Knowledge-based model building for treatment planning for prostate cancer using commercial treatment planning quality assurance software tools.

This study devised a method to efficiently launch the RapidPlan model for volumetric-modulated arc therapy for prostate cancer in small- and medium-sized facilities using high-quality treatment plans with the PlanIQ software as a reference. Treatment plans were generated for 30 patients with prostate cancer to construct the RapidPlan model using PlanIQ as a reference. In the context of PlanIQ-referenced treatment planning, treatment plans were developed, such that the feasibility dose-volume histogram of each organ-at-risk fell within F ≤ 0.1. For validation of the RapidPlan model, treatment plans were formulated for 20 patients using both RapidPlan and PlanIQ, and the differences were evaluated. The results of RapidPlan model validity assessment revealed that the RapidPlan-produced treatment plans exhibited higher quality in 11 of 20 patients. No significant differences were found between the treatment plans. In conclusion, high-quality treatment plans formulated using PlanIQ as reference facilitated efficient implementation of RapidPlan modeling.

Differences between professionals in treatment planning for patients with stage III lung cancer using treatment-planning QA software.

Background: The quality of treatment planning for stage III non-small cell lung cancer varies within and between facilities due to the different professions involved in planning. Dose estimation parameters were calculated using a feasibility dose-volume histogram (FDVH) implemented in the treatment planning quality assurance software PlanIQ. This study aimed to evaluate differences in treatment planning between occupations using manual FDVH-referenced treatment planning to identify their characteristics. Materials and methods: The study included ten patients with stage III non-small cell lung cancer, and volumetric-modulated arc therapy was used as the treatment planning technique. Fifteen planners, comprising five radiation oncologists, five medical physicists, and five radiological technologists, developed treatment strategies after referring to the FDVH. Results: Medical physicists had a higher mean dose at D98% of the planning target volume (PTV) and a lower mean dose at D2% of the PTV than those in other occupations. Medical physicists had the lowest irradiation lung volumes (V5 Gy and V13 Gy) compared to other professions, and radiation oncologists had the lowest V20 Gy and mean lung dose. Radiological technologists had the highest irradiation volumes for dose constraints at all indexes on the normal lung volume. Conclusions: The quality of the treatment plans developed in this study differed between occupations due to their background expertise, even when an FDVH was used as a reference. Therefore, discussing and sharing knowledge and treatment planning techniques among professionals is essential to determine the optimal treatment plan for each facility and patient.

Quantitative parameter mapping of contrast agent concentration and relaxivity and brain tumor extracellular pH.

In clinical magnetic resonance imaging, gadolinium-based contrast agents are commonly used for detecting brain tumors and evaluating the extent of malignancy. We present a new method to evaluate relaxivity (r1) and contrast agent concentration separately in contrast-enhanced lesions using quantitative parameter mapping (QPM). Furthermore, we also aimed to estimate the extracellular pH (pHe) of tumor lesions. We demonstrated that it is possible to evaluate pathophysiological tumor changes due to therapeutic efficacy by measuring r1 in contrast-enhanced lesions. In this study, the primary brain tumor group showed significantly higher r1 values than other brain disease groups (P < 0.001). Moreover, mean pHe value showed a trend for tumor malignancy having a lower pHe value and primary brain tumor having a significantly lower pHe than other brain diseases (P < 0.001). Our results might suggest that QPM can separately quantify r1 and CA concentration in brain tumors and that pHe brain tumor mapping could serve as a tumor biomarker. In conclusion, our method has potential clinical applications for assessing the treatment effects.

A disposable OSL dosimeter for in vivo measurement of rectum dose during brachytherapy.

