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BACKGROUND AND PURPOSE: Over the past decade, tools for automation of various sub-tasks in radiotherapy planning have been introduced, such as auto-contouring and auto-planning. The purpose of this study was to benchmark what degree of automation is possible. MATERIALS AND METHODS: A challenge to perform automated treatment planning for prostate and prostate bed radiotherapy was set up. Participants were provided with simulation CTs and a treatment prescription and were asked to use automated tools to produce a deliverable radiotherapy treatment plan with as little human intervention as possible. Plans were scored for their adherence to the protocol when assessed using consensus expert contours. RESULTS: Thirteen entries were received. The top submission adhered to 81.8% of the minimum objectives across all cases using the consensus contour, meeting all objectives in one of the ten cases. The same system met 89.5% of objectives when assessed with their own auto-contours, meeting all objectives in four of the ten cases. The majority of systems used in the challenge had regulatory clearance (Auto-contouring: 82.5%, Auto-planning: 77%). Despite the 'hard' rule that participants should not check or edit contours or plans, 69% reported looking at their results before submission. CONCLUSIONS: Automation of the full planning workflow from simulation CT to deliverable treatment plan is possible for prostate and prostate bed radiotherapy. While many generated plans were found to require none or minor adjustment to be regarded as clinically acceptable, the result indicated there is still a lack of trust in such systems preventing full automation.

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BACKGROUND AND PURPOSE: Our goal was to develop a workflow to automatically evaluate delivered dose on daily cone beam computed tomography (CBCT) in all breast cancer patients to assess dosimetric impact of anatomical changes and guide decision-making for offline plan adaptation. MATERIALS AND METHODS: The workflow automatically processes the daily CBCTs of all breast cancer patients receiving local and locoregional radiotherapy. The planning-CT is registered to the CBCT to create a synthetic CT and propagate contours. A forward dose calculation is performed, and DVH parameters are extracted and printed in a report. We evaluated the workflow on a group level and in a subset of 30 patients on a patient-specific level, including comparison to clinical evaluation on additional planning-CT in 10 patients. RESULTS: 7454 fractions in 647 patients were analyzed over a period of seven months. Median breast clinical target volume V95% was ≥95 % for 97 % of the patients. The workflow would have provided useful additional insights for decision-making for the requirement of plan adaptation, based on debatable disagreement with the clinical decision in half of the cases with an additional planning-CT. The workflow also identified cases with suboptimal coverage not identified in the clinical procedure. CONCLUSION: We developed a fully automated workflow for dose evaluation on daily CBCT for local and locoregional breast radiotherapy. We have demonstrated its potential for aiding decision-making for plan adaptation in patients with changing anatomy and its capability to highlight patients that may receive suboptimal treatment and require closer clinical evaluation of treatment quality.

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Background and Objective: Magnetic resonance guided radiotherapy (MRgRT) is an emerging technological innovation with more and more institutions gaining clinical experience in this new field of radiation oncology. The ability to better visualize both tumors and healthy tissues due to excellent soft tissue contrast combined with new possibilities regarding motion management and the capability of online adaptive radiotherapy might increase tumor control rates while potentially reducing the risk of radiation-induced toxicities. As conventional computed tomography (CT)-based image guidance methods are insufficient for adaptive workflows in abdominal tumors, MRgRT appears to be an optimal method for this tumor site. The aim of this narrative review is to outline the opportunities and challenges in magnetic resonance guided radiation therapy in gastrointestinal cancers. Methods: We searched for studies, reviews and conceptual articles, including the general technique of MRgRT and the specific utilization in gastrointestinal cancers, focusing on pancreatic cancer, liver metastases and primary liver cancer, rectal cancer and esophageal cancer. Key Content and Findings: This review is highlighting the innovative approach of MRgRT in gastrointestinal cancer and gives an overview of the currently available literature with regard to clinical experiences and theoretical background. Conclusions: MRgRT is a promising new tool in radiation oncology, which can play off several of its beneficial features in the specific field of gastrointestinal cancers. However, clinical data is still scarce. Nevertheless, the available literature points out large potential for improvements regarding dose coverage and escalation as well as the reduction of dose exposure to critical organs at risk (OAR). Further prospective studies are needed to demonstrate the role of this innovative technology in gastrointestinal cancer management, in particular trials that randomly compare MRgRT with conventional CT-based image-guided radiotherapy (IGRT) would be of high value.

