A. Koong

TU‐D‐J‐6C‐08: Enhancing 4D PET Through Retrospective Stacking

Purpose: Four‐dimensional (4D) PET presents challenges distinct from 4D CT owing to radiotracer dose limitations. A single‐bed field‐of‐view (FOV) PET scan typically requires several minutes to acquire adequate data for reconstruction, necessarily spanning several respiratory cycles and smearing the radiotracer signal within a given lesion over an increased volume. Although prospective or retrospective gating captures the PETimage at a single point in the respiratory cycle, restricting the data to events within the gating interval increases the signal‐to‐noise ratio (SNR). We propose a method, coined “retrospective stacking” (RS), to combine the data from the entire respiratory cycle through deformable registration. In addition, we use the transformation maps to generate a 4D PET with statistics comparable to the single RS image.Method and Materials: A single FOV of a pancreatic cancer patient was acquired via the gated PET mode on a GE Discovery ST PET‐CT scanner. These gated images were registered using a mutual information / B‐splines registration algorithm, and superimposed. A 4D PET series spanning the full respiratory cycle was generated, and fused onto a 4D CT.Results: The SNR of the RS image showed an increase of 15% over a single gated reconstruction. Activity‐volume histograms of radiotracer activity surrounding the pancreatic lesion revealed that the ungated PET showed 33% greater tumor volume (using a 40%‐of‐maximum threshold) than the RS image. The reconstructed 4D PET fused well with the 4D CT, providing a clearer view of radiotracer distribution over the respiratory cycle than was possible using gated reconstructions.Conclusion: Retrospective stacking enabled better integration of temporally varying PET and CT series by reducing radiotracer smearing due to respiratory motion, while at the same time increasing the SNR beyond the poorer statistics inherent in gated PET acquisition. Noise‐reduced 4D PETimages could also be generated for fusion with 4D CT.1

Reirradiation with stereotactic body radiation therapy after prior conventional fractionation radiation for locally recurrent pancreatic adenocarcinoma

Purpose Locally recurrent pancreatic cancer after prior radiotherapy is a therapeutic challenge with limited treatment options. This study examines the safety and efficacy of stereotactic body radiation therapy (SBRT) for locally recurrent pancreatic adenocarcinoma after prior conventional fractionation radiotherapy (CRT). Methods and materials Outcomes from all patients treated with SBRT for locally recurrent pancreatic adenocarcinoma after prior CRT at our institution were reviewed. A total of 23 patients were identified. Prior CRT median dose was 50.4 Gy (range, 30-60 Gy). Twelve patients (52%) had previously undergone surgery and received CRT as neo- or adjuvant treatment. Nine patients (39.1%) were reirradiated with SBRT with a dose of 25 Gy in a single fraction, and 14 patients (60.8%) received a 5-fraction SBRT schedule with a median dose of 25 Gy (range, 20-33 Gy) in 5 fractions (1-5 fractions). Results Median follow-up time was 28 months (range, 9-77 months). The median planning target volume was 46 cm3 (range, 14-89 cm3). Median overall survival from diagnosis and from reirradiation were 27.5 months (range, 10-77 months) and 8.5 months (range, 1 month to not reached) respectively. The cumulative incidence of local failures at the last follow-up was 19%. For the 4 patients who presented with local failure, one was treated with a single fraction of 25 Gy, and the other 3 were treated with 25 Gy in 5 fractions. Three patients presented regional failure, with a cumulative incidence of 14%, all with concurrent distant progression. The cumulative incidence of distant progression was 64% at last follow-up. After reirradiation, 6 patients (26.1%) developed a grade 2 or 3 gastrointestinal toxicity, 4 of them occurring among patients treated with a single-fraction SBRT regimen. Conclusions Our report shows that SBRT for reirradiation of locally recurrent pancreas adenocarcinoma is a feasible option with good local control and acceptable toxicity rates, especially with a multifraction schedule.

SU-C-BRE-06: Radiobiological Advantage of Very Rapid Irradiation

PURPOSE To characterize the effect of very rapid dose delivery as compared to conventional therapeutic irradiation times on clonogenic cell survival. METHODS We used a Varian Trilogy linear accelerator to deliver doses up to 10 Gy using a 6 MV SRS photon beam. We irradiated four cancer cell lines in times ranging from 30 sec to 30 min. We also used a Varian TrueBeam linear accelerator to deliver 9 MeV electrons at 10 Gy in 10 s to 30 min to determine the effect of irradiation time on cell survival. We then evaluated the effect of using 60 and 120 MeV electrons on cell survival using the Next Linear Collider Test Accelerator (NLCTA) beam line at the SLAC National Accelerator Laboratory. During irradiation, adherent cells were maintained at 37oC with 20%O2/5%CO2. Clonogenic assays were completed following irradiation to determine changes in cell survival due to dose delivery time and beam quality, and the survival data were fitted with the linear-quadratic model. RESULTS Cell lines varied in radiosensitivity, ranging from two to four logs of cell kill at 10 Gy for both conventional and very rapid irradiation. Delivering radiation in shorter times decreased survival in all cell lines. Log differences in cell kill ranged from 0.2 to 0.7 at 10 Gy for the short compared to the long irradiation time. Cell kill differences between short and long irradiations were more pronounced as doses increased for all cell lines. CONCLUSION Our findings suggest that shortening delivery of therapeutic radiation doses to less than 1 minute may improve tumor cell kill. This study demonstrates the potential advantage of technologies under development to deliver stereotactic ablative radiation doses very rapidly. Bill Loo and Peter Maxim have received Honoraria from Varian and Research Support from Varian and RaySearch.

