Comparison of 3D and 2D gamma passing rate criteria for detection sensitivity to IMRT delivery errors.

This study compared three-dimensional (3D) and two-dimensional (2D) percentage gamma passing rates (%GPs) for detection sensitivity to IMRT delivery errors and investigated the correlation between two kinds of %GP. Eleven prostate IMRT cases were selected, and errors in multileaf collimator (MLC) bank sag, MLC leaf traveling, and machine output were simulated by recalculating the dose distributions in patients. 2D doses were extracted from the 3D doses at the isocenter position. The 3D and 2D %GPs with different gamma criteria were then obtained by comparing the recalculated and original doses in specific regions of interest (ROI), such as the whole body, the planning target volume (PTV), the bladder, and the rectum. The sensitivities to simulated errors of the two types of %GP were compared, and the correlation between the 2D and 3D %GPs for different ROIs were analyzed. For the whole-body evaluation, both the 2D and 3D %GPs with the 3%/3 mm criterion were above 90% for all tested MLC errors and for MU deviations up to 4%, and the 3D %GP was higher than the 2D %GP. In organ-specific evaluations, the PTV-specific 2D and 3D %GP gradients were -4.70% and -5.14% per millimeter of the MLC traveling error, and -17.79% and -20.50% per percentage of MU error, respectively. However, a stricter criterion (2%/1 mm) was needed to detect the tested MLC sag error. The Pearson correlation analysis showed a significant strong correlation (r > 0.8 and P < 0.001) between the 2D and 3D %GPs in the whole body and PTV-specific gamma evaluations. The whole-body %GP with the 3%/3 mm criterion was inadequate to detect the tested MLC and MU errors, and a stricter criterion may be needed. The PTV-specific gamma evaluation helped to improve the sensitivity of the error detection, especially using the 3D GP%.

GPX2 overexpression indicates poor prognosis in patients with hepatocellular carcinoma.

Glutathione peroxidase 2 has important role of tumor progression in lots of carcinomas, yet little is known about the prognosis of glutathione peroxidase 2 in hepatocellular carcinoma. Glutathione peroxidase 2 expression was assessed by immunohistochemistry in hepatocellular carcinoma tissues. The association between glutathione peroxidase 2 expression with clinicopathological/prognostic value was examined. Glutathione peroxidase 2 overexpression was correlated with alpha-fetoprotein level, larger tumor, BCLC stage, and tumor recurrence. Kaplan-Meier analysis showed that glutathione peroxidase 2 was an independent predictor for overall survival and time to recurrence. glutathione peroxidase 2 overexpression was correlated with poor prognosis in patient subgroups stratified by tumor size, differentiation, tumor-node-metastasis, and BCLC stage. Moreover, stratified analysis showed that tumor-node-metastasis stage-I patients with high glutathione peroxidase 2 expression had poor prognosis than those with low glutathione peroxidase 2 expression. Additionally, combination of glutathione peroxidase 2 and serum alpha-fetoprotein was correlated with prognosis in hepatocellular carcinoma. In conclusion, glutathione peroxidase 2 overexpression contributes to poor prognosis of hepatocellular carcinoma patients and helps to identify the high-risk hepatocellular carcinoma patients.

Robotic radiosurgery system patient-specific QA for extracranial treatments using the planar ion chamber array and the cylindrical diode array.

