Skip to main content

Publications

Publications

    2025

    • Radiotherapy dose prediction using off-the-shelf segmentation networks: A feasibility study with GammaPod planning.

      Wang, Q., Chen, M., Kazemimoghadam, M., Yang, Z., Zhang, K., Gu, X., Lu, W.

      Medical physics

      ABSTRACT
      For patients with spine metastases, stereotactic radiosurgery (SRS) provides excellent local control and pain response. Despite increasing use of this treatment modality, there is no consensus on the optimal dose and fractionation of spine SRS for efficacy and toxicity. We have initiated a single-center phase III randomized trial that compares two dose regimens with similar biological equivalent dose (BED) to determine the isolated effect of SRS fractionation on local control.Patients with one to three cervical, thoracic, or lumbar spine metastases spanning no more than two contiguous vertebral levels in need of radiation will be eligible for enrollment. Patients will be assigned 1:1 to receive either 22 Gy in 1 fraction or 28 Gy in 2 fractions. Biased coin randomization will be used to randomly assign patients while balancing the following stratifying variables between the two treatment arms at baseline: gastrointestinal histology (yes/no), paraspinal tissue extension (yes/no), epidural compression (low-/high-grade), and number of sites treated (one to three). The primary endpoint is one-year local control, defined per Spine Response Assessment in Neuro-Oncology (SPINO) criteria. The secondary endpoints include patient-reported health-related quality of life (HRQOL), pain associated with the treated site, vertebral compression fracture (VCF), and two-year local control. Patients will be followed for these outcomes at one to two weeks, one month, three months, and six months after treatment, and every six months thereafter until 24 months after treatment. While on the study, patients will receive routine co-interventions as clinically indicated.The studies published thus far comparing the single- and multi-fraction SRS are lacking long-term local control outcomes and are limited by selection bias as well as single-fraction arms with higher BED, which is correlated with improved local control. Our study will isolate the effect of fractionation by comparing one-year local control in patients treated with single- and multi-fraction SRS with equivalent BED. We anticipate that the results of this, as well as secondary endpoints such as pain response, adverse effects, and quality of life will provide much-needed guidance regarding optimal dose and fractionation for both maximizing local control and minimizing toxicity.NCT#06173401. Approved by Stanford Scientific Review Committee (study ID: BRN0060) on 9/12/2023 and Stanford Institutional Review Board (study ID: IRB-72248) on 11/14/2023.
    • Efficacy and Safety of Donut-Shaped Circumferential Spine CyberKnife Stereotactic Body Radiotherapy for Metastatic Spine Disease.

      Park, D. J., Lee, I., Annagiri, S., Chou, K. N., Zamarud, A., Akhavan-Sigari, A., Hori, Y. S., Persad, A. R., Abu-Reesh, D., Lam, F. C., Tayag, A., Ustrzynski, L., Emrich, S. C., Gu, X., Pollom, E. L., Chang, S. D.

      Neurosurgery

      ABSTRACT
      Radiotherapy requires precise, patient-specific treatment planning to achieve high-quality dose distributions that improve patient outcomes. Traditional manual planning is time-consuming and clinically impractical for performing necessary plan trade-off comparisons, including treatment modality selection, prescription dose settings, and organ at risk (OAR) constraints. A time-efficient dose prediction tool could accelerate the planning process by guiding clinical plan optimization and adjustments. While the deep convolutional neural networks (CNNs) are prominent in radiotherapy dose prediction tasks, most studies have attempted to customize network architectures for different diseases and treatment modalities.This study proposes a universal and efficient strategy, Seg2Dose, leveraging a state-of-the-art segmentation network for radiotherapy dose prediction without the need for model architecture modifications. We aim to provide a convenient off-the-shelf dose prediction tool that simplifies the dose prediction process, enhancing planning speed, and plan quality while minimizing the need for extensive coding and customization.The proposed Seg2Dose consists of three modules: the Adapter, the segmentation network, and the Smoother. Prior to model training, the Adapter processes dose distributions into dose level map with an adjustable interval, which serves as the ground truth of the segmentation network, and generates two input channels: weighted avoidance image and normalized prescribed dose image. The segmentation network predicts dose levels from input channels using the nnU-Net, which was trained, validated and tested on 304, 77, and 64 breast cancer GammaPod treatment plans from 90 patients. The Smoother converts the predicted dose levels into continuous dose distribution with a Gaussian filter. The performance of Seg2Dose models with two different dose level intervals, 2% (Seg2Dose 2%) and 5% (Seg2Dose 5%), was evaluated by the Dice similarity coefficients (DSCs), voxel-based mean absolute percent error (MAPE), dose-volume histogram (DVH) metrics, global 3%/2 mm and 3%/1 mm gamma passing rate (GPR), and a case study including normal and worst cases. Additionally, Seg2Dose was compared with an exciting cutting-edge Cascade 3D (C3D) dose prediction model, which was trained on continuous dose distributions, to investigate the impact of using dose level map.For dose level prediction, Seg2Dose achieved average DSCs of 0.94 and 0.93 for the 2% and 5% intervals, respectively. For dose distribution prediction, both Seg2Dose 2% and Seg2Dose 5% achieved MAPEs within 6% for targets and most OARs, with the exception of the skin, which had the highest MAPE at 8.58% for Seg2Dose 2% and 15.25% for Seg2Dose 5%. The DVH metrics showed consistent findings. The C3D model has a better performance in GPR than Seg2Dose models. However, the C3D model exhibited higher MAPEs in target areas with lower dose predictions. In the case study, Seg2Dose 2% and C3D predictions were more consistent with clinical plans, showing smaller dose differences compared to Seg2Dose 5%.Our study confirms the feasibility of leveraging the segmentation network for dose prediction and provides an efficient and off-the-shelf approach for dose prediction without requiring extensive coding efforts. This plug-in tool holds promise for quick dose planning, potentially aiding in the identification of optimal radiotherapy techniques and dosimetric tradeoffs prior to tedious treatment planning.
    • Efficient and accurate commissioning and quality assurance of radiosurgery beam via prior-embedded implicit neural representation learning.

