Cancer Stereotactic Body Radiotherapy Research Articles

Dosimetric impact of respiratory motion on proximal bronchial tree during lung cancer stereotactic body radiation therapy: A patient-specific phantom study

IntroductionThe respiratory motion of the proximal bronchial tree (PBT) adjacent to the tumor is not taken into consideration in the treatment plan, and there is a risk that the PBT may be irradiated with a higher dose. Therefore, this study aimed to measure the PBT dose directly using patient-specific phantoms of patients treated with SBRT for a centrally located lung tumor and to determine the dose variation with the respiratory motion of the PBT. Materials and methodsThis study included 10 patients who received SBRT for central lung tumors. We utilized patient-specific tumor phantoms fabricated with a three-dimensional printer using the patient's computed tomography (CT) data to analyze the dose variation in PBT owing to respiratory motion. Two SBRT plans were generated: a full-phase plan and a 30−70 gating plan. Dose measurements were performed using glass dosimeters. We measured the dose three times for each plan, with the phantom either in motion or fixed at the 50% phase. ResultsWe analyzed the target volumes and measured doses for each SBRT plan. Compared with the gross tumor volume on the 50% phase CT image, the internal target volume was larger by approximately 13.1% and 45.9% during the 30−70% phase and full phases CT images, respectively. Similarly, the planning target volumes increased by 9.3% and 34.4%, respectively. The average variations in the measured dose of the glass dosimeter owing to patient-specific motion were 3.85% for the full-phase plans and 1.92% for the 30−70 gating plans. ConclusionRespiratory motion can affect the absorbed dose of the PBT, and this effect is particularly pronounced when the PBT is near the tumor. The gating method reduces the degree of dose variation. This study highlights the importance of understanding the respiratory motion of the PBT in SBRT for centrally located lung tumors.

Cyclotron and linear accelerator generated scanning proton beams for lung cancer SBRT: Interplay effects and mitigations.

Pencil beam scanning (PBS) proton therapy for moving targets is known to be impacted by interplay effects between the scanning beam and organ motion. While respiratory motion in the thoracic region is the major cause for organ motion, interplay effects depend on the delivery characteristics of proton accelerators. To evaluate the impact of different types of PBS proton accelerators and spot sizes on interplay effects, mitigations, and plan quality for Stereotactic Body Radiation Therapy (SBRT) treatment of non-small cell lung cancer (NSCLC). Twenty NSCLC patients treated with photon SBRT were selected to represent varying tumor volumes and respiratory motion amplitudes (median: 0.6cm with abdominal compression) for this retrospective study. For each patient, plans were created using: (1) cyclotron-generated proton beams (CPB) with spot sizes of σ=2.7-7.0mm; (2) linear accelerator proton beams (LPB) (σ=2.9-5.5mm); and (3) linear accelerator proton minibeams (LPMB) (σ=0.9-3.9mm). The energy switching time is one second for CPB, and 0.005 s for LPMB and LPB. Plans were robustly optimized on the gross tumor volume (GTV) using each individual phase of four-dimensional computed tomography (4DCT) scans. Initially, single-field optimization (SFO) plans were evaluated; if the plan quality did not meet the dosimetric requirement, multi-field optimization (MFO) was used. MFO plans were created for all patients for comparisons. For each patient, all plans were normalized to have the same dose received by 99% of the GTV. Interplay effects were evaluated by computing the dose on 10 breathing phases, based on the spot distribution. Volumetric repainting (VR) was performed 2-6 times for each plan. We compared volume receiving 100% of the prescribed dose (V100%RX) of the GTV, and normal lung V20Gy. Twelve of 20 plans can be optimized sufficiently with SFO. SFO plans were less sensitive to the interplay effect compared to MFO plans in terms of target coverage for both LPB and LPMB. The following comparisons showed results utilizing the MFO technique. In the interplay evaluation without repainting, the mean V100%RX of the GTV were 99.42±0.6%, 97.52±3.9%, and 94.49±7.3% for CPB, LPB, and LPMB plans, respectively. Following VR (2 × for CPB; 3 × for LPB; 5 × for LPMB), V100%RX of the GTV were improved (on average) by 0.13%, 1.84%, and 4.63%, respectively, achieving the acceptance criteria of V100%RX>95%. Because of fast energy switch in linear accelerator proton machines, the delivery time for VR plans was the lowest for LPB plans, while delivery time for LPMB was on average 1 min longer than CPB plans. The advantage of small spot machines was better sparing in normal lung V20Gy, even when VR was applied. In the absence of repainting, proton machines with large spot sizes generated more robust plans against interplay effects. The number of VR increased with decreasing spot sizes to achieve the acceptance criteria. VR improved the plan robustness against interplay effects for modalities with small spot sizes and fast energy changes, preserving the low dose sparing aspect of the LPMB, even when motion is included.

