Re-evaluation of the prospective risk analysis for artificial-intelligence driven cone beam computed tomography-based online adaptive radiotherapy after one year of clinical experience.

Cone-beam computed tomography (CBCT)-based online adaptation is increasingly being introduced into many clinics. Upon implementation of a new treatment technique, a prospective risk analysis is required and enhances workflow safety. We conducted a risk analysis using Failure Mode and Effects Analysis (FMEA) upon the introduction of an online adaptive treatment programme (Wegener et al., Z Med Phys. 2022). A prospective risk analysis, lacking in-depth clinical experience with a treatment modality or treatment machine, relies on imagination and estimates of the occurrence of different failure modes. Therefore, we systematically documented all irregularities during the first year of online adaptation, namely all cases in which quality assurance detected undesired states potentially leading to negative consequences. Additionally, the quality of automatic contouring was evaluated. Based on those quantitative data, the risk analysis was updated by an interprofessional team. Furthermore, a hypothetical radiation therapist-only workflow during adaptive sessions was included in the prospective analysis, as opposed to the involvement of an interprofessional team performing each adaptive treatment. A total of 126 irregularities were recorded during the first year. During that time period, many of the previously anticipated failure modes (almost) occurred, indicating that the initial prospective risk analysis captured relevant failure modes. However, some scenarios were not anticipated, emphasizing the limits of a prospective risk analysis. This underscores the need for regular updates to the risk analysis. The most critical failure modes are presented together with possible mitigation strategies. It was further noted that almost half of the reported irregularities applied to the non-adaptive treatments on this treatment machine, primarily due to a manual plan import step implemented in the institution's workflow.

Feasibility of Ethos adaptive treatments of lung tumors and associated quality assurance.

MOTIVATION: Online adaptive radiotherapy with Ethos is based on the anatomy determined from daily cone beam computed tomography (CBCT) images. Dose optimization and computation are performed on the density map of a synthetic CT (sCT), a deformable registration of the initial planning CT (pCT) onto the current CBCT. Large density changes as present in the lung region are challenging the system. METHODS: Treatment plans for Ethos were created and delivered for 1, 2, and 3 cm diameter lung lesions in an anthropomorphic phantom, combining different insets in the pCT and during adaptive and non-adaptive treatment sessions. Primary and secondary dose calculations as well as back-projected dose from portal images were evaluated. RESULTS: Density changes due to changed insets were not considered in the sCTs. This resulted in errors in the dose; for example, -15.9% of the mean dose for a plan when changing from a 3 cm inset in the pCT to 1 cm at the time of treatment. Secondary dose calculation is based on the sCT and could therefore not reveal these dose errors. However, dose calculation on the CBCT, either as a recalculation in the treatment planning system or as pre-treatment quality assurance (QA) before the treatment, indicated the differences. EPID in-vivo QA also reported discrepancies between calculated and delivered dose distributions. CONCLUSIONS: An incorrect density distribution in the sCT has an impact on the dose calculation accuracy in the adaptive treatment workflow with the Ethos system. Additional quality checks of the sCT can detect such errors.

Impact of Radiotherapy on Malfunctions and Battery Life of Cardiac Implantable Electronic Devices in Cancer Patients.

PURPOSE: This study analyses a large number of cancer patients with CIEDs for device malfunction and premature battery depletion by device interrogation after each radiotherapy fraction and compares different guidelines in regard to patient safety. METHODS: From 2007 to 2022, a cohort of 255 patients was analyzed for CIED malfunctions via immediate device interrogation after every RT fraction. RESULTS: Out of 324 series of radiotherapy treatments, with a total number of 5742 CIED interrogations, nine device malfunctions (2.8%) occurred. Switching into back-up/safety mode and software errors occurred four times each. Once, automatic read-out could not be performed. The median prescribed cumulative dose at planning target volume (PTV) associated with CIED malfunction was 45.0 Gy (IQR 36.0-64.0 Gy), with a median dose per fraction of 2.31 Gy (IQR 2.0-3.0 Gy). The median maximum dose at the CIED at time of malfunction was 0.3 Gy (IQR 0.0-1.3 Gy). No correlation between CIED malfunction and maximum photon energy (p = 0.07), maximum dose at the CIED (p = 0.59) nor treatment localization (p = 0.41) could be detected. After excluding the nine malfunctions, premature battery depletion was only observed three times (1.2%). Depending on the national guidelines, 1-9 CIED malfunctions in this study would have been detected on the day of occurrence and in none of the cases would patient safety have been compromised. CONCLUSION: Radiation-induced malfunctions of CIEDs and premature battery depletion are rare. If recommendations of national safety guidelines are followed, only a portion of the malfunctions would be detected directly after occurrence. Nevertheless, patient safety would not be compromised.

