Early outcomes of MR-guided SBRT for patients with recurrent pancreatic adenocarcinoma.

BACKGROUND: Local treatment options for locally recurrent pancreatic adenocarcinoma (LR-PAC) are limited, with median survival time (MST) of 9-13 months (mos) following recurrence. MRI-guided stereotactic body radiation therapy (MRgSBRT) provides the ability to dose escalate while sparing normal tissue. Here we report on the early outcomes of MRgSBRT for LR-PAC. METHODS: Patients with prior resection of pancreatic adenocarcinoma with local recurrence treated with MRgSBRT at a single tertiary referral center from 5-2021 to 2-2023 were identified from our prospective database. MRgSBRT was delivered to 40-50 Gy in 4-5 fractions with target and OAR delineation per institutional standards. Endpoints included local control per RECIST v1.1, distant failure, overall survival (OS), and acute and chronic toxicities per Common Terminology Criteria for Adverse Events, v5. RESULTS: Fifteen patients with LR-PAC were identified with median follow-up of 10.6 mos (2.8-26.5 mos) from MRgSBRT. There were 8 females and 7 males, with a median age of 69 years (50-83). One patient underwent neoadjuvant radiation for 50.4 Gy in 28 fractions followed by resection, and one underwent adjuvant radiation for 45 Gy in 25 fractions prior to recurrence. MRgSBRT was delivered a median of 18.8 mos (3.5-52.8 mos) following resection. OS following recurrence at 6 and 12 mos were 87% and 51%, respectively, with a median survival time of 14.1 mos (3.2-27.4 mos). Three patients experienced local failure at 5.9, 7.8, and 16.6 months from MgSBRT with local control of 92.3% and 83.9% at 6 and 12 months. 10 patients experienced distant failure at a median of 2.9 mos (0.3-6.7 mos). Grade 1-2 acute GI toxicity was noted in 47% of patients, and chronic GI toxicity in 31% of patients. No grade > 3 toxicities were noted. CONCLUSIONS: This is the first report on toxicity and outcomes of MRgSBRT for LR-PAC in the literature. MRgSBRT is a safe, feasible treatment modality with the potential for improved local control in this vulnerable population. Future research is necessary to better identify which patients yield the most benefit from MRgSBRT, which should continue to be used with systemic therapy as tolerated. TRIAL REGISTRATION: Jefferson IRB#20976, approved 2/17/21.

Stereotactic MR-guided on-table adaptive radiation therapy (SMART) for borderline resectable and locally advanced pancreatic cancer: A multi-center, open-label phase 2 study.

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity. MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 patients (LAPC 56.6 %; BRPC 43.4 %) after ≥ 3 months of any chemotherapy without distant progression and CA19-9 ≤ 500 U/mL. SMART was delivered on a 0.35 T MR-guided system prescribed to 50 Gy in 5 fractions (biologically effective dose10 [BED10] = 100 Gy). Elective coverage was optional. Surgery and chemotherapy were permitted after SMART. RESULTS: Mean age was 65.7 years (range, 36-85), induction FOLFIRINOX was common (81.7 %), most received elective coverage (57.4 %), and 34.6 % had surgery after SMART. Median FU was 22.9 months from diagnosis and 14.2 months from SMART, respectively. 2-year OS from diagnosis and SMART were 53.6 % and 40.5 %, respectively. Late grade ≥ 3 toxicity definitely, probably, or possibly attributed to SMART were observed in 0 %, 4.6 %, and 11.5 % patients, respectively. CONCLUSIONS: Long-term outcomes from the phase 2 SMART trial demonstrate encouraging OS and limited severe toxicity. Additional prospective evaluation of this novel strategy is warranted.

A Multi-Institutional Phase 2 Trial of Ablative 5-Fraction Stereotactic Magnetic Resonance-Guided On-Table Adaptive Radiation Therapy for Borderline Resectable and Locally Advanced Pancreatic Cancer.

PURPOSE: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC). METHODS AND MATERIALS: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART. RESULTS: One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade ≥3 GI toxicity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%. CONCLUSIONS: The primary endpoint of this study was met with no acute grade ≥3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy.

Dosimetric comparison of Gamma Knife® IconTM and linear accelerator-based fractionated stereotactic radiotherapy (FSRT) plans for the re-irradiation of large (>14 cm3) recurrent glioblastomas.

