Stereotactic Body Radiation Therapy Treatment Research Articles

An Interpretable Planning Bot for Pancreas Stereotactic Body Radiation Therapy

Pancreas stereotactic body radiation therapy (SBRT) treatment planning requires planners to make sequential, time-consuming interactions with the treatment planning system to reach the optimal dose distribution. We sought to develop a reinforcement learning (RL)-based planning bot to systematically address complex tradeoffs and achieve high plan quality consistently and efficiently. The focus of pancreas SBRT planning is finding a balance between organ-at-risk sparing and planning target volume (PTV) coverage. Planners evaluate dose distributions and make planning adjustments to optimize PTV coverage while adhering to organ-at-risk dose constraints. We formulated such interactions between the planner and treatment planning system into a finite-horizon RL model. First, planning status features were evaluated based on human planners' experience and defined as planning states. Second, planning actions were defined to represent steps that planners would commonly implement to address different planning needs. Finally, we derived a reward system based on an objective function guided by physician-assigned constraints. The planning bot trained itself with 48 plans augmented from 16 previously treated patients, and generated plans for 24 cases in a separate validation set. All 24 bot-generated plans achieved similar PTV coverages compared with clinical plans while satisfying all clinical planning constraints. Moreover, the knowledge learned by the bot could be visualized and interpreted as consistent with human planning knowledge, and the knowledge maps learned in separate training sessions were consistent, indicating reproducibility of the learning process. We developed a planning bot that generates high-quality treatment plans for pancreas SBRT. We demonstrated that the training phase of the bot is tractable and reproducible, and the knowledge acquired is interpretable. As a result, the RL planning bot can potentially be incorporated into the clinical workflow and reduce planning inefficiencies.

Portal dosimetry scripting application programming interface (PDSAPI) for Winston-Lutz test employing ceramic balls.

PurposeStereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) treatments require a high degree of accuracy. Mechanical, imaging, and radiation isocenter coincidence is especially important. As a common method, the Winston‐Lutz (WL) test plays an important role. However, weekly or daily WL test can be very time consuming. We developed novel methods using Portal Dosimetry Scripting Application Programming Interface (PDSAPI) to facilitate the test as well as documentation.MethodsWinston‐Lutz PDSAPI was developed and tested on our routine weekly WL imaging. The results were compared against two commercially available software RIT (Radiological Imaging Technology, Colorado Springs, CO) and DoseLab (Varian Medical Systems, Inc. Palo Alto, CA). Two manual methods that served as ground truth were used to verify PDSAPI results. Twenty WL test image data sets (10 fields per tests, and 200 images in total) were analyzed by these five methods in this report.ResultsMore than 99.5% of WL PDSAPI 1D shifts agreed with each of four other methods within ±0.33 mm, which is roughly the pixel width of a‐Si 1200 portal imager when source to imager distance (SID) is at 100 cm. 1D shifts agreement for ±0.22 mm and 0.11 mm were 96% and 63%, respectively. Same trend was observed for 2D displacement.ConclusionsWinston‐Lutz PDSAPI delivers similar accuracy as two commercial applications for WL test. This new application can save time spent transferring data and has the potential to implement daily WL test with reasonable test time. It also provides the data storage capability, and enables easy access to imaging and shift data.

Initial Clinical Outcomes of Stereotactic Body Radiotherapy (SBRT) Treatment of Multiple Synchronous Lung Lesions

Stereotactic body radiotherapy (SBRT) treatment of early-stage inoperable non-small-cell lung cancer (NSCLC) patients has shown greater than 90% local control rates at 3 years. However, patients with significant co-morbidities who present with multiple synchronous lung masses may benefit from treatment of multiple lesions synchronously by either single isocenter volumetric modulated arc therapy (VMAT) flattening filter free (FFF) or a 3DCRT and IMRT system plans. The goal is to reduce treatment time and improve patient compliance. We report our initial clinical outcomes of cancer patients with multiple (<5) lung lesions synchronously treated with lung SBRT. Thirty patients with multiple peripherally located lung masses (two n = 27, three n = 2, five n = 1, total 65 lesions) were treated synchronously with either single isocenter non-coplanar VMAT-SBRT (23 patients) or Tomotherapy (7 patients). Respiratory control of target movement was accomplished with abdominal compression. Dose and fractionation varied but the most common prescriptions were 54 Gy/3 fractions and 50 Gy/5 fractions prescribed to 80% isodose line covering the planning target volume. Patients were treated every other day with a daily cone beam-CT/MVCT guided imaging. Average treatment time was less than 10 min /fraction for VMAT and 20 min/fraction for Tomotherapy. Outcomes evaluated include local control rates, radiation pneumonitis and rib toxicity. Median follow-up interval was 8 months (range, 2 to 21 months). The median age of patients treated was 75 years. 20 patients had primary lung disease and 10 patients had metastatic disease to the lung. All plans met RTOG compliance criteria for target coverage and dose to organs at risk and all patients tolerated SBRT treatment. Mean V20Gy was 7.8 ± 4% (range, 3.2-15.7%). Maximal and 1 cc of rib doses were 40 Gy and 31.5 Gy, respectively. Four patients died before follow up and two were lost to follow up. Three patients have initial post-treatment imaging pending. Of twenty-one patients, all achieved complete response to treatment with only one lesion of one patient progressing. However, 10 patients developed distant metastases. During the follow-up period, no patients had adverse pulmonary side effects, developed grade 2+ pneumonitis, chest wall pain or rib fracture. However, 50% of the patients developed radiographic changes that were asymptomatic in nature. Synchronous lung SBRT treatment using a single-isocenter VMAT plan or Tomotherapy to multiple lung lesions was fast, safe and highly effective, with promising initial clinical results in terms of local control rates and no adverse treatment related side effects to lung or ribs. Although ten patients developed either further distant metastases, the local control achieved of treated lesions could preserve the patient’s quality of life or delay systemic therapy. Longer clinical follow up of these patients is needed.