P057 - One is better than two: A comparative study of single-arc versus dual-arc planning techniques in linac-based localized prostate cancer stereotactic body radiation therapy

P057 - One is better than two: A comparative study of single-arc versus dual-arc planning techniques in linac-based localized prostate cancer stereotactic body radiation therapy

Deep learning model fusion improves lung tumor segmentation accuracy across variable training-to-test dataset ratios.

This study aimed to investigate the robustness of a deep learning (DL) fusion model for low training-to-test ratio (TTR) datasets in the segmentation of gross tumor volumes (GTVs) in three-dimensional planning computed tomography (CT) images for lung cancer stereotactic body radiotherapy (SBRT). A total of 192 patients with lung cancer (solid tumor, 118; part-solid tumor, 53; ground-glass opacity, 21) who underwent SBRT were included in this study. Regions of interest in the GTVs were cropped based on GTV centroids from planning CT images. Three DL models, 3D U-Net, V-Net, and dense V-Net, were trained to segment the GTV regions. Nine fusion models were constructed with logical AND, logical OR, and voting of the two or three outputs of the three DL models. TTR was defined as the ratio of the number of cases in a training dataset to that in a test dataset. The Dice similarity coefficients (DSCs) and Hausdorff distance (HD) of the 12 models were assessed with TTRs of 1.00 (training data: validation data: test data = 40:20:40), 0.791 (35:20:45), 0.531 (31:10:59), 0.291 (20:10:70), and 0.116 (10:5:85). The voting fusion model achieved the highest DSCs of 0.829 to 0.798 for all TTRs among the 12 models, whereas the other models showed DSCs of 0.818 to 0.804 for a TTR of 1.00 and 0.788 to 0.742 for a TTR of 0.116, and an HD of 5.40 ± 3.00 to 6.07 ± 3.26mm better than any single DL models. The findings suggest that the proposed voting fusion model is a robust approach for low TTR datasets in segmenting GTVs in planning CT images of lung cancer SBRT.

Implementation and evaluation of an intelligent automatic treatment planning robot for prostate cancer stereotactic body radiation therapy

PurposeWe previously developed a virtual treatment planner (VTP), an artificial intelligence robot, operating a treatment planning system (TPS). Using deep reinforcement learning guided by human knowledge, we trained the VTP to autonomously adjust relevant parameters in treatment plan optimization, similar to a human planner, to generate high-quality plans for prostate cancer stereotactic body radiation therapy (SBRT). This study describes the clinical implementation and evaluation of VTP. Materials and methodsWe integrate VTP with Eclipse TPS using scripting Application Programming Interface. VTP observes dose-volume histograms of relevant structures, decides how to adjust dosimetric constraints, including doses, volumes, and weighting factors, and applies the adjustments to the TPS interface to launch the optimization engine. This process continues until a high-quality plan is achieved. We evaluated VTP’s performance using the prostate SBRT case from the 2016 American Association of Medical Dosimetrist/Radiosurgery Society plan study with its plan scoring system, and compared to human-generated plans submitted to the challenge. Using the same scoring system, we also compared the plan quality of 36 prostate SBRT cases (20 planned with IMRT and 16 planned with VMAT) treated at our institution for both VTP and human-generated plans. ResultsIn the plan study case, VTP achieved a score of 142.1/150.0, ranking the third in the competition (median 134.6). For the clinical cases, VTP achieved 110.6 ± 6.5 for 20 IMRT plans and 126.2 ± 4.7 for 16 VMAT plans, similar to scores of human-generated plans with 110.4 ± 7.0 for IMRT plans and 125.4 ± 4.4 for VMAT plans. The workflow, plan quality and planning time of VTP were reviewed to be satisfactory by experienced physicists. ConclusionWe successfully implemented VTP to operate a TPS for autonomous human-like treatment planning for prostate SBRT.

