Hypofractionated Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost and Simultaneous Integrated Protection in Pancreatic Ductal Adenocarcinoma.

AIMS: To evaluate the safety and feasibility of stereotactic body radiation therapy (SBRT) with simultaneous integrated boost (SIB) and simultaneous integrated protection (SIP) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma. MATERIALS AND METHODS: Patients receiving SBRT following induction chemotherapy from January 2017 to December 2018 were included in this observational analysis. SBRT was delivered in five consecutive daily fractions by administering 30 Gy to the planning target volume while simultaneously delivering a 50 Gy SIB to the tumour-vessel interface. SIP was created by lowering the dose to 25 Gy on the overlap area between the planning target volume and the planning organ at risk volume. The primary end point was acute and late gastrointestinal grade ≥3 toxicity. Secondary end points were freedom from local progression, overall survival and progression-free survival (PFS). RESULTS: Fifty-nine consecutive patients (27 borderline resectable and 32 locally advanced) were included. Fifty-eight patients (98.3%) completed the SBRT planned treatment and 35 patients (59.4%) received surgical resection following SBRT. No acute or late grade ≥3 SBRT-related adverse events were observed. The median follow-up time was 15.1 months in the overall cohort and 18.1 months in censored patients. One- and 2-year freedom from local progression rates were 85% and 80% versus 79.7% and 60.6% in resected and unresected patients, respectively (P = 0.33). The median overall survival and PFS were 30.2 months and 19 months from diagnosis and 19.1 months and 10.7 months from SBRT in the entire cohort. Resected patients had improved 2-year overall survival rates (72.5% versus 49%, P = 0.012) and median PFS (13 months versus 5 months; P < 0.001) relative to unresected patients. There was no survival difference between borderline resectable and locally advanced patients. CONCLUSIONS: SBRT with SIB/SIP had an excellent toxicity profile and could be administered safely on pancreatic ductal adenocarcinoma patients, even in a total neoadjuvant setting.

An Adaptive Thresholding Method for BTV Estimation Incorporating PET Reconstruction Parameters: A Multicenter Study of the Robustness and the Reliability.

OBJECTIVE: The aim of this work was to assess robustness and reliability of an adaptive thresholding algorithm for the biological target volume estimation incorporating reconstruction parameters. METHOD: In a multicenter study, a phantom with spheres of different diameters (6.5-57.4 mm) was filled with (18)F-FDG at different target-to-background ratios (TBR: 2.5-70) and scanned for different acquisition periods (2-5 min). Image reconstruction algorithms were used varying number of iterations and postreconstruction transaxial smoothing. Optimal thresholds (TS) for volume estimation were determined as percentage of the maximum intensity in the cross section area of the spheres. Multiple regression techniques were used to identify relevant predictors of TS. RESULTS: The goodness of the model fit was high (R(2): 0.74-0.92). TBR was the most significant predictor of TS. For all scanners, except the Gemini scanners, FWHM was an independent predictor of TS. Significant differences were observed between scanners of different models, but not between different scanners of the same model. The shrinkage on cross validation was small and indicative of excellent reliability of model estimation. CONCLUSIONS: Incorporation of postreconstruction filtering FWHM in an adaptive thresholding algorithm for the BTV estimation allows obtaining a robust and reliable method to be applied to a variety of different scanners, without scanner-specific individual calibration.

SU-E-J-168: 4D-PET for Target Volume Delineation in Respiratory-Gated Radiation Therapy.

