Biology-guided Radiotherapy Research Articles

Eligibility of patients with esophageal and gastroesophageal cancer for biology-guided radiotherapy in a retrospective cohort.

e16100 Background: Biology-guided radiotherapy (BgRT) is a novel radiotherapy modality that uses real-time positron emission tomography (PET) to guide radiotherapy beamlets. The FDA recently cleared BgRT for clinical use for tumors in lung and bone using 18F FDG radiotracer. We sought to identify esophageal cancer (EC) and gastroesophageal junction cancer (GEJC) patients who may be BgRT candidates based on diagnostic FDG PET/CT imaging. Methods: Through IRB-approved extraction of patient medical record data from an institutional repository of prospectively maintained data, we verified a database of EC and GEJC patients diagnosed at a US tertiary care center between 01/01/2006 and 12/31/2013. When insufficient diagnostic clinical information was present, patients were excluded. Patient and tumor qualities were quantified and subjected to parameters of tumor diameter (≥2cm, <5cm) and maximum standardized uptake value (≥6) to observe potential characteristics of a patient population eligible for this novel BgRT mechanism. Results: Thirty patients met tumor size and FDG uptake criteria for BgRT therapy out of an overall patient cohort of 90 patients. A significantly greater proportion of patients within the BgRT-eligible cohort presented with esophageal tumors (83.3%) compared to non-eligible patients (58.3%, P=0.0177). Otherwise, there was no significant variation of patient sex, race, tumor histology, tumor stage, comorbidity score, and pre-treatment weight loss between patients eligible and not eligible for BgRT therapy. Conclusions: After applying current boundaries of tumor size and radiotracer uptake for effective BgRT intervention, we observed broad applicability of the novel treatment modality across EC/ GEJC patients of varying characteristics and tumor qualities. The high eligibility of patients with tumors located within the esophagus supports further investigation of BgRT in their management. [Table: see text]

Clinical characteristics of patients with non-small cell lung cancer eligible for biology-guided radiotherapy.

e20523 Background: Biology-guided radiotherapy (BgRT) is a novel radiotherapy modality that uses real-time positron emission tomography (PET) to guide radiotherapy beamlets. BgRT recently received FDA clearance for clinical use using the 18F FDG radiotracer for the treatment of tumors in lung and bone. We sought to identify non-small cell lung cancer (NSCLC) patients who may be candidates for BgRT based on diagnostic FDG PET/CT imaging. Methods: We conducted an IRB-approved retrospective assessment of NSCLC patients diagnosed between 01/01/2006 and 12/31/2013 at a tertiary care center in the United States. Patient and tumor characteristics were verified by an institutional data repository team and through electronic medical record review. Patients were excluded from analysis when documentation of clinical/ imaging findings was insufficient. Frequency of characteristics were interpreted with and without tumor diameter and maximum standardized uptake value (SUVMax) parameters, to confirm eligibility for BgRT on this novel radiotherapy device. Results: Of the 686 patients eligible for analysis, 523 presented with tumor SUVMax of ≥6 on diagnostic PET imaging and 360 presented with tumor diameters of at least 2 cm and below 5 cm. Of the 277 patients who met both SUVMax and size parameters, respectively, 75 (27.1%), 145 (52.3%), and 57 (20.6%) presented with squamous, adenocarcinoma, or other/unknown histology, and 77 (27.9%), 29 (10.5%), 92 (33.3%), and 78 (28.3%) presented with stage I, II, III, or IV tumors (AJCC 7th edition). Conclusions: Theoretical applicability of biology-guided radiotherapy was observed in our NSCLC patient cohort. Therefore, despite current limitations of radiotracer uptake thresholds and tumor size restrictions, there is broad potential applicability of this treatment modality, either as a single modality treatment or in conjunction with active systemic therapy. [Table: see text]

PD-0908 Suitability of biology-guided radiotherapy for metastatic renal cell carcinoma directed by PSMA PET

PD-0908 Suitability of biology-guided radiotherapy for metastatic renal cell carcinoma directed by PSMA PET

MO-0876 BIOGUIDE-X: A First-in-Human Study of the Performance and Safety of Biology-Guided Radiotherapy

MO-0876 BIOGUIDE-X: A First-in-Human Study of the Performance and Safety of Biology-Guided Radiotherapy

Evaluation of fan-beam kilovoltage computed tomography image quality on a novel biological-guided radiotherapy platform.

