Image-guided Adaptive Radiotherapy Research Articles

Correlation of microscopic tumor extension with tumor microenvironment in esophageal cancer patients.

In the era of image-guided adaptive radiotherapy, definition of the clinical target volume (CTV) is achallenge in various solid tumors, including esophageal cancer (EC). Many tumor microenvironmental factors, e.g., tumor cell proliferation or cancer stem cells, are hypothesized to be involved in microscopic tumor extension (MTE). Therefore, this study assessed the expression of FAK, ILK, CD44, HIF-1α, and Ki67 in EC patients after neoadjuvant radiochemotherapy followed by tumor resection (NRCHT+R) and correlated these markers with the MTE. Formalin-fixed paraffin-embedded tumor resection specimens of ten EC patients were analyzed using multiplex immunofluorescence staining. Since gold fiducial markers had been endoscopically implanted at the proximal and distal tumor borders prior to NRCHT+R, correlation of the markers with the MTE was feasible. In tumor resection specimens of EC patients, the overall percentages of FAK+, CD44+, HIF-1α+, and Ki67+ cells were higher in tumor nests than in the tumor stroma, with the outcome for Ki67+ cells reaching statistical significance (p < 0.001). Conversely, expression of ILK+ cells was higher in tumor stroma, albeit not statistically significantly. In three patients, MTE beyond the fiducial markers was found, reaching up to 31 mm. Our findings indicate that the overall expression of FAK, HIF-1α, Ki67, and CD44 was higher in tumor nests, whereas that of ILK was higher in tumor stroma. Differences in the TME between patients with residual tumor cells in the original CTV compared to those without were not found. Thus, there is insufficient evidence that the TME influences the required CTV margin on an individual patient basis. BO-EK-148042017 and BO-EK-177042022 on 20.06.2022, DRKS00011886, https://drks.de/search/de/trial/DRKS00011886 .

Image quality characterization of an ultra-high-speed kilovoltage cone-beam computed tomography imaging system on an O-ring linear accelerator.

The quality of on-board imaging systems, including cone-beam computed tomography (CBCT), plays a vital role in image-guided radiation therapy (IGRT) and adaptive radiotherapy. Recently, there has been an upgrade of the CBCT systems fused in the O-ring linear accelerators called HyperSight, featuring a high imaging performance. As the characterization of a new imaging system is essential, we evaluated the image quality of the HyperSight system by comparing it with Halcyon 3.0 CBCT and providing benchmark data for routine imaging quality assurance. The HyperSight features ultra-fast scan time, a larger kilovoltage (kV) detector, a more substantial kV tube, and an advanced reconstruction algorithm. Imaging protocols in the two modes of operation, treatment mode with IGRT and the CBCT for planning(CBCTp) mode were evaluated and compared with Halcyon 3.0 CBCT. Image quality metrics, including spatial resolution, contrast resolution, uniformity, noise, computed tomography (CT) number linearity, and calibration error, were assessed using a Catphan and an electron density phantom and analyzed with TotalQA software. HyperSight demonstrated substantial improvements in contrast-to-noise ratio and noise in both IGRT and CBCTp modes compared to Halcyon 3.0 CBCT. CT number calibration error of HyperSight CBCTp mode (1.06%) closely matches that of a full CT scanner (0.72%), making it suitable for adaptive planning. In addition, the advanced hardware of HyperSight, such as ultra-fast scan time (5.9s) or 2.5 times larger heat unit capacity, enhanced the clinical efficiency in our experience. HyperSight represented a significant advancement in CBCT imaging. With its image quality, CT number accuracy, and ultra-fast scans, HyperSight has a potential to transform patient care and treatment outcomes. The enhanced scan speed and image quality of HyperSight are expected to significantly improve the quality and efficiency of treatment, particularly benefiting patients.

Towards tumour hypoxia imaging: Incorporating relative oxygen extraction fraction mapping of prostate with multi-parametric quantitative MRI on a 1.5T MR-linac.

