Dosimetric comparison of stereotactic MR-guided radiation therapy (SMART) and HDR brachytherapy boost in cervical cancer.

PURPOSE: The standard of care in locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy followed by high-dose-rate brachytherapy (HDR-BT). Although previous studies compared HDR-BT with stereotactic body radiotherapy (SBRT), there is scarce data regarding the dosimetric outcomes of stereotactic MR-guided adaptive radiation therapy (SMART) boost in lieu of HDR-BT. METHODS AND MATERIALS: In this single-institutional in-silico comparative study, LACC patients who were definitively treated with external beam radiotherapy followed by HDR-BT were selected. Target volumes and organs at risk (OARs) were delineated in MRI and HDR-planning CT. An HDR-BT and a SMART boost plan were generated with a prescribed dose of 28 Gy in four fractions for all patients. The HDR-BT and SMART boost plans were compared in regard to target coverage as well OARs doses. RESULTS: Mean EQD2 D90 to HR-CTV and IR-CTV for HDR-BT plans were 89.7 and 70.5 Gy, respectively. For SMART, the mean EQD2 D90 to HR-PTV, HR-CTV, and IR-CTV were 82.9, 95.4, and 70.2 Gy, respectively. The mean D2cc EQD2 of bladder, rectum, and sigmoid colon for HDR-BT plans were 86.4, 70.7, and 65.7 Gy, respectively. The mean D2cc EQD2 of bladder, rectum, and sigmoid colon for SMART plans were 81.4, 70.8, and 73.6 Gy, respectively. All dose constraints in terms of target coverage and OARs constraints were met for both HDR-BT and SMART plans. CONCLUSIONS: This dosimetric study demonstrates that SMART can be applied in cases where HDR-BT is not available or ineligible with acceptable target coverage and OAR sparing. However, prospective clinical studies are needed to validate these results.

Time Analysis of Online Adaptive Magnetic Resonance-Guided Radiation Therapy Workflow According to Anatomical Sites.

PURPOSE: To document time analysis of detailed workflow steps for the online adaptive magnetic resonance-guided radiation therapy treatments (MRgRT) with the ViewRay MRIdian system and to identify the barriers to and solutions for shorter treatment times. METHODS AND MATERIALS: A total of 154 patients were treated with the ViewRay MRIdian system between September 2018 and October 2019. The time process of MRgRT workflow steps of 962 fractions for 166 treatment sites was analyzed in terms of patient and online adaptive treatment (ART) characteristics. RESULTS: Overall, 774 of 962 fractions were treated with online ART, and 83.2% of adaptive fractions were completed in less than 60 minutes. Sixty-three percent, 50.3%, and 4.2% of fractions were completed in less than 50 minutes, 45 minutes, and 30 minutes, respectively. Eight-point-three percent and 3% of fractions were completed in more than 70 minutes and 80 minutes, respectively. The median time (tmed) for ART workflow steps were as follows: (1) setup tmed: 5.0 minutes, (2) low-resolution scanning tmed: 1 minute, (3) high-resolution scanning tmed: 3 minutes, (4) online contouring tmed: 9 minutes, (5) reoptimization with online quality assurance tmed: 5 minutes, (6) real targeting tmed: 3 minutes, (7) beam delivery with gating tmed: 17 minutes, and (8) net total treatment time tmed: 45 minutes. The shortest and longest tmean rates of net total treatment time were 41.59 minutes and 64.43 minutes for upper-lung-lobe-located thoracic tumors and ultracentrally located thoracic tumors, respectively. CONCLUSIONS: To our knowledge, this is the first broad treatment-time analysis for online ART in the literature. Although treatment times are long due to human- and technology-related limitations, benefits offered by MRgRT might be clinically important. In the future, implementation of artificial intelligence segmentation, an increase in dose rate, and faster multileaf collimator and gantry speeds may lead to achieving shorter MRgRT treatments.

Long-term toxicity and survival outcomes after stereotactic ablative radiotherapy for patients with centrally located thoracic tumors.