Assessment of dual-energy computed tomography derived virtual monoenergetic imaging for target volume delineation of brain metastases.

BACKGROUND: Objective and subjective assessment of image quality of brain metastases on dual-energy computed tomography (DECT) virtual monoenergetic imaging (VMI) and its impact on target volume delineation. MATERIALS AND METHODS: 26 patients with 37 brain metastases receiving Magnetic Resonance Imaging (MRI) and DECT for stereotactic radiotherapy planning were included in this retrospective analysis. Lesion contrast (LC), contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were assessed for reconstructed VMI at 63 keV and artificial 120 kV Computed Tomography (CT). Image contrast and demarcation of metastases between 120 kV CT, VMI and MRI were subjectively assessed. Brain metastases were delineated by four radiation oncologists on VMI with a fixed or free brain window and contours were compared to solely MRI-based delineation using the Dice similarity coefficient. RESULTS: LC, CNR and SNR were significantly higher in VMI than in 120 kV CT (p < 0.0001). Image contrast and lesion demarcation were significantly better on VMI compared to 120 kV CT (p < 0.0001). Mean gross tumor volume (GTV)/planning target volume (PTV) Dice similarity coefficients were 0.87/0.9 for metastases without imaging uncertainties (no artifacts, calcification or impaired visibility with MRI) but worse for metastases with imaging uncertainties (0.71/0.74). Target volumes delineated on VMI were around 5-10% smaller compared to MRI. CONCLUSION: Image quality of VMI is objectively and subjectively superior to conventional CT. VMI provides significant advantages in stereotactic radiotherapy planning with improved visibility of brain metastases and geometrically distortion-free representation of brain metastases. Beside a plausibility check of MRI-based target volume delineation, VMI might improve reliability and accuracy in target volume definition particularly in cases with imaging uncertainties with MRI.

Obesity-Related Pitfalls of Virtual versus True Non-Contrast Imaging-An Intraindividual Comparison in 253 Oncologic Patients.

OBJECTIVES: Dual-source dual-energy CT (DECT) facilitates reconstruction of virtual non-contrast images from contrast-enhanced scans within a limited field of view. This study evaluates the replacement of true non-contrast acquisition with virtual non-contrast reconstructions and investigates the limitations of dual-source DECT in obese patients. MATERIALS AND METHODS: A total of 253 oncologic patients (153 women; age 64.5 ± 16.2 years; BMI 26.6 ± 5.1 kg/m2) received both multi-phase single-energy CT (SECT) and DECT in sequential staging examinations with a third-generation dual-source scanner. Patients were allocated to one of three BMI clusters: non-obese: <25 kg/m2 (n = 110), pre-obese: 25-29.9 kg/m2 (n = 73), and obese: >30 kg/m2 (n = 70). Radiation dose and image quality were compared for each scan. DECT examinations were evaluated regarding liver coverage within the dual-energy field of view. RESULTS: While arterial contrast phases in DECT were associated with a higher CTDIvol than in SECT (11.1 vs. 8.1 mGy; p < 0.001), replacement of true with virtual non-contrast imaging resulted in a considerably lower overall dose-length product (312.6 vs. 475.3 mGy·cm; p < 0.001). The proportion of DLP variance predictable from patient BMI was substantial in DECT (R2 = 0.738) and SECT (R2 = 0.620); however, DLP of SECT showed a stronger increase in obese patients (p < 0.001). Incomplete coverage of the liver within the dual-energy field of view was most common in the obese subgroup (17.1%) compared with non-obese (0%) and pre-obese patients (4.1%). CONCLUSION: DECT facilitates a 30.8% dose reduction over SECT in abdominal oncologic staging examinations. Employing dual-source scanner architecture, the risk for incomplete liver coverage increases in obese patients.