PURPOSE: To find an optimized workflow for the use of respiratory-gated PET (4D-PET) in target volume delineation of tumors subject to respiratory-gated radiation therapy. METHODS: 15 patients with lung (11) and pancreas (4) tumors who had FDG-PET-CT for target delineation prior to EBRT were studied. Patients were selected among the group that showed respiratory-induced tumor motion 〉5mm. 4D-PET was performed by means of a Philips Gemini BigBore scanner, using the Varian RPM gating system. An identical system was available at the linac for treatment. The breathing cycle was equally divided in 4 phases, according to a previous study. Since planning was made on a single CT-phase, no ITV was explicitly built from the set of phases. The BTV was identified with SUV=2.2 threshold and the PTV was obtained expanding the BTV by 8mm(S-I), 5mm(A-P) and 3mm(L-R) to account for residual motion and setup errors. The most advantageous CT-phase for treatment planning was then identified by simulating plans on each phase and analyzing the resulting DVHs of OARs (lung, trachea, oesophagus, spinal cord, left ventricle). RESULTS: The observed maximum range of motion was 5.5mm(L-R), 12.3mm(A-P) and 19.2mm(S-I). The standard deviation of the BTV volume in the 4 phases ranged from 6% to 13.7%. V20 (lung) ranged 7.1%-15.2% in inspiration and 7.8%-18.6% in expiration. The mean dose to the oesophagus ranged 0.1-2.2Gy in inspiration and 1.4-2.0Gy in expiration. In general, the dose to OARs was smaller when planning on a single phase than on the overall, respiratory-uncontrolled volume (p-value〈0.05). CONCLUSIONS: The BTV volume was almost constant between phases, confirming that the motion might be described by 4 phases. There was no obvious choice of the optimal phase for treatment planning, suggesting patient-by-patient studies. However, planning and delivery on one phase consistently allowed dose sparing to be obtained compared to non-gated techniques.

Use of motion tracking in stereotactic body radiotherapy: Evaluation of uncertainty in off-target dose distribution and optimization strategies.

Spatial accuracy in extracranial radiosurgery is affected by organ motion. Motion tracking systems may be able to avoid PTV enlargement while preserving treatment times, however special attention is needed when fiducial markers are used to identify the target can move with respect to organs at risk (OARs). Ten patients treated by means of the Synchrony system were taken into account. Sparing of irradiated volume and of complication probability were estimated by calculating treatment plans with a motion tracking system (Cyberknife Synchrony, Sunnyvale, CA, USA) and a PTV-enlargement strategy for ten patients. Six patients were also evaluated for possible inaccuracy of estimation of dose to OARs due to relative movement between PTV and OAR during respiration. Dose volume histograms (DVH) and Equivalent Uniform Dose (EUD) were calculated for the organs at risk. In the cases for which the target moved closer to the OAR (three cases of six), a small but significant increase was detected in the DVH and EUD of the OAR. In three other cases no significant variation was detected. Mean reduction in PTV volume was 38% for liver cases, 44% for lung cases and 8.5% for pancreas cases. NTCP for liver reduced from 23.1 to 14.5% on average, for lung it reduced from 2.5 to 0.1% on average. Significant uncertainty may arise from the use of a motion-tracking device in determination of dose to organs at risk due to the relative motion between PTV and OAR. However, it is possible to limit this uncertainty. The breathing phase in which the OAR is closer to the PTV should be selected for planning. A full understanding of the dose distribution would only be possible by means of a complete 4D-CT representation.

CT-3D rotational angiography automatic registration: a sensitivity analysis.

Preprocessing, binning and dataset subsampling are investigated with regard to simultaneous maximisation of the speed, accuracy and robustness of CT-3D rotational angiography (3DRA) registration. Clinical diagnosis and treatment can both take advantage of this integration, because 3DRA allows the shape of vessel structures to be evaluated three-dimensionally with respect to standard 2D projective angiography. The method for optimising preprocessing, binning and subsampling consisted of independent variation of the corresponding parameters to maximise robustness and speed while maintaining subvoxel accuracy; the latter was computed as the sum of the mean squared errors initially present in the registrations with the errors relative to both binning and subsampling. The results suggest the choice of 256 bins, steps between 14 mm (coarse optimisation) and 2.5 mm (fine optimisation) and bone segmentation by threshold, for binning, subsampling and preprocessing, respectively. The application of this parameter set-up to 50 CT-3DRA registrations resulted in a saving, on average, of 40% of the time with respect to the method previously used, while registration error was maintained within 2 mm (1.97 mm, 90% confidence interval) and robustness was increased, so that no manual initial realignment was needed in 48 registrations. Validation by the registration of images acquired for a head phantom showed subvoxel residual errors. In conclusion, the proposed procedure can be considered a satisfactory strategy to optimise CT-3DRA registration.

