An offline technique to evaluate residual motion of the diaphragm during deep inspiratory breath-hold from cone-beam CT datasets.

PURPOSE: In radiation therapy, the computer-assisted deep inspiration breath-hold (DIBH) technique is one approach to deal with respiratory motion of tumors in the lung, liver, or upper abdomen. However, inter- and intra-breath-hold deviations from an optimal static tumor position might occur. A novel method is presented to noninvasively measure the diaphragm position and thus estimate its residual deviation (as surrogate for the tumor position) based on cone-beam computed tomography (CBCT) projection data using active breathing control during acquisition. METHODS: The diaphragm dome (DD) position relative to the isocenter of a linear accelerator is known from the static (DIBH) planning CT. A ball-bearing phantom (BB) is placed at this position, a CBCT dataset is acquired, and in each projection the position of the projected BB is determined automatically based on thresholding. The position of the DD is determined manually in CBCT projections of a patient. The distance between DD and BB (ideal static setting) in craniocaudal direction is calculated for a given angle based on the distance in the projection plane and the relative position of the BB referring to the source and the detector. An angle-dependent correction factor is introduced which takes this geometrical setting into account. The accuracy of the method is assessed. RESULTS: The method allows a CBCT projection-based estimation of the deviation between the DD and its optimal position as defined in the planning CT, i.e., the residual motion of the DD can be assessed. The error of this estimation is 2.2 mm in craniocaudal direction. CONCLUSIONS: The developed method allows an offline estimation of the inspiration depth (inter- and intra-breath-hold) over time. It will be useful as a reference for comparison to other methods of residual motion estimation, e.g., surface scanning.

Automatically gated image-guided breath-hold IMRT is a fast, precise, and dosimetrically robust treatment for lung cancer patients.

BACKGROUND: High-dose radiotherapy of lung cancer is challenging. Tumors may move by up to 2 cm in craniocaudal and anteroposterior directions as a function of breathing cycle. Tumor displacement increases with treatment time, which consequentially increases the treatment uncertainty. OBJECTIVE: This study analyzed whether automatically gated cone-beam-CT (CBCT)-controlled intensity modulated fast deep inspiration breath hold (DIBH) stereotactic body radiation therapy (SBRT) in flattening filter free (FFF) technique and normofractionated lung DIBH intensity-modulated radiotherapy (IMRT)/volumetric-modulated arc therapy (VMAT) treatments delivered with a flattening filter can be applied with sufficient accuracy within a clinically acceptable timeslot. MATERIALS AND METHODS: Plans of 34 patients with lung tumors were analyzed. Of these patients, 17 received computer-controlled fast DIBH SBRT with a dose of 60 Gy (5 fractions of 12 Gy or 12 fractions of 5 Gy) in an FFF VMAT technique (FFF-SBRT) every other day and 17 received conventional VMAT with a flattening filter (conv-VMAT) and 2-Gy daily fractional doses (cumulative dose 50-70 Gy). RESULTS: FFF-SBRT plans required more monitor units (MU) than conv-VMAT plans (2956.6 ± 885.3 MU for 12 Gy/fraction and 1148.7 ± 289.2 MU for 5 Gy/fraction vs. 608.4 ± 157.5 MU for 2 Gy/fraction). Total treatment and net beam-on times were shorter for FFF-SBRT plans than conv-VMAT plans (268.0 ± 74.4 s vs. 330.2 ± 93.6 s and 85.8 ± 25.3 s vs. 117.2 ± 29.6 s, respectively). Total slot time was 13.0 min for FFF-SBRT and 14.0 min for conv-VMAT. All modalities could be delivered accurately despite multiple beam-on/-off cycles and were robust against multiple interruptions. CONCLUSION: Automatically gated CBCT-controlled fast DIBH SBRT in VMAT FFF technique and normofractionated lung DIBH VMAT can be applied with a low number of breath-holds in a short timeslot, with excellent dosimetric accuracy. In clinical routine, these approaches combine optimally reduced lung tissue irradiation with maximal delivery precision for patients with small and larger lung tumors.

Homogenous dose prescription in Gamma Knife Radiotherapy: Combining the best of both worlds.

