Complementing Prostate SBRT VMAT With a Two-Beam Non-Coplanar IMRT Class Solution to Enhance Rectum and Bladder Sparing With Minimum Increase in Treatment Time.

PURPOSE: Enhance rectum and bladder sparing in prostate SBRT with minimum increase in treatment time by complementing dual-arc coplanar VMAT with a two-beam non-coplanar IMRT class solution (CS). METHODS: For twenty patients, an optimizer for automated multi-criterial planning with integrated beam angle optimization (BAO) was used to generate dual-arc VMAT plans, supplemented with five non-coplanar IMRT beams with individually optimized orientations (VMAT+5). In all plan generations, reduction of high rectum dose had the highest priority after obtaining adequate PTV coverage. A CS with two most preferred directions in VMAT+5 and largest rectum dose reductions compared to dual-arc VMAT was then selected to define VMAT+CS. VMAT+CS was compared with automatically generated i) dual-arc coplanar VMAT plans (VMAT), ii) VMAT+5 plans, and iii) IMRT plans with 30 patient-specific non-coplanar beam orientations (30-NCP). Plans were generated for a 4 x 9.5 Gy fractionation scheme. Differences in PTV doses, healthy tissue sparing, and computation and treatment delivery times were quantified. RESULTS: For equal PTV coverage, VMAT+CS, consisting of dual-arc VMAT supplemented with two fixed, non-coplanar IMRT beams with fixed Gantry/Couch angles of 65°/30° and 295°/-30°, significantly reduced OAR doses and the dose bath, compared to dual-arc VMAT. Mean relative differences in rectum Dmean, D1cc, V40GyEq and V60GyEq were 19.4 ± 10.6%, 4.2 ± 2.7%, 34.9 ± 20.3%, and 39.7 ± 23.2%, respectively (all p<0.001). There was no difference in bladder D1cc, while bladder Dmean reduced by 17.9 ± 11.0% (p<0.001). Also, the clinically evaluated urethra D5%, D10%, and D50% showed small, but statistically significant improvements. All patient VX with X = 2, 5, 10, 20, and 30 Gy were reduced with VMAT+CS, with a maximum relative reduction for V10Gy of 19.0 ± 7.3% (p<0.001). Total delivery times with VMAT+CS only increased by 1.9 ± 0.7 min compared to VMAT (9.1 ± 0.7 min). The dosimetric quality of VMAT+CS plans was equivalent to VMAT+5, while optimization times were reduced by a factor of 25 due to avoidance of individualized BAO. Compared to VMAT+CS, the 30-NCP plans were only favorable in terms of dose bath, at the cost of much enhanced optimization and delivery times. CONCLUSIONS: The proposed two-beam non-coplanar class solution to complement coplanar dual-arc VMAT resulted in substantial plan quality improvements for OARs (especially rectum) and reduced irradiated patient volumes with minor increases in treatment delivery times.

The Risk of Second Primary Cancers in Prostate Cancer Survivors Treated in the Modern Radiotherapy Era.

PURPOSE: Concerns have been raised that modern intensity modulated radiotherapy (IMRT) may be associated with increased second primary cancer risks (SPC) compared to previous three-dimensional conformal radiation techniques (3DCRT), due to increased low dose volumes and more out-of-field ionizing dose to peripheral tissue further away from the target. We assessed the impact of treatment technique on SPC risks in a cohort of prostate cancer (PCa) survivors. MATERIAL AND METHODS: The study cohort comprised 1,561 PCa survivors aged 50-79 years at time of radiotherapy, treated between 2006-2013 (N=707 IMRT, N=854 3DCRT). Treatment details were extracted from radiotherapy systems and merged with longitudinal data of the Netherlands Cancer Registry to identify SPCs. Primary endpoint was the development of a solid SPC (excluding skin cancer) in peripheral anatomical regions, i.e. non-pelvic. Applied latency period was 12 months. SPC rates in the IMRT cohort (total cohort and age subgroups) were compared to 1) the 3DCRT cohort by calculating Sub-Hazard Ratios (sHR) using a competing risk model, and 2) to the general male population by calculating Standardized Incidence Ratios (SIR). Models were adjusted for calendar period and age. RESULTS: Median follow-up was 8.0 years (accumulated 11,664 person-years at-risk) with 159 cases developing ≥1 non-pelvic SPC. For IMRT vs 3DCRT we observed a significantly (p=0.03) increased risk (sHR=1.56, 95% Confidence Interval (CI) 1.03-2.36, corresponding estimated excess absolute risk (EAR) of +7 cases per 10,000 person-years). At explorative analysis, IMRT was in particular associated with increased risks within the subgroup of active smokers (sHR 2.94, p=0.01). Within the age subgroups 50-69 and 70-79 years, the sHR for non-pelvic SPC was 3.27 (p=0.001) and 0.96 (p=0.9), respectively. For pelvic SPC no increase was observed (sHR=0.8, p=0.4). Compared to the general population, IMRT was associated with significantly increased risks for non-pelvic SPC in the 50-69 year age group (SIR=1.90, p<0.05) but not in the 70-79 years group (SIR=1.08). CONCLUSION: IMRT is associated with increased SPC risks for subjects who are relatively young at time of treatment. Additional research on aspects of IMRT that may cause this effect is essential to minimize risks for future patients receiving modern radiotherapy.

