Ultra-High-Resolution Computed Tomography of the Lung: Image Quality of a Prototype Scanner

Purpose: The image noise and image quality of a prototype ultra-high-resolution computed tomography (U-HRCT) scanner was evaluated and compared with those of conventional high-resolution CT (C-HRCT) scanners. Materials and Methods: This study was approved by the institutional review board. A U-HRCT scanner prototype with 0.25 mm × 4 rows and operating at 120 mAs was used. The C-HRCT images were obtained using a 0.5 mm × 16 or 0.5 mm × 64 detector-row CT scanner operating at 150 mAs. Images from both scanners were reconstructed at 0.1-mm intervals; the slice thickness was 0.25 mm for the U-HRCT scanner and 0.5 mm for the C-HRCT scanners. For both scanners, the display field of view was 80 mm. The image noise of each scanner was evaluated using a phantom. U-HRCT and C-HRCT images of 53 images selected from 37 lung nodules were then observed and graded using a 5-point score by 10 board-certified thoracic radiologists. The images were presented to the observers randomly and in a blinded manner. Results: The image noise for U-HRCT (100.87 ± 0.51 Hounsfield units [HU]) was greater than that for C-HRCT (40.41 ± 0.52 HU; P <.0001). The image quality of U-HRCT was graded as superior to that of C-HRCT (P <.0001) for all of the following parameters that were examined: margins of subsolid and solid nodules, edges of solid components and pulmonary ves sels in subsolid nodules, air bronchograms, pleural indentations, margins of pulmonary vessels, edges of bronchi, and interlobar fissures. Conclusion: Despite a larger image noise, the prototype U-HRCT scanner had a significantly better image quality than the C-HRCT scanners

Immunostimulatory Effects of Radiotherapy for Local and Systemic Control of Melanoma: A Review

Recently, modern therapies involving immune checkpoint inhibitors, cytokines, and oncolytic virus have been developed. Because of the limited treatment effect of modern therapy alone, the immunostimulatory effect of radiotherapy attracted increasing attention. The combined use of radiotherapy and modern therapy has been examined clinically and non-clinically, and its effectiveness has been confirmed recently. Because melanomas have high immunogenicity, better therapeutic outcomes are desired when using immunotherapy. However, sufficient therapeutic effects have not yet been achieved. Thus far, radiotherapy has been used only for local control of tumors. Although extremely rare, radiotherapy has also been reported for systemic control, i.e., abscopal effect. This is thought to be due to an antitumor immune response. Therefore, we herein summarize past information on not only the mechanism of immune effects on radiotherapy but also biomarkers reported in case reports on abscopal effects. We also reviewed the animal model suitable for evaluating abscopal effects. These results pave the way for further basic research or clinical studies on new treatment methods for melanoma. Currently, palliative radiation is administered to patients with metastatic melanoma for local control. If it is feasible to provide both systemic and local control, the treatment benefit for the patients is very large

Why Concurrent CDDP and Radiotherapy Has Synergistic Antitumor Effects: A Review of In Vitro Experimental and Clinical-Based Studies

Chemo-radiotherapy, which combines chemotherapy with radiotherapy, has been clinically practiced since the 1970s, and various anticancer drugs have been shown to have a synergistic effect when used in combination with radiotherapy. In particular, cisplatin (CDDP), which is often the cornerstone of multi-drug combination cancer therapies, is highly versatile and frequently used in combination with radiotherapy for the treatment of many cancers. Therefore, the mechanisms underlying the synergistic effect of CDDP and radiotherapy have been widely investigated, although no definitive conclusions have been reached. We present a review of the combined use of CDDP and radiotherapy, including the latest findings, and propose a mechanism that could explain their synergistic effects. Our hypothesis involves the concepts of overlap and complementation. “Overlap” refers to the overlapping reactions of CDDP and radiation-induced excessive oxidative loading, which lead to accumulating damage to cell components, mostly within the cytoplasm. “Complementation” refers to the complementary functions of CDDP and radiation that lead to DNA damage, primarily in the nucleus. In fact, the two concepts are inseparable, but conceptualizing them separately will help us understand the mechanism underlying the synergism between radiation therapy and other anticancer drugs, and help us to design future radiosensitizers

DNA Strand Break Properties of Protoporphyrin IX by X-ray Irradiation against Melanoma

Recent reports have suggested that 5-aminolevulinic acid (5-ALA), which is a precursor to protoporphyrin IX (PpIX), leads to selective accumulation of PpIX in tumor cells and acts as a radiation sensitizer in vitro and in vivo in mouse models of melanoma, glioma, and colon cancer. In this study, we investigated the effect of PpIX under X-ray irradiation through ROS generation and DNA damage. ROS generation by the interaction between PpIX and X-ray was evaluated by two kinds of probes, 3&prime;-(p-aminophenyl) fluorescein (APF) for hydroxyl radical (&bull;OH) detection and dihydroethidium (DHE) for superoxide (O2&bull;-). &bull;OH showed an increase, regardless of the dissolved oxygen. Meanwhile, the increase in O2&bull;- was proportional to the dissolved oxygen. Strand breaks (SBs) of DNA molecule were evaluated by gel electrophoresis, and the enhancement of SBs was observed by PpIX treatment. We also studied the effect of PpIX for DNA damage in cells by X-ray irradiation using a B16 melanoma culture. X-ray irradiation induced &gamma;H2AX, DNA double-strand breaks (DSBs) in the context of chromatin, and affected cell survival. Since PpIX can enhance ROS generation even in a hypoxic state and induce DNA damage, combined radiotherapy treatment with 5-ALA is expected to improve therapeutic efficacy for radioresistant tumors

In Vivo Study of the Efficacy and Safety of 5-Aminolevulinic Radiodynamic Therapy for Glioblastoma Fractionated Radiotherapy

To treat malignant glioma, standard fractionated radiotherapy (RT; 60 Gy/30 fractions over 6 weeks) was performed post-surgery in combination with temozolomide to improve overall survival. Malignant glioblastoma recurrence rate is extremely high, and most recurrent tumors originate from the excision cavity in the high-dose irradiation region. In our previous study, protoporphyrin IX physicochemically enhanced reactive oxygen species generation by ionizing radiation and combined treatment with 5-aminolevulinic acid (5-ALA) and ionizing radiation, while radiodynamic therapy (RDT) improved tumor growth suppression in vivo in a melanoma mouse model. We examined the effect of 5-ALA RDT on the standard fractionated RT protocol using U251MG- or U87MG-bearing mice. 5-ALA was orally administered at 60 or 120 mg/kg, 4 h prior to irradiation. In both models, combined treatment with 5-ALA slowed tumor progression and promoted regression compared to treatment with ionizing radiation alone. The standard fractionated RT protocol of 60 Gy in 30 fractions with oral administration of 120 and 240 mg/kg 5-ALA, the human equivalent dose of photodynamic diagnosis, revealed no significant increase in toxicity to normal skin or brain tissue compared to ionizing radiation alone. Thus, RDT is expected to enhance RT treatment of glioblastoma without severe toxicity under clinically feasible conditions