Steep Dose Gradients Research Articles

Online daily adaptive proton therapy.

It is recognized that the use of a single plan calculated on an image acquired some time before the treatment is generally insufficient to accurately represent the daily dose to the target and to the organs at risk. This is particularly true for protons, due to the physical finite range. Although this characteristic enables the generation of steep dose gradients, which is essential for highly conformal radiotherapy, it also tightens the dependency of the delivered dose to the range accuracy. In particular, the use of an outdated patient anatomy is one of the most significant sources of range inaccuracy, thus affecting the quality of the planned dose distribution. A plan should be ideally adapted as soon as anatomical variations occur, ideally online. In this review, we describe in detail the different steps of the adaptive workflow and discuss the challenges and corresponding state-of-the art developments in particular for an online adaptive strategy.

Cost-effectiveness analysis (CEA) of IMRT plus C12 boost vs IMRT only in adenoid cystic carcinoma (ACC) of the head and neck

BackgroundParticle therapy provides steep dose gradients to facilitate dose escalation in challenging anatomical sites which has been shown not only to improve local control but also overall survival in patients with ACC. Cost-effectiveness of intensity-modulated radiotherapy (IMRT) plus carbon ion (C12) boost vs IMRT alone was performed in order to objectivise and substantiate more widespread use of this technology in ACC.MethodsPatients with pathologically confirmed ACC received a combination regimen of IMRT plus C12 boost. Patients presenting outside C12 treatment slots received IMRT only. Clinical results were published; economic analysis on patient-level data was carried out from a healthcare purchaser’s perspective based on costs of healthcare utilization. Cost histories were generated from resource use recorded in individual patient charts and adjusted for censoring using the Lin I method. Cost-effectiveness was measured as incremental cost-effectiveness ratio (ICER). Sensitivity analysis was performed regarding potentially differing management of recurrent disease.ResultsThe experimental treatment increased overall costs by € 18,076 (€13,416 – €22,922) at a mean survival benefit of 0.86 years. Despite improved local control, following costs were also increased in the experimental treatment. The ICER was estimated to 26,863 €/LY. After accounting for different management of recurrent disease in the two cohorts, the ICER was calculated to 20,638 €/LY.ConclusionThe combined treatment (IMRT+C12 boost) substantially increased initial and overall treatment cost. In view of limited treatment options in ACC, costs may be acceptable though. Investigations into quality of life measures may support further decisions in the future.

Inorganic scintillation detectors for 192Ir brachytherapy

Many brachytherapy (BT) errors could be detected with real-time in vivo dosimetry technology. Inorganic scintillation detectors (ISDs) have demonstrated promising capabilities for BT, because some ISD materials can generate scintillation signals large enough that (a) the background signal emitted in the fiber-optic cable (stem signal) is insignificant, and (b) small detector volumes can be used to avoid volume averaging effects in steep dose gradients near BT sources. We investigated the characteristics of five ISD materials to identify one that is appropriate for BT. ISDs consisting of a 0.26 to 1.0 mm3 volume of ruby (Al2O3:Cr), a mixture of Y2O3:Eu and YVO4:Eu, ZnSe:O, or CsI:Tl coupled to a fiber-optic cable were irradiated in a water-equivalent phantom using a high-dose-rate 192Ir BT source. Detectors based on plastic scintillators BCF-12 and BCF-60 (0.8 mm3 volume) were used as a reference. Measurements demonstrated that the ruby, Y2O3:Eu+YVO4:Eu, ZnSe:O, and CsI:Tl ISDs emitted scintillation signals that were up to 19, 19, 250, and 880 times greater, respectively, than that of the BCF-12 detector. While the total signals of the plastic scintillation detectors were dominated by the stem signal for source positions 0.5 cm from the fiber-optic cable and >3.5 cm from the scintillator volume, the stem signal for the ruby and Y2O3:Eu+YVO4:Eu ISDs were <1% of the total signal for source positions <3.4 and <4.4 cm from the scintillator, respectively, and <0.7% and <0.5% for the ZnSe:O and CsI:Tl ISDs, respectively, for positions ⩽8.0 cm. In contrast to the other ISDs, the Y2O3:Eu+YVO4:Eu ISD exhibited unstable scintillation and significant afterglow. All ISDs exhibited significant energy dependence, i.e. their dose response to distance-dependent 192Ir energy spectra differed significantly from the absorbed dose in water. Provided that energy dependence is accounted for, ZnSe:O ISDs are promising for use in error detection and patient safety monitoring during BT.

