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Purpose This article reports on the integration of a sliding-gantry CT-on-rails with a robotic linear accelerator. Methods The system consists of a SOMATOM Definition AS CT scanner (Siemens Healthcare, Forchheim, Germany) and a CyberKnife M6 FIM (Accuray, Inc., Sunnyvale, CA, USA). Additional movement programs were implemented in the robotic treatment table (RoboCouch, Accuray Inc.) to move between CT and treatment position. Acceptance testing was performed on the CT scanner according to AAPM83 guidelines, as well as safety tests for collision avoidance and electromagnetic ( EM) compatibility. For the first clinical application of the system, daily dose was evaluated in five pancreas SBRT patients. A second envisioned use is the optimal alignment of the treatment beams to soft-tissue targets without the use of implanted fiducials. To this end, an offset vector feature has been implemented, which shifts the treatment center according to the daily position of the tumor relative to the spine (established by a CT scan). This offset can be applied by either moving the treatment couch (physical couch shift) or by moving the CyberKnife robot (virtual couch shift). An End-to-End (E2E) test was specifically designed to evaluate the accuracy of this feature using the Xsight Lung Tracking Phantom (Computerized Imaging Reference Systems, Inc., Norfolk, VA, USA). The position of the tumor with respect to the spine was varied by moving the insert inside the phantom and a CT scan was made for each position. The treatment plan was subsequently delivered to the phantom employing spine tracking. The test was repeated four times for a physical couch shift and four times for a virtual couch shift. Results All acceptance, safety and EM compatibility testing was successful. For the first pancreas SBRT patients treated using daily CT imaging, the volume of stomach, duodenum, or small bowel receiving >35 Gy was found to increase or remain constant during treatment; however, the clinical constraint of 5 cc was not violated. For the offset vector E2E test, the reference accuracy (without any tumor shift) was (0.74, −0.61, −0.33) mm in the inferior, left, and anterior direction respectively. The difference in deviation with respect to the reference was (−0.1 ± 0.15, 0.01 ± 0.16, −0.17 ± 0.25) mm, when applying a physical couch shift. With a virtual couch shift, the deviations were (0.02 ± 0.15, 0.06 ± 0.23, −0.4 ± 0.31) mm. Conclusions The first combination of a CyberKnife treatment unit with a sliding-gantry CT scanner is operational in our department enabling future developments toward image-guided online-adaptive SBRT supported by diagnostic-quality CT imaging. [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 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 investigate how dose distributions for liver stereotactic body radiation therapy (SBRT) can be improved by using automated, daily plan reoptimization to account for anatomy deformations, compared with setup corrections only. Methods and Materials: For 12 tumors, 3 strategies for dose delivery were simulated. In the first strategy, computed tomography scans made before each treatment fraction were used only for patient repositioning before dose delivery for correction of detected tumor setup errors. In adaptive second and third strategies, in addition to the isocenter shift, intensity modulated radiation therapy beam profiles were reoptimized or both intensity profiles and beam orientations were reoptimized, respectively. All optimizations were performed with a recently published algorithm for automated, multicriteria optimization of both beam profiles and beam angles. Results: In 6 of 12 cases, violations of organs at risk (ie, heart, stomach, kidney) constraints of 1 to 6 Gy in single fractions occurred in cases of tumor repositioning only. By using the adaptive strategies, these could be avoided (<1 Gy). For 1 case, this needed adaptation by slightly underdosing the planning target volume. For 2 cases with restricted tumor dose in the planning phase to avoid organ-at-risk constraint violations, fraction doses could be increased by 1 and 2 Gy because of more favorable anatomy. Daily reoptimization of both beam profiles and beam angles (third strategy) performed slightly better than reoptimization of profiles only, but the latter required only a few minutes of computation time, whereas full reoptimization took several hours. Conclusions: This simulation study demonstrated that replanning based on daily acquired computed tomography scans can improve liver stereotactic body radiation therapy dose delivery. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Abstract: 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 (V95) and the near-minimum dose (D99) 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, V95 reduced by 7.2%±5.4% (1 SD) (p <0.03). The mean reduction in D99 was 14.2Gy (range 1–54Gy). Even for Dice coefficients >0.8 and mean contour distances <1mm, reductions in D99 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 −0.6Gy±1.0Gy (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. [Copyright &y& Elsevier]

Abstract: Purpose: To provide a prescription dose for Monte Carlo (MC) treatment planning in patients with non-small-cell lung cancer according to tumor size and location. Methods: Fifty-three stereotactic radiotherapy plans designed using the equivalent path-length (EPL) algorithm were re-calculated using MC. Plans were compared by the minimum dose to 95% of the PTV (D95), the heterogeneity index (HI) and the mean dose to organs at risk (OARs). Based on changes in D95, the prescription dose was converted from EPL to MC. Based on changes in HI, we examined the feasibility of MC prescription to plans re-calculated but not re-optimized with MC. Results: The MC fraction dose for peripheral tumors is 16–18Gy depending on tumor size. For central tumors the MC dose was reduced less than for peripheral tumors. The HI decreased on average by 4–9% in peripheral tumors and 3–5% in central tumors. The mean dose to OARs was lower for MC than EPL, and correlated strongly (R 2 =0.98–0.99). Conclusion: For the conversion from EPL to MC we recommend a separate prescription dose according to tumor size. MC optimization is not required if a HI⩾70% is accepted. Dose constraints to OARs can be easily converted due to the high EPL–MC correlation. [Copyright &y& Elsevier]

