Single-Fraction Stereotactic Body Radiation Research Articles

Single Fraction Stereotactic Body Radiation Therapy Induces Dynamic Changes to the Peripheral Blood T Cell Repertoire in Renal Cell Carcinoma Patients

Clinical studies combining radiation and immunotherapy have shown promising response rates, strengthening efforts to sensitize tumors to immune-mediated attack. Thus, there is an ongoing surge in trials using preconditioning regimens with immunotherapy. Yet, due to scarcity of resected tumors treated in situ with radiotherapy, there has been little investigation of radiation’s sole contributions towards local and systemic anti-tumor immunity in patients. Without this access, translational studies have been limited to evaluating circulating immune subsets and systemic remodeling of peripheral T cell receptor repertoires. This constraint has left gaps in how radiation impacts intratumoral responses and whether tumor-resident T cell clones are amplified following treatment. Therefore, to interrogate the immune impact of radiation on the tumor microenvironment and test the hypothesis that radiation initiates local and systemic expansion of tumor-resident clones, we analyzed renal cell carcinoma from patients treated with stereotactic body radiation therapy. Blood and tumor samples were collected from patients prior to nephrectomy for renal cell carcinoma. These samples were compared to samples from patients treated on a 15 patient clinical trial of single fraction stereotactic body radiation therapy delivered 4 weeks prior to nephrectomy. Transcriptomic comparisons were evaluated by bulk RNA sequencing. T cell receptor sequencing monitored repertoires during the 4-week period between SBRT and nephrectomy. Pathway analysis from tumor transcriptomic data showed radiation-specific enrichment of immune-related processes. T cell receptor sequencing revealed increased clonality in radiation-treated tumors. The frequency of identified, tumor-enriched clonotypes was tracked across serial blood samples. Compared to pre-treatment, we observed increased abundance of tumor-enriched clonotypes 2 weeks post-radiation. However, this expansion was not sustained and contracted towards baseline levels 4 weeks after treatment. Altogether, these results indicate robust intratumoral immune remodeling and a window of tumor-resident T cell expansion following radiation that may be leveraged for rational design of combinatorial strategies. Samples from renal cell carcinoma (RCC) patients underwent high-throughput analysis to reveal transcriptional immune activation and increased clonality in irradiated tumors. Analysis across longitudinal blood samples showed tumor-enriched clonotypes undergo phases of peripheral expansion and contraction following radiation. Collectively, these findings demonstrate radiotherapy remodels intratumoral T cell responses and have significant implications for refined sequencing of combination strategies in RCC.

Simulated Single Fraction Stereotactic Body Radiation Therapy for the Treatment of Abdominal Oligometastatic Disease with Online Adaptive Magnetic Resonance Guidance: A Feasibility Study

Local ablative therapy improves overall survival in patients with limited oligometastatic disease. Single fraction SBRT is efficient and is safe in several body sites and can provide a high rate of local control, with 20Gy in 1 fraction commonly used in Europe. However, treating metastases in the abdomen is difficult due close proximity to mobile luminal organs and poor visualization on cone beam CT. The purpose of this study is to determine the feasibility of delivering MR-guided adaptive stereotactic body radiation therapy (SBRT) in a single fraction for abdominal metastases. Patients with abdominal metastases within 8mm from luminal organs treated with hypofractionation or SBRT using maximum inhale breath hold (MIBH) respiratory gating on an integrated MR-Linac or MR-cobalt radiotherapy system were retrospectively analyzed. Single fraction SBRT plans were created on the original MRI simulation with dose constraints from the AAPM Task Group 101 and Timmerman et al. Optimized PTVs (PTVopt) created by a Boolean subtraction of the 3-5mm expansion around luminal organs from the 3mm expansion around the GTV. Using a prescription of 24Gy in 1 fraction, goals included PTV V95% > 90%, PTVopt V95% > 90%, and PTVopt D99% > 20Gy with no OAR dose violations. The single fraction plans were tested on 5 fractional MRI scans. Dosimetric data was collected with the original plan (“predicted”) and after the plan was adapted using an isotoxic approach to the daily re-contoured luminal organ anatomy (“Re-optimized”). The Wilcoxon rank sum test was used to compare dosimetric data and the frequency of meeting dosimetric goals between the multi-fraction and single fraction baseline plans and between the predicted and re-optimized fractional plans. Ten patients with abdominal metastases (4 liver, 3 lymph node, 2 kidney, and 1 adrenal site) with GTV mean and range of 25.5 (1.64, 84.2) mL of various histologies were analyzed. The multi-fraction and single fraction plans mean PTV V95% and PTVopt V95% were 89.7% vs. 81.5% and 97.0% vs. 90.9% respectively (all p>0.05), while 2/10 of both the multi-fraction and single fraction plans had a PTVopt V95% < 90%, and no OAR dose constraints were violated. Comparing the predicted and re-optimized fractional plans, there was a statistically significant, 32.8% increase in the mean PTVopt D99% and 68% decrease in the mean frequency of OAR dose violations (Table 1). Single fraction SBRT for the treatment of abdominal metastases with online adaptive MR guidance is feasible and may be an efficient alternative to multi-fraction treatments. Online MR-guided adaptation is required to maintain adequate target coverage while respecting OAR dose constraints.Abstract 2406; TableTable 1: Isotoxic OptimizationMeanFrequencyPTV V95% (%)PTVopt V95% (%)PTVopt D99% (Gy)PTV V95% > 90%PTVopt V95% > 90%PTVopt D99% > 20GyOAR ViolationsPredicted81.187.917.40.240.680.240.68Re-optimized84.892.822.60.420.820.740p-value0.680.310.01*0.160.360.01*0.001* Open table in a new tab