A recently developed biology-guided radiotherapy platform, equipped with positron emission tomography (PET) and computed tomography (CT), provides both anatomical and functional image guidance for radiotherapy. This study aimed to characterize performance of the kilovoltage CT (kVCT) system on this platform using standard quality metrics measured on phantom and patient images, using CT simulator images as reference. Image quality metrics, including spatial resolution/modular transfer function (MTF), slice sensitivity profile (SSP), noise performance and image uniformity, contrast-noise ratio (CNR) and low-contrast resolution, geometric accuracy, and CT number (HU) accuracy, were evaluated on phantom images. Patient images were evaluated mainly qualitatively. On phantom images the MTF10% is about 0.68 lp/mm for kVCT in PET/CT Linac. The SSP agreed with nominal slice thickness within 0.7mm. The diameter of the smallest visible target (1% contrast) is about 5mm using medium dose mode. The image uniformity is within 2.0 HU. The geometric accuracy tests passed within 0.5mm. Relative to CT simulator images, the noise is generally higher and the CNR is lower in PET/CT Linac kVCT images. The CT number accuracy is comparable between the two systems with maximum deviation from the phantom manufacturer range within 25 HU. On patient images, higher spatial resolution and image noise are observed on PET/CT Linac kVCT images. Major image quality metrics of the PET/CT Linac kVCT were within vendor-recommended tolerances. Better spatial resolution but higher noise and better/comparable low contrast visibility were observed as compared to a CT simulator when images were acquired with clinical protocols.

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer.

Lutetium-177 [177Lu]-PSMA-617 is a targeted radioligand that binds to prostate-specific membrane antigen (PSMA) and delivers radiation to metastatic prostate cancer. The presence of PSMA-negative/FDG-positive metastases can preclude patients from being eligible for this treatment. Biology-guided radiotherapy (BgRT) is a treatment modality that utilises tumour PET emissions to guide external beam radiotherapy. The feasibility of combining BgRT and Lutetium-177 [177Lu]-PSMA-617 for patients with PSMA-negative/FDG-positive metastatic prostate cancer was explored. All patients excluded from the LuPSMA clinical trial (ID: ANZCTR12615000912583) due to PSMA/FDG discordance were retrospectively reviewed. A hypothetical workflow where PSMA-negative/FDG-positive metastases would be treated with BgRT whilst PSMA-positive metastases would be treated with Lutetium-177 [177Lu]-PSMA-617 was considered. Gross tumour volume (GTV) of PSMA-negative/FDG-positive tumours were delineated on the CT component of the FDG PET/CT scan. Tumours were deemed suitable for BgRT if (1) normalised SUV (nSUV), defined as the ratio of maximum SUV (SUVmax) inside the GTV to mean SUV inside a 5 mm/10 mm/20mm margin expansion of the GTV, was larger than a pre-specified nSUV threshold and (2) there was no PET avidity inside the margin expansion. In 75 patients screened for Lutetium-177 [177Lu]-PSMA-617 treatment, 6 patients were excluded due to PSMA/FDG discordance and 89 PSMA-negative/FDG-positive targets were identified. GTV volumes ranged from 0.3 cm3 to 186 cm3 (median GTV volume = 4.3 cm3, IQR = 2.2 cm3 - 7.4 cm3). SUVmax inside GTVs ranged between 3 and 12 (median SUVmax = 4.8, IQR = 3.9 - 6.2). With nSUV ≥ 3, 67%/54%/39% of all GTVs were suitable for BgRT within 5 mm/10 mm/20mm from the tumour. Bone and lung metastases were the best candidates for BgRT (40%/27% of all tumours suitable for BgRT with nSUV ≥ 3 within 5mm from the GTV were bone/lung GTVs). Combined BgRT/Lutetium-177 [177Lu]-PSMA-617 therapy is feasible for patients with PSMA/FDG discordant metastases.

Feasibility of biology-guided radiotherapy for metastatic renal cell carcinoma driven by PSMA PET imaging

BackgroundBiology-guided radiotherapy (BgRT) is a novel treatment where the detection of positron emission originating from a volume called the biological tracking zone (BTZ) initiates dose delivery. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is a novel imaging technique that may improve patient selection for metastasis-directed therapy in renal cell carcinoma (RCC). This study aims to determine the feasibility of BgRT treatment for RCC. Material and methodsAll consecutive patients that underwent PSMA PET/CT scan for RCC staging at our institution between 2014 and 2020 were retrospectively considered for inclusion. GTVs were contoured on the CT component of the PET/CT scan. The tumor-to-background ratio was quantified from the normalized standardized uptake value (nSUV), defined as the ratio between SUVmax inside the GTV and SUVmean inside the margin expansion. Tumors were classified suitable for BgRT if (1) nSUV was greater or equal to an nSUV threshold and (2) if the BTZ was free of any PET-avid region other than the tumor. ResultsOut of this cohort of 83 patients, 47 had metastatic RCC and were included in this study. In total, 136 tumors were delineated, 1 to 22 tumors per patient, mostly in lung (40%). Using a margin expansion of 5 mm/10 mm/20 mm and nSUV threshold = 3, 66%/63%/41% of tumors were suitable for BgRT treatment. Uptake originating from another tumor, the kidney, or the liver was typically inside the BTZ in tumors judged unsuitable for BgRT. ConclusionsMore than 60% of tumors were found to be suitable for BgRT in this cohort of patients with RCC. However, the proximity of PET-avid organs such as the liver or the kidney may affect BgRT delivery.

Image-mode performance characterisation of a positron emission tomography subsystem designed for Biology-guided radiotherapy (BgRT).