Hypoxia plays a central role in tumour radioresistance. Reliable tumour hypoxia imaging would allow the monitoring of tumour response and a more personalized adaptation of radiotherapy planning. Here, we showed a proof of concept of the feasibility and repeatability of relative oxygen extraction fraction (rOEF) mapping of prostate using multi-parametric quantitative MRI (qMRI) achieved for the first time on a 1.5T MR-linac. T2, T2* relaxation times maps, and intra-voxel incoherent motion (IVIM) parametric maps mapping were computed on a 29 years old healthy volunteer. R2' and rOEF maps werecalculated based on a multi-parametric model. Long-term repeatability and repeatability coefficient (RC) were determined for each parameter according to QIBA recommendations. Mean values for the entire healthy prostate were 0.99 ± 0.14 × 10-3 mm/s2, 81 ± 2.1 × 10-3 mm/s2, 21.6 ± 3.6%, 92.7 ± 19.7 ms and 62.4 ± 17.3 ms for Dslow, Dfast, f, T2 and T2*, respectively. R2' and rOEF in the prostate were 6.1 ± 3.4 s-1 and 18.2 ± 10.1% respectively. The RC of rOEF was 4.43%. Long-term repeatability of quantitative parameters based on a test-retest ranged from 2 to 18%. qMRI parameters are measurable and repeatable on 1.5T MR LINAC. From T2, T2* and IVIM parameters maps, we were able to obtain a rOEF mapping of the prostate.These results are the first step to a non-invasive imaging of tumour hypoxia during radiotherapy leading to a biological image-guided adaptive radiotherapy.

Impact of cone-beam computed tomography artifacts on dose calculation accuracy for lung cancer.

To implement image-guided adaptive radiotherapy (IGART), many studies investigated dose calculations on cone-beam computed tomography (CBCT). A high HU accuracy is crucial for a high dose calculation accuracy and many imaging sites showed satisfactory results. It has been shown that the dose calculation accuracy for lung cancer lags behind. To examine why the dose calculation accuracy for lung is insufficient, the relative effects of the field-of-view (FOV), breathing motion, and scatter on dose calculation accuracy were studied. A framework was built to simulate CBCT scans for lung cancer patients by forward projecting repeat CT (rCT) scans for two scan geometries: small (SFOV) and medium FOV (MFOV). Breathing motion was modeled by applying a 4D deformation vector field to the mid-position rCT. Scatter was modeled by Monte-Carlo simulations with/without an anti-scatter grid (ASG). Simulated projections were reconstructed using filtered back-projection with/without scatter correction. In case of the SFOV, the CBCT images were patched with the planning CT scan in axial direction. The treatment plan was recalculated on the rCT and simulated CBCT. The mean Hounsfield unit (HU) difference (ΔHUmean ), the structural similarity index measure (SSIM), and γ metrics were calculated for the CBCT datasets of various imaging settings. The differences in HU, SSIM and dose calculation accuracy for CBCTs with and without breathing motion were negligible (mean ΔHUmean =6.4vs. 13.7, mean SSIM=0.941vs. 0.957, mean γ (ref=MFOV)=0.75). The SFOV resulted in a lower HU (mean ΔHUmean =-9.2vs. 13.7) and SSIM (mean SSIM=0.912vs. 0.957), and therefore in dose differences compared to the MFOV (mean γ=1.22). Scatter led to considerable discrepancies in all metrics. Adding only the ASG improved the results more than only applying a scatter correction algorithm. Combining ASG and scatter correction algorithm resulted in an even higher dose calculation accuracy. Scatter and FOV are the main contributors to dose inaccuracies and motion has only a minor effect on dose calculation accuracy. Therefore, utilizing an appropriate scatter correction and FOV is important to achieve sufficient dose calculation accuracy to facilitate IGART for lung.

The Lives Saved: A Literature Review on the Role of Radiotherapy Improving Prognosis in Cancer Patients

Radiotherapy, also known as radiation therapy, is a treatment modality based on the use of high energy rays or radioactive substances, to damage tumoral cells and halt their growth and division. It is an effective tool for treating cancer of different kinds for more than 100 years with remarkable outcomes for cancer patients. This technique is characterised by notable technological innovations and methodologies, enhanced precision and effectiveness. Initially, precision and efficacy of radiotherapy are improved by technological advancements, such as the development of linear accelerators and brachytherapy. As a result, Radiotherapy has transformed the prognosis for cancer patients enhancing survival rates and improving quality of life. Also, it offers targeted and personalized treatment with advancements in imaging techniques such as Intensity- Modulated Radiation Therapy (IMRT) and Stereotactic Body Radiation Therapy (SBRT) and innovations like Image-Guided Radiation Therapy (IGRT), Adaptive Radiotherapy (ART) and Artificial Intelligence (AI). Additionally, techniques like proton therapy result in reduced side effects and collateral damage. Although, among the challenges and future perspectives we note the issue of affordability and accessibility. Ongoing research into immunotherapy and nanotechnology and their synergy with radiation therapy shows potential for further improving treatment outcomes. In conclusion, the evolution of radiotherapy has been a transformative journey, reshaping the prognosis and outcomes for cancer patients

ART2Dose: A comprehensive dose verification platform for online adaptive radiotherapy.