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Purpose: Despite the efficacy of endorectal balloon (ERB) in reducing rectal radiation dose, the effectiveness of upper rectal fixation remains to be evaluated. The purpose of this study was to evaluate the impact of ERB on upper rectal fixation in patients diagnosed with localized prostate cancer. Materials: Cine MRI was performed in 46 patients with localized prostate cancer to assess the stability of the anterior rectal wall with and without ERB by calculating the standard deviation of the normalized signal intensity at the level of the midgland or the seminal vesicle. Results: The standard deviation of the normalized signal intensity for the anterior rectal wall decreased significantly with the use of ERB both at the level of the midgland (p < 0.05) and the seminal vesicle (p < 0.05). The standard deviation of the anterior rectal wall at the level of the seminal vesicle was significantly higher than at the level of the midgland without ERB (p < 0.05). But with ERB, the standard deviation of the normalized signal intensity at the level of the seminal vesicle became comparable to that at the level of the midgland (p = 0.392). Conclusion: The anterior rectal wall is stabilized by ERBs not only at the level of the midgland but also at the level of the seminal vesicle. ERBs can transform the rectum from a moving and deformable organ into a static and rigid organ.

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BACKGROUND: There are no reports of concurrent chemoradiotherapy for gastric cancer with peritoneal oligometastases. CASE DESCRIPTION: A 70-year-old man with gastric cancer and peritoneal oligometastases received concurrent adaptive radiotherapy and oral S-1. After radiotherapy, S-1 was discontinued, and 2 years later the tumor had completely regressed, with no recurrence or metastasis 6 years after radiotherapy. CONCLUSION: Peritoneal oligometastatic gastric cancer may be a candidate for curative treatment with concurrent adaptive radiotherapy and oral S-1.

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BACKGROUND: We report the results of a retrospective analysis of localized prostate cancer (LPCa) treated with transperineal ultrasound image-guided radiotherapy (TPUS-IGRT). METHODS: A total of 124 patients (median age: 74 y, 46-84 y) with LPCa who underwent TPUS-IGRT (Clarity Autoscan system; CAS, Elekta; Stockholm, Sweden) between April 2016 and October 2021 for curative/after hormone induction were enrolled. The number of patients by risk (National Comprehensive Cancer Network 2019) was 7, 25, 42, and 50 for low (LR), good intermediate (good IR), poor intermediate (poor IR), and high (HR)/very high (VHR), respectively. Ninety-five patients were given neoadjuvant hormonal therapy. The planning target volume margin setting was 3 mm for rectal in most cases, 5-7 mm for superior/inferior, and 5 mm for anterior/right/left. The principle prescribed dose is 74 Gy (LR), 76 Gy (good IR), and 76-78 Gy (poor IR or above). CAS was equipped with a real-time prostate intrafraction monitoring (RTPIFM) system. When a displacement of 2-3 mm or more was detected, irradiation was paused, and the patients were placed on standby for prostate reinstatement/recorrection. Of the 3135 fractions in 85 patients for whom RTPIFM was performed, 1008 fractions (32.1%) were recorrected at least once after starting irradiation. RESULTS: A total of 123 patients completed the radiotherapy course. The 5-year overall survival rate was 95.9%. The 5-year biological prostate-specific antigen relapse-free survival rate (bPFS) was 100% for LR, 92.9% for intermediate IR, and 93.2% for HR/VHR (Phoenix method). The 5-year late toxicity rate of Grade 2+ was 7.4% for genitourinary (GU) and 6.5% for gastrointestinal (GI) organs. Comparing the ≤ 76 Gy group to the 78 Gy group for both GU and GI organs, the incidence was higher in the 78 Gy group for both groups. CONCLUSION: These results suggest that TPUS-IGRT is well tolerated, as the bPFS and incidence of late toxicity are almost comparable to those reported by other sources of image-guided radiotherapy.