P2.17-21 A Post-Hoc Analysis of TROG 09.02 (CHISEL) Phase III Trial Investigating Pulmonary Function Changes After SABR and Conformal Radiation Therapy

The TROG 09.02 (CHISEL) trial compared conventional radiotherapy (CRT) administered over a period of four to six weeks with stereotactic ablative body radiotherapy (SABR).(1) Patients randomised to the SABR arm had superior freedom from local failure and longer overall survival.(1) The aim of this analysis was to assess differences in lung function and spirometry tests between SABR and CRT and describe longitudinal changes in respiratory function. We conducted a post-hoc analysis of all patients recruited to the CHISEL trial. During this trial patients underwent serial Respiratory Function Tests (RFT) including Forced Expiratory Volume in one second (FEV1), Diffusing capacity of the lungs for carbon monoxide (DLCO), Distance Walked in 6 minutes (SMWT) and Forced Vital Capacity (FVC). These were performed at baseline then 3-6 monthly post-treatment. Patients were assessed per treatment received. Linear regression models were used to compare FEV1, FVC and DLCO between SABR and CRT. Separate models at 3 and 12 months post-treatment were created to assess the two different processes impacting lung function post radiation therapy (acute pneumonitis and chronic fibrosis). Linear regression models were used to assess the association of baseline PFT Measures with decline in respiratory function at 3 and 12 months. Between December 2009 and June 2015, 101 patients were treated in 11 centres in Australia and New Zealand. 34 patients were treated with CRT and 63 with SABR. On regression analysis at 3 months there was no evidence of a difference between arms in the change from baseline in absolute values of FEV1 (beta 0.037, 95% CI [-0.063, 0.14], p=0.47), DLCO (beta -0.5, 95% CI [-1.4, 0.37], p=0.26) nor forced VC (beta 0.024, 95% CI [-0.17, 0.22], p=0.81). At 12 months there were no differences observed in change from baseline of FEV1 (beta0.031, 95% CI [-0.12, 0.18], p=0.69), DLCO (beta -0.43, 95% CI [-1.7, 0.84], p=0.51) nor forced VC (beta 0.047, 95% CI [-0.28, 0.18], p=0.69) between arms.There was no evidence of a difference in the change from baseline in SMWT (m) between two arms at 3 months (beta 35.9, 95% CI [-10, 82.3], p=0.13).Patients in both arms demonstrated similar deterioration in all RFT parameters with time. Despite the considerably higher biologically effective doses delivered to the tumour in SABR there was no difference in decline in respiratory function observed between the two groups. This is likely due to the higher integral dose, steep dose gradients and reduced margins possible with SABR relative to CRT.

Intrafractional motion in stereotactic body radiotherapy of spinal metastases utilizing cone beam computed tomography image guidance.

Spine stereotactic body radiotherapy (SBRT) requires a high degree of accuracy due to steep dose gradients close to the spinal cord. This study aimed to (1) evaluate intrafractional motion in spine SBRT utilizing flattening filter free (FFF) beam delivery and cone beam computed tomography (CBCT) image guidance and (2) evaluate if adding another CBCT acquisition and corrections prior to treatment improves the overall position accuracy. Intrafractional motion was retrospectively analyzed for 78 fractions in 54 patients. All patients were immobilized with an evacuated cushion. Before treatment, a CBCT was acquired, a bony fusion with the planning CT was performed and translational and rotational errors were corrected. For 30 of the patients (39 fractions) acquisition of another CBCT and corrections were performed before treatment. A post treatment CBCT was acquired for all patients, and translational and rotational errors measured by fusion of the post treatment CBCT with the planning CT were recorded to calculate means and standard deviations (SDs). The positional errors were significantly smaller in 4 out of 6 error values in the patient group treated with verification CBCT. In this group, translational and rotational SDs ranged from 0.5 to 0.6 mm and 0.3°, respectively. Corresponding values in the group treated without verification CBCT were 0.7-1.0 mm and 0.4-0.7°. With proper CBCT image guidance, patient immobilization and FFF-beam delivery, one can obtain very high patient position accuracy in spine SBRT. Inclusion of a verification CBCT prior to treatment increases the overall position accuracy.