A Data-Driven Analytical Framework To Learn And Improve Clinical Workflow In Radiation Oncology

Radiation treatment planning is a complex process with multiple, dependent steps involving an interdisciplinary patient care team. We have previously implemented an interactive, web-based dashboard, which integrates with the departmental electronic medical record system (EMR), and provides real-time monitoring and visualization of the treatment planning workflow and resource utilization. In addition, the dashboard implements a standardized, integrated framework to acquire and analyze data for clinical workflow evaluation. We present this framework and the results of data-driven analyses to learn and evaluate clinical practice performance in an effort to improve clinical efficiency and assess the impact of potential workflow changes. Process maps and flowcharts were created to model the treatment planning workflow. The flowcharts described: (1) standardized activities associated with a patient’s care path for distinct treatment modalities from the time of CT simulation to treatment, (2) activity order and timeline, (3) activity ownership, and (4) staff interaction. Three treatment modalities, 3D, intensity modulated radiotherapy (IMRT), and stereotactic body radiotherapy (SBRT), were modeled. For each modality, an ideal timeline with a duration of 6 days for 3D and IMRT and 9 days for SBRT, and amenable to future refinement, was formulated based on perceived timelines, staffing levels and departmental throughput goals. Care team physicians, dosimetrists, physicists and therapists were trained in the use of the EMR to record activity status, which was also visualizable on the web-based dashboard. A quantitative representation of how different care path activities unfold was obtained from queryable timestamps in the EMR. Staff-reported actual completion times for the care path activities were computed and compared to their ideal timeline. We collected and analyzed data for 133 new patient treatments (72 3D, 55 IMRT, 6 SBRT) and 793 associated care path activities. The mean (standard deviation) of reported actual completion times in working days for the main activities are listed in the table below. On average, 3D, IMRT and SBRT treatments required 4.9, 6.6 and 9.2 days, respectively, from CT simulation to treatment. Actual total completion times for 3D treatments were significantly better than ideal (p < 0.05), but not for IMRT and SBRT treatments. The framework developed allows for informed, data-driven decisions regarding clinical workflow management and the impact of changes on existing workflow as we seek to optimize clinical efficiency and incorporate new interventions due to new treatments into clinical practice.Abstract 3799; TableCT importPhysician contour/beam placementTreatment planningPhysician plan approvalIMRT QAPre-treatment physics chart review3D0.1 (0.2)0.9 (1.0)4.2 (2.3)4.0 (2.3)4.9 (2.7)IMRT0.1 (0.3)1.8 (1.1)6.3 (2.2)5.8 (2.3)6.5 (2.3)6.6 (2.1)SBRT0.03 (0.02)2.6 (2.3)3.0 (2.2)8.7 (2.5)7.3 (2.5)9.2 (2.7) Open table in a new tab

Breath Hold Upper Abdominal Stereotactic Body Radiotherapy (SBRT) with Surface Guidance: Single Center Experience

Surface tracking systems which is integrated to SBRT treatments enables motion tracking with 3D camera technology. We aim to evaluate treatment related outcomes in breath hold upper abdominal SBRT with surface guidance. Patients with upper abdominal lesions treated with breath hold and SGRT were evaluated retrospectively. Half an hour coaching was given to each patient prior to simulation. The CT scans were performed with IV contrast mostly in end insprium or end exprium phases whichever more comfortable and reproducible. The planning CTs were fused with magnetic resonance images (MRI) and positron emission CTs (PET-CT). Target and critical structures were contoured. All treatments were done in Varian EDGE (Varian, Palo Alto, CA, USA). Patients were navigated both with verbal guidance and tracking screen. Cone beam CTs (CBCT) were acquired with breath hold before treatment and 6D couch corrections were done. Optical Surface Management System (OSMS; Varian, Palo Alto, CA, USA) was used both in setup and motion tracking. Automated beam hold control was used during the treatment when patients moved outside of pre-defined range. Treatment duration varied depending on patient’s breath hold performance, prescribed dose, field number and modulation. Local recurrence is defined as size increase in MRI or increase in uptake in PET-CT. Fifty lesions were treated between May 2017 and July 2019. There are 33 liver metastases, 10 pancreatic tumors, 4 primary liver tumors and 3 paraaortic lymph node metastases. Thirty-eight patients have regular follow ups. Median follow up is 9 months. The doses are 25-60 Gy in 3-5 fractions. Ten patients experienced local failure. Local control rates for liver metastases, pancreatic tumors and hepatocellular carcinoma 85%, 60% and 66% respectively. Gastric bleeding is observed in one patient who has a pancreatic tail tumor after 1 year of treatment. It is possible to reduce respiratory organ motion with breath hold in SBRT treatments. SGRT is a noninvasive, real time method without using ionized radiation and allow us to make a correct setup and intra fractional monitoring.

