RANGE ADAPTIVE PROTON THERAPY FOR PROSTATE CANCER

Purpose: The rapid distal falloff of a proton beam allows for sparing of normal tissues distal to the target. However proton beams that aim directly towards critical structures are avoided due to concerns of range uncertainties, such as CT number conversion and anatomy variations. We propose to eliminate range uncertainty and enable prostate treatment with a single anterior beam by detecting the proton’s range at the prostate-rectal interface and adaptively adjusting the range in vivo and in real-time. Materials and Methods: A prototype device, consisting of an endorectal liquid scintillation detector and dual-inverted Lucite wedges for range compensation, was designed to test the feasibility and accuracy of the technique. Liquid scintillation filled volume was fitted with optical fiber and placed inside the rectum of an anthropomorphic pelvic phantom. Photodiode-generated current signal was generated as a function of proton beam distal depth, and the spatial resolution of this technique was calculated by relating the variance in detecting proton spills to its maximum penetration depth. The relative water-equivalent thickness of the wedges was measured in a water phantom and prospectively tested to determine the accuracy of range corrections. Treatment simulation studies were performed to test the potential dosimetric benefit in sparing the rectum. Results: The spatial resolution of the detector in phantom measurement was 0.5 mm. The precision of the range correction was 0.04 mm. The residual margin to ensure CTV coverage was 1.1 mm. The composite distal margin for 95% treatment confidence was 2.4 mm. Planning studies based on a previously estimated 2mm margin (90% treatment confidence) for 27 patients showed a rectal sparing up to 51% at 70 Gy and 57% at 40 Gy relative to IMRT and bilateral proton treatment. Conclusion: We demonstrated the feasibility of our design. Use of this technique allows for proton treatment using a single anterior beam, significantly reducing the rectal dose

Is a 3-mm intrafractional margin sufficient for daily image-guided intensity-modulated radiation therapy of prostate cancer?

PURPOSE: To determine whether a 3-mm isotropic target margin adequately covers the prostate and seminal vesicles (SVs) during administration of an intensity-modulated radiation therapy (IMRT) treatment fraction, assuming that daily image-guided setup is performed just before each fraction. MATERIALS AND METHODS: In-room computed tomographic (CT) scans were acquired immediately before and after a daily treatment fraction in 46 patients with prostate cancer. An eight-field IMRT plan was designed using the pre-fraction CT with a 3-mm margin and subsequently recalculated on the post-fraction CT. For convenience of comparison, dose plans were scaled to full course of treatment (75.6 Gy). Dose coverage was assessed on the post-treatment CT image set. RESULTS: During one treatment fraction (21.4+/-5.5 min), there were reductions in the volumes of the prostate and SVs receiving the prescribed dose (median reduction 0.1% and 1.0%, respectively, p\u3c0.001) and in the minimum dose to 0.1 cm(3) of their volumes (median reduction 0.5 and 1.5 Gy, p\u3c0.001). Of the 46 patients, three patients\u27 prostates and eight patients\u27 SVs did not maintain dose coverage above 70 Gy. Rectal filling correlated with decreased percentage-volume of SV receiving 75.6, 70, and 60 Gy (p\u3c0.02). CONCLUSIONS: The 3-mm intrafractional margin was adequate for prostate dose coverage. However, a significant subset of patients lost SV dose coverage. The rectal volume change significantly affected SV dose coverage. For advanced-stage prostate cancers, we recommend to use larger margins or improve organ immobilization (such as with a rectal balloon) to ensure SV coverage

Ozanimod to treat relapsing forms of multiple sclerosis: A comprehensive review of disease, drug efficacy and side effects

Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing–remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators

Ozanimod to treat relapsing forms of multiple sclerosis: A comprehensive review of disease, drug efficacy and side effects

Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing–remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators

Technical Note: A Monte Carlo study of magnetic-field-induced radiation dose effects in mice.

PURPOSE:Magnetic fields are known to alter radiation dose deposition. Before patients receive treatment using an MRI-linear accelerator (MRI-Linac), preclinical studies are needed to understand the biological consequences of magnetic-field-induced dose effects. In the present study, the authors sought to identify a beam energy and magnetic field strength combination suitable for preclinical murine experiments. METHODS:Magnetic field dose effects were simulated in a mouse lung phantom using various beam energies (225 kVp, 350 kVp, 662 keV [Cs-137], 2 MV, and 1.25 MeV [Co-60]) and magnetic field strengths (0.75, 1.5, and 3 T). The resulting dose distributions were compared with those in a simulated human lung phantom irradiated with a 6 or 8 MV beam and orthogonal 1.5 T magnetic field. RESULTS:In the human lung phantom, the authors observed a dose increase of 45% and 54% at the soft-tissue-to-lung interface and a dose decrease of 41% and 48% at the lung-to-soft-tissue interface for the 6 and 8 MV beams, respectively. In the mouse simulations, the magnetic fields had no measurable effect on the 225 or 350 kVp dose distribution. The dose increases with the Cs-137 beam for the 0.75, 1.5, and 3 T magnetic fields were 9%, 29%, and 42%, respectively. The dose decreases were 9%, 21%, and 37%. For the 2 MV beam, the dose increases were 16%, 33%, and 31% and the dose decreases were 9%, 19%, and 30%. For the Co-60 beam, the dose increases were 19%, 54%, and 44%, and the dose decreases were 19%, 42%, and 40%. CONCLUSIONS:The magnetic field dose effects in the mouse phantom using a Cs-137, 3 T combination or a Co-60, 1.5 or 3 T combination most closely resemble those in simulated human treatments with a 6 MV, 1.5 T MRI-Linac. The effects with a Co-60, 1.5 T combination most closely resemble those in simulated human treatments with an 8 MV, 1.5 T MRI-Linac