      Liu, L., Chang, C., Wang, L., Gu, X., Szalkowski, G., Xing, L.

      Medical physics

      ABSTRACT
      Accurate and automated early survival prediction is critical for patients with glioblastoma (GBM) as their poor prognosis requires timely treatment decision-making. To address this need, we developed a deep learning (DL)-based end-to-end workflow for GBM overall survival (OS) prediction using pre-resection basic structural multiparametric magnetic resonance images (Bas-mpMRI) with a multi-institutional public dataset and evaluated it with an independent dataset of patients on a prospective institutional clinical trial.The proposed end-to-end workflow includes a skull-stripping model, a GBM sub-region segmentation model and an ensemble learning-based OS prediction model. The segmentation model utilizes skull-stripped Bas-mpMRIs to segment three GBM sub-regions. The segmented GBM is fed into the contrastive learning-based OS prediction model to classify the patients into different survival groups. Our datasets include both a multi-institutional public dataset from Medical Image Computing and Computer Assisted Intervention (MICCAI) Brain Tumor Segmentation (BraTS) challenge 2020 with 235 patients, and an institutional dataset from a 5-fraction SRS clinical trial with 19 GBM patients. Each data entry consists of pre-operative Bas-mpMRIs, survival days and patient ages. Basic clinical characteristics are also available for SRS clinical trial data. The multi-institutional public dataset was used for workflow establishing (90% of data) and initial validation (10% of data). The validated workflow was then evaluated on the institutional clinical trial data.Our proposed OS prediction workflow achieved an area under the curve (AUC) of 0.86 on the public dataset and 0.72 on the institutional clinical trial dataset to classify patients into 2 OS classes as long-survivors (>12 months) and short-survivors (<12 months), despite the large variation in Bas-mpMRI protocols. In addition, as part of the intermediate results, the proposed workflow can also provide detailed GBM sub-regions auto-segmentation with a whole tumor Dice score of 0.91.Our study demonstrates the feasibility of employing this DL-based end-to-end workflow to predict the OS of patients with GBM using only the pre-resection Bas-mpMRIs. This DL-based workflow can be potentially applied to assist timely clinical decision-making.
    • Assessment of cardiac radiation dose in the Co-60 prone-based stereotactic partial breast irradiation using distance metrics.

      Kwon, Y. S., Parsons, D., Arbab, M., Wandrey, N., Yarlagadda, P., Stojadinovic, S., Lu, W., Alluri, P., Li, X., Chiu, T., Lin, M., Chen, L., Kim, D. W., Gonzalez, Y., Gu, X., Zhang, Y., Timmerman, R., Rahimi, A.

      Frontiers in oncology

      ABSTRACT
      Spinal metastases (SM) with epidural spinal cord compression (ESCC) present a significant challenge because of the high risk of radiation-induced injury to critical structures such as the spinal cord and nerve roots. Traditional treatment approaches often avoid circumferential stereotactic body radiotherapy (SBRT) to reduce these risks. The efficacy and safety of donut-shaped circumferential SBRT, designed to target the spinal column while sparing the spinal cord, remains underexplored. The aim of this study was to evaluate the safety and efficacy of donut-shaped circumferential CyberKnife SBRT for SM, particularly in preventing radiation-induced myelopathy and achieving local tumor control (LTC).We retrospectively analyzed data from patients treated with donut-shaped circumferential SBRT between 2014 and 2023. Key parameters examined included patient demographics, ESCC grade (Bilsky), prior treatments, clinical symptoms, and treatment parameters. We focused on SBRT dosimetric data, radiation exposure to the spinal cord and cauda equina, adherence to dose-volume constraints, and post-SBRT outcomes, including myelopathy and LTC.Forty-eight lesions in 43 patients (median age: 65; range: 20-78) were reviewed. One patient required separation surgery for severe ESCC (Bilsky grade 3). The median clinical target volume was 63.77 cm3, and the median margin dose was 24 Gy. Over a median follow-up of 8 months, LTC was 91.1% at 6 months, 87.1% at 1 year, 82.8% at 3 years, and 62.1% at 5 years. The median overall survival was 17 months. Of the 21 lesions exceeding dose constraints, only one patient exhibited clinical myelopathy, which correlated with local tumor recurrence. No radiographic myelopathy or other radiation-induced complications were observed.Donut-shaped circumferential CyberKnife SBRT is a safe and effective treatment of SM, achieving high LTC with minimal radiation-induced complications, including myelopathy.
    • Use of Carbon Fiber Implants to Improve the Safety and Efficacy of Radiation Therapy for Spine Tumor Patients.

