Therapeutic Radiation Delivery Research Articles

Targeted Radionuclide Therapy for the Treatment of Metastatic Bone Disease: A Retrospective Analysis in Moscow, Russia

Introduction: Metastatic bone disease (MBD) is a common complication of advanced cancer, causing significant morbidity and negatively impacting patients' quality of life. Targeted radionuclide therapy (TRT) has emerged as a promising treatment modality for MBD, offering targeted delivery of therapeutic radiation to bone metastases while minimizing damage to healthy tissues. Methods: A retrospective cohort study was conducted at leading oncology centers in Moscow, Russia, between 2018 and 2023. Patients with MBD who received TRT with either Strontium-89 or Samarium-153 were included. Data on patient demographics, primary tumor type, number of bone metastases, pre-treatment pain scores, performance status, and survival outcomes were collected. Results: A total of 150 patients were included in the study (mean age 62 years, 55% female). The most common primary tumor types were prostate (35%), breast (25%), and lung (15%). The median number of bone metastases was 5 (range 1-20). Pre-treatment pain scores were high (median 7 on a 0-10 scale). A significant reduction in pain scores was observed post-TRT (median 3, p<0.001). Overall survival at 1 year was 75%, with a median survival of 18 months. Favorable prognostic factors included a lower number of bone metastases, good performance status, and absence of visceral metastases. Conclusion: TRT is a safe and effective treatment option for patients with MBD in Moscow, Russia, offering significant pain palliation and improved quality of life.

380TiP A phase I/II dose-escalation and expansion cohort study of intracerebroventricular radioimmunotherapy using 177Lu-DTPA-omburtamab in pediatric and adolescent patients with recurrent or refractory medulloblastoma

Medulloblastoma represents 20% of all pediatric brain tumors. Recurrent/refractory medulloblastoma is particularly challenging, with no standard of care and poor treatment outcomes. The B7-H3 receptor is an attractive target for radioimmunotherapy as it is overexpressed on the cell surface of >96% of medulloblastomas. Omburtamab is a monoclonal antibody that specifically binds to B7-H3 and can be radiolabeled allowing targeted delivery of therapeutic radiation to tumor cells. Intracerebroventricular administration of 131I-omburtamab is currently under study in patients (pts) with neuroblastoma and CNS/leptomeningeal metastases and has received breakthrough designation by the FDA.

Photoperiodic Flower Mimicking Metallic Nanoparticles for Image-Guided Medicine Applications.

Nanoradiosensitizers have been developed to enhance localization and precision of therapeutic radiation delivery. A specific volume of comprising surface atoms is known to be the radiosensitizing region. However, the shape-dependent local dose enhancement of nanoparticles is often underestimated and rarely reported. Here, a noble metal nanostructure, inspired by the photoperiodic day-flowers, was synthesized by metal reduction with bile acid molecules. The impact of high surface area of day-flowermimicking metallicnanoparticles (D-NP) on radiosensitizing effect was demonstrated with assays for ROS generation, cellular apoptosis, and clonogenic survival of human liver cancer cells (HepG2) cells. In comparison with lower-surface-area spherical night-flower mimickingmetallicnanoparticles (N-NP), exposure of our D-NP to external beam radiation doses led to a significant increase in reactive oxygen species (ROS) production and radiosensitizing cell cycle synchronization, resulting in an enhanced cancer-cell-killing effect. In clonogenic survival studies, dose-enhancing factor (DEF) of D-NP was 16.5-fold higher than N-NP. Finally, we demonstrated in vivo feasibility of our D-NP as a potent nanoradiosensitizer and CT contrast agent for advanced image-guided radiation therapy.

Noninvasive measurement of tissue blood oxygenation with Cerenkov imaging during therapeutic radiation delivery.

