Stereotactic Radiotherapy Dose Research Articles

How Does the Number of Brain Metastases Correlate With Normal Brain Exposure in Single-Isocenter Multitarget Multifraction Stereotactic Radiosurgery

PurposeTo investigate the relationship between normal brain exposure in linac-based single-isocenter multi-target multi-fraction stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) and the number or volume of treated brain metastases, especially for high numbers of metastases. Methods and MaterialsA cohort of 44 SRT patients with 709 brain metastases was studied. Renormalizing to a uniform prescription of 27 Gy in 3 fractions, normal brain dose volume indices, including V23Gy (volume receiving >23Gy), V18Gy (volume receiving >18Gy), and mean dose, were evaluated on these plans against the number and the total volume of targets for each plan. To compare with exposures from whole-brain radiotherapy (WBRT), the SRT dose distributions were converted to equivalent dose in 3 Gy fractions (EQD3) using an alpha-beta ratio of 2 Gy. ResultsWith increasing number of targets and increasing total target volume, normal brain exposures to dose ≥18 Gy increases, and so does the mean normal brain dose. The factors of number of targets and total target volume are both significant, though the number of targets has a larger effect on the mean normal brain dose and the total target volume has a larger effect on V23Gy and V18Gy. The EQD3 mean normal brain dose with SRT planning is lower than conventional WBRT. On the other hand, SRT results in higher hot spot (i.e. maximum dose outside of tumor) EQD3 dose than WBRT. ConclusionsBased on clinical SRT plans, our study provides information on correlations between normal brain exposure and the number and total volume of targets. As SRT becomes more greatly utilized for patients with increasingly extensive brain metastases, more clinical data on outcomes and toxicities is necessary to better define the normal brain dose constraints for high-exposure cases and to optimize the SRT management for those patients.

Hypofractionated stereotactic re-irradiation for progressive glioblastoma: twelve years’ experience of a single center

PurposeWe aimed to evaluate the prognostic factors and the role of stereotactic radiotherapy (SRT) as a re-irradiation technique in the management of progressive glioblastoma.MethodsThe records of 77 previously irradiated glioblastoma patients who progressed and received second course hypofractionated SRT (1–5 fractions) between 2009 and 2022 in our department were evaluated retrospectively. Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was utilized for all statistical analyses.ResultsThe median time to progression from the end of initial radiotherapy was 14 months (range, 6–68 months). The most common SRT schedule was 30 Gy (range, 18–50 Gy) in 5 fractions (range, 1–5 fractions). The median follow-up after SRT was 9 months (range, 3–80 months). One-year overall (OS) and progression-free survival (PFS) rates after SRT were 46% and 35%, respectively. Re-irradiation dose and the presence of pseudoprogression were both significant independent positive prognostic factors for both OS (p = 0.009 and p = 0.04, respectively) and PFS (p = 0.008 and p = 0.04, respectively). For PFS, progression-free interval > 14 months was also a prognostic factor (p = 0.04). The treatment was well tolerated without significant acute toxicity. During follow-up, radiation necrosis was observed in 17 patients (22%), and 14 (82%) of them were asymptomatic.ConclusionHypofractionated SRT is an effective treatment approach for patients with progressive glioblastoma. Younger patients who progressed later than 14 months, received higher SRT doses, and experienced pseudoprogression following SRT had improved survival rates.

CNN-based multi-modal radiomics analysis of pseudo-CT utilization in MRI-only brain stereotactic radiotherapy: a feasibility study

