Multileaf collimator characterization and modeling for a 1.5 T MR-linac using static synchronous and asynchronous sweeping gaps.

Objective.The Elekta unity MR-linac delivers step-and-shoot intensity modulated radiotherapy plans using a multileaf collimator (MLC) based on the Agility MLC used on conventional Elekta linacs. Currently, details of the physical Unity MLC and the computational model within its treatment planning system (TPS)Monacoare lacking in published literature. Recently, a novel approach to characterize the physical properties of MLCs was introduced using dynamic synchronous and asynchronous sweeping gap (aSG) tests. Our objective was to develop a step-and-shoot version of the dynamic aSG test to characterize the Unity MLC and the computational MLC models in theMonacoandRayStationTPSs.Approach.Dynamic aSG were discretized into a step-and-shoot aSG by investigating the number of segments/sweep and the minimal number of monitor units (MU) per segment. The step-and-shoot aSG tests were compared to the dynamic aSG tests on a conventional linac at a source-to-detector distance of 143.5 cm, mimicking the Unity configuration. the step-and-shoot aSG tests were used to characterize the Unity MLC through measurements and dose calculations in both TPSs.Main results.The step-and-shoot aSGs tests with 100 segments and 5 MU/segment gave results very similar to the dynamic aSG experiments. The effective tongue-and-groove width of the Unity gradually increased up to 1.4 cm from the leaf tip end. The MLC models inRayStationandMonacoagreed with experimental data within 2.0% and 10%, respectively. The largest discrepancies inMonacowere found for aSG tests with >10 mm leaf interdigitation, which are non-typical for clinical plans.Significance.The step-and-shoot aSG tests accurately characterize the MLC in step-and-shoot delivery mode. The MLC model inRayStation2023B accurately describes the tongue-and-groove and leaf tip effects whereasMonacooverestimates the tongue-and-groove shadowing further away from the leaf tip end.

Characterization of the on-board megavoltage imager in a magnetic resonance-guided radiotherapy machine for beam output checks.

We characterized the on-board megavoltage imager (MVI) of a magnetic resonance-guided radiotherapy machine for beam output checks. Linearity and repeatability of its dose response were investigated. Alignment relative to the beam under clinical circumstances was evaluated for a year using daily measurements. Linearity and short-term repeatability were excellent. Long-term repeatability drifted 0.8 % per year, which can be overcome by monthly cross calibrations. Long-term alignment was stable. Thus, the MVI has suitable characteristics for beam output checks.

Advances in radiotherapy and its impact on second primary cancer risk: A multi-center cohort study in prostate cancer patients.

BACKGROUND: Modelling studies suggest that advanced intensity-modulated radiotherapy may increase second primary cancer (SPC) risks, due to increased radiation exposure of tissues located outside the treatment fields. In the current study we investigated the association between SPC risks and characteristics of applied external beam radiotherapy (EBRT) protocols for localized prostate cancer (PCa). METHODS: We collected EBRT protocol characteristics (2000-2016) from five Dutch RT institutes for the 3D-CRT and advanced EBRT era (N = 7908). From the Netherlands Cancer Registry we obtained patient/tumour characteristics, SPC data, and survival information. Standardized incidence ratios (SIR) were calculated for pelvis and non-pelvis SPC. Nationwide SIRs were calculated as a reference, using calendar period as a proxy to label 3D-CRT/advanced EBRT. RESULTS: From 2000-2006, 3D-CRT with 68-78 Gy in 2 Gy fractions, delivered with 10-23 MV and weekly portal imaging was the most dominant protocol. By the year 2010 all institutes routinely used advanced EBRT (IMRT, VMAT, tomotherapy), mainly delivering 78 Gy in 2 Gy fractions, using various kV/MV imaging protocols. Sixteen percent (N = 1268) developed ≥ 1 SPC. SIRs for pelvis and non-pelvis SPC (all institutes, advanced EBRT vs 3D-CRT) were 1.17 (1.00-1.36) vs 1.39 (1.21-1.59), and 1.01 (0.89-1.07) vs 1.03 (0.94-1.13), respectively. Nationwide non-pelvis SIR was 1.07 (1.01-1.13) vs 1.02 (0.98-1.07). Other RT protocol characteristics did not correlate with SPC endpoints. CONCLUSION: None of the studied RT characteristics of advanced EBRT was associated with increased out-of-field SPC risks. With constantly evolving EBRT protocols, evaluation of associated SPC risks remains important.