Acute toxicities of patients with locally advanced rectal cancer treated with intensified chemoradiotherapy within the CAO/ARO/AIO-12 trial: comparing conventional versus VMAT planning at a single center.

In locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is regarded as standard treatment. We assessed acute toxicities in patients receiving conventional 3D-conformal radiotherapy (3D-RT) and correlated them with dosimetric parameters after re-planning with volumetric modulated arc therapy (VMAT). Patients were randomized within the multicenter CAO/ARO/AIO-12 trial and received 50.4 Gy in 28 fractions and simultaneous chemotherapy with fluorouracil and oxaliplatin. Organs at risk (OAR) were contoured in a standardized approach. Acute toxicities and dose volume histogram parameters of 3D-RT plans were compared to retrospectively calculated VMAT plans. From 08/2015 to 01/2018, 35 patients with LARC were treated at one study center. Thirty-four patients were analyzed of whom 1 (3%) was UICC stage II and 33 (97%) patients were UICC stage III. Grade 3 acute toxicities occurred in 5 patients (15%). Patients with acute grade 1 cystitis (n = 9) had significantly higher Dmean values for bladder (29.4 Gy vs. 25.2 Gy, p < 0.01) compared to patients without bladder toxicities. Acute diarrhea was associated with small bowel volume (grade 2: 870.1 ccm vs. grade 0-1: 647.3 ccm; p < 0.01) and with the irradiated volumes V5 to V50. Using VMAT planning, we could reduce mean doses and irradiated volumes for all OAR: Dmean bladder (21.9 Gy vs. 26.3 Gy, p < 0.01), small bowel volumes V5-V45 (p < 0.01), Dmean anal sphincter (34.6 Gy vs. 35.6 Gy, p < 0.01) and Dmean femoral heads (right 11.4 Gy vs. 25.9 Gy, left 12.5 Gy vs. 26.6 Gy, p < 0.01). Acute small bowel and bladder toxicities were dose and volume dependent. Dose and volume sparing for all OAR could be achieved through VMAT planning and might result in less acute toxicities.

Prospective risk analysis of the online-adaptive artificial intelligence-driven workflow using the Ethos treatment system.

PURPOSE: The recently introduced Varian Ethos system allows adjusting radiotherapy treatment plans to anatomical changes on a daily basis. The system uses artificial intelligence to speed up the process of creating adapted plans, comes with its own software solutions and requires a substantially different workflow. A detailed analysis of possible risks of the associated workflow is presented. METHODS: A prospective risk analysis of the adaptive workflow with the Ethos system was performed using Failure Modes and Effects Analysis (FMEA). An interprofessional team collected possible adverse events and evaluated their severity as well as their chance of occurrence and detectability. Measures to reduce the risks were discussed. RESULTS: A total of 122 events were identified, and scored. Within the 20 events with the highest-ranked risks, the following were identified: Challenges due to the stand-alone software solution with very limited connectivity to the existing record and verify software and digital patient file, unfamiliarity with the new software and its limitations and the adaption process relying on results obtained by artificial intelligence. The risk analysis led to the implementation of additional quality assurance measures in the workflow. CONCLUSIONS: The thorough analysis of the risks associated with the new treatment technique was the basis for designing details of the workflow. The analysis also revealed challenges to be addressed by both, the vendor and customers. On the vendor side, this includes improving communication between their different software solutions. On the customer side, this especially includes establishing validation strategies to monitor the results of the black box adaption process making use of artificial intelligence.

Propensity score-matched analysis comparing dose-escalated intensity-modulated radiation therapy versus external beam radiation therapy plus high-dose-rate brachytherapy for localized prostate cancer.

