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Purpose: To propose and validate a fully automated multicriterial treatment planning solution for a CyberKnife® equipped with an InCiseTM 2 multileaf collimator. Methods: The AUTO BAO plans are generated using fully automated prioritized multicriterial optimization (AUTO MCO) of pencil‐beam fluence maps with integrated noncoplanar beam angle optimization (BAO), followed by MLC segment generation. Both the AUTO MCO and segmentation algorithms have been developed in‐house. AUTO MCO generates for each patient a single, high‐quality Pareto‐optimal IMRT plan. The segmentation algorithm then accurately mimics the AUTO MCO 3D dose distribution, while considering all candidate beams simultaneously, rather than replicating the fluence maps. Pencil‐beams, segment dose depositions, and final dose calculations are performed with a stand‐alone version of the clinical dose calculation engine. For validation, AUTO BAO plans were generated for 33 prostate SBRT patients and compared to reference plans (REF) that were manually generated with the commercial treatment planning system (TPS), in absence of time pressure. REF plans were also compared to AUTO RB plans, for which fluence map optimization was performed for the beam angle configuration used in the REF plan, and the segmentation could use all these beams or only a subset, depending on the dosimetry. Results: AUTO BAO plans were clinically acceptable and dosimetrically similar to REF plans, but had on average reduced numbers of beams ((beams in AUTO BAO)/(beams in REF) (relative improvement): 24.7/48.3 (−49%)), segments (59.5/98.9 (−40%)), and delivery times (17.1/22.3 min. (−23%)). Dosimetry of AUTO RB and REF were also similar, but AUTO RB used on average fewer beams (38.0/48.3 (−21%)) and had on average shorter delivery times (18.6/22.3 min. (−17%)). Delivered Monitor Units (MU) were similar for all three planning approaches. Conclusions: A new, vendor‐independent optimization workflow for fully automated generation of deliverable high‐quality CyberKnife® plans was proposed, including BAO. Compared to manual planning with the commercial TPS, fraction delivery times were reduced by 5.3 min. (−23%) due to large reductions in beam and segment numbers. [ABSTRACT FROM AUTHOR]

Purpose To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system “Erasmus-iCycle.” The method consisted of 2 components: ( 1 ) minimizing the logarithm of the total spot weight per energy layer; and ( 2 ) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust “time-efficient plan” (with energy layer reduction) with a robust “standard clinical plan” (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases. Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs. [ABSTRACT FROM AUTHOR]

Background and purpose Planned doses are used as surrogate for the actually delivered dose in radiotherapy. We have estimated the delivered dose in a dose-escalation trial of locally advanced prostate cancer by statistical dose-accumulation and by DVH-summation, and compared to planned dose. Materials and method Prescribed dose-escalation to the prostate was 67.5 Gy/25fr., corresponding to 81GyEQD2 assuming α/β  = 1.5. The 21 patients had three targets (i.e. CTV67.5 + 2 mm, CTV60 + 5 mm, CTV50 + 10 mm) irradiated by a simultaneous-integrated-boost technique. Analysis was based on 213 CT scans and 5-years of follow-up. For statistical dose-accumulation, we modelled 10 000 possible treatment courses based on planned dose and deformation-vector-fields from contour-based registration. For DVH-summation we recalculated dose on repeat-CTs and estimated median D98%/EUD. Groups with/without disease recurrence were compared. Results Discrepancies between planned and accumulated dose were mostly seen for CTV67.5, where under-dosage was found at different locations in the prostate in 12/21 patients. Delivered dose-escalation (D98%) was on average 73.9GyEQD2 (range: 68.3–78.7GyEQD2). No significant difference in accumulated-D98% was found in patients with ( n  = 8) and without ( n  = 13) recurrence ( p  > 0.05). Average D98%/EUD with statistical dose-accumulation vs DVH-summation was significantly different in CTV60, CTV50, rectum and bladder but not in CTV67.5. Conclusion The planned dose escalation was not received by more than half-of-the patients. Robustness of the prostate target (CTV67.5) should therefore be better prioritized in these patients given the low toxicity profile. Estimates of delivered dose were less conservative for dose-accumulation due to interaction of random organ motion with the dose matrix. [ABSTRACT FROM AUTHOR]