Quantifying the Intra-fraction Treatment Variation in the Shift Off Bone in Fiducial-Based IG-SBRT for Pancreatic Adenocarcinoma

Given the proximity of the radio-sensitive bowel, stereotactic body radiotherapy (SBRT) for pancreatic cancer requires precise immobilization and target localization, which can allow for steeper dose gradients and tighter margins. Currently, however, wide variation exists in the selection of planning target volume (PTV) margins that should be used in this setting. As intra-fraction variation represents a primary component of an appropriate PTV margin, we present our experience with intra-fraction shifts required during pancreatic SBRT, which has not previously been characterized in the literature. We analyzed 30 consecutively patients treated with SBRT for pancreatic cancer at our institution using volumetric modulated arc therapy (VMAT), active breathing control (ABC), and image-guided (IG) cone-beam computed tomography (CBCT). Patients were initially aligned to bony landmarks and then shifted to fiducials that had been endoscopically-placed. Halfway through treatment, an intra-fraction CBCT was obtained. Using the pre-treatment and intra-fraction CBCT, with the spine as a reference point, we calculated the intra-fraction shift in each axis along with a three-dimensional (3D) vector shift. The mean, maximum, and standard deviation of the intra-fraction shift in each direction, including the 3D vector, were calculated for individual patients across the five fractions. Population averages and standard deviations of each of these metrics were also calculated. Additionally, a linear regression model was developed to understand if the pre-treatment shift from bone to fiducial was related to the intra-fraction shift. On average, the mean intra-fraction shifts in the L-R, A-P, and S-I directions were 1.91± 0.82 mm, 1.62 ± 0.70 mm, and 2.33 ± 1.45 mm, respectively, and the mean intra-fraction shift as a 3D vector was 4.06 ± 1.51 mm. On average, the maximum intra-fraction shifts in the L-R, A-P, and S-I directions were 4.41 ± 2.37 mm, 3.51 ± 1.68 mm and 5.22 ± 3.79 mm, and the maximum intra-fraction shift as a 3D vector was 7.46 ± 3.70 mm. The linear regression model identified a statistically significant relationship between the mean pre-treatment shift from bone to fiducial and the mean intra-fraction shift in the A-P (p = 0.003) and S-I (p = 0.004) directions, along with for the 3D vector (p = 0.019). We report a single-institutional experience with intra-fractions shifts for patients undergoing SBRT for pancreatic cancer. These values can better inform appropriate PTV margins. As an example, to ensure a 95% likelihood that the target is encompassed within the PTV throughout treatment, radial margins of roughly 3-3.5mm and an SI margin of roughly 5mm should be considered. However, more data across institutions and using different motion management strategies is required for more generalizable results.

Protonthérapie des carcinomes épidermoïdes des voies aérodigestives supérieures : de la physique à la clinique

Intensity-modulated radiation therapy (IMRT) is presently the recommended technique for the treatment of locally advanced head and neck carcinomas. Proton therapy would allow to reduce the volume of irradiated normal tissue and, thus, to decrease the risk of late dysphagia, xerostomia, dysgeusia and hypothyroidism. An exhaustive research was performed with the search engine PubMed by focusing on the papers about the physical difficulties that slow down use of proton therapy for head and neck carcinomas. Range uncertainties in proton therapy (±3 %) paradoxically limit the use of the steep dose gradient in distality. Calibration uncertainties can be important in the treatment of head and neck cancer in the presence of materials of uncertain stoichiometric composition (such as with metal implants, dental filling, etc.) and complex heterogeneities. Dental management for example may be different with IMRT or proton therapy. Some uncertainties can be somewhat minimized at the time of optimization. Inter- and intrafractional variations and uncertainties in Hounsfield units/stopping power can be integrated in a robust optimization process. Additional changes in patient's anatomy (tumour shrinkage, changes in skin folds in the beam patch, large weight loss or gain) require rescanning. Dosimetric and small clinical studies comparing photon and proton therapy have well shown the interest of proton therapy for head and neck cancers. Intensity-modulated proton therapy is a promising treatment as it can reduce the substantial toxicity burden of patients with head and neck squamous cell carcinoma compared to IMRT. Robust optimization will allow to perform an optimal treatment and to use proton therapy in current clinical practice.

Patient-specific quality assurance for proton depth dose distribution using a multi-layer ionization chamber in a single-ring wobbling method.