Phase I Trial of The Combined Treatment of Nivolumab and Stereotactic Body Radiotherapy for Patients with Metastatic Non-Small Cell Lung Cancer

The purpose of this study was to prospectively clarify the safety and efficacy of the combination therapy of stereotactic body radiotherapy on a thoracic lesion and PD-1 blocker in patients with metastatic non-small cell lung cancer. This is a prospective phase I study performed in the single institution. Metastatic histologically-proven non-small cell cancer patients with at least two measurable lesions including one or more in the thorax were enrolled in the study. The treatment protocol was the combination of an administration of totally 12 courses of nivolumab (3 mg/kg, every 2weeks) and stereotactic body radiotherapy (SBRT) on one of thoracic metastases at the 3rd course of nivolumab. Single dose of SBRT was set more than 5 Gy and total biological effective dose (BED, alfa / beta was 10 Gy) was decided from 40 Gy to 55 Gy as much as possible according to the dose constraints for critical organs nearby irradiated lesion. The primary endpoint was the ratio of cases with grade 3 or more toxicity using CTCAE ver. 4.0 within 24 weeks after the start of the therapy. The secondary endpoints were the tumor responses using RECIST 1.1 of the irradiated and non-irradiated lesions at 24 weeks after start of treatment. If the result reached the dose limiting toxicity (grade 4 and 5 adverse effects or the grade aggravation by 3 or more compared to pre-treatment status in one of six cases) at the time when six patients registered, the dose of SBRT would be deceased in next 6 patients. But if not, the treatment protocol would be judged as feasible and the patient registration would be stopped in the study design. The result did not reach the dose limiting toxicity at the time when six patients registered, and therefore totally 6 patients (gender; 4 male and 2 female, age; 54-84 year old, histology; adenocarcinoma in all) were enrolled in the study, but 3 patients could not complete full of the treatment due to disease progression in two patients and grade 3 pneumonitis in one patient. SBRT dose / fractionation were 24 Gy / 2 fractions in 3 patients, 24 Gy / 3 fractions in 2 patients, and 29.6Gy / 4 fractions in 1 patient. Regarding toxicity, grade 3 pneumonitis occurred in one patient but no other adverse events more than grade 2 were observed. Local response of the irradiated lesion was complete remission in 1 patient, partial remission in 2 patients, and stable disease in 3 patients. The response of the non-irradiated lesions response was partial remission in 1 patient, stable disease in 2 patients, and progressive disease in 3 patients. The overall survival at 1 and 2 years were 83.3% and 62.5%, respectively. The combined therapy of 12 courses of nivolumab and SBRT on thoracic lesion at the 3rd course for the patients with metastatic non-small cell lung was feasible. The survival might be promising in comparison with previous reports of stage IV patients in spite of the advanced status after other treatments. Prospective phase II study is mandatory to examine our conclusion.

Hilar Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer: Analysis of Outcomes in Patients Receiving One or Multiple Courses of Treatment

This study reports the outcomes of a single high-volume radiosurgery center in treating non-small cell lung cancer (NSCLC) involving the pulmonary hilum with stereotactic body radiation therapy (SBRT). The authors also aim to present the first series of cases regarding repeat hilar SBRT after prior therapy with SBRT. The hypothesis is that hilar SBRT will provide acceptable local control with limited grade ≥3 toxicity for both primary and repeat treatments. Inclusion criteria required treatment with SBRT for NSCLC involving the: (1) hilum, (2) mediastinum, (3) aortopulmonary window, or (4) mainstem bronchus. At least one clinical follow-up with imaging was required, unless the patient had a documented death from the cancer prior to that time. Imaging follow-up was conducted at regular 2-3 month intervals with CT and/or PET imaging. Statistical analysis was conducted using univariate and multivariate analyses, as well the Kaplan-Meier method. 32 patients with 44 treatments were included in the study. Patients presented primarily at stage 3 (57%) or 4 (20%). 37 of 44 treatments targeted the hilum directly, with 7 concerning the mediastinum, AP window, or mainstem bronchus. Median dose was 28 Gy in 4 fractions, with a median BED of 47.6 Gy. At a median clinical follow-up of 22.70 months, local control was 64%, with 16 cases of local failure, 9 regional failures, and 6 distant failures. Median overall survival was 23.51 months, and median progression-free survival was 15.34 months. Complete radiographic response was achieved after 48% of treatments. No factors were found to be predictive of local control or overall survival. No cases of grade ≥ 3 toxicity or radiation pneumonitis were reported. For repeat SBRT treatments, local control was 92%, with only one case of local failure, 3 regional failures, and 2 distant failures. Median overall survival was 19.63 months, and median progression-free survival was 19.07 months. On univariate and Kaplan-Meier analyses, there was no difference in overall survival between patients with one versus multiple treatments. Imaging demonstrated complete radiographic response after 58% of treatments, with 0 instances of progressive response. None of the 8 patients suffered from any side effects during the course of the repeat treatments. Hilar SBRT was efficacious and well-tolerated, with impressive overall survival and no cases of grade ≥ 3 toxicity. Repeat treatments with SBRT were feasible and effective, demonstrating overall survival, local control, and toxicity comparable to primary treatments.

Amiodarone Use and Radiation Pneumonitis in Patients Undergoing Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer

Stereotactic body radiation therapy (SBRT) has become a standard of care for inoperable early-stage non-small cell lung cancer (NSCLC) patients. Amiodarone is a well-known cause of pneumonitis and an increasing number of patients treated with SBRT are also on amiodarone. Given this potential risk of pulmonary toxicity, it is of interest to examine whether amiodarone may potentiate the risk of RP. We sought to examine the impact of amiodarone use on RP in patients treated with SBRT. Patients with early-stage NSCLC who were taking amiodarone and underwent SBRT from January 2005 to January 2019 were identified from an IRB-approved institutional database. Amiodarone was required to be taken within 3 months before or after SBRT for inclusion. RP status was confirmed using CTCAE guidelines. Follow-up was defined as the time from the end of SBRT treatment until the most recent follow-up or date of death. Thirty-three patients met the inclusion criteria. Median follow up was 14 months (range, 1 to 55 months). The median dose of radiation was 54 Gy (range, 45 to 60) delivered in 3 to 12 fractions. Three patients (9%) developed radiation pneumonitis; all cases of pneumonitis were grade 2. One patient (3%) had a diagnosis of interstitial lung disease (ILD) and no presence of pneumonitis. In this single-institution series, the use of amiodarone in concert with lung SBRT was not associated with numerically increased rates of RP compared with the established literature. These results will need to be validated in larger cohorts with proper control of established metrics (lung V20, ILD), as well as other patient populations such as those undergoing cardiac radio-ablation, where the risks and mechanisms of injury may be different.