In this study, we characterise the imaging-mode performance of the positron emission tomography (PET) subsystem of the RefleXion X1 machine using the NEMA NU-2 2018 standard. The X1 machine consists of two symmetrically opposing 900 arcs of PET detectors incorporated into the architecture of a ring-gantry linear accelerator rotating up to 60 RPM. PET emissions from a tumour are detected by the PET detectors and used to guide the delivery of radiation beam. Imaging performance of the PET subsystem on X1 machine was evaluated based on sensitivity of the PET detectors, spatial resolution, count-loss performance, image quality, and daily system performance check. PET subsystem sensitivity was measured as 0.183 and 0.161 cps/kBq at the center and off-center positions, respectively. Spatial resolution: average FWHM values of 4.3, 5.1, and 6.7 mm for the point sources at 1, 10, and 20 cm off center, respectively were recorded. For count loss, max NECR: 2.63 kcps, max true coincidence rate: 5.56 kcps, and scatter fraction: 39.8%. The 10 mm sphere was not visible. Image-quality contrast values were: 29.6%, 64.9%, 66.5%, 81.8%, 81.2%, and background variability: 14.8%, 12.4%, 10.3%, 8.8%, 8.3%, for the 13, 17, 22, 28, 37 mm sphere sizes, respectively. When operating in an imaging mode, the spatial resolution and image contrast of the X1 PET subsystem were comparable to those of typical diagnostic imaging systems for large spheres, while the sensitivity and count rate were lower due to the significantly smaller PET detector area in the X1 system. Clinical efficacy when used in BgRT remains to be validated. This is the first performance evaluation of the PET subsystem on the novel BgRT machine. The dual arcs rotating PET subsystem on RefleXion X1 machine performance is comparable to those of the typical diagnostic PET system based on the spatial resolution and image contrast for larger spheres.

Combined Biology-Guided Radiotherapy and Lutetium PSMA Treatment in Metastatic Prostate Cancer

<h3>Purpose/Objective(s)</h3> Biology-guided radiotherapy (BgRT) is a new technology that delivers radiation based on positron emission tomography (PET) signal. Lutetium-177 (¹⁷⁷Lu) prostate-specific membrane antigen (PSMA) is a novel theranostic treatment that demonstrated high response and low toxicities in patients with metastatic castrate-resistant prostate cancer. However, patients may be excluded from this theranostic treatment due to discordance between Gallium-68 (⁶⁸Ga)-PSMA-11 and ¹⁸F-fluorodeoxyglucose (FDG) PET uptake at screening. Using the theranostic treatment alone on these excluded patients would result in untreated FDG-only avid tumor deposits. However, FDG-only avid tumor deposits may be treated with BgRT. This study investigates the feasibility of a combined theranostic/BgRT treatment to excluded patients with discordant uptake. <h3>Materials/Methods</h3> Patients excluded from the LuPSMA clinical trial (ID ANZCTR12615000912583) were retrospectively reviewed. A hypothetical hybrid treatment was considered in which BgRT would supplement ¹⁷⁷Lu-PSMA treatment in discordant FDG-avid tumors. In this treatment, FDG-only avid tumors would be treated with BgRT whereas PSMA-avid tumors would be treated with LuPSMA treatment (100% efficacy was assumed). PSMA PET uptake was mapped to the FDG PET frame of reference using deformable registration between the CT-component of the two PET scans. Gross tumor volume (GTV) of FDG-only avid tumors were contoured on the CT-component of the FDG PET/CT scan by a radiation oncologist. Biological tracking zones (BTZ) for BgRT dose delivery were generated from GTV outer margin expansion of 5 mm / 10 mm / 20 mm. Normalized SUV (nSUV) was calculated as the ratio of the maximum SUV inside the GTV to the mean of SUV inside the outer margin expansions. Tumors were considered suitable to BgRT if nSUV was larger than 3 and if the normal tissue surrounding the tumor was free of any PET signal inside the BTZ. <h3>Results</h3> Of 75 patients screened for LuPSMA treatment, 7 patients had discordant PSMA and FDG uptake, 6 of which had FDG-only avid tumors and were included in this study. In these 6 patients, 89 potential BgRT targets were identified. GTV volumes ranged from 0.3 cm³ to 186 cm³ (median GTV volume = 4.3 cm³, IQR = 2.2 cm³ – 7.4 cm³). SUVmax inside GTVs was between 3 and 12 (median SUVmax = 4.8, IQR = 3.9 – 6.2). With nSUV ≥ 3, 67% / 48% / 28% of all GTVs were free of FDG uptake within 5 mm / 10 mm / 20 mm from the tumor and therefore suitable to BgRT. Bone and lung sites were the best candidates for BgRT (27% / 18% of all tumors were bone / lung GTVs with nSUV ≥ 3 and were isolated from PET uptake within 5 mm). <h3>Conclusion</h3> 67% of FDG-only avid tumors were suitable to BgRT treatment inside a BTZ generated from a margin expansion of 5 mm. BgRT treatment to FDG-only avid tumor in combination with Lutetium PSMA theranostic treatment is therefore feasible.