      Lam, F. C., Guru, S., AbuReesh, D., Hori, Y. S., Chuang, C., Liu, L., Wang, L., Gu, X., Szalkowski, G. A., Wang, Z., Wohlers, C., Tayag, A., Emrich, S. C., Ustrzynski, L., Zygourakis, C. C., Desai, A., Hayden Gephart, M., Byun, J., Pollom, E. L., Rahimy, E., Soltys, S., Park, D. J., Chang, S. D.

      Brain sciences

      ABSTRACT
      Dosimetric commissioning and quality assurance (QA) for linear accelerators (LINACs) present a significant challenge for clinical physicists due to the high measurement workload and stringent precision standards. This challenge is exacerbated for radiosurgery LINACs because of increased measurement uncertainty and more demanding setup accuracy for small-field beams. Optimizing physicists' effort during beam measurements while ensuring the quality of the measured data is crucial for clinical efficiency and patient safety.To develop a radiosurgery LINAC beam model that embeds prior knowledge of beam data through implicit neural representation (NeRP) learning and to evaluate the model's effectiveness in guiding beam data sampling, predicting complete beam dataset from sparse samples, and verifying detector choice and setup during commissioning and QA.Beam data including lateral profile and tissue-phantom-ratio (TPR), collected from CyberKnife LINACs, were investigated. Multi-layer perceptron (MLP) neural networks were optimized to parameterize a continuous function of the beam data, implicitly defined by the mapping from measurement coordinates to measured dose values. Beam priors were embedded into network weights by first training the network to learn the NeRP of a vendor-provided reference dataset. The prior-embedded network was further fine-tuned with sparse clinical measurements and used to predict unacquired beam data. Prospective and retrospective evaluations of different beam data samples in finetuning the model were performed using the reference beam dataset and clinical testing datasets, respectively. Model prediction accuracy was evaluated over 10 clinical datasets collected from various LINACs with different manufacturing modes and collimation systems. Model sensitivity in detecting beam data acquisition errors including inaccurate detector positioning and inappropriate detector choice was evaluated using two additional datasets with intentionally introduced erroneous samples.Prospective and retrospective evaluations identified consistent beam data samples that are most effective in fine-tuning the model for complete beam data prediction. Despite of discrepancies between clinical beam and the reference beam, fine-tuning the model with sparse beam profile measured at a single depth or with beam TPR measured at a single collimator size predicted beam data that closely match ground truth water tank measurements. Across the 10 clinical beam datasets, the averaged mean absolute error (MAE) in percentage dose was lower than 0.5% and the averaged 1D Gamma passing rate (1%/0.5  mm for profile and 1%/1  mm for TPR) was higher than 99%. In contrast, the MAE and Gamma passing rates were above 1% and below 95% between the reference beam dataset and clinical beam datasets. Model sensitivity to beam data acquisition errors was demonstrated by significant model prediction changes when fine-tuned with erroneous versus correct beam data samples, as quantified by a Gamma passing rate as low as 18.16% between model predictions.A model for small-field radiosurgery beam was proposed that embeds prior knowledge of beam properties and predicts the entire beam data from sparse measurements. The model can serve as a valuable tool for clinical physicists to verify the accuracy of beam data acquisition and promises to improve commissioning and QA reliability and efficiency with substantially reduced number of beam measurements.
    • Single- versus multi-fraction spine stereotactic radiosurgery (ALL-STAR) for patients with spinal metastases: a randomized phase III trial protocol.

      Pratapneni, A., Klebaner, D., Soltys, S. G., Rahimy, E., Gibbs, I. C., Chang, S. D., Li, G., Hayden Gephart, M., Veeravagu, A., Szalkowski, G. A., Gu, X., Wang, L., Chuang, C., Liu, L., Jackson, S., Lu, R., Skerchak, J. A., Huang, K. Z., Wong, S., Brown, E., Pollom, E. L.

      BMC cancer

      ABSTRACT
      Current standard of care treatment for patients with spine tumors includes multidisciplinary approaches, including the following: (1) surgical tumor debulking, epidural spinal cord decompression, and spine stabilization techniques; (2) systemic chemo/targeted therapies; (3) radiation therapy; and (4) surveillance imaging for local disease control and recurrence. Titanium pedicle screw and rod fixation have become commonplace in the spine surgeon's armamentarium for the stabilization of the spine following tumor resection and separation surgery. However, the high degree of imaging artifacts seen with titanium implants on postoperative CT and MRI scans can significantly hinder the accurate delineation of vertebral anatomy and adjacent neurovascular structures to allow for the safe and effective planning of downstream radiation therapies and detection of disease recurrence. Carbon fiber-reinforced polyetheretherketone (CFR-PEEK) spine implants have emerged as a promising alternative to titanium due to the lack of artifact signals on CT and MRI, allowing for more accurate and safe postoperative radiation planning. In this article, we review the tenants of the surgical and radiation management of spine tumors and discuss the safety, efficacy, and current limitations of CFR-PEEK spine implants in the multidisciplinary management of spine oncology patients.

    2024

    • Stereotactic Radiosurgery for Ependymoma in Pediatric and Adult Patients: A Single-Institution Experience.

      Yoo, K. H., Marianayagam, N. J., Park, D. J., Persad, A., Zamarud, A., Shaghaghian, E., Tayag, A., Ustrzynski, L., Emrich, S. C., Gu, X., Ho, Q. A., Soltys, S. G., Meola, A., Chang, S. D.