PURPOSE: We aimed to develop a disposable rectum dosimeter and to demonstrate its ability to measure exposure dose to the rectum during brachytherapy for cervical cancer treatment using high-dose rate 192 Ir. Our rectum dosimeter measures the dose with an optically stimulated luminescence (OSL) sheet which was furled to a catheter. The catheter we used is 6 mm in diameter; therefore, it is much less invasive than other rectum dosimeters. The rectum dosimeter developed in this study has the characteristics of being inexpensive and disposable. It is also an easy-to-use detector that can be individually sterilized, making it suitable for clinical use. METHODS: To obtain a dose calibration curve, phantom experiments were performed. Irradiation was performed using a cubical acrylic phantom, and the response of the OSL dosimeter was calibrated with the calculation value predicted by the treatment planning system (TPS). Additionally, the dependence of catheter angle on the dosimeter position and repeatability were evaluated. We also measured the absorbed dose to the rectum of patients who were undergoing brachytherapy for cervical cancer (n = 64). The doses measured with our dosimeters were compared with the doses calculated by the TPS. In order to examine the causes of large differences between measured and planned doses, we classified the data into common and specific cases when performing this clinical study. For specific cases, the following three categories were considered: (a) patient movement, (b) gas in the vagina and/or rectum, and (c) artifacts in the X-ray image caused by applicators. RESULTS: A dose calibration curve was obtained in the range of 0.1 Gy-10.0 Gy. From the evaluation of the dependence of catheter angle on the dosimeter position and repeatability, we determined that our dosimeter can measure rectum dose with an accuracy of 3.1% (k = 1). In this clinical study, we succeeded in measuring actual doses using our rectum dosimeter. We found that the deviation of the measured dose from the planned dose was derived to be 12.7% (k = 1); this result shows that the clinical study included large elements of uncertainty. The discrepancies were found to be due to patient motion during treatment, applicator movement after planning images were taken, and artifacts in the planning images. CONCLUSIONS: We present the idea that a minimally invasive rectum dosimeter can be fabricated using an OSL sheet. Our clinical study demonstrates that a rectum dosimeter made from an OSL sheet has sufficient ability to evaluate rectum dose. Using this dosimeter, valuable information concerning organs at risk can be obtained during brachytherapy.

Adjuvant Antitumor Immunity Contributes to the Overall Antitumor Effect of Pegylated Liposomal Doxorubicin (Doxil®) in C26 Tumor-Bearing Immunocompetent Mice.

Doxorubicin (DXR) has been reported to have direct cytotoxicity against cancer cells and indirect immunotoxicity by modulation of host antitumor immunity. Hence, it may prevent cancer progression by a dual mechanism. Doxil®, a formulation of DXR encapsulated in polyethylene glycol modified (PEGylated) liposomes, is the most widely used of the clinically approved liposomal anticancer drugs. However, the effect of Doxil® on host antitumor immunity is not well understood. In this study, Doxil® efficiently suppressed tumor growth in immunocompetent mice bearing C26 murine colorectal carcinomas, but not in T cell-deficient nude mice, indicating a contribution of T cells to the overall antitumor effect of Doxil®. In immunocompetent mice, Doxil® increased major histocompatibility complex (MHC-1) levels in C26 tumors, which may be an indicator of increased immunogenicity of tumor cells, and potentially amplified tumor immunogenicity by decreasing immunosuppressive cells such as regulatory T cells, tumor-associated microphages and myeloid-derived suppressor cells that collectively suppress T cell-mediated antitumor responses. This suggests that encapsulation of DXR into PEGylated liposomes increased the therapeutic efficacy of DXR though effects on host antitumor immunogenicity in addition to direct cytotoxic effects on tumor cells. This report describes the role of host antitumor immunity in the overall therapeutic effects of Doxil®. Manipulating pharmacokinetics and biodistribution of chemotherapeutic agents with immunomodulatory properties may increase their therapeutic efficacies by amplifying host antitumor immunity in addition to direct cytotoxic effects on tumor cells.

Correlation and Characteristics of Intravoxel Incoherent Motion and Arterial Spin Labeling Techniques Versus Multiple Parameters Obtained on Dynamic Susceptibility Contrast Perfusion MRI for Brain Tumors.