Background Stereotactic ablative radiotherapy (SABR) is effective for thoracic cancer and metastases; however, adverse effects are greater for central tumors. We evaluated factors affecting outcomes and toxicities after SABR for patients with primary lung and oligometastatic tumors. Patients and methods We retrospectively identified consecutive patients with centrally located lung tumors that were treated at our hospital from 2009-2016. The effects of patient, disease, and treatment-related parameters on local control (LC), overall survival (OS), and toxicity-free survival (TFS) were evaluated with multivariate analyses. Results Among 65 consecutive patients identified with 70 centrally located tumors, 20 tumors (28%) were reirradiated. Median (range) total dose for all tumors was 55 (30-60) Gy in 5 (3-10) fractions. Radiographic complete response was obtained in 43 lesions (61%). None of the analyzed factors were correlated with complete response. After a median follow-up of 57 (95% CI, 48-65) months, 10 tumors (14%) relapsed and 37 patients (57%) died; the actuarial 2- and 5-year OS rates were 52% and 28%, respectively. Median OS was significantly lower in patients with grade 3 or higher toxicity vs. lower toxicity (5 vs. 39 months; P < 0.001). Among 17 severe toxicities, 5 were grade 5, and 3 of them were reirradiated to the same field. Grade 3 to 5 TFS was lower with vs. without reirradiation (2-year TFS, 63% vs. 96%; P = 0.02). Conclusions Our study showed that modern SABR is effective for central lung tumors, and toxicities are acceptable. SABR for reirradiated central lung lesions and possibly for lesions abutting the tracheobronchial tree may result in higher risk of serious toxicities.

Multichannel Film Dosimetry for Quality Assurance of Intensity Modulated Radiotherapy Treatment Plans Under 0.35 T Magnetic Field.

Purpose To evaluate the intensity modulated radiotherapy (IMRT) quality assurance (QA) results of the multichannel film dosimetry analysis with single scan method by using Gafchromic™ EBT3 (Ashland Inc., Covington, KY, USA) film under 0.35 T magnetic field. Methods Between September 2018 and June 2019, 70 patients were treated with ViewRay MRIdian® (ViewRay Inc., Mountain View, CA) linear accelerator (Linac). Film dosimetry QA plans were generated for all IMRT treatments. Multichannel film dosimetry for red, green and blue (RGB) channels were compared with treatment planning system (TPS) dose maps by gamma evaluation analysis. Results The mean gamma passing rates of RGB channels are 97.3% ± 2.26%, 96.0% ± 3.27% and 96.2% ± 3.14% for gamma evaluation with 2% DD/2 mm distance to agreement (DTA), respectively. Moreover, the mean gamma passing rates of RGB channels are 99.7% ± 0.41%, 99.6% ± 0.59% and 99.5% ± 0.67% for gamma evaluation with 3% DD/3 mm DTA, respectively. Conclusion The patient specific QA using Gafchromic™ EBT3 film with multichannel film dosimetry seems to be a suitable tool to implement for MR-guided IMRT treatments under 0.35 T magnetic field. Multichannel film dosimetry with Gafchromic™ EBT3 is a consistent QA tool for gamma evaluation of the treatment plans even with 2% DD/2 mm DTA under 0.35 T magnetic field presence.

First 500 Fractions Delivered with a Magnetic Resonance-guided Radiotherapy System: Initial Experience.