BackgroundPseudo-computed tomography (pCT) quality is a crucial issue in magnetic resonance image (MRI)-only brain stereotactic radiotherapy (SRT), so this study systematically evaluated it from the multi-modal radiomics perspective.Methods34 cases (< 30 cm³) were retrospectively included (2021.9-2022.10). For each case, both CT and MRI scans were performed at simulation, and pCT was generated by a convolutional neural network (CNN) from planning MRI. Conformal arc or volumetric modulated arc technique was used to optimize the dose distribution. The SRT dose was compared between pCT and planning CT with dose volume histogram (DVH) metrics and gamma index. Wilcoxon test and Spearman analysis were used to identify key factors associated with dose deviations. Additionally, original image features were extracted for radiomic analysis. Tumor control probability (TCP) and normal tissue complication probability (NTCP) were employed for efficacy evaluation.ResultsThere was no significant difference between pCT and planning CT except for radiomics. The mean value of Hounsfield unit of the planning CT was slightly higher than that of pCT. The Gadolinium-based agents in planning MRI could increase DVH metrics deviation slightly. The median local gamma passing rates (1%/1 mm) between planning CTs and pCTs (non-contrast) was 92.6% (range 63.5–99.6%). Also, differences were observed in more than 85% of original radiomic features. The mean absolute deviation in TCP was 0.03%, and the NTCP difference was below 0.02%, except for the normal brain, which had a 0.16% difference. In addition, the number of SRT fractions and lesions, and lesion morphology could influence dose deviation.ConclusionsThis is the first multi-modal radiomics analysis of CNN-based pCT from planning MRI for SRT of small brain lesions, covering dosiomics and radiomics. The findings suggest the potential of pCT in SRT plan design and efficacy prediction, but caution needs to be taken for radiomic analysis.

Proton minibeam radiation therapy for treating metastases: A treatment plan study.

Proton minibeam radiation therapy (pMBRT) is a new radiotherapy approach that has shown a significant increase in the therapeutic window in glioma-bearing rats compared to conventional proton therapy. Such preclinical results encourage the preparation of clinical trials. In this study, the potential of pMBRT for treating clinical indications candidates for the first clinical trials (i.e., brain, lung, and liver metastases) was evaluated. Four clinical cases, initially treated with stereotactic radiotherapy (SRT), were selected for this study. pMBRT, SRT, and conventional proton therapy (PT) dose distributions were compared by using three main criteria: (i) the tumor coverage, (ii) the mean dose to organs-at-risk, and (iii) the possible adverse effects in normal tissues by considering valley doses as the responsible for tissue sparing. pMBRT plans consisted of one fraction and one-two fields. Dose calculations were computed by means of Monte Carlo simulations. pMBRT treatments provide a similar or superior target coverage than SRT, even using fewer fields. pMBRT also significantly reduces the biologically effective dose (BED) to organs-at-risk. In addition, valley and mean doses to normal tissues remain below tolerance limits when treatments are delivered in a single fraction, contrary to PT treatments. This work provides a first insight into the possibility of treating metastases with pMBRT. More favorable dose distributions and treatment delivery regimes may be expected from this new approach than SRT. The advantages of pMBRT would need to be confirmed by means of Phase I clinical trials.

Survival in Metastatic Renal Cell Carcinoma Treated with Immunotherapy and Stereotactic Radiation Therapy or Immunotherapy Alone: A National Cancer Database Analysis

<h3>Purpose/Objective(s)</h3> Immunotherapy (IO) has significantly improved outcomes in metastatic renal cell carcinoma (mRCC). Preclinical evidence suggests that responses to IO may be enhanced through the immunomodulatory effects of stereotactic radiation therapy (SRT). We hypothesized that clinical outcomes from the National Cancer Database (NCDB) would demonstrate improved overall survival (OS) in mRCC patients receiving IO+SRT versus IO alone. <h3>Materials/Methods</h3> Patients with mRCC diagnosed from 2012-2016 and receiving first-line IO±SRT were identified from the NCDB. Complete staging details and radiation treatment characteristics were required for study inclusion. The definition of SRT was ≥10 Gy in 1 fraction, ≥20 Gy in 2 fractions, ≥24 Gy in 3 fractions, or ≥25 Gy in 5 fractions. Conventional radiation therapy was allowed in the IO alone cohort. The primary endpoint was OS (from date of stage IV diagnosis) stratified by the receipt of SRT (IO+SRT versus IO alone). Secondary endpoints included OS stratified by the presence of brain metastases (BM) and timing of SRT (before or after IO). Events beyond 24 months were censored. Survival was estimated using Kaplan-Meier methodology and compared via the log-rank test. Adjustments for multiple comparisons were performed. <h3>Results</h3> Of 644 eligible patients, 63 (9.8%) received IO+SRT and 581 (90.2%) received IO alone. The median follow-up time was 17.7 months (range, 2-24 months). Baseline characteristics were similar between cohorts, although SRT+IO patients were more frequently <60 years old (57.1% vs 40.3%, P=0.010) and had higher rates of BM (71.4% vs 11.2%, P<0.001). There was no difference in metastatic tumor burden (defined as the number of involved organ systems) between cohorts (P=0.48). Sites treated with SRT included the brain (71.4%), lung/chest (6.4%), spine (6.4%), bones (3.2%), and other (12.6%). While there was no significant difference in OS for patients receiving IO+SRT vs IO alone (log-rank P=0.11), OS was consistently higher at 1-year (74.4% vs 65.0%) and 2-years (71.0% vs 58.4%). In patients with BM, 1-year survival rates were 73.0% (95% CI, 57.4-83.7) with IO+SRT and 54.7% (95% CI, 41.8-65.9) with IO alone (P=<0.026). The timing of SRT (before or after IO) did not appear to influence OS (P=0.32). <h3>Conclusion</h3> Patients with BM secondary to mRCC had prolonged OS with the addition of SRT to IO. Prospective clinical trials are warranted to better identify mRCC populations which may benefit from combined modality therapy. Potential synergistic factors, such as oligometastatic tumor burden, IO mechanism of action, and SRT dose should be considered in future analyses of mRCC patients receiving IO+SRT.