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METHOD: 2D/3D kV imaging and CBCT data using 6 degrees of freedom (6DoF) were compared to evaluate inter and intrafraction motion. RESULTS: Results showed that intrafraction errors were low and interfraction levels were within institutional protocols. CONCLUSION: Confidence was given to use low dose 2D/3D kV imaging to confirm daily patient set up errors, and to use pre-treatment CBCT only once weekly for additional imaging information. IMPLICATIONS FOR PRACTICE: Further research is necessary to assess other uncertainties, to enable the calculation of a margin and determining the feasibility of further reduction of this.

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Stereotactic body radiotherapy (SBRT) to the central and ultra-central thorax is associated with infrequent but potentially serious adverse events. Adaptive SBRT, which provides more precise treatment planning and inter-fraction motion management, may allow the delivery of ablative doses to ultra-central tumors with effective local control and improved toxicity profiles. Herein, we describe the first reported case of cone beam computed tomography (CBCT)-guided stereotactic adaptive radiotherapy (CT-STAR) in the treatment of ultra-central non-small cell lung cancer (NSCLC) in a prospective clinical trial (NCT05785845). An 80-year-old man with radiographically diagnosed early-stage NSCLC presented for definitive management of an enlarging ultra-central lung nodule. He was prescribed 55 Gy in five fractions with CT-STAR. A simulation was performed using four-dimensional CT, and patients were planned for treatment at end-exhale breath-hold. Treatment plans were generated using a strict isotoxicity approach, which prioritized organ at risk (OAR) constraints over target coverage. During treatment, daily CBCTs were acquired and used to generate adapted contours and treatment plans based on the patient's anatomy-of-the-day, all while the patient was on the treatment table. The initial and adapted plans were compared using dose-volume histograms, and the superior plan was selected for treatment. The adapted plan was deemed superior and used for treatment in three out of five fractions. The adapted plan provided improved target coverage in two fractions and resolved an OAR hard constraint violation in one fraction. We report the successful treatment of a patient with ultra-central NSCLC utilizing CT-STAR. This case report builds on previously published in silico data to support the viability and dosimetric advantages of CT-STAR in the ablative treatment of this challenging tumor location. Further data are needed to confirm the toxicity and efficacy of this technique.

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Image-guided radiotherapy supported by surface guidance can help to track lower lung lesions' respiratory motion while reducing a patient's exposure to ionizing radiation. However, it is not always clear how the skin's respiratory motion magnitude and its correlation with the lung lesion's respiratory motion vary between different skin regions of interest (ROI). Four-dimensional computed tomography (4DCT) images provide information on both the skin and lung respiratory motion and are routinely acquired for the purpose of treatment planning in our institution. An analysis of 4DCT images for 57 patients treated in our institution has been conducted to provide information on the respiratory motion magnitudes of nine skin ROIs of the torso, a tracking structure (TS) representing a lower lung lobe lesion, as well as the respiratory motion correlations between the nine ROIs and the TS. The effects of gender and the adipose tissue volume and distribution on these correlations and magnitudes have been analyzed. Significant differences between the ROIs in both the respiratory motion magnitudes and their correlations with the TS have been detected. An overall negative correlation between the ROI respiratory magnitudes and the adipose tissue has been detected for ROIs with rib cage support. A weak to moderate negative correlation between the adipose tissue volume and ROI-to-TS respiratory correlations has been detected for upper thorax ROIs. The respiratory magnitudes in regions without rib support tend to be larger for men than for women, but no differences in the ROI-to-TS correlation between sexes have been detected. The described findings should be considered when choosing skin surrogates for lower lung lesion motion management.