PURPOSE: Dose-escalated external beam radiation therapy (EBRT) and EBRT + high-dose-rate brachytherapy (HDR-BT) boost are guideline-recommended treatment options for localized prostate cancer. The purpose of this study was to compare long-term outcome and toxicity of dose-escalated EBRT versus EBRT + HDR-BT boost. METHODS: From 2002 to 2019, 744 consecutive patients received either EBRT or EBRT + HDR-BT boost, of whom 516 patients were propensity score matched. Median follow-up was 95.3 months. Cone beam CT image-guided EBRT consisted of 33 fractions of intensity-modulated radiation therapy with simultaneous integrated boost up to 76.23 Gy (DMean). Combined treatment was delivered as 46 Gy (DMean) EBRT, followed by two fractions HDR-BT boost with 9 Gy (D90%). Propensity score matching was applied before analysis of the primary endpoint, estimated 10-year biochemical relapse-free survival (bRFS), and the secondary endpoints metastasis-free survival (MFS) and overall survival (OS). Prognostic parameters were analyzed by Cox proportional hazard modelling. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation used the Common Toxicity Criteria for Adverse Events (v5.0). RESULTS: The estimated 10-year bRFS was 82.0% vs. 76.4% (p = 0.075) for EBRT alone versus combined treatment, respectively. The estimated 10-year MFS was 82.9% vs. 87.0% (p = 0.195) and the 10-year OS was 65.7% vs. 68.9% (p = 0.303), respectively. Cumulative 5­year late GU ≥ grade 2 toxicities were seen in 23.6% vs. 19.2% (p = 0.086) and 5­year late GI ≥ grade 2 toxicities in 11.1% vs. 5.0% of the patients (p = 0.002); cumulative 5­year late grade 3 GU toxicity occurred in 4.2% vs. 3.6% (p = 0.401) and GI toxicity in 1.0% vs. 0.3% (p = 0.249), respectively. CONCLUSION: Both treatment groups showed excellent long-term outcomes with low rates of severe toxicity.

Comparing Iridium-192 with Cobalt-60 sources in high-dose-rate brachytherapy boost for localized prostate cancer.

BACKGROUND: Dosimetric and clinical comparison of two cohorts of Iridium-192 (Ir-192) and Cobalt-60 (Co-60) high-dose-rate brachytherapy (DR-BT) boost for localized prostate cancer. MATERIAL AND METHODS: Patients with localized prostate cancer receiving either Ir-192 or Co-60 high-dose-rate brachytherapy (HDR-BT) boost in combination with external beam radiotherapy (EBRT) in the period of 2002-2019 were evaluated for dosimetric differences, side effects, biochemical relapse-free survival (bRFS), metastasis-free survival (MFS), and overall survival (OS). EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90%) 2 and 4 weeks after EBRT. Genitourinary (GU)/gastrointestinal (GI) toxicity were evaluated utilizing the Common Toxicity Criteria for Adverse Events version 5.0 and biochemical failure was defined according to the Phoenix definition. RESULTS: A total of 338 patients with a median follow-up of 101.8 (IQR 65.7-143.0) months were evaluated. At 10 years the estimated bRFS, MFS, and OS in our patient sample were 81.1%/71.2% (p=.073), 87.0%/85.7% (p=.862), and 70.1%/69.7% (p=.998) for Ir-192/Co-60, respectively. Cumulative 5-year late grade ≥2 GU toxicity was 20% for Ir-192 and 18.3% for Co-60 (p=.771). Cumulative 5-year late grade ≥2 GI toxicity was 5.8% for Ir-192 and 4.6% for Co-60 (p=.610). Grade 3 late GU side effects were pronounced in the Ir-192 cohort with 8.1% versus 1.4% in the Co-60 cohort (p=.01), which was associated with significantly lower dose to the organs at risk in the Co-60 cohort. PTV D90% was 9.3 ± 0.8 Gy versus 9.0 ± 1.1 Gy (p=.027) for Ir-192 versus Co-60. PTV V100% and PTV V150% were not significantly different between both cohorts. CONCLUSION: Co-60 brachytherapy sources are an effective alternative to Ir-192 in combined prostate HDR-BT boost + EBRT.

Two-Weekly High-Dose-Rate Brachytherapy Boost After External Beam Radiotherapy for Localized Prostate Cancer: Long-Term Outcome and Toxicity Analysis.