RADI-11. Evaluating the Tissue Effects of Dose-escalated Pre-operative Stereotactic Radiotherapy for Resectable Brain Metastasis

BackgroundAlthough the classic radiobiologic principles of radiotherapy are well understood, the unique effects of the large fractional does that characterize stereotactic radiotherapy (SRT), specifically in terms of antitumor immune cellular processes, vascular damage, tumor necrosis, and apoptosis on brain metastasis have yet to be adequately demonstrated. The objective of this study is to provide the first in-human evaluation of the biological effects of SRT in resected brain metastasis.MethodsAll paired primary tumors and metastases for patients who underwent dose-escalated preoperative SRT followed by resection were evaluated for tumor necrosis using hematoxylin-eosin staining. T cells (CD3+, CD4+, CD8+), natural killer cells (CD56+), vessel density (CD31+), and apoptotic factors (caspase-3) were determined by immunohistochemical analysis.ResultsFifteen patients with brain metastases from solid tumors received a median preoperative SRT dose of 18 Gy (range: 15–18 Gy) in 1 fraction, with 2 patients receiving 27–30 Gy in 3–5 fractions, followed by resection within a median interval of 90 hours (Range: 17.1–260 hours). The rate of necrosis was found to be significantly higher in irradiated brain metastases than in non-irradiated primary tumor samples (mean paired difference: 30.47, SD: 29.28, p=0.001). A decrease in all immunomodulatory cell populations was found in irradiated metastasis: CD3 (mean paired difference -19.4, SD: 31.7, p=0.03), CD4 (-10.0, SD: 20, p=0.01), and CD8 (-17.4, SD: 22.1, p=0.008). While irradiated samples had numerically lower CD 31+, CD 56+, and caspase-3 scores, the difference was not statistically significant. Time interval from SRT to surgery had no effect on these parameters.ConclusionsThere is complex interplay between tumor-associated cells and the unique radiobiological effects of SRT on tumor tissue. Although time interval from SRT to surgery was associated with increased tumor necrosis, differences in immunomodulatory factors may be multifactorial, including concurrent corticosteroids or the immunosuppressive effect of SRT.

PO-1169 30 Gy single dose stereotactic radiation therapy in a series of patients with lung oligometastasis

PO-1169 30 Gy single dose stereotactic radiation therapy in a series of patients with lung oligometastasis

Out-of-field dose in stereotactic radiotherapy for paediatric patients.

Stereotactic radiotherapy combines image guidance and high precision delivery with small fields to deliver high doses per fraction in short treatment courses. In preparation for extension of these treatment techniques to paediatric patients we characterised and compared doses out-of-field in a paediatric anthropomorphic phantom for small flattened and flattening filter free (FFF) photon beams. Dose measurements were taken in several organs and structures outside the primary field in an anthropomorphic phantom of a 5year old child (CIRS) using thermoluminescence dosimetry (LiF:Mg,Cu,P). Out-of-field doses from a medical linear accelerator were assessed for 6MV flattened and FFF beams of field sizes between 2×2 and 10×10cm2. FFF beams resulted in reduced out-of-field doses for all field sizes when compared to flattened beams. Doses for FFF and flattened beams converged for all field sizes at larger distances (>40cm) from the central axis as leakage becomes the primary source of out-of-field dose. Rotating the collimator to place the MLC bank in the longitudinal axis of the patient was shown to reduce the peripheral doses measured by up to 50% in Varian linear accelerators. Minimising out-of-field doses by using FFF beams and aligning the couch and collimator to provide tertiary shielding demonstrated advantages of small field, FFF treatments in a paediatric setting.