Single Fraction Stereotactic Body Radiation Therapy After Surgery in Treating Patients With Non-small Cell Lung Cancer

Single Fraction Stereotactic Body Radiation Therapy After Surgery in Treating Patients With Non-small Cell Lung Cancer

Stereotactic Body Versus Hypofractionated Radiation Therapy for Local Control of Prostate Cancer Bone Metastases

To compare the rate of radiographic in field failure (IFF) for prostate cancer bone metastases treated with single fraction stereotactic body radiation therapy (SBRT) and hypofractionated radiation therapy (HRT), and secondarily describe the rate of subsequent distant failure (DF). An institutional, retrospective review was conducted of all patients with prostate cancer receiving RT to bone metastases between January 2013 and May 2017. Patients were excluded if less than 6 months of clinical and imaging follow-up was available. IFF was defined as any increase in the size and/or radiotracer avidity of the treated lesion, subsequent use of a secondary local salvage therapy to the treated site, or the appearance of a new lesion within the initial 50% isodose line. DF, defined as new metastatic disease following RT, was a secondary outcome. The cumulative incidence of IFF and DF was determined using the Fine-Gray method with death as a competing risk. Hazard ratios (HR) for single variable associations with outcomes were calculated using the Cox model and a P value of 0.05 was set to determine significance. A total of 201 patients with 249 metastases (191 SBRT, 58 HRT) with a median follow-up of 2.2 (IQR 1.2-3.0) years were analyzed. Patients treated with SBRT more frequently had 1-3 metastases compared to those receiving HRT (85% vs 40%, P<0.0001). The presence of castrate resistant disease was not significantly different between the SBRT and HRT groups (41% vs 35%, P=0.39). The SBRT prescription dose ranged from 16 to 24 Gy in a single fraction, with most receiving 18 (46%) or 20 (47%) Gy. HRT was mainly 8 Gy in 1 fraction (57%) or 20 Gy in 5 fractions (41%). Imaging follow-up was primarily with 11C-choline PET/CT (79%), technetium 99m-MDP bone scan (10%), or CT scan (5%). The one and three-year IFF rates were 34% (95% CI 20-46) and 53% (34-67) for lesions treated with HRT compared to 5% (1.4-7.5) and 13% (7-19) in those treated with SBRT. On single variable regression, the HR for IFF with HRT compared to SBRT was 6.8 (3.7-12.5; P <.0001). No other variables assessed, including Gleason score, castrate resistant disease status, or anatomical location of metastasis were associated with an increased risk of IFF (P >0.05). There was no difference in DF for patients treated with HRT compared with SBRT [3-year cumulative incidence estimate 94% (77-98) vs. 82% (75-88); HR 1.33 (0.97-1.81), P=0.08]. Single fraction SBRT at doses ≥ 16 Gy is an effective means of local therapy and significantly improves radiographic IFF compared to HRT in prostate cancer patients with bone metastases. In this large cohort of patients, local control using SBRT was 95% and 87% at one and three years respectively. The subsequent risk of DF was high. Thus, optimizing patient selection and multidisciplinary management of local and systemic therapies remains essential.

Impact of Tumor Location & Dosimetric Predictors for Chest Wall Toxicity in Single Fraction SBRT for Stage I Non-Small Cell Lung Cancer

