solution based on the Vero SBRT gimbaled linac system for treatment of moving tumors. Methods and materialsA first group of 10 SBRT patients diagnosed with NSCLC or oligometastatic disease in lung or liver was treated with the RTTT technique. The PTV volumes and OAR exposure were benchmarked against the widely used ITV approach. Based on data acquired during execution of RTTT treatments, a first review was performed of the process. ResultsThe 35% PTV volume reduction with RTTT of the studied single lesions SBRT irradiations of small target volumes is expected to result in a small (<1%) reduction of lung or liver NTCP. A GTV–PTV margin of 5.0mm was applied for treatment planning of RTTT. From patient data on residual geometric uncertainties, a CTV–PTV margin of 3.2mm was calculated. Reduction of the GTV–PTV margin below 5.0mm without better understanding of biological definition of tumor boundaries was discouraged. Total treatment times were reduced to 34.4min on average. ConclusionA considerable PTV volume reduction was achieved applying RTTT and time efficiency for respiratory correlated SBRT was reestablished with Vero RTTT.

TH‐A‐BRF‐05: MRI of Individual Lymph Nodes to Guide Regional Breast Radiotherapy

Purpose:In regional radiotherapy (RT) for breast‐cancer patients, direct visualization of individual lymph nodes (LNs) may reduce target volumes and Result in lower toxicity (i.e. reduced radiation pneumonitis, arm edema, arm morbidity), relative to standard CT‐based delineations. To this end, newly designed magnetic resonance imaging (MRI) sequences were optimized and assessed qualitatively and quantitatively.Methods:In ten healthy female volunteers, a scanning protocol was developed and optimized. Coronal images were acquired in supine RT position positioned on a wedge board on a 1.5 T Ingenia (Philips) wide‐bore MRI. In four volunteers the optimized MRI protocol was applied, including a 3‐dimensional (3D) T1‐weighted (T1w) fast‐field‐echo (FFE). T2w sequences, including 3D FFE, 3D and 2D fast spin echo (FSE), and diffusion‐weighted single‐shot echo‐planar imaging (DWI) were also performed. Several fatsuppression techniques were used. Qualitative evaluation parameters included LN contrast, motion susceptibility, visibility of anatomical structures, and fat suppression. The number of visible axillary and supraclavicular LNs was also determined.Results:T1 FFE, insensitive to motion, lacked contrast of LNs, which often blended in with soft tissue and blood. T2 FFE showed high contrast, but some LNs were obscured due to motion. Both 2D and 3D FSE were motion‐insensitive having high contrast, although some blood remained visible. 2D FSE showed more anatomical details, while in 3D FSE, some blurring occurred. DWI showed high LN contrast, but suffered from geometric distortions and low resolution. Fat suppression by mDixon was the most reliable in regions with magnetic‐field inhomogeneities. The FSE sequences showed the highest sensitivity for LN detection.Conclusion:MRI of regional LNs was achieved in volunteers. The FSE techniques were robust and the most sensitive. Our optimized MRI sequences can facilitate direct delineation of individual LNs. This can Result in smaller target volumes and reduced toxicity in regional RT compared to standard CT planning.

