Pediatric I-131 MIBG therapy is a complex treatment that requires careful consideration during commissioning. With a properly trained multidisciplinary team, robust procedures and checklists, and appropriate resources, it can be implemented safely and effectively.

PURPOSE: To assist radiation oncology centers in implementing Lutetium-177-dotatate (Lu-177) radiopharmaceutical therapy for midgut neuroendocrine tumors. Here we describe our workflow and how it was revised based on our initial experience on an expanded access protocol (EAP). METHODS: A treatment team/area was identified. An IV-pump-based infusion technique was implemented. Exposure-based techniques were implemented to determine completion of administration, administered activity, and patient releasability. Acute toxicities were assessed at each fraction. A workflow failure modes and effects analysis (FMEA) was performed. RESULTS: A total of 22 patients were treated: 11 patients during EAP (36 administrations) and 11 patients after EAP (44 administrations). Mean Lu-177 infusion time was 37 min (range 26-65 min). Mean administered activity was 97% (range 90-99%). Mean patient exposures at 1 m were 1.9 mR/h (range 1.0-4.1 mR/h) post-Lu-177 and 0.9 mR/h (range 0.4-1.8 mR/h) at discharge, rendering patients releasable with instructions. Treatment area was decontaminated and released same day. All patients in the EAP experienced nausea, and nearly half experienced emesis despite premedication with antiemetics. Peripheral IV-line complications occurred in six treatments (16.7%), halting administration in 2 cases (5.6%). We transitioned to peripherally inserted central catheter (PICC)-lines and revised amino acid formulary after the EAP. The second cohort of 11 patients after EAP were analyzed for PICC-line complications and acute toxicity. Nausea and emesis rates decreased (nausea G1+ 61%-27%; emesis G1+ 23%-7%), and no PICC complications were observed. FMEA revealed that a failure in amino acid preparation was the highest risk. CONCLUSION: Lu-177-dotatate can be administered safely in an outpatient radiation oncology department. (c) 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

In lung cancer, deformation of lung and tumor due to respiratory motion can cause harmful mistargeting of radiation therapy. We examined interfractional lung deformation, which we characterized by using the distance between electromagnetic transponder pairs implanted in or near lung tumors. Our hypothesis is that there is a positive correlation between lung tumor deformation and both the number of treatment fractions and the intertransponder implantation distance. Continuous electromagnetic transponder data of lung tumor motion was collected from 45 patients (572 total fractions) across 6 institutions during external beam radiation therapy in a prospective clinical trial (NCT01396551). External intervention from the clinician, such as couch shifts, instructed breath holds, and acquisition pauses, were manually removed from the 10 Hz tracking data according to recorded notes. A total of 129 transponder pairs were analyzed, typically 3/patient. For each pair in each fraction, we calculated the median of the 3-dimensional intertransponder distance time series. Then for each patient we calculated whether these distances changed throughout treatment. We grouped results for each patient depending on whether lung deformation was considered negligible (≤3 mm) or nonnegligible (>3 mm); whether they were conventionally fractionated (≥10 fractions) or hypofractionated (<10 fractions); and whether there was a large implantation distance (>3 cm) or adequate implantation distance (≤3 cm). A pair of -tests were used to determine whether lung deformation was related to implantation distance and/or the number of fractions across a patient's treatment. The median fraction number was 10. The median implantation distance was 3.1 cm. The mean ± SD deformation was 2.23±2.31 mm, with a range of 0 to 12.8 mm. Out of 129 transponder pairs, the majority (n=100) had negligible lung deformation. In the transponder pairs that had nonnegligible deformation, the mean ± SD implantation distance was 5.56±2.33 cm and 17.4±8.4 for fraction number. The -tests found significant relationships between nonnegligible deformation and (1) large implantation distance (P<0.025) and (2) conventional fractionation (P<0.0025). Both the overall length of treatment and the implantation distance greatly affect lung deformation. The relationships we found suggest that care should be taken when selecting patients for fiducial guided lung cancer therapy with conventionally fractionated treatment plans or implantation distance.