PURPOSE: Stereotactic radiosurgery with linear accelerators (LINACs) or Leksell Gamma Knife® (LGK, Elekta AB) is an established treatment option for intracranial tumors. When those are involving/abutting organs at risk (OAR), homogenous and normofractionated treatments outmatch single fraction deliveries. In such situations, it would be desirable to balance LINAC's homogeneity benefits with LGK's dose gradient attributes. In this study, we determined homogeneity and OAR sparing ranges using a non-clinical, homogenous prototype version of LGK Lightning. METHODS: We retrospectively analyzed thirty fractionated LGK Icon in-house patients with acoustic neuromas, pituitary adenomas and meningiomas. Four treatment plans were generated (54 Gy,1.8 Gy/fx) per patient: one LINAC plan, one clinical Lightning plan ("LGK") and two prototype Lightning plans ("LGK Hom" and "LGK OAR"). We analyzed Dmean and D2% for different OAR, Gradient Index (GI), Paddick Conformity Index (PCI), Homogeneity Index (HI) and beam-on-time (BOT). RESULTS: While the LINAC vs. Lightning plans (LGK Hom|LGK OAR|LGK) boast better homogeneity (median: 1.08 vs. 1.18|1.24|1.35) and shorter BOT (median: 137 s vs. 432 s|510 s|510 s), Lightning plans show improved GI (median: 6.68 vs. 3.86|3.50|3.19), similar PCI (median: 0.75 vs. 0.76|0.75|0.82) and significantly reduced OAR doses. For in-tumor OAR, LGK Hom and LINAC plans achieves similar OAR sparing with improved GI for LGK Hom. CONCLUSIONS: This study is a preliminary attempt to combine the dosimetric advantages of LINAC and LGK treatment planning. We observed that LGK plan homogeneity can be improved toward LINAC standards while maintaining the LGK advantage of favorable OAR doses and GI. Additionally, in-tumor OAR hotspots can be considerably reduced.

Impact of the Novel MRI Contrast Agent Gadopiclenol on Radiotherapy Decision Making in Patients With Brain Metastases.

PURPOSE: The aim of this study was to assess the effect of gadopiclenol versus gadobenate dimeglumine contrast-enhanced magnetic resonance imaging (MRI) on decision-making between whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) for treatment of brain metastases (BMs). METHODS: Patients with BMs underwent 2 separate MRI examinations in a double-blind crossover phase IIb comparative study between the MRI contrast agents gadopiclenol and gadobenate dimeglumine, both administered at 0.1 mmol/kg. The imaging data of a single site using identical MRI scanners and protocols were included in this post hoc analysis. Patients with 1 or more BMs in any of both MRIs were subjected to target volume delineation for treatment planning. Two radiation oncologists contoured all visible lesions and decided upon SRS or WBRT, according to the number of metastases. For each patient, SRS or WBRT treatment plans were calculated for both MRIs, considering the gross target volume (GTV) as the contrast-enhancing aspects of the tumor. Mean GTVs and volume of healthy brain exposed to 12 Gy (V12), as well as Dice similarity coefficient scores, were obtained. The Spearman rank (ρ) correlation was additionally calculated for assessing linear differences. Three different expert radiation oncologists blindly rated the contrast enhancement for contouring purposes. RESULTS: Thirteen adult patients were included. Gadopiclenol depicted additional BM as compared with gadobenate dimeglumine in 7 patients (54%). Of a total of 63 identified metastatic lesions in both MRI sets, 3 subgroups could be defined: A, 48 (24 pairs) detected equal GTVs visible in both modalities; B, 13 GTVs only visible in the gadopiclenol set (mean ± SD, 0.16 ± 0.37 cm3); and C, 2 GTVs only visible in the gadobenate dimeglumine set (mean ± SD, 0.01 ± 0.01). Treatment indication was changed for 2 (15%) patients, 1 from no treatment to SRS and for 1 from SRS to WBRT. The mean GTVs and brain V12 were comparable between both agents (P = 0.694, P = 0.974). The mean Dice similarity coefficient was 0.70 ± 0.14 (ρ = 0.82). According to the readers, target volume definition was improved in 63.9% of cases (23 of 36 evaluations) with gadopiclenol and 22.2% with gadobenate dimeglumine (8 of 36), whereas equivalence was obtained in 13.9% (5 of 36). CONCLUSIONS: Gadopiclenol-enhanced MRI improved BM detection and characterization, with a direct impact on radiotherapy treatment decision between WBRT and SRS. Additionally, a more exact target delineation and planning could be performed with gadopiclenol. A prospective evaluation in a larger cohort of patients is required to confirm these findings.