Impact of Advanced Radiotherapy on Second Primary Cancer Risk in Prostate Cancer Survivors: A Nationwide Cohort Study.

PURPOSE: External Beam Radiotherapy (EBRT) techniques dramatically changed over the years. This may have affected the risk of radiation-induced second primary cancers (SPC), due to increased irradiated low dose volumes and scatter radiation. We investigated whether patterns of SPC after EBRT have changed over the years in prostate cancer (PCa) survivors. MATERIALS AND METHODS: PCa survivors diagnosed between 1990-2014 were selected from the Netherlands Cancer Registry. Patients treated with EBRT were divided in three time periods, representing 2-dimensional Radiotherapy (RT), 3-dimensional conformal RT (3D-CRT), and the advanced RT (AdvRT) era. Standardized incidence ratios (SIR) and absolute excess risks (AER) were calculated to estimate relative and excess absolute SPC risks. Sub-hazard ratios (sHRs) were calculated to compare SPC rates between the EBRT and prostatectomy cohort. SPCs were categorized by subsite and anatomic region. RESULTS: PCa survivors who received EBRT had an increased risk of developing a solid SPC (SIR=1.08; 1.05-1.11), especially in patients aged <70 years (SIR=1.13; 1.09-1.16). Pelvic SPC risks were increased (SIR=1.28; 1.23-1.34), with no obvious differences between the three EBRT eras. Non-pelvic SPC were only significantly increased in the AdvRT era (SIR=1.08; 1.02-1.14), in particular for the 1-5 year follow-up period. Comparing the EBRT cohort to the prostatectomy cohort, again an increased pelvic SPC risk was found for all EBRT periods (sHRs= 1.61, 1.47-1.76). Increased non-pelvic SPC risks were present for all RT eras and highest for the AdvRT period (sHRs=1.17, 1.06-1.29). CONCLUSION: SPC risk in patients with EBRT is increased and remained throughout the different EBRT eras. The risk of developing a SPC outside the pelvic area changed unfavorably in the AdvRT era. Prolonged follow-up is needed to confirm this observation. Whether this is associated with increased irradiated low-dose volumes and scatter, or other changes in clinical EBRT practice, is the subject of further research.

Photons or protons for reirradiation in (non-)small cell lung cancer: Results of the multicentric ROCOCO in silico study.

OBJECTIVE: Locally recurrent disease is of increasing concern in (non-)small cell lung cancer [(N)SCLC] patients. Local reirradiation with photons or particles may be of benefit to these patients. In this multicentre in silico trial performed within the Radiation Oncology Collaborative Comparison (ROCOCO) consortium, the doses to the target volumes and organs at risk (OARs) were compared when using several photon and proton techniques in patients with recurrent localised lung cancer scheduled to undergo reirradiation. METHODS: 24 consecutive patients with a second primary (N)SCLC or recurrent disease after curative-intent, standard fractionated radio(chemo)therapy were included in this study. The target volumes and OARs were centrally contoured and distributed to the participating ROCOCO sites. Remaining doses to the OARs were calculated on an individual patient's basis. Treatment planning was performed by the participating site using the clinical treatment planning system and associated beam characteristics. RESULTS: Treatment plans for all modalities (five photon and two proton plans per patient) were available for 22 patients (N = 154 plans). 3D-conformal photon therapy and double-scattered proton therapy delivered significantly lower doses to the target volumes. The highly conformal techniques, i.e., intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), CyberKnife, TomoTherapy and intensity-modulated proton therapy (IMPT), reached the highest doses in the target volumes. Of these, IMPT was able to statistically significantly decrease the radiation doses to the OARs. CONCLUSION: Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. They, however, significantly differ in the dose deposited in the OARs. The therapeutic options, i.e., reirradiation or systemic therapy, need to be carefully weighed and discussed with the patients. ADVANCES IN KNOWLEDGE: Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. In light of the abilities of the various highly conformal techniques to spare specific OARs, the therapeutic options need to be carefully weighed and patients included in the decision-making process.