      Neurosurgery

      ABSTRACT
      Detection and segmentation of brain metastases (BMs) play a pivotal role in diagnosis, treatment planning, and follow-up evaluations for effective BM management. Given the rising prevalence of BM cases and its predominantly multiple onsets, automated segmentation is becoming necessary in stereotactic radiosurgery. It not only alleviates the clinician's manual workload and improves clinical workflow efficiency but also ensures treatment safety, ultimately improving patient care. Recent strides in machine learning, particularly in deep learning (DL), have revolutionized medical image segmentation, achieving state-of-the-art results. This review aims to analyze auto-segmentation strategies, characterize the utilized data, and assess the performance of cutting-edge BM segmentation methodologies. Additionally, we delve into the challenges confronting BM segmentation and share insights gleaned from our algorithmic and clinical implementation experiences.
    • Auto-delineation of treatment target volume for radiation therapy using large language model-aided multimodal learning.

      Rajendran, P., Chen, Y., Qiu, L., Niedermayr, T., Liu, W., Buyyounouski, M., Bagshaw, H., Han, B., Yang, Y., Kovalchuk, N., Gu, X., Hancock, S., Xing, L., Dai, X.

      International journal of radiation oncology, biology, physics

      ABSTRACT
      Surface-guided imaging (SGI) is increasingly utilized to monitor patient motion during deep inspiration breath hold (DIBH) in radiotherapy. Understanding the association between surface and internal motion is crucial for effective monitoring.To investigate the relation between motion detected by SGI using surface-guided radiotherapy (SGRT) and internal motion measured through diaphragm tracking on kV projections acquired with DIBH for online CBCT.Both SGI and kV were simultaneously acquired for ten patients over a total of 200 breath holds (BH). Diaphragm tracking was performed using second-degree polynomial curve fitting on the derivative images for each kV projection and high-pass filtering at 1/30 Hz to remove rotational effects. The superior-inferior (SI) and anterior-posterior (AP) motions of SGI were then compared to kV tracking using various statistical measures.The correlation (individuals' median: -0.07 to 0.73) was a suboptimal metric for the BH data. The median and 95th percentile absolute differences between SGI-SI and kV were 0.73 mm and 3.46 mm, respectively, during DIBH. For SGI-AP, the corresponding values were 0.55 mm and 2.80 mm. For inter-BH measurements, the contingency table based on a 3 mm threshold indicated surface/diaphragm motion agreement for SGI-SI/kV and SGI-AP/kV was 61 % and 56 %, respectively.Both intra- and inter-BH measurements indicated a limited association between surface and diaphragm motion, with certain constraints noted due to kV tracking and DIBH data. These findings warrant further investigation into the association between surface and internal motion.
    • Where Does Auto-Segmentation for Brain Metastases Radiosurgery Stand Today?

      Kim, M., Wang, J. Y., Lu, W., Jiang, H., Stojadinovic, S., Wardak, Z., Dan, T., Timmerman, R., Wang, L., Chuang, C., Szalkowski, G., Liu, L., Pollom, E., Rahimy, E., Soltys, S., Chen, M., Gu, X.

      Bioengineering (Basel, Switzerland)

      ABSTRACT
      Ultra-high dose rate (FLASH) irradiation has been reported to reduce normal tissue damage compared with conventional dose rate (CONV) irradiation without compromising tumor control. This proof-of-concept study aims to develop a deep learning (DL) approach to quantify the FLASH isoeffective dose (dose of CONV that would be required to produce the same effect as the given physical FLASH dose) with post-irradiation mouse intestinal histological images.84 healthy C57BL/6J female mice underwent 16 MeV electron CONV (0.12Gy/s; n=41) or FLASH (200Gy/s; n=43) single fraction whole abdominal irradiation. Physical dose ranged from 12 to 16Gy for FLASH and 11 to 15Gy for CONV in 1Gy increments. 4 days after irradiation, 9 jejunum cross-sections from each mouse were H&E stained and digitized for histological analysis. CONV dataset was randomly split into training (n=33) and testing (n=8) datasets. ResNet101-based DL models were retrained using the CONV training dataset to estimate the dose based on histological features. The classical manual crypt counting (CC) approach was implemented for model comparison. Cross-section-wise mean squared error (CS-MSE) was computed to evaluate the dose estimation accuracy of both approaches. The validated DL model was applied to the FLASH dataset to map the physical FLASH dose into the isoeffective dose.The DL model achieved a CS-MSE of 0.20Gy2 on the CONV testing dataset compared with 0.40Gy2 of the CC approach. Isoeffective doses estimated by the DL model for FLASH doses of 12, 13, 14, 15, and 16 Gy were 12.19±0.46, 12.54±0.37, 12.69±0.26, 12.84±0.26, and 13.03±0.28 Gy, respectively.Our proposed DL model achieved accurate CONV dose estimation. The DL model results indicate that in the physical dose range of 13 to 16 Gy, the biological dose response of small intestinal tissue to FLASH irradiation is represented by a lower isoeffective dose compared to the physical dose. Our DL approach can be a tool for studying isoeffective doses of other radiation dose modifying interventions.
    • Motion analysis comparing surface imaging and diaphragm tracking on kV projections for deep inspiration breath hold (DIBH).

      Chen, M., Chiu, T., Folkert, M. R., Timmerman, R., Gu, X., Lu, W., Parsons, D.

      Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB)

      ABSTRACT
      BACKGROUND AND OBJECTIVES: Hemangiopericytomas are infrequent vascular tumors originating from Zimmermann pericytes. The conventional treatment involves gross total resection, followed by adjuvant radiotherapy. Nevertheless, their tendency to infiltrate dural sinuses, high vascularity, and anatomic complexity pose challenges for radical resection, leading to a significant risk of recurrence. Stereotactic radiosurgery (SRS) has emerged as a promising adjuvant therapy to address these challenges. Our study provides the largest single-institutional retrospective, aiming to evaluate the effectiveness and safety of SRS as a treatment modality for residual, recurrent, and metastatic hemangiopericytomas.METHODS: From 1998 to 2023, 27 patients with 101 tumors underwent CyberKnife SRS at Stanford University Medical Center. The median age was 51 years at the time of treatment. The median follow-up period from SRS was 103 months (range: 6-250). All patients underwent upfront surgical resection. The median tumor volume was 1.5 cc. The median single-fraction equivalent dose was 19 Gy. The SRS was administered at the 76% of the median isodose line (range: 64-89).RESULTS: Of the 101 treated tumors, 24 (23.8%) progressed with a median time to recurrence of 30 months. At 10 years, the rates of local tumor control (LTC), overall survival (OS), and progression-free survival (PFS) were 74.3%, 80.8%, and 67%, respectively. In patients with metastatic lesions, the LTC rates were significantly greater when compared with those with residual or recurrent tumors. There was no significant difference between patients with residual, recurrent, and metastatic hemangiopericytomas in OS and PFS. Notably, no cases of radiation-induced adverse events were detected.CONCLUSION: SRS leads to excellent LTC, PFS, and OS at 10 years with negligible risk for adverse events. Therefore, it is an effective and safe management modality for patients with residual, recurrent, and metastatic hemangiopericytomas.
    • Exploring deep learning for estimating the isoeffective dose of FLASH irradiation from mouse intestinal histology images.

      Fu, J., Yang, Z., Melemenidis, S., Viswanathan, V., Dutt, S., Manjappa, R., Lau, B., Soto, L. A., Ashraf, R., Skinner, L., Yu, S. J., Surucu, M., Casey, K. M., Rankin, E. B., Graves, E., Lu, W., Loo, B. W., Gu, X.

      International journal of radiation oncology, biology, physics

      ABSTRACT
      Stereotactic radiosurgery (SRS) has been an attractive treatment modality for both cranial and spinal hemangioblastomas, especially for multiple lesions commonly associated with von Hippel-Lindau (VHL) disease. This study aims to provide the largest long-term analysis of treatment efficacy and adverse effects of SRS for cranial and spinal hemangioblastomas at a single institution.We evaluated the clinical and radiological outcomes of patients with hemangioblastomas treated with CyberKnife SRS at our institute from 1998 to 2022. The follow-up data were available for 135 hemangioblastomas in 35 patients. Twenty-eight patients had 123 hemangioblastomas associated with VHL, and 7 had 12 sporadic hemangioblastomas. The median age was 36 years, and the median tumor volume accounted for 0.4 cc. The SRS was administered with the median single-fraction equivalent dose of 18 Gy to the 77% median isodose line.At a median follow-up of 57 months (range: 3-260), only 20 (16.2%) of the VHL-associated and 1 (8.3%) sporadic hemangioblastomas progressed. The 5-year local tumor control rate was 91.3% for all hemangioblastomas, 91.7% among the sporadic lesions, and 92.9% in patients with VHL. SRS improved tumor-associated symptoms of 98 (74.8%) of 131 symptomatic hemangioblastomas, including headache, neck pain, dizziness, visual disturbances, dysesthesia, ataxia, motor impairment, seizures, and dysphagia. Two patients developed radiation necrosis (5.7%), and 1 of them required surgical resection.SRS is a safe and effective treatment option for patients with hemangioblastomas in critical locations, such as the brainstem, cervicomedullary junction, and spinal cord, and in patients with multiple hemangioblastomas associated with VHL disease.
    • Stereotactic Radiosurgery for Residual, Recurrent, and Metastatic Hemangiopericytomas: A Single-Institution Retrospective Experience.

      Yoo, K. H., Park, D. J., Veeravagu, A., Persad, A., Lee, M., Marianayagam, N. J., Zamarud, A., Gu, X., Pollom, E. L., Soltys, S. G., Meola, A., Chang, S. D.

      Neurosurgery

      ABSTRACT
      Background/Objectives: Medulloblastoma is the most common malignant brain tumor in children. In recent decades, the therapeutic landscape has undergone significant changes, with stereotactic radiosurgery (SRS) emerging as a promising treatment for recurrent cases. Our study provides a comprehensive analysis of the long-term efficacy and safety of SRS in recurrent medulloblastomas across both pediatric and adult patients at a single institution. Methods: We retrospectively reviewed the clinical and radiological records of patients who underwent CyberKnife SRS for recurrent cranial medulloblastomas at our institution between 1998 and 2023. Follow-up data were available for 15 medulloblastomas in 10 patients. The cohort comprised eight pediatric patients (ages 3-18) and two adult patients (ages 19-75). The median age at the time of SRS was 13 years, the median tumor volume accounted for 1.9 cc, the median biologically equivalent dose (BED) was 126 Gy, and the single-fraction equivalent dose (SFED) was 18 Gy. The SRS was administered at 75% of the median isodose line. Results: Following a median follow-up of 39 months (range: 6-78), 53.3% of the medulloblastomas progressed, 13.3% regressed, and 33.3% remained stable. The 3-year local tumor control (LTC) rate for all medulloblastomas was 65%, with lower rates observed in the adult cohort (50%) and higher rates in pediatric patients (67%). The 3-year overall survival (OS) rate was 70%, with significantly higher rates in pediatric patients (75%) compared to adult patients (50%). The 3-year progression-free survival (PFS) rate was 58.3%, with higher rates in pediatric patients (60%) compared to adult patients (50%). Two pediatric patients developed radiation-induced edema, while two adult patients experienced radiation necrosis at the latest follow-up, with both adult patients passing away. Conclusions: Our study provides a complex perspective on the efficacy and safety of CyberKnife SRS in treating recurrent cranial medulloblastomas across pediatric and adult populations. The rarity of adverse radiation events (AREs) underscores the safety profile of SRS, reinforcing its role in enhancing treatment outcomes. The intricacies of symptomatic outcomes, intertwined with factors such as age, tumor location, and prior surgeries, emphasize the need for personalized treatment approaches. Our findings underscore the imperative for ongoing research and the development of more refined treatment strategies for recurrent medulloblastomas. Given the observed disparities in treatment outcomes, a more meticulous tailoring of treatment approaches becomes crucial.
    • Stereotactic Radiosurgery for Cranial Nerve Metastases: A Single Institution Experience.