Surface guidance compared with ultrasound-based monitoring and diaphragm position in cone-beam computed tomography during abdominal stereotactic radiotherapy in breath-hold.

Background and purpose: Spirometry induced deep-inspiration-breath-hold (DIBH) reduces intrafractional motion during upper abdominal stereotactic body radiotherapy (SBRT). The aim of this prospective study was to evaluate whether surface scanning (SGRT) is an adequate surrogate for monitoring residual internal motion during DIBH. Residual motion detected by SGRT was compared with experimental 4D-ultrasound (US) and an internal motion detection benchmark (diaphragm-dome-position in kV cone-beam computed tomography (CBCT) projections). Materials and methods: Intrafractional monitoring was performed with SGRT and US in 460 DIBHs of 12 patients. Residual motion detected by all modalities (SGRT (anterior-posterior (AP)), US (AP, craniocaudal (CC)) and CBCT (CC)) was analyzed. Agreement analysis included Wilcoxon signed rank test, Maloney and Rastogi's test, Pearson's correlation coefficient (PCC) and interclass correlation coefficient (ICC). Results: Interquartile range was 0.7 mm (US(AP)), 0.8 mm (US(CC)), 0.9 mm (SGRT) and 0.8 mm (CBCT). SGRT(AP) vs. CBCT(CC) and US(CC) vs. CBCT(CC) showed comparable agreement (PCCs 0.53 and 0.52, ICCs 0.51 and 0.49) with slightly higher precision of CBCT(CC). Most agreement was observed for SGRT(AP) vs. US(AP) with largest PCC (0.61) and ICC (0.60), least agreement for SGRT(AP) vs. US(CC) with smallest PCC (0.44) and ICC (0.42). Conclusions: Residual motion detected during spirometry induced DIBH is small. SGRT alone is no sufficient surrogate for residual internal motion in all patients as some high velocity motion could not be detected. Observed patient-specific residual errors may require individualized PTV-margins.

Reirradiation of spinal column metastases: comparison of several treatment techniques and dosimetric validation for the use of VMAT.

BACKGROUND: For reirradiation of spinal column metastases, intensity-modulated radiation therapy (IMRT) reduces the dose to the spinal cord, while allowing longer treatment times. We analyzed the potential of volumetric modulated arc therapy (VMAT) to reduce treatment time and number of monitor units (MU). PATIENTS AND METHODS: In CT datasets of 9 patients with spinal column metastases, the planned target volume (PTV) encompassed the macroscopic tumor including the spinal cord or medullary cone, respectively. The prescribed dose for the target was 40 Gy, but median spinal cord dose was intended to be < 26 Gy. We compared a posterior (3D-PA) static field technique, a two-field wedge technique (3D-wedge) and 5-/7-beam IMRT with VMAT. Conformity index (CI), homogeneity index (HI40), dose volume histogram (DVH) parameters, treatments delivery time (T), and MU were analyzed. Dosimetry was validated with EDR2-film/ionization chambers. RESULTS: PTV coverage was insufficient for 3D-conformal radiotherapy (3D-CRT) when spinal cord tolerance was respected. The IMRT approach provided excellent results but has the longest treatment time. VMAT produced dose distributions similar to IMRT with shorter treatment times (VMAT: mean 4:49 min; IMRT: mean 6:50 min) and fewer MU (VMAT: 785; IMRT: 860). Reduced conformity and increased homogeneity for VMAT when compared to IMRT were observed. An absolute deviation between measured and calculated dose of +0.70 ± 3.69% was recorded. γ-Index analysis showed an agreement of 91.33 ± 3.53% for the 5%/5 mm criteria. CONCLUSION: For this paradigm, VMAT produces high quality treatment plans with homogeneity/conformity similar to static IMRT, shorter treatment times, and fewer MU. Verification measurements showed good agreement between calculation and delivered dose, leading to clinical implementation.