The use of a multi-layer ionization chamber, Zebra, in patient-specific quality assurance (QA) for proton depth dose distributions in a single-ring wobbling method is investigated. The depth dose distributions measured using Zebra are compared with those calculated using the treatment planning system (TPS), XiO-M, and measured using an ionization chamber with a motorized water phantom system. Because the TPS only provides point doses, the average doses are calculated using in-house software. The detector size-corrected depth dose distributions are obtained by determining the average of the dose distributions from the TPS over a cylindrical region similar to the size of the Zebra detectors. The calculated depth dose distributions from the cases with a simple compensator shape are in good agreement with those obtained from the TPS without performing volume averaging; however, a 15% difference was shown when compared with those from the cases with a complex compensator shape. Then, the measurements are compared with the detector size-corrected depth dose distributions, showing an improved agreement within 3% for the highly steep dose gradient regions. Although there are some field size limitations, the Zebra system is a useful device for the fast measurement of patient-specific QA for depth dose distributions in wobbled proton beams. However, careful consideration is required for complex dose distribution fields, because the measurements obtained using Zebra cannot be directly compared to the depth dose distributions from the TPS owing to the finite detector size of the Zebra chamber.

DOSIMETRIC INVESTIGATION OF RADIOTHERAPY OF SMALL SIZE TUMORS IN RADIOSURGERY DEVICES

In stereotactic radiotherapy, high radiation doses were delivered to tumors using small fields in 1-5 fractions. It is very important to make sure accuracy of dose and position of given dose in stereotactic radiotherapy. In this study, dosimetric measurements of small sized brain tumors irradiated in CONE- based linear accelator (linac) and the volumetric arc therapy (VMAT) linac modalities were performed with EBT3 film. 1,2 and 3 cm diameter tumors were virtually created in Cyberknife head and neck phantom. Gafchromic EBT3 film was placed into the phantom to evaluate the accuracy of the doses given. The phantom was irradiated with Gafchromic EBT3 film according to treatment plans created in the treatment planning system of two separate devices for each tumor size. Conformity Index (CI) and Homogeneity Index (HI) were calculated for the quality of created treatment plans. The dose distributions calculated in the film and the TPS were compared. When the CI and HI values were examined, the CI and HI values of the cone-based linac device were close to 1. The EBT3 measurement results indicate that all SRT treatment modalities achieved accurate doses. According to results, if a critical organ, such as the brainstem, is located near the tumor and the situation requires a steep dose gradient, the cone-based linac should be used for SRT therapy. This study has shown that on CONE-based linac or VMAT-based linac devices can be used instead of each other in small-area irradiations.

Fractionated Gamma Knife radiosurgery for skull base meningiomas: a single-institution experience

OBJECTIVEGamma Knife radiosurgery (GKRS) has been successfully used for the treatment of intracranial meningiomas given its steep dose gradients and high-dose conformality. However, treatment of skull base meningiomas (SBMs) may pose significant risk to adjacent radiation-sensitive structures such as the cranial nerves. Fractionated GKRS (fGKRS) may decrease this risk, but until recently it has not been practical with traditional pin-based systems. This study reports the authors' experience in treating SBMs with fGKRS, using a relocatable, noninvasive immobilization system.METHODSThe authors performed a retrospective review of all patients who underwent fGKRS for SBMs between 2013 and 2018 delivered using the Extend relocatable frame system or the Icon system. Patient demographics, pre- and post-GKRS tumor characteristics, perilesional edema, prior treatment details, and clinical symptoms were evaluated. Volumetric analysis of pre-GKRS, post-GKRS, and subsequent follow-up visits was performed.RESULTSTwenty-five patients met inclusion criteria. Nineteen patients were treated with the Icon system, and 6 patients were treated with the Extend system. The mean pre-fGKRS tumor volume was 7.62 cm3 (range 4.57-13.07 cm3). The median margin dose was 25 Gy delivered in 4 (8%) or 5 (92%) fractions. The median follow-up time was 12.4 months (range 4.7-17.4 months). Two patients (9%) experienced new-onset cranial neuropathy at the first follow-up. The mean postoperative tumor volume reduction was 15.9% with 6 patients (27%) experiencing improvement of cranial neuropathy at the first follow-up. Median first follow-up scans were obtained at 3.4 months (range 2.8-4.3 months). Three patients (12%) developed asymptomatic, mild perilesional edema by the first follow-up, which remained stable subsequently.CONCLUSIONSfGKRS with relocatable, noninvasive immobilization systems is well tolerated in patients with SBMs and demonstrated satisfactory tumor control as well as limited radiation toxicity. Future prospective studies with long-term follow-up and comparison to single-session GKRS or fractionated stereotactic radiotherapy are necessary to validate these findings and determine the efficacy of this approach in the management of SBMs.