Stereotactic radiotherapy combined with immunotherapy or targeted therapy for metastatic renal cell carcinoma.

To evaluate the safety and efficacy of stereotactic radiotherapy (SRT) in patients with metastatic renal cell carcinoma (mRCC) concurrently receiving targeted therapy (TT) or immunotherapy. Data on patients with mRCC were extracted from a retrospective international multicentre register study (TOaSTT), investigating SRT concurrent (≤30days) with TT/immune checkpoint inhibitor (ICI) therapy. Overall survival (OS), progression-free survival (PFS), local metastasis control (LC) and time to systemic therapy switch were analysed using Kaplan-Meier curves and log-rank testing. Clinical and treatment factors influencing survival were analysed using multivariate Cox regression. Acute and late SRT-induced toxicity were defined according to the Common Terminology Criteria for Adverse Events v.4.03. Fifty-three patients who underwent 128 sessions of SRT were included, of whom 58% presented with oligometastatic disease (OMD). ICIs and TT were received by 32% and 68% of patients, respectively. Twenty patients (37%) paused TT for a median (range) of 14 (2-21) days. ICI therapy was not paused in any patient. A median (range) of 1 (1-5) metastatic tumour was treated per patient, with a median (range) SRT dose of 65 (40-129.4) Gy (biologically effective dose). The OS, LC and PFS rates at 1year were 71%, 75% and 25%, respectively. The median OS and PFS were not significantly different among patients receiving TT vs those receiving ICIs (P = 0.329). New lesions were treated with a repeat radiotherapy course in 46% of patients. After 1year, 62% of patients remained on the same systemic therapy as at the time of SRT; this was more frequent for ICI therapy compared to TT (83% vs 36%; P = 0.035). OMD was an independent prognostic factor for OS (P = 0.004, 95% confidence interval [CI] 0.035-0.528) and PFS (P = 0.004; 95% CI 0.165-0.717) in multivariate analysis. Eastern Cooperative Oncology Group performance status (ECOG-PS) was the other independent prognostic factor for OS (P = 0.001, 95% CI 0.001-0.351). Acute grade 3 toxicity was observed in two patients, and late grade 3 toxicity in one patient. No grade 4 or 5 toxicity was observed. Combined treatment with TT or immunotherapy and concurrent SRT was safe, without signals of increased severe toxicity. As we observed no signal of excess toxicity, full-dose SRT should be considered to achieve optimal metastasis control in patients receiving TT or immunotherapy. Favourable PFS and OS were observed for patients with oligometastatic RCC with a good ECOG-PS, which should form the basis for prospective testing of this treatment strategy in properly designed clinical trials.

Salvage Re-Irradiation with Stereotactic Radiotherapy for In-Field Neck Lymph Node Recurrence: A Retrospective Study