Inverse planning in Gamma Knife radiosurgery: A comparative planning study.

PURPOSE: To determine the advantages of inverse planning using a prerelease version of Leksell Gamma Knife® (LGK) Lightning (Elekta AB, Sweden) compared to manual forward planning. METHODS: Thirty-eight patients with metastases (MET, n = 15), vestibular schwannomas (VS, n = 11) and meningiomas (MEN, n = 12), treated with LGK Icon™ at our institution, were analyzed retrospectively. For each case, an inverse (inv) and inverse full coverage (fc) treatment plan was generated using LGK Lightning and compared to the clinical plans. Several dosimetry and efficiency characteristics were compared for each indication. The mean, median difference and interquartile range were reported and the significance was assessed with a paired-sample Wilcoxon test (significance level < 0.05). Further, the inter operator variability was analyzed for multiple users. RESULTS: Inv and fc treatment plans show improved target coverage (up to 3.6%) for all analyzed paradigms. For inv plans, the selectivity is enhanced (MET: 2.9%; VS: 1.8%; MEN: 1%) and the organ at risk doses are significantly reduced (VS: up to 4.5%; MEN: up to 17.5%). For inv and fc plans, the beam on time (BOT) is shortened (MET: up to 7.9%; benign tumors: 49.5%). The inter operator variability analysis shows similar treatment plan quality with small differences in plan efficiency (difference in BOT: 1-3.3 min). CONCLUSIONS: LGK Lightning allows to generate improved LGK treatment plans regarding plan quality with reduced BOT compared to manual forward plans. The inter operator variability showed that multiple users with different experiences can generate similar treatment plan quality using LGK Lightning.

Clinical implementation of volumetric intensity-modulated arc therapy (VMAT) with ERGO++.

BACKGROUND AND PURPOSE: Volumetric modulated arc therapy (VMAT) has the potential to deliver dose distributions comparable to the established intensity-modulated radiotherapy techniques for a multitude of target paradigms. Prior to implementing VMAT into their clinical routine in December 2008, the authors evaluated the dose calculation/delivery accuracy of 24 sample VMAT plans (prostate and anal cancer target paradigms) with film and ionization dosimetry. After the start of the clinical program, in vivo measurements with a rectal probe were performed. MATERIAL AND METHODS: The VMAT plans were generated by the treatment-planning system (TPS) ERGO++ (Elekta, Crawley, UK) and transferred to a phantom. Film dosimetry was performed with Kodak EDR2 films, and evaluated with dose profiles and gamma-index analysis. Appropriate ionization chambers were used for absolute dose measurements in the phantom and for in vivo measurements. The ionization chamber was used with localization of the measurement volume based on positioning cone-beam computed tomography. RESULTS: Plans were transferred from ERGO++ to the record and verify (R&V) system/linear accelerator (linac). The absolute dose deviations recorded with the ionization chamber were 1.74% +/- 1.62% across both indications. The gamma-index analysis of the film dosimetry showed no deviation > 3%/3 mm in the high-dose region. On in vivo measurements, a deviation between calculation and measurement of 2.09% +/- 2.4% was recorded, when the chamber was successfully positioned in the high-dose region. CONCLUSION: VMAT plans can be planned and treated reproducibly in high quality after the commissioning of the complete delivery chain consisting of TPS, R&V system and linac. The results of the individual plan verification meet the commonly accepted requirements. The first in vivo measurements confirm the reproducible precision of the delivered dose during clinical treatments.

Postoperative stereotactic radiosurgery and hypofractionated radiotherapy for brain metastases using Gamma Knife and CyberKnife: a dual-center analysis.