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 4.1 min on average, compared to VMAT (8.4 min). Improvements in OAR sparing with 25-NCP, compared to VMAT+, were generally modest and/or statistically insignificant, while delivery times were on average 20.5 min 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. [ABSTRACT FROM AUTHOR]

Purpose To quantify the impact of the degree of robustness against setup errors and range errors on organ-at-risk (OAR) dose and normal tissue complication probabilities (NTCPs) in intensity-modulated proton therapy for oropharyngeal cancer patients. Material and methods For 20 oropharyngeal cases (10 unilateral and 10 bilateral), robust treatment plans were generated using ‘minimax’ worst-case optimization. We varied the robustness against setup errors (‘setup robustness’) from 1 to 7 mm and the robustness against range errors (‘range robustness’) from 1% to 7% (+1 mm). We evaluated OAR doses and NTCP-values for xerostomia, dysphagia and larynx edema. Results Varying the degree of setup robustness was found to have a considerably larger impact than varying the range robustness. Increasing setup robustness from 1 mm to 3, 5, and 7 mm resulted in average NTCP-values to increase by 1.9, 4.4 and 7.5 percentage point, whereas they increased by only 0.4, 0.8 and 1.2 percentage point when increasing range robustness from 1% to 3%, 5% and 7%. The degree of setup robustness was observed to have a clinically significant impact in bilateral cases in particular. Conclusions For oropharyngeal cancer patients, minimizing setup errors should be given a higher priority than minimizing range errors. [ABSTRACT FROM AUTHOR]