Intensity-modulated proton therapy decreases dose to organs at risk in low-grade glioma patients: results of a multicentric in silico ROCOCO trial.

BACKGROUND AND PURPOSE: Patients with low-grade glioma (LGG) have a prolonged survival expectancy due to better discriminative tumor classification and multimodal treatment. Consequently, long-term treatment toxicity gains importance. Contemporary radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), tomotherapy (TOMO) and intensity-modulated proton therapy (IMPT) enable high-dose irradiation of the target but they differ regarding delivered dose to organs at risk (OARs). The aim of this comparative in silico study was to determine these dosimetric differences in delivered doses. MATERIAL AND METHODS: Imaging datasets of 25 LGG patients having undergone postoperative radiotherapy were included. For each of these patients, in silico treatment plans to a total dose of 50.4 Gy to the target volume were generated for the four treatment modalities investigated (i.e., IMRT, VMAT, TOMO, IMPT). Resulting treatment plans were analyzed regarding dose to target and surrounding OARs comparing IMRT, TOMO and IMPT to VMAT. RESULTS: In total, 100 treatment plans (four per patient) were analyzed. Compared to VMAT, the IMPT mean dose (Dmean) for nine out of 10 (90%) OARs was statistically significantly (p < .02) reduced, for TOMO this was true in 3/10 (30%) patients and for 1/10 (10%) patients for IMRT. IMPT was the prime modality reducing dose to the OARs followed by TOMO. DISCUSSION: The low dose volume to the majority of OARs was significantly reduced when using IMPT compared to VMAT. Whether this will lead to a significant reduction in neurocognitive decline and improved quality of life is to be determined in carefully designed future clinical trials.

Dosimetric impact of contouring and image registration variability on dynamic 125I prostate brachytherapy.

PURPOSE: The quality of permanent prostate brachytherapy can be increased by addition of imaging modalities in the intraoperative procedure. This addition involves image registration, which inherently has inter- and intraobserver variabilities. We sought to quantify the inter- and intraobserver variabilities in geometry and dosimetry for contouring and image registration and analyze the results for our dynamic 125I brachytherapy procedure. METHODS AND MATERIALS: Five observers contoured 11 transrectal ultrasound (TRUS) data sets three times and 11 CT data sets one time. The observers registered 11 TRUS and MRI data sets to cone beam CT (CBCT) using fiducial gold markers. Geometrical and dosimetrical inter- and intraobserver variabilities were assessed. For the contouring study, structures were subdivided into three parts along the craniocaudal axis. RESULTS: We analyzed 165 observations. Interobserver geometrical variability for prostate was 1.1 mm, resulting in a dosimetric variability of 1.6% for V100 and 9.3% for D90. The geometric intraobserver variability was 0.6 mm with a V100 of 0.7% and D90 of 1.1%. TRUS-CBCT registration showed an interobserver variability in V100 of 2.0% and D90 of 3.1%. Intraobserver variabilities were 0.9% and 1.6%, respectively. For MRI-CBCT registration, V100 and D90 were 1.3% and 2.1%. Intraobserver variabilities were 0.7% and 1.1% for the same. CONCLUSIONS: Prostate dosimetry is affected by interobserver contouring and registration variability. The observed variability is smaller than underdosages that are adapted during our dynamic brachytherapy procedure.

Cone-beam CT-based adaptive planning improves permanent prostate brachytherapy dosimetry: An analysis of 1266 patients.