WE‐C‐BRB‐05: Monte Carlo Simulations and Experimental Validation of Rapid Dose Delivery with Very High‐Energy Electron Beams

Purpose: To evaluate the feasibility to treat lungcancer with very high‐ energy electrons (VHEE) by Monte Carlo(MC) simulations and to estimate the beam‐on time based on experimental dose measurements on an existing VHEE beam line. Methods: Manually optimized VHEE treatment plans for a simulated lungtumor were calculated for beam energies ranging from 50 to 150 MeV in the EGSnrc/DOSXYZnrc MC code. A state‐of‐the‐art RapidArc plan with a 6 MV photon beam was calculated for the same scenario using the Eclipse treatment planning system. The minimal electron beam energy matching the 6MV photon RapidArc plan was identified. VHEE dose from 50 and 70 MeV electrons was measured with Gafchromic EBT2 films on the Next Linear Collider Test Accelerator (NLCTA) beam line adapted to our experiments at the SLAC National Accelerator Laboratory. The experimental setup was modeled in the MCNPX code and the proton and neutron contributions to the total dose were quantified. The total treatment time for the lung case was estimated based on the parameters of the NLCTA beam line and experimental data. Results: For the selected clinical scenario, 75–100 MeV electron beams produced plans of comparably high quality to the best photon plans. The simulated NLCTA percentage depth dose curves and beam profiles at 6 mm depth generally agreed with measurements within 5% for both energies and all beam sizes. The dose contribution from protons and neutrons was negligible, accounting for less than 1×10−2% of the maximum total dose. Based on the beam line parameters and the measurements, a dose of 10 Gy to 95% of the 8 cc PTV could be in principle delivered in 1.3 s. Conclusions: Our results combining MC simulations with experimental measurements suggest that treatments of lungcancer with VHEE are feasible and very fast. We anticipate superior results with plan optimization.

Strategies for prediction and mitigation of radiation-induced liver toxicity

Abstract Although well described in the 1960s, liver toxicity secondary to radiation therapy, commonly known as radiation-induced liver disease (RILD), remains a major challenge. RILD encompasses two distinct clinical entities, a ‘classic’ form, composed of anicteric hepatomegaly, ascites and elevated alkaline phosphatase; and a ‘non-classic’ form, with liver transaminases elevated to more than five times the reference value, or worsening of liver metabolic function represented as an increase of 2 or more points in the Child–Pugh score classification. The risk of occurrence of RILD has historically limited the applicability of radiation for the treatment of liver malignancies. With the development of 3D conformal radiation therapy, which allowed for partial organ irradiation based on computed tomography treatment planning, there has been a resurgence of interest in the use of liver irradiation. Since then, a large body of evidence regarding the liver tolerance to conventionally fractionated radiation has been produced, but severe liver toxicities has continued to be reported. More recently, improvements in diagnostic imaging, radiation treatment planning technology and delivery systems have prompted the development of stereotactic body radiotherapy (SBRT), by which high doses of radiation can be delivered with high target accuracy and a steep dose gradient at the tumor – normal tissue interface, offering an opportunity of decreasing toxicity rates while improving tumor control. Here, we present an overview of the role SBRT has played in the management of liver tumors, addressing the challenges and opportunities to reduce the incidence of RILD, such as adaptive approaches and machine-learning–based predictive models.

Stereotactic body radiation therapy for adrenal gland metastases: Outcomes and toxicity