Objectives Improved soft-tissue visualization, afforded by magnetic resonance imaging integrated into a radiation therapy linear accelerator-based radiation delivery system (MR-linac) promises improved image-guidance. The availability of MR-imaging can facilitate on-table adaptive radiation planning and enable real-time intra-fraction imaging with beam gating without additional exposure to radiation. However, the novel use of magnetic resonance-guided radiation therapy (MRgRT) in the field of radiation oncology also potentially poses challenges for routine clinical implementation. Herein the early experience of a single institution, implementing the first MRgRT system in the country is reported. We aim to describe the workflow and to characterize the clinical utility and feasibility of routine use of an MR-linac system. Methods The ViewRay MRIdian MR-linac system consists of a split-magnet 0.35 T MR-imaging scanner with a double focused multi-leaf collimator (MLC) equipped 6MV linear accelerator. Unique to the system are the control console integrated on-table adaptive radiation therapy (oART) planning capabilities as well as automated beam gating based on real-time intra-fraction MR imaging. From the first day of clinical implementation, oART was performed according to physicians' discretion when medically indicated. All fractions were delivered under real-time imaging with soft tissue-based automated beam gating with individualized gating boundary settings. Patients actively assisted in breath-hold beam gating with the help of custom designed prismatic glasses allowing sight of a computer monitor mounted on the back wall just behind the MRI system bore. Patient demographics and treatment experience, indications for MRgRT including diagnosis and disease site, radiation dose prescribed and fractionation scheme, utilization of oART, respiratory gating settings, as well as duration of each treatment phase were analyzed. Results Between September 2018 and May 2019, 72 patients with 84 tumor sites were treated with MRgRT in 500 total fractions. Median patient age was 66 years (range: 28-83 years). Among 84 tumor sites, the most frequently treated regions were upper abdominal and pelvic (n = 36, 43% and n = 29, 34%, respectively). The most common diagnosis was prostate cancer, with 14 patients treated. In 69 patients (93.2%) oART was used at least once during a treatment course. Twenty-nine targets (43.1%) with significant breathing-related motion were treated in breath-hold with patient visual feedback. Median prescribed dose was 36.25 Gy (range: 24-70 Gy) in median five fractions (range: 3-28 fractions). A gating boundary of 3 mm around a gating region of interest (gROI) was most commonly used (range: 3-5 mm) with 95% of the gROI (range: 93-97%) required to be within the gating boundary for the beam to automatically engage. Mean total treatment time was 47 min (range: 21-125 min) and mean beam-on time was 16.7 min (range: 6-62 min). Conclusions MRgRT afforded by an MR-linac system has been successfully implemented into routine clinical use at our institution as the first system of its kind in Turkey. While the overall number of patients treated and fractions delivered is still limited, we have demonstrated the feasibility of both on-table adaptive radiation therapy as well as automated real-time beam gating on a daily basis in acceptable time schedules.

Robotic radiosurgery of head and neck paragangliomas: a single institution experience.

AIM: CyberKnife® is a robotic stereotactic radiotherapy system. The aim of this study is to evaluate the effectiveness and the safety of CyberKnife® on treating head and neck paragangliomas and to report our results. METHODS: Between March 2009 and June 2014, 12 patients with head and neck paragangliomas have been referred to our clinic: in three cases had jugular paragangliomas, five cases had carotid body paragangliomas and three cases had tympanic paragangliomas. One patient had bilateral neck paragangliomas (right neck; carotid body paraganglioma, left neck; jugular pargangliomas). All of them received fractionated stereotactic radiotherapy with CyberKnife® up to a total median dose of 24 Gy (reference isodose 67-90%). The median tumor volume was 35.5 cc (range, 5.3-113.8 cc). The median follow up was 30 months (range, 0-66 months). Local tumor control was assessed according to RECIST criteria on follow-up imaging studies. RESULTS: There were no acute or late toxicity related with stereotactic radiotherapy after treatment. No local tumor progression was observed on magnetic resonance imaging and none of our patients showed progressive clinical status. Seven tumors shrinked in size (54%). Five tumors (46%) had stable size during follow up. Local control rate was 100%. CONCLUSION: Stereotactic radiotherapy is a good alternative to surgery for the treatment of head and neck paragangliomas coming up with a clear benefit of acute and late side effects. CyberKnife® seems to be a safe and efficient system treating head and neck paragangliomas.