Neck lymph node (LN) recurrence in the irradiated field is an important characteristic of treatment failure after primary radiotherapy owing to the lack of standard treatment. Recent technological advances have led to the possibility of achieving highly conformal dose distributions of recurrent tumors using stereotactic radiotherapy (SRT), resulting in high local control (LC) and low toxicity, with reduced dose to organs at risk (OAR). We aimed to investigate the efficacy and safety of SRT for neck LN recurrence after radiotherapy. Between 2008 and 2016, 58 neck LN recurrences after radiotherapy in 18 patients with head and neck cancer were treated using a treatment system specialized for stereotactic irradiation. The nasopharynx (17 lesions), oropharynx (4 lesions), hypopharynx (7 lesions), buccal mucosal (13 lesions), tongue (2 lesions), and larynx (15 lesions) were the primary tumor sites. No patient exhibited recurrences at the primary sites during SRT. The target marginal dose (18–20 Gy) was administered in one fraction. Treatment doses and fractions were determined according to the tumor volume and OAR. If the dose for 10 cm3 of the skin or mucosa exceeded 14 Gy in one fraction because of large tumor volume or if the target area was in close proximity to OAR, the number of fractions was increased to prevent adverse effects, e.g., skin ulcers. Diagnostic imaging techniques, such as CT, MRI, and FDG-PET/CT, were used to evaluate tumor response every 2–3 months after SRT. Kaplan–Meier method was used to calculate overall survival (OS) and LC rates, and log-rank test was used to compare 1-year LC differences as per LN volume. The median follow-up period and target volume was 16 (range, 1–80) months and 1.3 (range, 0.05–91) cm3, respectively. The median previous radiotherapy dose and marginal dose of SRT as equivalent dose delivered in 2-Gy fractions (α/β = 10) was 66 (range, 40–70) Gy and 50 (range, 40–58) Gy, respectively. Moreover, the median interval between completion of prior radiotherapy and SRT was 23.5 (range, 4–69) months and 1-year LC and OS rates were 81% and 61%, respectively. Local recurrence was observed in 12 lesions from nine patients. LC was higher with a target volume ≤ 1.0 cm3 than with a target volume > 1.0 cm3 (p = 0.016). The 1-year LC was higher with a target volume ≤ 1.0 cm3 than with a target volume > 1.0 cm3 (92% vs. 68%, respectively). No significant difference in LC was observed when considering other clinical factors. Regarding the cutaneous region and mucosa, grade ≥3 adverse effects were not observed. One patient with large (91 cm3) and widespread tumor that metastasized the carotid artery before SRT showed fatal bleeding. SRT for neck LN recurrence is safe and feasible in most cases, but the treatment indication should be carefully considered for large and widespread tumors.

The Impact of Tumor Volume in Breast Cancer Liver Metastasis Patients Treated with Stereotactic Radiotherapy – Does Size Matter?

To investigate the relationship between tumor volume and survival in breast cancer liver metastasis (BCLM) patients treated with stereotactic radiotherapy. 39 biopsy proven breast cancer patients whom liver metastasis was treated with stereotactic radiotherapy (SRT) were retrospectively investigated. Patient characteristics, survival and their relation with tumor volume were analyzed. Median age was 47 years (range; 27-78 years). Median tumor size was 1.8 ± 1.1 cm. Median gross tumor volume (GTV) and planning tumor volume (PTV) were 6.8 cc (range, 0.7-55.2 cc) and 38.7 cc (range; 9.3-163.8 cc), respectively. SRT dose prescription was 3 fr x 18 Gy in 37 patients (96%), 3 fr x 20 Gy in 1 patient (2%) and 3 fr x 16 Gy in 1 patient (2%). 13 patients (33%) had solitary liver metastasis while 26 patients (67%) also had other organ metastases beyond liver. Median follow-up for entire cohort was 15.4 months (range; 1-49 months). At last visit 26 patients (67%) had disease progression. Among these patients 25 patients (64%) had distant metastasis while 2 patients (5%) had isolated local recurrence. The 1- and 2- years overall survival (OS) rates were %79.1 and %46.0, respectively. Median OS was 23.8 months (95% CI: 13.3-34.3 months). 1 and 2-years progression-free survival (PFS) rates were 38.1% and 11.5%, respectively. Median PFS was 8.7 months (95%CI: 5.6-11.8 months). 1 and 2-years of local control (LC) per tumor were 92.9% and 85%, respectively. Patients were divided into two groups according to tumor volume £30 cc or >30 cc. 1-year OS was 100% for patients with tumor volume £30 cc while 1-year OS was 34% for patients with tumor volume > 30 cc (p = 0.04). 4 patients developed grad 3 late toxicity. Among them 1 had duodenal ulcer, received medical treatment without any surgical intervention and 3 of them had rib fracture treated with symptomatic medical treatment. SRT is an efficient treatment with optimal LC and low toxicity profile in BCLM patients. Tumor volume of £30 cc had better survival.

A phase II multicenter study of stereotactic radiotherapy (SRT) for oligoprogression in metastatic renal cell cancer (mRCC) patients receiving tyrosine kinase inhibitor (TKI) therapy.