BACKGROUND: Postoperative stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hFSRT) to tumor cavities is emerging as a new standard of care after resection of brain metastases. Both Gamma Knife (GK) and CyberKnife (CK) are modalities commonly used for stereotactic radiotherapy, but fractional schemes are not consistent. The objective of this study was to evaluate outcomes in patients receiving postoperative stereotactic radiotherapy of resected brain metastases (BM) using different fractionation schedules and modalities in two large centers. METHODS: Patients with newly diagnosed BM who underwent postoperative SRS or hFSRT with either GK or CK at two large cancer centers were retrospectively evaluated. We analyzed local control (LC), regional control (RC) and overall survival (OS). RESULTS: From 04/14 to 05/18 79 patients with 81 resection cavities were treated. Forty-seven patients (59.5%) received GK and 32 patients (40.5%) received CK treatment. Fifty-four cavities (66.7%) were treated with hFSRT and 27 (33.3%) with SRS. The most common hFSRT and SRS scheme was 3x10 Gy and 1x16 Gy, respectively. Median OS was 11.7 months with survival rates of 44.7% at 1 year and 18.5% at 2 years. LC was 83.3% after 1 year. Median time to regional progression was 12.0 months with RC rates of 61.1% at 6 months and 41.0% at 12 months. There was no difference in OS, LC or RC between GK and CK treatments or SRS and hFSRT. CONCLUSIONS: Both SRS and hFSRT provide high local control rates in resected BM regardless of the applied modality.

Prospective assessment of mask versus frame fixation during Gamma Knife treatment for brain metastases.

PURPOSE: The newest generation of the Leksell Gamma Knife (GK) allows frame based as well as frameless treatment. We here report outcomes of a prospective non-randomized study on mask fixation (MF) versus frame fixation (FF) for GK treatment of brain metastases. METHODS: The decision for FF or MF was made on a case-by-case basis. Factors considered were patients' preference, proximity of critical structures, V12 and treatment time. Either stereotactic radiosurgery or fractionated stereotactic radiotherapy in up to 3 fractions was performed. For MF, a PTV margin of 1 mm was added. Follow-up included quarterly MRI scans. The primary outcome was local control. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and the incidence of radionecrosis. RESULTS: A total of 197 lesions (169 FF and 28 MF) were treated in 76 patients (59 FF and 17 MF). 187 lesions were treated with SRS and 10 with FSRT. Median dose was 22 Gy in both groups and median follow-up was 9.3 months. There was a higher local failure rate (HR: 3.69; 95%CI: 1.13-12.0; p = 0.03) with 11 local failures in the FF and none in the MF cohort. No differences were observed between the groups for OS (median: n.r. vs. 16.9 months; HR:1.00; 95%CI: 0.41-2.46; p = 0.999) and PFS (median: 6.9 vs. 8.4 months; HR: 0.92; 95%CI: 0.47-1.79; p = 0.800). Three cases of radionecrosis occurred with FF but none with MF (p = 0.67). CONCLUSIONS: Gamma Knife treatment with MF does not result in worse outcome or increased rates of radionecrosis in this non-randomized study.

Radiation-induced optic neuropathy after stereotactic and image guided intensity-modulated radiation therapy (IMRT).

BACKGROUND/PURPOSE: To quantify the risk of radiation-induced optic neuropathy (RION) after stereotactic/image-guided positioning and intensity-modulated radiotherapy (IMRT) with ≥50 Gy to the anterior visual pathway (AVP). METHODS: Patients irradiated with ≥50 Gy to the AVP using stereotactic/image-guided positioning between 2002 and 2011 in Mannheim were identified. Detailed dosimetric data were collected and patients or family members were retrospectively asked to rate visual acuity and visual disorders. RESULTS: 125 patients fulfilled the eligibility criteria. Average maximum equivalent point dose (Dmax-EQD-2[α/ß=1.6]) to the AVP was 53.1 ±â€¯3.9 Gy. 99 patients received ≥50 Gy bilaterally (chiasm or both optic nerves), resulting in 224 (99x2 bilateral plus 26 unilateral) visual-fields-at-risk (VFAR) for RION. Eighty-two patients provided pre/post-IMRT visual status information (n = 151 VFARs). Permanent visual deterioration occurred in 18 (22%) patients. In seven, visual deterioration was possibly related to radiotherapy (two-sided deterioration in one patient) for a crude incidence of 8.5% (7/82 patients) and 5.3% (8/151 VFARs). Two cases were caused by chronic keratitis/conjunctivitis; in five patients RION could not be excluded (one two-sided). In one of 13 patients with Dmax-EQD-2 > 58 Gy, RION could not be excluded. In all affected patients, visual acuity post-IMRT had decreased only mildly (1-2 points on the 5-point-scale). One patient with relevant baseline visual impairment (3/5) developed unilateral blindness (crude incidence of blindness on patient-/VFAR-level: 1.2% and 0.66%; competing risk-adjusted/actuarial 24-month incidence: patient/VFAR-level: 1.8% and 0.95%). CONCLUSION: Risk of RION was low in this cohort with accurate positioning and precise dosimetric information. Less conservative tolerance doses may be considered in patients with high risk of recurrence.