BgRT Motion Management Maintains Target Dose Coverage for Respiratory and Non-Respiratory Motion

<h3>Purpose/Objective(s)</h3> Biology-guided radiotherapy (BgRT) uses outgoing emissions after administration of an injected radiotracer to dynamically guide the delivery of radiation treatment to PET-avid targets. In this study, we evaluated the tracking performance of FDG-guided BGRT for two potential types of motion management (respiratory and non-respiratory (gastrointestinal)) while exploring different target shapes: spherical and non-spherical. BgRT is designed to ensure target coverage while keeping organ-at-risk (OAR) doses low. <h3>Materials/Methods</h3> A large custom anthropomorphic phantom with 2 robotic articulating arms was used to place a target and organ-at-risk inside a 27-liter water filled cavity. The targets consisted of an integrated ion chamber inside a 3D printed 22 mm sphere or a small non-spherical ovoid shape filled with FDG. The hot FDG-filled OAR consisted of either a 3D printed large C-shape annulus (mimicking a heart), large ovoid (mimicking a kidney), or a 30 mm sphere, all with integrated ion chambers. Both the 3D printed target and the OAR were filled with an 8:1 concentration ratio versus the water background. Three different 10 Gy/fraction treatment plans with two different target shapes and realistic nearby OARs were created with a 5 mm margin added to the CTV to generate the PTV. 3D printed targets and OARs were loaded with EBT-XD radiographic film. A 3D elliptical motion trajectory with breathing induced hysteresis with a maximum amplitude of +/- 12 mm was used for the respiratory motion model. An asymmetric slow-moving drift waveform with long-step shifts of +13/-5mm mm was used for the non-respiratory (gastrointestinal) motion model. Dosimetric results were evaluated based on 2-dimensional comparisons between measured film and planned dose distributions for the target and OAR. BgRT must maintain a prescription dose margin greater than 2 mm on the CTV for the three different motion experiments. Also, ion-chamber point dose and maximum film dose on the OAR must be within bounds predicted by the treatment planning system. <h3>Results</h3> BgRT was able to meet minimum margin requirements (a margin loss < 3mm) and meet prescription dose coverage in both motion management scenarios while maintaining OAR dose limits within the plan predicted bounds (see Table 1). <h3>Conclusion</h3> BgRT is able to provide motion management in complex cases that is agnostic to the type of motion. BgRT is able to maintain the PTV coverage with less than 3 mm reduction from the original 5mm margin.

Robustness of Biology-Guided Radiotherapy Delivery to PET Biodistribution Changes within Target

<h3>Purpose/Objective(s)</h3> Biology-guided radiotherapy (BgRT) is a novel tracked dose delivery modality that uses positron emission tomography (PET) emissions to deliver hypofractionated planned fluence to the target. This study evaluated PET biodistribution changes within target during BgRT delivery. <h3>Materials/Methods</h3> Two phantom experiments were designed to evaluate the FDG signal variations and dosimetric effects under stationary target and moving target on a non-clinical investigational radiotherapy system. For the stationary case, a custom built cylindrical 4-D detector phantom insert with a spherical target of 22 mm in diameter containing 4 quadrants that can be filled independently was used to mimic homogenous and non-homogenous FDG uptake conditions. A C-shape insert was used as a PET avid OAR. For simulating PET signal loss within tumor: BgRT plan was created for the spherical target with all quadrants filled and the plan was delivered when ¾ volume of the target was PET-avid. For the PET signal gain within tumor scenario: BgRT plan was created for the same spherical CTV structure where ¾ volume of the target was filled with FDG, mimicking non-homogeneous uptake, and delivered to a full volume PET-avid target. The dosimetric accuracy of BgRT delivery was evaluated using 3%/3 mm Gamma criterion using 4-D detector measurements. Target biodistribution changes under motion was evaluated by creating a BgRT plan with an FDG filled 26 mm diameter spherical target as a CTV and C-shape OAR moving independently (target:3D respiratory, OAR: sinusoidal motions) within a large water filled phantom. During BgRT delivery the PET avid target insert was switched to a smaller 22 mm spherical insert, simulating 40% uniform PET distribution reduction within 26mm CTV. For the moving target experiment, BgRT delivered dose was evaluated using the radiographic film under the condition of CTV coverage ≥97% and maximum dose ≤130%. For all the experiments, the target and the C-shaped OAR were filled with FDG at a ratio of 8:1 with respect to the water background mimicking normal tissue uptake, and a 5 mm CTV to PTV expansion to be targeted with a prescription of 50Gy in 5 fractions. <h3>Results</h3> For the stationary scenarios, BgRT delivery at remissive and progressive conditions achieved gamma pass-rate of 93.2 and 97.7%, respectively. The CTV coverage goals for the motion experiment were met where the minimum CTV dose was 103.3% and the maximum dose was 123.8%. <h3>Conclusion</h3> This study evaluated the biodistribution changes within CTV from planning to delivery suggesting the BgRT delivery is robust with respect to daily variations of PET signal within the PTV under these experimental conditions. Clinical feasibility of BgRT needs further evaluation.