Preliminary study on the use of nonrigid registration for thoraco-abdominal radiosurgery.

The inclusion of organ deformation and movement in radiosurgery treatment planning is of increasing importance as research and clinical applications begin to take into consideration the effects of physiological processes, like breathing, on the shape and position of lesions. In this scenario, the challenge is to localize the target in toto (not only by means of marker sampling) and to calculate the dose distribution as the sum of all the contributions from the positions assumed by the target during the respiratory cycle. The aim of this work is to investigate the use of nonrigid registration for target tracking and dynamic treatment planning, i.e., treatment planning based not on one single CT scan but on multiple CT scans representative of the respiration. Twenty patients were CT scanned at end-inhale and end-exhale. An expert radiation oncologist identified the PTV in both examinations. The two CT data sets per patient were nonrigidly registered using a free-form deformation algorithm based on B-splines. The optimized objective function consisted of a weighted sum of a similarity criterion (Mutual Information) and a regularization factor which constrains the transformation to be locally rigid. Once the transformation was obtained and the registration validated, its parameters were applied to the target only. Finally, the deformed target was compared to the PTV delineated by the radiation oncologist in the other study. The results of this procedure show an agreement between the center of mass as well as volume of the target identified automatically by deformable registration and manually by the radiation oncologist. Moreover, obtained displacements were in agreement with body structure constraints and considerations usually accepted in radiation therapy practice. No significant influence of initial target volume on displacements was found. In conclusion, the proposed method seems to offer the possibility of using nonrigid registrations in radiosurgery treatment planning, even if more cases need to be investigated in order to give a statistical consistency to parameter setup and proposed considerations.

Interstitial radiosurgery with the photon radiosurgery system in the minimally-invasive treatment of selected deep-seated brain tumors.

The purpose of this study was to evaluate the results of interstitial radiosurgery (IR) with Photon Radiosurgery System (PRS) in 18 patients (P) with deep-seated brain primary or secondary tumors. Follow-up varied from 2 to 53 months (mean, 13.6 mo). Seven P with glioblastomas died due to tumor progression. Five P with metastases died for systemic disease while local control was achieved in all. Six P with low-grade astrocytomas were well and imaging showed tumor control. We conclude that PRS IR is effective in the treatment of metastases while it provides lower benefit in malignant gliomas. It could play a major role in low-grade astrocytomas.

Employ of a new device for intra-operative radiotherapy of intracranial tumours.

BACKGROUND: This paper presents the operating experience acquired during 18 months of use of the Photon Radiosurgery System manufactured by Photo-electron Corp. as an intra-operative radiation therapy device. The device is based on a miniature x-ray source that delivers low energy x-rays from the tip of a 3.2 mm thick needle-like probe. The interstitial stereotactic employ of the source has already been reported, while there is no evidence of the open-field intra-operative use in the literature. METHOD: Open field intra-operative radiation therapy (IORT) is possible inserting the probe into spherical applicators with diameters ranging from 1.5 to 5 cm. The applicators are made to fit the surgical cavity in order to provide uniform distance between the x-ray source and the tumour bed. Delivery of the prescribed dose takes typically 10 to 45 minutes. Radiation characteristics of the source were measured by means of ionization chambers and radiochromic films positioned in a water phantom. Operating procedures aimed at quality assurance and radiation safety were developed. IORT was administered to 14 patients affected by malignant intracranial tumours. Doses from 10 to 15 Gy at 5 mm depth from the tumour bed were delivered after tumour removal. FINDINGS: This preliminary experience does not afford any clinical evidence of IORT efficacy for intracranial lesions: it permits one however to state the feasibility and safety of the procedure. INTERPRETATION: This system could favour a rapid and significant increase of the experience of intra-operative irradiation in the treatment of CNS tumours. A role in the treatment of extracranial neoplasms can be also foreseen but needs to be more extensively investigated.

Photon dose calculation of a three-dimensional treatment planning system compared to the Monte Carlo code BEAM.