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Current online adaptive radiotherapy (oART) workflows require dedicated equipment. Our aim was to develop and implement an oART workflow for a C-arm linac which can be performed using standard clinically available tools. A workflow was successfully developed and implemented. Three patients receiving palliative radiotherapy for bladder cancer were treated, with 33 of 35 total fractions being delivered with the cone-beam computed tomography (CBCT)-guided oART workflow. Average oART fraction duration was 24 min from start of CBCT acquisition to end of beam on. This work shows how oART could be performed without dedicated equipment, broadening oART availability for application at existing treatment machines.

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Purpose: Repeated cone-beam CT (CBCT) scans for image-guided radiotherapy (IGRT) increase the health risk of radiation-induced malignancies. Patient-enrolled studies to optimize scan protocols are inadequate. We proposed a virtual clinical trial-based approach to evaluate projection-reduced low-dose CBCT for IGRT. Materials and methods: A total of 71 patients were virtually enrolled with 26 head, 23 thorax and 22 pelvis scans. Projection numbers of full-dose CBCT scans were reduced to 1/2, 1/4, and 1/8 of the original to simulate low-dose scans. Contrast-to-noise ratio (CNR) values in fat and muscle were measured in the full-dose and low-dose images. CBCT images were registered to planning CT to derive 6-degree-of-freedom couch shifts. Registration errors were statistically analyzed with the Wilcoxon paired signed-rank test. Results: As projection numbers were reduced, CNR values descended and the magnitude of registration errors increased. The mean CNR values of full-dose and half-dose CBCT were >3.0. For full-dose and low-dose CBCT (i.e. 1/2, 1/4 and 1/8 full-dose), the mean registration errors were< ± 0.4 mm in translational directions (LAT, LNG, VRT) and ±0.2 degree in rotational directions (Pitch, Roll, Yaw); the mean magnitude of registration errors were< 1 mm in translation and< 0.5 degree in rotation. The couch shift differences between full-dose and low-dose CBCT were not statistically significant (p>0.05) in all the directions. Conclusion: The results indicate that while the impact of dose-reduction on CBCT couch shifts is not significant, the impact on CNR values is significant. Further validation on optimizing CBCT imaging dose is required.

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INTRODUCTION: Magnetic resonance guided radiotherapy (MRgRT) allows daily adaptation of treatment plans to compensate for positional changes of target volumes and organs at risk (OARs). However, current adaptation times are relatively long and organ movement occurring during the adaptation process might offset the benefit gained by adaptation. The aim of this study was to evaluate the dosimetric impact of these intrafractional changes. Additionally, a method to predict the extent of organ movement before the first treatment was evaluated in order to have the possibility to compensate for them, for example by adding additional margins to OARs. MATERIALS & METHODS: Twenty patients receiving adaptive MRgRT for treatment of abdominal lesions were retrospectively analyzed. Magnetic resonance (MR) images acquired at the start of adaptation and immediately before irradiation were used to calculate adapted and pre-irradiation dose in OARs directly next to the planning target volume. The extent of organ movement was determined on MR images acquired during simulation sessions and adaptive treatments, and their agreement was evaluated. Correlation between the magnitude of organ movement during simulation and the duration of simulation session was analyzed in order to assess whether organ movement might be relevant even if the adaptation process could be accelerated in the future. RESULTS: A significant increase in dose constraint violations was observed from adapted (6.9%) to pre-irradiation (30.2%) dose distributions. Overall, OAR dose increased significantly by 4.3% due to intrafractional organ movement. Median changes in organ position of 7.5 mm (range 1.5-10.5 mm) were detected within a median time of 17.1 min (range 1.6-28.7 min). Good agreement was found between the range of organ movement during simulation and adaptation (66.8%), especially if simulation sessions were longer and multiple MR images were acquired. No correlation was determined between duration of simulation sessions and magnitude of organ movement. CONCLUSION: Intrafractional organ movement can impact dose distributions and lead to violations of OAR tolerance doses, which impairs the benefit of daily on-table plan adaptation. By application of simulation images, the extent of intrafractional organ movement can be predicted, which possibly allows to compensate for them.