PURPOSE: Evaluation of clinical outcome of two-weekly high-dose-rate brachytherapy boost after external beam radiotherapy (EBRT) for localized prostate cancer. METHODS: 338 patients with localized prostate cancer receiving definitive EBRT followed by a two-weekly high-dose-rate brachytherapy boost (HDR-BT boost) in the period of 2002 to 2019 were analyzed. EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90%) two and four weeks after EBRT. Androgen deprivation therapy (ADT) was added in 176 (52.1%) patients. Genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated utilizing the Common Toxicity Criteria for Adverse Events (version 5.0) and biochemical failure was defined according to the Phoenix definition. RESULTS: Median follow-up was 101.8 months. 15 (4.4%)/115 (34.0%)/208 (61.5%) patients had low-/intermediate-/high-risk cancer according to the D`Amico risk classification. Estimated 5-year and 10-year biochemical relapse-free survival (bRFS) was 84.7% and 75.9% for all patients. The estimated 5-year bRFS was 93.3%, 93.4% and 79.5% for low-, intermediate- and high-risk disease, respectively. The estimated 10-year freedom from distant metastasis (FFM) and overall survival (OS) rates were 86.5% and 70.0%. Cumulative 5-year late GU toxicity and late GI toxicity grade ≥ 2 was observed in 19.3% and 5.0% of the patients, respectively. Cumulative 5-year late grade 3 GU/GI toxicity occurred in 3.6%/0.3%. CONCLUSIONS: Two-weekly HDR-BT boost after EBRT for localized prostate cancer showed an excellent toxicity profile with low GU/GI toxicity rates and effective long-term biochemical control.

Comparison of sliding window and field-in-field techniques for tangential whole breast irradiation using the Halcyon and Synergy Agility systems.

BACKGROUND: To implement a tangential treatment technique for whole breast irradiation using the Varian Halcyon and to compare it with Elekta Synergy Agility plans. METHODS: For 20 patients two comparable treatment plans with respect to dose coverage and normal tissue sparing were generated. Tangential field-in-field treatment plans (Pinnacle/Synergy) were replanned using the sliding window technique (Eclipse/Halcyon). Plan specific QA was performed using the portal Dosimetry and the ArcCHECK phantom. Imaging and treatment dose were evaluated for treatment delivery on both systems using a modified CIRS Phantom. RESULTS: The mean number of monitor units for a fraction dose of 2.67 Gy was 515 MUs and 260 MUs for Halcyon and Synergy Agility plans, respectively. The homogeneity index and dose coverage were similar for both treatment units. The plan specific QA showed good agreement between measured and calculated plans. All Halcyon plans passed portal dosimetry QA (3%/2 mm) with 100% points passing and ArcCheck QA (3%/2 mm) with 99.5%. Measurement of the cumulated treatment and imaging dose with the CIRS phantom resulted in lower dose to the contralateral breast for the Halcyon plans. CONCLUSIONS: For the Varian Halcyon a plan quality similar to the Elekta Synergy device was achieved. For the Halcyon plans the dose contribution from the treatment fields to the contralateral breast was even lower due to less interleaf transmission of the Halcyon MLC and a lower contribution of scattered dose from the collimator system.

Comparison of treatment plans for hypofractionated high-dose prostate cancer radiotherapy using the Varian Halcyon and the Elekta Synergy platforms.

PURPOSE: To compare radiotherapy plans between an O-ring and a conventional C-arm linac for hypofractionated high-dose prostate radiotherapy in terms of plan quality, dose distribution, and quality assurance in a multi-vendor environment. METHODS: Twenty prostate cancer treatment plans were irradiated on the O-ring Varian Halcyon linac and were re-optimized for the C-arm Elekta Synergy Agility linac. Dose-volume histogram metrics for target coverage and organ at risk dose, quality assurance, and monitor units were retrospectively compared. Patient-specific quality assurance with ion chamber measurements, gamma index analysis, and portal dosimetry was performed using the Varian Portal Dosimetry system and the ArcCHECK® phantom (Sun Nuclear Corporation). Prostate-only radiotherapy was delivered with simultaneous integrated boost (SIB) volumetric modulated arc therapy (VMAT) in 20 fractions of 2.5/3.0 Gy each. RESULTS: For both linacs, target coverage was excellent and plan quality comparable. Homogeneity in PTVBoost was high for Synergy as well as Halcyon with a mean homogeneity index of 0.07 ± 0.01 and 0.05 ± 0.01, respectively. Mean dose for the organs at risk rectum and bladder differed not significantly between the linacs but were higher for the femoral heads and penile bulb for Halcyon. Quality assurance showed no significant differences in terms of ArcCHECK gamma pass rates. Median pass rate for 3%/2 mm was 99.3% (96.7 to 99.8%) for Synergy and 99.8% (95.6 to 100%) for Halcyon. Agreement between calculated and measured dose was high with a median deviation of -0.6% (-1.7 to 0.8%) for Synergy and 0.2% (-0.6 to 2.3%) for Halcyon. Monitor units were higher for the Halcyon by approximately 20% (p < 0.001). CONCLUSION: Hypofractionated high-dose prostate cancer SIB VMAT on the Halcyon system is feasible with comparable plan quality in reference to a standard C-arm Elekta Synergy linac.