Comparison of Diagnostic PET and 4D CT-Based Tumor Delineation for Oligometastatic Lung Tumors

<h3>Purpose/Objective(s)</h3> Stereotactic body raiation therapy (SBRT) is increasingly used to treat oligometastatic tumors. To account for internal motion, 4D-CT is commonly used for lung SBRT. Biology-guided radiotherapy (BgRT) is an emerging concept that may allow for reduction of treatment volumes using positron emission tomography (PET) signal guidance. Benchtop testing of BgRT technology suggests target delineation on a single respiratory phase with 5 mm biology-guided margin may be sufficient, however this has not been clinically validated. We tested our hypothesis that PET-based tumor delineation would result in smaller target volumes than 4D-CT. <h3>Materials/Methods</h3> We retrospectively reviewed a single-institution lung radiotherapy database to identify patients with oligometastatic lung tumors treated with ablative doses of biologically effective dose (BED10) >=100 Gy. We included patients treated from 2015-2020 with a diagnostic PET performed within 30 days of CT simulation. Tumors were contoured on the diagnostic PET using an auto-threshold of 40% of the lesion SUVmax, followed by manual editing to include CT-based tumor accounting for possible PET signal misregistration. A 5 mm isotropic expansion was applied to generate the planning target volume (PTV). We compared these to existing 4D CT-based tumor volumes accounting for internal motion and their associated PTVs. <h3>Results</h3> Of 102 patients with oligometastatic lung tumors, we included 13 patients with 15 lung tumors. There were 7 female and 6 male patients, with a median age of 72 (range 52 – 89) at the time of treatment. Primary tumor types included 4 colorectal, 2 head and neck, 1 non-small cell lung cancer, 1 melanoma, and 5 other cancer types. Patients were treated to 50 to 54 Gy in 3 to 5 fractions. Median time from diagnostic PET scan to CT simulation was 17 days (range 0 – 27). Median lesion diameter was 1.2 cm (IQR 0.9 – 1.7) with median SUVmax of 5.4 (IQR 4.0 – 7.7). Diagnostic PET-based tumor contours had a median volume of 2.5 cc (IQR 1.7 – 3.1 cc), whereas 4D CT-based tumor contours had a median volume of 3.0 cc (IQR 2.4 – 9.9 cc). Diagnostic PET-based PTV had a median volume of 10.4 cc (IQR 8.4 – 12.6 cc), whereas 4D CT-based PTV had a median volume of 11.8 cc (IQR 10.8 – 31.5). <h3>Conclusion</h3> Diagnostic PET-based tumor delineation resulted in smaller tumor and planning target volumes compared to 4D-based tumor delineation. This data will serve as a benchmark for future research focusing on imaging modality concordance and clinical impact of reduced biology-guided margins in BgRT for oligometastatic patients undergoing lung SBRT.

Patient-Specific Auto-Segmentation of Target and OARs via Deep Learning on Daily Fan-Beam CT for Adaptive Prostate Radiotherapy

<h3>Purpose/Objective(s)</h3> Contouring the target and organs at risk (OARs) of the treated patient in each fraction is a key step of daily adaptive radiotherapy. We designed a patient-specific deep learning study to improve the auto-segmentation performance for adaptive prostate radiotherapy, by leveraging the daily image-guidance fan-beam CT images of the specific patient available in the current IGRT workflow. <h3>Materials/Methods</h3> Our institution has set up a newly developed biology-guided radiotherapy (BgRT) system enabling high-quality fan-beam CT imaging for daily treatments. The data of the first prostate patient treated with this system including 26 daily fan-beam CT scans were utilized in this study. A population network was first trained for the auto-segmentation of the prostate and seven pelvic OARs, based on a population dataset containing 56 different patient cases treated on the regular Linac. The pre-trained population network was intentionally fine-tuned to adapt to this specific patient with a transfer learning method. The selected OARs of this patient were contoured by two radiation oncologists on the initial treatment planning and all sets of daily fan-beam CT images as the ground truth for the patient-specific learning. Three different fine-tuning methods, i.e., fine-tuning the last convolution layer, the last convolution block and the whole network were analyzed. A longitudinal study was conducted by exploring the relationship between the auto-segmentation performance and the number of the sequential prior data used for learning. The performance of the patient-specific network was compared with the population network as well as the clinical rigid registration method to highlight its efficiency in radiotherapy practice. <h3>Results</h3> The Dice similarity coefficient (DSC) results of the proposed patient-specific network were 0.882, 0.934, 0.864, 0.827, 0.952, 0.954, 0.921 and 0.904 for the prostate, bladder, rectum, seminal vesicle, left and right femoral head, bowel and lymph nodes, respectively, outperforming the population network (mean DSC of 0.627) and the clinical registration method (mean DSC of 0.716). The whole network fine-tuning method outperformed the other two fine-tuning methods, showing it is more effective in this study. The contouring accuracy of the patient-specific network gradually increased with the increment of longitudinal training cases and approached saturation with more than four training cases. <h3>Conclusion</h3> This study proposes an accurate auto-segmentation method based on the patient-specific deep learning for adaptive prostate radiotherapy. By utilizing the image and contour similarity between the treatment fractions, the patient-specific auto-segmentation could outperform the common population network and the clinical registration method by a large margin, and thus is promising to facilitate more precise radiotherapy based on the new BgRT system.