Lower doses to hippocampi and other brain structures for skull-base meningiomas with intensity modulated proton therapy compared to photon therapy.

BACKGROUND AND PURPOSE: Radiotherapy of skull-base meningiomas is challenging due to the close proximity of multiple sensitive organs at risk (OARs). This study systematically compared intensity modulated proton therapy (IMPT), non-coplanar volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) based on automated treatment planning. Differences in OARs sparing, with specific focus on the hippocampi, and low-dose delivery were quantified. MATERIALS AND METHODS: Twenty patients, target diameter >3 cm, were included. Automated plan generation was used to calculate a VMAT plan with three non-coplanar arcs, an IMRT plan with nine non-coplanar beams with optimized gantry and couch angles, and an IMPT plan with three patient-specific selected non-coplanar beams. A prescription dose of 50.4 GyRBE in 28 fractions was used. The same set of constraints and prioritized objectives was used. All plans were rescaled to the same target coverage. Repeated measures ANOVA was used to assess the statistical significance of differences in OAR dose parameters between planning techniques. RESULTS: Compared to VMAT and IMRT, IMPT significantly improved dose conformity to the target volume. Consequently, large dose reductions in OARs were observed. With respect to VMAT, the mean dose and D40% in the bilateral hippocampus were on average reduced by 48% and 74%, respectively (p ≤ 0.005). With IMPT, the mean dose in the normal brain and volumes receiving 20-30 Gy were up to 47% lower (p ≤ 0.01). When comparing IMPT and IMRT, even larger dose differences in those OARs were observed. CONCLUSION: For skull-base meningiomas IMPT allows for a considerable dose reduction in the hippocampi, normal brain and other OARs compared to both non-coplanar VMAT and IMRT, which may lead to a clinically relevant reduction of late neurocognitive side effects.

Late toxicity in the randomized multicenter HYPRO trial for prostate cancer analyzed with automated treatment planning.

PURPOSE/OBJECTIVE: Assess to what extent the use of automated treatment planning would have reduced organ-at-risk dose delivery observed in the randomized HYPRO trial for prostate cancer, and estimate related toxicity reductions. Investigate to what extent improved plan quality for hypofractionation scheme as achieved with automated planning can potentially reduce observed enhanced toxicity for the investigated hypofractionation scheme to levels observed for conventional fractionation scheme. MATERIAL/METHODS: For 725 trial patients, VMAT plans were generated with an algorithm for automated multi-criterial plan generation (autoVMAT). All clinically delivered plans (CLINICAL), generated with commonly applied interactive trial-and-error planning were also available for the investigations. Analyses were based on dose-volume histograms (DVH) and predicted normal tissue complication probabilities (NTCP) for late gastrointestinal (GI) toxicity. RESULTS: Compared to CLINICAL, autoVMAT plans had similar or higher PTV coverage, while large and statistically significant OAR sparing was achieved. Mean doses in the rectum, anus and bladder were reduced by 7.8 ±â€¯4.7 Gy, 7.9 ±â€¯6.0 Gy and 4.2 ±â€¯2.9 Gy, respectively (p < 0.001). NTCPs for late grade ≥2 GI toxicity, rectal bleeding and stool incontinence were reduced from 23.3 ±â€¯9.1% to 19.7 ±â€¯8.9%, from 9.7 ±â€¯2.8% to 8.2 ±â€¯2.8%, and from 16.8 ±â€¯8.5% to 13.1 ±â€¯7.2%, respectively (p < 0.001). Reductions in rectal bleeding NTCP were observed for all published Equivalent Uniform Dose volume parameters, n. AutoVMAT allowed hypofractionation with predicted toxicity similar to conventional fractionation with CLINICAL plans. CONCLUSION: Compared to CLINICAL, autoVMAT had superior plan quality, with meaningful NTCP reductions for both conventional fractionation and hypofractionation schemes. AutoVMAT plans might reduce toxicity for hypofractionation to levels that were clinically observed (and accepted) for conventional fractionation. This may be relevant when considering clinical use of the investigated hypofractionation schedule with relatively high fraction dose (3.4 Gy).

Automated VMAT planning for postoperative adjuvant treatment of advanced gastric cancer.