WE‐D‐17A‐04: Magnetically Focused Proton Irradiation of Small Volume Targets

Purpose:To explore the advantages of magnetic focusing for small volume proton irradiations and the potential clinical benefits for radiosurgery targets. The primary goal is to create narrow elongated proton beams of elliptical cross section with superior dose delivery characteristics compared to current delivery modalities (eg, collimated beams). In addition, more general beam shapes are also under investigation.Methods:Two prototype magnets consisting of 24 segments of samarium‐cobalt (Sm2Co17) permanent magnetic material adhered into hollow cylinders were manufactured for testing. A single focusing magnet was placed on a positioning track on our Gantry 1 treatment table and 15 mm diameter proton beams with energies and modulation relevant to clinical radiosurgery applications (127 to 186 MeV, and 0 to 30 mm modulation) were delivered to a terminal water tank. Beam dose distributions were measured using a PTW diode detector and Gafchromic EBT2 film. Longitudinal and transverse dose profiles were analyzed and compared to data from Monte Carlo simulations analogous to the experimental setup.Results:The narrow elongated focused beam spots showed high elliptical symmetry indicating high magnet quality. In addition, when compared to unfocused beams, peak‐to‐entrance depth dose ratios were 11 to 14% larger (depending on presence or extent of modulation), and minor axis penumbras were 11 to 20% smaller (again depending on modulation) for focused beams. These results suggest that the use of rare earth magnet assemblies is practical and could improve dose‐sparing of normal tissue and organs at risk while delivering enhanced dose to small proton radiosurgery targets.Conclusion:Quadrapole rare earth magnetic assemblies are a promising and inexpensive method to counteract particle out scatter that tends to degrade the peak to entrance performance of small field proton beams. Knowledge gained from current experiments will inform the design of a prototype treatment nozzle that incorporates similar focusing magnets.This project was sponsored in part by funding from the Department of Defense (DOD# W81XWH‐BAA‐10‐1).

Single-Fraction Proton Beam Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations

To evaluate the obliteration rate and potential adverse effects of single-fraction proton beam stereotactic radiosurgery (PSRS) in patients with cerebral arteriovenous malformations (AVMs). From 1991 to 2010, 248 consecutive patients with 254 cerebral AVMs received single-fraction PSRS at our institution. The median AVM nidus volume was 3.5 cc (range, 0.1-28.1 cc), 23% of AVMs were in critical/deep locations (basal ganglia, thalamus, or brainstem), and the most common prescription dose was 15 Gy(relative biological effectiveness [RBE]). Univariable and multivariable analyses were performed to assess factors associated with obliteration and hemorrhage. At a median follow-up time of 35 months (range, 6-198 months), 64.6% of AVMs were obliterated. The median time to total obliteration was 31 months (range, 6-127 months), and the 5-year and 10-year cumulative incidence of total obliteration was 70% and 91%, respectively. On univariable analysis, smaller target volume (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.86-0.93, P<.0001), smaller treatment volume (HR 0.93, 95% CI 0.90-0.96, P<.0001), higher prescription dose (HR 1.16, 95% CI 1.07-1.26, P=.001), and higher maximum dose (HR 1.14, 95% CI 1.05-1.23, P=.002) were associated with total obliteration. Deep/critical location was also associated with decreased likelihood of obliteration (HR 0.68, 95% CI 0.47-0.98, P=.04). On multivariable analysis, critical location (adjusted HR [AHR] 0.42, 95% CI 0.27-0.65, P<.001) and smaller target volume (AHR 0.81, 95% CI 0.68-0.97, P=.02) remained associated with total obliteration. Posttreatment hemorrhage occurred in 13 cases (5-year cumulative incidence of 7%), all among patients with less than total obliteration, and 3 of these events were fatal. The most common complication was seizure, controlled with medications, both acutely (8%) and in the long term (9.1%). The current series is the largest modern series of PSRS for cerebral AVMs. PSRS can achieve a high obliteration rate with minimal morbidity. Post-treatment hemorrhage remains a potentially fatal risk among patients who have not yet responded to treatment.

Role of Radiation Therapy for Non-small Cell Lung Cancer: Focused on Stereotactic Ablative Radiation Therapy in Stage I

Radiation therapy has played a key role, together with surgery and systemic chemotherapy, in treating in all stages of non-small cell lung cancer. We have witnessed remarkable improvements in radiation therapy techniques, with the innovations in hardware and software. Stereotactic ablative radiation therapy, which can deliver high radiation dose focused to small target volume, represents one of the state-of-the-art radiation therapy techniques. The technical development of radiation therapy and the role of stereotactic ablative radiation therapy in treating inoperable stage I non-small cell lung cancer are briefly reviewed.