Robotic radiosurgery system has been increasingly employed for extracranial treatments. This work is aimed to study the feasibility of a cylindrical diode array and a planar ion chamber array for patient-specific QA with this robotic radiosurgery system and compare their performance. Fiducial markers were implanted in both systems to enable image-based setup. An in-house program was developed to postprocess the movie file of the measurements and apply the beam-by-beam angular corrections for both systems. The impact of noncoplanar delivery was then assessed by evaluating the angles created by the incident beams with respect to the two detector arrangements and cross-comparing the planned dose distribution to the measured ones with/without the angular corrections. The sensitivity of detecting the translational (1-3 mm) and the rotational (1°-3°) delivery errors were also evaluated for both systems. Six extracranial patient plans (PTV 7-137 cm³) were measured with these two systems and compared with the calculated doses. The plan dose distributions were calculated with ray-tracing and the Monte Carlo (MC) method, respectively. With 0.8 by 0.8 mm² diodes, the output factors measured with the cylindrical diode array agree better with the commissioning data. The maximum angular correction for a given beam is 8.2% for the planar ion chamber array and 2.4% for the cylindrical diode array. The two systems demonstrate a comparable sensitivity of detecting the translational targeting errors, while the cylindrical diode array is more sensitive to the rotational targeting error. The MC method is necessary for dose calculations in the cylindrical diode array phantom because the ray-tracing algorithm fails to handle the high-Z diodes and the acrylic phantom. For all the patient plans, the cylindrical diode array/ planar ion chamber array demonstrate 100% / > 92% (3%/3 mm) and > 96% / ~ 80% (2%/2 mm) passing rates. The feasibility of using both systems for robotic radiosurgery system patient-specific QA has been demonstrated. For gamma evaluation, 2%/2 mm criteria for cylindrical diode array and 3%/3 mm criteria for planar ion chamber array are suggested. The customized angular correction is necessary as proven by the improved passing rate, especially with the planar ion chamber array system.

Optimization strategies for pulsed low-dose-rate IMRT of recurrent lung and head and neck cancers.

Pulsed low-dose-rate radiotherapy (PLDR) has been proven to be a valid method of reirradiation. Previous studies of recurrent cancer radiotherapy were mainly based on conventional 3D CRT and VMAT delivery techniques. There are difficulties in IMRT planning using existing commercial treatment planning systems (TPS) to meet the PLDR protocol. This work focuses on PLDR using ten-field IMRT and a commercial TPS for two specific sites: recurrent lung cancers and head and neck cancers. Our PLDR protocol requires that the maximum dose to the PTV be less than 0.4 Gy and the mean dose to be 0.2 Gy per field. We investigated various planning strategies to meet the PLDR requirements for 20 lung and head and neck patients. The PTV volume for lung cases ranged from 101.7 to 919.4 cm3 and the maximum dose to the PTV ranged from 0.22 to 0.39 Gy. The PTV volume for head and neck cases ranged from 66.2 to 282.1 cm3 and the maximum dose to the PTV ranged from 0.21 to 0.39 Gy. With special beam arrangements and dosimetry parameters, it is feasible to use a commercial TPS to generate quality PLDR IMRT plans for lung and head and neck reirradiation.

Conditional Dependency of LP-184 on Prostaglandin Reductase 1 is Synthetic Lethal in Pancreatic Cancers with DNA Damage Repair Deficiencies.

The greater efficacy of DNA-damaging drugs for pancreatic adenocarcinoma (PDAC) relies on targeting cancer-specific vulnerabilities while sparing normal organs and tissues due to their inherent toxicities. We tested LP-184, a novel acylfulvene analog, for its activity in preclinical models of PDAC carrying mutations in the DNA damage repair (DDR) pathways. Cytotoxicity of LP-184 is solely dependent on prostaglandin reductase 1 (PTGR1), so that PTGR1 expression robustly correlates with LP-184 cytotoxicity in vitro and in vivo. Low-passage patient-derived PDAC xenografts with DDR deficiencies treated ex vivo are more sensitive to LP-184 compared with DDR-proficient tumors. Additional in vivo testing of PDAC xenografts for their sensitivity to LP-184 demonstrates marked tumor growth inhibition in models harboring pathogenic mutations in ATR, BRCA1, and BRCA2. Depletion of PTGR1, however, completely abrogates the antitumor effect of LP-184. Testing combinatorial strategies for LP-184 aimed at deregulation of nucleotide excision repair proteins ERCC3 and ERCC4 established synergy. Our results provide valuable biomarkers for clinical testing of LP-184 in a large subset of genetically defined characterized refractory carcinomas. High PTGR1 expression and deleterious DDR mutations are present in approximately one third of PDAC making these patients ideal candidates for clinical trials of LP-184.

A novel sensor-embedded holding device for monitoring upper extremity functions.

