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Twelve Asian patients with sarcoma received interval-compressed (ic-) chemotherapy scheduled every 14 days with a regimen of vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1200–2200 mg/m2) (VDC) alternating with a regimen of ifosfamide (9000 mg/m2) and etoposide (500 mg/m2) (IE), with filgrastim (5–10 mcg/kg/day) between cycles. Carboplatin (800 mg/m2) was added for CIC-rearranged sarcoma. The patients were treated with 129 cycles of ic-VDC/IE with a median interval of 19 days (interquartile range [IQR], 15–24 days. Median nadirs (IQR) were neutrophil count, 134 (30–396) × 106/L at day 11 (10–12), recovery by day 15 (14–17) and platelet count, 35 (23–83) × 109/L at day 11 (10–13), recovery by day 17 (14–21). Fever and bacteremia were observed in 36% and 8% of cycles, respectively. The diagnoses were Ewing sarcoma (6), rhabdomyosarcoma (3), myoepithelial carcinoma (1), malignant peripheral nerve sheath tumor (1), and CIC-DUX4 Sarcoma (1). Seven of the nine patients with measurable tumors responded (one CR and six PR). Interval-compressed chemotherapy is feasible in the treatment of Asian children and young adults with sarcomas.

Rare subpopulations of cancer stem cells (CSCs) have the ability to self-renew and are the primary driving force behind cancer metastatic dissemination and the preeminent hurdle to cancer treatment. As opposed to differentiated, non-malignant tumor offspring, CSCs have sophisticated metabolic patterns that, depending on the kind of cancer, rely mostly on the oxidation of major fuel substrates such as glucose, glutamine, and fatty acids for survival. Glutaminolysis is a series of metabolic reactions that convert glutamine to glutamate and, eventually, α-ketoglutarate, an intermediate in the tricarboxylic acid (TCA) cycle that provides biosynthetic building blocks. These building blocks are mostly utilized in the synthesis of macromolecules and antioxidants for redox homeostasis. A recent study revealed the cellular and molecular interconnections between glutamine and cancer stemness in the cell. Researchers have increasingly focused on glutamine catabolism in their attempt to discover an effective therapy for cancer stem cells. Targeting catalytic enzymes in glutaminolysis, such as glutaminase (GLS), is achievable with small molecule inhibitors, some of which are in early-phase clinical trials and have promising safety profiles. This review summarizes the current findings in glutaminolysis of CSCs and focuses on novel cancer therapies that target glutaminolysis in CSCs.

Purpose This study optimized our previously proposed simulation program for the approximate irregular field dose distribution (SPAD) and applied it to a respiratory motion compensation system (RMCS) and respiratory motion simulation system (RMSS). The main purpose was to rapidly analyze the two-dimensional dose distribution and evaluate the compensation effect of the RMCS during radiotherapy. Methods This study modified the SPAD to improve the rapid analysis of the dose distribution. In the experimental setup, four different respiratory signal patterns were input to the RMSS for actuation, and an ultrasound image tracking algorithm was used to capture the real-time respiratory displacement, which was input to the RMCS for actuation. A linear accelerator simultaneously irradiated the EBT3 film. The gamma passing rate was used to verify the dose similarity between the EBT3 film and the SPAD, and conformity index (CI) and compensation rate (CR) were used to quantify the compensation effect. Results The Gamma passing rates were 70.48–81.39% (2%/2mm) and 88.23–96.23% (5%/3mm) for various collimator opening patterns. However, the passing rates of the SPAD and EBT3 film ranged from 61.85% to 99.85% at each treatment time point. Under the four different respiratory signal patterns, CR ranged between 21% and 75%. After compensation, the CI for 85%, 90%, and 95% isodose constraints were 0.78, 0.57, and 0.12, respectively. Conclusions This study has demonstrated that the dose change during each stage of the treatment process can be analyzed rapidly using the improved SPAD. After compensation, applying the RMCS can reduce the treatment errors caused by respiratory movements.

This study evaluated dose differences in normal organs at risk, such as the lungs, heart, left anterior descending artery (LAD), right coronary artery, left ventricle, and right breast under personalized breast holder (PERSBRA), when using intensity-modulated radiation therapy (IMRT). This study evaluated the radiation protection offered by PERSBRA in left breast cancer radiation therapy. Here, we retrospectively collected data from 24 patients with left breast cancer who underwent breast-conserving surgery as well as IMRT radiotherapy. We compared the dose differences in target coverage and organs at risk with and without PERSBRA. For target coverage, tumor prescribed dose 95% coverage, conformity index, and homogeneity index were evaluated. For organs at risk, we compared the mean heart dose, mean left ventricle dose, LAD maximum and mean dose, mean left lung receiving 20 Gy, 10 Gy, and 5 Gy of left lung volume, maximum and mean coronary artery of the right, maximum of right breast, and mean dose. Good target coverage was achieved with and without PERSBRA. When PERSBRA was used with IMRT, the mean dose of the heart decreased by 42%, the maximum dose of LAD decreased by 26.4%, and the mean dose of LAD decreased by 47.0%. The mean dose of the left ventricle decreased by 54.1%, the volume (V20) of the left lung that received 20 Gy decreased by 22.8%, the volume (V10) of the left lung that received 10 Gy decreased by 19.8%, the volume (V5) of the left lung that received 5 Gy decreased by 15.7%, and the mean dose of the left lung decreased by 23.3%. Using PERSBRA with IMRT greatly decreases the dose to organs at risk (left lung, heart, left ventricle, and LAD). This study found that PERSBRA with IMRT can achieve results similar to deep inspiration breath-hold radiotherapy (DIBH) in terms of reducing the heart radiation dose and the risk of developing heart disease in patients with left breast cancer who cannot undergo DIBH.