Ultrasound-based repositioning and real-time monitoring for abdominal SBRT in DIBH.

AIM: Ultrasound-based repositioning and real-time-monitoring aim at the improvement of the precision of SBRT in deep inspiration breath-hold (DIBH). Accuracy of ultrasound-based daily repositioning was estimated by comparison with DIBH-cone-beam-CT. Intrafraction motion during beam-delivery was assessed by ultrasound-real-time-monitoring. PATIENTS/METHODS: Residual error after ultrasound-based interfractional repositioning (85 fractions, 16 SBRT-series; 14 patients) was assessed by marker-based (7 series) or liver-contour-based (9 series) matching in DIBH-CBCT. During beam-delivery, the percentage of 3D misalignment vector below 2 mm, between 2 and 5 mm, 5-7 mm and over 7 mm was estimated. Percentage of relevant target-displacements was analyzed as a function of DIBH-duration. RESULTS: Residual error after ultrasound-based positioning was 0.4 ±â€¯3.3 mm in LR (left-right), 0.2 ±â€¯4.3 mm in CC (cranio-caudal) and 1.0 ±â€¯3.0 mm in AP (anterior-posterior) directions (vector magnitude 5.4 ±â€¯3.3 mm, MV ±â€¯SD). Over 544 DIBHs, target displacement was 1.3 ±â€¯0.5 mm, 0.7 ±â€¯0.3 mm, 1.6 ±â€¯0.6 mm for CC, LR and AP directions, respectively (3D-vector 2.5 ±â€¯0.7 mm). 3D misalignment vector length was below 2 mm in 49.8%, between 2 and 7 mm in 46.3%, and over 7 mm in 3.9% of the beam-delivery-time. During the first 5 s of the DIBH, 3D-misalignment vector length was always below 10 mm. Percentage of target displacements over 10 mm was 0.2%, 0.5% and 0.8% for 10 s, 15 s and 20 s DIBH-duration. CONCLUSIONS: Ultrasound-based interfractional repositioning is an accurate method for daily localization of abdominal DIBH-SBRT targets. Residual motion is <7 mm in 96% of the beam-delivery-time. Deviations >10 mm occur rarely and can be avoided by gating the beam at a predefined threshold. Ideal DIBH-duration should not exceed 15 s.

Study Protocol: Early Stereotactic Gamma Knife Radiosurgery to Residual Tumor After Surgery of Newly Diagnosed Glioblastoma (Gamma-GBM).

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor in adult patients. Tumor recurrence commonly occurs around the resection cavity, especially after subtotal resection (STR). Consequently, the extent of resection correlates with overall survival (OS), suggesting that depletion of postoperative tumor remnants will improve outcome. OBJECTIVE: To assess safety and efficacy of adding stereotactic radiosurgery (SRS) to the standard treatment of GBM in patients with postoperative residual tumor. METHODS: Gamma-GBM is a single center, open-label, prospective, single arm, phase II study that includes patients with newly diagnosed GBM (intraoperative via frozen sections) who underwent STR (residual tumor will be identified by native and contrast enhanced T1-weighted magnetic resonance imaging scans). All patients will receive SRS with 15 Gy (prescribed to the 50% isodose enclosing all areas of residual tumor) early (within 24-72 h) after surgery. Thereafter, all patients undergo standard-of-care therapy for GBM (radiochemotherapy with 60 Gy external beam radiotherapy [EBRT] plus concomitant temozolomide and 6 cycles of adjuvant temozolomide chemotherapy). The primary outcome is median progression-free survival, secondary outcomes are median OS, occurrence of radiation induced acute (<3 wk), early delayed (<3 mo), and late (>3 mo post-SRS) neurotoxicity and incidence of symptomatic radionecrosis. EXPECTED OUTCOMES: We expect to detect efficacy and safety signals by the immediate application of SRS to standard-of-care therapy in newly diagnosed GBM. DISCUSSION: Early postoperative SRS to areas of residual tumor could bridge the therapeutic gap between surgery and adjuvant therapies.