Physiological motion of the optic chiasm and its impact on stereotactic radiosurgery dose.

Avoidance of radiation-induced optic neuropathy (RION) from stereotactic radiosurgery (SRS) requires precise anatomical localization; however, no prior studies have characterized the physiologic motion of the optic chiasm. We measured the extent of chiasm motion and its impact on SRS dose. In this cross-sectional study, serial MRI was performed in multiple planes in 11 human subjects without optic pathway abnormalities to determine chiasm motion across time. Subsequently, the measured displacement was applied to the hypothetical chiasm dose received in 11 patients treated with SRS to a perichiasmatic lesion. On sagittal images, the average anteroposterior chiasm displacement was 0.51 mm [95% confidence interval (CI) 0.27 - 0.75 mm], and the average superior-inferior displacement was 0.48 mm (95% CI 0.22 - 0.74 mm). On coronal images, the average superior-inferior displacement was 0.42 mm (95% CI 0.13 - 0.71 mm), and the average lateral displacement was 0.75 mm (95% CI 0.42 - 1.08 mm). In 11 patients who underwent SRS to a perichiasmatic lesion, the average displacements increased the maximum chiasm dose (Dmax) by a mean of 14 % (range 6-23 %; p < 0.001). Average motion of the optic chiasm was approximately 0.50-0.75 mm, which increased chiasm Dmax by a mean of 14%. In the occasional patient with higher-than-average chiasm motion in a region of steep dose gradient, the increase in chiasm Dmax and risk of RION could be even larger. Similarly, previously reported chiasm dose constraints may underestimate the true dose received during radiosurgery. To limit the risk of RION, clinicians may consider adding a 0.50-0.75 mm expansion to the chiasm avoidance structure.

Characterization of a novel 3D printed patient specific phantom for quality assurance in cranial stereotactic radiosurgery applications

In single-isocenter stereotactic radiosurgery/radiotherapy (SRS/SRT) intracranial applications, multiple targets are being treated concurrently, often involving non-coplanar arcs, small photon beams and steep dose gradients. In search for more rigorous quality assurance protocols, this work presents and evaluates a novel methodology for patient-specific pre-treatment plan verification, utilizing 3D printing technology.In a patient’s planning CT scan, the external contour and bone structures were segmented and 3D-printed using high-density bone-mimicking material. The resulting head phantom was filled with water while a film dosimetry insert was incorporated. Patient and phantom CT image series were fused and inspected for anatomical coherence. HUs and corresponding densities were compared in several anatomical regions within the head. Furthermore, the level of patient-to-phantom dosimetric equivalence was evaluated both computationally and experimentally. A single-isocenter multi-focal SRS treatment plan was prepared, while dose distributions were calculated on both CT image series, using identical calculation parameters. Phantom- and patient-derived dose distributions were compared in terms of isolines, DVHs, dose-volume metrics and 3D gamma index (GI) analysis. The phantom was treated as if the real patient and film measurements were compared against the patient-derived calculated dose distribution.Visual inspection of the fused CT images suggests excellent geometric similarity between phantom and patient, also confirmed using similarity indices. HUs and densities agreed within one standard deviation except for the skin (modeled as ‘bone’) and sinuses (water-filled). GI comparison between the calculated distributions resulted in passing rates better than 97% (1%/1 mm). DVHs and dose-volume metrics were also in satisfying agreement. In addition to serving as a feasibility proof-of-concept, experimental absolute film dosimetry verified the computational study results. GI passing rates were above 90%.Results of this work suggest that employing the presented methodology, patient-equivalent phantoms (except for the skin and sinuses areas) can be produced, enabling literally patient-specific pre-treatment plan verification in intracranial applications.

Spine SBRT With Halcyon™: Plan Quality, Modulation Complexity, Delivery Accuracy, and Speed.