Purpose: Breast immobilization with personalized breast holder (PERSBRA) is a promising approach for normal organ protection during whole breast radiotherapy. The aim of this study is to evaluate the skin surface dose for breast radiotherapy with PERSBRA using different radiotherapy techniques. Materials and methods: We designed PERSBRA with three different mesh sizes (large, fine and solid) and applied them on an anthropomorphic(Rando) phantom. Treatment planning was generated using hybrid, intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques to deliver a prescribed dose of 5000 cGy in 25 fractions accordingly. Dose measurement with EBT3 film and TLD were taken on Rando phantom without PERSBRA, large mesh, fine mesh and solid PERSBRA for (a) tumor doses, (b) surface doses for medial field and lateral field irradiation undergoing hybrid, IMRT, VMAT techniques. Results: The tumor dose deviation was less than five percent between the measured doses of the EBT3 film and the TLD among the different techniques. The application of a PERSBRA was associated with a higher dose of the skin surface. A large mesh size of PERSBRA was associated with a lower surface dose. The findings were consistent among hybrid, IMRT, or VMAT techniques. Conclusions: Breast immobilization with PERSBRA can reduce heart toxicity but leads to a build-up of skin surface doses, which can be improved with a larger mesh design for common radiotherapy techniques.

Background: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal brain tumor most commonly presenting in young children. Methods: We performed a nationwide, population-based study of AT/RT (ICD-O-3 code: 9508/3) in Taiwan using the Taiwan Cancer Registry Database and the National Death Certificate Database. Results: A total of 47 cases (male/female = 29:18; median age at diagnosis, 23.3 months (IQR: 12.5–87.9)) were diagnosed with AT/RT between 1999 and 2014. AT/RT had higher prevalence in males (61.70%), in children < 36 months (55.32%), and at infratentorial or spinal locations (46.81%). Survival analyses demonstrated that patients ≥ 3 years of age (n = 21 (45%)) had a 5y-OS of 41% (p < 0.0001), treatment with radiotherapy only (n = 5 (11%)) led to a 5y-OS of 60%, treatment with chemotherapy with or without radiotherapy (n = 27 (62%)) was associated with a 5y-OS of 45% (p < 0.0001), and patients with a supratentorial tumor (n = 11 (23%)) had a 5y-OS of 51.95%. Predictors of better survival on univariate Cox proportional hazard modeling and confirmed with multivariate analysis included older age (≥1 year), supratentorial sites, and the administration of radiotherapy, chemotherapy, or both. Gender had no effect on survival. Conclusion: Older age, supratentorial site, and treatment with radiotherapy, chemotherapy, or both significantly improves the survival of patients with AT/RT.

PURPOSE This study evaluates the feasibility of our previously developed Respiratory Motion Compensation System (RMCS) combined with the Phase Lead Compensator (PLC) to eliminate system delays during the compensation of respiration-induced tumor motion. The study objective is to improve the compensation effect of RMCS and the efficay of radiation therapy to reduce its side effects to the patients. MATERIAL AND METHODS In this study, LabVIEW was used to develop the proposed software for calculating real-time adaptive control parameters, combined with PLC and RMCS for the compensation of total system delay time. Experiments of respiratory motion compensation were performed using 6 pre-recorded human respiration patterns and 7 sets of different sine waves. During the experiments, a respiratory simulation device, Respiratory Motion Simulation System (RMSS), was placed on the RMCS, and the detected target motion signals by the Ultrasound Image Tracking Algorithm (UITA) were transmitted to the RMCS, and the compensation of respiration induced motion was started. Finally, the tracking error of the system is obtained by comparing the encoder signals bwtween RMSS and RMCS. The compensation efficacy is verified by the root mean squared error (RMSE) and the system compensation rate (CR). RESULTS The experimental results show that the calcuated CR with the simulated respiration patterns is between 42.85% ∼3.53% and 33.76% ∼2.62% in the Right-Left (RL) and Superior-Inferior (SI), respectively, after the RMCS compensation of using the adaptive control parameters in PLC. For the compensation results of human respiration patterns, the CR is between 58.95% ∼8.56% and 62.87% ∼9.05% in RL and SI, respectively. CONCLUSIONS During the respiratory motion compensation, the influence of the delay time of the entire system (RMCS+RMSS+UITA) on the compensation effect was improved by adding an adaptive control PLC, which reduces compensation error and helps improve efficacy of radiation therapy.