Our objective is to investigate dosimetric differences between clinically deliverable Gamma Knife® (GK) Icon™ and linac-based FSRT plans on the basis of normal brain dose sparing for large (>14 cm3) recurrent glioblastomas (GBM). Sixteen patients with large, recurrent GBM were treated using re-irradiation via linac-based FSRT, 35 Gy in 10 fractions. For each patient, a new GK FSRT plan was created in Leksell GammaPlan® V11 (LGP). To maintain clinical deliverability, the LGP optimization included a planning goal of treatment time <20 minutes per fraction. Dosimetric comparison of coverage and normal brain dose between the linac and GK treatment plans was performed in MIM. The GK FSRT plans had significantly (p < 0.05) lower mean normal brain dose values (-8.85%), mean values of normal brain V20 (-32.4%) and V12 (-25.9%), and a lower mean V4 (-10.0%). GK FSRT plans have the potential to reduce the risk of radiation-related toxicities.

Geometric and dosimetric effects of image co-registration workflows for Gamma Knife frameless radiosurgery.

The Gamma Knife® Icon™ CBCT facilitates frameless radiosurgery. In the vendor-recommended workflow, MRI is co-registered directly to CBCT for planning. Alternatively, MRI is co-registered to a diagnostic CT, which is then co-registered to CBCT. Our objective is to evaluate if this additional CT is necessary for more accurate registrations. Nine small spherical targets were generated onto 14 patient data-sets. Single-shot treatment plans were created. Geometric and dosimetric differences between the two workflows were determined. Mean target displacement was 0.5±0.3mm; average PTV coverage loss was 4.3±5.0%. For 19 clinical targets in 14 patients, the mean displacement and coverage change was 0.6±0.4mm and 1.3±1.6%. Eleven surrogate landmarks were contoured on a phantom MRI and registered to the CBCT using both workflows. The registration uncertainty was 0.50±0.65mm and 0.32±0.47mm for the MRI-CT-CBCT and MRI-CBCT respectively. As neither workflow was significantly more accurate, the additional CT is unnecessary for most cases.

Improving treatment geometries in total skin electron therapy: Experimental investigation of linac angles and floor scatter dose contributions using Cherenkov imaging.

PURPOSE: The purpose of this study was to identify the optimal treatment geometry for total skin electron therapy (TSET) using a new optimization metric from Cherenkov image analysis, and to investigate the sensitivity of the Cherenkov imaging method to floor scatter effects in this unique treatment setup. METHODS: Cherenkov imaging using an intensified charge coupled device (ICCD) was employed to measure the relative surface dose distribution as a 2D image in the total skin electron treatment plane. A 1.2 m × 2.2 m × 1 cm white polyethylene sheet was placed vertically at a source to surface distance (SSD) of 300 cm, and irradiated with 6 MeV high dose rate TSET beams. The linear accelerator coordinate system used stipulates 0° is the bottom of the gantry arc, and progresses counterclockwise so that gantry angle 270° produces a horizontal beam orthogonal to the treatment plane. First, all unique pairs of treatment beams were analyzed to determine the performance of the currently recommended symmetric treatment angles (±20° from the horizontal), compared to treatment geometries unconstrained to upholding gantry angle symmetry. This was performed on two medical linear accelerators (linacs). Second, the extent of the floor scatter contributions to measured surface dose at the extended SSD required for TSET were imaged using three gantry angles of incidence: 270° (horizontal), 253° (-17°), and 240° (-30°). Images of the surface dose profile at each angle were compared to the standard concrete floor when steel plates, polyvinyl chloride (PVC), and solid water were placed on the ground at the base of the treatment plane. Postprocessing of these images allowed for comparison of floor material-based scatter profiles with previously published simulation results. RESULTS: Analysis of the symmetric treatment geometry (270 ± 20°) and the identified optimal treatment geometry (270 + 23° and 270 - 17°) showed a 16% increase in the 90% isodose area for the latter field pair on the first linac. The optimal asymmetric pair for the second linac (270 + 25° and 270 - 17°) provided a 52% increase in the 90% isodose area when compared to the symmetric geometry. Difference images between Cherenkov images captured with test materials (steel, PVC, and solid water) and the control (concrete floor) demonstrated relative changes in the two-dimensional (2D) dose profile over a 1 × 1.9 m region of interest (ROI) that were consistent with published simulation data. Qualitative observation of the residual images demonstrates localized increases and decreases with respect to the change in floor material and gantry angle. The most significant changes occurred when the beam was most directly impinging the floor (gantry angle 240°, horizontal -30°), where the PVC floor material decreased scatter dose by 1-3% in 7.2% of the total ROI area, and the steel plate increased scatter dose by 1-3% in 7.0% of the total ROI area. CONCLUSIONS: An updated Cherenkov imaging method identified asymmetric, machine-dependent TSET field angle pairs that provided much larger 90% isodose areas than the commonly adopted symmetric geometry suggested by Task Group 30 Report 23. A novel demonstration of scatter dose Cherenkov imaging in the TSET field was established.