There are several causes that can lead to functional weakness in the hands or upper extremities (UE), such as stroke, trauma, or aging. Therefore, evaluation and monitoring of UE rehabilitation have become essential. However, most traditional evaluation tools (TETs) and assessments require clinicians to assist or are limited to specific clinical settings. Several novel assessments might apply to wearable devices, yet those devices will still need clinicians or caretakers to help with further tests. Thus, a novel UE assessment device that is user-friendly and requires minimal assistance would be needed. The cylindrical grasp is one of the common UE movements performed in daily life. Therefore, a cylindrical sensor-embedded holding device (SEHD) for training and monitoring was developed for a usability test within this research. The SEHD has 14 force sensors with an array designed to fit holding positions and a six-axis inertial measurement unit (IMU) to monitor grip strength, hand dexterity, acceleration, and angular velocity. Six young adults, six healthy elderly participants, and three stroke survivors had participated in this study to see if the SEHD could be used as a reference to TETs. During result analyses, where the correlation coefficient analyses were applied, forearm rotation smoothness and the Purdue Pegboard Test (PPT) showed a moderate negative correlation [r (16) = -0.724, p < 0.01], and the finger independence showed a moderate negative correlation with the PPT [r (10) = -0.615, p < 0.05]. There was also a highly positive correlation between the maximum pressing task and Jamar dynamometer in maximum grip strength [r (16) = 0.821, p < 0.01]. These outcomes suggest that the SEHD with simple movements could be applied as a reference for users to monitor their UE ability.

Practical Clinical Implementation of the Special Physics Consultation Process in the Re-irradiation Environment.

PURPOSE: The purpose of this work is to present a practical, structured process allowing for consistent, safe radiation therapy delivery in the re-treatment environment. METHODS AND MATERIALS: A process for reirradiation is described with documentation in the form of a special physics consultation. Data acquisition associated with previous treatment is described from highest to lowest quality. Methods are presented for conversion to equieffective dose, as well as our departmental assumptions for tissue repair. The generation of organ-at-risk available physical dose for use in treatment planning is discussed. Results using our methods are compared with published values after conversion to biologically effective dose. Utilization of pulsed-low-dose-rate delivery is described, and data for reirradiation using these methods over the previous 5 years are presented. RESULTS: Between 2015 and 2019, the number of patients in our department requiring equieffective dose calculation has doubled. We have developed guidelines for estimation of sublethal damage repair as a function of time between treatment courses ranging from 0% for <6 months to 50% for >1 year. These guidelines were developed based on available spinal cord data because we found that 84% of organs at risk involved nerve-like tissues. The average percent repair used increased from 32% to 37% over this time period. When comparing the results obtained using our methods with published values, 99% of patients had a cumulative biologically effective dose below the limits established for acceptable myelopathy rates. Pulsed-low-dose-rate use over this period tripled with an average prescription dose of 49 Gy. CONCLUSIONS: The methods described result in safe, effective treatment in the reirradiation setting. Further correlation with patient outcomes and side effects is warranted.

Dosimetric characteristics of an electron multileaf collimator for modulated electron radiation therapy.

Modulated electron radiation therapy (MERT) has been proven as an effective way to deliver conformal dose distributions to shallow tumors while sparing distal critical structures and surrounding normal tissues. It had been shown that a dedicated electron multileaf collimator (eMLC) is necessary to reach the full potential of MERT. In this study, a manually-driven eMLC for MERT was investigated. Percentage depth dose (PDD) curves and profiles at different depths in a water tank were measured using ionization chamber and were also simulated using the Monte Carlo method. Comparisons have been performed between PDD curves and profiles collimated using the eMLC and conventional electron applicators with similar size of opening. Monte Carlo simulations were performed for all electron energies available (6, 9, 12, 15, 18 and 20 MeV) on a Varian 21EX accelerator. Monte Carlo simulation results were compared with measurements which showed good agreement (< 2%/1mm). The simulated dose distributions resulting from multiple static electron fields collimated by the eMLC agreed well with measurements. Further studies were carried out to investigate the properties of abutting electron beams using the eMLC, as it is an essential issue that needs to be addressed for optimizing the MERT outcome. A series of empirical formulas for abutting beams of different energies have been developed for obtaining the optimum gap sizes, which can highly improve the target dose uniformity.

Highly efficient phototheranostics of macrophage-engulfed Gram-positive bacteria using a NIR luminogen with aggregation-induced emission characteristics.