Background The reduction of the delaying effect in the respiratory motion compensation system (RMCS) is still impossible to completely correct the respiratory waveform of the human body due to each patient has a unique respiratory rate. In order to further improve the effectiveness of radiation therapy, this study evaluates our previously developed RMCS and uses the fast Fourier transform (FFT) algorithm combined with the phase lead compensator (PLC) to further improve the compensation rate (CR) of different respiratory frequencies and patterns of patients. Methods In this study, an algorithm of FFT automatic frequency detection was developed by using LabVIEW software, uisng FFT combined with PLC and RMCS to compensate the system delay time. Respiratory motion compensation experiments were performed using pre-recorded respiratory signals of 25 patients. During the experiment, the respiratory motion simulation system (RMSS) was placed on the RMCS, and the pre-recorded patient breathing signals were sent to the RMCS by using our previously developed ultrasound image tracking algorithm (UITA). The tracking error of the RMCS is obtained by comparing the encoder signals of the RMSS and RMCS. The compensation effect is verified by root mean squared error (RMSE) and system CR. Results The experimental results show that the patient's respiratory patterns compensated by the RMCS after using the proposed FFT combined with PLC control method, the RMSE is between 1.50-5.71 and 3.15-8.31 mm in the right-left (RL) and superior-inferior (SI) directions, respectively. CR is between 72.86-93.25% and 62.3-83.81% in RL and SI, respectively. Conclusions This study used FFT combined with PLC control method to apply to RMCS, and used UITA for respiratory motion compensation. Under the automatic frequency detection, the best dominant frequency of the human respiratory waveform can be determinated. In radiotherapy, it can be used to compensate the tumor movement caused by respiratory motion and reduce the radiation damage and side effects of normal tissues nearby the tumor.

BACKGROUND: An ultrasound image tracking algorithm (UITA) was combined with four-dimensional computed tomography (4DCT) to create a real-time tumor motion-conversion model. The real-time position of a lung tumor phantom based on the real-time diaphragm motion trajectories detected by ultrasound imaging in the superior-inferior (SI) and medial-lateral (ML) directions were obtained. METHODS: Three different tumor motion-conversion models were created using a respiratory motion simulation system (RMSS) combined with 4DCT. The tumor tracking error was verified using cone-beam computed tomography (CBCT). The tumor motion-conversion model was produced by using the UITA to monitor the motion trajectories of the diaphragm phantom in the SI direction, and using 4DCT to monitor the motion trajectories of the tumor phantom in the SI and ML directions over the same time period, to obtain parameters for the motion-conversion model such as the tumor center position and the amplitude and phase ratios. RESULTS: The tumor movement was monitored for 90 s using CBCT to determine the real motion trajectories of the tumor phantom and using ultrasound imaging to simultaneously record the diaphragm movement. The absolute error of the motion trajectories of the real and estimated tumor varied between 0.5 and 2.1 mm in the two directions. CONCLUSIONS: This study has demonstrated the feasibility of using ultrasound imaging to track diaphragmatic motion combined with a 4DCT tumor motion-conversion model to track tumor motion in the SI and ML directions. The proposed method makes tracking a lung tumor feasible in real time, including under different breathing conditions.

Simple Summary We report a local control prediction model for patients undergoing MRgFUS ablation, and provide promising guidance for clinicians to identify a suitable treatment strategy for bone metastatic lesions. We propose a few-shot learning approach to establish the quick prediction of clinical and radiographic responses. On the basis of demographic data, pre-/post-treatment immune-related cytokine change, and MRI imaging, the most suitable parameters were selected to assess potential treatment outcomes during the acute inflammatory stages within 24 h. Traditional logistic regression and few-shot learning models were compared to identify the best model on an independent test. The best predictive few-shot learning model (accuracy of 85.2%, sensitivity of 88.6%, and AUC of 0.95) was achieved by combining the clinical features with the levels of significant cytokines IL-6, IL-13, IP-10, and eotaxin. Abstract Magnetic resonance-guided focused ultrasound surgery (MRgFUS) constitutes a noninvasive treatment strategy to ablate deep-seated bone metastases. However, limited evidence suggests that, although cytokines are influenced by thermal necrosis, there is still no cytokine threshold for clinical responses. A prediction model to approximate the postablation immune status on the basis of circulating cytokine activation is thus needed. IL-6 and IP-10, which are proinflammatory cytokines, decreased significantly during the acute phase. Wound-healing cytokines such as VEGF and PDGF increased after ablation, but the increase was not statistically significant. In this phase, IL-6, IL-13, IP-10, and eotaxin expression levels diminished the ongoing inflammatory progression in the treated sites. These cytokine changes also correlated with the response rate of primary tumor control after acute periods. The few-shot learning algorithm was applied to test the correlation between cytokine levels and local control (p = 0.036). The best-fitted model included IL-6, IL-13, IP-10, and eotaxin as cytokine parameters from the few-shot selection, and had an accuracy of 85.2%, sensitivity of 88.6%, and AUC of 0.95. The acceptable usage of this model may help predict the acute-phase prognosis of a patient with painful bone metastasis who underwent local MRgFUS. The application of machine learning in bone metastasis is equivalent or better than the current logistic regression.

This study applied an ultrasound image tracking algorithm (UITA) for tracking respiration and developed a 2D dose distribution simulation program (DDSP) for simulating a dose distribution map. We evaluated the feasibility of a 2D respiratory motion simulation system combined with the UITA during radiotherapy for tracking respiration. The recorded respiration signals were input to the DDSP to generate a simulated dose distribution map and verify the effectiveness of the Gafchromic Film EBT3 (EBT3 film) as a measured dose distribution map (MDDM), to validate the DDSP. A radiation dose was delivered to EBT3 film and the film response was quantified using the isodose area rate (IAR), average dose rate within the field (ADFR), conformity index rate (CIR), and gamma passing rate. The tracking performance was evaluated by calculating the root mean squared error (RMSE). The calculated RMSEs were 1.67–5.34 and 0.42–2.53 mm in superior–inferior and right–left directions, respectively. The ADFR was 0.93–1.21 and the IARs at 20, 50, 70, and 80% were 0.87–1.29, 0.84–1.16, 0.79–1.61, and 0.48–6.64, respectively. The CIRs at 50, 70, and 80% were 0.87–1.23, 0.84–1.29, and 0.81–4.40, respectively. The human respiration patterns exhibited a 3%/3 mm gamma passing rate of 76.56–96.94%. This study successfully used an ultrasound imaging system to capture human respiration signals and transmit them to the DDSP for simulating radiation dose distributions, thus demonstrating the feasibility of the system.