Online adaptive radiotherapy (ART) involves the development of adaptable treatment plans that consider patient anatomical data obtained right prior to treatment administration, facilitated by cone-beam computed tomography guided adaptive radiotherapy (CTgART) and magnetic resonance image-guided adaptive radiotherapy (MRgART). To ensure accuracy of these adaptive plans, it is crucial to conduct calculation-based checks and independent verification of volumetric dose distribution, as measurement-based checks are not practical within online workflows. However, the absence of comprehensive, efficient, and highly integrated commercial software for secondary dose verification can impede the time-sensitive nature of online ART procedures. The main aim of this study is to introduce an efficient online quality assurance (QA) platform for online ART, and subsequently evaluate it on Ethos and Unity treatment delivery systems in our clinic. To enhance efficiency and ensure compliance with safety standards in online ART, ART2Dose, a secondary dose verification software, has been developed and integrated into our online QA workflow. This implementation spans all online ART treatments at our institution. The ART2Dose infrastructure comprises four key components: an SQLite database, a dose calculation server, a report generator, and a web portal. Through this infrastructure, file transfer, dose calculation, report generation, and report approval/archival are seamlessly managed, minimizing the need for user input when exporting RT DICOM files and approving the generated QA report. ART2Dose was compared with Mobius3D in pre-clinical evaluations on secondary dose verification for 40 adaptive plans. Additionally, a retrospective investigation was conducted utilizing 1302 CTgART fractions from ten treatment sites and 1278 MRgART fractions from seven treatment sites to evaluate the practical accuracy and efficiency of ART2Dose in routine clinical use. With dedicated infrastructure and an integrated workflow, ART2Dose achieved gamma passing rates that were comparable to or higher than those of Mobius3D. Additionally, it significantly reduced the time required to complete pre-treatment checks by 3-4 min for each plan. In the retrospective analysis of clinical CTgART and MRgART fractions, ART2Dose demonstrated average gamma passing rates of 99.61±0.83% and 97.75±2.54%, respectively, using the 3%/2mm criteria for region greater than 10% of prescription dose. The average calculation times for CTgART and MRgART were approximately 1 and 2 min, respectively. Overall, the streamlined implementation of ART2Dose notably enhances the online ART workflow, offering reliable and efficient online QA while reducing time pressure in the clinic and minimizing labor-intensive work.

Different benefits of adaptive radiotherapy for different histologies of NSCLC

Background Adenocarcinoma (AC) and squamous cell carcinoma (SCC) are the most frequent histological subtypes of non-small cell lung cancer (NSCLC). The aim of this study was to investigate how patients with AC and SCC benefit from image-guided adaptive radiotherapy (ART) with tumour match. Material and methods Consecutive patients diagnosed with AC or SCC of the lung treated with definitive chemo-radiotherapy before and after the implementation of ART and tumour match were retrospectively included for analyses. Data collection included baseline patient and treatment characteristics in addition to clinical data on radiation pneumonitis (RP), failure, and survival. Patients were divided into four categories based on their histology and treatment before (n = 173 [89 AC and 84 SCC]) and after implementation of ART (n = 240 [141 AC and 99 SCC]). Results Median follow-up was 5.7 years for AC and 6.3 years for SCC. Mean lung dose decreased for both histologies with ART, whereas mean heart dose only decreased for patients with AC. Incidences of grade 3 and 5 RP decreased for both histologies with ART. Loco-regional failure (LRF) rates decreased significantly for patients with SCC after ART (p = .04), no significant difference was observed for AC. Overall survival (OS) increased significantly for SCC after ART (p < .01): the 2-year OS increased from 31.0% (95% confidence interval [CI] [22.5–42.6]) to 54.5% (95% CI [45.6–65.3]). No significant effect on OS was observed for patients with AC. Conclusion ART and tumour match in the radiotherapeutic treatment of patients with locally advanced NSCLC primarily led to decreased LRF and improved OS for patients with SCC.

Current Perspectives on the Evolving Role of Radiation Therapists – Highlights from ESTRO23

Radiation therapists, also called Therapeutic Radiographers or Radiation therapy technologists (RTTs) are uniquely placed within the radiotherapy (RT) multidisciplinary team, as the use the technology and deliver the treatment but they are also patient focused. The implementation of technological advancements such as image-guided radiotherapy (IGRT), adaptive radiotherapy (ART), surface-guided radiotherapy (SGRT), and AI-based solutions necessitates acquiring new skills and competences. RTTs' daily involvement in patient's treatment allows the assessment of their needs and perspectives. Implementing a holistic approach to patients' comfort during RT, beyond positioning and immobilisation, reduces anxiety and increases compliance. The RTTs offer valuable feedback regarding potential challenges or improvements after new technology or new procedures’ implementation, essential for the enhancement of these innovations. Complex educational interventions focused on modern technology, communication and research competencies are required so that RTTs can optimally fulfil their essential role in cancer care.