Chemoradiotherapy by intensity-modulated radiation therapy with simultaneous integrated boost in locally advanced or oligometastatic non-small-cell lung cancer-a two center experience.

PURPOSE: Integrating moderate hypofractionation to the macroscopic tumor with elective nodal irradiation while sparing the organs at risk (OAR) in chemoradiotherapy of locally advanced non-small-cell lung cancer. METHODS: From 2010-2018, treatment, patient and tumor characteristics of 138 patients from two radiation therapy centers were assessed. Chemoradiotherapy by intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) to the primary tumor and macroscopic lymph node metastases was used. RESULTS: A total of 124 (90%) patients received concurrent chemotherapy. 106 (76%) patients had UICC (Union for International Cancer Control) stage ≥IIIB and 21 (15%) patients had an oligometastatic disease (UICC stage IV). Median SIB and elective total dose was 61.6 and 50.4 Gy in 28 fractions, respectively. Furthermore, 64 patients (46%) had an additional sequential boost to the primary tumor after the SIB-IMRT main series: median 6.6 Gy in median 3 fractions. The median cumulative mean lung dose was 15.6 Gy (range 6.2-29.5 Gy). Median follow-up and radiological follow-up for all patients was 18.0 months (range 0.6-86.9) and 16.0 months (range 0.2-86.9), respectively. Actuarial local control rates at 1, 2 and 3 years were 80.4, 68.4 and 57.8%. Median overall survival and progression-free survival was 30.0 months (95% confidence interval [CI] 23.5-36.4) and 12.1 months (95% CI 8.2-16.0), respectively. Treatment-related toxicity was moderate. Radiation-induced pneumonitis grade 2 and grade 3 occurred in 13 (9.8%) and 3 (2.3%) patients. CONCLUSIONS: Chemoradiotherapy using SIB-IMRT showed promising local tumor control rates and acceptable toxicity in patients with locally advanced and in part oligometastatic lung cancer. The SIB concept, resulting in a relatively low mean lung dose, was associated with low numbers of clinically relevant pneumonitis. The overall survival appears promising in the presence of a majority of patients with UICC stage ≥IIIB disease.

Moderately hypofractionated radiotherapy for localized prostate cancer: updated long-term outcome and toxicity analysis.

PURPOSE: Evaluation of long-term outcome and toxicity of moderately hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost treatment planning and cone beam CT-based image guidance for localized prostate cancer. METHODS: Between 2005 and 2015, 346 consecutive patients with localized prostate cancer received primary radiotherapy using cone beam CT-based image-guided intensity-modulated radiotherapy (IG-IMRT) and volumetric modulated arc therapy (IG-VMAT) with a simultaneous integrated boost (SIB). Total doses of 73.9 Gy (n = 44) and 76.2 Gy (n = 302) to the high-dose PTV were delivered in 32 and 33 fractions, respectively. The low-dose PTV received a dose (D95) of 60.06 Gy in single doses of 1.82 Gy. The pelvic lymph nodes were treated in 91 high-risk patients to 45.5 Gy (D95). RESULTS: Median follow-up was 61.8 months. The 5­year biochemical relapse-free survival (bRFS) was 85.4% for all patients and 93.3, 87.4, and 79.4% for low-, intermediate-, and high-risk disease, respectively. The 5­year prostate cancer-specific survival (PSS) was 94.8% for all patients and 98.7, 98.9, 89.3% for low-, intermediate-, and high-risk disease, respectively. The 5­year and 10-year overall survival rates were 83.8 and 66.3% and the 5­year and 10-year freedom from distant metastasis rates were 92.2 and 88.0%, respectively. Cumulative 5­year late GU toxicity and late GI toxicity grade ≥2 was observed in 26.3 and 12.1% of the patients, respectively. Cumulative 5­year late grade 3 GU/GI toxicity occurred in 4.0/1.2%. CONCLUSION: Moderately hypofractionated radiotherapy using SIB treatment planning and cone beam CT image guidance resulted in high biochemical control and survival with low rates of late toxicity.