This study proposed respiratory motion compensation system (RMCS) combined with an ultrasound image tracking algorithm (UITA) to compensate for respiration-induced tumor motion during radiotherapy, and to address the problem of inaccurate radiation dose delivery caused by respiratory movement. This study used an ultrasound imaging system to monitor respiratory movements combined with the proposed UITA and RMCS for tracking and compensation of the respiratory motion. Respiratory motion compensation was performed using prerecorded human respiratory motion signals and also sinusoidal signals. A linear accelerator was used to deliver radiation doses to GAFchromic EBT3 dosimetry film, and the conformity index (CI), root-mean-square error, compensation rate (CR), and planning target volume (PTV) were used to evaluate the tracking and compensation performance of the proposed system. Human respiratory pattern signals were captured using the UITA and compensated by the RMCS, which yielded CR values of 34–78%. In addition, the maximum coronal area of the PTV ranged from 85.53 mm2 to 351.11 mm2 (uncompensated), which reduced to from 17.72 mm2 to 66.17 mm2 after compensation, with an area reduction ratio of up to 90%. In real-time monitoring of the respiration compensation state, the CI values for 85% and 90% isodose areas increased to 0.7 and 0.68, respectively. The proposed UITA and RMCS can reduce the movement of the tracked target relative to the LINAC in radiation therapy, thereby reducing the required size of the PTV margin and increasing the effect of the radiation dose received by the treatment target.

Many studies use ultrasound for diaphragmatic excursion (DE) evaluation. The calculation of DE value requires recording the diaphragm movement, freezing the ultrasound image, recalling video and measuring target distance which is time consuming. We aimed at using an ultrasound image tracking algorithm (UITA) to trace diaphragm movement and reveal DE values in real time. We tested UITA with 40 young volunteers under four respiration conditions: standing with quiet breathing (SQB), supine with quiet breathing (SuQB), standing with deep breathing (SDB), and supine with deep breathing (SuDB). The value of DE during SQB, SuQB, SDB, and SuDB was 24.5 ± 10.2, 31.9 ± 10.5, 68.9 ± 15.9, and 98.1 ± 27.4 mm, respectively. We found displacement of diaphragm can be translated to waveforms like spirometry graphs with real-time DE value. DE decreased about 30% in the standing position than in the supine position. Quiet breathing or deep breathing had similar effect on the percent decrease of DE. Further studies are needed to validate this tracking algorithm as a clinical tool in patients with the diaphragm dysfunction.

Magnetic resonance-guided focused ultrasound (MRgFUS) is an alternative local therapy for patients with painful bone metastasis for whom standard conventional radiation therapy (RT) has failed. However, the therapeutic effects of MRgFUS as a first-line treatment for bone metastasis remain uncertain.A matched-pair study was conducted to compare the therapeutic effects of MRgFUS with those of conventional RT as a first-line treatment for patients with painful bone metastasis. The MRgFUS and RT-treated groups were matched 1:2 by age, sex, primary cancer, pretreatment pain score, and treated site.According to the criteria for patient eligibility and matching, 21 and 42 patients (total, 63 patients) with bone metastasis treated with MRgFUS and conventional RT, respectively, were enrolled for analyses. The median ages of the MRgFUS and RT-treated patients were 59 and 61 years, respectively. Among the enrolled patients, 52% were male and 48% were female. The results showed that both MRgFUS and RT were effective. However, MRgFUS was more efficient than RT in terms of the time course of pain palliation as it yielded a significantly higher response rate at 1 week after treatment (71% versus 26%, p = 0.0009).MRgFUS provides a similar overall treatment response rate but faster pain relief compared with conventional RT and has the potential to serve as the first-line treatment for painful bone metastasis in selected patients.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

This study developed an in vitro diaphragm motion reproduction system (IVDMRS) based on noninvasive and real-time ultrasound imaging to track the internal displacement of the human diaphragm and diaphragm phantoms with a respiration simulation system (RSS). An ultrasound image tracking algorithm (UITA) was used to retrieve the displacement data of the tracking target and reproduce the diaphragm motion in real time using a red laser to irradiate the diaphragm phantom in vitro. This study also recorded the respiration patterns in 10 volunteers. Both simulated and the respiration patterns in 10 human volunteers signals were input to the RSS for conducting experiments involving the reproduction of diaphragm motion in vitro using the IVDMRS. The reproduction accuracy of the IVDMRS was calculated and analyzed. The results indicate that the respiration frequency substantially affects the correlation between ultrasound and kV images, as well as the reproduction accuracy of the IVDMRS due to the system delay time (0.35s) of ultrasound imaging and signal transmission. The utilization of a phase lead compensator (PLC) reduced the error caused by this delay, thereby improving the reproduction accuracy of the IVDMRS by 14.09-46.98%. Applying the IVDMRS in clinical treatments will allow medical staff to monitor the target displacements in real time by observing the movement of the laser beam. If the target displacement moves outside the planning target volume (PTV), the treatment can be immediately stopped to ensure that healthy tissues do not receive high doses of radiation.

