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This study combined the use of radiation dosimeteric measurements and a custom-made anthropomorphic phantom in order to evaluate the accuracy of therapeutic dose calculations at the nasopharyngeal air-tissue interface. The doses at the nasopharyngeal air-tissue interface obtained utilizing the Pinnacle and TomoTherapy TPS, which are based on collapsed cone convolution superposition (CCCS) algorithms, were evaluated and measured under single 10 × 10 c m 2 , 2 × 2 c m 2 , two parallel opposed 2 × 2 c m 2 and clinical fields for early stage of nasopharyngeal carcinoma by using EBT3, GR-200F, and TLD 100. At the air-tissue interface under a 10 × 10 c m 2 field, the TPS dose calculation values were in good agreement with the dosimeter measurement with all differences within 3.5%. When measured the single field 2 × 2 c m 2 , the differences between the average dose were measured at the distal interface for EBT3, GR-200F, and TLD-100 and the calculation values were -15.8%, -16.4%, and -4.9%, respectively. When using the clinical techniques such as IMRT, VMAT, and tomotherapy, the measurement results at the interface for all three techniques did not imply under dose. Small-field sizes will lead to dose overestimation at the nasopharyngeal air-tissue interface due to electronic disequilibrium when using CCCS algorithms. However, under clinical applications of multiangle irradiation, the dose errors caused by this effect were not significant.

Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive and has poor prognosis. There are few biomarkers to inform treatment decisions, and collecting tumour samples for testing is challenging.Circulating tumour cells (CTCs) from patients with PDAC liquid biopsies were expanded ex vivo to form CTC-derived organoid cultures, using a laboratory-developed biomimetic cell culture system. CTC-derived organoids were tested for sensitivity to a PDAC panel of nine drugs, with tests conducted in triplicate, and a weighted cytotoxicity score (CTS) was calculated from the results. Clinical response to treatment in patients was evaluated using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria at the time of blood sampling and 3 months later. The correlation between CTS and clinical response was then assessed.A total of 41 liquid biopsies (87.8% from patients with Stage 4 disease) were collected from 31 patients. The CTC-derived organoid expansion was achieved in 3 weeks, with 87.8% culture efficiency. CTC-derived organoid cultures were positive for EpCAM staining and negative for CD45 staining in the surface marker analysis. All patients had received a median of two lines of treatment prior to enrolment and prospective utility analysis indicated significant correlation of CTS with clinical treatment response. Two representative case studies are also presented to illustrate the relevant clinical contexts.CTCs were expanded from patients with PDAC liquid biopsies with a high success rate. Drug sensitivity profiles from CTC-derived organoid cultures correlated meaningfully with treatment response. Further studies are warranted to validate the predictive potential for this approach.

Kaplan-Meier curve demonstrating overall survival and cancer-specific survival for patients with squamous cell carcinoma (n = 215) according to (A, B) pre-treatment skeletal muscle index, (C, D) pre-treatment skeletal muscle density, (E, F) skeletal muscle change, (G, H) subcutaneous adipose tissue index, (I, J) visceral adipose tissue index groups. SMD, skeletal muscle density; SMI, skeletal muscle index; SATI, subcutaneous adipose tissue index; VATI visceral adipose tissue index.