Systematic Study of Patient-Specific Organs at Risk Auto-Segmentation on Daily kVCT Images for Adaptive Head and Neck Radiotherapy

<h3>Purpose/Objective(s)</h3> A newly developed biology-guided radiotherapy (BgRT) system has been set up in our institution, which enables high-quality kVCT imaging for each treatment fraction. This study explored deep learning-based patient-specific auto-segmentation to facilitate adaptive radiotherapy, based on data of the first head and neck patient case treated with this new system. <h3>Materials/Methods</h3> The esophagus, larynx, and pharynx were selected as the organs at risk (OAR) for auto-segmentation analysis. A population network was first learned on a population dataset, which contains 67 different patient cases from conventional intensity-modulated radiotherapy (IMRT). Then the pre-trained population network was adapted to this specific patient using a transfer learning method based on the longitudinal data from the initial treatment planning and 17 sets of daily image guidance kVCT images. The selected OARs were contoured by a radiation oncologist on 18 sets of images as the ground truth. The performance of the patient-specific network was compared with the population network as well as the clinical rigid registration method. The corresponding dosimetric impacts resulting from different segmentation and registration methods were also investigated. <h3>Results</h3> The initial Dice similarity coefficient (DSC) results of the population network on the patient-specific evaluation set were 0.821, 0.537, 0.739 for esophagus, larynx, and pharynx respectively, and they were markedly improved to 0.887, 0.889, 0.850 with the proposed patient-specific network. These results also outperformed the results of 0.670, 0.792, 0.709 with the registration-based method in current clinical practice. The contouring accuracy of the patient-specific network gradually increased with the increase of longitudinal training cases and approached saturation with more than six training cases. The qualification result also shows the population network was adapted to the specific manual contouring style after the patient-specific learning. Discrepancies of the mean doses by using the manual contour and the patient-specific auto-segmentation result were -1.29%, -1.05%, -0.13% for the three OARs respectively, better than the differences of 4.80%, -6.56%, -1.84% using the registration contour. The OAR dose underestimation in some treatment fractions based on the registration contour was markedly improved when using the patient-specific auto-segmentation result. <h3>Conclusion</h3> Auto-segmentation of daily kVCT images was studied based on patient-specific learning to facilitate future adaptive radiotherapy. Compared with the common population network and the clinical registration method, the patient-specific network could achieve a much better contouring and dosimetric accuracy and thus is promising to become a powerful tool in adaptive radiotherapy applications.

IMRT and SBRT Treatment Planning Study for the First Clinical Biology-Guided Radiotherapy System

<h3>Purpose/Objective(s)</h3> The first clinical biology-guided radiation therapy (BgRT) system – RefleXion^TM X1 - was installed and commissioned for clinical use at our institution. This study aimed at evaluating the treatment plan quality and delivery efficiency for IMRT/SBRT cases without PET-guidance. <h3>Materials/Methods</h3> Forty-two patient plans across six cancer sites (conventionally-fractionated lung, head and neck, anus, prostate, brain, and lung SBRT) planned with the Eclipse^TM treatment planning system (TPS) and treated with either a TrueBeam® or Trilogy® were selected for this retrospective study. For each Eclipse VMAT plan, two corresponding plans were generated on the X1 TPS with 10 mm jaws (X1 10mm) and 20 mm jaws (X1 20mm) using our institutional planning constraints. All clinically relevant metrics in this study, including PTV D95%, PTV D2%, Conformity Index (CI), R50, organs- at-risk (OAR) constraints, and beam-on time were analyzed and compared between 126 VMAT and RefleXion plans using paired t-tests. <h3>Results</h3> All but three planning metrics were either equivalent or superior for the X1 10mm plans as compared to the Eclipse VMAT plans across all planning sites investigated. The Eclipse VMAT and X1 10mm plans generally achieved superior plan quality and sharper dose fall-off superior/inferior to targets as compared to the X1 20mm plans, however, the X1 20mm plans were still considered acceptable for treatment. Strong correlation was observed between the TPS-calculated beam-on time and PTV length in the superior-inferior direction for the X1 10mm (<i>R</i>² = 0<i>.</i>87) and X1 20mm (<i>R</i>² = 0<i>.</i>85) plans. On average, the required beam-on time increased by a factor of 1.6 across all sites for X1 10mm compared to X1 20mm plans. <h3>Conclusion</h3> Clinically acceptable IMRT/SBRT treatment plans were generated with the X1 TPS for both the 10 mm and 20 mm jaw settings. The X1 10mm plans were equivalent or superior to the Eclipse VMAT plans, however the beam-on times were longer.