Tumor tissue oxygenation significantly affects the outcome of radiotherapy. Real-time monitoring of tumor hypoxia is highly desirable for effective radiotherapy, and is the basis for improved treatment because hypoxic tumor cells are more resistant to radiation damage than fully oxygenated cells. We propose to use Cerenkov imaging to monitor tumor hypoxia by means of tissue blood oxygenation without the need for any exogenous contrast agent. Using a rodent hypoxia model, we demonstrate that Cerenkov imaging can be used as a noninvasive and noncontact method to measure tissue blood oxygenation level during radiation delivery. The data from Cerenkov imaging were validated using near infrared spectrometry methods. The results demonstrate the feasibility of using Cerenkov imaging to monitor tumor hypoxia during therapeutic radiation delivery.

Noninvasive measurement of tissue blood oxygenation with Cerenkov imaging during therapeutic radiation delivery

Noninvasive measurement of tissue blood oxygenation with Cerenkov imaging during therapeutic radiation delivery

Impact of therapeutic irradiation on healthy articular cartilage.

Radiation-induced complications in bone and cartilage are of increasing concern due to potential long-term effects in cancer survivors. Healthy articular cartilage may be exposed to radiation during either chondrosarcoma treatment or in-field radiotherapy of tumors located in close proximity to articulation. Cartilage exposed to radiation undergoes bone differentiation and senescence, which can lead to painful and disabling sequelae that can impair patient quality of life. An understanding of the biological processes involved in healthy cartilage response to radiotherapy may not only optimize the delivery of therapeutic radiation but also reduce the risk of long-term sequelae in irradiated cartilage. Over the last few decades, radiobiology studies have focused primarily on signaling and repair of DNA damage pathways induced by ionizing radiation in immortalized cells under conditions dramatically different from human homeostasis. This research needs to be continued and broadened, since the range of normal tissue responses to radiation exposure is still not fully understood, despite being recognized as the major limiting factor in the rupture of tissue homeostasis after radiotherapy. Human articular cartilage is an avascular tissue with low intracellular oxygen levels and is comprised of a single cell lineage of chondrocytes embedded in a highly dense and structured extracellular matrix. These relatively unique features may impact inherent cell radiation sensitivity and suggests that canonical cell responses to ionizing radiation may not be applicable to articular cartilage. Despite the number of studies in this field, radiation-induced modifications of chondrocyte proteome remain unclear because of the dramatic variability in reported experimental conditions. In this review, we propose to introduce cartilage tissue physiology and microenvironment concepts, and then present a comprehensive synthesis of cartilage radiation biology.

The role of modern radiation therapy in the management of extremity sarcomas

For nearly half a decade, surgery and radiation therapy have been used in combination to achieve the goal of limb preservation in extremity soft tissue sarcoma, with success rates in excess of 90%. Common decision points in therapeutic radiation delivery for sarcoma are discussed, including preoperative versus postoperative irradiation, the postoperative boost, and when irradiation might be unnecessary. We describe specialized techniques, such as brachytherapy and intraoperative irradiation. The data driving current practice is summarized.

An Analysis of Radiation Therapy Medical Events in New York State

From 2001 through 2009, the New York State Department of Health (NYSDOH) has documented 244 reports of radiation therapy events, of which 228 have resulted from the delivery of radiation beam therapy using linear accelerators (LINACs). Historically, radiation therapy events involving LINACs have not been uniformly reported across the country because LINACs are regulated by state radiation control programs, and reporting requirements vary among states. The Nuclear Regulatory Commission's Nuclear Material Events Database (NMED) only tracks events involving radioactive materials (RAM). Efforts to track medical events involving LINACs at a national level have begun only recently. This article highlights the importance of tracking and analyzing all medical radiation events in order to improve quality of care and patient safety. An analysis of a subset of the data collected by the NYSDOH from 2001-2009 is presented. This subset consists of only events arising from the use of LINACs in radiation therapy. There are very few publications on errors and error rates in the use of medical accelerators in radiation therapy. This analysis highlights the most common types of errors, causes and contributing factors, areas for improvement and actions taken to bring this information to the regulated community. An error rate of 0.07% per patient receiving radiation treatment is estimated using these data and the New York State Tumor Registry data for the same period. NY State Regulations governing the practice of Radiation Oncology have been revised recently to reflect the increased complexity in the delivery of therapeutic radiation. Collaboration and sharing of data such as those presented here, between federal, state and local regulators, professional organizations such as the Conference of Radiation Control Program Directors (CRCPD), American Society for Radiation Oncology (ASTRO), American Association of Physicists in Medicine (AAPM), American College of Radiology (ACR), American College of Radiation Oncology (ACRO), manufacturers of medical radiation equipment and software developers and the regulated community has begun and will contribute to improved quality of care and patient safety.