Purpose : To compare data on brain tumors derived from intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) imaging with multiple parameters obtained on dynamic susceptibility contrast (DSC) perfusion MRI and to clarify the characteristics of IVIM and ASL perfusion data from the viewpoint of cerebral blood flow (CBF) analysis. Methods : ASL-CBF and IVIM techniques as well as DSC examination were performed in 24 patients with brain tumors. The IVIM data were analyzed with the two models. The relative blood flow (rBF), relative blood volume (rBV) corrected relative blood volume (crBV), mean transit time (MTT), and leakage coefficient (K2) were obtained from the DSC MRI data. Results : The ASL-CBF had the same tendency as the perfusion parameters derived from the DSC data, but the permeability from the vessels had less of an effect on the ASL-CBF. The diffusion coefficient of the fast component on IVIM contained more information on permeability than the f value. Conclusion : ASL-CBF is more suitable for the evaluation of perfusion in brain tumors than IVIM parameters. ASL-CBF and IVIM techniques should be carefully selected and the biological significance of each parameter should be understood for the correct comprehension of the pathological status of brain tumors. J. Med. Invest. 66 : 308-313, August, 2019.

B1 Power Optimization for Chemical Exchange Saturation Transfer Imaging: A Phantom Study Using Egg White for Amide Proton Transfer Imaging Applications in the Human Brain.

The chemical exchange saturation transfer (CEST) effect on an egg white (EW) suspension was investigated for optimization of magnetization transfer (MT) power (B1,rms) and pH dependency with the addition of lactic acid. Applying a higher MT pulse, B1,rms, Z-spectrum shows higher asymmetry and the magnetisation transfer ratio (MTR)asym signal increases to around 1-3.5 ppm, indicating a higher CEST effect. Amide proton transfer (APT) at 3.5 ppm shows a signal elevation in MTRasym with the application of higher B1,rms power and high pH. In addition, the hydroxyl proton signal in MTRasym increases as pH is reduced by lactic acid. In Z-spectrum of B1,rms at 1.0 µT and 2.0 µT, the dependence on CEST effect of amide proton and hydroxyl proton could be observed by using an EW suspension phantom. The CEST MT power was optimized on the EW suspension phantom with pH dependency and further confirmed on volunteers. In addition, APT imaging at 3.5 ppm using B1,rms at 1.0 µT performed on two human brains with different pathophysiological conditions indicated appropriate ATP effect.

Hydrodynamic Tail Vein Injection as a Simple Tool for Yielding Extended Transgene Expression in Solid Tumors.

Hydrodynamic tail vein injection was considered an in vivo transfection method that yields a higher level of gene expression mainly in the liver. This method has been applied to cancer gene therapy targeting both hepatic and non-hepatic cancers. However, intratumor transgene expression in non-hepatic tumors has not been well studied. In this study, we showed an extended transgene expression of ß-galactosidase (LacZ), a nonsecretory protein, in a subcutaneously implanted murine solid tumor following the hydrodynamic injection of plasmid DNA (LacZ pDNA). Our result may indicate that the hydrodynamic injection method is a powerful tool that can be used to gain transgene expression not only in the liver but also in solid tumors.

Hemodynamic analysis of bladder tumors using T1-dynamic contrast-enhanced fast spin-echo MRI.

OBJECTIVES: To evaluate the hemodynamics of bladder tumors, we developed a method to calculate change in R(1) value (ΔR(1)) from T(1)-dynamic contrast-enhanced fast spin-echo magnetic resonance imaging (T(1)DCE-FSE-MRI). MATERIALS AND METHODS: On a 1.5-T MR system, T(1)DCE-FSE-MRI was performed. This study was applied to 12 patients with urinary bladder tumor, i.e. urothelial carcinoma. We compared ΔR(1)-time and ΔSI-time between a peak in the ΔR(1)-time and ΔSI-time curve occurred during the first pass within 60s. Next, we assessed the slope of increase for 180s after CA injection (Slope(0-180)). RESULTS: The mean slope of the first pass was significantly higher for bladder tumors on both the ΔR(1)-time and the ΔSI-time curve compared with normal bladder walls. Moreover, a significant difference was apparent between bladder tumors and normal bladder walls on the mean Slope(0-180) in the ΔR(1)-time curve. However, no significant difference in the mean Slope(0-180) was observed on the ΔSI-time curve between bladder tumors and normal bladder walls. CONCLUSION: T(1)DCE-FSE-MRI offers three advantages: quantitative analysis; high-quality (i.e., artifact-free) images; and high temporal resolution even for SE images. Use of ΔR(1) analysis with T(1)DCE-FSE-MRI allows more detailed information on the hemodynamics of bladder tumors to be obtained and assists in differentiation between bladder tumors and the normal bladder wall.