BACKGROUND: Postoperative/adjuvant radiotherapy of advanced gastric cancer involves a large planning target volume (PTV) with multi-concave shapes which presents a challenge for volumetric modulated arc therapy (VMAT) planning. This study investigates the advantages of automated VMAT planning for this site compared to manual VMAT planning by expert planners. METHODS: For 20 gastric cancer patients in the postoperative/adjuvant setting, dual-arc VMAT plans were generated using fully automated multi-criterial treatment planning (autoVMAT), and compared to manually generated VMAT plans (manVMAT). Both automated and manual plans were created to deliver a median dose of 45 Gy to the PTV using identical planning and segmentation parameters. Plans were evaluated by two expert radiation oncologists for clinical acceptability. AutoVMAT and manVMAT plans were also compared based on dose-volume histogram (DVH) and predicted normal tissue complication probability (NTCP) analysis. RESULTS: Both manVMAT and autoVMAT plans were considered clinically acceptable. Target coverage was similar (manVMAT: 96.6 ± 1.6%, autoVMAT: 97.4 ± 1.0%, p = 0.085). With autoVMAT, median kidney dose was reduced on average by > 25%; (for left kidney from 11.3 ± 2.1 Gy to 8.9 ± 3.5 Gy (p = 0.002); for right kidney from 9.2 ± 2.2 Gy to 6.1 ± 1.3 Gy (p <  0.001)). Median dose to the liver was lower as well (18.8 ± 2.3 Gy vs. 17.1 ± 3.6 Gy, p = 0.048). In addition, Dmax of the spinal cord was significantly reduced (38.3 ± 3.7 Gy vs. 31.6 ± 2.6 Gy, p <  0.001). Substantial improvements in dose conformity and integral dose were achieved with autoVMAT plans (4.2% and 9.1%, respectively; p <  0.001). Due to the better OAR sparing in the autoVMAT plans compared to manVMAT plans, the predicted NTCPs for the left and right kidney and the liver-PTV were significantly reduced by 11.3%, 12.8%, 7%, respectively (p ≤ 0.001). Delivery time and total number of monitor units were increased in autoVMAT plans (from 168 ± 19 s to 207 ± 26 s, p = 0.006) and (from 781 ± 168 MU to 1001 ± 134 MU, p = 0.003), respectively. CONCLUSIONS: For postoperative/adjuvant radiotherapy of advanced gastric cancer, involving a complex target shape, automated VMAT planning is feasible and can substantially reduce the dose to the kidneys and the liver, without compromising the target dose delivery.

A novel method for sub-arc VMAT dose delivery verification based on portal dosimetry with an EPID.

PURPOSE: The EPID-based sub-arc verification of VMAT dose delivery requires synchronization of the acquired electronic portal images (EPIs) with the VMAT delivery, that is, establishment of the start- and stop-MU of the acquired images. To realize this, published synchronization methods propose the use of logging features of the linac or dedicated hardware solutions. In this study, we developed a novel, software-based synchronization method that only uses information inherently available in the acquired images. METHOD: The EPIs are continuously acquired during pretreatment VMAT delivery and converted into Portal Dose Images (PDIs). Sub-arcs of approximately 10 MU are then defined by combining groups of sequentially acquired PDIs. The start- and stop-MUs of measured sub-arcs are established in a synchronization procedure, using only dosimetric information in measured and predicted PDIs. Sub-arc verification of a VMAT dose delivery is based on comparison of measured sub-arc PDIs with synchronized, predicted sub-arc PDIs, using γ-analyses. To assess the accuracy of this new method, measured and predicted PDIs were compared for 20 clinically applied VMAT prostate cancer plans. The sensitivity of the method for detection of delivery errors was investigated using VMAT deliveries with intentionally inserted, small perturbations (25 error scenarios; leaf gap deviations ≤ 1.5 mm, leaf motion stops during ≤ 15 MU, linac output error ≤ 2%). RESULTS: For the 20 plans, the average failed pixel rates (FPR) for full-arc and sub-arc dose QA were 0.36% ± 0.26% (1 SD) and 0.64% ± 0.88%, based on 2%/2 mm and 3%/3 mm γ-analyses, respectively. Small systematic perturbations of up to 1% output error and 1 mm leaf offset were detected using full-arc QA. Sub-arc QA was able to detect positioning errors in three leaves only during approximately 20 MU and small dose delivery errors during approximately 40 MU. In an ROC analysis, the area under the curve (AUC) for the combined full-arc/sub-arc approach was 0.90. CONCLUSIONS: A novel method for sub-arc VMAT dose delivery verification with EPIDs is proposed, using only dosimetric information in acquired EPIs for synchronization. Especially in combination with full-arc QA, the established sensitivity for detection of very small errors is high, with also a high specificity.

VMAT plus a few computer-optimized non-coplanar IMRT beams (VMAT+) tested for liver SBRT.