PURPOSE: To evaluate adaptive planning for permanent prostate brachytherapy and to identify the prostate regions that needed adaptation. METHODS AND MATERIALS: After the implantation of stranded seeds, using real-time intraoperative planning, a transrectal ultrasound (TRUS)-scan was obtained and contoured. The positions of seeds were determined on a C-arm cone-beam computed tomography (CBCT)-scan. The CBCT-scan was registered to the TRUS-scan using fiducial gold markers. If dose coverage on the combined image-dataset was inadequate, an intraoperative adaptation was performed by placing remedial seeds. CBCT-based intraoperative dosimetry was analyzed for the prostate (D90, V100, and V150) and the urethra (D30). The effects of the adaptive dosimetry procedure for Day 30 were separately assessed. RESULTS: We analyzed 1266 patients. In 17.4% of the procedures, an adaptation was performed. Without the dose contribution of the adaptation Day 30 V100 would be < 95% for half of this group. On Day 0, the increase due to the adaptation was 11.8 ± 7.2% (1SD) for D90 and 9.0 ± 6.4% for V100. On Day 30, we observed an increase in D90 of 12.3 ± 6.0% and in V100 of 4.2 ± 4.3%. For the total group, a D90 of 119.6 ± 9.1% and V100 of 97.7 ± 2.5% was achieved. Most remedial seeds were placed anteriorly near the base of the prostate. CONCLUSION: CBCT-based adaptive planning enables identification of implants needing adaptation and improves prostate dose coverage. Adaptations were predominantly performed near the anterior base of the prostate.

Edema and Seed Displacements Affect Intraoperative Permanent Prostate Brachytherapy Dosimetry.

PURPOSE: We sought to identify the intraoperative displacement patterns of seeds and to evaluate the correlation of intraoperative dosimetry with day 30 for permanent prostate brachytherapy. METHODS AND MATERIALS: We analyzed the data from 699 patients. Intraoperative dosimetry was acquired using transrectal ultrasonography (TRUS) and C-arm cone beam computed tomography (CBCT). Intraoperative dosimetry (minimal dose to 40%-95% of the volume [D40-D95]) was compared with the day 30 dosimetry for both modalities. An additional edema-compensating comparison was performed for D90. Stranded seeds were linked between TRUS and CBCT using an automatic and fast linking procedure. Displacement patterns were analyzed for each seed implantation location. RESULTS: On average, an intraoperative (TRUS to CBCT) D90 decline of 10.6% ± 7.4% was observed. Intraoperative CBCT D90 showed a greater correlation (R(2) = 0.33) with respect to Day 30 than did TRUS (R(2) = 0.17). Compensating for edema, the correlation increased to 0.41 for CBCT and 0.38 for TRUS. The mean absolute intraoperative seed displacement was 3.9 ± 2.0 mm. The largest seed displacements were observed near the rectal wall. The central and posterior seeds showed less caudal displacement than lateral and anterior seeds. Seeds that were implanted closer to the base showed more divergence than seeds close to the apex. CONCLUSIONS: Intraoperative CBCT D90 showed a greater correlation with the day 30 dosimetry than intraoperative TRUS. Edema seemed to cause most of the systematic difference between the intraoperative and day 30 dosimetry. Seeds near the rectal wall showed the most displacement, comparing TRUS and CBCT, probably because of TRUS probe-induced prostate deformation.

An automated, fast and accurate registration method to link stranded seeds in permanent prostate implants.