Free-breathing self-gated 4D lung MRI using wave-CAIPI.

PURPOSE: The aim of this study was to compare the wave-CAIPI (controlled aliasing in parallel imaging) trajectory to the Cartesian sampling for accelerated free-breathing 4D lung MRI. METHODS: The wave-CAIPI k-space trajectory was implemented in a respiratory self-gated 3D spoiled gradient echo pulse sequence. Trajectory correction applying the gradient system transfer function was used, and images were reconstructed using an iterative conjugate gradient SENSE (CG SENSE) algorithm. Five healthy volunteers and one patient with squamous cell carcinoma in the lung were examined on a clinical 3T scanner, using both sampling schemes. For quantitative comparison of wave-CAIPI and standard Cartesian imaging, the normalized mutual information and the RMS error between retrospectively accelerated acquisitions and their respective references were calculated. The SNR ratios were investigated in a phantom study. RESULTS: The obtained normalized mutual information values indicate a lower information loss due to acceleration for the wave-CAIPI approach. Average normalized mutual information values of the wave-CAIPI acquisitions were 10% higher, compared with Cartesian sampling. Furthermore, the RMS error of the wave-CAIPI technique was lower by 19% and the SNR was higher by 14%. Especially for short acquisition times (down to 1 minute), the undersampled Cartesian images showed an increased artifact level, compared with wave-CAIPI. CONCLUSION: The application of the wave-CAIPI technique to 4D lung MRI reduces undersampling artifacts, in comparison to a Cartesian acquisition of the same scan time. The benefit of wave-CAIPI sampling can therefore be traded for shorter examinations, or enhancing image quality of undersampled 4D lung acquisitions, keeping the scan time constant.

Non-rigid image registration of 4D-MRI data for improved delineation of moving tumors.

BACKGROUND: To increase the image quality of end-expiratory and end-inspiratory phases of retrospective respiratory self-gated 4D MRI data sets using non-rigid image registration for improved target delineation of moving tumors. METHODS: End-expiratory and end-inspiratory phases of volunteer and patient 4D MRI data sets are used as targets for non-rigid image registration of all other phases using two different registration schemes: In the first, all phases are registered directly (dir-Reg) while next neighbors are successively registered until the target is reached in the second (nn-Reg). Resulting data sets are quantitatively compared using diaphragm and tumor sharpness and the coefficient of variation of regions of interest in the lung, liver, and heart. Qualitative assessment of the patient data regarding noise level, tumor delineation, and overall image quality was performed by blinded reading based on a 4 point Likert scale. RESULTS: The median coefficient of variation was lower for both registration schemes compared to the target. Median dir-Reg coefficient of variation of all ROIs was 5.6% lower for expiration and 7.0% lower for inspiration compared with nn-Reg. Statistical significant differences between the two schemes were found in all comparisons. Median sharpness in inspiration is lower compared to expiration sharpness in all cases. Registered data sets were rated better compared to the targets in all categories. Over all categories, mean expiration scores were 2.92 ± 0.18 for the target, 3.19 ± 0.22 for nn-Reg and 3.56 ± 0.14 for dir-Reg and mean inspiration scores 2.25 ± 0.12 for the target, 2.72 ± 215 0.04 for nn-Reg and 3.78 ± 0.04 for dir-Reg. CONCLUSIONS: In this work, end-expiratory and inspiratory phases of a 4D MRI data sets are used as targets for non-rigid image registration of all other phases. It is qualitatively and quantitatively shown that image quality of the targets can be significantly enhanced leading to improved target delineation of moving tumors.