      Persad, A. R., Shahsavari, N., Ahmad, M., McCleary, T., Park, D. J., Hori, Y. S., Emrich, S. C., Ustrzynski, L., Tayag, A., Gu, X., Rahimy, E., Pollom, E. L., Soltys, S. G., Meola, A., Chang, S. D.

      ABSTRACT
      Deep learning (DL) models for medical image segmentation are highly influenced by intensity variations of input images and lack generalization due to primarily utilizing pixels' intensity information for inference. Acquiring sufficient training data is another challenge limiting models' applications. Here, we proposed to leverage the consistency of organs' anatomical position and shape information in medical images. We introduced a framework leveraging recurring anatomical patterns through global binary masks for organ segmentation. Two scenarios were studied: (1) Global binary masks were the only input for the U-Net based model, forcing exclusively encoding organs' position and shape information for rough segmentation or localization. (2) Global binary masks were incorporated as an additional channel providing position/shape clues to mitigate training data scarcity. Two datasets of the brain and heart CT images with their ground-truth were split into (26:10:10) and (12:3:5) for training, validation, and test respectively. The two scenarios were evaluated using full training split as well as reduced subsets of training data. In scenario (1), training exclusively on global binary masks led to Dice scores of 0.77±0.06 and 0.85±0.04 for the brain and heart structures respectively. Average Euclidian distance of 3.12±1.43mm and 2.5±0.93mm were obtained relative to the center of mass of the ground truth for the brain and heart structures respectively. The outcomes indicated encoding a surprising degree of position and shape information through global binary masks. In scenario (2), incorporating global binary masks led to significantly higher accuracy relative to the model trained on only CT images in small subsets of training data; the performance improved by 4.3-125.3% and 1.3-48.1% for 1-8 training cases of the brain and heart datasets respectively. The findings imply the advantages of utilizing global binary masks for building models that are robust to image intensity variations as well as an effective approach to boost performance when access to labeled training data is highly limited.
    • Deep learning-based overall survival prediction in patients with glioblastoma: An automatic end-to-end workflow using pre-resection basic structural multiparametric MRIs.

      Yang, Z., Zamarud, A., Marianayagam, N. J., Park, D. J., Yener, U., Soltys, S. G., Chang, S. D., Meola, A., Jiang, H., Lu, W., Gu, X.

      Computers in biology and medicine

      ABSTRACT
      Artificial intelligence (AI)-aided methods have made significant progress in the auto-delineation of normal tissues. However, these approaches struggle with the auto-contouring of radiotherapy target volume. Our goal is to model the delineation of target volume as a clinical decision-making problem, resolved by leveraging large language model-aided multimodal learning approaches.A vision-language model, termed Medformer, has been developed, employing the hierarchical vision transformer as its backbone, and incorporating large language models to extract text-rich features. The contextually embedded linguistic features are seamlessly integrated into visual features for language-aware visual encoding through the visual language attention module. Metrics, including Dice similarity coefficient (DSC), intersection over union (IOU), and 95th percentile Hausdorff distance (HD95), were used to quantitatively evaluate the performance of our model. The evaluation was conducted on an in-house prostate cancer dataset and a public oropharyngeal carcinoma (OPC) dataset, totaling 668 subjects.Our Medformer achieved a DSC of 0.81 ± 0.10 versus 0.72 ± 0.10, IOU of 0.73 ± 0.12 versus 0.65 ± 0.09, and HD95 of 9.86 ± 9.77 mm versus 19.13 ± 12.96 mm for delineation of gross tumor volume (GTV) on the prostate cancer dataset. Similarly, on the OPC dataset, it achieved a DSC of 0.77 ± 0.11 versus 0.72 ± 0.09, IOU of 0.70 ± 0.09 versus 0.65 ± 0.07, and HD95 of 7.52 ± 4.8 mm versus 13.63 ± 7.13 mm, representing significant improvements (p < 0.05). For delineating the clinical target volume (CTV), Medformer achieved a DSC of 0.91 ± 0.04, IOU of 0.85 ± 0.05, and HD95 of 2.98 ± 1.60 mm, comparable to other state-of-the-art algorithms.Auto-delineation of the treatment target based on multimodal learning outperforms conventional approaches that rely purely on visual features. Our method could be adopted into routine practice to rapidly contour CTV/GTV.
    • The Role of CyberKnife Stereotactic Radiosurgery in Recurrent Cranial Medulloblastomas across Pediatric and Adult Populations.