Purpose This study aimed to determine the feasibility of using an ultrasound image tracking algorithm (UITA) combined with a respiration compensating system (RCS) to track and compensate the respiration pattern of the diaphragm in real time. Methods Diaphragm motions and various respiration patterns were tracked and captured in volunteers using our previously developed UITA (Kuo et al., J Xray Sci Technol, 2016:875). A diaphragm phantom was placed on a respiration simulation system (RSS) that received signals with different respiration patterns to simulate actual human respiration signals. The RSS was mounted on the RCS, which is 180 cm long and driven by inputting a compensating signal to a linear actuator underneath with and without using a phase-lead compensator (PLC) (Chuang et al., J Xray Sci Technol, 2015:503). The target displacement was calculated automatically by the UITA and compensated by the RCS. The phantom displacements were observed using a fluoroscopic imaging system on the linear accelerator at the Department of Radiation Oncology, Taipei Medical University Hospital, and the results were also compared with the displacements measured by the UITA and the RSS for correlation verification. In addition, the compensating effect was analyzed after activating the RCS. Results The experimental results indicate a significant correlation between the UITA-calculated and actual displacements, with a correlation coefficient of up to 91% for the simulated respiration patterns. After activating the RCS, the obtained compensating effect was more than 65%, and even up to 85% if a PLC was used. Moreover, the compensation of 10 extreme respiration patterns of diaphragm was improved significantly through the use of a PLC, with a peak compensating rate of 88.92% being achieved. Finally, compensation effects ranging from 52% to 74% were obtained in 10 human volunteers. Conclusions This study combined ultrasound imaging tracking technology with the RCS to offset the respiration-induced diaphragm displacement and compensate the various respiration patterns, even including those with baseline-shift phenomenon in real time with the aid of a noninvasive ultrasound imaging system.

Pancreatic cancer represents one of the most aggressive types of malignancy due to its high resistance toward most clinically available treatments. The presence of pancreatic cancer stem-like cells (CSCs) has been attributed to the intrinsically high resistance and highly metastatic potential of this disease. Here, we identified and isolated pancreatic CSCs using the side population (SP) method from human pancreatic cancer cell line, PANC-1. We then compared the SP and non-SP PANC-1 cells genetically. PANC-1 SP cells exhibited CSC properties including enhanced self-renewal ability, increased metastatic potential, and resistance toward gemcitabine treatment. These cancer stem-like phenotypes were supported by their enhanced expression of ABCG2, Oct4, and CD44. A traditional plant-derived antioxidant, garcinol, has been implicated for its anticancer properties. Here, we found that garcinol treatment to PANC-1 SP cells significantly suppressed the stem-like properties of PANC-1 SP cells and metastatic potential by downregulating the expression of Mcl-1, EZH2, ABCG2, Gli-1, and Notch1. More importantly, garcinol treatment led to the upregulation of several tumor suppressor microRNAs, and miR-200c increased by garcinol treatment was found to target and downregulate Notch1. Thus, PANC-1 SP cells may serve as a model for studying drug-resistant pancreatic CSCs, and garcinol has the potential as an antagonist against pancreatic CSCs.

Background: Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is an alternative local therapy for patients with painful bone metastasis. However, little is known about the prognostic and predictive factors of MRgFUS in treating bone metastasis. Materials and methods: This retrospective study analyzed the performance status, treated site, pretreatment pain score, pretreatment tumor volume and lesion coverage volume factor (CVF) of 31 patients who underwent MRgFUS. A numerical rating scale for pain was used at the same time to assess the clinical response. Radiographic responses were evaluated using a modified version of The University of Texas MD Anderson Cancer Center criteria and reference to the MR imaging or computed tomography scans obtained 3 months after treatment. Univariate and multivariate logistic regression analyses were conducted to examine the effect of variables on clinical and radiographic responses. Results: The overall clinical response rate was 83.9% and radiographic response rate was 67.7%. Multivariate logistic regression analysis revealed that the better pretreatment Karnofsky performance status (KPS) (odds ratio: 1.220, 95% confidence interval (CI): 1.033–1.440; p = 0.019) was significantly associated with a more positive clinical response, and that the lesion CVF (odds ratio: 1.183, 95% CI: 1.029–1.183; p = 0.0055) was an independent prognostic factor for radiographic responses. The radiographic response of patients with lesion CVF ≥70% and CVF

Purpose This study used an ultrasound image tracking algorithm (UITA) in combination with a proposed simulation program for the approximate irregular field dose distribution (SPAD) to assess the feasibility of performing dose distribution simulations for two-dimensional radiotherapy. Methods This study created five different types of multileaf collimator openings, and applied a SPAD to analyze the matrix position parameters for each regular field to generate a static program-simulation dose distribution map (PDDM), whose similarity was then compared with a static radiochromic film experimental-measurement dose distribution map (EDDM). A two-dimensional respiration motion simulation system (RMSS) was used to reproduce the respiration motion, and the UITA was used to capture the respiration signals. Respiration signals were input to the SPAD to generate two dynamic PDDMs, which were compared for similarity with the dynamic EDDM. Results In order to verify the dose distribution between different dose measurement techniques, the gamma passing rate with 2%/2 mm criterion was used for the EDDM and PDDM, the passing rates were between 94.31% and 99.71% in the static field analyses, and between 84.45% and 96.09% for simulations with the UITA signal input and between 89.35% and 97.78% for simulations with the original signal input in the dynamic field analyses. Conclusions Static and dynamic dose distribution maps can be simulated based on the proposed matrix position parameters of various fields and by using the UITA to track respiration signals during radiation therapy. The present findings indicate that it is possible to develop a reusable and time-saving dose distribution measurement tool.