Trial in Progress: Adaptive RADiation Therapy with Concurrent Sacituzumab Govitecan (SG) for Bladder Preservation in Patients with MIBC (RAD-SG).

A substantial proportion of patients with muscle invasive bladder cancer do not receive curative intent therapy, especially if unfit for or refuse radical cystectomy. Concurrent chemoradiation is an effective alternative to radical cystectomy, however systemic radio-sensitizing chemotherapy may have off target side effects. A Phase I study is accruing which will investigate the concurrent administration of a bladder cancer targeted antibody drug conjugate (Sacituzumab Govitecan) with radiotherapy. This trial in progress is a Phase I study of Adaptive RADiation therapy with concurrent Sacituzumab Govitecan (SG) for bladder preservation in patients with muscle invasive bladder cancer (MIBC). Eligible patients will have localized muscle invasive bladder cancer (MIBC) confined to the bladder. The initial cohort is expected to accrue 20 patients. The primary endpoint is to establish the safety, tolerability, and feasibility of bladder preservation therapy treatment with concurrent SG and adaptive image-guided radiation therapy for patients with localized MIBC. The secondary endpoints are to determine the bladder intact event-free survival (BI-EFS) with concurrent SG and radiation therapy for MIBC and compare to historical controls with other concurrent chemoradiation regimens. BI-EFS is defined as the time from treatment to the first documented occurrence of residual/recurrent MIBC, nodal or distant metastases on imaging, radical cystectomy, or death from any cause. Sacituzumab Govitecan targets TROP-2, a surface protein expressed in urothelial cancers of the bladder. SG will be delivered IV, 10 mg/kg, 21-day cycles for 1 loading cycle prior to radiation and two subsequent cycles with concurrent adaptive radiotherapy over a period of 6 weeks (64 Gy). Correlative objectives (Supported by NCI/NIH U54) and will involve 1) elucidation of the genetic and microenvironmental mechanisms that drive efficacy and resistance to combined ADC plus radiation therapy and 2) characterization of tumor clonal dynamics, immune repertoire editing, and imaging changes following treatment with SG plus radiation. To be determined. To be determined.

The Feasibility of Dose-Escalated Radiation Therapy for Glioblastoma Using Biological Image Guided Adaptive Radiotherapy (BIGART)

Radiotherapy dose escalation (DE) for glioblastoma (GBM) has been an area of active research. We aimed to study the imaging changes within residual gross tumor volumes (GTV) through the course of concurrent chemo-radiotherapy (CCRT) using multiparametric magnetic resonance imaging (mpMRI). Diffusion, perfusion and chemical exchange saturation transfer (CEST) characteristics of the tumor and its microenvironment were investigated to identify a GTV subvolume potentially associated with radio resistance. We used biological image-guided adaptive radiotherapy (BIGART) to study the feasibility of DE to this GTV subvolume using either photon or proton beam therapy (PBT). We prospectively identified GBM patients with >5cc residual tumor post-resection who were candidates for radical CCRT (60 Gy in 30 daily fractions over 6-weeks with concurrent temozolomide 75mg/m2 daily). We observed the imaging changes with serial mpMRI scans done at baseline, after 2, 4 and 6-weeks of CCRT. Regions of interest (ROIs) within the GTV associated with the following abnormal values at week 2 were identified: apparent diffusion coefficient (ADC): 750-1000 ×10-6 mm2/s; relative cerebral blood volume (rCBV): 1.75-6; and APT-w CEST signal intensity >1.79%. The overlap regions of these ROIs were defined as a novel biological target volume (BTV), identifying the potential area of maximal radioresistance. An in silico study was performed using a technology company's treatment planning system to evaluate the feasibility of planning adaptive treatment to the BTV to total dose of 75 Gy in 30 fractions. This is given in two phases: 30 Gy/15# to the whole PTV as per standard practice, followed by a simultaneous integrated boost (SIB) of 45 Gy/15 fractions while maintaining the dose to the rest of the of the PTV to 60 Gy. Either photons or PBT were used to keep doses to organs at risk (OARs) within standard clinical tolerances. Nine patients were recruited for this analysis and a total of 27 mpMRI scans were studied. Median BTVs to GTVs ratio was 35% (range 22-47%). Volumetric-modulated arc (VMAT) photon and PBT adaptive plans for dose escalation to BTVs were created in all cases whilst maintaining OAR tolerances. Both VMAT and PBT provided acceptable target coverage with average BTV-PTV D98% of 73 Gy (range 71.5-73.8 Gy) and average D2% of 76 Gy (range 75.4-77 Gy) while effectively sparing OARs. Sharper dose gradient between DE-BTV and PTV was achieved with VMAT. PBT was particularly advantageous in minimizing the low-dose spillage outside the BTV. We hereby propose a platform for adaptive radiotherapy to GBM tumors with biological-image guidance through the utilization of mpMRI to evaluate the tumor and its microenvironment during CCRT. We identified thresholds for tumor sub volumes showing the most resistant imaging features and created precise BTVs that allowed for dose escalation. PBT represents an additional useful tool for BIGART planning that will be investigated further in our ongoing work.