5065 Background: SRT is increasingly considered to delay the need to change systemic therapy in metastatic cancer patients who develop oligoprogression. This prospective phase II study evaluated the use of SRT in the setting of mRCC patients who developed oligoprogression while on 1st or 2nd line TKI therapy. Methods: IMDC favourable or intermediate risk mRCC patients (pts) who had previous stability or response on ≥ 3 months of TKI therapy were eligible if they developed radiographic progression of ≤ 5 metastases. The oligoprogressive tumours were treated with SRT while other metastases which were stable or responding to TKI therapy were left alone. TKI therapy was temporarily stopped during SRT, and the same TKI drug then resumed. Endpoints included local control of the irradiated lesions, progression free survival (PFS), overall survival (OS), and cumulative incidence of changing systemic therapy after study entry. Results: 37 pts (median age 63, IMDC favourable 12, intermediate 25) with 57 oligoprogressive tumours were enrolled. 35 pts were on sunitinib and 2 on pazopanib. Median duration of TKI therapy prior to study entry was 18.6 months. 4 pts had IL-2 therapy prior to a 2nd line TKI. 21 pts had a solitary oligoprogressive tumour, while 17 pts had 2-3 oligoprogressive tumours treated with SRT. Median biological effective dose (BED10) was 72 Gy, corresponding to an SRT dose of 40 Gy in 5 fractions. Irradiated tumour sites were the following: 21 lung/pleural, 15 bone, 7 lymph node, 4 adrenal, 4 liver, 3 brain, 2 spleen, and 1 pancreas. At a median followup of 11.6 (1.8-53.5) months the median PFS from study entry was 9.6 months (95%CI 7.4-20.5) with the vast majority of progression occurring outside of the irradiated areas. The 2-year local control of the irradiated tumours was 96%. The 2-year OS from study entry was 77%. The cumulative incidence of changing systemic therapy was 47% at 1 year and 75% at 2 years, with a median time to a change in systemic therapy of 12.6 months. There were no grade 3-5 SRT related toxicities. Conclusions: To our knowledge, this is the first prospective evaluation of the use of SRT for oligoprogressive metastatic cancer. Local control of irradiated oligoprogressive mRCC tumours was high. After delivering SRT, mRCC patients did not need a change in their systemic therapy for a median of 1 year, effectively increasing the PFS of their TKI therapy. This novel approach should be studied in patients with oligoprogression on immunotherapy. Clinical trial information: NCT02019576 .

DOSIMETRIC INVESTIGATION OF RADIOTHERAPY OF SMALL SIZE TUMORS IN RADIOSURGERY DEVICES

In stereotactic radiotherapy, high radiation doses were delivered to tumors using small fields in 1-5 fractions. It is very important to make sure accuracy of dose and position of given dose in stereotactic radiotherapy. In this study, dosimetric measurements of small sized brain tumors irradiated in CONE- based linear accelator (linac) and the volumetric arc therapy (VMAT) linac modalities were performed with EBT3 film. 1,2 and 3 cm diameter tumors were virtually created in Cyberknife head and neck phantom. Gafchromic EBT3 film was placed into the phantom to evaluate the accuracy of the doses given. The phantom was irradiated with Gafchromic EBT3 film according to treatment plans created in the treatment planning system of two separate devices for each tumor size. Conformity Index (CI) and Homogeneity Index (HI) were calculated for the quality of created treatment plans. The dose distributions calculated in the film and the TPS were compared. When the CI and HI values were examined, the CI and HI values of the cone-based linac device were close to 1. The EBT3 measurement results indicate that all SRT treatment modalities achieved accurate doses. According to results, if a critical organ, such as the brainstem, is located near the tumor and the situation requires a steep dose gradient, the cone-based linac should be used for SRT therapy. This study has shown that on CONE-based linac or VMAT-based linac devices can be used instead of each other in small-area irradiations.

Integration of stereotactic radiotherapy in the treatment of metastatic colorectal cancer patients: a real practice study with long-term outcome and prognostic factors.