      Yoo, K. H., Marianayagam, N. J., Park, D. J., Zamarud, A., Gu, X., Pollom, E., Soltys, S. G., Meola, A., Chang, S. D.

      Journal of clinical medicine

      ABSTRACT
      Ependymoma is commonly classified as World Health Organization grade 2 with the anaplastic variant categorized as grade 3. Incomplete resection or anaplastic features can result in unfavorable outcomes. Stereotactic radiosurgery (SRS) provides a minimally invasive approach for recurrent ependymomas. Our study investigates the efficacy and safety of SRS for grade 2 and 3 ependymomas in pediatric and adult populations.We conducted a retrospective analysis on 34 patients with 75 ependymomas after CyberKnife SRS between 1998 and 2023. Fourteen were pediatric (3-18 years), and 20 were adult (19-75 years) patients. The median age was 21 years, and the median tumor volume was 0.64 cc. The median single-fraction equivalent dose was 16.6 Gy, with SRS administered at 77% of the median isodose line.After a median follow-up of 42.7 months (range: 3.8-438.3), 22.7% of ependymomas progressed. The 5-year local tumor control rate was 78.1%, varying between 59.6% and 90.2% for children and adults, with grade 2 at 85.9% compared with 58.5% for grade 3 tumors. The 5-year overall survival rate was 73.6%, notably higher in adults (94.7%) than in children (41%), and 100% for grade 2 but decreased to 35.9% for grade 3 patients. The 5-year progression-free survival rate was 68.5%, with 78.3% and 49.2% for adults and children, respectively, and a favorable 88.8% for grade 2, contrasting with 32.6% for grade 3 patients. Symptom improvement was observed in 85.3% of patients. Adverse radiation effects occurred in 21.4% of pediatric patients.Our study supports SRS as a viable modality for pediatric and adult patients with grade 2 and 3 ependymomas. Despite lower local tumor control in pediatric and grade 3 cases, integrating SRS holds promise for improved outcomes. Emphasizing careful patient selection, personalized treatment planning, and long-term follow-up is crucial for optimal neurosurgical outcomes.

    2023

    • STEREOTACTIC RADIOSURGERY FOR RESIDUAL, RECURRENT, AND METASTATIC HEMANGIOPERICYTOMAS: A SINGLE INSTITUTION EXPERIENCE

      Yoo, K., Park, D., Veeravagu, A., Lee, M., Marianayagam, N., Zamarud, A., Gu, X., Pollom, E., Soltys, S., Chang, S., Meola, A.

      ABSTRACT
      We compiled a sampling of the treatment techniques of intensity-modulated total body irradiation, total marrow irradiation and total marrow and lymphoid irradiation utilized by several centers across North America and Europe. This manuscript does not serve as a consensus guideline, but rather is meant to serve as a convenient reference for centers that are considering starting an intensity-modulated program.
    • Angular correction methodology and characterization of a high-resolution CMOS array for patient specific quality assurance on a robotic arm linac.

      Ashraf, M. R., Krimmer, J., Zalavri, L., Gu, X., Wang, L., Chuang, C. F.

      Journal of applied clinical medical physics

      ABSTRACT
      &#xD;To develop, characterize and improve upon a high-resolution 3D printed radioluminescence-based imaging phantom for quality assurance (QA) of a robotic arm linear accelerator.&#xD;Approach: &#xD;A phantom was constructed which consisted of a scintillating sheet, fiducial markers, a low-cost CMOS camera and a 3D printed light-tight enclosure. The camera, equipped with a 12 mm lens, was angled 45 degrees from the horizontal axis with a direct line of sight of the scintillating sheet. A perspective image transformation with optical distortion correction was employed to obtain beam's eye view images for different collimators. Beam profiles, Iris™ field size, MLC leaf positioning and central laser-radiation field coincidence QA tests were performed and compared against data obtained with gafchromic film. The phantom's short-term stability, sensitivity to changes in output, field size and leaf positioning were also assessed. &#xD;Main Results:&#xD;The limiting resolution of the optical system was measured to be ~ 0.26 mm. Field size, as measured by the radioluminescence system for Iris apertures, agreed to within 0.2 mm of the values measured using film. The imaging system was sensitive to field size changes well below 0.2 mm and output changes as small as 1 Monitor Unit (MU). For the optical setup, the mean leaf deviation error for banks X1 and X2 was 0.21 and 0.17 mm at 800 mm SAD, whereas the mean difference for the film dataset was 0.16 mm and 0.22 mm for banks X1 and X2, respectively. The optical system was able to detect leaf positioning errors as small as 0.2 mm. Compared with film data, excellent agreement was seen for relative central axis beam profiles for 10 mm and 5 mm beams. &#xD;Significance: &#xD;The phantom presented here is an alternative to film and electronic portal imager devices, due to its low-cost, portability, and high spatial and temporal resolution. &#xD.
    • Considerations for intensity modulated total body or total marrow and lymphoid irradiation.

      Parsons, D., Lim, T. Y., Teruel, J. R., Galavis, P., Agostinelli, S., Liang, J., Mancosu, P., Cherpak, A., Stanley, D. N., Ahn, K., Guo, B., Gonzalez, Y., Burmeister, J., Wong, J. Y., Gu, X., Kim, G. G.