Patient Selection is Critical When Evaluating Candidates for 5-Fraction Stereotactic MRI-Guided Adaptive Radiotherapy (SMART) for Locally Advanced Pancreatic Cancer

Stereotactic magnetic resonance image-guided adaptive radiotherapy (SMART) allows for the safe delivery of biologically effective doses (BED10 ∼ 100 Gy) to patients with pancreatic cancer who otherwise have limited therapeutic avenues. In this study, we analyze long-term outcomes in the largest cohort of patients with borderline-resectable (BR), locally advanced (LA), or medically inoperable (MI) pancreatic cancer treated with a 5-fraction SMART technique. A single institution analysis of patients with BR, LA, or MI pancreatic cancer treated with SMART between 2015 and 2021 was performed. Patients with locally recurrent disease, non-adenocarcinoma histology, de-novo metastatic disease, or who did not receive induction chemotherapy were excluded. Baseline and treatment characteristics were collected. Local control (LC), progression free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method, and factors associated with outcomes were evaluated using Cox regression analyses. Oncologic outcomes measured from time of initial diagnosis; local control defined as freedom from local progression. A total of 129 patients were reviewed. Median age at diagnosis was 67 years. The majority were male (60%) and White (84%). 23% of patients had an ECOG 2. Most patients had LA disease (66%), followed by BR (20%) and MI (14%). Median follow up was 17.0 months (6-61 months). Median LC was not reached, and LC was 81%, 54%, and 48% at 1, 2, and 3-years, respectively. Median PFS was 12.9 months [95% confidence interval 11.8-14.71] with 1, 2, and 3-year PFS of 60%, 20%, and 7%, respectively. Median OS was 17.7 months [15.7-19.7] with 1, 2, and 3-year OS of 78%, 28%, 11%, respectively. On univariate analysis, increased duration of induction chemotherapy had a statistically significant impact on PFS and OS. Those receiving equal to or greater than 4 months of induction chemotherapy had a median OS of 19.2 months [17.2-21.2] as compared to 13.6 [11.9-15.3] for those with less than 4 months. In this patient population which included a large portion of patients with ECOG of 2 or greater and those deemed MI, a 5-fraction SMART regimen yielded durable long-term LC. The impact of increasing duration of induction chemotherapy underlies the importance of patient selection and improved understanding of tumor-specific biology when selecting patient's with locally advanced pancreatic cancer for aggressive local therapy.

Recent Advances and Adaptive Strategies in Image Guidance for Cervical Cancer Radiotherapy.

The standard of care for locally advanced cervical cancer is external beam radiotherapy (EBRT) with simultaneous chemotherapy followed by an internal radiation boost. New imaging methods such as positron-emission tomography and magnetic resonance imaging have been implemented into daily practice for better tumor delineation in radiotherapy planning. The method of delivering radiation has changed with technical advances in qualitative imaging and treatment delivery. Image-guided radiotherapy (IGRT) plays an important role in minimizing treatment toxicity of pelvic radiation and provides a superior conformality for sparing the organs at risk (OARs) such as bone marrow, bowel, rectum, and bladder. Similarly, three-dimensional image-guided adaptive brachytherapy (3D-IGABT) with computed tomography (CT) or magnetic resonance imaging (MRI) has been reported to improve target coverage and reduce the dose to normal tissues. Brachytherapy is a complementary part of radiotherapy treatment for cervical cancer and, over the past 20 years, 3D-image-based brachytherapy has rapidly evolved and established itself as the gold standard. With new techniques and adaptive treatment in cervical cancer, the concept of personalized medicine is introduced with an enhanced comprehension of the therapeutic index not only in terms of volume (three-dimensional) but during treatment too (four-dimensional). Current data show promising results with integrated IGRT and IGABT in clinical practice and, therefore, better local control and overall survival while reducing treatment-related morbidity. This review gives an overview of the substantial impact that occurred in the progress of image-guided adaptive external beam radiotherapy and brachytherapy.