// Che-Yu Hsu 1 , Chun-Wei Wang 2, 4 , Chia-Chun Kuo 3 , Yu-Hsuan Chen 2, 4 , Keng-Hsueh Lan 2, 4 , Ann-Lii Cheng 4, 5, 6 , Sung-Hsin Kuo 2, 4, 5, 6 1 Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital Yun-Lin Branch, Yunlin, Taiwan 2 Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan 3 Division of Radiation Oncology, Department of Oncology, Taiwan Medical University Hospital, Taipei, Taiwan 4 National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan 5 Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan 6 Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan Correspondence to: Sung-Hsin Kuo, email: shkuo101@ntu.edu.tw Keywords: rectal cancer, tumor compactness, pathologic complete remission, preoperative, chemoradiotherapy Received: March 30, 2016 Accepted: November 21, 2016 Published: December 10, 2016 ABSTRACT In addition to clinical factors (tumor and node stage) and treatment factors (equivalent radiotherapy dose and chemotherapy regimen), we assessed whether different performances of various tumor volume measurements help predict the pathological complete response (pCR) of locally advanced rectal cancer (LARC) after preoperative concurrent chemoradiotherapy (CCRT). A total of 122 patients with LARC treated with a long course of CCRT, between December 2009 and March 2015, were enrolled in this bi-institutional study. Tumor delineation was based on standard T2-weighted magnetic resonance imaging or contrast-enhanced computed tomography before CCRT. Tumor compactness was defined as the ratio of the volume and the surface area. The tumor compactness-corrected TV (TCTV) was defined as the ratio of the real TV (RTV) and tumor compactness. Twenty-three (18.9%) patients had a pCR. Areas under the curve of the receiver operating characteristic for pCR prediction calculated using the RTV, cylindrical approximated TV (CATV), and TCTV were 0.724, 0.747, and 0.780, respectively. The prediction performance of TCTV was significantly more efficient than that of both RTV ( P = 0.0057) and CATV ( P = 0.0329). Multivariate logistic regression analysis revealed tumor compactness ( P = 0.001), RTV ( P = 0.042), and preoperative clinical nodal status ( P = 0.044) as significant predictors of a pCR. In addition, poor tumor compactness was closely associated with lymphovascular space invasion ( P = 0.008) and pathological nodal status ( P = 0.003). For patients with LARC receiving preoperative CCRT, tumor compactness is a useful radiomic parameter for improving the volumetric based prediction model.

The expression of annexin A2 (ANXA2) in nasopharyngeal carcinoma (NPC) cells induces the immunosuppressive response in dendritic cells; however, the oncogenic effect and clinical significance of ANXA2 have not been fully investigated in NPC cells. Immunohistochemical staining for ANXA2 was performed in 61 patients and the association with clinicopathological status was determined. Short hairpin (sh)RNA knockdown of ANXA2 was used to examine cellular effects of ANXA2, by investigating alterations in cell proliferation, migration, invasion, adhesion, tube-formation assay, and chemo- and radiosensitivity assays were performed. RT-qPCR, Western blotting, and immunofluorescence were applied to determine molecular expression levels. Clinical association studies showed that the expression of ANXA2 was significantly correlated with metastasis (p = 0.0326) and poor survival (p = 0.0256). Silencing of ANXA2 suppressed the abilities of cell proliferation, adhesion, migration, invasion, and vascular formation in NPC cell. ANXA2 up-regulated epithelial-mesenchymal transition associated signal proteins. Moreover, ANXA2 reduced sensitivities to irradiation and chemotherapeutic drugs. These results define ANXA2 as a novel prognostic factor for malignant processes, and it can serve as a molecular target of therapeutic interventions for NPC.

Debris flows are natural disasters, with soil mass, rocks, and water traveling down a mountainside slope. Debris flows are extremely dangerous; their occurrence incurs huge losses to life and property. The purpose of this research is to develop debris flow detection and emergency evacuation systems. A bag-of-words model is established for analyzing the features of debris flow events, and an anomaly-detection principal component analysis (PCA) model is proposed to detect debris flow. Using real-time debris flow prediction and monitoring, a stochastic optimization model for evacuation planning is formulated. Case studies of debris flow detection in Shenmu village and Fengchiu, central Taiwan, are conducted. Shenmu village and Fengchiu are areas of high potential debris flow, and each has a population of around 800 people. The results show that combining bag-of-words and anomaly-detection PCA methods could predict 6 out of 8 occurrences of actual events, providing a prediction rate of 75 %. In addition, the models make 13 predictions, and 6 of them are correct, providing a prediction accuracy of 46 %. Optimal parameters (including window size, bag length, filter ratio of training data, and anomaly threshold) of the models are also examined to increase the accuracy of debris flow prediction.