Purpose: Spine SBRT requires treatment plans with steep dose gradients and tight limits to the cord maximal dose. A new dual-layer staggered 1-cm MLC in Halcyon™ treatment platform has improved leakage, speed, and DLG compared to 120-Millennium (0.5-cm) and High-Definition (0.25-cm) MLCs in the TrueBeam platform. Halcyon™ 2.0 with SX2 MLC modulates fluence with the upper and lower MLCs, while in Halcyon™ 1.0 with SX1 only the lower MLC modulates the fluence and the upper MLC functions as a back-up jaw. We investigated the effects of four MLC designs on plan quality for spine SBRT treatments.Methods: 15 patients previously treated at our institution were re-planned according to the NRG-BR-002 guidelines with a prescription of 3,000 cGy in 3 fractions, 6xFFF, 800 MU/min, and 3-arc VMAT technique. Planning objectives were adjusted manually by an experienced planner to generate optimal plans and kept the same for different MLCs within the same platform.Results: All treatment plans were able to achieve adequate target coverage while meeting NRG-BR002 dosimetric constraints. Planning parameters were evaluated including: conformity index, homogeneity index, gradient measure, and global point dose maximum. Delivery accuracy, modulation complexity, and delivery time were also analyzed for all MLCs.Conclusion: The Halcyon™ dual-layer MLC can generate comparable and clinically equivalent spine SBRT plans to TrueBeam plans with less rapid dose fall-off and lower conformity. MLC width leaf can impact maximum dose to organs at risk and plan quality, but does not cause limitations in achieving acceptable plans for spine SBRT treatments.

Management of vertebral radiotherapy dose in paediatric patients with cancer: consensus recommendations from the SIOPE radiotherapy working group.

Inhomogeneities in radiotherapy dose distributions covering the vertebrae in children can produce long-term spinal problems, including kyphosis, lordosis, scoliosis, and hypoplasia. In the published literature, many often interrelated variables have been reported to affect the extent of potential radiotherapy damage to the spine. Articles published in the 2D and 3D radiotherapy era instructed radiation oncologists to avoid dose inhomogeneity over growing vertebrae. However, in the present era of highly conformal radiotherapy, steep dose gradients over at-risk structures can be generated and thus less harm is caused to patients. In this report, paediatric radiation oncologists from leading centres in 11 European countries have produced recommendations on how to approach dose coverage for target volumes that are adjacent to vertebrae to minimise the risk of long-term spinal problems. Based on available information, it is advised that homogeneous vertebral radiotherapy doses should be delivered in children who have not yet finished the pubertal growth spurt. If dose fall-off within vertebrae cannot be avoided, acceptable dose gradients for different age groups are detailed here. Vertebral delineation should include all primary ossification centres and growth plates, and therefore include at least the vertebral body and arch. For partial spinal radiotherapy, the number of irradiated vertebrae should be restricted as much as achievable, particularly at the thoracic level in young children (<6 years old). There is a need for multicentre research on vertebral radiotherapy dose distributions for children, but until more valid data become available, these recommendations can provide a basis for daily practice for radiation oncologists who have patients that require vertebral radiotherapy.

Patterns of Failure Among Patients With Low-grade Glioma Treated With Proton Radiation Therapy

PurposeProton treatment may be a useful radiation therapy modality for long-term surviving patients with glioma to reduce normal tissue toxicities. Photon studies demonstrate that most low-grade glioma (LGG) failures occur within the radiation field, supporting the use of more conformal treatment plans, yet it is unclear whether this can be translated to proton radiation therapy (PRT). Our objective is to examine our institutional experience to determine patterns of failure in patients with LGG with respect to the volume irradiated with PRT. Methods and materialsPatients with World Health Organization 2007 grade I to II or isocitrate dehydrogenase 1–positive mutation grade III LGG treated with PRT between 2005 and 2015 were retrospectively reviewed. Patients with documented local recurrences on magnetic resonance imaging after receipt of PRT underwent a comparison with the initial treatment plan dosimetry to evaluate patterns of failure. A total of 141 patients were included in the final cohort. ResultsThe median follow-up time was 46.7 months (range, 2.8-144 months), and 5-year overall survival was 84%. The median PRT dose delivered was 54 Gy (relative biological effectiveness) (range, 45-60 Gy). There were 42 failures after PRT (30%). The median time to progression after treatment was 32.7 months (range, 4.8-93.6 months). Thirty-one patients (74%) failed in-field (defined as within the 95% isodose volume), 5 patients (12%) failed out-of-field, and 5 patients (12%) had marginal failures (defined as within the 50%-95% isodose volume). The 5-year freedom from progression after PRT was 60.1% (95% confidence interval, 48.7-70.0). The 5-year cumulative incidence of overall survival was 33% among those with recurrence after PRT and 96% among those without recurrence after PRT (P < .001). ConclusionsOf the patients with LGG who had documented failures after PRT, most recurred within the radiation field with few marginal failures, indicating that even with PRT, which often can have steeper dose gradients, coverage is adequate. Survival was poor for patients whose tumors recurred.