BackgroundThere are very few clinical or prognostic studies on the role of SRT (Stereotactic Radiation Therapy) in the continuum of care of metastatic colorectal cancer (mCRC) patients.Patients and methodsPatients affected by oligo-mCRC were treated with SRT before or after front-line standard treatments. SRT was delivered according to a risk-adapted protocol. Total body CT (Computed Tomography) scan was done before therapy and every three months thereafter. The radiologic responses to therapy were evaluated by RECIST (Response Evaluation Criteria In Solid Tumors). FDG-PET (FluoroDeoxyGlucose - Positron Emission Tomography) was done before and after SRT; metabolic responses were evaluated by using the EORTC (European Organization for Research and Treatment of Cancer) criteria. The Kaplan-Meier product limit method was applied to graph Overall Survival (OS) and Progression-Free Survival (PFS).ResultsForty-seven patients were included. Twenty-one patients had disease limited to lungs, 9 to lung and liver, 7 only to liver, 10 to multiple sites. The median prescription SRT dose was 60 Gy per organ in 3 fractions (median biological effective dose of 180 Gy). The reduction of delta SUVmax (maximum Standardized Uptake Value) correlated with the local control (p<0.001) and two-years survival (p=0.003). At univariate analysis, localization of primary tumor, site of metastases, KRAS (Kirsten RAt Sarcoma) oncogene mutational status, response to first-line chemotherapy, response to SRT and number of treated lesions predicted both PFS and OS.DiscussionThis real practice experience suggests that further studies are needed to analyze the promising role of SRT in the multidisciplinary management of mCRC.

Dosimetric verification of flattening filter free model based on TrueBeam accelerator using ArcCheck system

To study the feasibility of ArcCheck verification system in dosimetric verification for stereotactic radiotherapy (SRT) the stereotactic radiotherapy (SRT) with flattening filter free (FFF) model. Methods: A total of 76 cases under SRT treatment plans were introduced into ArcCheck phantom and recalculated. Threshold criteria was set as (3%, 3 mm, 10%) or (2%, 2 mm, 10%). The calculated dose distribution and the measured dose distribution of ArcCheck phantom were compared by means of distance to agree (DTA) and Gamma analysis method respectively. Results: Based on the threshold criteria (3%, 3 mm, 10%), the relative and absolute mean pass rates of SRT treatment plans by DTA and Gamma analysis were greater than 95%. Based on the threshold criteria (2%, 2 mm, 10%), the relative and absolute mean pass rates of SRT treatment plan by DTA and Gamma analysis were about 90%. The dose pass rate of Gamma analysis method was slightly higher than that of DTA analysis method (P<0.001). Conclusion: The ArcCheck verification system is a rapid and accurate method for SRT dose verification, and discrepancies are found in different analysis methods.

Inhomogeneous tumor dose distribution provides better local control than homogeneous distribution in stereotactic radiotherapy for brain metastases

IntroductionThe aim of this study was to analyze the impact of inhomogeneous versus homogeneous dose distribution on local control (LC) and radionecrosis (RN) in patients treated with fractionated stereotactic radiotherapy (SRT) for newly-diagnosed brain metastases (BM). Patients and methodsFrom 2014 to 2017, 134 patients (median age 61 years) underwent SRT for BM (n = 114 with ≤2, n = 20 with 3–6 BM) at our institution. Treatment was delivered using volumetric modulated arc therapy on a linear accelerator. Ninety-one consecutive patients (BM = 136) were irradiated at a dose of 21–23.1 Gy in 3 fractions delivered homogeneously (99% of the dose had to cover 99% of the planning target volume (PTV)) (group 1) whereas the following 43 patients (BM = 72) received an inhomogeneous dose of 10 or 11 Gy prescribed to the isocenter with the 70% isodose line covering the PTV (group 2). Variables analyzed included dose distribution, age, gender, histology, diagnosis-specific Graded Prognostic Assessment score, number of brain metastases, presence of extracranial metastases, and tumor volumes. ResultsAfter a median follow-up of 12.4 months (range, 1.4–33.1), the 1-year LC and RN rate were 78% and 7.5% in group 1 and 93% and 0% in group 2, respectively (p = 0.005). In multivariate analysis, improved LC was significantly correlated with SRT dose distribution (p = 0.009) and tumor volume (p = 0.03). The number of metastases (p = 0.03) and SRT dose distribution (p = 0.04) were both associated with increased risk of RN. ConclusionSRT delivered with inhomogeneous dose distribution resulted in better LC and a lower risk of RN compared to homogeneous distribution.