Validation of frame-based positioning accuracy with cone-beam computed tomography in Gamma Knife Icon radiosurgery.

BACKGROUND: Frame based positioning accuracy in Gamma Knife (GK) stereotactic radiosurgery (SRS) is extremely high but removal of a post may be necessary to enable the treatment in selected patients. OBJECTIVE: To verify the positioning accuracy in clinical scenarios with 4 and 3 posts in patients and phantoms using cone-beam CT (CBCT) of Gamma Knife Icon™. METHODS: We analyzed positioning accuracy for 12 patients with standard 4 post setup using pretreatment CBCT (pre-CBCT) on GK Icon™ and report 4 patients with different clinical scenarios (removal of a post). We performed phantom measurements to verify the frame accuracy via CBCT in different clinical scenarios without the influence of the human patient. RESULTS: Mean frame accuracy for 12 patients with 4 posts was 0.35 mm/0.34 degree. Mean motion during treatment was 0.11 mm/0.04 degree. For two of the clinical scenarios where a post was removed, we found acceptable deviations within 0.66 mm/0.61 degree. For 2 patients, a deviation of 2.94 mm/-3.47 degree and 1.85 mm/-0.74 degree was found and replanning was necessary. Phantom measurements showed good agreement when planning MR/CT was performed with 4 or 3 post. Larger deviations of 0.86 mm/0.88 degree were detected when a post was removed after planning MR/CT. CONCLUSION: The frame accuracy with 4 posts before and during GK treatments is as high as expected. For clinical situations, where a post is removed after planning-CT/MR, pre-treatment position verification is strongly suggested using stereotactic CBCT or the P-CT/MR should be repeated to avoid possible mistreatments.

Treatment of Adrenal Metastases with Conventional or Hypofractionated Image-guided Radiation Therapy - Patterns and Outcomes.

BACKGROUND/AIM: Metastases involving the adrenal glands can be treated surgically or with radiation therapy. Retrospective studies indicate that radiotherapy for this indication is safe, well-tolerated and associated with symptom palliation and good local control. We conducted this analysis to report on patterns and outcomes of patients with adrenal metastases treated with hypo- or conventionally fractionated image-guided radiotherapy. PATIENTS AND METHODS: Patients with adrenal metastases from solid tumors treated at our department between 01/2010-12/2017 were reviewed. A total of 22 lesions were treated in 18 patients with a median dose of 35 Gy (20-60 Gy) in a median number of 7 (4-25) fractions. RESULTS: No grade ≥3 toxicity occurred. Median overall survival was 11.9 months. Five local failures occurred (22.7%). Lesion sizes or radiation dose were not correlated with local control. Patients treated for oligometastatic and oligoprogressive disease had a median overall survival of 33 and 6.5 months, respectively (palliative/polymetastatic: 1.6 months). Symptoms improved in all patients treated for clinically apparent lesions. CONCLUSION: Stereotactic radiotherapy of adrenal metastases was safe and effective in patients with oligometastases or oligoprogression. In palliative patients, short-course radiotherapy complemented with supportive care should be preferred.

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.

Intra-breath-hold residual motion of image-guided DIBH liver-SBRT: An estimation by ultrasound-based monitoring correlated with diaphragm position in CBCT.