The geometry of a permanent prostate implant varies over time. Seeds can migrate and edema of the prostate affects the position of seeds. Seed movements directly influence dosimetry which relates to treatment quality. We present a method that tracks all individual seeds over time allowing quantification of seed movements. This linking procedure was tested on transrectal ultrasound (TRUS) and cone-beam CT (CBCT) datasets of 699 patients. These datasets were acquired intraoperatively during a dynamic implantation procedure, that combines both imaging modalities. The procedure was subdivided in four automatic linking steps. (I) The Hungarian Algorithm was applied to initially link seeds in CBCT and the corresponding TRUS datasets. (II) Strands were identified and optimized based on curvature and linefits: non optimal links were removed. (III) The positions of unlinked seeds were reviewed and were linked to incomplete strands if within curvature- and distance-thresholds. (IV) Finally, seeds close to strands were linked, also if the curvature-threshold was violated. After linking the seeds an affine transformation was applied. The procedure was repeated until the results were stable or the 6th iteration ended. All results were visually reviewed for mismatches and uncertainties. Eleven implants showed a mismatch and in 12 cases an uncertainty was identified. On average the linking procedure took 42 ms per case. This accurate and fast method has the potential to be used for other time spans, like Day 30, and other imaging modalities. It can potentially be used during a dynamic implantation procedure to faster and better evaluate the quality of the permanent prostate implant.

Helical 4D CT pitch management for the Brilliance CT Big Bore in clinical practice.

In external beam radiotherapy treatment planning for patients with thoracic malignancies, respiratory-correlated CT (4D CT) is used to obtain high quality studies in the presence of respiratory motion. When helical 4D CT scans are acquired with a Brilliance CT Big Bore, the pitch must meet two conditions. It must be low enough to avoid motion artifacts, and high enough to cover the entire scan length within 120 s to prevent overheating of the X-ray tube. We developed a nomogram that can be used to obtain a suitable pitch satisfying both requirements. We also assessed the effects on the image quality of a pitch that exceeds the maximum pitch, and of a field of view (FOV) reduction. It was shown that, for AVG and MIP reconstructions, the manufacturer's maximum pitch equation yields an underestimation due to its FOV term.

The CT number accuracy of a novel commercial metal artifact reduction algorithm for large orthopedic implants.

Philips Healthcare released a novel metal artifact reduction algorithm for large orthopedic implants (O-MAR). Little information was available about its CT number accuracy. Since CT numbers are used for tissue heterogeneity corrections in external beam radiotherapy treatment planning, we performed a phantom study to assess the CT number accuracy of O-MAR. Two situations were simulated: a patient with a unilateral metallic hip prosthesis and a patient with bilateral metallic hip prostheses. We compared the CT numbers in the O-MAR reconstructions of the simulations to those in the nonO-MAR reconstruction and to those in a metal-free baseline reconstruction. In both simulations, the CT number accuracy of the O-MAR reconstruction was better than the CT number accuracy of the nonO- MAR reconstruction. In the O-MAR reconstruction of the unilateral simulation, all CT numbers were accurate within ± 5 HU (AAPM criterion). In the O-MAR reconstruction of the bilateral simulation, CT numbers were found that differed more than ± 5 HU from the metal-free baseline values. However, none of these differences were clinically relevant.

High-dose-rate prostate brachytherapy based on registered transrectal ultrasound and in-room cone-beam CT images.

PURPOSE: To present a high-dose-rate (HDR) brachytherapy procedure for prostate cancer using transrectal ultrasound (TRUS) to contour the regions of interest and registered in-room cone-beam CT (CBCT) images for needle reconstruction. To characterize the registration uncertainties between the two imaging modalities and explore the possibility of performing the procedure solely on TRUS. METHODS AND MATERIALS: Patients were treated with a TRUS/CBCT-based HDR brachytherapy procedure. For 100 patients, dosimetric results were analyzed. For 40 patients, registration uncertainties were examined by determining differences in fiducial marker positions on TRUS and registered CBCT. The accuracy of needle reconstruction on TRUS was investigated by determining the position differences of needle tips on TRUS and CBCT. The dosimetric impact of reregistration and needle reconstruction on TRUS only was studied for 8 patients. RESULTS: The average prostate V100 was 97.8%, urethra D10 was 116.3%, and rectum D1 cc was 66.4% of the prescribed dose. For 85% of the patients, registration inaccuracies were within 3 mm. Large differences were found between needle tips on TRUS and CBCT, especially in cranial-caudal direction, with a maximum of 10.4 mm. Reregistration resulted in a maximum V100 reduction of 0.9%, whereas needle reconstruction on TRUS only gave a maximum reduction of 9.4%. CONCLUSIONS: HDR prostate brachytherapy based on TRUS combined with CBCT is an accurate method. Registration uncertainties, and consequently dosimetric inaccuracies, are small compared with the uncertainties of performing the procedure solely based on static TRUS images. CBCT imaging is a requisite in our current procedure.