Deep learning framework to improve the quality of cone-beam computed tomography for radiotherapy scenarios.

The application of cone-beam computed tomography (CBCT) in image-guided radiotherapy and adaptive radiotherapy remains limited due to its poor image quality. In this study, we aim to develop a deep learning framework to generate high-quality CBCT images for therapeutic applications. The synthetic CT (sCT) generation from the CBCT was proposed using a transformer-based network with a hybrid loss function. The network was trained and validated using the data from 176 patients to produce a general model that can be extensively applied to enhance CBCT images. After the first therapy, each patient can receive paired CBCT/planning CT (pCT) scans, and the obtained data were used to fine-tune the general model for further improvement. For subsequent treatment, a patient-specific, personalized model was made available. In total, 34 patients were examined for general model testing, and another six patients who underwent rescanned pCT scan were used for personalized model training and testing. The general model decreased the mean absolute error (MAE) from 135 HU to 59 HU as compared to the CBCT. The hybrid loss function demonstrated superior performance in CT number correction and noise/artifacts reduction. The proposed transformer-based network also showed superior power in CT number correction compared to the classical convolutional neural network. The personalized model showed improvement based on the general model in some details, and the MAE was reduced from 59 HU (for the general model) to 57 HU (p<0.05 Wilcoxon signed-rank test). We established a deep learning framework based on transformer for clinical needs. The deep learning model demonstrated potential for continuous improvement with the help of a suggested personalized training strategy compatible with the clinical workflow.

Influence of different factors on registration error in a 1.5 T MR-guided linac

Purpose. Accurate image registration is an important step in online image-guided adaptive radiotherapy. The aim of this study was to investigate the effects of different factors on registration accuracy in a magnetic resonance (MR)-guided adaptive radiotherapy workflow. Materials and Methods. A thorax motion phantom was used to obtain computed tomography (CT) simulations in 8 different motion modes and to generate 8 reference plans. Daily pretreatment online MR images were obtained at 5 different positions in each reference plan. Online MR and CT simulations were separately registered using bone structures and the gross tumor volume (GTV) as ROIs, and the image shift distance was recorded by the online treatment planning system. The difference between the shift distance and the real isocentric distance was the registration error. The registration error was analyzed, and the effects of the setup position, motion mode and ROI selection on the registration error were investigated by multivariate analysis of variance. Result. The minimum values of registration error (ΔX, ΔY, ΔZ) were −1.90 mm, −2.70 mm and −2.40 mm, respectively, and the maximum values were 1.70 mm, 4.30 mm and −0.90 mm. ΔY showed the maximum mean standard deviation of 1.25 mm, and ΔZ showed the minimum mean standard deviation of 0.27 mm. The standard deviation of the registration error is largest in the inferior/superior direction. The motion mode of the phantom and ROI selection were significantly correlated with ΔX, ΔY, and ΔZ (p < 0.05). Conclusion. The registration result with the spine as the selected ROI was better than that with the GTV as the ROI. In 1.5 T MR-linac clinical treatment, more attention should be given to patient movement repeatability and to controlling the intrafractional motion as much as possible. It is not recommended to make the GTV-PTV margin expansion less than 2 mm for MR-linac.

Adaptive hypofractionted and stereotactic body radiotherapy for lung tumors with real-time MRI guidance.

The treatment of central and ultracentral lung tumors with radiotherapy remains an ongoing clinical challenge. The risk of Grade 5 toxicity with ablative radiotherapy doses to these high-risk regions is significant as shown in recent prospective studies. Magnetic resonance (MR) image-guided adaptive radiotherapy (MRgART) is a new technology and may allow the delivery of ablative radiotherapy to these high-risk regions safely. MRgART is able to achieve this by utilizing small treatment margins, real-time gating/tracking and on-table plan adaptation to maintain dose to the tumor but limit dose to critical structures. The process of MRgART is complex and has nuances and challenges for the treatment of lung tumors. We outline the critical steps needed for appropriate delivery of MRgART for lung tumors safely and effectively.

Multi-Institutional Outcomes of Patients Aged 75 years and Older With Pancreatic Ductal Adenocarcinoma Treated With 5-Fraction Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy (A-SMART).