This study evaluates four databases from PhysioNet: The American Heart Association database (AHADB), Creighton University Ventricular Tachyarrhythmia database (CUDB), MIT-BIH Arrhythmia database (MITDB), and MIT-BIH Noise Stress Test database (NSTDB). The ANSI/AAMI EC57:2012 is used for the evaluation of the algorithms for the supraventricular ectopic beat (SVEB), ventricular ectopic beat (VEB), atrial fibrillation (AF), and ventricular fibrillation (VF) via the evaluation of the sensitivity, positive predictivity and false positive rate. Sample entropy, fast Fourier transform (FFT), and multilayer perceptron neural network with backpropagation training algorithm are selected for the integrated detection algorithms. For this study, the result for SVEB has some improvements compared to a previous study that also utilized ANSI/AAMI EC57. In further, VEB sensitivity and positive predictivity gross evaluations have greater than 80%, except for the positive predictivity of the NSTDB database. For AF gross evaluation of MITDB database, the results show very good classification, excluding the episode sensitivity. In advanced, for VF gross evaluation, the episode sensitivity and positive predictivity for the AHADB, MITDB, and CUDB, have greater than 80%, except for MITDB episode positive predictivity, which is 75%. The achieved results show that the proposed integrated SVEB, VEB, AF, and VF detection algorithm has an accurate classification according to ANSI/AAMI EC57:2012. In conclusion, the proposed integrated detection algorithm can achieve good accuracy in comparison with other previous studies. Furthermore, more advanced algorithms and hardware devices should be performed in future for arrhythmia detection and evaluation. Cal-Comp Electronics & Communications Co., Ltd.; Kinpo Electronics, Inc. New Taipei City, Taiwan. Innovation Center for Big Data and Digital Convergence; Yuan Ze University, Taiwan.

Background Full-thickness local excision (FTLE) for rectal cancer showing clinical complete remission (cCR) after neoadjuvant chemoradiation therapy (NCRT) is associated with good oncological results. The purpose of this study was to report the results of robotic transanal minimally invasive surgery for such patients. Methods Patients were treated with a 5-fluorouracil-based NCRT regimen. The determination of cCR was based on digital rectal examination, colonoscopy, and magnetic resonance imaging. Results Six patients underwent transanal FTLE using the da Vinci Xi surgical system. The median operative time was 106.5 minutes, and the estimated blood loss was minimal. The mean length of hospital stay was 4.2 days. After 18.2 months of follow-up, none of the patients developed local recurrences or distant disease. Conclusions With the use of robotic technology, FTLE can be performed with relative ease and can be considered as a viable alternative to radical resection or a "Watch and Wait" strategy.

Piperlongumine (PL), a natural product of Piper longum, inhibits multiple malignant phenotypes. Therefore, the present study examined whether PL suppresses cancer stemness in oral cancer. The cellular effects of PL were determined by examining alterations in tumor sphere formation, cell migration, invasion, proliferation ability, chemosensitivity and radiosensitivity. Reverse transcription-quantitative polymerase chain reaction analysis and western blotting were performed in order to determine molecular expression levels. The present study revealed that PL inhibited cancer stem cell-forming ability and suppressed the expression of the stemness-related transcription factors SRY-Box 2, POU class 5 homeobox 1, and Nanog homeobox. However, it increased the expression of the differentiation marker cytokeratin 18. PL also suppressed cell migration and invasion, resulting in the elimination of the epithelial-mesenchymal transition. Furthermore, PL increased chemo- and radiosensitivity and suppressed tumor growth in vitro and in vivo. The results of the present study suggested that PL inhibits malignant phenotypes via the suppression of cancer stemness in oral cancer. Thus, PL may serve as an effective therapeutic agent for oral cancer.

Purpose This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. Conclusions When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

Introduction Brain metastases (BM) commonly occur in patients with lung adenocarcinoma and usually lead to a poor prognosis and quality of life despite of radiotherapy. Epidermal growth factor receptor ( EGFR ) mutations have been widely demonstrated to be a predictive and prognostic factor for lung adenocarcinoma, however, its impact on BM from lung adenocarcinoma remains inconclusive. The present study aimed to elucidate the predictive role of EGFR mutations in BM treatment response and survival after BM in patients with lung adenocarcinoma. Material and methods From January 2006 through February 2012, 180 of 505 lung adenocarcinoma patients developed BM during their disease course were reviewed for eligibility, and 139 patients, including 89 EGFR -mutant and 50 EGFR wild-type patients, were identified for analysis. Results Of the patients eligible for evaluation of treatment response, up to 85% received radiotherapy and the remaining took EGFR tyrosine kinase inhibitors (TKIs) as the front modality for BM. EGFR -mutant patients, compared with EGFR wild-type patients, had significantly greater intracranial treatment response of BM (84% vs. 48%, P =0.002), experienced higher therapeutic efficacy to radiotherapy (86% vs. 52%, P =0.005), and had longer median survival after BM diagnosis (13.2 vs. 6.8 months, P EGFR mutation ( P =0.002) and performance status ( P =0.009) were independently associated with BM treatment response. Additionally, EGFR mutation ( P =0.005), good performance status ( P P =0.033) correlated with better survival. Conclusion EGFR mutation is an independent predictive factor for both BM treatment response and survival after BM in patients with lung adenocarcinoma. Further prospective studies on incorporation of EGFR mutation status into therapeutic strategy and survival prediction system for lung adenocarcinoma with BM are warranted.