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PURPOSE: To provide more accurate and definitive conclusions regarding the clinical and technical complications associated with the transperineal (TP) and transrectal (TR) approaches, a comprehensive review of observational studies and randomized controlled trials was conducted. This systematic review covered all eligible studies to facilitate a thorough comparison of complications linked to the two fiducial marker insertion methods, TP and TR. METHODS: A comprehensive search of the literature was conducted, encompassing databases such as PubMed, Embase, and the Cochrane Library, up to July 7, 2023. The relative risk and 95% confidence interval were utilized to evaluate the diagnosis and complication rates. RESULTS: The final selection for the methodological quality analysis included 13 observational studies that utilized TP and TR gold fiducial insertion approaches. The meta-analysis revealed significantly lower risks of urinary tract infections (UTI) and rectal bleeding with the TP approach. CONCLUSION: The use of both TP and TR techniques for placing gold seed fiducial markers has proven to be an effective, safe, and well-tolerated method for image-guided radiation therapy in prostate cancer patients. A significant benefit of the TP technique is its ability to avoid rectal puncture, thereby reducing the risk of UTIs. Although the incidence of UTIs and rectal bleeding associated with the TR method is relatively low, these complications can disrupt patient wellbeing and potentially cause delays in treatment.

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Intensity-based 2D/3D registration using kilo-voltage (kV) and mega-voltage (MV) on-board imaging is a promising approach for real-time tumor motion tracking. So far, the performance of the kV images as well as kV-MV image pairs for 2D/3D registration using only one gantry angle (in anterior-posterior (AP) direction) has been investigated on patient data. In stereotactic body radiation therapy (SBRT), however, various gantry angles are typically used. This study attempts to answer the question of whether automatic 2D/3D registration is possible using kV images as well as kV-MV image pairs for gantry angles other than the AP direction. We also investigated the effect of additional portal MV images paired with kV images to improve 2D/3D registration in extracting cranio-caudal (CC) and AP displacement at arbitrary gantry angles and different fractions. The kV and MV image sequences as well as 3D volume data from five patients suffering from non-small cell lung cancer undergoing SBRT were used. Diaphragm motion served as the reference signal. The CC and AP displacements resulting from the registration results were compared with the corresponding reference motion signal. Pearson correlation coefficients (R value) was used to calculate the similarity measure between reference signal and the extracted displacements resulting from the registration. Signals we found that using 2D/3D registration tumor motion in 5 degrees of freedom (DOF) with kV images and in 6 degrees of freedom with kV-MV image pairs can be extracted for most gantry angles in all patients. Furthermore, our results have shown that the use of kV-MV image pairs increases the overall chance of tumor visibility and therefore leads to more successful extraction of CC as well as AP displacements for almost all gantry angles in all patients. We observed an improvement in registration of at least 0.29% more gantry angle for all patients when we used kV-MV images compared to kV images alone. In addition, an improvement in the R-value was observed in up to 16 fractions in various patients.

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Introduction: Invisible ink tattoos (IITs) avoid cosmetic permanence of visible ink tattoos (VITs) while serving as more reliable landmarks for radiation setup than tattooless setups. This trial evaluated patient-reported preference and feasibility of IIT implementation. Methods and materials: In an IRB-approved, single institution, prospective trial, patients receiving proton therapy underwent IIT-based treatment setup. A survey tool assessed patient preference on tattoos using a Likert scale. Matched patients treated using our institutional standard tattooless setup were identified; treatment times and image guidance requirements were evaluated between tattooless and IIT-based alignment approaches. Distribution differences were estimated using Wilcoxon rank-sum tests or Chi-square tests. Results: Of 94 eligible patients enrolled, median age was 58 years, and 58.5% were female. Most common treatment sites were breast (18.1%), lung (17.0%) and pelvic (14.9%). Patients preferred to receive IITs versus VITs (79.8% pre-treatment and 75.5% post-treatment, respectively). Patients were willing to travel farther from home to avoid VITs versus IITs (p<0.01). Females were willing to travel (45.5% vs. 23.1%; p=0.04) and pay additional money to avoid VITs (34.5% vs. 5.1%; p<0.01). Per-fraction average +treatment time and time from on table/in room to first beam were shorter with IIT-based vs. tattooless setup (12.3min vs. 14.1min; p=0.04 and 24.1min vs. 26.2min; p=0.02, respectively). Discussion: In the largest prospective trial on IIT-based radiotherapy setup to date, we found that patients prefer IITs to VITs. Additionally, IIT-based alignment is an effective and efficient strategy in comparison with tattooless setup. Standard incorporation of IITs for patient setup should be strongly considered.