A quality assurance tool for helical tomotherapy using a step-wedge phantom and the on-board MVCT detector.

The purpose of this study was to develop and evaluate filmless quality assurance (QA) tools for helical tomotherapy by using the signals from the on-board megavoltage computed tomography (MVCT) detector and applying a dedicated step-wedge phantom. The step-wedge phantom is a 15 cm long step-like aluminum block positioned on the couch. The phantom was moved through the slit beam and MVCT detector signals were analyzed. Two QA procedures were developed, with gantry fixed at 0°: 1) step-wedge procedure: to check beam energy consistency, field width, laser alignment with respect to the virtual isocenter, couch movement, and couch velocity; and 2) completion procedure: to check the accuracy of a field abutment made by the tomotherapy system after a treatment interruption. The procedures were designed as constancy tool and were validated by measurement of deliberately induced variations and comparison with a reference method. Two Hi-Art II machines were monitored over a period of three years using the step-wedge procedures. The data acquisition takes 5 minutes. The analysis is fully automated and results are available directly after acquisition. Couch speed deviations up to 2% were induced. The mean absolute difference between expected and measured couch speed was 0.2% ± 0.2% (1 standard deviation SD). Field width was varied around the 10 mm nominal size, between 9.7 and 11.1 mm, in steps of 0.2 mm. Mean difference between the step-wedge analysis and the reference method was < 0.01 mm ± 0.03 mm (1 SD). Laser (mis)alignment relative to a reference situation was detected with 0.3 mm precision (1SD). The step-wedge profile was fitted to a PDD in water. The PDD ratio D20/D10, measured at depths of 20 cm and 10 cm, was used to check beam energy consistency. Beam energy variations were induced. Mean difference between step-wedge and water PDD ratios was 0.2% ± 0.3% (1SD). The completion procedure was able to reveal abutment mismatches with a mean error of -0.6 mm ± 0.2 mm (1SD). The trending data over a period of three years showed a mean deviation of 0.4% ± 0.1% (1 SD) in couch speed. The spread in field width was 0.15 mm (1 SD). The sagittal and transverse lasers showed a variation of 0.5 mm (1 SD). Beam energy varied 1.0% (1 SD). A mean abutment mismatch was found of -0.4 mm ± 0.2 mm (1 SD) between interrupted treatments. The on-board MVCT detector, in combination with the step-wedge phantom, is a suitable tool for a QA program for helical tomotherapy. The method allowed frequent monitoring of machine behavior for the past three years.

Objective automated assessment of time trends in prostate edema after (125)I implantation.

PURPOSE: To present an objective automated method to determine time trends in prostatic edema resulting from iodine-125 brachytherapy. METHODS AND MATERIALS: We followed 20 patients, implanted with stranded seeds, with seven consecutive CT scans to establish a time trend in prostate edema. Seed positions were obtained automatically from the CT series. The change in seed positions was used as surrogate for edema. Two approaches were applied to model changes in volume. (1) A cylindrical model: seeds from the compared distribution were linked to the reference distribution of Day 28. After alignment, the compared distribution was scaled in cylindrical coordinates, leading to the changes in radial and craniocaudal directions. The volume changes were calculated using these scaling factors. (2) A spherical model: distances of seeds to the center of gravity of all seeds were used as a measure to model volume changes. RESULTS: With Day 28 as reference, the observed volume changes were smaller than 18% ± 6% (1 standard deviation) for the cylindrical model and 12% ± 7% for the spherical model. One day after implantation, the implanted prostate was less than 10% larger than in the reference scan for both models. Apart from Day 0, both models showed similar volume changes. CONCLUSIONS: We present an objective automated method to determine changes in the implanted prostate volume, eliminating the influence of an observer in the assessment of the prostate size. The implanted volume change was less than 18% ± 7% for the studied group of 20 patients. Edema was 9% ± 5% from 1 day after implantation onward.