Background: Hypoxia-induced factors (HIF) has a role in angiogenesis and regulate tumorigenesis of cancer cell. The HIF is the best-identified mechanism that shows imbalance between consumption and oxygen supply in progressing tumor. This study of HIF-2α expression in oral squamous cell carcinoma (OSCC) aimed to investigate the relationship of HIF-2α and pathology characteristics related to its clinical correlation. Methods: Fifty-eight samples of OSCC and adjacent tissues were fixed in paraffin for microarray preparation. The tissue array then was stained using primary antibody HIF-2α (NB100-122) and autoprobe II ABC universal staining kit. Each tissue sample was captured using camera microscope, and images were analyzed with Photoshop 6.0 using the CMYK method. A statistical analysis was performed with the two-tailed t-test, Kaplan–Meier and log-rank test using Prism for Windows version 5.0. Results: The samples of the non-cancerous matched tissues (NCMTs) paired with their OSCC samples showed HIF-2α overexpression with significance difference p

Background Few data are available on the tolerance of reirradiation in patients with hepatocellular carcinoma (HCC). This study determined the clinical parameters contributing to the development of radiation-induced liver disease (RILD). Methods We included 36 patients with HCC who received 2 courses of radiotherapy (RT) to the liver. Using α/β = 15 for tumor and α/β =8 for normal liver tissue for biologically equivalent doses in 2 Gy fractions, mean cumulative to the hepatic tumor and normal liver were 87.7 Gy15 and 31.1 Gy8, respectively. Hepatic toxicities were classified according to the Common Terminology Criteria for Adverse Events, Version 4.0. Clinical data, including liver function test results, radiological study findings, and RT parameters before and after both courses of RT were retrieved for analysis. Using multivariate analysis, logistic regression was used to identify the predictors of RILD, and Cox regression was performed to explore the prognostic factors for overall survival (OS). Results Thirteen patients (36 %) developed RILD after reirradiation. Nine of them died because of progressive liver failure without evidence of tumor progression and were categorized to have lethal RILD. A pretreatment Child–Turcotte–Pugh (CTP) score ≥6 was the only predictor of RILD [odds ratio (OR): 15.83, p = 0.001] and lethal RILD [OR: 72.56, p = 0.005]. In addition, a CTP score ≥6 and the presence of portal vein tumor thrombosis before reirradiation were 2 prognostic factors for OS. Conclusion Despite a limited sample size, residual liver function using a preirradiation CTP score ≥6 is a clinical parameter associated with an increased risk of RILD in patients requiring hepatic reirradiation.

Sulforaphane (SFN) has been indicated for the prevention and suppression of tumorigenesis in solid tumors. Herein, we evaluated SFN's effects on imatinib (IM)-resistant leukemia stem cells (LSCs). CD34(+)/CD38(-) and CD34(+)/CD38(+) LSCs were isolated from KU812 cell line flowcytometrically. Isolated LSCs showed high expression of Oct4, CD133, β-catenin, and Sox2 and IM resistance. Differentially, CD34(+)/CD38(-) LSCs demonstrated higher BCR-ABL and β-catenin expression and imatinib (IM) resistance than CD34(+)/CD38(+) counterparts. IM and SFN combined treatment sensitized CD34(+)/CD38(-) LSCs and induced apoptosis, shown by increased caspase 3, PARP, and Bax while decreased Bcl-2 expression. Additionally, the combined treatment reduced BCR-ABL and β-catenin and MDR-1 protein expression. Mechanistically, IM and SFN combined treatment resensitized LSCs by inducing intracellular reactive oxygen species (ROS). Importantly, β-catenin-silenced LSCs exhibited reduced glutathione S-transferase pi 1 (GSTP1) expression and intracellular GSH level, which led to increased sensitivity toward IM and SFN. We demonstrated that IM and SFN combined treatment effectively eliminated CD34(+)/CD38(-) LSCs. Since SFN has been shown well tolerated in both animals and human, this regimen could be considered for clinical trials.

Pancreatic cancer represents one of the most aggressive types of malignancy due to its high resistance toward most clinically available treatments. The presence of pancreatic cancer stem-like cells (CSCs) has been attributed to the intrinsically high resistance and highly metastatic potential of this disease. Here, we identified and isolated pancreatic CSCs using the side population (SP) method from human pancreatic cancer cell line, PANC-1. We then compared the SP and non-SP PANC-1 cells genetically. PANC-1 SP cells exhibited CSC properties including enhanced self-renewal ability, increased metastatic potential, and resistance toward gemcitabine treatment. These cancer stem-like phenotypes were supported by their enhanced expression of ABCG2, Oct4, and CD44. A traditional plant-derived antioxidant, garcinol, has been implicated for its anticancer properties. Here, we found that garcinol treatment to PANC-1 SP cells significantly suppressed the stem-like properties of PANC-1 SP cells and metastatic potential by downregulating the expression of Mcl-1, EZH2, ABCG2, Gli-1, and Notch1. More importantly, garcinol treatment led to the upregulation of several tumor suppressor microRNAs, and miR-200c increased by garcinol treatment was found to target and downregulate Notch1. Thus, PANC-1 SP cells may serve as a model for studying drug-resistant pancreatic CSCs, and garcinol has the potential as an antagonist against pancreatic CSCs.

In patients with unresectable hepatocellular carcinoma (HCC), radiotherapy is considered for patients with a large tumor burden or tumors with portal vein tumor thrombosis, which is not indicated for operation or transarterial chemoembolization. Sorafenib has proved to be effective as a first-line treatment for locally advanced and metastatic HCC. Preclinical and clinical studies have shown the efficacy of the combined therapeutic effects of radiotherapy (RT) with sorafenib used either concurrently or sequentially. We presented a patient with multiple recurrent HCCs successfully treated with combined RT and sorafenib.

Magnetic Resonance guided Focused Ultrasound (MRgFUS) has been recently proven and was approved by the FDA as an effective method for pain palliation in patients with painful bone metastases from the US, Europe and Russia. This report describes the first clinical experience in Taiwan.