BACKGROUND AND PURPOSE: Craniocaudal motion during image-guided abdominal SBRT can be reduced by computer-controlled deep-inspiratory-breath-hold (DIBH). However, a residual motion can occur in the DIBH-phases which can only be detected with intrafractional real-time-monitoring. We assessed the intra-breath-hold residual motion of DIBH and compared residual motion of target structures during DIBH detected by ultrasound (US). US data were compared with residual motion of the diaphragm-dome (DD) detected in the DIBH-CBCT-projections. PATIENTS AND METHODS: US-based monitoring was performed with an experimental US-system simultaneously to DIBH-CBCT acquisition. A total of 706 DIBHs during SBRT-treatments of metastatic lesions (liver, spleen, adrenal) of various primaries were registered in 13 patients. Residual motion of the target structure was documented with US during each DIBH. Motion of the DD was determined by comparison to a reference phantom-scan taking the individual geometrical setting at a given projection angle into account. Residual motion data detected by US were correlated to those of the DD (DIBH-CBCT-projection). RESULTS: US-based monitoring could be performed in all cases and was well tolerated by all patients. Additional time for daily US-based setup required 8 ±â€¯4 min. 385 DIBHs of 706 could be analyzed. In 59% of all DIBHs, residual motion was below 2 mm. In 36%, residual motion of 2-5 mm and in 4% of 5-8 mm was observed. Only 1% of all DIBHs and 0.16% of all readings revealed a residual motion of >8 mm during DIBH. For DIBHs with a residual motion over 2 mm, 137 of 156 CBCT-to-US curves had a parallel residual motion and showed a statistical correlation. DISCUSSION AND CONCLUSION: Soft-tissue monitoring with ultrasound is a fast real-time method without additional radiation exposure. Computer-controlled DIBH has a residual motion of <5 mm in >95% which is in line with the published intra-breath-hold-precision. Larger intrafractional deviations can be avoided if the beam is stopped at an US-defined threshold.

Fully automated, multi-criterial planning for Volumetric Modulated Arc Therapy - An international multi-center validation for prostate cancer.

BACKGROUND AND PURPOSE: Reported plan quality improvements with autoplanning of radiotherapy of the prostate and seminal vesicles are poor. A system for automated multi-criterial planning has been validated for this treatment in a large international multi-center study. The system is configured with training plans using a mechanism that strives for quality improvements relative to those plans. MATERIAL AND METHODS: Each of the four participating centers included thirty manually generated clinical Volumetric Modulated Arc Therapy prostate plans (manVMAT). Ten plans were used for autoplanning training. The other twenty were compared with an automatically generated plan (autoVMAT). Plan evaluations considered dosimetric plan parameters and blinded side-by-side plan comparisons by clinicians. RESULTS: With equivalent Planning Target Volume (PTV) V95%, D2%, D98%, and dose homogeneity autoVMAT was overall superior for rectum with median differences of 3.4 Gy (p < 0.001) in Dmean, 4.0% (p < 0.001) in V60Gy, and 1.5% (p = 0.001) in V75Gy, and for bladder Dmean (0.9 Gy, p < 0.001). Also the clinicians' plan comparisons pointed at an overall preference for autoVMAT. Advantages of autoVMAT were highly treatment center- and patient-specific with overall ranges for differences in rectum Dmean and V60Gy of [-4,12] Gy and [-2,15]%, respectively. CONCLUSION: Observed advantages of autoplanning were clinically relevant and larger than reported in the literature. The latter is likely related to the multi-criterial nature of the applied autoplanning algorithm, with for each center a dedicated configuration that aims at plan improvements relative to its (clinical) training plans. Large variations among patients in differences between manVMAT and autoVMAT point at inconsistencies in manual planning.

Fully automated treatment planning of spinal metastases - A comparison to manual planning of Volumetric Modulated Arc Therapy for conventionally fractionated irradiation.

BACKGROUND: Planning for Volumetric Modulated Arc Therapy (VMAT) may be time consuming and its use is limited by available staff resources. Automated multicriterial treatment planning can eliminate this bottleneck. We compared automatically created (auto) VMAT plans generated by Erasmus-iCycle to manually created VMAT plans for treatment of spinal metastases. METHODS: Forty-two targets in 32 patients were analyzed. Lungs and kidneys were defined as organs at risk (OARs). Twenty-two patients received radiotherapy on kidney levels, 17 on lung levels, and 3 on both levels. RESULTS: All Erasmus-iCycle plans were clinically acceptable. When compared to manual plans, planning target volume (PTV) coverage of auto plans was significantly better. The Homogeneity Index did not differ significantly between the groups. Mean dose to OARs was lower in auto plans concerning both kidneys and the left lung. One hotspot (>110% of D50%) occurred in the spinal cord of one auto plan (33.2 Gy, D50%: 30 Gy). Treatment time was 7% longer in auto plans. CONCLUSIONS: Erasmus-iCycle plans showed better target coverage and sparing of OARs at the expense of minimally longer treatment times (for which no constraint was set).