Remote Cherenkov imaging-based quality assurance of a magnetic resonance image-guided radiotherapy system.

PURPOSE: Tools to perform regular quality assurance of magnetic resonance image-guided radiotherapy (MRIgRT) systems should ideally be independent of interference from the magnetic fields. Remotely acquired optical Cherenkov imaging-based dosimetry measurements in water were investigated for this purpose, comparing measures of dose accuracy, temporal dynamics, and overall integrated IMRT delivery. METHODS: A 40 × 30.5 × 37.5 cm3 water tank doped with 1 g/L of quinine sulfate was imaged using an intensified charge-coupled device (ICCD) to capture the Cherenkov emission while being irradiated by a commercial MRIgRT system (ViewRay™). The ICCD was placed down-bore at the end of the couch, 4 m from treatment isocenter and behind the 5-Gauss line of the 0.35-T MRI. After establishing optimal camera acquisition settings, square beams of increasing size (4.2 × 4.2 cm2 , 10.5 × 10.5 cm2 , and 14.7 × 14.7 cm2 ) were imaged at 0.93 frames per second, from an individual cobalt-60 treatment head, to develop projection measures related to percent depth dose (PDD) curves and cross beam profiles (CPB). These Cherenkov-derived measurements were compared to ionization chamber (IC) and radiographic film dosimetry data, as well as simulation data from the treatment planning system (TPS). An intensity-modulated radiotherapy (IMRT) commissioning plan from AAPM TG-119 (C4:C-Shape) was also imaged at 2.1 frames per second, and the single linear sum image from 509 s of plan delivery was compared to the dose volume prediction generated by the TPS using gamma index analysis. RESULTS: Analysis of standardized test target images (1024 × 1024 pixels) yielded a pixel resolution of 0.37 mm/pixel. The beam width measured from the Cherenkov image-generated projection CBPs was within 1 mm accuracy when compared to film measurements for all beams. The 502 point measurements (i.e., pixels) of the Cherenkov image-based projection percent depth dose curves (pPDDs) were compared to pPDDs simulated by the treatment planning system (TPS), with an overall average error of 0.60%, 0.56%, and 0.65% for the 4.2, 10.5, and 14.7 cm square beams, respectively. The relationships between pPDDs and central axis PDDs derived from the TPS were used to apply a weighting factor to the Cherenkov pPDD, so that the Cherenkov data could be directly compared to IC PDDs (average error of -0.07%, 0.10%, and -0.01% for the same sized beams, respectively). Finally, the composite image of the TG-119 C4 treatment plan achieved a 95.1% passing rate using 4%/4 mm gamma index agreement criteria between Cherenkov intensity and TPS dose volume data. CONCLUSIONS: This is the first examination of Cherenkov-generated pPDDs and pCBPs in an MR-IGRT system. Cherenkov imaging measurements were fast to acquire, and minimal error was observed overall. Cherenkov imaging also provided novel real-time data for IMRT QA. The strengths of this imaging are the rapid data capture ability providing real-time, high spatial resolution data, combined with the remote, noncontact nature of imaging. The biggest limitation of this method is the two-dimensional (2D) projection-based imaging of three-dimensional (3D) dose distributions through the transparent water tank.

Efficiency of using the day-of-implant CT for planning of SAVI APBI.