Omission of MRI For Treatment Planning Does Not Affect Long-Term Outcomes after Prostate SBRT.

Stereotactic Body Radiation Therapy (SBRT) is increasingly being used to treat men with localized prostate cancer. Diagnostic MRI imaging as well as MRI-guided treatment for these patients have become widely utilized. A minority of patients are not candidates for MRI imaging due to pre-existing conditions or patient intolerance. To our knowledge, this is the largest series to investigate long-term outcomes in men for whom MRI imaging is not employed as a component of their prostate SBRT treatment. A total of 2775 patients with localized prostate cancer were treated with inhomogeneous-dosed SBRT at an academic institution between April 11, 2006 and November 23, 2019. By NCCN categorization, patients were treated for low (29.6%), favorable intermediate (26.0%), unfavorable intermediate (34.9%), and high risk (9.6%) disease. The majority (84.0%) of patients were treated with a median dose of 3500cGy (3500-3625) over 5 fractions. Androgen deprivation Therapy (ADT) was prescribed in 17.1% of cases. Disease Free Survival (DFS) was scored using the “nadir + 2” definition and long-term urinary and rectal toxicity was characterized as occurring ≥6 months post radiation. Correlation analyses were performed using the Pearson Chi-Square test. Estimates for DFS and toxicity were determined using the Kaplan-Meier method. 132 (4.8%) patients in this series received treatment without a planning MRI, with the most common reason being a history of implanted defibrillator (46.2%). Those treated without an MRI were slightly older (69.8 vs. 67.2 years, p<.001), and were more likely to have Gleason 8-10 histology (14.4% vs. 7.5%, p = .01) and high-risk disease (15.9% vs. 8.7%, p = .02). There was no difference in pre-treatment PSA. Those treated with MR imaging were more likely to be prescribed 3625cGy (12.1% vs. 4.6%, p = .004). The CTV was larger in men for whom an MRI was not utilized (84.3cc’s vs. 77.8cc’s, p = .029) as was maximum penile bulb dose (3061cGy vs. 2181cGy, p = .002). There was no difference in the use of ADT or in rectal or bladder dosimetry between these groups. Patients treated without MR imaging had no difference in 6-year freedom from grade 2+ rectal (96.6% vs. 97.1%, p = 0.42) and genitourinary toxicity (97.7% vs. 97.2%, p = 0.76). Similarly, there was no difference between these groups in 6-year DFS for low (97.7% vs. 97.2%, p = 0.60), favorable intermediate (100% vs. 83.1%, p = 0.61), unfavorable intermediate (84.3% vs. 84.5%, p = 0.19), or high-risk disease (64% vs. 67.5%, p = .06). This is the largest study to explore long-term outcomes in men treated with SBRT without MR imaging for localized prostate cancer. These patients are at risk for treatment with larger CTV size and penile bulb dose. Despite this, along with slight differences in baseline clinicopathologic features, the omission of MR imaging is safe and does not appear to affect long-term DFS or toxicity profiles.

Thoracic Reirradiation with Stereotactic Body Radiation Therapy (SBRT) for Recurrent Advanced Non-Small Cell Lung Cancer (NSCLC)

Locoregional failure is common among patients with advanced non-small cell lung cancer (NSCLC) treated with definitive chemoradiation +/- immunotherapy, and palliative systemic therapy is the most common treatment for locoregional failure. SBRT with ≤5 fractions have been described for small volume local recurrences, but may not be amenable to recurrences that are large or centrally located near critical structures. The purpose of this study is to evaluate the safety and efficacy of hypofractionated RT with 60 Gy in 8 using SBRT treatment techniques as salvage therapy for local failure for patients with advanced NSCLC previously treated with external beam radiation therapy (EBRT). Between July 2013 and February 2020, 5 patients were re-irradiated with SBRT of 60 Gy in 8 fractions for recurrence in the lung parenchyma after previous EBRT delivered to the same site. Patients with lymph node recurrence were excluded from analysis. Internal target volume (ITV) was created on 4D-CT with +0.5cm uniform margin to create the planning target volume (PTV). LINAC-based SBRT was delivered on non-consecutive days. Toxicity was assessed by CTCAE v5.0. Median follow-up from re-irradiation was 36 months (5.9 – 55.3 months). Median age was 67 years (range, 63 – 80 years), with KPS > 70. Patients were previously treated with a median dose of 60 Gy in median number of 30 fractions (59.4 – 66 Gy in 30 – 33 fractions). Median time to re-irradiation was 15 months (7.3 – 28.6 months). Median re-treated tumor size was 4.8 cm, with median re-treated ITV of 58.3 cc (18.3 – 344.6 cc) and median re-treated PTV of 121.3 cc (44.3 – 506.9 cc). Local control was 100%, and 60% patients remained free of any progression of disease at time of analysis. All patients remain alive at follow-up. One patient experienced grade 3 rib fracture as late toxicity for a chest wall invasive recurrence. Our institutional experience shows that SBRT-like 60 Gy in 8 fractions appears to be a safe and effective means of salvaging recurrent advanced NSCLC that was previously irradiated.Abstract 2415; TablePatient NumberInitial StageTime to re-irradiation (months)ITV of re-irradiation (cc)PTV of re-irradiation (cc)Follow-up after re-irradiation (months)Disease StatusAdditional treatment rendered1IIB, T3 N0 M07.3133.822918.1Locally controlled but metastatic disease in spinePembrolizumab and SBRT to oligometastatic adrenal gland2IIIA, T4 N0 M011.657.9113.655.3No evidence of diseaseNone3Recurrence at suture line after wedge resection for IA128.658.3121.350.3Locally controlled but metastatic disease in bilateral lungs, adrenal, and ribCarboplatin, Pemetrexed, and Pembrolizumab followed by SBRT to 3 oligoprogressive lung metastases and maintenance Pemetrexed/Pembrolizumab4IIIA, T2a N2 M018.3344.6506.936.0No evidence of diseaseNone5IIIB, T3 N2 M015.018.344.35.9No evidence of diseaseNone Open table in a new tab