Although phagocytosis serves as the front line to attack invading pathogens, its low bacterial encounter and killing rates leads to an ineffective bactericidal output. In view of this, developing multifunctional theranostic probe to effectively discriminate and ablate intracellular bacteria is highly desirable. However, the shielding effect of the host macrophages put the detection and elimination of macrophage-engulfed bacteria into a challenging task. Herein, we utilize a luminogen with aggregation-induced emission (AIE) characteristics, namely TTVP, as a simple and effective probe for simultaneous tracing and photodynamic killing of intracellular Gram-positive bacteria. With the help of the AIE property, excellent water solubility, near-infrared (NIR) emission and strong reactive oxygen species (ROS) generating ability, TTVP performed ideally to be a targeting agent to intracellular Gram-positive bacteria with high signal contrast, as well as to be a photosensitizer to effectively ablate intracellular bacteria without attacking host macrophages. This work thus provides insights for the next generation antibiosis theranostic application for potential clinical trials.

Ten-Year Update of a Randomized, Prospective Trial of Conventional Fractionated Versus Moderate Hypofractionated Radiation Therapy for Localized Prostate Cancer.

PURPOSE: The previously published single institution randomized prospective trial failed to show superiority in the 5-year biochemical and/or clinical disease failure (BCDF) rate with moderate hypofractionated intensity-modulated radiation therapy (H-IMRT) versus conventionally fractionated IMRT (C-IMRT). We now present 10-year disease outcomes using updated risk groups and definitions of biochemical failure. METHODS: Men with protocol-defined intermediate- and high-risk prostate adenocarcinoma were randomly assigned to receive C-IMRT (76 Gy in 38 fractions) or H-IMRT (70.2 Gy in 26 fractions). Men with high-risk disease were all prescribed 24 months of androgen deprivation therapy (ADT) and had lymph node irradiation. Men with intermediate risk were prescribed 4 months of ADT at the discretion of the treating physician. The primary endpoint was cumulative incidence of BCDF. We compared disease outcomes and overall mortality by treatment arm, with sensitivity analyses for National Comprehensive Cancer Network (NCCN) risk group adjustment. RESULTS: Overall, 303 assessable men were randomly assigned to C-IMRT or H-IMRT. The median follow-up was 122.9 months. Per updated NCCN risk classification, there were 28 patients (9.2%) with low-risk, 189 (62.4%) with intermediate-risk, and 86 (28.4%) with high-risk prostate cancer. The arms were equally balanced for clinicopathologic factors, except that there were more black patients in the C-IMRT arm (17.8% v 7.3%; P = .02). There was no difference in ADT use (P = .56). The 10-year cumulative incidence of BCDF was 25.9% in the C-IMRT arm and was 30.6% in the H-IMRT arm (hazard ratio, 1.31; 95% CI, 0.82 to 2.11). The two arms also had similar cumulative 10-year rates of biochemical failure, prostate cancer-specific mortality, and overall mortality; however, the 10-year cumulative incidence of distant metastases was higher in the H-IMRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%). CONCLUSION: H-IMRT failed to demonstrate superiority compared with C-IMRT in long-term disease outcomes.

A prediction study on radiation-induced second malignancies for IMRT treatment delivery.

Low-level peripheral organ dose and its effect on second malignancies for patients undergoing radiation therapy have been reported in the literature. However, a comprehensive database outlining the treatment modalities, the tumor location, and a quantification of the overall relative risk of second malignancies is rather limited. In this work, we quantify the relative risks or percent likelihood of second malignancies for patients undergoing IMRT and conventional radiotherapy for four different tumor sites: breast, head and neck, lung, and prostate. We utilize Monte Carlo methods based on actual patient plans to compute the whole body effective dose equivalent for each plan and then deduce the percent likelihood of the occurrence of second malignancy. Based on an evaluation of over 30 actual patient plans and Monte Carlo simulations using 6, 10, and 18MV photon beam energies, we observed that the IMRT patients treated for head and neck cancer showed a 40% increase in risk for developing a second malignancy compared to those treated with conventional radiotherapy. The increase in risk for prostrate patients was 30% while the IMRT lung patients gave the highest relative risk almost tripling that observed in their conventionally treated counterparts. There was negligible difference in risk between breast patients undergoing IMRT treatment versus conventional therapy. The overall relative risk of radiation induced malignancy observed was below 6% in all treatment plans considered.

