Introduction: High-dose total body irradiation (TBI) is often part of myeloablative conditioning in acute leukemia. Modern volumetric modulated arc therapy (VMAT)-based plans employ arcs to the ...inferior-most portion of the body that can be simulated in a head-first position and use 2D planning for the inferior body which can result in heterogeneous doses. Here, we describe our institution's unique protocol for delivering high-dose TBI entirely with VMAT and retrospectively compare dosimetric outcomes with helical tomotherapy (HT) plans. Additionally, we describe our method of oropharyngeal mucosal sparing that was implemented after fatal mucositis occurred in two patients. Methods: Thirty-one patients were simulated and treated in head-first (HFS) and feet-first (FFS) orientations. Patients were treated with VMAT (n = 26) or HT (n = 5). In VMAT plans, to synchronize doses between the orientations, images were deformably registered and the HFS dose was transferred to the FFS plan and used as a background dose when optimizing plans. Six to eight isocenters with two arcs per isocenter were generated. HT was delivered with an established technique. Patients were treated to 13.2 Gy over eight twice daily fractions. Dosimetric outcomes and toxicities were retrospectively compared. Results: Prescription dose and organ at risk (OAR) constraints were met for all patients. Lower lung doses were achieved with VMAT relative to HT plans (7.4 vs 7.7 Gy, P = .009). Statistically significant improvement in mucositis was not achieved after adopting a mucosal-sparing technique, however lower doses to the oropharyngeal mucosal were achieved (6.9 vs 14.1 Gy, P = .009), and no further mucositis-related deaths occurred. Conclusions: This full-body VMAT method of TBI achieves dose goals, eliminates risk of heterogenous doses within the femur, and demonstrates that selective OAR sparing with the purpose of reducing TBI-related morbidity and mortality is possible at any institution with a VMAT-capable linear accelerator.
Purpose: To monitor intrafraction motion during spine stereotactic body radiotherapy(SBRT) treatment delivery with readily available technology, we implemented triggered kV imaging using the on-board ...imager(OBI) of a modern medical linear accelerator with an advanced imaging package. Methods: Triggered kV imaging for intrafraction motion management was tested with an anthropomorphic phantom and simulated spine SBRT treatments to the thoracic and lumbar spine. The vertebral bodies and spinous processes were contoured as the image guided radiotherapy(IGRT) structures specific to this technique. Upon each triggered kV image acquisition, 2D projections of the IGRT structures were automatically calculated and updated at arbitrary angles for display on the kV images. Various shifts/rotations were introduced in x, y, z, pitch, and yaw. Gantry-angle-based triggering was set to acquire kV images every 45°. A group of physicists/physicians(n = 10) participated in a survey to evaluate clinical efficiency and accuracy of clinical decisions on images containing various phantom shifts. This method was implemented clinically for treatment of 42 patients(94 fractions) with 15 second time-based triggering. Result: Phantom images revealed that IGRT structure accuracy and therefore utility of projected contours during triggered imaging improved with smaller CT slice thickness. Contouring vertebra superior and inferior to the treatment site was necessary to detect clinically relevant phantom rotation. From the survey, detectability was proportional to the shift size in all shift directions and inversely related to the CT slice thickness. Clinical implementation helped evaluate robustness of patient immobilization. Based on visual inspection of projected IGRT contours on planar kV images, appreciable intrafraction motion was detected in eleven fractions(11.7%). Discussion: Feasibility of triggered imaging for spine SBRT intrafraction motion management has been demonstrated in phantom experiments and implementation for patient treatments. This technique allows efficient, non-invasive monitoring of patient position using the OBI and patient anatomy as a direct visual guide.
Hypofractionated radiation therapy (RT) offers benefits in the treatment of soft tissue sarcomas (STS), including exploitation of the lower α/β, patient convenience, and cost. This study evaluates ...the acute toxicity of a hypofractionated accelerated RT dose-painting (HARD) approach for postoperative treatment of STS.
This is a retrospective review of 53 consecutive patients with STS who underwent resection followed by postoperative RT. Standard postoperative RT dosing for R0/R1/gross disease with sequential boost (50 Gy + 14/16/20 Gy in 32-35 fractions) were replaced with dose-painting, which adapts dose based on risk of disease burden, to 50.4 and 63, 64.4, 70 Gy in 28 fractions, respectively. The first 10 patients were replanned with a sequential boost RT approach and dosimetric indices were compared. Time-to-event outcomes, including local control, regional control, distant control, and overall survival, were estimated with Kaplan-Meier analysis.