PURPOSE: To propose a novel treatment approach, designated VMAT+, involving addition of <5 IMRT beams with computer-optimized non-coplanar orientations to VMAT, and evaluate it for liver Stereotactic Body Radiation Therapy (SBRT). VMAT+ is investigated as an alternative for (1) coplanar VMAT and (2) multi-beam non-coplanar treatment. METHODS/MATERIALS: For fifteen patients with liver metastases, VMAT+ plans were compared with (1) dual-arc VMAT and (2) 25-beam, non-coplanar treatment with computer-optimized beam orientations (25-NCP). All plans were generated fully automatically for delivery of the highest feasible tumor Biologically Effective Dose (BED). OAR doses, intermediate-dose-spillage, dose-compactness, and measured delivery times were evaluated. RESULTS: With VMAT+ the maximum achievable tumor BED was equal to that of 25-NCP. Conversely, VMAT resulted in a lower tumor BED in 5 patients. Compared to VMAT, VMAT+ yielded significant dose reductions in OARs. Intermediate-dose-spillage and dose-compactness were significantly improved by 9.8% and 17.3% (p≤0.002), respectively. Treatment times with VMAT+ were only enhanced by 4.1min on average, compared to VMAT (8.4min). Improvements in OAR sparing with 25-NCP, compared to VMAT+, were generally modest and/or statistically insignificant, while delivery times were on average 20.5min longer. CONCLUSIONS: For liver SBRT, VMAT+ is equivalent to time-consuming treatment with 25 non-coplanar beams in terms of achievable tumor BED. Compared to VMAT, OAR sparing and intermediate-dose-spillage are significantly improved, with minor increase in delivery time.

Fully automated VMAT treatment planning for advanced-stage NSCLC patients.

PURPOSE: To develop a fully automated procedure for multicriterial volumetric modulated arc therapy (VMAT) treatment planning (autoVMAT) for stage III/IV non-small cell lung cancer (NSCLC) patients treated with curative intent. MATERIALS AND METHODS: After configuring the developed autoVMAT system for NSCLC, autoVMAT plans were compared with manually generated clinically delivered intensity-modulated radiotherapy (IMRT) plans for 41 patients. AutoVMAT plans were also compared to manually generated VMAT plans in the absence of time pressure. For 16 patients with reduced planning target volume (PTV) dose prescription in the clinical IMRT plan (to avoid violation of organs at risk tolerances), the potential for dose escalation with autoVMAT was explored. RESULTS: Two physicians evaluated 35/41 autoVMAT plans (85%) as clinically acceptable. Compared to the manually generated IMRT plans, autoVMAT plans showed statistically significant improved PTV coverage (V95% increased by 1.1% ± 1.1%), higher dose conformity (R50 reduced by 12.2% ± 12.7%), and reduced mean lung, heart, and esophagus doses (reductions of 0.9 Gy ± 1.0 Gy, 1.5 Gy ± 1.8 Gy, 3.6 Gy ± 2.8 Gy, respectively, all p < 0.001). To render the six remaining autoVMAT plans clinically acceptable, a dosimetrist needed less than 10 min hands-on time for fine-tuning. AutoVMAT plans were also considered equivalent or better than manually optimized VMAT plans. For 6/16 patients, autoVMAT allowed tumor dose escalation of 5-10 Gy. CONCLUSION: Clinically deliverable, high-quality autoVMAT plans can be generated fully automatically for the vast majority of advanced-stage NSCLC patients. For a subset of patients, autoVMAT allowed for tumor dose escalation.

Fully automated volumetric modulated arc therapy plan generation for prostate cancer patients.

PURPOSE: To develop and evaluate fully automated volumetric modulated arc therapy (VMAT) treatment planning for prostate cancer patients, avoiding manual trial-and-error tweaking of plan parameters by dosimetrists. METHODS AND MATERIALS: A system was developed for fully automated generation of VMAT plans with our commercial clinical treatment planning system (TPS), linked to the in-house developed Erasmus-iCycle multicriterial optimizer for preoptimization. For 30 randomly selected patients, automatically generated VMAT plans (VMATauto) were compared with VMAT plans generated manually by 1 expert dosimetrist in the absence of time pressure (VMATman). For all treatment plans, planning target volume (PTV) coverage and sparing of organs-at-risk were quantified. RESULTS: All generated plans were clinically acceptable and had similar PTV coverage (V95% > 99%). For VMATauto and VMATman plans, the organ-at-risk sparing was similar as well, although only the former plans were generated without any planning workload. CONCLUSIONS: Fully automated generation of high-quality VMAT plans for prostate cancer patients is feasible and has recently been implemented in our clinic.

Accurate IMRT fluence verification for prostate cancer patients using 'in-vivo' measured EPID images and in-room acquired kilovoltage cone-beam CT scans.