Dosimetry Study of [I-131] and [I-125]-Meta-Iodobenzyl Guanidine in a Simulating Model for Neuroblastoma Metastasis

The physical properties of I-131 may be suboptimal for the delivery of therapeutic radiation to bone marrow metastases, which are common in the natural history of neuroblastoma. In vitro and preliminary clinical studies have implied improved efficacy of I-125 relative to I-131 in certain clinical situations, although areas of uncertainty remain regarding intratumoral dosimetry. This prompted our study using human neuroblastoma multicellular spheroids as a model of metastasis. 3D dose calculations were made using voxel-based Medical Internal Radiation Dosimetry (MIRD) and dose-point-kernel (DPK) techniques. Dose distributions for I-131 and I-125 labeled mIBG were calculated for spheroids (metastases) of various sizes from 0.01 cm to 3 cm diameter, and the relative dose delivered to the tumors was compared for the same limiting dose to the bone marrow. Based on the same data, arguments were advanced based upon the principles of tumor control probability (TCP) to emphasize the potential theoretical utility of I-125 over I-131 in specific clinical situations. I-125-mIBG can deliver a higher and more uniform dose to tumors compared to I-131 mIBG without increasing the dose to the bone marrow. Depending on the tumor size and biological half-life, the relative dose to tumors of less than 1 mm diameter can increase several-fold. TCP calculations indicate that tumor control increases with increasing administered activity, and that I-125 is more effective than I-131 for tumor diameters of 0.01 cm or less. This study suggests that I-125-mIBG is dosimetrically superior to I-131-mIBG therapy for small bone marrow metastases from neuroblastoma. It is logical to consider adding I-125-mIBG to I-131-mIBG in multi-modality therapy as these two isotopes could be complementary in terms of their cumulative dosimetry.

SU-E-J-40: Lung Lesion Tracking Using Fixed-Spaced Non-Migrating Fiducial Markers in Robotic Radiosurgery.

With lung lesion treatment being a major indication of the use of the CyberKnife (CK) robotic radiosurgery system (Accuray Inc, Sunnyvale, CA), the ability for the CK's stereoscopic kV imaging system to accurately track implanted fiducial markers becomes vital in the accurate delivery of therapeutic radiation. This study examines a novel fixed-space fiducial marker delivery system which is capable of delivering two VISICOIL (IBA Dosimetry America, Memphis, TN) non-migrating fiducial markers simultaneously at a fixed spacing through a single 20-gauge needle. More specifically, presented herein is a preliminary study which tests the CK'streatment localization system's (TLS) ability to track markers of varying size and spacing, comparing subsequent stereoscopic kV imaging to DRR's generated during the planning stages. Three markers were placed in an XLT Lung Phantom (CIRS Inc, Norfolk, VA); two markers inserted along a diagonal line in a coronal plane, separated by biocompatible spacersof varying size, and a common third marker being placed in a non-varyinglocation in a coronal plane anterior to the marker pair. This third marker allows the calculation of rotational and translation corrections. Differentcombinations were scanned, planned, and simulated; 3.5mm- and 5.0mm- long markers, each 5mm in diameter, were separated by 15mm, 17mm, and 20mm spacers. The TLS system was able to track each of the aforementioned configurations with standard lung imaging parameters.Longer markers were not included in the study since earlier studies showed that without the natural deformation that would occur upon implantation, the length would induce false tracking. This is a necessary firststep in determining the minimum spacing with which the CK's TLS can track, a study which can now proceed with the use of phantom treatments elivered to orthogonally-overlapping radiochromic film, bisecting a tumor volume which is implanted with this fiducial marker system. Research supported in-part by IBA Dosimetry America.