Purpose: This study investigates the association between body composition change during concurrent chemoradiotherapy (CCRT) and outcome in patients with locally advanced cervical cancer (LACC).Experimental Design: Pre- and posttreatment CT images of 245 patients with LACC who were treated between 2004 and 2015 were analyzed. Skeletal muscle index (SMI) and density (SMD), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured from two sets of CT images at the level of the L3 vertebra. Sarcopenia and a low SMD were defined using published cut-off points. Predictors of overall survival (OS) and cancer-specific survival (CSS) were analyzed using Cox regression models.Results: The median follow-up was 62.7 (range, 7.3–152.3) months. Among the 245 patients, 127 (51.8%) had pretreatment sarcopenia, and 154 (62.9%) had a low SMD. SMI did not decrease significantly during CCRT, 0.6%/150 days [95% confidence interval (CI), −1.8–0.6; P = 0.35]. However, SMI loss during CCRT of >10.0%/150 days was independently associated with poorer OS (HR, 6.02; 95% CI, 3.04–11.93; P < 0.001) and CSS (HR, 3.49; 95% CI, 1.44–8.42; P = 0.006) when adjusted for FIGO stage, pathology, and treatment. Pretreatment sarcopenia and change of SMD, SATI, and VATI during CCRT were not associated with survival.Conclusions: Skeletal muscle measurements could be imaging biomarkers to predict outcomes for patients with LACC in clinical practice. Further studies are needed to determine whether multimodal interventions can preserve skeletal muscle mass and thereby improve survival. Clin Cancer Res; 24(20); 5028–36. ©2018 AACR.

Supplementary Table S1 Patient and tumour characteristics according to muscle change (n = 245); Supplementary Table S2 Univariable Cox proportional hazards model for overall survival and cancer-specific survival (n = 245); Supplementary Table S3 Univariable and multivariable Cox proportional hazards model for overall survival and cancer-specific survival for patients with squamous cell carcinoma (n = 215); Supplementary Table S4 Acute toxicities by SATI and VATI groups (n = 245).

(1) Background: The purpose of this study was to evaluate the radiation awareness level of the public in Taiwan. (2) Methods: This study designed an online survey form to investigate the radiation awareness level with six topics: basic knowledge of radiation, environmental radiation, medical radiation, radiation protection, and university/corporate social responsibility. The score of respondents were converted into knowledge and responsibility indexes for the quantitative evaluation. Logistic regression was used to assess the correlation between the knowledge index and individual factors. Paired t-test was used to assess the significant difference in knowledge index between pre-training and post-training. (3) Results: The knowledge index of each job category reflected the proportion of radiation awareness of the job. The logistic regression result indicated that radiation-related people could get higher knowledge index. The paired t-test indicated that the knowledge index before and after class had significant differences in all question topics. (4) Conclusions: The public’s awareness of medical radiation was the topic that needed to be strengthened the most—the responses with high knowledge index significantly correlated with their experience in radiation education training or radiation-related jobs. It significantly increased the knowledge index of radiation if the public received radiation education training.

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.

Background: Neoadjuvant chemoradiation therapy (NCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC); approximately 80% of patients do not achieve complete response. Identifying prognostic factors predictive of survival in these patients to guide further management is needed. The intratumoural lymphocytic response (ILR), peritumoural lymphocytic reaction (PLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PtLR) are correlated with the tumour microenvironment and cancer-related systemic inflammation. This study aimed to explore the ability of the ILR, PLR, NLR, and PtLR to predict survival in LARC patients without a complete response to NCRT. Methods: Sixty-nine patients who underwent NCRT and surgery were retrospectively reviewed. The ILR and PLR were assessed in surgical specimens, and the NLR and PtLR were calculated using pre- and post-NCRT blood count data. The Kaplan–Meier method and Cox regression analyses were performed for survival analysis. Results: A high PLR and high post-NCRT NLR and PtLR were significantly associated with better prognosis. Lymphovascular invasion (LVI), post-NCRT neutrophil count, and lymphocyte count were significant predictors of overall survival. LVI and the PLR were independent predictors of disease-free survival. Conclusions: NCRT-induced local and systemic immune responses are favourable prognostic predictors in LARC patients without complete response to NCRT.