BACKGROUND: To investigate for prostate cancer patients the comparison of 'in-vivo' measured portal dose images (PDIs) with predictions based on a kilovoltage cone-beam CT scan (CBCT), acquired during the same treatment fraction, as an alternative for pre-treatment verification. For evaluation purposes, predictions were also performed using the patients' planning CTs (pCT). METHODS: To get reliable CBCT electron densities for PDI predictions, Hounsfield units from the pCT were mapped onto the CBCT, while accounting for non-rigidity in patient anatomy in an approximate way. PDI prediction accuracy was first validated for an anatomical phantom, using IMRT treatment plans of ten prostate cancer patients. Clinical performance was studied using data acquired for 50 prostate cancer patients. For each patient, 4-5 CBCTs were available, resulting in a total of 1413 evaluated images. Measured and predicted PDIs were compared using γ-analyses with 3% global dose difference and 3 mm distance to agreement as reference criteria. Moreover, the pass rate for automated PDI comparison was assessed. To quantify improvements in IMRT fluence verification accuracy results from multiple fractions were combined by generating a γ-image with values halfway the minimum and median γ values, pixel by pixel. RESULTS: For patients, CBCT-based PDI predictions showed a high agreement with measurements, with an average percentage of rejected pixels of 1.41% only. In spite of possible intra-fraction motion and anatomy changes, this was only slightly larger than for phantom measurements (0.86%). For pCT-based predictions, the agreement deteriorated (average percentage of rejected pixels 2.98%), due to an enhanced impact of anatomy variations. For predictions based on CBCT, combination of the first 2 fractions yielded gamma results in close agreement with pre-treatment analyses (average percentage of rejected pixels 0.63% versus 0.35%, percentage of rejected beams 0.6% versus 0%). For the pCT-based approach, only combination of the first 5 fractions resulted in acceptable agreement with pre-treatment results. CONCLUSION: In-room acquired CBCT scans can be used for high accuracy IMRT fluence verification based on in-vivo measured EPID images. Combination of γ results for the first 2 fractions can largely compensate for small accuracy reductions, with respect to pre-treatment verification, related to intra-fraction motion and anatomy changes.

Automated generation of IMRT treatment plans for prostate cancer patients with metal hip prostheses: comparison of different planning strategies.

PURPOSE: To compare IMRT planning strategies for prostate cancer patients with metal hip prostheses. METHODS: All plans were generated fully automatically (i.e., no human trial-and-error interactions) using iCycle, the authors' in-house developed algorithm for multicriterial selection of beam angles and optimization of fluence profiles, allowing objective comparison of planning strategies. For 18 prostate cancer patients (eight with bilateral hip prostheses, ten with a right-sided unilateral prosthesis), two planning strategies were evaluated: (i) full exclusion of beams containing beamlets that would deliver dose to the target after passing a prosthesis (IMRT remove) and (ii) exclusion of those beamlets only (IMRT cut). Plans with optimized coplanar and noncoplanar beam arrangements were generated. Differences in PTV coverage and sparing of organs at risk (OARs) were quantified. The impact of beam number on plan quality was evaluated. RESULTS: Especially for patients with bilateral hip prostheses, IMRT cut significantly improved rectum and bladder sparing compared to IMRT remove. For 9-beam coplanar plans, rectum V60 Gy reduced by 17.5% ± 15.0% (maximum 37.4%, p = 0.036) and rectum D mean by 9.4% ± 7.8% (maximum 19.8%, p = 0.036). Further improvements in OAR sparing were achievable by using noncoplanar beam setups, reducing rectum V 60Gy by another 4.6% ± 4.9% (p = 0.012) for noncoplanar 9-beam IMRT cut plans. Large reductions in rectum dose delivery were also observed when increasing the number of beam directions in the plans. For bilateral implants, the rectum V 60Gy was 37.3% ± 12.1% for coplanar 7-beam plans and reduced on average by 13.5% (maximum 30.1%, p = 0.012) for 15 directions. CONCLUSIONS: iCycle was able to automatically generate high quality plans for prostate cancer patients with prostheses. Excluding only beamlets that passed through the prostheses (IMRTcut strategy) significantly improved OAR sparing. Noncoplanar beam arrangements and, to a larger extent, increasing the number of treatment beams further improved plan quality.

Toward fully automated multicriterial plan generation: a prospective clinical study.

PURPOSE: To prospectively compare plans generated with iCycle, an in-house-developed algorithm for fully automated multicriterial intensity modulated radiation therapy (IMRT) beam profile and beam orientation optimization, with plans manually generated by dosimetrists using the clinical treatment planning system. METHODS AND MATERIALS: For 20 randomly selected head-and-neck cancer patients with various tumor locations (of whom 13 received sequential boost treatments), we offered the treating physician the choice between an automatically generated iCycle plan and a manually optimized plan using standard clinical procedures. Although iCycle used a fixed "wish list" with hard constraints and prioritized objectives, the dosimetrists manually selected the beam configuration and fine tuned the constraints and objectives for each IMRT plan. Dosimetrists were not informed in advance whether a competing iCycle plan was made. The 2 plans were simultaneously presented to the physician, who then selected the plan to be used for treatment. For the patient group, differences in planning target volume coverage and sparing of critical tissues were quantified. RESULTS: In 32 of 33 plan comparisons, the physician selected the iCycle plan for treatment. This highly consistent preference for the automatically generated plans was mainly caused by the improved sparing for the large majority of critical structures. With iCycle, the normal tissue complication probabilities for the parotid and submandibular glands were reduced by 2.4% ± 4.9% (maximum, 18.5%, P=.001) and 6.5% ± 8.3% (maximum, 27%, P=.005), respectively. The reduction in the mean oral cavity dose was 2.8 ± 2.8 Gy (maximum, 8.1 Gy, P=.005). For the swallowing muscles, the esophagus and larynx, the mean dose reduction was 3.3 ± 1.1 Gy (maximum, 9.2 Gy, P<.001). For 15 of the 20 patients, target coverage was also improved. CONCLUSIONS: In 97% of cases, automatically generated plans were selected for treatment because of the superior quality. Apart from the improved plan quality, automatic plan generation is economically attractive because of the reduced workload.