Every-Other-Day Versus Once-a-Week Urethra-Sparing Prostate Stereotactic Body Radiation Therapy: 5-Year Results of a Randomized Phase 2 Trial

To present the 5-year results from a prospective multicenter phase II randomized trial of every-other-day (EOD) vs. once-a-week (QW) urethra-sparing stereotactic body radiotherapy (SBRT) for localized prostate cancer. Between 2012 and 2015, 170 patients from nine European institutions with cT1c-3aN0M0 prostate cancer were randomized to 36.25 Gy in 5 fractions (6.5 Gy/fraction to the urethra) delivered either EOD (arm A, n=84), or QW (arm B, n=86). The median follow-up was 78 months (interquartile range, IQR 23 months) and 77 months (IQR 16 months) for arms A and B, respectively. Among the 165 patients treated and retained for the final analysis (arm A, n=82; arm B= 83), acute toxicity (CTCAE v4.03 scale) was mild or absent with no differences between arms. The 5-year ≥ grade-2 genitourinary (GU) toxicity-free survival was 75.9% and 76.1% for arms A and B, respectively (p=0.945), while the 5-year ≥ grade-2 gastrointestinal (GI) toxicity-free survival was 89% and 92% for arms A and B, respectively (p=0.596). No changes in EORTC QLQ-PR25 scores were observed in both arms for GU, GI, and sexual domains at 5-year follow-up compared to baseline. At the last follow-up, biochemical failure was observed in 14 patients in the EOD arm and in 7 patients in the QW arm with a 5-year biochemical relapse-free survival rate of 92.2% and 93% for arms A and B, respectively (p=0.13). Prostate cancer SBRT with a 10% dose reduction to urethra was associated with a minimal impact on urinary function and quality of life regardless of a EOD or QW fractionation schedule. Biochemical control so far, has been encouraging and much alike in both study arms, though longer follow-up is probably needed to assess the true value of overall treatment time on disease outcome.

The effect of integrating knowledge-based planning with multicriteria optimization in treatment planning for prostate SBRT.

Knowledge-based planning (KBP) and multicriteria optimization (MCO) are two powerful tools to assist treatment planners in achieving optimal target coverage and organ-at-risk (OAR) sparing. The purpose of this work is to investigate if integrating MCO with conventional KBP can further improve treatment plan quality for prostate cancer stereotactic body radiation therapy (SBRT). A two-phase study was designed to investigate the impact of MCO and KBP in prostate SBRT treatment planning. The first phase involved the creation of a KBP model based on thirty clinical SBRT plans, generated by manual optimization (KBP_M). A ten-patient validation cohort was used to compare manual, MCO, and KBP_M optimization techniques. The next phase involved replanning the original model cohort with additional tradeoff optimization via MCO to create a second model, KBP_MCO. Plans were then generated using linear integration (KBP_M+MCO), non-linear integration (KBP_MCO), and a combination of integration methods (KBP_MCO+MCO). All plans were analyzed for planning target volume (PTV) coverage, OAR constraints, and plan quality metrics. Comparisons were generated to evaluate plan and model quality. Phase 1 highlighted the necessity of KBP and MCO in treatment planning, as both optimization methods improved plan quality metrics (Conformity and Heterogeneity Indices) and reduced mean rectal dose by 2Gy, as compared to manual planning. Integrating MCO with KBP did not further improve plan quality, as little significance was seen over KBP or MCO alone. Principal component score (PCS) fitting showed KBP_MCO improved bladder and rectum estimated and modeled dose correlation by 5% and 22%, respectively; however, model improvements did not significantly impact plan quality. KBP and MCO have shown to reduce OAR dose while maintaining desired PTV coverage in this study. Further integration of KBP and MCO did not show marked improvements in treatment plan quality while requiring increased time in model generation and optimization time.

Angiotensin receptor blockade and stereotactic body radiation therapy for early stage lung cancer ARB & SBRT for early stage lung cancer

ABSTRACT Stereotactic body radiotherapy (SBRT) demonstrates excellent local control in early stage lung cancer, however a quarter of patients develop recurrence or distant metastasis. Transforming growth factor-beta (TGF-β) supports metastasis and treatment resistance, and angiotensin receptor blockade (ARB) indirectly suppresses TGF-β signaling. This study investigates whether patients taking ARBs while undergoing SBRT for early stage lung cancer exhibited improved overall survival (OS) or recurrence free survival (RFS) compared to patients not taking ARBs. This was a single institution retrospective analysis of 272 patients treated with SBRT for early stage lung cancer between 2009 and 2018. Patient health data was abstracted from the electronic medical record. OS and RFS were assessed using Kaplan–Meier method. Log-rank test was used to compare unadjusted survival between groups. Univariable and multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs). Of 247 patients analyzed, 24 (10%) patients took ARBs for the duration of radiotherapy. There was no difference in mean age, median tumor diameter, or median biologic effective dose between patients taking ARBs or not. Patients taking ARBs exhibited increased OS (ARB = 96.7 mo.; no ARB = 43.3 mo.; HR = 0.25 [95% CI: 0.10 to 0.62, P = .003]) and increased RFS (median RFS, ARB = 64.3 mo.; No ARB = 35.1 mo.; HR = 0.26 [95% CI: 0.10 to 0.63, P = .003]). These effects were not seen in patients taking angiotensin converting enzyme inhibitors (ACEIs) or statins. ARB use while undergoing SBRT for early stage lung cancer may increase OS and RFS, but ACEI use does not show the same effect.