PURPOSE: The purpose of the study was to develop an optimized, efficient workflow for using the day-of-implant (DOI) CT for treatment planning of accelerated partial breast irradiation brachytherapy using the strut-adjusted volume implant (SAVI) device. METHODS AND MATERIALS: For 62 consecutive SAVI patients, a DOI CT was acquired and used for treatment planning. A "verification" CT was acquired 24-72 h after implant and immediately before the first fraction, then registered to the DOI CT. If the DOI CT-based plan was no longer optimal, a replan was performed. An array of metrics describing the geometry of the device and its relative position in the patient from the DOI CTs for these patients was collected. These metrics from the DOI CT were evaluated to determine what features could predict for the need to replan before the first treatment fraction. Logistical regression analysis including χ2 tests was used to determine if different factors correlated with replanning. RESULTS: Twenty-two of 62 patients (35%) required replanning. Only the presence of splayed struts, where splay was toward the skin, and the use of a nine strut ("8-1") SAVI were significantly correlated (p < 0.05) with replanning. Within these individual populations, no additional factors showed a significant statistical correlation for requiring replanning. CONCLUSIONS: For strut-based accelerated partial breast irradiation brachytherapy, it was feasible to treat with a plan based on the DOI CT for a majority (65%) of patients. Some factors correlate to needing replanning; recognizing these could be used to optimize treatment workflow for certain patients, increasing clinical efficiency while enhancing the quality of patient care.

Accelerated partial breast irradiation dosimetric criteria for the strut-adjusted volume implant.

PURPOSE: Current guidelines for high-dose-rate accelerated partial breast irradiation using single-entry implants are based on the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol, which assumed a balloon implant geometry. We have developed robust plan evaluation criteria specifically for the strut-adjusted volume implant (SAVI). METHODS AND MATERIALS: Plan evaluation criteria were established using a "training data set" of 62 SAVI treatment plans and included the percentage volume of target receiving 90%, 95%, and 100% of the prescription dose (V90, V95, and V100), the absolute volume of target receiving 150% and 200% of prescription (V150 and V200), and the maximum doses to skin (Dskin max) and ribs (Drib max). "Ideal" and "expected" (routinely achievable) thresholds were determined for each criterion and compared to B-39 guidelines. A "test data set" collected from the next 25 patients was analyzed using the developed plan evaluation criteria. RESULTS: Ideal (expected) dosimetric thresholds established from the training data set were V90 ≥ 98% (95%), V95 ≥ 95% (92%), V100 ≥ 91% (88%), Dskin max < 90% (100%), and Drib max < 100%. Thresholds for V150 and V200 were stratified by SAVI size: V150 ≤ 30 cc (50 cc) and V200 ≤ 15 cc (20 cc) for 6-1 and Mini; V150 ≤ 50 cc (50 cc) and V200 ≤ 20 cc (20 cc) for 8-1 and 10-1. There was no significant difference between the training and test data sets in the fractions of patients meeting the criteria. Overall, 58% and 95% of 87 plans met all ideal and all expected criteria, respectively. CONCLUSIONS: The plan evaluation criteria developed specifically for the SAVI device are robust, providing increased target coverage and increased skin sparing compared to B-39 guidelines.

Evaluation of template matching for tumor motion management with cine-MR images in lung cancer patients.

PURPOSE: Accurate determination of tumor position is crucial for successful application of motion compensated radiotherapy in lung cancer patients. This study tested the performance of an automated template matching algorithm in tracking the tumor position on cine-MR images by examining the tracking error and further comparing the tracking error to the interoperator variability of three human reviewers. METHODS: Cine-MR images of 12 lung cancer patients were analyzed. Tumor positions were determined both automatically with template matching and manually by a radiation oncologist and two additional reviewers trained by the radiation oncologist. Performance of the automated template matching was compared against the ground truth established by the radiation oncologist. Additionally, the tracking error of template matching, defined as the difference in the tumor positions determined with template matching and the ground truth, was investigated and compared to the interoperator variability for all patients in the anterior-posterior (AP) and superior-inferior (SI) directions, respectively. RESULTS: The median tracking error for ten out of the 12 patients studied in both the AP and SI directions was less than 1 pixel (= 1.95 mm). Furthermore, the median tracking error for seven patients in the AP direction and nine patients in the SI direction was less than half a pixel (= 0.975 mm). The median tracking error was positively correlated with the tumor motion magnitude in both the AP (R = 0.55, p = 0.06) and SI (R = 0.67, p = 0.02) directions. Also, a strong correlation was observed between tracking error and interoperator variability (y = 0.26 + 1.25x, R = 0.84, p < 0.001) with the latter larger. CONCLUSIONS: Results from this study indicate that the performance of template matching is comparable with or better than that of manual tumor localization. This study serves as preliminary investigations towards developing online motion tracking techniques for hybrid MRI-Linac systems. Accuracy of template matching makes it a suitable candidate to replace the labor intensive manual tumor localization for obtaining the ground truth when testing other motion management techniques.