Intensity Modulated Radiotherapy on a Novel Ring Gantry-Based Linac with Integrated Dual PET-CT Imaging Systems: Dosimetric Plan Comparison and Initial Clinical Delivery Experience

<h3>Purpose/Objective(s)</h3> This study aims to report our initial clinical experience on using a new external-beam radiotherapy delivery system on a ring gantry with dual PET-CT imaging capabilities for IMRT treatments at different anatomical sites. The study also evaluates the system's plan quality compared to an existing ring gantry-based Linac. This new external-beam radiotherapy delivery system has the potential to be used for biology-guided radiotherapy. <h3>Materials/Methods</h3> We performed a single-institution retrospective review of patients treated on the machine since commissioning. The initial five patients treated to a thoracic site and five patients treated to a pelvic site were included in this study. The dose per fraction ranged from 1.8 to 3.0 Gy. The treatment plans for the machine used a 2-cm jaw size along the longitudinal direction and used the IMRT delivery mode. A 64-leaf binary MLC was used to modulate a flattening filter free 6-MV photon beam. A helical tomotherapy plan (HT plan) using a 2.5-cm jaw size was generated for each RFX plan to serve as the backup plan in clinical treatments. Dosimetric parameters used in institutional treatment protocols were compared between RFX plans and HT plans. Daily delivery records were reviewed, and actual beam-on time was compared between the two machine types. <h3>Results</h3> On average, 12 dosimetric parameters (range: 7 – 14) for critical organs and the primary PTV were used in each treatment plan as clinically relevant planning optimization parameters and were analyzed in this study. Among the critical organ dose parameters, 19 (22.4%) dosimetric parameters were lower by more than 10% in the study's plans compared to the HT plans, while 11 (12.9%) dosimetric parameters were higher by more than 10% in the study's plans compared to the HT plans. The other dosimetric parameters had less than 10% or no clinically relevant difference between the two plans. There was no statistically significant difference in integrated dose between the new machine and HT plans. All the plans were normalized so that the prescription dose covered 95% of the primary planning target volume (PTV). The average D_mean of the primary PTV were 103.5±1.1% and 102.6±0.8% of the prescription dose in the new external-beam radiotherapy delivery system and HT plans, respectively, and the average D(1%) of the primary PTV (dose covering the hottest 1% of the PTV) were 107.1±2.0% and 105.2%±1.6% in the new external-beam radiotherapy delivery system and HT plans, respectively (two-tailed p-value = 0.06 in the paired t-test). The beam-on time was not significantly different between the two machines. The average daily beam-on time was 438.8±151.2 seconds and 427.6±183.1 seconds with the new external-beam radiotherapy delivery system and HT systems, respectively (two-tailed p-value = 0.76 in the paired t-test). <h3>Conclusion</h3> Our initial clinical experience with the external-beam radiotherapy delivery system showed that image guided IMRT could be delivered to different anatomical sites with adequate clinical workflow efficiency. The new machine achieved clinically comparable treatment plan quality compared to helical tomotherapy. The beam-on time was comparable to that on helical tomotherapy.

The potential of biology-guided radiation therapy in thoracic cancer: A preliminary treatment planning study.

PurposeWe investigated the feasibility of biology-guided radiotherapy (BgRT), a technique that utilizes real-time positron emission imaging to minimize tumor motion uncertainties, to spare nearby organs at risk.MethodsVolumetric modulated arc therapy (VMAT), intensity-modulated proton (IMPT) therapy, and BgRT plans were created for a paratracheal node recurrence (case 1; 60 Gy in 10 fractions) and a primary peripheral left upper lobe adenocarcinoma (case 2; 50 Gy in four fractions).ResultsFor case 1, BgRT produced lower bronchus V40 values compared to VMAT and IMPT. For case 2, total lung V20 was lower in the BgRT case compared to VMAT and IMPT.ConclusionsBgRT has the potential to reduce the radiation dose to proximal critical structures but requires further detailed investigation.

Treatment planning system commissioning of the first clinical biology-guided radiotherapy machine.