Dosimetric and biological comparisons of single planning and double plannings for bilateral lung cancer SBRT planning based on the Cyber-Knife system.

The aim is to investigate the influence of single planning (Plan S) and double plannings (Plan D) on bilateral lung cancer stereotactic body radiation therapy planning from the perspective of dosimetry and biology respectively. Methods Cases with bilateral lung cancer patients who had undergone SBRT with the Cyber-Knife were enrolled, and a single planning and double plannings were designed in the Multiplan@4.2 treatment planning system equipped with the Cyber-Knife system. The single plan was to optimize the two target volumes in a separate plan, while the dual plan is to optimize two target volumes respectively in two separate plans, then perform dose superposition. Then based on the dosimetric results, the biological parameters were calculated. Thus the quality of SBRT plans for those bilateral lung cancer designed by the two methods were compared and evaluated according to the dosimetric and biological results. The dose distribution of both planning target volumes and surrounding organs at risk in Plan S and Plan D could meet the clinical prescription requirements. The target conformity index and the new conformity index of PTV were closer to 1 in the Double plannings, and the dose gradient GI in the Plan D was smaller than Plan S. For organs at risks, the doses received by the Plan D were relatively small. In terms of biological models, for the equivalent uniform dose of normal lung tissue, heart and esophagus, the Plan D was 6.51% (P=0.045), 19.8% (P=0.022), 27.08% (P>0.05) lower than Plan S respectively. The results showed that the equivalent uniform dose of normal tissue in the Plan D was lower relative to Plan S. Dosimetric and biological results show that both the use of Plan D have an advantage of protecting normal tissues, and it was suggested that to design double plannings for bilateral lung cancer stereotactic body radiation therapy planning based on Cyber-Knife in the clinical practice.

End-to-end test of respiratory gating radiation therapy for lung stereotactic body radiation therapy treatments.

In this paper, a dosimetric end-to-end test of respiratory gated radiation therapy (RGRT) applied in lung cancer stereotactic body radiation therapy (SBRT) was performed. The test was performed from treatment simulation to treatment delivery using a QUASAR phantom, for regular, slightly irregular and irregular breathing patterns in phase- and amplitude-gated modes. A mechanical and dosimetric verification was performed to evaluate all steps of the proposed treatment workflow. Dose measurements were performed using a PinPoint ion chamber and GafChromic EBT3 films. Mechanical verification confirmed good function of the chosen systems. Dosimetric verification showed good agreement between planned and measured doses, for the phase-gated versus amplitude-gated modes: 1.4 ± 0.4% versus 1.2 ± 0.2% for regular, 2.8 ± 0.3% versus 3.0 ± 0.3% for slightly irregular, and 6.2 ± 0.7% versus 7.4 ± 0.5% for irregular breathing patterns. The gamma passing rates for 3%/3mm and 2%/2mm criteria, comparing phase- versus amplitude-gated modes, were 99.0 ± 0.3% versus 99.5 ± 0.2% and 95.2 ± 0.2% versus 96.1 ± 0.2% for the regular, 97.4 ± 0.8% versus 98.0 ± 0.6% and 91.7 ± 0.5% versus 92.4 ± 0.4% for the slightly irregular, and 96.4 ± 0.5% versus 95.3 ± 0.7% and 86.4 ± 0.5% versus 84.6 ± 0.7% for the irregular breathing patterns, respectively. It is concluded that using equipment and workflow for the treatment of lung cancer by means of SBRT in RGRT mode is safe and efficient, for regular and slightly irregular breathing patterns.

Modeling physician’s preference in treatment plan approval of stereotactic body radiation therapy of prostate cancer

Objective. Treatment planning of radiation therapy is a time-consuming task. It is desirable to develop automatic planning approaches to generate plans favorable to physicians. The purpose of this study is to develop a deep learning based virtual physician network (VPN) that models physician’s preference on plan approval for prostate cancer stereotactic body radiation therapy (SBRT). Approach. VPN takes one planning target volume (PTV) and eight organs at risk structure images, as well as a dose distribution of a plan seeking approval as input. It outputs a probability of approving the plan, and a dose distribution indicating improvements to the input dose. Due to the lack of unapproved plans in our database, VPN is trained using an adversarial framework. 68 prostate cancer patients who received 45 in 5-fraction SBRT were selected in this study, with 60 patients for training and cross validation, and 8 patients for independent testing. Main results. The trained VPN was able to differentiate approved and unapproved plans with Area under the curve 0.97 for testing data. For unapproved plans, after applying VPN’s suggested dose improvement, the improved dose agreed with ground truth with relative differences for PTV for PTV for penile bulb for rectum and for bladder Significance. VPN was developed to accurately model a physician’s preference on plan approval and to provide suggestions on how to improve the dose distribution.