Compatibility of 3D printing materials and printing techniques with PAGAT gel dosimetry

Polymer gel (PG) dosimetry enables three dimensional (3D) measurement of complex dose distributions. However, PGs are strongly reactive with oxygen and other contaminations, limiting their applicability by the need to use specific container materials. We investigate different 3D printing materials and printing techniques for their compatibility with PG. Suitable 3D printing materials may provide the possibility to perform PG dosimetry in complex-shaped phantoms. 3D printed and PG-filled test vials were irradiated homogenously. The signal response was evaluated with respect to homogeneity and compared to the signal in already validated reference vials. In addition, for the printing material VeroClear™ (StrataSys, Eden Prairie, USA) different methods to remove support material, which was required during the printing process, were investigated. We found that the support material should be used only on the outer side of the container wall with no direct contact to the PG. With the VeroClear™ material a homogenous signal response was achieved with a mean deviation of relative to the reference vials. In addition, the homogeneous irradiation of an irregularly-shaped gel container designed with the same printing material and technique also lead to a homogenous PG response. Furthermore, a small field irradiation of an additional test-vial showed an accurate representation of steep dose gradients with a deviation of the maximum position of relative to the reference vial.

Stereotactic body radiotherapy for patients with non-small-cell lung cancer using RapidArc delivery and a steep dose gradient: prescription of 60% isodose line of maximum dose fitting to the planning target volume.

We retrospectively investigated outcomes, including pulmonary toxicities, of stereotactic body radiation therapy using RapidArc and a risk-adapted 60% isodose plan for early-stage non-small-cell lung cancer patients. We evaluated patients staged as cT1a–2bN0M0 between 2011 and 2017 and treated with a total dose of 40–60 Gy in five fractions to the 60% isodose line of the maximum dose encompassing the planning target volume with curative intent. Comorbidities and age were rated using an age-adjusted Charlson comorbidity index (AACCI). Factors associated with overall survival (OS) were investigated. A total of 237 patients with 250 lesions were eligible. The median follow-up was 28.0 months. The local recurrence rate at 3 years was 0.8%; none of the patients developed isolated local recurrence. OS, deaths from lung cancer, and deaths from intercurrent disease at 3 years were 72.7%, 8.2% and 19.1%, respectively. On multivariate analysis for correlating factors with OS, AACCI and maximal standardized uptake value on [18F]-fluorodeoxyglucose positron emission tomography/computed tomography remained significant. Grade ≥3 toxicities were limited to radiation pneumonitis in six (2.4%) patients (Grade 3 in four patients and Grade 5 in two patients). Among those, three patients had idiopathic interstitial pneumonia. The total dose was unrelated to the incidence of Grade ≥3 radiation pneumonitis (P = 0.69). Using the 60% isodose prescription and RapidArc, maximal local control was achieved with acceptable toxicities. Although the OS may depend on patient background, dose escalation aiming at higher local control can be beneficial for medically inoperable patients.

On the Instantaneous Dose Rate and Angular Dependence of Monolithic Silicon Array Detectors

The use of small radiation fields characterized by very steep dose gradients is common in modulated arc X-ray radiotherapy. Dosimeters for quality assurance (QA) applications would ideally have sensitive volumes (SVs) relatively small with respect to the field, along with negligible instantaneous dose rate and angular dependence. Silicon-based dosimeters can be fabricated with SVs $ across, provide a stable and near energy-independent response in megavoltage photon beams, along with a good linearity with accumulated dose and real-time readout. However, their sensitivity is instantaneous dose rate and angular dependent. Monolithic silicon array detectors with sufficiently small SVs and pitch are suitable for high-resolution 2-D dose mapping in radiation fields with steep dose gradients. The Octa is a 2-D monolithic silicon array detector. It has 512 diode- SVs arranged with a sub-millimeter pitch. The physical characteristics of the substrate on which it is based, in terms of resistivity and defects concentration, strongly affect its performance. We report on the experimental characterization of two versions of the Octa, manufactured on a bulk and on an epitaxial substrate, respectively. Their performance is compared and discussed in terms of their instantaneous dose rate and angular dependence in the context of QA applications in small radiation fields delivered with modulated arc radiotherapy.