HI-CHART: a phase I/II study on the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer.

PURPOSE: To determine the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: In a prospective, Phase I/II study, according to the risk for radiation pneumonitis, three risk groups were defined: V(20) <25%, V(20) 25-37%, and V(20) >37%. The dose was administered in three steps from 61.2 Gy/34 fractions/23 days to 64.8 Gy/36 fractions/24 days to 68.40 Gy/38 fractions/25 days (1.8 Gy b.i.d. with 8-h interval), using a three-dimensional conformal technique. Only the mediastinal lymph node areas that were positive on the pretreatment (18)F-deoxy-D-glucose positron emission tomography scan were included in the target volume. The primary endpoint was toxicity. RESULTS: A total of 48 Stage I-IIIB patients were included. In all risk groups, 68.40 Gy/38 fractions/25 days could be administered. Maximal toxicity according to the risk groups was as follows: V(20) <25% (n = 35): 1 Grade 4 (G4) lung and 1 G3 reversible esophageal toxicity; V(20) 35-37% (n = 12): 1 G5 lung and 1 G3 reversible esophageal toxicity. For the whole group, local tumor recurrence occurred in 25% (95% confidence interval 14%-40%) of the patients, with 1 of 48 (2.1%; upper one-sided 95% confidence limit 9.5%) having an isolated nodal recurrence. The median actuarial overall survival was 20 months, with a 2-year survival rate of 36%. CONCLUSIONS: High-dose continuous hyperfractionated accelerated radiotherapy up to a dose of 68.40 Gy/38 fractions/25 days (a biologic equivalent of approximately 80 Gy when delivered in conventional fractionation) in patients with inoperable NSCLC and a V(20) up to 37% is feasible.

Intraoperative adaptive brachytherapy of iodine-125 prostate implants guided by C-arm cone-beam computed tomography-based dosimetry.

PURPOSE: (1) To demonstrate the feasibility of C-arm cone-beam computed tomography (CBCT)-based postplanning and subsequent adaptation of underdosed critical areas by adding remedial seeds during the transrectal ultrasound (TRUS)-guided implantation of (125)I seeds and (2) to assess the duration of this procedure. METHODS AND MATERIALS: After finishing the implant, three fiducial markers were implanted and a TRUS study was performed to delineate the prostate. A C-arm CBCT unit with isocentric design was used to generate a CT data set to localize the seeds. The TRUS and CBCT data sets were coregistered by the radiation oncologist to assess the dosimetry of the implant. If underdosages existed at critical areas, dosimetry was adapted by adding remedial seeds while the patient was still under anesthesia. RESULTS: Of 20 patients studied, 9 demonstrated underdosage in critical areas. On average four additional seeds were implanted, resulting in a mean D(90) of 100.7% (increase 4.9%) and 117.5% (increase 17.8%) of the prescribed dose of 145 and 110 Gy, respectively. The average additional time involved in performing the adaptation procedure was less than 30 min. CONCLUSIONS: C-arm CBCT-guided intraoperative postplanning during TRUS-guided brachytherapy for prostate cancer is both feasible and time efficient. The adaptation resulted in improved dosimetry of the prostate implants.

Routine individualised patient dosimetry using electronic portal imaging devices.