Single fraction stereotactic body radiation therapy (SF-SBRT) is an acceptable regimen for the treatment of peripheral Stage I Non-Small Cell Lung Cancer (NSCLC). Rates of chest wall toxicity (CWT) reported by phase II trials did not stratify by distance of tumor to chest wall (CW) and dosimetric parameters to limit CWT are not well defined. We sought to determine the relationship of tumor location and dosimetric parameters with CWT in SF-SBRT for peripheral Stage I NSCLC. An institutional review board-approved prospective SBRT registry of 1,462 patients (pts) was used to identify pts treated with 30 Gy or 34 Gy in one fraction, on or off relevant protocols. Tumors were ≤ 5 cm, node-negative, and ≥ 2 cm from the proximal tracheo-bronchial tree. The ribs and CW were retrospectively contoured (CW as a 3 cm soft-tissue structure between the sternum and vertebral body). Gross tumor volume was measured as abutting, ≤ 1 cm, 1-2 cm or > 2 cm from the CW. CWT was graded according to CTCAE 3.0 criteria. Rates of CWT were compared using unpaired t-test. Logistic regression analysis was used to identify tumor and dosimetric parameters associated with CWT. This study included 138 pts treated with SF-SBRT to 146 lesions. Median follow-up was 23.8 months (34.7 months for living pts). There were 80 pts (55%) treated with 30 Gy and 66 pts (45%) treated with 34 Gy. The rate of CWT was 30.6% for lesions abutting CW, 8.2% for lesions ≤ 1 cm from CW, 3.8% for lesions 1-2 cm from CW, and 5.7% for lesions > 2 cm from CW. Grade ≥ 3 CWT for the whole cohort was modest (1.4%). Tumor abutment (OR 6.5; p=0.0005), BMI (OR 1.1; p= 0.02), rib D1cc (defined as dose to 1 cc) (OR 1.01 per Gy; p= 0.03), CW D1cc (OR= 1.08 per Gy; p=0.03), and CW D5cc (OR 1.10 per Gy; p= 0.01) were significant predictors for CWT on univariate analysis. Tumor abutment was the only significant predictor for CWT (OR 7.5; p= 0.007) on multivariate analysis. CWT remained low until a dose threshold and then increased more rapidly. CWT occurred in only 1 out of 40 pts with CW D5cc < 18 Gy (defined as dose to 5 cc less than 18 Gy), while our model suggested a 15% risk of CWT with D5cc of 27.2 Gy to the CW. CWT occurred in only 1 out of 39 pts with rib D1cc < 19 Gy, while our model suggested a 15% risk of CWT with D1cc of 30.2 Gy to the rib. The rate of CWT is significantly associated with distance from the CW. When considering only lesions adjacent to the CW, the rate of CWT in this series (30.6%) does not appear to exceed rates in the published fractionated SBRT literature (20-33%). This suggests location adjacent to the CW should not be a contraindication to SF-SBRT. Rib D1cc and CW D1cc and D5cc may be used as predictors of CWT rates, as noted in this model. As most CWT is low-grade and self-limited, these dosimetric parameters should be utilized as a guideline, rather than an absolute constraint.

Low rate of thoracic toxicity in palliative paraspinal single fraction stereotactic body radiation therapy

Background There has been an increase in the utilization of single-fraction stereotactic body radiation therapy (SBRT) to treat thoracic structures, but there have been few reports describing toxicity outcomes with this treatment.

Using Pre-radiation PET Parameters to Predict Survival in Adenocarcinoma of the Pancreas Treated With Gemcitabine and Single Fraction Stereotactic Body Radiation Therapy

Although positron emission tomography (PET) scanning has been influential in radiation treatment planning and target delineation, tumor metabolic activity has not been studied as a prognostic factor in predicting individual patient outcomes in pancreatic cancer. In a cohort of 35 patients treated with stereotactic body radiation therapy (SBRT) we analyzed whether pretreatment PET scan parameters could predict for patient survival. This study consists of 35 patients with pancreatic cancer (29 locally advanced and 6 metastatic disease) who had a pre-treatment PET scan and at least 4 months of follow-up. All PET scans were carried out on our GE Discovery-ST CT-PET scanner. PET images were imported into RT_Image (an application developed in our laboratory) for analysis. Pancreatic tumor volume, Maximum SUV, Mean SUV, Minimum SUV and integrated SUV over the tumor volume were calculated for each patient. Survival times from date of pathologic diagnosis were available for all patients. Stereotactic radiation doses of 25 Gy in a single fraction were administered. Among the various PET parameters, maximum SUV (SUVmax) demonstrated the greatest correlation with patient survival. Patients were sorted into two groups based on their SUVmax values. The Hi-SUV group consisted of patients with SUVmax values above the median and the Low-SUV group consisted of patients with SUVmax values below the median. Mean survival from diagnosis was 221 days (stdev 112) in the Hi-SUV group and 469 days (stdev 267) in the Low-SUV group (p value of 0.12 by t-test). Kaplan-Meier survival curves for all patients (Figure 1-Left) and locally advanced patients only (Figure 1-Right) are below. Neither reached significance by log-rank testing (p = 0.63 and 0.20 respectively). Our preliminary data demonstrates a trend between greater maximum SUV on pre-treatment PET scan and a reduction in overall survival. A larger sample size and longer follow-up will be available at time of presentation.