An Experimental Slope Method for a More Accurate Measurement of Relative Radiation Doses using Radiographic and Radiochromic Films and Its Application to Megavoltage Small-Field Dosimetry.

Purpose:An experimental method using the linear portion of the relative film dose–response curve for radiographic and radiochromic films is presented, which can be used to determine the relative depth doses in a variety of very small, medium, and large radiation fields and relative output factors (ROFs) for small fields.Materials and Methods:The film slope (FS) method was successfully applied to obtain the percentage depth doses (PDDs) for external beams of photon and electrons from a Synergy linear accelerator (Elekta AB, Stockholm, Sweden) under reference conditions of 10 cm × 10 cm for photon beam and nominal 10 cm × 10 cm size applicator for electron beam. For small-field dosimetry, the FS method was applied to EDR2 films (Carestream Health, Rochester, NY) for 6 MV photon beam from a linac (Elekta AB, Stockholm, Sweden) and small, circular radiosurgery cones (Elekta AB, Stockholm, Sweden) with diameters of 5, 7.5, 10, 12.5, and 15 mm. The ROFs for all these cones and central axis PDDs for 5, 10, and 15 mm diameter cones were determined at source-to-surface distance of 100 cm. The ROFs for small fields of CyberKnife system were determined using this technique with Gafchromic EBT3 film (Ashland, NJ, USA). The PDDs and ROFs were compared with ion chamber (IC) and Monte Carlo (MC) simulated values.Results:The maximum percentage deviation of PDDFS with PDDIC for 4, 6, and 15 MV photon beams was within 1.9%, 2.5%, and 1.4%, respectively, up to 20-cm depth. The maximum percentage deviation of PDDFS with PDDIC for electron beams was within 3% for energy range studied of 8–15 MeV. The gamma passing rates of PDDFS with PDDIC were above 96.5% with maximum gamma value of >2, occurring at the zero depths for 4, 6, and 15 MV photons. For electron beams, the gamma passing rates between PDDFS with PDDIC were above 97.7% with a maximum gamma value of 0.9, 1.3, and 0.7 occurring at the zero depth for 8, 12, and 15 MeV. For small field of 5-mm cone, the ROFFS was 0.665 ± 0.021 as compared to 0.674 by MC method. The maximum percentage deviation between PDDFS and PDDMC was 3% for 5 mm and 10 mm and 2% for 15 mm cones with 1D gamma passing rates, respectively, of 95.5%, 96%, and 98%. For CyberKnife system, the ROFFS using EBT3 film and MC published values agrees within 0.2% for for 5 mm cone.Conclusions:The authors have developed a novel and more accurate method for the relative dosimetry of photon and electron beams. This offers a unique method to determine PDD and ROF with a high spatial resolution in fields of steep dose gradient, especially in small fields.

Intensity-modulated radiation therapy of anal squamous cell carcinoma: Relationship between delineation quality and regional recurrence

Background and purposeIntensity-modulated radiation therapy (IMRT) is currently indicated to treat anal squamous cell carcinoma (ASCC). Conformal dose delivery and steep dose gradients may cause marginal misses. We analyzed patterns of locoregional recurrences (LRR) and delineation quality to determine IMRT-specific predictive factors. Material and methodsLymph node area delineation was classified as “compliant” or “non-compliant” according to experts’ workgroup recommendations. The recurrence volume (Vrecur) was delineated on initial planning-CT by recurrence imaging registration. The Vrecur was determined to be “in-field” (IF), “marginal” (ML), or “out-of-field” (OF) in regard to the 95% isodose coverage. ResultsOut of 165 patients, 30 had LRR. Among the 27 local recurrences (LR), 20 (74%) were IF, 4 (15%) ML, and 2 (7%) OF. Fourteen patients had regional recurrence (RR), amounted to 33 separate recurrence sites (RS). RS were mostly localized in inguinal (n = 12;36,4%), external iliac (n = 7;21.1%), presacral (n = 4;12.1%) and common iliac (n = 3;9.1%) nodes. Eighteen (54.5%) RS were IF, 6 (18.2%) ML, and 9 (27.3%) OF. Performance status ≥2 (p = 0.007) and active smoking (p = 0.025) were predictors of LR. Immunodepression (p = 0.012), external iliac involvement (p < 0.001), and non-compliant delineation for ≥10 areas (p = 0.005) were predictors of RR. ConclusionsNew predictive factors for recurrences of ASSC treated with IMRT have been found, suggesting that the delineation accuracy is essential for regional control.