Early-Stage Non-Small Cell Lung Cancer Stereotactic Body Radiation Therapy Outcomes in a Single Institution.

IntroductionThe gold standard treatment of stage I non-small cell lung cancer (NSCLC) is surgical resection. For medically inoperable patients, stereotactic body radiation therapy (SBRT) can provide comparable local control (LC) and overall survival (OS). The objectives of this study are to determine the three-year LC and OS for SBRT compared to early-stage NSCLC patients treated with alternative radiation modalities at our institution.Materials and methodsThis retrospective study included a total of 139 consecutive patients who were diagnosed with stage I (T1-2 N0 M0) NSCLC and treated with radiation therapy at our institution between 2015 and 2020. Patient demographics and clinical data were obtained from chart reviews. Treatment subgroups were: SBRT (48Gy/4 or 60Gy/8), hypofractionation (60Gy/15), conventional fractionation (60Gy/30 or 50Gy/20), and palliative radiation (20Gy/5, 30Gy/10, or 40Gy/15). Kaplan-Meier curves were plotted for LC and OS. We also performed Cox’s proportional hazard regression analysis.ResultsThe median patient age was 74 (range 52-91). The numbers of patients in each treatment subgroup were: SBRT (44), hypofractionation (78), conventional fractionation (8), and palliative (9). Differences in age, gender, and histopathological cell type between subgroups were not statistically significant. Metastatic progression was the most common outcome amongst treatment failures, followed by local recurrence and regional spread. Median post-treatment follow-up in months for each subgroup was: SBRT (20.2), hypofractionated (20.7), conventional fractionation (13.9), and palliative (14.4). Post-treatment three-year LC was found to be significantly better with SBRT (94%) versus hypofractionation (71%), conventional fractionation (80%), and palliative (71%). OS at three years were SBRT (67%), hypofractionation (59%), conventional fractionation (66%), and palliative (44%). As a whole, 72% (100/139) of patients had biopsy-proven NSCLC. Analysis showed biopsy status had no statistical significance with regards to LC or OS. Every 20 years of age had a 3.2x risk of death (95% CI: 1.425-7.268). Concerning the treatment modalities, there were significant differences for the hazard of death compared to SBRT: hypofractionation had 2.58x increased risk while palliative had 5.83x increased risk.The proportion of patients who experienced post-treatment radiation pneumonitis or dermatitis were: SBRT (7%, 2%), hypofractionation (8%, 3%), conventional fractionation (13%, 25%), and palliative (0%, 0%), respectively. No patients who experienced grade III or higher toxicities were observed as defined by Common Terminology Criteria for Adverse Events (CTCAE). ConclusionOur experience confirms SBRT can provide durable three-year local control with a comparable rate of post-treatment complications versus other radiation modalities for early-stage NSCLC. SBRT appears to be non-inferior to hypofractionation with regards to three-year LC.

The prognostic value of circulating lymphocyte counts and ABO blood group in lung cancer stereotactic body radiation therapy: a retrospective study

BackgroundClinically, there is a lack of simple and feasible indicators to predict the efficacy of stereotactic body radiation therapy (SBRT). Circulating lymphocyte counts (CLCs) is considered to be related to curative effect in conventional radiotherapy of lung cancer, and blood groups are also associated with the survival. In this study, we investigate the prognostic value of CLCs and ABO blood groups in lung cancer patients treated with SBRT.MethodsWe retrospectively analyzed 191 patients who were treated with lung cancer SBRT in Taizhou Hospital of Zhejiang Province from September 2014 to December 2018. The medical record system of Taizhou Hospital was used to collect relevant clinical data, such as stage, CLC, ABO blood groups and other important clinical co-variates. The effects of SBRT were evaluated by patient reexamination image data and telephone follow-up. The RECIST 1.1 standard was used to evaluate the short-term efficacy in the first, third, and sixth months after SBRT. Progression-free survival (PFS) was defined as the time from the day of SBRT to disease progression or death from any cause. Overall survival (OS) was measured from the day of SBRT until the last follow-up or death. Survival curves and univariate, multivariate logistic-regression analyses were used to expound the prognostic factors for local control (LC), PFS, and OS of lung cancer SBRT patients.ResultsUnivariate and multivariate analysis results showed that post-SBRT CLCs were independent factors for the short-term efficacy 3 and 6 months after lung cancer SBRT [hazard ratio (HR) =0.249, P=0.037; HR =0.347, P=0.012]. Survival analyses showed that the PFS and OS of lung cancer SBRT patients with A blood type was significantly shorter than that in the other three non-A blood groups (PFS: 6.5 vs. 10 months, HR =1.535, P=0.020; OS: 24 vs. 41 months, HR =1.578, P=0.048). Moreover, the patients with high post-SBRT CLCs in the non-A blood group had the longest PFS and OS after lung cancer SBRT (HR =0.551, P=0.043).ConclusionsLung cancer SBRT patients with high-post-SBRT CLCs and non-A blood groups seem to exhibits best curative effect, which represent a potential opportunity to improve the clinical management of these patients. The mechanisms of this association deserve further verification and investigation.