Integrated multicriterial optimization of beam angles and intensity profiles for coplanar and noncoplanar head and neck IMRT and implications for VMAT.

PURPOSE: To quantify improved salivary gland sparing for head and neck cancer patients using intensity-modulated radiotherapy (IMRT) plans based on integrated computerized optimization of beam orientations and intensity profiles. To assess if optimized nonzero couch angles also improve VMAT plans. METHODS: Our in-house developed algorithm iCycle was used for automated generation of multicriterial optimized plans with optimized beam orientations and intensity profiles, and plans with optimized profiles for preselected beam arrangements. For 20 patients, five IMRT plans, based on one "wish-list," were compared: (i) and (ii) seven- and nine-beam equiangular coplanar plans (iCycle(7equi), iCycle(9equi)), (iii) and (iv) nine-beam plans with optimized coplanar and noncoplanar beam orientations (iCycle(copl), iCycle(noncopl)), and (v) a nine-beam coplanar plan with optimized gantry angles and one optimized couch rotation (iCycle(couch)). VMAT plans without and with this optimized couch rotation were evaluated. RESULTS: iCycle(noncopl) resulted in the best salivary gland sparing, while iCycle(couch) yielded similar results for 18 patients. For iCycle(7equi), submandibular gland NTCP values were on average 5% higher. iCycle(9equi) performed better than iCycle(7equi). iCycle(copl) showed further improvement. Application of the optimized couch angle from iCycle(couch) also improved NTCP values in VMAT plans. CONCLUSIONS: iCycle allows objective comparison of competing planning strategies. Integrated optimization of beam profiles and angles can significantly improve normal tissue sparing, yielding optimal results for iCycle(noncopl).

Software-controlled, highly automated intrafraction prostate motion correction with intrafraction stereographic targeting: System description and clinical results.

PURPOSE: A new system for software-controlled, highly automated correction of intrafraction prostate motion," intrafraction stereographic targeting" (iSGT), is described and evaluated. METHODS: At our institute, daily prostate positioning is routinely performed at the start of treatment beam using stereographic targeting (SGT). iSGT was implemented by extension of the SGT software to facilitate fast and accurate intrafraction motion corrections with minimal user interaction. iSGT entails megavoltage (MV) image acquisitions with the first segment of selected IMRT beams, automatic registration of implanted markers, followed by remote couch repositioning to correct for intrafraction motion above a predefined threshold, prior to delivery of the remaining segments. For a group of 120 patients, iSGT with corrections for two nearly lateral beams was evaluated in terms of workload and impact on effective intrafraction displacements in the sagittal plane. RESULTS: SDs of systematic (Σ) and random (σ) displacements relative to the planning CT measured directly after initial SGT setup correction were <0.5 and <0.8 mm, respectively. Without iSGT corrections, effective Σ and σ for the 11-min treatments would increase to Σ(eff) < 1.1 mm and σ(eff) < 1.2 mm. With the iSGT procedure with an action level of 4 mm, effective positioning errors were reduced to Σ(eff) < 0.8 mm and σ(eff) < 1.0 mm, with 23.1% of all fractions requiring a correction. Computer simulations demonstrated that with an action level of 2 mm, the errors would have been reduced to Σ(eff) < 0.6 mm and σ(eff) < 0.7 mm, requiring corrections in 82.4% of the fractions. Because iSGT is highly automated, the extra time added by iSGT is <30 s if a correction is required. CONCLUSIONS: Without increasing imaging dose, iSGT successfully reduces intrafraction prostate motion with minimal workload and increase in fraction time. An action level of 2 mm is recommended.

Day-to-day reproducibility of prostate intrafraction motion assessed by multiple kV and MV imaging of implanted markers during treatment.

PURPOSE: When one is performing online setup correction for prostate positioning displacements prior to daily dose delivery, intrafraction motion can become a limiting factor to prostate targeting accuracy. The aim of this study was to quantify and characterize prostate intrafraction motion assessed by multiple kilovoltage (kV) and megavoltage (MV) imaging of implanted markers during treatment in a large patient group. METHODS AND MATERIALS: Intrafraction motion in the sagittal plane was studied by retrospective analysis of displacements of implanted gold markers on (nearly) lateral kV and MV images obtained at various time points during the treatment fractions (mean, 27 per patient) in 108 consecutive patients. The effective prostate motion in a fraction was defined as the time-weighted mean displacement. RESULTS: Prostate displacements in the sagittal plane increased during the fraction (mean, 0.2 ± 0.2 mm/min). Forty percent of patients had a systematic (i.e., appearing in all fractions) effective displacement in the sagittal plane greater than 2 mm. Observed effective population mean-of-means (µeff) +/- systematic (Σeff) intrafraction motion (µ(eff) ± Σ(eff)) was 0.9 ± 1.1 mm and 0.6 ± 1.0 mm for the anterior-posterior and superior inferior directions, respectively. Corresponding random motion (σ(eff)) was 1.2 mm and 1.1 mm. Mean effective prostate motion in the first 5 fractions was predictive for mean effective displacement in the remaining fractions (p < 0.001). CONCLUSION: For a large subgroup of patients, the systematic component of intrafraction prostate motion was substantial. Intrafraction motion correction prior to each beam delivery or offline corrections could likely be beneficial for the subgroup of patients with significant motion. The systematic component is well predicted by measurements in the initial fractions.