Radiation Pneumonitis Following Lung SBRT: The Role of Circumferential Irradiation to the Anatomic Levels of the Proximal Bronchial Tree

Stereotactic body radiation therapy (SBRT) to the lung with dose escalated, hypofractionated treatments can lead to clinically significant lung toxicity in patients including radiation pneumonitis (RP), fistula, and even fatal hemoptysis. Despite adherence to established dosimetric parameters for the lung and proximal bronchial tree (PBT) patients can still develop RP. Prior analysis of our institution’s lung SBRT cohort indicated that high-dose circumferential radiation (HDCR) of the PBT was associated with development of RP. In this study, we sought to determine if the sensitivity of the PBT to HDCR was consistent throughout the structure. A retrospective analysis was conducted for 42 patients who were treated with lung SBRT at one institution between 2010 and 2018. Treatment plans were evaluated for doses delivered to the lung and PBT as well as for presence of circumferential overlap of fractionation relevant isodose lines with the PBT. The isodose lines that defined HDCR were 15, 16, and 18 Gy, which correspond with the PBT D4cc dose limit for 3x18 Gy, 4x12 Gy, and 5x10 Gy fractionation schemes, respectively. The PBT was divided into trachea, primary bronchi, and secondary bronchi to assess if the effect of HDCR varied based on anatomic location. Posttreatment chest imaging and patient charts were evaluated and RP was graded according to the RTOG Toxicity Criteria. This was classified as mild if RTOG grades 0-1 and moderate if RTOG grades 2-3. There were no grades 4-5 toxicity in this group of patients. Statistical analysis was performed using logistic regression. There was a significant association between HDCR of the secondary bronchi and development of RP (OR, 5.0; 95% CI, 1.21-20.6) but no significant association with HDCR of the primary bronchi (OR, 1.38; 95% CI, 0.18-10.8.) There were no patients with HDCR of the trachea. There was no significant association between D4cc (OR, 0.98; 95% CI, 0.90-1.07) or D.03cc (OR, 1.03; 95% CI, 0.99-1.07) to the PBT, mean lung dose (OR, 2.36; 95% CI, 0.67-8.39), lung V5 (OR, 2.2; 95% CI, 0.63-7.66) or lung V20 (OR, 3.07; 95% CI, 0.83-11.4) and grade of RP. This data suggests that circumferential overlap of the secondary bronchi of the PBT with isodose lines corresponding with the D4cc limit plays a role in the development of symptomatic RP. We postulate that this may be due to the smaller diameter of secondary bronchi, which make them more susceptible to luminal stenosis. This should be considered in SBRT treatment planning as conformal dose delivery can result in high doses to a small portion of the airway. Further investigation and validation of these findings with a larger data set is warranted.

The Development of Rib Fractures after Stereotactic Body Radiation Therapy to the Liver

Chest wall toxicity – pain and/or fracture – is well described complication of thoracic stereotactic body radiation therapy (SBRT). While well described for lung SBRT, limited data exists on the frequency and predictors for chest wall toxicity with SBRT to the liver for primary or metastatic lesions. We aimed to characterize the incidence and predictors of rib fractures in these patients. With IRB approval, we retrospectively reviewed the records of patients treated at a single NCI designated cancer center with SBRT to the liver from 2014-2019. Inclusion criteria included: (1) Age of ≥18 years; (2) SBRT defined as the delivery of at least 5 Gy per fraction in ≤ 5 fractions; (3) at least one follow-up scan that included imaging of the chest wall and liver ≥ 3 months. Using the linear quadratic model, a/b ratios of 10 Gy and 3 Gy were used to evaluate the impact of dose as a continuous variable. Univariate logistic regression was used to characterize predictors for the development of rib fractures, where the null hypothesis was rejected for p<0.05. All statistical analyses were conducted in R Studio Version 1.1.383. Three hundred eighty-one courses of liver SBRT were queried from 2014-2019. Of these, 319 SBRT treatments delivered to 283 patients (204 male and 79 female) met inclusion criteria. The median age was 65 years (range: 22-91 years). The median follow-up was 9.3 months (range: 3-50 months). With respect to primary site, 81% were primary liver tumors and 19% metastases. SBRT doses ranged from 60 Gy in 5 fractions to 30 Gy in 5 fractions. The most commonly used doses were: 40 Gy in 5 fractions (29%), 45 Gy in 5 fractions (23%), 50 Gy in 5 fractions (18%), 35 Gy in 5 fractions (9%), 48 Gy in 3 fractions (8%), and 30 Gy in 5 fractions (5%). A total of 17 patients (6%) experienced rib fractures at least 3 months after completing liver SBRT. Of these patients, three (17.6%) and one (6%) underwent two and three liver SBRT courses, respectively. On logistic regression, female gender (odds ratio [OR]: 3.7; 95% confidence interval [CI]: 1.41-10.02; p = 0.008), increasing BED3 Gy (OR: 1.01; 1.00-1.01; p = 0.05), and BED10 Gy (OR: 1.02; 95% CI: 1.00-1.04; p = 0.047) were associated with the development of rib fractures. Undergoing more than one course of SBRT to the liver (OR: 1.32; 95% CI: 0.41-3.63; p = 0.61) and administration of 3 fractions versus 5 fractions (OR: 1.98; 95% CI: 0.44-6.57; p = 0.31) were not associated with the development of rib fractures. The incidence of rib fractures after undergoing liver SBRT remains low at approximately 5%. Female gender and increasing BED appear to increase this risk. Future investigation will aim further characterize dosimetric parameters to better define this risk.