Median follow-up was 25.2 months. Most patients had high-grade (59%) STS of the extremity (63%) who underwent resection with either R1 (40%) or close (36%) margins. Four patients experienced grade 3 acute dermatitis which resolved by the 3-month follow-up visit. The 2-year local control, regional control, distant control, and overall survival were 100%, 92%, 68%, and 86%, respectively. Compared with the sequential boost plan, HARD had a significantly lower field size (total V50 Gy; P = .002), bone V50 (P = .031), and maximum skin dose (P = .008). Overall treatment time was decreased by 4 to 7 fractions, which translated to a decrease in estimated average treatment cost of $3056 (range, $2651-$4335; P < .001).
In addition to benefits in cost, convenience, and improved biologic effect in STS, HARD regimen offers a safe treatment approach with dosimetric advantages compared with conventional sequential boost, which may translate to improved long-term toxicity.
We extracted image features from serial
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F-labeled fluorodeoxyglucose (FDG) positron emission tomography (PET) / computed tomography (CT) scans of anal cancer patients for the prediction of tumor ...recurrence after chemoradiation therapy (CRT). Seventeen patients (4 recurrent and 13 non-recurrent) underwent three PET/CT scans at baseline (Pre-CRT), in the middle of the treatment (Mid-CRT) and post-treatment (Post-CRT) were included. For each patient, Mid-CRT and Post-CRT scans were aligned to Pre-CRT scan. Comprehensive image features were extracted from CT and PET (SUV) images within manually delineated gross tumor volume, including geometry features, intensity features and texture features. The difference of feature values between two time points were also computed and analyzed. We employed univariate logistic regression model, multivariate model, and naïve Bayesian classifier to analyze the image features and identify useful tumor recurrent predictors. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the accuracy of the prediction. In univariate analysis, six geometry, three intensity, and six texture features were identified as significant predictors of tumor recurrence. A geometry feature of Roundness between Post-CRT and Pre-CRT CTs was identified as the most important predictor with an AUC value of 1.00 by multivariate logistic regression model. The difference of Number of Pixels on Border (geometry feature) between Post-CRT and Pre-CRT SUVs and Elongation (geometry feature) of Post-CRT CT were identified as the most useful feature set (AUC = 1.00) by naïve Bayesian classifier. To investigate the early prediction ability, we used features only from Pre-CRT and Mid-CRT scans. Orientation (geometry feature) of Pre-CRT SUV, Mean (intensity feature) of Pre-CRT CT, and Mean of Long Run High Gray Level Emphasis (LRHGLE) (texture feature) of Pre-CRT CT were identified as the most important feature set (AUC = 1.00) by multivariate logistic regression model. Standard deviation (intensity feature) of Mid-CRT SUV and difference of Mean of LRHGLE (texture feature) between Mid-CRT and Pre-CRT SUVs were identified as the most important feature set (AUC = 0.86) by naïve Bayesian classifier. The experimental results demonstrated the potential of serial PET/CT scans in early prediction of anal tumor recurrence.
The use of stereotactic body radiation therapy (SBRT) is widely utilized for treatment of localized prostate cancer. Magnetic-resonance-guided radiotherapy (MRgRT) was introduced in 2014 and has ...recently been implemented in SBRT for prostate cancer as it provides an opportunity for smaller margins and adaptive daily planning. Currently, the only publications of MRgRT for prostate SBRT describe European clinical experiences which utilized adaptive planning. However, adaptive planning adds significantly to the time required for daily treatment.
Since prostate SBRT has demonstrated acceptable toxicity for several years, we did not consider daily adaptation critical to the process of prostate SBRT. After Institutional Review Board approval, we analyzed and now report our experience using MRgRT without adaptation.
Between 25 September 2019 and 21 December 2020, 35 consecutive patients were treated with MRgRT prostate SBRT at our center. Patients treated with MRgRT included favorable intermediate risk (43%) and unfavorable intermediate risk (54%), and only one patient had low-risk prostate cancer. Nine patients (25%) received adjuvant leuprolide for a median of 4.5 months (range 4-6 m). Our clinical pathway allows for a maximum prostate gland volume of 60 cc; median prostate volume of this cohort was 35.0 cc (range 17-58.4 cc). Median pre-treatment PSA was 6.30 (range 2.55-16.77). Each patient was treated with 36.25 Gy delivered in five fractions over 2 weeks with urethral sparing to a maximal dose of 35 Gy. Target volumes included the prostate gland and proximal seminal vesicles with a 3 mm margin.