Effect of collimator and couch angle change on breast IMRT dose distributions.

Intensity modulated tangential photon beams for breast cancer treatment can improve the dose uniformity significantly throughout the whole breast and reduce the dose to the lung and the heart comparing with the conventional technique. Before the first treatment, patient setup may require a change on the collimator angle and/or the couch angle based on the chest wall coverage according to the port films. The objective of this work is to investigate the effects of the collimator and the couch angle change on the dose distribution for breast cancer treatment using intensity modulated tangential photon beams, and thus to determine the clinical acceptable range of the angle change for routine treatment. Ten breast cases treated with intensity modulated tangential photon beams were analyzed in this study. Patient-specific CT data and the RTP files obtained from our home-grown Monte Carlo based breast IMRT treatment planning system were used for IMRT dose re-calculation with collimator or couch angle changes. The isodose distributions and DVHs were compared with the original plans and the effects of the collimator and couch angle change to breast IMRT dose distributions were evaluated. Our results show that a 4-degree change in the collimator angle or the couch angle did not affect the dose distribution significantly and it is acceptable in the clinic for patient treatment.

LINC01939 inhibits the metastasis of gastric cancer by acting as a molecular sponge of miR-17-5p to regulate EGR2 expression.

Accumulating evidence have suggested that long noncoding RNAs (lncRNAs) are known to regulate diverse tumorigenic processes. Recently, a novel lncRNA LINC01939 was underexpressed and emerged as a tumor suppressive lncRNA in gastric cancer (GC). In this study, we aimed to investigate the biological function and molecular mechanism of LINC01939 in GC. We found that LINC01939 expression was significantly downregulated in GC tissues and cell lines. Low expression of LINC01939 was correlated with tumor metastasis and shorter survival in GC patients. Functionally, LINC01939 overexpression remarkably inhibited the invasion and migration of GC cells in vitro and in vivo. Mechanistically, LINC01939 regulated the expression of early growth response 2 (EGR2) protein by competitively binding to miR-17-5p. Upregulation of miR-17-5p reversed GC metastasis and EMT process caused by LINC01939 by rescue analysis. Taken together, these results suggested that LINC01939 repressed GC invasion and migration by functioning as a ceRNA for miR-17-5p to regulate EGR2 expression. Our findings provided a novel prognostic marker and therapeutic target for GC patients.

A textured insole improves gait symmetry in individuals with stroke.

PURPOSE: Gait asymmetry is a common consequence of stroke and improving gait symmetry is an important goal of rehabilitation. We investigated the effect of a single textured insole in improving gait symmetry in individuals with stroke. METHOD: Seventeen individuals with stroke who had asymmetrical gait were recruited and required to walk with a textured insole positioned in the shoe on the unaffected side or without the insole. Gait parameters were evaluated using the instrumented walkway. Gait velocity, cadence, and symmetry indices for the spatial and temporal parameters of gait and center of pressure displacements were obtained. RESULTS: When walking with a textured insole, symmetry indexes for stance, single support phases of gait, as well as center of pressure displacements improved significantly. While using a textured insole, the duration of the stance phase and a single support phase decreased on the unaffected side and increased on the affected side significantly. Gait velocity and cadence were not affected by the use of the insole. CONCLUSIONS: Individuals with stroke walking with a textured insole placed in the shoe on the unaffected side improved the symmetry of their gait. The outcome provides a foundation for future investigations of the efficacy of using a single textured insole in gait rehabilitation of individuals with unilateral impairment. Implications for Rehabilitation A single textured insole positioned in the shoe on the unaffected side improved gait symmetry in individuals with stroke. Gait velocity and cadence were not affected by the use of the insole.

Melatonin suppresses thyroid cancer growth and overcomes radioresistance via inhibition of p65 phosphorylation and induction of ROS.