Purpose: To report, from a retrospective analysis of prospectively collected data, on the feasibility, outcome, toxicity, and voice-handicap index (VHI) of patients with T1a glottic cancer treated by a novel intensity modulated radiation therapy technique developed at our institution to treat only the involved vocal cord: single vocal cord irradiation (SVCI). Methods and Materials: Thirty patients with T1a glottic cancer were treated by means of SVCI. Dose prescription was set to 16 × 3.63 Gy (total dose 58.08 Gy). The clinical target volume was the entire vocal cord. Setup verification was done by means of an online correction protocol using cone beam computed tomography. Data for voice quality assessment were collected prospectively at baseline, end of treatment, and 4, 6, and 12 weeks and 6, 12, and 18 months after treatment using VHI questionnaires. Results: After a median follow-up of 30 months (range, 7-50 months), the 2-year local control and overall survival rates were 100% and 90% because no single local recurrence was reported and 3 patients died because of comorbidity. All patients have completed the intended treatment schedule; no treatment interruptions and no grade 3 acute toxicity were reported. Grade 2 acute dermatitis or dysphagia was reported in only 5 patients (17%). No serious late toxicity was reported; only 1 patient developed temporary grade 2 laryngeal edema, and responded to a short-course of corticosteroid. The VHI improved significantly, from 33.5 at baseline to 9.5 and 10 at 6 weeks and 18 months, respectively (P<.001). The control group, treated to the whole larynx, had comparable local control rates (92.2% vs 100%, P=.24) but more acute toxicity (66% vs 17%, P<.0001) and higher VHI scores (23.8 and 16.7 at 6 weeks and 18 months, respectively, P<.0001). Conclusion: Single vocal cord irradiation is feasible and resulted in maximal local control rate at 2 years. The deterioration in VHI scores was slight and temporary and subsequently improved to normal levels. Long-term follow-up is needed to consolidate these promising results. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to verify clinical target volume–planning target volume (CTV-PTV) margins in single vocal cord irradiation (SVCI) of T1a larynx tumors and characterize inter- and intrafraction target motion. Methods and Materials For 42 patients, a single vocal cord was irradiated using intensity modulated radiation therapy at a total dose of 58.1 Gy (16 fractions × 3.63 Gy). A daily cone beam computed tomography (CBCT) scan was performed to online correct the setup of the thyroid cartilage after patient positioning with in-room lasers (interfraction motion correction). To monitor intrafraction motion, CBCT scans were also acquired just after patient repositioning and after dose delivery. A mixed online-offline setup correction protocol (“O2 protocol”) was designed to compensate for both inter- and intrafraction motion. Results Observed interfraction, systematic (Σ), and random (σ) setup errors in left-right (LR), craniocaudal (CC), and anteroposterior (AP) directions were 0.9, 2.0, and 1.1 mm and 1.0, 1.6, and 1.0 mm, respectively. After correction of these errors, the following intrafraction movements derived from the CBCT acquired after dose delivery were: Σ = 0.4, 1.3, and 0.7 mm, and σ = 0.8, 1.4, and 0.8 mm. More than half of the patients showed a systematic non-zero intrafraction shift in target position, (ie, the mean intrafraction displacement over the treatment fractions was statistically significantly different from zero; P <.05). With the applied CTV-PTV margins (for most patients 3, 5, and 3 mm in LR, CC, and AP directions, respectively), the minimum CTV dose, estimated from the target displacements observed in the last CBCT, was at least 94% of the prescribed dose for all patients and more than 98% for most patients (37 of 42). The proposed O2 protocol could effectively reduce the systematic intrafraction errors observed after dose delivery to almost zero (Σ = 0.1, 0.2, 0.2 mm). Conclusions With adequate image guidance and CTV-PTV margins in LR, CC, and AP directions of 3, 5, and 3 mm, respectively, excellent target coverage in SVCI could be ensured. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the clinical implementation of an online adaptive plan-of-the-day protocol for nonrigid target motion management in locally advanced cervical cancer intensity modulated radiation therapy (IMRT). Methods and Materials Each of the 64 patients had four markers implanted in the vaginal fornix to verify the position of the cervix during treatment. Full and empty bladder computed tomography (CT) scans were acquired prior to treatment to build a bladder volume-dependent cervix-uterus motion model for establishment of the plan library. In the first phase of clinical implementation, the library consisted of one IMRT plan based on a single model-predicted internal target volume (mpITV), covering the target for the whole pretreatment observed bladder volume range, and a 3D conformal radiation therapy (3DCRT) motion-robust backup plan based on the same mpITV. The planning target volume (PTV) combined the ITV and nodal clinical target volume (CTV), expanded with a 1-cm margin. In the second phase, for patients showing >2.5-cm bladder-induced cervix-uterus motion during planning, two IMRT plans were constructed, based on mpITVs for empty-to-half-full and half-full-to-full bladder. In both phases, a daily cone beam CT (CBCT) scan was acquired to first position the patient based on bony anatomy and nodal targets and then select the appropriate plan. Daily post-treatment CBCT was used to verify plan selection. Results Twenty-four and 40 patients were included in the first and second phase, respectively. In the second phase, 11 patients had two IMRT plans. Overall, an IMRT plan was used in 82.4% of fractions. The main reasons for selecting the motion-robust backup plan were uterus outside the PTV (27.5%) and markers outside their margin (21.3%). In patients with two IMRT plans, the half-full-to-full bladder plan was selected on average in 45% of the first 12 fractions, which was reduced to 35% in the last treatment fractions. Conclusions The implemented online adaptive plan-of-the-day protocol for locally advanced cervical cancer enables (almost) daily tissue-sparing IMRT. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Pretreatment verification with an electronic portal imaging device is an important part of our patient-specific quality assurance program for advanced treatment techniques. Up to now, this verification has been performed for over 400 IMRT patient plans. For every treatment field, a 2D portal dose image (PDI) is measured and compared with a predicted PDI. Often it is not straightforward to interpret dose deviations found in these 2D comparisons in terms of clinical implications for the patient. Therefore, a method to derive the 3D patient dose based on the measured PDIs was implemented. Methods and materials: For reconstruction of the 3D patient dose, the actual fluences delivered by the accelerator are derived from measured portal dose images using an iterative method. The derived fluence map for each beam direction is then used as input for the treatment planning system to generate an adapted 3D patient dose distribution. The accuracy of this method was assessed by measurements in a water phantom. Clinical evaluation of the 3D dose reconstruction was performed for 17 IMRT patients with different tumor sites. Dose differences with respect to the original treatment plan were evaluated in individual CT slices using dose difference maps and a 3D γ analysis and by comparing dose-volume histograms (DVHs). Results: The measurements indicated that the accuracy of the 3D dose reconstruction was within 2%/2mm. For the patients observed dose differences with respect to the original plan were generally within 2%, except at the field edges and in the sharp dose gradients around the planning target volume (PTV). Gamma analysis showed that the dose differences were within 2%/2mm for more than 95% of the points in all cases. Differences in DVH parameters for the PTV and organs at risk were also within 2% in nearly all cases. Conclusion: A method to derive actual delivered fluence maps from measured PDIs and to use them to reconstruct the 3D patient dose was implemented. The reconstruction eases the estimation of the clinical relevance of observed dose differences in the pretreatment measurements. [Copyright &y& Elsevier]