The purpose of this work is to compare the photon dose calculation of a commercially available three-dimensional (3D) treatment planning system based on the collapsed cone convolution technique against BEAM, a Monte Carlo code that allows detailed simulation of a radiotherapy accelerator. The first part of the work is devoted to the commissioning of BEAM for a 6 MV photon beam and to the optimization of the linac description to fit the experimental data. This step also involves a comparison with radiochromic film data on an inhomogeneous phantom built to simulate electronic nonequilibrium conditions. Commissioning the selected photon beams required a careful description of the treatment head and the fine tuning of physical parameters such as electron beam energy and radius. The second part shows the dose comparison for real patient's CT data sets: A mediastinal treatment and a breast treatment were simulated. Doses in terms of absolute values per monitor unit were calculated based on the BEAM simulation of the CT data sets. For comparisons of real-patient cases, differences between the treatment planning system and BEAM ranged from 0 to 2.6% and were within +/-2 standard deviations for the dose calculated at the prescription point. Dose-volume histogram analysis indicated that there is no consistent difference between the Monte Carlo and the convolution calculations. On the basis of the results presented in this study, we can conclude that the CCC algorithm is capable of giving results absolutely comparable to those of a Monte Carlo calculation, as far as common 3D radiotherapy planning is concerned.

A simple method to verify in vivo the accuracy of target coordinates in linear accelerator radiosurgery.

PURPOSE: A simple method that verifies the coincidence of the isocenter with the center of the target volume in radiosurgery treatment conditions is described. The accuracy is compared to that of accepted computerized procedures employing fiducial markers. METHODS AND MATERIALS: The center of the beam is identified by a cylindrical localizer, fixed to the plate of the supplemental collimator, with a 2 x 50 mm tungsten rod coincident with the beam axis and is projected onto the x-ray portal verification films. Prior to irradiation, the coordinates of the intersection of the beams axes, which is in a known spatial relationship with the isocenter, are read directly on portal x-ray films and their coincidence with the coordinates set during patient positioning, is checked. RESULTS: The mean displacement in AP, Lat, and Vert coordinates respectively, over 84 patients, between the coordinates calculated by the computerized procedure employing fiducial markers and the coordinates calculated by using the rulers was 0.3 +/- 0.4 mm. CONCLUSIONS: From the results obtained with the two methods we can conclude that rulers method can be used as a fast indirect control of the position of the radiation isocenter. Moreover, the dimensions of the radiation field and the correct alignment of the tertiary circular collimator can be also documented.

Use of a new type of radiochromic film, a new parallel-plate micro-chamber, MOSFETs, and TLD 800 microcubes in the dosimetry of small beams.

The dosimetry of the fields usually employed in radiosurgery requires the use of small detectors to measure Total Scatter Factor (Sc,p), Tissue Maximum Ratio (TMR), Percentage Depth Dose (PDD), and Off Axis Ratio (OAR). In this paper new dosimeters are investigated: a new type of radiochromic film, a micro parallel-plate chamber (filled with both air and tetramethylsilane, TMS), MOSFETs, and TLD-800 microcubes. Their behavior has been compared with the response of radiographic film and with the values obtained with BEAM Monte Carlo simulation. The experimental data confirm that dosimetry with radiochromic films and TLDs gives consistent results for all beam diameters. The parallel-plate micro chamber underestimates the Sc,p for the smallest field diameters (4.4 mm and 6.7 mm); MOSFETs show an over-estimation for the Sc,p of the 4.4 mm, 6.7 mm, and 10.5 mm field diameters. BEAM Monte Carlo simulation employing a parallel beam and a standard 6 MV x-ray spectrum has been used to obtain a correction factor as a function of the field size for both the parallel-plate micro chamber and MOSFETs. High accuracy measurements of PDD and TMR have been made in a water phantom both with radiochromic film and with the micro parallel-plate chamber and have been compared with the data computed by BEAM Monte Carlo simulation. The latter dosimeter is preferred because of the quicker and simpler use and because it gives immediate readout. Measurements of OAR made with radiochromic films and with radiographic films give differences in the 80%-20% penumbra width within 0.6 mm for field diameters ranging from 4.4 mm to 19 mm.