Improvement of conformal arc plans by using deformable margin delineation method for stereotactic lung radiotherapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) is an established treatment technique in the management of medically inoperable early stage non-small cell lung cancer (NSCLC). Different techniques such as volumetric modulated arc (VMAT) and three-dimensional conformal arc (DCA) can be used in SBRT. Previously, it has been shown that VMAT is superior to DCA technique in terms of plan evaluation parameters. However, DCA technique has several advantages such as ease of use and considerable shortening of the treatment time. DCA technique usually results in worse conformity which is not possible to ameliorate by inverse optimization. In this study, we aimed to analyze whether a simple method - deformable margin delineation (DMD) - improves the quality of the DCA technique, reaching similar results to VMAT in terms of plan evaluation parameters. METHODS: Twenty stage I-II (T1-2, N0, M0) NSCLC patients were included in this retrospective dosimetric study. Noncoplanar VMAT and conventional DCA plans were generated using 6 MV and 10 MV with flattening filter free (FFF) photon energies. The DCA plan with 6FFF was calculated and 95% of the PTV was covered by the prescription isodose line. Hot dose regions (receiving dose over 100% of prescription dose) outside PTV and cold dose regions (receiving dose under 100% of prescription dose) inside PTV were identified. A new PTV (PTV-DMD) was delineated by deforming PTV margin with respect to hot and cold spot regions obtained from conventional DCA plans. Dynamic multileaf collimators (MLC) were set to PTV-DMD beam eye view (BEV) positions and the new DCA plans (DCA-DMD) with 6FFF were generated. Three-dimensional (3D) dose calculations were computed for PTV-DMD volume. However, the prescription isodose was specified and normalized to cover 95% volume of original PTV. Several conformity indices and lung doses were compared for different treatment techniques. RESULTS: DCA-DMD method significantly achieved a superior conformity index (CI), conformity number (CIPaddick ), gradient index (R50% ), isodose at 2 cm (D2 cm ) and external index (CΔ) with respect to VMAT and conventional DCA plans (P < 0.05 for all comparisons). CI ranged between 1.00-1.07 (Mean: 1.02); 1.00-1.18 (Mean: 1.06); 1.01-1.23 (Mean 1.08); 1.03-1.29 (Mean: 1.15); 1.04-1.29 (Mean: 1.18) for DCA-DMD-6FFF, VMAT-6FFF, VMAT-10FFF DCA-6FFF and DCA-10FFF respectively. DCA-DMD-6FFF technique resulted significantly better CI compared to others (P = 0.002; < 0.001; < 0.001; < 0.001). R50% ranged between 3.22-4.74 (Mean: 3.99); 3.24-5.92 (Mean: 4.15) for DCA-DMD-6FFF, VMAT-6FFF, respectively. DCA-DMD-6FFF technique resulted lower intermediate dose spillage compared to VMAT-6FFF, though the difference was statistically insignificant (P = 0.32). D2 cm ranged between 35.7% and 67.0% (Mean: 53.2%); 42.1%-79.2% (Mean: 57.8%) for DCA-DMD-6FFF, VMAT-6FFF respectively. DCA-DMD-6FFF have significantly better and sharp falloff gradient 2 cm away from PTV compared to VMAT-6FFF (P = 0.009). CΔ ranged between 0.052 and 0.140 (Mean: 0.085); 0,056-0,311 (Mean: 0.120) for DCA-DMD, VMAT-6FFF, respectively. DCA-DMD-6FFF have significantly improved CΔ (P = 0.002). VMAT- V20 Gy , V2.5 Gy and mean lung dose (MLD) indices are calculated to be 4.03%, 23.83%, 3.42 Gy and 4.19%, 27.88%,3.72 Gy, for DCA-DMD-6FFF and DCA techniques, respectively. DCA-DMD-6FFF achieved superior lung sparing compared to DCA technique. DCA-DMD-6FFF method reduced MUs 44% and 33% with respect to VMAT-6FFF and 10FFF, respectively, without sacrificing dose conformity (P < 0.001; P < 0.001). CONCLUSIONS: Our results demonstrated that DCA plan evaluation parameters can be ameliorated by using the DMD method. This new method improves DCA plan quality and reaches similar results with VMAT in terms of dosimetric parameters. We believe that DCA-DMD is a simple and effective technique for SBRT and can be preferred due to shorter treatment and planning time.

Use of volumetric modulated arc radiotherapy in patients with early stage glottic cancer.