Median follow-up as of 26 May 2021 was 11.97 months (range 4.37-19.80). First follow-up data are available for all patients, with a median of 1.10 month from completion of treatment (0.63-3.40). The median PSA at first visit was 2.75 (range 0.02-9.00) with a median AUA symptom score of 9 (range 1-24). Second follow-up data are available for 34 patients at a median of 4.45 months (range 2.57-8.90). At second follow-up, the median PSA was 1.60 (range 0.02-5.40) with a median AUA symptom score of 6 (range 1-33). Seventeen patients had third follow-up data with a median of 9.77 months (range 4.70-12.33) after SBRT. The median PSA was 1.13 (range 0.02-4.73) with an AUA score of 9 (2-22) at the third follow-up. We observed a statistically significant decrease in PSA between pre-treatment and at first follow-up (
< 0.005). The most common toxicity was grade 2 urethritis, managed in all cases by tamsulosin. One patient developed grade 2 tenesmus relieved by topical steroids. No cases of grade ≥ 3 toxicity were seen in our patient population.
By avoiding the extra time required for plan adaptation, MRgRT without daily adaptation allows for successful prostate SBRT with manageable toxicity. We continue to reserve our limited adaptive treatment slots for preoperative pancreatic and ultra-central lung SBRT patients, which require time-intensive respiratory gating and adaptive planning.
Intensity-modulated radiation therapy (IMRT) may be useful to reduce toxicity in gynecologic cancer patients requiring postoperative pelvic irradiation. This study was undertaken to quantify vaginal ...wall organ motion during the course of postoperative pelvic irradiation using pelvic IMRT.
Twenty-two consecutive patients treated with postoperative pelvic IMRT on helical tomotherapy had fiducial markers placed at the vaginal apex prior to simulation then daily megavoltage computed tomography (CT) scans for positioning. The daily positions of the fiducials were registered and measured in reference to the initial CT scan to quantify the degree of vaginal wall organ motion during the entire course of therapy.
The total motion of the fiducials center of mass (COM) was a median of 5.8 mm (range, 0.6-20.2 mm), and 95% of all COM positions fell within 15.7 mm of their original position. Directional margins of 3.1 mm along the right-left axis, 9.5 mm along the superoinferior axis, and of 12.1 mm along the anteroposterior axis encompassed the vaginal fiducials in 95% of treatments. Mean organ deformation for all patients was 3.9 mm, (range, 0-27.5 mm; standard deviation, 3.1 mm), with significant distortions of greater than 10 mm in 17% of secondary image sets.
These data suggest a planning target volume margin of 16 mm will account for maximal organ motion in the majority of gynecologic patients undergoing postoperative pelvic IMRT, and it may be possible to incorporate directional motion into the planning target volume margin.
Definitive local therapy with stereotactic ablative radiation therapy (SABR) for ultracentral lung lesions is associated with a high risk of toxicity, including treatment related death. Stereotactic ...MR-guided adaptive radiation therapy (SMART) can overcome many of the challenges associated with SABR treatment of ultracentral lesions.
We retrospectively identified 14 consecutive patients who received SMART to ultracentral lung lesions from 10/2019 to 01/2021. Patients had a median distance from the proximal bronchial tree (PBT) of 0.38 cm. Tumors were most often lung primary (64.3%) and HILUS group A (85.7%). A structure-specific rigid registration approach was used for cumulative dose analysis. Kaplan-Meier log-rank analysis was used for clinical outcome data and the Wilcoxon Signed Rank test was used for dosimetric data.
Here we show that SMART dosimetric improvements in favor of delivered plans over predicted non-adapted plans for PBT, with improvements in proximal bronchial tree DMax of 5.7 Gy (p = 0.002) and gross tumor 100% prescription coverage of 7.3% (p = 0.002). The mean estimated follow-up is 17.2 months and 2-year local control and local failure free survival rates are 92.9% and 85.7%, respectively. There are no grade ≥ 3 toxicities.
SMART has dosimetric advantages and excellent clinical outcomes for ultracentral lung tumors. Daily plan adaptation reliably improves target coverage while simultaneously reducing doses to the proximal airways. These results further characterize the therapeutic window improvements for SMART. Structure-specific rigid dose accumulation dosimetric analysis provides insights that elucidate the dosimetric advantages of SMART more so than per fractional analysis alone.
Soft tissue sarcomas (STS) are historically radioresistant, with surgery being an integral component of their treatment. With their low α/β, STS may be more responsive to hypofractionated radiation ...therapy (RT), which is often limited by long-term toxicity risk to surrounding normal tissue. An isotoxic approach using a hypofractionated accelerated radiation dose-painting (HARD) regimen allows for dosing based on clinical risk while sparing adjacent organs at risk.