This study was to determine the artificial factors considered for the measurement accuracy of personal dosimeter in dosimetry services under current performance test criteria. The investigation included management information questionnaire, on-site visit and blind test. The blind test with random selected personal badge was used in inter-comparison of eight dosimetry services, and the test results followed ANSI/HPS N13.11 criteria. This study also analyzed the measurement deviations if they felt in the criteria of ICRP 75 or not. One-way ANOVA tests were used to analyze the significant difference of the measurement deviations in different dosimetry services, irradiation categories, and years of use. Simple linear-regression test was performed for the significance of the prediction model between measurement deviations (category I, category II deep, and category II shallow) and readout frequencies. All visited dosimetry services followed the proper statue of basic management and passed the performance check of the tolerance level. There had significant differences of measurement deviation in different dosimetry services and irradiation categories but no significant difference in years of use. There was no significance in the linear-regression model between measurement deviation and badge readout frequencies. Based on the regular calibration of the personal dosimeter, the deviation of the measured value is mainly affected by different dosimetry services and irradiation categories; and there shows no significant influence by years of use and readout frequency.

5-iododeoxyuridine (IUdR), a radiosensitizer able to be incorporated into nascent DNA during synthesis, makes the DNA easy to break upon irradiation. IUdR has been used together with low energy radiation in cancer treatments mechanistically by Auger electron induction to damage DNA. In this study, a small-sized transmission X-ray tube equipped with a Lanthalum target (La-tX ray) generating 33–40 keV-enriched photons was used in combination with IUdR for Auger cancer therapy, and the performance was evaluated by multiple assays in vitro and in vivo. Cytotoxicity, thymidine replacement and nuclear incorporation of IUdR were evaluated in NG4TL4 fibrosarcoma cells and SAS head and neck cancer cells. After treatment of IUdR + La-tX ray irradiation or IUdR + Co-60 irradiation, cell survival and DNA damages were evaluated by colony forming assay and comet assay/γH2AX staining, respectively. Growth of tumor xenografts receiving an intratumoral IUdR injection (45 μg) and/or La-tX ray irradiation were measured. For NG4TL4 and SAS cells, the IC50 of IUdR were ~ 7 and ~ 10 μg/ml, respectively. As compared to IUdR + Co-60 irradiation, IUdR + La-tX ray resulted in higher DNA breaks in cancer cells. Also, IUdR + La-tX ray resulted in higher cell toxicity than IUdR + Co-60. In the in vivo study, tumor xenografts showed inhibited growth in the IUdR + La-tX ray treatment, compared to those in the IUdR or La-tX ray treatment alone. This study demonstrated the potential of cancer Auger electron therapy using a small-sized transmission X ray tube that generated enriched specific energy X rays for Auger electron induction.

This paper discusses the feasibility of a monitoring program for the quality assurance status of activity meters. We sent a questionnaire to clinical nuclear medicine departments of medical institutions, requesting information on their activity meters and quality assurance practices. On-site visits were conducted with exemption-level standard sources (Co-57, Cs-137 and Ba-133) for dose calibrators in nuclear medicine departments including physical inspection, accuracy and reproducibility. A method offering a quick check on the detection efficiency of the space dimension inside the activity meters was also introduced. For dose calibrator quality assurance, the daily checks had the highest implementation. However, annual checks and upon acceptance/after a repair check were reduced to 50% and 44%, respectively. The accuracy results of dose calibrators showed that all models exceeded the ±10% criteria with Co-57 and Cs-137 sources. The reproducibility results showed that some models exceeded the ±5% criteria with Co-57 and Cs-137 sources. The appropriate application of exemption-level standard sources considering the uncertainty that affects the measurement is discussed.