Purpose This study aimed to report on our institutional experience in the use of stereotactic body radiation therapy (SBRT) for the treatment of adrenal gland metastases. Specifically, we examined the outcomes and toxicity from this treatment modality on adjacent organs at risk. Methods and Materials Data were retrieved from patients with adrenal metastases who were treated with SBRT between 2008 and 2017. Patients with primary adrenal malignancies were excluded. Toxicities were graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Time-to-event rates were calculated from the date of SBRT delivery. Results In total, 35 patients with adrenal metastases were identified. Four patients were treated for bilateral disease. The median dose was 40 Gy (range, 20-54 Gy) in 5 fractions (range, 1-6 fractions). The median follow-up time was 37 months (range, 14-451 months) from disease diagnosis and 7 months (range, 1-54 months) from the SBRT start date. With death treated as a competing risk event, the cumulative incidence of local failure was 7.6% at 1 year after SBRT and 19.2% at 3 years. The median overall survival (OS) time was 19 months (95% confidence interval, 8-54 months) and tumor size correlated with survival (P = .0006). Patients with metastases <2.9 cm had a median OS of 54 months compared with 11 months for those with adrenal metastases ≥2.9 cm (P = .01). Incidence of grade 2 toxicity was 17% with no case of grade ≥3 toxicity. SBRT did not impact renal function with a mean estimated decline in glomerular filtration rate of only 2.6 ± 8 mL/min/1.73 m2 compared with baseline. Combined kidneys V5 and combined renal cortex V17.5 did not correlate with a change in estimated glomerular filtration rate (P = .7 and P = .9, respectively). Conclusions SBRT offers excellent local control for the treatment of adrenal gland metastases with very low toxicity rates and no significant short-term impact on renal function.

TU‐CD‐BRB‐08: Radiomic Analysis of FDG‐PET Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated with SBRT

Purpose: This study aims to identify novel prognostic imaging biomarkers in locally advanced pancreatic cancer (LAPC) using quantitative, high-throughput image analysis. Methods: 86 patients with LAPC receiving chemotherapy followed by SBRT were retrospectively studied. All patients had a baseline FDG-PET scan prior to SBRT. For each patient, we extracted 435 PET imaging features of five types: statistical, morphological, textural, histogram, and wavelet. These features went through redundancy checks, robustness analysis, as well as a prescreening process based on their concordance indices with respect to the relevant outcomes. We then performed principle component analysis on the remaining features (number ranged from 10 to 16), and fitted a Cox proportional hazard regression model using the first 3 principle components. Kaplan-Meier analysis was used to assess the ability to distinguish high versus low-risk patients separated by median predicted survival. To avoid overfitting, all evaluations were based on leave-one-out cross validation (LOOCV), in which each holdout patient was assigned to a risk group according to the model obtained from a separate training set. Results: For predicting overall survival (OS), the most dominant imaging features were wavelet coefficients. There was a statistically significant difference in OS between patients with predicted high and low-risk based on LOOCV (hazard ratio: 2.26, p<0.001). Similar imaging features were also strongly associated with local progression-free survival (LPFS) (hazard ratio: 1.53, p=0.026) on LOOCV. In comparison, neither SUVmax nor TLG was associated with LPFS (p=0.103, p=0.433) (Table 1). Results for progression-free survival and distant progression-free survival showed similar trends. Conclusion: Radiomic analysis identified novel imaging features that showed improved prognostic value over conventional methods. These features characterize the degree of intra-tumor heterogeneity reflected on FDG-PET images, and their biological underpinnings warrant further investigation. If validated in large, prospective cohorts, this method could be used to stratify patients based on individualized risk.

WE‐C‐108‐01: JUNIOR INVESTIGATOR WINNER — Towards Radiation Therapy with Very High‐Energy Electron Beams

PURPOSE To experimentally validate Monte Carlo (MC) simulations for dose calculations with very high-energy electron (VHEE) beams in the presence of heterogeneities and to use MC simulations for treatment planning optimization of ultra-fast radiation therapy with VHEE beams. METHODS Polystyrene phantom with heterogeneities made of nine materials of various thicknesses was irradiated at a VHEE beam line at SLAC National Accelerator Laboratory. Films were used to measure the dose delivered to the phantom by 60-110MeV VHEE beams of 0.6-2.2mm in size. A MC model of the beam line was built and validated against the experimental data based on percentage depth-dose (PDD) curves. The MC validated code was used for VHEE radiotherapy planning of three patients. More specifically, MC beamlets were exported into a modified version of RayStation for spot-scanning optimization. The quality of VHEE dose distributions as a function of electron beam energy, beamlet size and spacing, source-to-isocenter distance, and number of beams was studied. RESULTS MC calculated PDD curves for heterogeneous phantoms were in agreement with the experimental PDD curves obtained at the VHEE beam line for all beam energies and beam sizes. VHEE treatment planning optimization study for a pediatric patient brain tumor revealed that significant normal tissue sparing was achieved in 60-100MeV VHEE plans compared to the state-of-the-art 6MV VMAT plan. The mean dose to the cochleae was by 56-72% lower in the VHEE plans. Out of the studied parameters, electron beam energy had the largest effect on the quality of VHEE treatment plans. In order to generate a VHEE plan matching a VMAT plan for a large patient, VHEE beams of 100-150MeV are needed. CONCLUSION We have validated VHEE beam MC dose calculations and we have developed a MC/RayStation treatment planning optimization tool for evaluation of the potential to rapidly treat cancer with VHEE beams. This work has been supported by the 2012 AAPM Research Seed Grant.