Treatment options for pancreatic ductal adenocarcinoma (PDAC) are commonly limited for patients with advanced age due to medical comorbidities and/or poor performance status. These patients may not be candidates for more aggressive chemotherapy regimens and/or surgical resection leaving few, if any, other effective treatments. Ablative stereotactic MRI-guided adaptive radiation therapy (A-SMART) is both efficacious and safe for PDAC and can achieve excellent long-term local control, however, the appropriateness of A-SMART for elderly patients with inoperable PDAC is not well understood. A retrospective analysis was performed of inoperable non-metastatic PDAC patients aged 75years or older treated on the MRIdian Linac at 2 institutions. Clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional (LRC). Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE, v5). A total of 49 patients were evaluated with a median age of 81years (range, 75-91) and a median follow-up of 14 months from diagnosis. PDAC was classified as locally advanced (46.9%), borderline resectable (36.7%), or medically inoperable (16.3%). Neoadjuvant chemotherapy was delivered to 84% of patients and all received A-SMART to a median 50Gy (range, 40-50Gy) in 5 fractions. 1Year LRC, PFS, and OS were 88.9%, 53.8%, and 78.9%, respectively. Nine patients (18%) had resection after A-SMART and benefited from PFS improvement (26 vs 6months, P = .01). ECOG PS <2 was the only predictor of improved OS on multivariate analysis. Acute and late grade 3 + toxicity rates were 8.2% and 4.1%, respectively. A-SMART is associated with encouraging LRC and OS in elderly patients with initially inoperable PDAC. This novel non-invasive treatment strategy appears to be well-tolerated in patients with advanced age and should be considered in this population that has limited treatment options.

PSA Kinetics and Outcomes after Magnetic Resonance Image-Guided Stereotactic Body Radiotherapy for Prostate Cancer

<h3>Purpose/Objective(s)</h3> Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. Assessment of the efficacy of treatment response after radiotherapy relies heavily on the monitoring of prostate specific antigen (PSA) levels and PSA kinetics. The aim of our study was to evaluate tumor control outcomes with PSA response and toxicity after magnetic resonance image-guided adaptive radiotherapy (MRgRT) for prostate cancer patients. <h3>Materials/Methods</h3> A total of 95 prostate cancer patients treated with MRgRT were included in the study. Treatment was performed with IMRT (step and shoot) technique and daily plan adaptation using MRgRT. Patients received 36.25 Gy in 5 fractions, per institutional standards. Outcome measurements included tumor control evaluation with PSA levels, acute and late toxicities. Nadir PSA was defined as the lowest serum PSA value from the time of SBRT completion to date of last follow-up. Biochemical failure (BCF) was defined using the Phoenix definition (nadir + 2 ng/mL). <h3>Results</h3> The median follow-up for our cohort was 23.7 months (range; 3-41.4 months). The median age was 74 years (range; 50-87 years). The median initial PSA (iPSA) was 7.6 ng/mL (range; 2.7-44 ng/mL) for all patients. According to the NCCN guidelines, 13 (13.7%), 53 (55.8%) and 29 (30.5%) patients were in low-, intermediate- and high-risk group, respectively. Twenty-nine patients (30.5%) received androgen deprivation therapy (ADT). The median nadir PSA (nPSA) for all patients was 0.72 ng/mL (range, 0.01-4.96 ng/mL). For the entire cohort, 52.6% patients had an nPSA <1 ng/mL, with 35.8% of patients reaching an nPSA 0.5 ng/mL and 20% reaching an nPSA 0.2 ng/mL. For the patients who didn't receive ADT, median nPSA was 1.26 ng/mL (range; 0.16-4.96 ng/mL); 45.0% patients had an nPSA <1 ng/mL, with 21.3% of patients reaching an nPSA 0.5 ng/mL and 3.3% reaching an nPSA 0.2 ng/mL. For the patients who received ADT, median nPSA was 0.06 ng/mL (range; 0.01-1.55 ng/mL); 95.8% patients had an nPSA <1 ng/mL, with 87.5% of patients reaching an nPSA 0.5 ng/mL and 70.8% reaching an nPSA 0.2 ng/mL. A patient who did not yet meet the Phoenix criteria for biochemical recurrence but a PSA rising was diagnosed with two bone metastases with imaging evaluation and one patient with a nPSA and positive PSMA-PET had radical prostatectomy. MRgRT was well tolerated by all patients. There was no Grade ≥3 GU or GI toxicity. <h3>Conclusion</h3> In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation with MRgRT has an acceptable toxicity profile with favorable efficacy and PSA response. Further studies with longer follow-up time and larger cohorts are warranted.

A traffic light protocol workflow for image-guided adaptive radiotherapy in lung cancer patients.