The Invasive Potential of Hepatoma Cells Induced by Radiotherapy is Related to the Activation of Hepatic Stellate Cells and Could be Inhibited by EGCG Through the TLR4 Signaling Pathway.

Post-radiotherapy recurrence and metastasis of liver cancer were thought to arise from the invasion and metastasis of residual hepatocellular carcinoma cells, but it has now been shown to be closely related to the increased metastatic potential of residual liver cancer cells mediated by radiotherapy. The changes of liver microenvironment after radiotherapy also provide a favorable condition for promoting the metastatic potential of hepatocellular carcinoma. Studies have shown that radiation-induced activation of hepatic stellate cells (HSCs) is one of the main changes in the microenvironment of hepatocellular carcinoma. Therefore, we hypothesized that activated HSCs are involved in regulating the metastatic capacity of residual cancer cells after radiotherapy. The present study observed that 48 h co-culture of three human hepatoma cell lines (MHCC97-L, Hep-3B, LM3) with a irradiated human HSC line (LX-2) in a transwell chamber could significantly improve the invasion of the human hepatoma cells; and the culture supernatant of activated HSCs could also enhance the invasion of the hepatoma cells. In contrast, co-culture with irradiated hepatoma cells enhanced the invasion of LX-2 cells. In vitro, irradiation enhanced the activation phenotype and the toll like receptor 4 (TLR4) signaling pathway of LX-2 cells or primary mouse HSCs, which upregulated intercellular cell adhesion molecule-1 (ICAM1), laminin receptor (67 LR), Interleukin- 6 (IL-6), and CX3C chemokine ligand 1 (CX3CL1) and downregulated toll-interacting proteins. The compound (-)-epigallocatechin-3-gallate (EGCG) inhibited signal transduction of activated TLR4 and radiation-induced invasion of LX-2 cells by binding to 67 LR. These observations indicated that the enhancement of the metastatic potential of hepatoma cells after irradiation was relevant to the activation of HSCs, and the activation of TLR4 signaling pathway was involved in this process, which was inhibited by EGCG. Our results will help enhance the therapeutic efficacy of liver cancer stereotactic body radiation therapy to prevent and decrease the risks of post-radiotherapy recurrence and metastasis.

OD45 - Clinical kick-off of Ra yPilot® HypoCath® real time tracking: a novel electromagnetic device without surgical intervention to evaluate the intrafraction motion during extreme hypofractionation of localized prostate cancer stereotactic body radiation therapy (SBRT)

OD45 - Clinical kick-off of Ra yPilot® HypoCath® real time tracking: a novel electromagnetic device without surgical intervention to evaluate the intrafraction motion during extreme hypofractionation of localized prostate cancer stereotactic body radiation therapy (SBRT)

Impact of Tumor Dosimetry on Clinical Outcomes after Stereotactic Body Radiation Therapy for Pancreatic Adenocarcinoma