AIMS AND BACKGROUND: We compared conformal, intensity-modulated radiotherapy (IMRT) and intensity-modulated arc therapy (IMAT) in early stage glottic cancer in terms of dosimetric features as target coverage, dose to the organs at risk and total treatment time. METHODS AND MATERIALS: Five consecutive T1 glottic squamous cell carcinoma patients were selected for the study. Three-dimensional conformal radiotherapy (3D-CRT), 3-field or 5-field intensity-modulated radiotherapy (3F-IMRT and 5F-IMRT), or IMAT, which was in 2 different forms--a regular IMAT (R-IMAT) and an alternative IMAT (A-IMAT) with an unirradiated section, was planned for each patient. The prescribed dose was 63 Gy in 28 fractions. The minimum dose for 95% of the clinical target volume (D95), maximum dose point at clinical target volume (Dmax), total monitor units, left and right carotid artery doses (V35 and V50 - percentage of volume receiving 35 Gy and 50 Gy), and total treatment time were calculated for each plan. RESULTS: Median D95 values in the 5 plans studied with each technique ranged between 63 and 63.3 Gy (P = NS). Median Dmax values for each technique ranged between 65.4 and 70.8 Gy. The number of hot spots with IMRT and IMAT was significantly higher than with 3D-CRT plans. Conformal radiotherapy plans median V35 (93.6%) and V50 (76.6-83.3%) values for carotid arteries were significantly higher than with IMRT and IMAT (2.9%-11.4% and 0.0%). Average treatment times for 3D-CRT, 3F-IMRT, 5F-IMRT, R-IMAT and A-IMAT techniques were calculated as 64, 119, 147, 39 and 32 seconds, respectively. CONCLUSIONS: IMAT has significantly decreased the treatment time compared to IMRT and 3D-CRT with acceptable homogeneous clinical target volume coverage and low carotid dose.

Spinal implants and radiation therapy: the effect of various configurations of titanium implant systems in a single-level vertebral metastasis model.

BACKGROUND: The combination of surgery and radiation therapy is a common clinical practice in the treatment of spinal tumors. Although it is known that metallic implants disturb radiation therapy beams, it is not known what kind of dose distributions appear with spinal irradiation in the presence of a spinal implant. The aim of the present study was to investigate the effect of various spinal implant constructs on the dose of radiation delivered to the spinal canal in a single-level metastasis model. METHODS: We performed four spinal implant reconstructions on standard sawbones spine models: posterior instrumentation without anterior column reconstruction, posterior instrumentation with anterior column reconstruction with use of a titanium cage, anterior instrumentation with anterior column reconstruction with use of a titanium cage, and anterior instrumentation with anterior column reconstruction with use of chest tubes filled with bone cement. Irradiation with two different radiation therapy units (a cobalt-60 teletherapy unit and a linear accelerator) was performed twice for each model in a posterior-to-anterior direction, and thermoluminescent dosimeters were used to measure the dose changes in the anterior, middle, and posterior portions of the spinal canal. RESULTS: Compared with the sawbones-only model, the posterior instrumentation reconstructions resulted in a 5% to 7% decrease in the radiation dose delivered to the spinal canal with both radiation therapy units, whereas the anterior instrumentation reconstructions resulted in a 1% decrease in the dose delivered with the linear accelerator unit and a < or = 2% increase in the dose delivered with the cobalt-60 teletherapy unit. When thermoluminescent dosimeters in the middle of the spinal canal were evaluated individually, anterior instrumentation with anterior column reconstruction with use of bone cement-filled chest tubes resulted in a 5.5% increase in the radiation dose delivered with the cobalt-60 teletherapy unit, whereas all of the other instrumentation models resulted in a <1% disturbance in the radiation dose delivered with both radiation therapy units. CONCLUSIONS: The posterior instrumentation systems did not result in the delivery of an increased dose of radiation to the spinal cord, suggesting that current radiation therapy regimens may be performed without additional harm. The anterior instrumentation systems also appeared to be relatively safe when irradiation was performed with the linear accelerator unit. However, when irradiation was performed with use of the cobalt-60 teletherapy unit, there was an increase in the dose of radiation delivered to the spinal canal in the presence of the anterior instrumentation systems, particularly the anterior column reconstruction with use of bone cement-filled chest tubes. These dose-perturbation characteristics might be important to consider during the calculation of radiation therapy protocols for patients who are going to receive high doses or recurrent treatments that would reach the tolerance limits of the spinal cord.