A Comparison Of Stereotactic Body Radiation Therapy For Metastases To The Sacral Spine And Treatment Of The Thoracolumbar Spine

Background: This study compares the outcomes of stereotactic body radiation therapy (SBRT) for sacral and thoracolumbar spine metastases. Methods: This analysis considered each sacral spine SBRT treatment at a single institution and a cohort of consecutive thoracolumbar treatments. Results: 28 patients with 35 sacral treatments and 41 patients with 49 thoracolumbar treatments were included. Local control was 63% and 90%, respectively. The sacral cohort contained more lesions with ≥2 vertebrae and epidural and paraspinal involvement. Sacral patients had larger treatment volumes, increased rates of subsequent SBRT, decreased propensity for pain improvement, and decreased local control (p=0.02 on Kaplan-Meier analysis). Multivariate analysis demonstrated that PTV > 50 cc and epidural involvement were correlated with decreased local control. No cases had grade ≥3 toxicity. Conclusion: SBRT for sacral spine metastases is a distinct disease process than metastases to the thoracolumbar spine, resulting in lower rates of local control and pain improvement.

Delivery Uncertainty Estimation Using Daily Breath-Hold Cone-Beam CTs For Liver Proton Stereotactic Body Radiotherapy

To estimate for proton stereotactic body radiotherapy (SBRT) plan delivery uncertainty with daily cone-beam CT (CBCT) imaging for liver patients under breath-hold with active breath coordinator (ABC). Images from 11 liver patients previously treated with photon SBRT with ABC at our institution are used for this study. The prescribed dose for the proton SBRT plan is 75 Gy (RBE) in 5 fractions. There is a total of 11 patients with 113 setup CBCT images collected during the patient’s previous photon SBRT treatment. The planning CT and all CBCT images are imported into Raystation 9A. A CT relative linear stopping power (RLSP) curve is calibrated for CBCT and used for proton dose calculation. A four beams proton SBRT plan is optimized with the single field optimization (SFO) technique. All 113 CBCT images are registered to planning CT with bony anatomy (rib cage and vertebrae) or liver to evaluate the delivery uncertainty. The delivery dose is estimated from the proton dose calculation on each CBCT image with the same proton plan. The dose coverages for targets are evaluated for: gross tumor volume (GTV), gtv_multABC_2mmRad_5mmSI, and ptv_5mmRad_7mmSI. Liver positions under DIBH with ABC are not consistent under bony alignment as measured. The inter-fractional and intra-fractional variation of DIBH for liver are analyzed. Proton plan delivery uncertainty can dramatically reduce under well liver alignment (up to 5% prescription dose). Daily CBCT images could be potentially used to estimate proton plan delivery uncertainty for liver patients.

Single Fraction (30 Gy) Stereotactic Body Radiation Treatment of Peripheral Lung Lesions using Flattening Filter Free Volumetric Modulated Arc Therapy (FFF-VMAT): Early Clinical Outcomes

To present early clinical outcomes utilizing stereotactic body radiation therapy (SBRT) to mid lung or peripheral lung lesions, delivering a dose of 30 Gy in a single fraction with flattening filter free volumetric modulated arc therapy (FFF-VMAT). Twenty-four lesions were identified from twenty-three patients with either early stage non-small cell lung cancer (lesions n = 17) or isolated, limited, thoracic progression from a known metastatic cancer diagnosis (lesions n = 2 head and neck, n = 2 rectal, n = 3 lung). Patients were prescribed a single dose of 30 Gy, delivered using FFF VMAT with noncoplanar 6MV beams and cone beam CT image guidance. Four-dimensional (4D) CT based treatment plans were generated using an advanced Acuros-based dose calculation engine for heterogeneity corrections. Plan quality and delivery efficiency were reported. Outcomes evaluated include local control, radiation-induced pneumonitis, and rib toxicity. Median follow-up time was 9 months (range: 1 to 38 months). Mean planning target volume (PTV) was 17.6 ± 13.9 cc. All plans met RTOG requirements for target coverage and dose to organs at risk (OAR). Average values of the conformity index, gradient index, maximum dose at 2 cm away from the PTV, normal lung V20Gy, and normal lung V10Gy were 1.06 ± 0.1, 5.4 ± 1.4, 49.5 ± 4.5%, 0.8 ± 0.5% and 3.2 ± 1.9 %, respectively. All OAR doses were well below RTOG compliance criteria. Average beam on time was 6.6 ± 1.3 min. Four patients were lost to follow up. One patient has initial post-treatment imaging pending. During the follow up period, all patients demonstrated local control of the treated lesion. Six patients developed new distant metastases, 4 of whom had prior stage 4 disease. All patients developed asymptomatic radiographic changes surrounding the treated lesion, though there were no reports of grade 2+ pneumonitis or chest wall pain and no radiographic evidence of rib fracture. Stereotactic delivery of 30 Gy in a single fraction using cone-beam CT image guidance with a non-coplanar FFF-VMAT plan is a fast, safe, and effective treatment modality for managing small mid-lung or peripherally located lung lesions. Local control is excellent and no symptomatic adverse events were noted over the follow up period. This is a promising strategy for rapidly delivering a meaningful oncologic dose to patients unable to tolerate a multi-fraction regimen due to discomfort, medical comorbidities, or socio-economic barriers hindering treatment compliance. Longer clinical follow up in a larger patient cohort is ongoing to further validate these outcomes.