Thyroid cancer is the most common endocrine carcinoma with increasing incidence worldwide and anaplastic subtypes are frequently associated with cancer related death. Radioresistance of thyroid cancer often leads to therapy failure and cancer-related death. In this study, we found that melatonin showed potent suppressive roles on NF-κB signaling via inhibition of p65 phosphorylation and generated redox stress in thyroid cancer including the anaplastic subtypes. Our data showed that melatonin significantly decreased cell viability, suppressed cell migration and induced apoptosis in thyroid cancer cell lines in vitro and impaired tumor growth in the subcutaneous mouse model in vivo. By contrast, irradiation of thyroid cancer cells resulted in elevated level of phosphorylated p65, which could be reversed by cotreatment with melatonin. Consequently, melatonin synergized with irradiation to induce cytotoxicity to thyroid cancer, especially in the undifferentiated subgroups. Taken together, our results suggest that melatonin may exert anti-tumor activities against thyroid carcinoma by inhibition of p65 phosphorylation and induction of reactive oxygen species. Radio-sensitization by melatonin may have clinical benefits in thyroid cancer.

HOXC6 predicts invasion and poor survival in hepatocellular carcinoma by driving epithelial-mesenchymal transition.

Aberrant expression of HOXC6 has been reported in several malignant tumors, yet little is known about the value of HOXC6 in invasion and prognosis of hepatocellular carcinoma (HCC). HOXC6 expression was positively correlated with high AFP level, liver cirrhosis, larger tumor, vascular invasion and BCLC stage. Kaplan-Meier analysis revealed that HOXC6 was an independent predictor for overall survival (OS) and time to recurrence (TTR). In addition, HOXC6 status could act as prognostic predictor in different risk subgroups. Moreover, HOXC6 maintained its prognostic value in different ability of invasiveness. Furthermore, combination of HOXC6 and serum AFP could be a potential predictor for survival in HCC patients. Additionally, further study showed that HOXC6 may promote invasion of HCC by driving epithelial-mesenchymal transition (EMT). Knockdown of HOXC6 significantly decreased the migration and invasion of HCC cells and changed the expression pattern of EMT markers. An opposite expression pattern of EMT markers was observed in HOXC6-transfected cells. In addition, immunohistochemistry and RT-PCR results further confirmed this correlation. In conclusion, HOXC6 contributes to invasion by inducing EMT pathway and predicts poor prognosis of HCC. HOXC6/AFP expression may help to distinguish the different risks of HCC patients after hepatectomy.

A treatment planning comparison between a novel rotating gamma system and robotic linear accelerator based intracranial stereotactic radiosurgery/radiotherapy.

To compare the dosimetric parameters of a novel rotating gamma ray system (RGS) with well-established CyberKnife system (CK) for treating malignant brain lesions. RGS has a treatment head of 16 cobalt-60 sources focused to the isocenter, which can rotate 360° on the ring gantry and swing 35° in the superior direction. We compared several dosimetric parameters in 10 patients undergoing brain stereotactic radiosurgery including plan normalization, number of beams and nodes for CK and shots for RGS, collimators used, estimated treatment time, D 2 cm and conformity index (CI) among two modalities. The median plan normalization for RGS was 56.7% versus 68.5% (p = 0.002) for CK plans. The median number of shots from RGS was 7.5 whereas the median number of beams and nodes for CK was 79.5 and 46. The median collimator's diameter used was 3.5 mm for RGS as compared to 5 mm for CK (p = 0.26). Mean D 2 cm was 5.57 Gy for CyberKnife whereas it was 3.11 Gy for RGS (p = 0.99). For RGS plans, the median CI was 1.4 compared to 1.3 for the CK treatment plans (p = 0.98). The average minimum and maximum doses to optic chiasm were 21 and 93 cGy for RGS as compared to 32 and 209 cGy for CK whereas these were 0.5 and 364 cGy by RGS and 18 and 399 cGy by CK to brainstem. The mean V12 Gy for brain predicting for radionecrosis with RGS was 3.75 cm3 as compared to 4.09 cm3 with the CK (p = 0.41). The dosimetric parameters of a novel RGS with a ring type gantry are comparable with CyberKnife, allowing its use for intracranial lesions and is worth exploring in a clinical setting.

CLCA4 inhibits cell proliferation and invasion of hepatocellular carcinoma by suppressing epithelial-mesenchymal transition via PI3K/AKT signaling.