Image-guided radiotherapy using cone beam-CT (CBCT) images is used to evaluate patient anatomy and positioning before radiotherapy. In this study we analyzed and optimized a traffic light protocol (TLP) used in lung cancer patients to identify patients requiring treatment adaptation. First, CBCT review requests of 243 lung cancer patients were retrospectively analyzed and divided into 6 pre-defined categories. Frequencies and follow-up actions were scored. Based on these results, the TLP was optimized and evaluated in the same way on 230 patients treated in 2018. In the retrospective study, a total of 543 CBCT review requests were created during treatment in 193/243 patients due to changed anatomy of lung (24%), change of tumor volume (24%), review of match (18%), shift of the mediastinum (15%), shift of tumor (15%) and other (4%). The majority of requests (474, 87%) did not require further action. In 6% an adjustment of the match criteria sufficed; in 7% treatment plan adaptation was required. Plan adaptation was frequently seen in the categories changed anatomy of lung, change of tumor volume and shift of tumor outside the PTV. Shift of mediastinum outside PRV and shift of GTV outside CTV (but inside PTV) never required plan adaptation and were omitted to optimize the TLP, which reduced the CBCT review requests by 23%. The original TLP selected patients that required a treatment adaptation, but with a high false positive rate. The optimized TLP reduced the amount of CBCT review requests, while still correctly identifying patients requiring adaptation.

One shot PACS: Patient specific Anatomic Context and Shape prior aware recurrent registration-segmentation of longitudinal thoracic cone beam CTs.

Image-guided adaptive lung radiotherapy requires accurate tumor and organs segmentation from during treatment cone-beam CT (CBCT) images. Thoracic CBCTs are hard to segment because of low soft-tissue contrast, imaging artifacts, respiratory motion, and large treatment induced intra-thoracic anatomic changes. Hence, we developed a novel Patient-specific Anatomic Context and Shape prior or PACS-aware 3D recurrent registration-segmentation network for longitudinal thoracic CBCT segmentation. Segmentation and registration networks were concurrently trained in an end-to-end framework and implemented with convolutional long-short term memory models. The registration network was trained in an unsupervised manner using pairs of planning CT (pCT) and CBCT images and produced a progressively deformed sequence of images. The segmentation network was optimized in a one-shot setting by combining progressively deformed pCT (anatomic context) and pCT delineations (shape context) with CBCT images. Our method, one-shot PACS was significantly more accurate (p <0.001) for tumor (DSC of 0.83 ± 0.08, surface DSC [sDSC] of 0.97 ± 0.06, and Hausdorff distance at 95th percentile [HD95] of 3.97±3.02mm) and the esophagus (DSC of 0.78 ± 0.13, sDSC of 0.90±0.14, HD95 of 3.22±2.02) segmentation than multiple methods. Ablation tests and comparative experiments were also done.

Induction Chemotherapy and Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy for Inoperable Pancreas Cancer.

BackgroundRadiation therapy (RT) dose for inoperable pancreatic ductal adenocarcinoma (PDAC) has historically been non-ablative to avoid injuring gastrointestinal (GI) organs at risk (OARs). Accruing data suggest that dose escalation, in select patients, may significantly improve clinical outcomes. Early results of ablative stereotactic magnetic resonance image-guided adaptive radiation therapy (A-SMART) have been encouraging, although long-term outcomes are not well understood.MethodsA single institution retrospective analysis was performed of inoperable non-metastatic PDAC patients who received induction chemotherapy then 5-fraction A-SMART on a 0.35T-MR Linac from 2018-2021.ResultsSixty-two patients were evaluated with a median age of 66 years (range 35-91) and nearly all achieved Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (96.8%). Locally advanced disease was common (72.6%), otherwise borderline resectable (22.6%), or medically inoperable (4.8%). All received induction chemotherapy for a median 4.2 months (range, 0.2-13.3) most commonly FOLFIRINOX (n=43; 69.4%). Median prescribed dose was 50 Gy (range 40-50); median biologically effective dose (BED10) was 100 Gy10. The median local control (LC), progression-free survival (PFS), and overall survival (OS) from diagnosis were not reached, 20 months, and 23 months, respectively. Also, 2-year LC, PFS, and OS were 68.8%, 40.0%, and 45.5%, respectively. Acute and late grade 3+ toxicity rates were 4.8% and 4.8%, respectively.ConclusionsTo our knowledge, this is the largest series of induction chemotherapy followed by ablative 5-fraction SMART delivered on an MR Linac for inoperable PDAC. The potential for this novel treatment strategy is to achieve long-term LC and OS, compared to chemotherapy alone, and warrants prospective evaluation.