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BACKGROUND: The aim of the study was to establish a weighted comprehensive evaluation model (WCEM) of image registration for cone-beam computed tomography (CBCT) guided lung cancer radiotherapy that considers the geometric accuracy of gross target volume (GTV) and organs at risk (OARs), and assess the registration accuracy of different image registration methods to provide clinical references. METHODS: The planning CT and CBCT images of 20 lung cancer patients were registered using diverse algorithms (bony and grayscale) and regions of interest (target, ipsilateral, and body). We compared the coverage ratio (CR) of the planning target volume (PTVCT) to GTVCBCT, as well as the dice similarity coefficient (DSC) of the GTV and OARs, considering the treatment position across various registration methods. Furthermore, we developed a mathematical model to assess registration results comprehensively. This model was evaluated and validated using CRFs across four automatic registration methods. RESULTS: The grayscale registration method, coupled with the registration of the ipsilateral structure, exhibited the highest level of automatic registration accuracy, the DSC were 0.87 ± 0.09 (GTV), 0.71 ± 0.09 (esophagus), 0.74 ± 0.09 (spinal cord), and 0.91 ± 0.05 (heart), respectively. Our proposed WCEM proved to be both practical and effective. The results clearly indicated that the grayscale registration method, when applied to the ipsilateral structure, achieved the highest CRF score. The average CRF scores, excellent rates, good rate and qualification rates were 58 ± 26, 40%, 75%, and 85%, respectively. CONCLUSIONS: This study successfully developed a clinically relevant weighted evaluation model for CBCT-guided lung cancer radiotherapy. Validation confirmed the grayscale method's optimal performance in ipsilateral structure registration.

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Globally, cervical cancer is the fourth leading cancer among women and is dominant in resource-poor settings in its occurrence and mortality. This study focuses on developing liquid immunogenic fiducial eluter (LIFE) Biomaterial with components that include biodegradable polymers, nanoparticles, and an immunoadjuvant. LIFE Biomaterial is designed to provide image guidance during radiotherapy similar to clinically used liquid fiducials while enhancing therapeutic efficacy for advanced cervical cancer. C57BL6 mice were used to grow subcutaneous tumors on bilateral flanks. The tumor on one flank was then treated using LIFE Biomaterial prepared with the immunoadjuvant anti-CD40, with/without radiotherapy at 6 Gy. Computed tomography (CT) and magnetic resonance (MR) imaging visibility were also evaluated in human cadavers. A pharmacodynamics study was also conducted to assess the safety of LIFE Biomaterial in healthy C57BL6 female mice. Results showed that LIFE Biomaterial could provide both CT and MR imaging contrast over time. Inhibition in tumor growth and prolonged significant survival (* p < 0.05) were consistently observed for groups treated with the combination of radiotherapy and LIFE Biomaterial, highlighting the potential for this strategy. Minimal toxicity was observed for healthy mice treated with LIFE Biomaterial with/without anti-CD40 in comparison to non-treated cohorts. The results demonstrate promise for the further development and clinical translation of this approach to enhance the survival and quality of life of patients with advanced cervical cancer.