Radiation Therapy in Cochlear Implant Recipients

Processes of scattering and attenuation were investigated to determine the consequence on dose distributions by having a cochlear implant in the field of therapeutic radiation. Radiation oncology medical accelerator beams of 6- and 18-MV x-ray energy were used. Five cochlear implants were investigated. Each implant model was individually studied using computer dose modeling and through exercises in radiation measurement during live delivery. No side scatter was detected, and negligible backscattering was observed for the primary device housing and electrodes. Attenuation consequences were found to be dependent on the model of cochlear implant studied and specifically dependent on the material composition of each device. The maximum attenuated dose change for the study was found to be -8.8% for 6 MV and -6.6% for 18 MV. This study presents the first comparison of therapeutic radiation delivery versus computerized treatment simulation involving cochlear implants.

Contamination dose from photoneutron processes in bodily tissues during therapeutic radiation delivery.

Dose to the total body from induced radiation resulting from primary exposure to radiotherapeutic beams is not detailed in routine treatment planning though this information is potentially important for better estimates of health risks including secondary cancers. This information can also allow better management of patient treatment logistics, suggesting better timing, sequencing, and conduct of treatment. Monte Carlo simulations capable of taking into account all interactions contributing to the dose to the total body, including neutron scattering and induced radioactivity, provide the most versatile and accurate tool for investigating these effects. MCNPX code version 2.2.6 with full IAEA library of photoneutron cross sections is particularly suited to trace not only photoneutrons but also protons and heavy ion particles that result from photoneutron interactions. Specifically, the MCNPX code is applied here to the problem of dose calculations in traditional (non-IMRT) photon beam therapy. Points of calculation are located in the head, where the primary irradiation has been directed, but also in the superior portion of the torso of the ORNL Mathematical Human Phantom. We calculated dose contributions from neutrons, protons, deutrons, tritons and He-3 that are produced at the time of photoneutron interactions in the body and that would not have been accounted for by conventional radiation oncology dosimetry.

Prophylactic treatment reduces the severity of xerostomia following radiation therapy for oral cavity cancer.

Hypothesis: The underlying mechanism of irradiation-induced injury to the salivary glands was an enigma for French radiobiologist Jean Bergonie, who first described the phenomenon in 1911. Bergonie was also the scientist who characterized as “radiosensitive” tissues that, like hematological stem cells, are composed of primitive, undifferentiated cells with a high mitotic rate; and yet he was aware that salivary cells, which are highly differentiated (especially serous acinar cells), and have a low mitotic rate, are particularly radiosensitive. The enigma has not been solved and xerostomia still causes much discomfort. Annually, irradiation-induced xerostomia affects between 30000 and 50000 individuals treated for head and neck cancer in the United States alone. Since irradiation-induced xerostomia was first described, much research has been devoted to understanding the mechanism of its development. This is due, in part, to its appeal as an enigma; additionally, there is no adequate therapy for its prevention or treatment. The delivery of therapeutic radiation was greatly improved during the last decade, mainly through 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT). These technologies allow high rates of salivary gland preservation in head and neck–irradiated patients, but they are either unavailable or insufficient for too many of them. Irradiation damage occurs because of the location of the glands (symmetrical and extended), the extent of the tumors, and the high doses of radiation that are often indicated. Can one expect that, in the near future, prophylactic treatment will reduce the severity of xerostomia following radiation therapy for oral cavity cancer?