Lung tumors are inherently subject to large and unpredictable motion, which make them difficult to treat with external beam radiation therapy. Missed targets can result in excessive radiation to healthy lung and other critical structures. Continuous, real-time tracking of this motion is an available solution to this problem but may not be fully necessary. We investigated the required intermittent imaging frequency necessary to accurately represent lung tumor motion during treatment. Continuous electromagnetic transponder data of lung tumor motion was collected from 45 patients (572 total fractions) across 6 institutions during external beam radiation therapy in a prospective clinical trial (NCT01396551). External intervention from the clinician, such as couch shifts, instructed breath-holds, and acquisition pauses, were manually removed from the 10 Hz tracking data according to recorded notes. The tracking data was converted to three-dimensional (3D) displacements from the initial location in each fraction. The resulting 3D data was sampled at 0.2-, 0.3-, 0.4-, and 0.5-second intervals and modeled linearly between points to represent the intermittent imaging models. Fractions lasting <60 seconds were excluded from the analysis. Sensitivity for identifying displacements greater than 3- and 5-mm throughout each patient's entire treatment was used to assess each imaging model. Imaging models were considered sufficient with ≥95% sensitivity for 3-mm displacements for ≥95% of the patients. A total of 563 fractions and 6153 minutes of tracking data met inclusion criteria. Both the 0.2-second (5 Hz) and 0.3-second (3.3 Hz) imaging models were sufficiently accurate in identifying 3-mm displacements (see Table 1). The 0.4-second (2.5 Hz) and 0.5-second (2.0 Hz) imaging models failed to reliably identify 3-mm or larger displacements.Abstract 3663; Table 1.ModelDisplacement3 mm5 mmPatients with ≥95% sensitivity (%)0.2 (5.0 Hz)100*930.3 sec (3.3 Hz)96*890.4 sec (2.5 Hz)89800.5 sec (2.0 Hz)7669% total time exceeding displacement5836 Open table in a new tab Imaging at least every 0.3 seconds (3.3 Hz) is necessary for accurate tracking of lung tumor motion. Less frequent imaging requires a supplemental respiratory motion model.

Standard of care for lung cancer patients includes cone beam computed tomography (CBCT) localization prior to treatment. Work has been done to obtain respiratory motion information during this time but has not been validated on whether this is an accurate measurement of tumor motion during the whole fraction. We wanted to evaluate the stability of the mean tumor position during the whole fraction as compared with the first minute of treatment. Continuous electromagnetic transponder data of lung tumor motion was collected from 45 patients (572 total fractions) across 6 institutions during external beam radiation therapy in a prospective clinical trial (NCT01396551). External intervention from the clinician, such as couch shifts, instructed breath holds, and acquisition pauses, were manually removed from the 10 Hz tracking data according to recorded notes. For each fraction, the isocenter position was extracted from the transponder data. The isocenter position was shifted by the mean isocenter position during the first minute of treatment. The mean change in position of the shifted isocenter data for the entire fraction compared to the first minute in the transponder data was used as an index to describe mean tumor position drift. Shifts greater than 3 mm were defined as clinically relevant and explored for commonalities. Twenty of 572 fractions were excluded from this study due to a lack of 1 minute's worth of transponder data. A total of 34 fractions (6%) were found to contain a shift of 3 mm or more. Seventeen of the 45 patients treated were found to have at least 1 fraction with a shift greater than 3 mm. Of these patients, half only had 1 fraction that shifted beyond 3 mm. No patient had more than 4 fractions with large shifts. Eleven of the 16 patients with large shifts were treated in 15 fractions or fewer. Of the fractions delivered in fewer than 15 minutes, 4% of them resulted in a shift greater than 3 mm. For patient treatments lasting longer than 15 minutes, 12% were found to have a shift greater than 3 mm. Continuous motion measurement from the first 60 s of treatment accurately predicted the mean target position of the lung tumor within 3 mm for 94% of the fractions analyzed. On the other hand, the 6% of fractions with greater than 3-mm shifts were spread across 1/3 of the patient population. Patients with treatment times longer than 15 min would most benefit from continued monitoring during treatment due to a higher probability of mean tumor position drift.