We hypothesized that escalated biological effective dose (BED) via stereotactic body radiation therapy (SBRT) would improve outcomes for patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC).A retrospective review was performed on consecutive patients who received pancreas SBRT from June 2009 to June 2020, were non-metastatic at the time of SBRT, received neoadjuvant chemotherapy, and had available gross tumor volume (GTV) dosimetry. Variables of interest included: age, gender, tumor location (body/tail vs head/neck), chemotherapy type (5-fluorouracil-based vs gemcitabine-based), AJCC V8 stage, pre- and post-radiotherapy (RT) CA19-9, GTV D95, and GTV V55-40 Gy. GTV volume variables were analyzed as continuous (cont) and as binary (+) functions. All patients with BRPC at diagnosis were analyzed by a logistic regression model for variables that predicted a higher likelihood of undergoing surgical resection (Model A). A second model of all patients (BRPC and LAPC) unable to undergo surgery was constructed by Cox regression analysis investigating variables that predicted for improved overall survival (OS), progression free survival (PFS), time to loco-regional failure (TTLRF), and time to distant failure (TTDF; Model B). All clinical time points were calculated from the end of SBRT and data analysis was performed in SAS with backward elimination variable selection.A total of 365 patients had a median follow up from SBRT of 12.1 months and 251 patients (69%) were diagnosed with BRPC. Model A composed of 200 BRPC patients (56% resected) with 3 clinical variables: chemotherapy (P = .39), AJCC stage (OR 0.54, P = 0.01), post-RT CA19-9 (OR 0.27, P = < 0.001); and 3 dosimetric variables: GTV D95 (OR 3.81, P = 0.03), GTV V40+ (OR 2.52, P = 0.07), and GTV V40cont (OR 0.98, P = 0.03). Model B included 168 patients (51% BRPC) unable to undergo surgery. In this group, 5-fluorouracil-based chemotherapy was associated with improved OS (HR 0.51, P = < 0.001), PFS (HR 0.48, P = < 0.001), TTLRF (HR 0.47, P = 0.004), and TTDF (HR 0.54, P = 0.006). GTV V40+ was significantly associated with improved PFS (HR 0.59, P = 0.005) and TTLRF (HR 0.58, P = 0.036), but not with OS (HR 1.06, P = 0.78) or TTDF (HR 0.68, P = 0.113). Pre-RT CA19-9 was associated with worse OS (HR 1.43, P = 0.010) and TTLRF (HR 1.59, P = 0.022). The proportion of patients receiving 5-flurouracil-based chemo and achieving GTV V40+ was evenly distributed across the cohort (χ2 = 0.55, P = 0.45).In the largest series of pancreatic cancer SBRT to date, dose-escalated tumor coverage specifically to 40 Gy (BED10 = 72 Gy) increases the likelihood of surgical resection in patients with upfront BRPC and is associated with improved PFS that is driven by improvement in loco-regional disease control for unresected patients. These data may help to inform the evolving landscape on the use of neoadjuvant and definitive radiotherapy in pancreatic cancer.

Prognostic Impact of Biologically Equivalent Dose in Stereotactic Body Radiation Therapy for Renal Cancer

Surgical resection is standard of care for initial management of localized renal cell cancer (RCC). Stereotactic body radiation therapy (SBRT) is an emerging therapy that has seen increased utilization for unresectable RCC. Due to the low α/β ratio of RCC, an improved therapeutic ratio would be predicted with the use of hypofractionated radiation treatment. While different SBRT fractionation schemes are utilized with a wide range of biologically equivalent dose (BED) for management of RCC, there is an absence of data evaluating the prognostic impact of BED for disease control.The National Cancer Database (NCDB) was queried (2004-2017) for patients with RCC (ICD C64.9) who did not have surgical resection but received definitive SBRT (defined as > 400 cGY/ fraction) to the kidney. BED was calculated using an α/β ratio of 3. Patients with a BED3 > 60 Gy were included. Kaplan-Meier analysis with log-rank test was used to evaluate overall survival (OS). Univariable (UVA) and multivariable (MVA) analysis were conducted using cox proportional hazard models to determine which clinical and treatment factors were prognostic for overall survival.A total of 344 patients with median age 77 (IQR 70 - 85) were included in this study. Histology was clear cell in 72.7%, papillary in 6.4%, transitional in 14.2%, and other/unknown in 6.7%. T stage was cT1a in 46.8%, cT1b in 25.9%, cT2 in 4.9%, cT3 in 6.1%, and cT4 in 1.2%. A total of 2.3% of patients were cN1, 6.1% of patients were cM1, and 7% received systemic therapy either before (72.7%), after (22.7%), or concurrent (4.5%) with radiation. Median BED3 was 180 Gy (IQR 126.03 - 233.97). Median OS was 90 months in the highest quartile compared to 36 - 52 months in the lower three quartiles (P = 0.007). On UVA, higher BED3 was a positive prognostic factor both as a continuous variable (HR 0.99, P = 0.001; CI 0.99 - 0.99) and as a categorical variable when stratifying patients by a BED3 of 180 Gy (HR 0.67, P = 0.008; CI 0.51 - 0.91). On MVA, higher BED3 measured as a continuous variable (HR 0.97, P = 0.005; CI 0.95 - 0.99) was a positive prognostic factor, while age (HR 1.03, P = 0.005; CI 1.01 - 1.04), transitional cell histology (HR 2.49, P = 0.004; CI 1.34 - 4.64), T stage (cT1b) (HR 1.69, P = 0.009; CI 1.14 - 2.51), and M stage (HR 14.01, P < 0.001; CI 5.90 - 33.27) were negative prognostic factors.This is the first study investigating the prognostic impact of BED for renal cancer SBRT. Higher BED is associated with improved OS. Prospective investigation is needed to clearly define optimal BED for SBRT used to treat RCC.