We retrospectively identified patients from 2019 to 2022 with unresected STS who received HARD with dose-painting to high, intermediate, and low-risk regions of 3.0 Gy, 2.5 Gy, and 2.0 to 2.3 Gy, respectively, in 20 to 22 fractions. Clinical endpoints included local control, locoregional control, progression free survival, overall survival, and toxicity outcomes.
Twenty-seven consecutive patients were identified and had a median age of 68 years and tumor size of 7.0 cm (range, 1.2-21.0 cm). Tumors were most often high-grade (70%), stage IV (70%), located in the extremities (59%), and locally recurrent (52%). With a median follow-up of 33.4 months, there was a 3-year locoregional control rate of 100%. The 3-year overall and progression-free survival were 44.9% and 23.3%, respectively. There were 5 (19%) acute and 2 (7%) late grade 3 toxicities, and there were no grade 4 or 5 toxicities at any point.
The HARD regimen is a safe method of dose-escalating STS, with durable 3-year locoregional control. This approach is a promising alternative for unresected STS, though further follow-up is required to determine long-term control and toxicity.
Background and purposeDiffusion weighted imaging (DWI) allows for the interrogation of tissue cellularity, which is a surrogate for cellular proliferation. Previous attempts to incorporate DWI into ...the workflow of a 0.35 T MR-linac (MRL) have lacked quantitative accuracy. In this study, accuracy, repeatability, and geometric precision of apparent diffusion coefficient (ADC) maps produced using an echo planar imaging (EPI)-based DWI protocol on the MRL system is illustrated, and in vivo potential for longitudinal patient imaging is demonstrated.Materials and methodsAccuracy and repeatability were assessed by measuring ADC values in a diffusion phantom at three timepoints and comparing to reference ADC values. System-dependent geometric distortion was quantified by measuring the distance between 93 pairs of phantom features on ADC maps acquired on a 0.35 T MRL and a 3.0 T diagnostic scanner and comparing to spatially precise CT images. Additionally, for five sarcoma patients receiving radiotherapy on the MRL, same-day in vivo ADC maps were acquired on both systems, one of which at multiple timepoints.ResultsPhantom ADC quantification was accurate on the 0.35 T MRL with significant discrepancies only seen at high ADC. Average geometric distortions were 0.35 (±0.02) mm and 0.85 (±0.02) mm in the central slice and 0.66 (±0.04) mm and 2.14 (±0.07) mm at 5.4 cm off-center for the MRL and diagnostic system, respectively. In the sarcoma patients, a mean pretreatment ADC of 910x10-6 (±100x10-6) mm2/s was measured on the MRL.ConclusionsThe acquisition of accurate, repeatable, and geometrically precise ADC maps is possible at 0.35 T with an EPI approach.
•Radiation is not typical in the standard of care for cardiac metastases.•MR-guided radiation uses real-time imaging and offers better soft tissue contrast.•Real-time MR-guidance allows for safe high ...dose radiation to cardiac metastases.•MR-guided stereotactic radiation can improve symptoms without acute toxicity.
To assess the safety and efficacy of MR-guided stereotactic body radiation therapy (MRgSBRT) for cardiac metastases.
This single institution retrospective analysis evaluated our experience with MRgSBRT for cardiac metastases. Response rate was compared between pre-RT and post-RT imaging. Symptomatic changes were also tracked and documented.
Between 4/2019 and 3/2020, five patients with cardiac metastases (4 intracardiac and 1 pericardial) were treated with MRgSBRT. Median age at treatment was 73 years (range 64–80) and two patients had pre-existing cardiac disease. Histologies included melanoma and breast adenocarcinoma. Median lesion diameter was 2 cm (range 1.96–5.8 cm). Three patients were symptomatic, one of whom had pulmonary hypertension and RV enlargement. Another patient had an asymptomatic arrythmia. Median PTV prescribed dose was 40 Gy (range 40–50 Gy) and delivered in five fractions on nonconsecutive days. Median PTV volume was 53.4 cc (range 8.7–116.6 cc) and median coverage was 95% (range 84.1–100%). A uniform 3 mm margin was used for real-time gating, allowing a median 7% (range 5–10%) pixel excursion tolerance. Median follow-up was 4.7 months (range 0.9–12.3). Two patients exhibited stable disease, two had a partial response and one exhibited a complete response. All symptomatic patients experienced some relief. There were no acute adverse events, however, one patient without prior cardiac disease developed atrial fibrillation 6 months after treatment. Two patients died of causes unrelated to cardiac MRgSBRT.
In this largest known series of cardiac metastasis MRgSBRT, real-time image guidance enables safe treatment resulting in good response with improving presenting symptoms without acute adverse events.