      Clinical and translational radiation oncology

      ABSTRACT
      Stereotactic radiosurgery (SRS) has been an attractive treatment modality for both cranial and spinal hemangioblastomas, especially for multiple lesions commonly associated with von Hippel-Lindau (VHL) disease. This study aims to provide the largest long-term analysis of treatment efficacy and adverse effects of SRS for cranial and spinal hemangioblastomas at a single institution.We evaluated the clinical and radiological outcomes of patients with hemangioblastomas treated with CyberKnife SRS at our institute from 1998 to 2022. The follow-up data were available for 135 hemangioblastomas in 35 patients. Twenty-eight patients had 123 hemangioblastomas associated with VHL, and 7 had 12 sporadic hemangioblastomas. The median age was 36 years, and the median tumor volume accounted for 0.4 cc. The SRS was administered with the median single-fraction equivalent dose of 18 Gy to the 77% median isodose line.At a median follow-up of 57 months (range: 3-260), only 20 (16.2%) of the VHL-associated and 1 (8.3%) sporadic hemangioblastomas progressed. The 5-year local tumor control rate was 91.3% for all hemangioblastomas, 91.7% among the sporadic lesions, and 92.9% in patients with VHL. SRS improved tumor-associated symptoms of 98 (74.8%) of 131 symptomatic hemangioblastomas, including headache, neck pain, dizziness, visual disturbances, dysesthesia, ataxia, motor impairment, seizures, and dysphagia. Two patients developed radiation necrosis (5.7%), and 1 of them required surgical resection.SRS is a safe and effective treatment option for patients with hemangioblastomas in critical locations, such as the brainstem, cervicomedullary junction, and spinal cord, and in patients with multiple hemangioblastomas associated with VHL disease.
    • An Integrated 3D Printed Enclosure for a Radioluminescent-Based Phantom for Quality Assurance on a Robotic-Arm Linac.

      Ashraf, M. R., Gibson, C., Skinner, L. B., Gu, X., Xing, L., Wang, L.

      Physics in medicine and biology

      ABSTRACT
      Accurate and efficient delineation of the clinical target volume (CTV) is of utmost significance in post-operative breast cancer radiotherapy. However, CTV delineation is challenging as the exact extent of microscopic disease encompassed by CTV is not visualizable in radiological images and remains uncertain. We proposed to mimic physicians' contouring practice for CTV segmentation in Stereotactic Partial Breast Irradiation (S-PBI) where CTV is derived from tumor bed volume (TBV) via a margin expansion followed by correcting the extensions for anatomical barriers of tumor invasion (e.g., skin, chest wall). We proposed a deep-learning model, where CT images and the corresponding TBV masks formed a multi-channel input for a 3D U-Net based architecture. The design guided the model to encode the location-related image features and directed the network to focus on TBV to initiate CTV segmentation. Gradient weighted Class Activation Map (Grad-CAM) visualizations of the model predictions revealed that the extension rules and geometric/anatomical boundaries were learnt during model training to assist the network to limit the expansion to a certain distance from the chest wall and the skin. We retrospectively collected 175 prone CT images from 35 post-operative breast cancer patients who received 5-fraction partial breast irradiation (PBI) regimen on GammaPod. The 35 patients were randomly split into training (25), validation (5) and test (5) sets. Our model achieved mean (standard deviation) of 0.94 (0.02), 2.46 (0.5) mm, and 0.53 (0.14) mm for Dice similarity coefficient, 95th percentile Hausdorff distance, and average symmetric surface distance respectively on the test set. The results are promising for improving the efficiency and accuracy of CTV delineation process during on-line treatment planning procedure.
    • Stereotactic Radiosurgery for Cranial and Spinal Hemangioblastomas: A Single-Institution Retrospective Series.

      Yoo, K. H., Park, D. J., Marianayagam, N. J., Gu, X., Pollom, E. L., Soltys, S. G., Chang, S. D., Meola, A.

      Neurosurgery

      ABSTRACT
      Deep learning (DL) models for medical image segmentation are highly influenced by intensity variations of input images and lack generalization due to primarily utilizing pixels' intensity information for inference. Acquiring sufficient training data is another challenge limiting models' applications. Here, we proposed to leverage the consistency of organs' anatomical position and shape information in medical images. We introduced a framework leveraging recurring anatomical patterns through global binary masks for organ segmentation. Two scenarios were studied: (1) Global binary masks were the only input for the U-Net based model, forcing exclusively encoding organs' position and shape information for rough segmentation or localization. (2) Global binary masks were incorporated as an additional channel providing position/shape clues to mitigate training data scarcity. Two datasets of the brain and heart CT images with their ground-truth were split into (26:10:10) and (12:3:5) for training, validation, and test respectively. The two scenarios were evaluated using full training split as well as reduced subsets of training data. In scenario (1), training exclusively on global binary masks led to Dice scores of 0.77±0.06 and 0.85±0.04 for the brain and heart structures respectively. Average Euclidian distance of 3.12±1.43mm and 2.5±0.93mm were obtained relative to the center of mass of the ground truth for the brain and heart structures respectively. The outcomes indicated encoding a surprising degree of position and shape information through global binary masks. In scenario (2), incorporating global binary masks led to significantly higher accuracy relative to the model trained on only CT images in small subsets of training data; the performance improved by 4.3-125.3% and 1.3-48.1% for 1-8 training cases of the brain and heart datasets respectively. The findings imply the advantages of utilizing global binary masks for building models that are robust to image intensity variations as well as an effective approach to boost performance when access to labeled training data is highly limited.