OC-0166: Dose of stereotactic radiotherapy, local control and overall survival in cholangiocarcinoma

OC-0166: Dose of stereotactic radiotherapy, local control and overall survival in cholangiocarcinoma

Dosimetric comparison of different treatment modalities for stereotactic radiotherapy

BackgroundThe modalities for performing stereotactic radiotherapy (SRT) on the brain include the cone-based linear accelerator (linac), the flattening filter-free (FFF) volumetric modulated arc therapy (VMAT) linac, and tomotherapy. In this study, the cone-based linac, FFF-VMAT linac, and tomotherapy modalities were evaluated by measuring the differences in doses delivered during brain SRT and experimentally assessing the accuracy of the output radiation doses through clinical measurements.MethodsWe employed a homemade acrylic dosimetry phantom representing the head, within which a thermoluminescent dosimeter (TLD) and radiochromic EBT3 film were installed. Using the conformity/gradient index (CGI) and Paddick methods, the quality of the doses delivered by the various SRT modalities was evaluated. The quality indicators included the uniformity, conformity, and gradient indices. TLDs and EBT3 films were used to experimentally assess the accuracy of the SRT dose output.ResultsThe dose homogeneity indices of all the treatment modalities were lower than 1.25. The cone-based linac had the best conformity for all tumors, regardless of the tumor location and size, followed by the FFF-VMAT linac; tomography was the worst-performing treatment modality in this regard. The cone-based linac had the best gradient, regardless of the tumor location and size, whereas the FFF-VMAT linac had a better gradient than tomotherapy for a large tumor diameter (28 mm). The TLD and EBT3 measurements of the dose at the center of tumors indicated that the average difference between the measurements and the calculated dose was generally less than 4%. When the 3% 3-mm gamma passing rate metric was used, the average passing rates of all three treatment modalities exceeded 98%.ConclusionsRegarding the dose, the cone-based linac had the best conformity and steepest dose gradient for tumors of different sizes and distances from the brainstem. The results of this study suggest that SRT should be performed using the cone-based linac on tumors that require treatment plans with a steep dose gradient, even as the tumor is slightly irregular, we should also consider using a high dose gradient of the cone base to treat and protect the normal tissue. If normal tissues require special protection exist at positions that are superior or inferior to the tumor, we can consider using tomotherapy or Cone base with couch at 0° for treatment.

Outcome and complications in dogs with appendicular primary bone tumors treated with stereotactic radiotherapy and concurrent surgical stabilization

To document the outcome of dogs with appendicular primary bone tumors treated with stereotactic radiotherapy (SRT) and concurrent stabilization. Multi-institutional retrospective case series. Eighteen dogs with presumptive or definitive diagnosis of appendicular osteosarcoma. Medical records of dogs with appendicular primary bone tumors treated with SRT and stabilization were reviewed for signalment, preoperative staging and diagnostics, radiation dose, stabilization method, and outcome. The distal radius was affected in 13/18 cases. Osteosarcoma or sarcoma was confirmed cytologically or histologically in 15/18 cases. Seven dogs were diagnosed with a pathological fracture at the time of treatment, and 11 were considered at high risk for pathological fracture. Dogs received a single dose (n = 5) or 3 doses (n = 13) of SRT. Surgical stabilization was performed under the same anesthetic event as the final dose of SRT in 10 dogs. Stabilization was achieved with a bone plate (n = 15) or interlocking nail (n = 3). Seventeen dogs received adjuvant chemotherapy. Complications occurred in 16/17 dogs, 15/17 of those being considered major complications. Four dogs experienced more than one complication. Infection was the most common complication, diagnosed in 15/17 cases, and considered as a major complication in 13/15 cases. Postoperative fracture was recorded as a major complication in 3 cases. Nine dogs were amputated at a median of 152 days. The median survival time was 344 days. Treatment of bone tumors with SRT and concurrent stabilization was associated with a prohibitively high complication rate in dogs. Alternative methods for limb salvage should be considered for dogs at risk for pathologic fracture.

Phase I trial combining ipilimumab + high dose stereotactic radiation: Results and serum immune correlates.

3022Background: Preclinical models suggest systemic disease control with ipilimumab (IPI) and radiation. Here we conducted a phase I trial of IPI and high dose stereotactic body radiation therapy (...