Abstract: Background and purpose: In our clinic a QA program for IMRT verification, fully based on dosimetric measurements with electronic portal imaging devices (EPID), has been running for over 3 years. The program includes a pre-treatment dosimetric check of all IMRT fields. During a complete treatment simulation at the linac, a portal dose image (PDI) is acquired with the EPID for each patient field and compared with a predicted PDI. In this paper, the results of this pre-treatment procedure are analysed, and intercepted errors are reported. An automated image analysis procedure is proposed to limit the number of fields that need human intervention in PDI comparison. Materials and methods: Most of our analyses are performed using the γ index with 3% local dose difference and 3mm distance to agreement as reference values. Scalar parameters are derived from the γ values to summarize the agreement between measured and predicted 2D PDIs. Areas with all pixels having γ values larger than one are evaluated, making decisions based on clinically relevant criteria more straightforward. Results: In 270 patients, the pre-treatment checks revealed four clinically relevant errors. Calculation of statistics for a group of 75 patients showed that the patient-averaged mean γ value inside the field was 0.43±0.13 (1SD) and only 6.1±6.8% of pixels had a γ value larger than one. With the proposed automated image analysis scheme, visual inspection of images can be avoided in 2/3 of the cases. Conclusion: EPIDs may be used for high accuracy and high resolution routine verification of IMRT fields to intercept clinically relevant dosimetric errors prior to the start of treatment. For the majority of fields, PDI comparison can fully rely on an automated procedure, avoiding excessive workload. [Copyright &y& Elsevier]

Abstract: Purpose: Intensity modulated radiotherapy (IMRT) requires dedicated quality assurance (QA). Recently, we have published a method for fast (1–2min) and accurate linac quality control for dynamic multileaf collimation, using a portal imaging device. This method is in routine use for daily leaf motion verification. The purpose of the present study was to develop an equivalent procedure for QA of IMRT with segmented (static) multileaf collimation (SMLC). Materials and methods: The QA procedure is based on measurements performed during 3- to 8-month periods at Elekta, Siemens and Varian accelerators. On each measurement day, images were acquired for a field consisting of five 3×22cm2 segments. These 10 monitor unit (MU) segments were delivered in SMLC mode, moving the leaves from left to right. Deviations of realized leaf gap widths from the prescribed width were analysed to study the leaf positioning accuracy. To assess hysteresis in leaf positioning, the sequential delivery of the SMLC segments was also inverted. A static 20×20cm2 field was delivered with exposures between 1 and 50 MU to study the beam output and beam profile at low exposures. Comparisons with an ionisation chamber were made to verify the EPID dose measurements at low MU. Dedicated software was developed to improve the signal-to-noise ratio and to correct for image distortion. Results and conclusions: The observed long-term leaf gap reproducibility (1 standard deviation) was 0.1mm for the Varian, and 0.2mm for the Siemens and the Elekta accelerators. In all cases the hysteresis was negligible. Down to the lowest MU, beam output measurements performed with the EPID agreed within 1±1% (1SD) with ionisation chamber measurements. These findings led to a fast (3–4min) procedure for accurate, daily linac quality control for SMLC. [Copyright &y& Elsevier]