160: Early Stage Lung Cancer Stereotactic Body Radiation Therapy Outcomes in a Single Instituiton

160: Early Stage Lung Cancer Stereotactic Body Radiation Therapy Outcomes in a Single Instituiton

Learning-based dose prediction for pancreatic stereotactic body radiation therapy using dual pyramid adversarial network

Treatment planning for pancreatic cancer stereotactic body radiation therapy (SBRT) is very challenging owing to vast spatial variations and close proximity of many organs-at-risk. Recently, deep learning (DL) based methods have been applied in dose prediction tasks of various treatment sites with the aim of relieving planning challenges. However, its effectiveness on pancreatic cancer SBRT is yet to be fully explored due to limited investigations in the literature. This study aims to further current knowledge in DL-based dose prediction tasks by implementing and demonstrating the feasibility of a new dual pyramid networks (DPNs) integrated DL model for predicting dose distributions of pancreatic SBRT. The proposed framework is composed of four parts: CT-only feature pyramid network (FPN), contour-only FPN, late fusion network and an adversarial network. During each phase of the network, combination of mean absolute error, gradient difference error, histogram matching, and adversarial loss is used for supervision. The performance of proposed model was demonstrated for pancreatic cancer SBRT plans with doses prescribed between 33 and 50 Gy across as many as three planning target volumes (PTVs) in five fractions. Five-fold cross validation was performed on 30 patients, and another 20 patients were used as holdout tests of trained model. Predicted plans were compared with clinically approved plans through dose volume parameters and two-paired t-test. For the same sets, our results were compared with three different DL architectures: 3D U-Net, 3D U-Net with adversarial learning, and DPN without adversarial learning. The proposed framework was able to predict 87% and 91% of clinically relevant dose parameters for cross validation sets and holdout sets, respectively, without any significant differences (P > 0.05). Dose distribution predicted by our framework was also able to predict the intentional hotspots as feature characteristics of SBRT plans. Our method achieved higher correlation coefficients with the ground truth in 22/26, 24/26 and 20/26 dose volume parameters compared to the network without adversarial learning, 3D U-Net, and 3D U-Net with adversarial learning, respectively. Overall, the proposed model was able to predict doses to cases with both single and multiple PTVs. In conclusion, the DPN integrated DL model was successfully implemented, and demonstrated good dose prediction accuracy and dosimetric characteristics for pancreatic cancer SBRT.

Dosimetric evaluation of analytic anisotropic algorithm and Acuros XB algorithm using in-house developed heterogeneous thorax phantom and homogeneous slab phantom for stereotactic body radiation therapy technique

To perform patient-specific quality assurance (QA), the accuracy of the dose calculation algorithm is vital, especially in the lung cancer stereotactic body radiation therapy (SBRT). The present study is based on the evaluation of two widely used algorithms, analytical anisotropic algorithm (AAA) and Acuros XB (AXB) inside the in-house developed heterogeneous thorax phantom (HTP) and a homogeneous slab phantom (HSP) simultaneously. To evaluate dosimetric differences between the two algorithms, point dose measurement was performed for pretreatment QA plans of 35 lung cancer patients by keeping the same monitor units and beam angles as those for the actual patient treatment. The dose was calculated on the Eclipse treatment planning system inside both the medium by using both AAA and AXB algorithms. Plans were delivered on the Edge linear accelerator (LA) (Varian Medical Systems, Palo Alto, CA, USA), and measurements were taken by using a 0.01 cc ion chamber and DOSE1 electrometer. Statistical analysis was performed on the observed data set, and percentage (%) variations between the measured and planned doses were calculated and analyzed. The mean % variations between the measured and planned doses inside HTP for all QA plans were found to be 2.61 (standard deviation [SD]: 0.66) and 2.19 (SD: 0.64) for AAA and AXB algorithms, respectively. Whereas, inside HSP, it was found to be 1.79 (SD: 0.74) and 1.64 (SD: 0.70) for AAA and AXB algorithms, respectively. The mean % difference between the measured dose and the planned dose was derived to be statistically significant for HTP, however, it was found to be statistically insignificant inside the HSP at P &lt; 0.01. The Pearson's correlation coefficient test showed a strong positive correlation between the measured dose and the planned dose for both AAA and AXB inside HTP as well for HSP. The results obtained from this study showed that as the actual patient body is heterogeneous, thus to get more realistic results, patient-specific QA must be performed inside the heterogeneous phantom instead of homogeneous. Moreover, in the homogeneous medium, both the algorithms predict the dose efficiently, however, in heterogeneous medium, AAA over/under predicts the dose, whereas AXB shows good concurrence with measurements.