BACKGROUND AND PURPOSE: To analyse the results of routine EPID measurements for individualised patient dosimetry. MATERIALS AND METHODS: Calibrated camera-based EPIDs were used to measure the central field dose, which was compared with a dose prediction at the EPID level. For transit dosimetry, dose data were calculated using patient transmission and scatter, and compared with measured values. Furthermore, measured transit dose data were back-projected to an in vivo dose value at 5 cm depth in water (D(5)) and directly compared with D(5) from the treatment planning system. Dose differences per treatment session were calculated by weighting dose values with the number of monitor units per beam. Reported errors were categorised and analysed for approximately 37,500 images from 2511 patients during a period of 24 months. RESULTS: Pre-treatment measurements showed a mean dose difference per treatment session of 0.0+/-1.7% (1 SD). Transfer errors were detected and corrected prior to the first treatment session. An accelerator output variation of about 4% was found between two weekly QC measurements. Patient dosimetry showed mean transit and D(5) dose differences of -0.7+/-5.2% (1 SD) and -0.3+/-5.6% (1 SD) per treatment session, respectively. Dose differences could be related to set-up errors, organ motion, erroneous density corrections and changes in patient anatomy. CONCLUSIONS: EPIDs can be used routinely to accurately verify treatment parameter transfer and machine output. By applying transit and in vivo dosimetry, more insight can be obtained with respect to the different error sources influencing dose delivery to a patient.

Time trends in the maximal uptake of FDG on PET scan during thoracic radiotherapy. A prospective study in locally advanced non-small cell lung cancer (NSCLC) patients.

BACKGROUND AND PURPOSE: 18F-fluoro-2-deoxy-glucose (FDG) uptake on PET scan is a prognostic factor for outcome in NSCLC. We investigated changes in FDG uptake during fractionated radiotherapy in relation to metabolic response with the ultimate aim to adapt treatment according to early response. METHODS AND MATERIALS: Twenty-three patients, medically inoperable or with advanced NSCLC, underwent four repeated PET-CT scans before, during and after radiotherapy. Changes in maximal standardized uptake value (SUVmax) were described. Patients were treated with accelerated radiotherapy with a total tumour-dose depending on normal tissue dose constraints. RESULTS: The most striking result was the large intra-individual heterogeneity in the evolution of SUVmax. For the total group a non-significant increase in the first week (p=0.05), and a decrease in the second week (p=0.02) and after radiotherapy (p<0.01) was observed. Different time trends were shown for responders (no change during radiotherapy) and non-responders (48% increase during first week, p=0.02 and 15% decrease in the second week, p=0.04). Non-responders had a higher SUVmax on all time points investigated. CONCLUSIONS: Time trends in SUVmax showed a large intra-individual heterogeneity and different patterns for metabolic responders and non-responders. These new findings may reflect intrinsic tumour characteristics and might finally be useful to adapt treatment.

Intra-patient variability of tumor volume and tumor motion during conventionally fractionated radiotherapy for locally advanced non-small-cell lung cancer: a prospective clinical study.

PURPOSE: The aim of this study was to investigate the change in tumor volume, motion, and breathing frequency during a course of radiotherapy, for locally advanced non-small-cell lung cancer. METHODS AND MATERIALS: A total of 23 patients underwent computed tomography-positron emission tomography (CT-PET) and respiration correlated CT scans before treatment, which was repeated in the first and second weeks after the start of radiotherapy. Patients were treated with an accelerated fractionation schedule, 1.8 Gy twice a day, with a total tumor dose depending on preset dose constraints for the lungs and spinal cord. RESULTS: A striking heterogeneity of tumor volume changes was observed at all time points. In some patients the volume decreased >30% (3/23), whereas in others the volume increased >30% (4/24); but for the majority of patients (16/23), the tumor volume changed only slightly (<30%). No significant changes in average tumor motion or breathing frequencies were observed during treatment. Although a number of changes in individual tumor motion were seen, only in 1 patient would this have led to an increase of the internal margin >1 mm in 1 direction, 1 week after the start of treatment, and in 3 patients for 1 direction, 2 weeks after the start of the treatment. CONCLUSION: In this patients in this study, a large variability in changes in tumor volume was observed. This underscores the need for repeated imaging during the course of radiotherapy. However, the changes in tumor motion are small, which indicates that repeated respiration correlated CT does not appear to be necessary.