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Background and Objective: As one of the main treatment modalities, radiotherapy (RT) (also known as radiation therapy) plays an increasingly important role in the treatment of cancer. RT could benefit greatly from the accurate localization of the gross tumor volume and circumambient organs at risk (OARs). Modern linear accelerators (LINACs) are typically equipped with either gantry-mounted or room-mounted X-ray imaging systems, which provide possibilities for marker-less tracking with two-dimensional (2D) kV X-ray images. However, due to organ overlapping and poor soft tissue contrast, it is challenging to track the target directly and precisely with 2D kV X-ray images. With the flourishing development of deep learning in the field of image processing, it is possible to achieve real-time marker-less tracking of targets with 2D kV X-ray images in RT using advanced deep-learning frameworks. This article sought to review the current development of deep learning-based target tracking with 2D kV X-ray images and discuss the existing limitations and potential solutions. Finally, it also discusses some common challenges and potential future developments. Methods: Manual searches of the Web of Science, and PubMed, and Google Scholar were carried out to retrieve English-language articles. The keywords used in the searches included "radiotherapy, radiation therapy, motion tracking, target tracking, motion estimation, motion monitoring, X-ray images, digitally reconstructed radiographs, deep learning, convolutional neural network, and deep neural network". Only articles that met the predetermined eligibility criteria were included in the review. Ultimately, 23 articles published between March 2019 and December 2023 were included in the review. Key Content and Findings: In this article, we narratively reviewed deep learning-based target tracking with 2D kV X-ray images in RT. The existing limitations, common challenges, possible solutions, and future directions of deep learning-based target tracking were also discussed. The use of deep learning-based methods has been shown to be feasible in marker-less target tracking and real-time motion management. However, it is still quite challenging to directly locate tumor and OARs in real-time with 2D kV X-ray images, and more technical and clinical efforts are needed. Conclusions: Deep learning-based target tracking with 2D kV X-ray images is a promising method in motion management during RT. It has the potential to track the target in real time, recognize motion, reduce the extended margin, and better spare the normal tissue. However, it still has many issues that demand prompt attention, and further development before it can be put into clinical practice.

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BACKGROUND: Intensity-modulated radiation therapy (IMRT) is considered standard of care for head and neck squamous cell carcinoma (HNSCC). Improved conformity of IMRT and smaller margins, however, have led to concerns of increased rates of marginal failures. We hypothesize that while patterns of failure (PoF) after IMRT for HNSCC have been published before, the quality of patient positioning and image guided radiotherapy (IGRT) have rarely been taken into account, and their importance remains unclear. This work provides a systematic review of the consideration of IGRT in PoF studies after IMRT for HNSCC. MATERIALS AND METHODS: A systematic literature search according to PRISMA guidelines was performed on PubMed for HNSCC, IMRT and PoF terms and conference abstracts from ESTRO and ASTRO 2020 and 2021 were screened. Studies were included if they related PoF of HNSCC after IMRT to the treated volumes. Data on patient and treatment characteristics, IGRT, treatment adaptation, PoF and correlation of PoF to IGRT was extracted, categorized and analyzed. RESULTS: One-hundred ten studies were included. The majority (70) did not report any information on IGRT. The remainder reported daily IGRT (18), daily on day 1-3 or 1-5, then weekly (7), at least weekly (12), or other schemes (3). Immobilization was performed with masks (78), non-invasive frames (4), or not reported (28). The most common PoF classification was "in-field/marginal/out-of-field", reported by 76 studies. Only one study correlated PoF in nasopharyngeal cancer patients to IGRT. CONCLUSION: The impact of IGRT on PoF in HNSCC is severely underreported in existing literature. Only one study correlated PoF to IGRT measures and setup uncertainty. Further, most PoF studies relied on outdated terminology ("in/out-of-field"). A clearly defined and up-to-date PoF terminology is necessary to evaluate PoFs properly, as is systematic and preferably prospective data generation. PoF studies should consistently and comprehensively consider and report on IGRT.

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