Acuros® dose verification of ultrasmall lung lesions with EBT-XD film in a homogeneous and heterogeneous anthropomorphic phantom setup.

Modern type 'c' dose calculation algorithms like Acuros® can predict dose for lung tumors larger than approximately 4cm3 with a relative uncertainty up to 5%. However, increasingly better tumor diagnostics are leading to the detection of very small early-stage lung tumors that can be treated with stereotactic body radiotherapy (SBRT) for inoperable patients. This raises the question whether dose algorithms like Acuros® can still accurately predict dose within 5% for challenging conditions involving small treatment fields. Current recommendations for Quality Assurance (QA) and dose verification in SBRT treatments are to use phantoms that are as realistic as possible to the clinical situation, although water-equivalent phantoms are still largely used for dose verification. In this work we aim to demonstrate that existing dose verification methods are inadequate for accurate dose verification in very small lung tumors treated with SBRT. The homogeneous PTW Octavius4D phantom with the Octavius 1000 SRS detector ("Octavius4D phantom") and the heterogeneous CIRS Dynamic Thorax phantom ('CIRS phantom') were used for dose measurements. The CIRS phantom contained different lung-equivalent film-holding cylindrical phantom inserts ("film inserts") with water-equivalent spherical targets with diameters 0.5, 0.75, 1, 2, and 3cm. Plans were calculated for 6 and 10MV for each spherical target in the CIRS phantom, resulting in 14 treatment plans. The plans were delivered to both Octavius4D and CIRS phantom to compare measured dose in a commonly used homogeneous and more realistic heterogeneous phantom setup. In addition, treatment plans of seven clinical lung cancer patients with lung tumors below approximately 1.0cm3 were irradiated in the heterogeneous CIRS phantom. The actual tumor size within the clinical treatment plans determined the choice of the spherical target size, such that both measurement geometry and clinical target volumes match as closely as possible. The Acuros® dose algorithm (version 15.5.11) was used for all dose calculations reporting dose-to-medium using a 0.1-cm-grid size. The measurement discrepancies in the homogeneous Octavius4D phantom for the fourteen treatment plans were within 1.5%. Dose discrepancies between measurement and treatment planning systems (TPS) for the heterogeneous CIRS phantom increased for both 6 and 10MV with decreasing target diameters up to 23.7±1.0% for 6MV and 8.8±1.1% for 10MV for the smallest target of 0.5cm in diameter with a 2-mm-CTV-PTV margin. For the seven clinical plans this trend of increasing dose difference with decreasing tumor size is less pronounced although the smallest tumors show the largest differences between measurement and TPS up to 16.6±0.9%. Current verification methods using homogenous phantoms are not adequate for lung tumors with diameters below approximately 0.75cm. The current Acuros® dose calculation algorithm underestimates dose in very small lung tumors. Dose verification of small lung tumors should be performed in an anthropomorphic lung phantom incorporating a water-equivalent target that matches clinical tumor size as closely as possible.

Intrafraction cone beam computed tomography verification of breath hold during liver stereotactic radiation therapy.

IntroductionIntrafraction imaging is an Elekta feature that enables cone beam computed tomography (CBCT) acquisition simultaneously with treatment arc delivery. It has facilitated the introduction of breath‐hold (BH) gated stereotactic body radiation therapy (SBRT) by enabling visualisation of tumour and organs at risk during treatment. The aims of this study were to assess BH reproducibility and use intrafraction CBCT (IF‐CBCT) to quantify any variation in diaphragm position (diaphragmatic feathering) during the multiple BHs performed during each arc.MethodsIF‐CBCTs for consecutive liver SBRT patients where BH was achieved using the Elekta Active Breathing Control (ABC) system were retrospectively evaluated. Average intrafraction couch shifts for deep‐inspiration BH (DIBH) or end‐expiration BH (EEBH) were recorded as an indication of reproducibility. Diaphragmatic feathering was quantified by measuring the difference between the most superior and inferior visible edges of the diaphragm on IF‐CBCTs.ResultsA total of 212 images from 30 patients were reviewed. Twenty‐two (73.3%) patients were treated in EEBH. The mean intrafraction shift was similar between DIBH and EEBH groups with the largest mean shift of 0.22cm occurring in the superior–inferior direction. Mean diaphragmatic feathering was similar between the DIBH and EEBH groups, 0.09cm (0‐0.44cm) and 0.14cm (0–1.89cm) respectively. A higher percentage of EEBH patients demonstrated no diaphragmatic feathering throughout treatment compared with DIBH patients (31.8% vs 25%).ConclusionThe results of this study indicate that BH is reproducible in both DIBH and EEBH for liver SBRT treatment using the ABC system. Appropriate patient selection and BH coaching prior to CT simulation are critical to its success.

Stereotactic body radiation therapy for empirically treated hypermetabolic lung lesions: a single-institutional experience identifying the Charlson score as a key prognostic factor.