Intensity modulated radiation therapy planning for patients with a metal hip prosthesis based on class solutions.

PURPOSE: With the aging of the population, an increasing number of patients with metallic hip implants are referred for radiotherapy treatment. Class solutions for intensity modulated radiation therapy (IMRT) treatment planning are generally not applicable for these patients due to the required avoidance of dose delivery through prostheses. In this work a new approach for IMRT planning is presented, allowing the use of a default beam setup. METHODS AND MATERIALS: For IMRT planning, Monaco (Elekta; CMS Software, Maryland Heights, MO) was used. In addition to the target and organs at risk, so-called prosthesis avoidance volumes (PAVs) were delineated in the beam's eye view projection for beams in which the prosthesis was partially in front of the target. By putting strict constraints on these virtual organs at risk, entrance dose delivery through a prosthesis is avoided while exit dose delivery is allowed. In this way, uncertainties in the dose delivery to the target and organs at risk, as derived by the treatment planning system, are largely minimized. To show the advantages of this IMRT-PAV technique, for 2 prostate cancer patients, 1 with bilateral and the other with unilateral metallic hip prostheses, obtained IMRT plans were compared with conventional IMRT plans using a prosthesis-avoiding beam setup. RESULTS: For both IMRT techniques a similar planning target volume coverage was achieved, but with the IMRT-PAV technique the mean doses to the bladder and the rectum were reduced by up to 25%. While the IMRT-PAV technique required more time for delineation, the time for treatment planning reduced because the default beam setup could be applied. The number of segments needed for dose delivery was comparable for both techniques. CONCLUSIONS: With the new IMRT-PAV technique IMRT class solutions can safely be applied for cancer patients with metallic hip prostheses, generally yielding a reduced dose delivery to organs at risk or improved target coverage.

Inclusion of the treatment couch in portal dose image prediction for high precision EPID dosimetry.

PURPOSE: When comparing predicted portal dose images (PDIs) to PDIs acquired by an EPID during treatment delivery, differences are often observed. These differences may be partially attributed to beam attenuation by parts of the treatment couch not taken into account in the PDI prediction. In order to improve the agreement, a model for the treatment couch was derived and included in the PDI prediction. METHODS: A CT scan was used to model the couch top. The model for the couch top base was derived by iteratively matching the predicted and measured PDIs for gantry angles of 0 degree, 45 degrees, and 90 degrees. For PDI prediction, the modeled treatment couch was added to the CT scan of a patient or phantom by using the recorded couch positions from the record and verify system. To validate the couch model, PDI measurements were performed for a range of couch positions and gantry angles, both with and without an anatomical phantom in the beam. RESULTS: After including the couch model in the PDI prediction for beams passing through the couch without phantom, the mean local dose differences between measured and predicted PDIs were reduced from up to 5.5% to less than 1.0% at each gantry angle. Similar results were obtained for measurements with a lung phantom on the couch. Although the couch model was originally derived by using a 6 MV photon beam, the results showed that it is also applicable for a 10 MV beam. CONCLUSIONS: A model of the treatment couch was derived and included in the PDI prediction, yielding a substantially improved agreement between measured and predicted PDIs, which makes interpretation of the observed deviations more straightforward.

Does atlas-based autosegmentation of neck levels require subsequent manual contour editing to avoid risk of severe target underdosage? A dosimetric analysis.