Feasibility of 4D T2* quantification in the lung with oxygen gas challenge in patients with non-small cell lung cancer.

Blood oxygen level-dependent (BOLD) MRI is a non-invasive diagnostic method for assessing tissue oxygenation level, by changes in the transverse relaxation time T2*. 3D BOLD imaging of lung tumours is challenging, because respiratory motion can lead to significant image quality degradation. The purpose of this work was to explore the feasibility of a three dimensional (3D) Cartesian multi gradient echo (MGRE) sequence for T2* measurements of non-small cell lung tumours during free-breathing. A non-uniform quasi-random reordering of the pahse encoding lines that allocates more sampling points near the k-space origin resulting in efficient undersampling pattern for parallel imaging was combined with multi echo acquisition and self-gating. In a series of three patients 3D T2* maps of lung carcinomas were generated with isotropic spatial resolution and full tumour coverage at air inhalation and after hyperoxic gas challenge in arbitrary respiratory phases using the proposed self-gated MGRE acquisition. The changes in T2* on the inhalation of hyperoxic gas relative to air were quantified. Significant changes in T2* were observed following oxygen inhalation in the tumour (p < 0.02). Thus, the self-gated MGRE sequence can be used for assessment of BOLD signal with isotropic resolution and arbitrary respiratory phases in non-small cell lung cancer.

Evaluation of intrafraction prostate motion tracking using the Clarity Autoscan system for safety margin validation.

BACKGROUND: The purpose of the study was to monitor intrafraction prostate motion in real-time using transperineal 4D ultrasound (TPUS) and analyze trajectories to validate clinical safety margins. METHODS: 401 trajectories of US monitoring sessions were retrospectively evaluated for 14 patients treated for prostate cancer. The Elekta Clarity Autoscan system was used for intrafraction monitoring along the 3 directions: superior-inferior (SI), left-right (LR) and anterior-posterior (AP). RESULTS: The intrafraction monitoring resulted in a mean prostate displacement of (-0.06 ± 0.49) mm, (-0.09 ± 0.61) mm and (-0.01 ± 0.78) mm in the SI, LR and AP directions, respectively. Even though large deviations up to 8 mm were detected, the frequency of occurrence was less than 0.1%. The prostate moved within ±2 mm in 99%, 98.1%, and 96.6% of the treatment time in the SI, LR and AP directions, respectively. During 100 s of monitoring, the median displacement increased from 0.2 mm to 0.8 mm and the maximum displacements increased from 5.2 mm to 7.8 mm. The majority of displacement values (99%) were within the clinical safety margins which ensures a good target coverage. CONCLUSIONS: The largest variation of intrafraction prostate displacement was observed along the AP direction. Throughout most of the treatment time, the prostate moved within a few millimeters. The extent of prostate displacement increased for longer monitoring times. During most of the tracking time, the prostate position was within the clinically safety margins.

Impact of beam configuration on VMAT plan quality for Pinnacle3Auto-Planning for head and neck cases.

BACKGROUND: The purpose of this study was to compare automatically generated VMAT plans to find the superior beam configurations for Pinnacle3 Auto-Planning and share "best practices". METHODS: VMAT plans for 20 patients with head and neck cancer were generated using Pinnacle3 Auto-Planning Module (Pinnacle3 Version 9.10) with different beam setup parameters. VMAT plans for single (V1) or double arc (V2) and partial or full gantry rotation were optimized. Beam configurations with different collimator positions were defined. Target coverage and sparing of organs at risk were evaluated based on scoring of an evaluation parameter set. Furthermore, dosimetric evaluation was performed based on the composite objective value (COV) and a new cross comparison method was applied using the COVs. RESULTS: The evaluation showed a superior plan quality for double arcs compared to one single arc or two single arcs for all cases. Plan quality was superior if a full gantry rotation was allowed during optimization for unilateral target volumes. A double arc technique with collimator setting of 15° was superior to a double arc with collimator 60° and a two single arcs with collimator setting of 15° and 345°. CONCLUSION: The evaluation showed that double and full arcs are superior to single and partial arcs in terms of organs at risk sparing even for unilateral target volumes. The collimator position was found as an additional setup parameter, which can further improve the target coverage and sparing of organs at risk.