Although 4DCT is most often used for motion management, research shows it does not adequately predict on-table tumor motion for abdominal radiation therapy. In this study, we demonstrated the use of Cone Beam CT (CBCT) projection data for predicting intrafraction tumor motion and compared our results to pre and post treatment fluoroscopy (FL). For 31 patients with abdominal tumors and implanted fiducial markers, tumor motion was measured with CBCT and fluoroscopy for 202 treatment fractions and compared to the planned tumor motion from 4DCT. We processed the CBCT projections using an in-house fiducial tracking algorithm and used maximum-likelihood to calculate the fiducial trajectories. The trajectories were also measured by pre and post treatment orthogonal fluoroscopy. The daily required internal margin (IM) was calculated for CBCT and fluoroscopy as the fifth through 95th percentiles of motion in each left-right (LR), superior-inferior (SI) and anterior-posterior (AP) direction. The planning IM4DCT (the range of fiducial motion on 4DCT) was determined to be adequate when it was within ±1.2 mm (AP, LR) and ±3 mm (SI) of the daily IMCBCT, IMpre-fluoro or IMfluoro (combined pre and post treatment fluoroscopy). To validate the CBCT technique as a predictive measure of intrafraction motion, we compared IMCBCT to IMpre-fluoro, which is our institutional standard for measuring daily intrafractional motion. Finally, we compared IMCBCT to IMfluoro to identify patients who could benefit from imaging during treatment. The planning 4DCT could not accurately predict the intrafractional tumor motion observed during CBCT in ≥80% of fractions for 97% of patients. As measured by IMpre-fluoro and IMfluoro, 4DCT failed to predict intrafractional tumor motion in ≥80% of fractions for 94% and 100% of patients, respectively. Comparing CBCT to fluoroscopy, IMCBCT was in agreement with or larger than IMpre-fluoro for 96.0%, 91.3% and 93.4% of fractions in LR, SI and AP directions, respectively. For conventionally fractionated patients (median treatment time, t = 8.8 min), IMCBCT was in agreement with or larger than IMfluoro for 97.3% of fractions (in SI direction); this decreased to 82.3% for SBRT patients (t = 17 min) demonstrating the need for imaging during treatment for patients with longer treatment times. Tumor motion determined from 4DCT-simulation does not accurately predict the daily motion observed on CBCT or fluoroscopy. Fiducial motion derived from CBCT projection data accurately reflects the motion observed on pre and posttreatment fluoroscopy; CBCT could replace fluoroscopy for pretreatment internal margin verification, potentially reducing patient setup time and imaging dose. For patients with longer treatment times, there is a need for imaging during treatment to verify internal margin accuracy.

Radioembolization via intra-arterial delivery of yttrium-90 (90Y) microspheres is a growing therapeutic option for primary or secondary hepatic malignancies; 90Y microspheres can be visualized by PET due to a small decay branch that results in β-/β+ pair production. Post-delivery imaging of 90Y microspheres may enable quantification of extrahepatic deposition and tumor coverage to predict toxicities and treatment response. We have used a hybrid PET/MRI scanner to assess 90Y microsphere distribution, estimate dose to target lesions, and compare quantitative dosimetry to treatment outcome in a prospective institutional protocol. Patients undergoing 90Y radioembolization for any indication were eligible for this study. Positron Emission Tomography/MRI was performed for 24 patients (8 with hepatocellular carcinoma, 16 with metastatic disease) within 25 hours following 90Y delivery; PET and MR images were fused and co-registered using image registration and analysis software. Target lesions were contoured on the 20-minute delayed VIBE MR sequence and transferred to PET images to quantify activity and dose. Dose maps were created by convolving the activity with a voxelized dose kernel, and dose-volume histograms (DVHs) were generated from these dose maps. Treated lesions were contoured on follow-up imaging (3 or 6 months post-treatment) and compared to the initial PET/MRI images. Lesions that decreased in volume by at least 20% were considered "responders," while those that did not were considered "non-responders." Student's t-tests were applied to the D20, D50, D75, and Davg of responders versus non-responders. Treatment response was assessed for 86 lesions in 24 patients. Of the 86 lesions, 64 responded to 90Y radioembolization. The average dose (Davg), D20, and D50 were significantly higher in the responding lesions than in non-responding lesions (P = .0093, .0102 and .0188, respectively). Upon evaluation by histologic subtype, 9 out of 10 hepatocellular carcinoma lesions responded to treatment. Out of the 42 metastatic colorectal cancer (CRC) lesions, 25 responded and had significantly higher Davg, D20, and D50 (P = .0170, .0119, and .0286, respectively) than those that did not respond to therapy. Simultaneous acquisition of contrast MRI with PET allows for highly accurate tumor segmentation, which is essential for quantification of the PET data; PET-generated DVHs can be used to predict dose response and treatment outcome in individual lesions. This may lead to early interventions on lesions that received suboptimal dosing.Oral Scientific Abstracts 219; Table 1All P < .05Responders (all)Non-responders (all)Responders (CRC)Non-responders (CRC)Mean Davg (Gy)66.532.951.124.9Mean D20 (Gy)94.544.371.833.9Mean D50 (Gy)58.531.047.322.9 Open table in a new tab