BACKGROUND AND PURPOSE: To investigate the dosimetric impact of not editing auto-contours of the elective neck and organs at risk (OAR), generated with atlas-based autosegmentation (ABAS) (Elekta software) for head and neck cancer patients. MATERIALS AND METHODS: For nine patients ABAS auto-contours and auto-contours edited by two observers were available. Based on the non-edited auto-contours clinically acceptable IMRT plans were constructed (designated 'ABAS plans'). These plans were then evaluated for the two edited structure sets, by quantifying the percentage of the neck-PTV receiving more than 95% of the prescribed dose (V(95)) and the near-minimum dose (D(99)) in the neck PTV. Dice coefficients and mean contour distances were calculated to quantify the similarity of ABAS auto-contours with the structure sets edited by observer 1 and observer 2. To study the dosimetric importance of editing OAR auto-contours a new IMRT plan was generated for each patient-observer combination, based on the observer's edited CTV and the non-edited salivary gland auto-contours. For each plan mean doses for the non-edited glands were compared with doses for the same glands edited by the observer. RESULTS: For both observers, edited neck CTVs were larger than ABAS auto-contours (p≤ 0.04), by a mean of 8.7%. When evaluating ABAS plans on the PTVs of the edited structure sets, V(95) reduced by 7.2%±5.4% (1 SD) (p<0.03). The mean reduction in D(99) was 14.2 Gy (range 1-54 Gy). Even for Dice coefficients >0.8 and mean contour distances <1mm, reductions in D(99) up to 11Gy were observed. For treatment plans based on observer PTVs and non-edited auto-contoured salivary glands, the mean doses in the edited glands differed by only -0.6 Gy±1.0 Gy (p=0.06). CONCLUSIONS: Editing of auto-contoured neck CTVs generated by ABAS is required to avoid large underdosages in target volumes. Often used similarity measures for evaluation of auto-contouring algorithms, such as dice coefficients, do not predict well for expected PTV underdose. Editing of salivary glands is less important as mean doses achieved for non-edited glands predict well for edited structures.

Clinical validation of atlas-based auto-segmentation of multiple target volumes and normal tissue (swallowing/mastication) structures in the head and neck.

PURPOSE: To validate and clinically evaluate autocontouring using atlas-based autosegmentation (ABAS) of computed tomography images. METHODS AND MATERIALS: The data from 10 head-and-neck patients were selected as input for ABAS, and neck levels I-V and 20 organs at risk were manually contoured according to published guidelines. The total contouring times were recorded. Two different ABAS strategies, multiple and single subject, were evaluated, and the similarity of the autocontours with the atlas contours was assessed using Dice coefficients and the mean distances, using the leave-one-out method. For 12 clinically treated patients, 5 experienced observers edited the autosegmented contours. The editing times were recorded. The Dice coefficients and mean distances were calculated among the clinically used contours, autocontours, and edited autocontours. Finally, an expert panel scored all autocontours and the edited autocontours regarding their adequacy relative to the published atlas. RESULTS: The time to autosegment all the structures using ABAS was 7 min/patient. No significant differences were observed in the autosegmentation accuracy for stage N0 and N+ patients. The multisubject atlas performed best, with a Dice coefficient and mean distance of 0.74 and 2 mm, 0.67 and 3 mm, 0.71 and 2 mm, 0.50 and 2 mm, and 0.78 and 2 mm for the salivary glands, neck levels, chewing muscles, swallowing muscles, and spinal cord-brainstem, respectively. The mean Dice coefficient and mean distance of the autocontours vs. the clinical contours was 0.8 and 2.4 mm for the neck levels and salivary glands, respectively. For the autocontours vs. the edited autocontours, the mean Dice coefficient and mean distance was 0.9 and 1.6 mm, respectively. The expert panel scored 100% of the autocontours as a "minor deviation, editable" or better. The expert panel scored 88% of the edited contours as good compared with 83% of the clinical contours. The total editing time was 66 min. CONCLUSION: Multiple-subject ABAS of computed tomography images proved to be a useful novel tool in the rapid delineation of target and normal tissues. Although editing of the autocontours is inevitable, a substantial time reduction was achieved using editing, instead of manual contouring (180 vs. 66 min).

Implications of artefacts reduction in the planning CT originating from implanted fiducial markers.

The efficacy of metal artefact reduction (MAR) software to suppress artefacts in reconstructed computed tomography (CT) images originating from small metal objects, like tumor markers and surgical clips, was evaluated. In addition, possible implications of using digital reconstructed radiographs (DRRs), based on the MAR CT images, for setup verification were analyzed. A phantom and 15 patients with different tumor sites and implanted markers were imaged with a multislice CT scanner. The raw image data was reconstructed both with the clinically used filtered-backprojection (FBP) and with the MAR software. Using the MAR software, improvements in image quality were often observed in CT slices with markers or clips. Especially when several markers were located near to each other, fewer streak artefacts were observed than with the FBP algorithm. In addition, the shape and size of markers could be identified more accurately, reducing the contoured marker volumes by a factor of 2. For the phantom study, the CT numbers measured near to the markers corresponded more closely to the expected values. However, the MAR images were slightly more smoothed compared with the images reconstructed with FBP. For 8 prostate cancer patients in this study, the interobserver variation in 3D marker definition was similar (<0.4 mm) when using DRRs based on either FBP or MAR CT scans. Automatic marker matches also showed a similar success rate. However, differences in automatic match results up to 1 mm, caused by differences in the marker definition, were observed, which turned out to be (borderline) statistically significant (p = 0.06) for 2 patients. In conclusion, the MAR software might improve image quality by suppressing metal artefacts, probably allowing for a more reliable delineation of structures. When implanted markers or clips are used for setup verification, the accuracy may slightly be improved as well, which is relevant when using very tight clinical target volume (CTV) to planning target volume (PTV) margins for planning.