BackgroundThough pathologic evidence for non-small cell lung cancer (NSCLC) is preferred, many patients do not receive a biopsy prior to treatment with stereotactic body radiation therapy (SBRT). This study seeks to analyze the overall survival (OS), local control, and toxicity rates for such patients.MethodsThis retrospective review included patients empirically treated with SBRT for presumed non-metastatic NSCLC at a single institution. Inclusion criteria included a hypermetabolic pulmonary lesion noted on positron emission tomography (PET) imaging but no pathological evidence of NSCLC. Patients with another known metastatic tumor were excluded. Statistical analysis was conducted with Cox proportional hazards analysis, univariate analysis, and the Kaplan-Meier method.ResultsNinety-one treatments in 90 unique patients met inclusion criteria. Patients were a median 77.9 years at the start of treatment and had a median Charlson score of 7. Pre-treatment standardized uptake value (SUV) was a median 4.5 and 1.5 after treatment. At a median follow-up of 12.9 months, 36-month local control of 91.3% was achieved. Twenty-four-month OS and progression-free survival were 65.4% and 44.8%, respectively. On univariate analysis, biologically effective dose (BED) ≥120 Gy was predictive of improved OS (P=0.001), with 36-month OS of 50.5% for patients with BED ≥120 Gy and only 31.6% for patients with BED <120 Gy. On Kaplan-Meier analysis, Charlson score ≥9 was predictive of decreased OS (P=0.04), and BED ≥120 Gy trended towards improved OS (P=0.08). Thirty-two cases of grade <3 toxicity were reported, and only two cases of grade 3 morbidity (fatigue) were noted.ConclusionsLocal control rates for empiric SBRT treatment for hypermetabolic, non-metastatic NSCLC are similar to those for biopsied NSCLC. OS is primarily dependent on a patient’s overall health status, which can be accurately assessed with the Charlson score. BED ≥120 Gy may also contribute to improved OS.

Full automation of spinal stereotactic radiosurgery and stereotactic body radiation therapy treatment planning using Varian Eclipse scripting.

The purpose of this feasibility study is to develop a fully automated procedure capable of generating treatment plans with multiple fractionation schemes to improve speed, robustness, and standardization of plan quality. A fully automated script was implemented for spinal stereotactic radiosurgery/stereotactic body radiation therapy (SRS/SBRT) plan generation using Eclipse v15.6 API. The script interface allows multiple dose/fractionation plan requests, planning target volume (PTV) expansions, as well as information regarding distance/overlap between spinal cord and targets to drive decision‐making. For each requested plan, the script creates the course, plans, field arrangements, and automatically optimizes and calculates dose. The script was retrospectively applied to ten computed tomography (CT) scans of previous cervical, thoracic, and lumbar spine SBRT patients. Three plans were generated for each patient — simultaneous integrated boost (SIB) 1800/1600 cGy to gross tumor volume (GTV)/PTV in one fraction; SIB 2700/2100 cGy to GTV/PTV in three fractions; and 3000 cGy to PTV in five fractions. Plan complexity and deliverability patient‐specific quality assurance (QA) was performed using ArcCHECK with an Exradin A16 chamber inserted. Dose objectives were met for all organs at risk (OARs) for each treatment plan. Median target coverage was GTV V100% = 87.3%, clinical target volume (CTV) V100% = 95.7% and PTV V100% = 88.0% for single fraction plans; GTV V100% = 95.6, CTV V100% = 99.6% and PTV V100% = 97.2% for three fraction plans; and GTV V100% = 99.6%, CTV V100% = 99.1% and PTV V100% = 97.2% for five fraction plans. All plans (n = 30) passed patient‐specific QA (>90%) at 2%/2 mm global gamma. A16 chamber dose measured at isocenter agreed with planned dose within 3% for all cases. Automatic planning for spine SRS/SBRT through scripting increases efficiency, standardizes plan quality and approach, and provides a tool for target coverage comparison of different fractionation schemes without the need for additional resources.

Neutrophil-lymphocyte ratio as a prognostic factor for stereotactic body radiotherapy treatment of metastatic liver tumors.

BackgroundThe neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response and may be able to predict clinical outcomes in patients with malignant solid tumors. However, the relationship between NLR and the prognosis of liver metastasis after stereotactic body radiotherapy (SBRT) is not well established.MethodsPatients with liver metastatic tumors who underwent SBRT in our center between 2015 and 2018 were enrolled, and their data were retrospectively analyzed. The patient’ baseline total white blood cell (WBC), neutrophil, lymphocyte, and platelet counts were recorded, along with their mean platelet volume (MPV) and red blood cell distribution width (RDW). The cut-off values for NLR and platelet-lymphocyte ratio (PLR) were determined by receiver operating characteristic (ROC) curves. Local control (LC) and overall survival (OS) were calculated using the Kaplan-Meier method. The Cox proportional hazards model was used to study significant variable line and factors associated with OS.ResultsA total of 65 patients with 82 lesions were enrolled. The median duration follow-up was 21 months. The local control (LC) rate was 76.8%, and the 1- and 2-year OS rates were 70.7% and 46.1%, respectively. The cut-off values of NLR and PLR were 3.16 and 201.33, respectively. Multivariate analysis identified the NLR cut-off value as a potential independent indicator of inferior OS [P=0.005, HR =3.317 (95% CI, 1.433–7.678)]. Biological effective dose (BED) was also associated with OS (P=0.035, HR =0.984 (95% CI, 0.969–0.999)].ConclusionsNLR showed a strong association with LC and OS, which could serve as a predictive guide in the treatment of liver metastasis with SRBT. BED is also an independent factor affecting OS.