Purpose: To assess day-to-day differences between planned and delivered target volume (TV) and organ-at-risk (OAR) dose distributions in liver stereotactic body radiation therapy (SBRT), and to investigate the dosimetric impact of setup corrections. Methods and Materials: For 14 patients previously treated with SBRT, the planning CT scan and three treatment scans (one for each fraction) were included in this study. For each treatment scan, two dose distributions were calculated: one using the planned setup for the body frame (no correction), and one using the clinically applied (corrected) setup derived from measured tumor displacements. Per scan, the two dose distributions were mutually compared, and the clinically delivered distribution was compared with planning. Doses were recalculated in equivalent 2-Gy fraction doses. Statistical analysis was performed with the linear mixed model. Results: With setup corrections, the mean loss in TV coverage relative to planning was 1.7%, compared with 6.8% without corrections. For calculated equivalent uniform doses, these figures were 2.3% and 15.5%, respectively. As for the TV, mean deviations of delivered OAR doses from planning were small (between −0.4 and +0.3 Gy), but the spread was much larger for the OARs. In contrast to the TV, the mean impact of setup corrections on realized OAR doses was close to zero, with large positive and negative exceptions. Conclusions: Daily correction of the treatment setup is required to obtain adequate TV coverage. Because of day-to-day patient anatomy changes, large deviations in OAR doses from planning did occur. On average, setup corrections had no impact on these doses. Development of new procedures for image guidance and adaptive protocols is warranted. [Copyright &y& Elsevier]

Abstract: Background and purpose: We are developing a technique for highly focused vocal cord irradiation in early glottic carcinoma to optimally treat a target volume confined to a single cord. This technique, in contrast with the conventional methods, aims at sparing the healthy vocal cord. As such a technique requires sub-mm daily targeting accuracy to be effective, we investigate the accuracy achievable with on-line kV-cone beam CT (CBCT) corrections. Materials and methods: CBCT scans were obtained in 10 early glottic cancer patients in each treatment fraction. The grey value registration available in X-ray volume imaging (XVI) software (Elekta, Synergy) was applied to a volume of interest encompassing the thyroid cartilage. After application of the thus derived corrections, residue displacements with respect to the planning CT scan were measured at clearly identifiable relevant landmarks. The intra- and inter-observer variations were also measured. Results: While before correction the systematic displacements of the vocal cords were as large as 2.4±3.3mm (cranial–caudal population mean±SD Σ), daily CBCT registration and correction reduced these values to less than 0.2±0.5mm in all directions. Random positioning errors (SD σ) were reduced to less than 1mm. Correcting only for translations and not for rotations did not appreciably affect this accuracy. The residue random displacements partly stem from intra-observer variations (SD=0.2–0.6mm). Conclusion: The use of CBCT for daily image guidance in combination with standard mask fixation reduced systematic and random set-up errors of the vocal cords to <1mm prior to the delivery of each fraction dose. Thus, this facilitates the high targeting precision required for a single vocal cord irradiation. [Copyright &y& Elsevier]

Purpose: To evaluate the efficacy of the No Action Level (NAL) off-line correction protocol in the reduction of systematic prostate displacements as determined from electronic portal images (EPI) using implanted markers. Methods and Materials: Four platinum markers, two near the apex and two near the base of the prostate, were implanted for localization purposes in patients who received fractionated high dose rate brachytherapy. During the following course of 25 fractions of external beam radiotherapy, the position of each marker relative to the corresponding position in digitally reconstructed radiographs (DRRs) was measured in EPI in 15 patients for on average 17 fractions per patient. These marker positions yield the composite displacements due to both setup error and internal prostate motion, relative to the planning computed tomography scan. As the NAL protocol is highly effective in reducing systematic errors (recurring each fraction) due to setup inaccuracy alone, we investigated its efficacy in reducing systematic composite displacements. The analysis was performed for the center of mass (COM) of the four markers, as well as for the cranial and caudal markers separately. Furthermore, the impact of prostate rotation on the achieved positioning accuracy was determined. Results: In case of no setup corrections, the standard deviations of the systematic composite displacements of the COM were 3-4 mm in the craniocaudal and anterior-posterior directions, and 2 mm in the left-right direction. The corresponding SDs of the random displacements (interfraction fluctuations) were 2-3 mm in each direction. When applying a NAL protocol based on three initial treatment fractions, the SDs of the systematic COM displacements were reduced to 1-2 mm. Displacements at the cranial end of the prostate were slightly larger than at the caudal end, and quantitative analysis showed this originates from left-right axis rotations about the prostate apex. Further analysis revealed that significant time trends are present in these prostate rotations. No significant trends were observed for the prostate translations. Conclusions: The NAL protocol based on marker positions in EPI halved the composite systematic displacements using only three imaged fractions per patient, and thus allowed for a significant reduction of planning margins. Although large rotations of the prostate, and time trends therein, were observed, the net impact on the measured displacements and on the accuracy obtained with NAL was small. [ABSTRACT FROM AUTHOR]