Calcium activated Chloride Channel A4 (CLCA4), as a tumor suppressor, was reported to contribute to the progression of several malignant tumors, yet little is known about the significance of CLCA4 in invasion and prognosis of hepatocellular carcinoma (HCC). CLCA4 expression was negatively correlated with tumor size, vascular invasion and TNM stage. Kaplan-Meier analysis showed that CLCA4 was an independent predictor for overall survival (OS) and time to recurrence (TTR). In addition, CLCA4 status could act as prognostic predictor in different risk of subgroups. Moreover, combination of CLCA4 and serum AFP could be a potential predictor for survival in HCC patients. Furthermore, CLCA4 may inhibit cell migration and invasion by suppressing epithelial-mesenchymal transition (EMT) via PI3K/ATK signaling. Knockdown of CLCA4 significantly increased the migration and invasion of HCC cells and changed the expression pattern of EMT markers and PI3K/AKT phosphorylation. An opposite expression pattern of EMT markers and PI3K/AKT phosphorylation was observed in CLCA4-transfected cells. Additionally, immunohistochemistry and RT-PCR results further confirmed this correlation. Taken together, CLCA4 contributes to migration and invasion by suppressing EMT via PI3K/ATK signaling and predicts favourable prognosis of HCC. CLCA4/AFP expression may help to distinguish different risks of HCC patients after hepatectomy.

Monte Carlo determination of radiation-induced cancer risks for prostate patients undergoing intensity- modulated radiation therapy.

The application of intensity-modulated radiation therapy (IMRT) has enabled the delivery of high doses to the target volume while sparing the surrounding normal tissues. The drawbacks of intensity modulation, as implemented using a computer controlled multileaf collimator (MLC), are the larger number of monitor units (MUs) and longer beam-on time as compared with conventional radiotherapy. Additionally, IMRT uses more beam directions--typically 5-- 9 for prostate treatment--to achieve highly conformal dose and normal-tissue sparing. In the present work, we study radiation-induced cancer risks attributable to IMRT delivery using MLC for prostate patients. Whole-body computed tomography scans were used in our study to calculate (according to report no. 116 from the National Council on Radiation Protection and Measurements) the effective dose equivalent received by individual organs. We used EGS4 and MCSIM to compute the dose for IMRT and three-dimensional conformal radiotherapy. The effects of collimator rotation, distance from the treatment field, and scatter and leakage contribution to the whole-body dose were investigated. We calculated the whole-body dose equivalent to estimate the increase in the risk of secondary malignancies. Our results showed an overall doubling in the risk of secondary malignancies from the application of IMRT as compared with conventional radiotherapy. This increase in the risk of secondary malignancies is not necessarily related to a relative increase in MUs. The whole-body dose equivalent was also affected by collimator rotation, field size, and the energy of the photon beam. Smaller field sizes of low energy photon beams (that is, 6 MV) with the MLC axis along the lateral axis of the patient resulted in the lowest whole-body dose. Our results can be used to evaluate the risk of secondary malignancies for prostate IMRT patients.

Comparing computed tomography localization with daily ultrasound during image-guided radiation therapy for the treatment of prostate cancer: a prospective evaluation.

In the present paper, we describe the results of a prospective trial that compared isocenter shifts produced by BAT Ultrasound (Nomos, Sewicky, PA) to those produced by a computed tomography (CT) unit in the treatment room to aid in positioning during image-guided radiation therapy. The trial included 15 consecutive patients with localized prostate cancer. All patients underwent CT and MR simulation immobilized supine in an Alpha Cradle and were treated with intensity-modulated radiation therapy. BAT Ultrasound was used daily to correct for interfraction motion by obtaining shift in the x, y, and z directions. Two days per week during therapy, CT scans blinded to the ultrasound shifts were obtained and recorded. We analyzed 218 alignments from the 15 patients and observed a high level of correlation between the CT and ultrasound isocenter shifts (correlation coefficients: 0.877 anterior-posterior, 0.842 lateral, and 0.831 superior-inferior). The systematic differences were less than 1 mm, and the random differences were approximately 2 mm. The average absolute differences, including both systemic and random differences, were less than 2 mm in all directions. The isocenter shifts generated by using a CT unit in the treatment room correlate highly with shifts produced by the BAT Ultrasound system.