Changes in the Pelvic Anatomy After an IMRT Treatment Fraction of Prostate Cancer

Purpose: To quantify the three-dimensional variations of pelvic anatomy after a single treatment fraction. Methods and Materials: Forty-six prostate cancer patients underwent computed tomography (CT) scanning with an in-room CT-on-rail system, before and immediately after one intensity-modulated radiotherapy (IMRT) session. To study the soft-tissue anatomy changes, the pre- and post-treatment CT images were registered using the bony structure with an in-house image registration software system. The center of volume for both the prostate and seminal vesicles was used to assess the relative displacement of the same structure after the treatment fraction. Results: During one treatment fraction (21 ± 4 min), both the prostate and seminal vesicles showed statistically significant systematic trends in the superior and anterior directions of the patient\u27s anatomy. The net increase in bladder volume was huge (127 ± 79 cm3), yet this change did not translate into large target displacements. Although the population mean displacements in either direction were 1.3 ± 2.9 mm for the prostate and 1.2 ± 4.1 mm for the seminal vesicles in the anterior direction, a few patients had displacements as large as 8.4 mm and 15.6 mm, respectively. These large displacements correlated strongly (p \u3c 0.001) with large rectal volume increases caused by gaseous build-up in the rectum. Conclusion: The observed intrafraction variations in anatomy during prostate IMRT sessions suggest that, for any given fraction, the organ motion and volume changes can potentially lead to compromised target coverage in about 15% of patients in whom the prostate position shifted \u3e4 mm. © 2007 Elsevier Inc. All rights reserved

Radiation-induced lung toxicity in mice irradiated in a strong magnetic field.

Strong magnetic fields affect radiation dose deposition in MRI-guided radiation therapy systems, particularly at interfaces between tissues of differing densities such as those in the thorax. In this study, we evaluated the impact of a 1.5 T magnetic field on radiation-induced lung damage in C57L/J mice. We irradiated 140 mice to the whole thorax with parallel-opposed Co-60 beams to doses of 0, 9.0, 10.0, 10.5, 11.0, 12.0, or 13.0 Gy (20 mice per dose group). Ten mice per dose group were irradiated while a 1.5 T magnetic field was applied transverse to the radiation beam and ten mice were irradiated with the magnetic field set to 0 T. We compared survival and noninvasive assays of radiation-induced lung damage, namely respiratory rate and metrics derived from thoracic cone-beam CTs, between the two sets of mice. We report two main results. First, the presence of a transverse 1.5 T field during irradiation had no impact on survival of C57L/J mice. Second, there was a small but statistically significant effect on noninvasive assays of radiation-induced lung damage. These results provide critical safety data for the clinical introduction of MRI-guided radiation therapy systems

Ozanimod to Treat Relapsing Forms of Multiple Sclerosis: A Comprehensive Review of Disease, Drug Efficacy and Side Effects

Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing–remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators

Synthetic Megavoltage Cone Beam Computed Tomography Image Generation for Improved Contouring Accuracy of Cardiac Pacemakers

In this study, we aimed to enhance the contouring accuracy of cardiac pacemakers by improving their visualization using deep learning models to predict MV CBCT images based on kV CT or CBCT images. Ten pacemakers and four thorax phantoms were included, creating a total of 35 combinations. Each combination was imaged on a Varian Halcyon (kV/MV CBCT images) and Siemens SOMATOM CT scanner (kV CT images). Two generative adversarial network (GAN)-based models, cycleGAN and conditional GAN (cGAN), were trained to generate synthetic MV (sMV) CBCT images from kV CT/CBCT images using twenty-eight datasets (80%). The pacemakers in the sMV CBCT images and original MV CBCT images were manually delineated and reviewed by three users. The Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), and mean surface distance (MSD) were used to compare contour accuracy. Visual inspection showed the improved visualization of pacemakers on sMV CBCT images compared to original kV CT/CBCT images. Moreover, cGAN demonstrated superior performance in enhancing pacemaker visualization compared to cycleGAN. The mean DSC, HD95, and MSD for contours on sMV CBCT images generated from kV CT/CBCT images were 0.91 ± 0.02/0.92 ± 0.01, 1.38 ± 0.31 mm/1.18 ± 0.20 mm, and 0.42 ± 0.07 mm/0.36 ± 0.06 mm using the cGAN model. Deep learning-based methods, specifically cycleGAN and cGAN, can effectively enhance the visualization of pacemakers in thorax kV CT/CBCT images, therefore improving the contouring precision of these devices