PurposeThe RefleXion X1 is a novel radiotherapy machine designed for image‐guided radiotherapy (IGRT) and biology‐guided radiotherapy (BgRT). Its treatment planning system (TPS) generates IMRT and SBRT plans for a 6MV‐FFF beam delivered axially via 50 firing positions with the couch advancing every 2.1 mm. The purpose of this work is to report the TPS commissioning results for the first clinical installation of RefleXion™ X1.MethodsCT images of multiple phantoms were imported into the RefleXion TPS to evaluate the accuracy of data transfer, anatomical modeling, plan evaluation, and dose calculation. Comparisons were made between the X1, Eclipse™, and MIM™. Dosimetric parameters for open static fields were evaluated in water and heterogeneous slab phantoms. Representative clinical IMRT and SBRT cases were planned and verified with ion chamber, film, and ArcCHECK@ measurements. The agreement between TPS and measurements for various clinical plans was evaluated using Gamma analysis with a criterion of 3%/2 mm for ArcCHECK@ and film. End‐to‐end (E2E) testing was performed using anthropomorphic head and lung phantoms.ResultsThe average difference between the TPS‐reported and known HU values was −1.4 ± 6.0 HU. For static fields, the agreements between the TPS‐calculated and measured PDD10, crossline profiles, and inline profiles (FWHM) were within 1.5%, 1.3%, and 0.5 mm, respectively. Measured output factors agreed with the TPS within 1.3%. Measured and calculated dose for static fields in heterogeneous phantoms agreed within 2.5%. The ArcCHECK@ mean absolute Gamma passing rate was 96.4% ± 3.4% for TG 119 and TG 244 plans and 97.8% ± 3.6% for the 21 clinical plans. E2E film analysis showed 0.8 mm total targeting error for isocentric and 1.1 mm for off‐axis treatments.ConclusionsThe TPS commissioning results of the RefleXion X1 TPS were within the tolerances specified by AAPM TG 53, MPPG 5.a, TG 119, and TG 148. A subset of the commissioning tests has been identified as baseline data for an ongoing QA program.

Feasibility of biology-guided radiotherapy using PSMA-PET to boost to dominant intraprostatic tumour

BackgroundBiology-guided radiotherapy (BgRT) delivers dose to tumours triggered from positron emission tomography (PET) detection. Prostate specific membrane antigen (PSMA) PET uptake is abundant in the dominant intraprostatic lesion (DIL). This study investigates the feasibility of BgRT to PSMA-avid subvolume in the prostate region. MethodsPatients enrolled in the prospective randomized trial ProPSMA at our institution were included (ID: ANZCTR12617000005358). Gross tumour volumes (GTVs) were delineated on the PET component of a PET/CT scan from a standardized uptake value (SUV) threshold technique. Suitability for BgRT requires a strong signal-to-background ratio with a surrounding tissue free of significant PSMA uptake. The signal-to-background ratio was quantified from the calculation of the normalized SUV (nSUV), defined as the ratio between SUVmax within the GTV and SUVmean inside a 3D margin expansion of the GTV. The PSMA distribution surrounding the tumour was quantified as a function of the distance from the GTV. ResultsIn this cohort of 84 patients, 83 primary tumours were included. Prostate volume ranged from 19 cm3 to 148 cm3 (median = 52 cm3; IQR = 39 cm3 – 63 cm3). SUVmax inside the prostate was between 2 and 125 (median = 19; IQR = 11 – 30). More than 50% of GTVs generated with threshold between 25%SUVmax (median volume = 10.0 cm3; IQR = 4.5 cm3 – 20.0 cm3) and 50%SUVmax (median volume = 1.9 cm3; IQR = 1.1 cm3 – 3.8 cm3) were suitable for BgRT by using nSUV ≥ 3 and a margin expansion of 5 mm. ConclusionsIt is feasible to identify GTVs suitable for BgRT in the prostate. These GTVs are characterized by a strong signal-to-background ratio and a surrounding tissue free of PSMA uptake.

A detailed process map for clinical workflow of a new biology-guided radiotherapy (BgRT) machine.

PurposeBiology‐guided radiotherapy (BgRT) is a new external beam radiation therapy modality combining PET‐CT with a linear accelerator that has the potential to track and treat one or more tumors in real‐time. The use of PET and radiopharmaceutical tracers introduces new processes that are different from the existing treatment processes. In this study, we have developed a process map for the clinical implementation of a prototype BgRT machine.MethodsA team of 13 members from various radiation therapy disciplines at our institution participated in developing a prospective process map for a prototype BgRT machine. The methodology provided by the AAPM TG 100 report was followed. In particular, the steps unique to the BgRT workflow, using hypofractionated stereotactic body radiation therapy with fluorodeoxyglucose radiolabeled with fluorine‐18 (FDG) to guide beam delivery, were analyzed.ResultsThe multi‐disciplinary team in the department of radiation oncology at our institution developed a prospective process map for the clinical BgRT workflow. By focusing on the appropriate level of detail, 15 major subprocesses, 133 steps, and 248 substeps were identified and the process map was agreed upon as being useful, implementable, and manageable. Seventy‐four steps from nine subprocesses, 55.6% of the whole process, were analyzed to be the BgRT unique steps. They originate mainly from: (1) acquiring multiple PET images at the BgRT machine with separate patient visits, (2) creating a unique biological treatment volume for BgRT plan (PTVBgRT), and (3) BgRT plan optimization and treatment delivery using PET images.ConclusionUsing BgRT to irradiate multiple metastases in the same session will impact clinical workflow, thus a graphical process map depicting the new clinical workflow with an appropriate level of detail is critical for efficient, safe, and high‐quality care. The prospective process map will guide the successful setup and use of the new BgRT system.