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.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is highly aggressive and has poor prognosis. There are few biomarkers to inform treatment decisions, and collecting tumor samples for genomic or drug sensitivity testing is challenging.MethodsCirculating tumor cells (CTCs) were prepared from the liquid biopsies of PDAC patients. These cells were subsequently expanded ex vivo to form CTC-derived organoid cultures, using a laboratory-developed biomimetic cell culture system. The CTC-derived organoids were tested for sensitivity to a PDAC panel of nine drugs, with tests conducted in triplicate, and a weighted cytotoxicity score (CTS) was calculated from the results. Clinical response to treatment in patients was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria at the time of blood sampling and 3 months later. CTS was then correlated with clinical response, and analyzed using 2 × 2 contingency tables.ResultsA total of 41 liquid biopsies were collected from 31 patients, with 87.8% of liquid biopsies from patients with Stage 4 disease. CTC-derived organoid expansion was achieved in 3 weeks, with 87.8% culture efficiency. CTC-derived organoid cultures were positive for EpCAM staining and negative for CD45 staining in surface marker analysis. All patients had received a median of two lines of treatment prior to enrollment, and prospective utility analysis indicated significant correlation of CTS with clinical treatment response. Two representative case studies are also presented to illustrate the relevant clinical contexts.ConclusionsIn this study, CTCs were expanded from the liquid biopsies of PDAC patients with a high success rate. Drug sensitivity profiles from CTC-derived organoid cultures correlated meaningfully with treatment response. Further studies are warranted to validate the predictive potential for this approach.Trial RegistrationTaipei Medical University Hospital Protocol Record N201803020, registered on July 10, 2018; ClinicalTrials.gov Identifier: NCT04972461, retrospectively registered on July 22, 2021.

This study aimed to investigate dosimeter characteristics by using a photon beam with and without the flattening filter of intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) by using a 3D N-isopropylacrylamide (NIPAM) polymer gel. A self-developed optical computed tomography scheme was used to measure the dose distribution. Gamma evaluation was performed between the dose distribution calculated by a treatment planning system and the measured dose distribution by using the criteria of 3% dose difference and 3 mm distance to agreement. Under these criteria, the passing rates showed no significant difference between IMRT and VMAT irradiation with and without the flattening filter. All these results revealed that the NIPAM gel dosimeter was for high-dose-rate radiation and clinical-pretreatment verifications.

OBJECTIVE Good bone quality is the key to avoiding osteoporotic fragility fractures and poor outcomes after lumbar instrumentation and fusion surgery. Although dual-energy x-ray absorptiometry (DEXA) screening is the current standard for evaluating osteoporosis, many patients lack DEXA measurements before undergoing lumbar spine surgery. The present study aimed to investigate the utility of using simple quantitative parameters generated with novel synthetic MRI to evaluate bone quality, as well as the correlations of these parameters with DEXA measurements. METHODS This prospective study enrolled patients with symptomatic lumbar degenerative disease who underwent DEXA and conventional and synthetic MRI. The quantitative parameters generated with synthetic MRI were T1 map, T2 map, T1 intensity, proton density (PD), and vertebral bone quality (VBQ) score, and these parameters were correlated with T-score of the lumbar spine. RESULTS There were 62 patients and 238 lumbar segments eligible for analysis. PD and VBQ score moderately correlated with T-score of the lumbar spine (r = −0.565 and −0.651, respectively; both p < 0.001). T1 intensity correlated fairly well with T-score (r = −0.411, p < 0.001). T1 and T2 correlated poorly with T-score. Receiver operating characteristic curve analysis demonstrated area under the curve values of 0.808 and 0.794 for detecting osteopenia/osteoporosis (T-score ≤ −1.0) and osteoporosis (T-score ≤ −2.5) with PD (both p < 0.001). CONCLUSIONS PD and T1 intensity values generated with synthetic MRI demonstrated significant correlation with T-score. PD has excellent ability for predicting osteoporosis and osteopenia.

Although boron neutron capture therapy (BNCT) is a promising treatment option for malignant brain tumors, the optimal BNCT parameters for patients with immediately life-threatening, end-stage brain tumors remain unclear. We performed BNCT on 34 patients with life-threatening, end-stage brain tumors and analyzed the relationship between survival outcomes and BNCT parameters. Before BNCT, MRI and 18F-BPA-PET analyses were conducted to identify the tumor location/distribution and the tumor-to-normal tissue uptake ratio (T/N ratio) of 18F-BPA. No severe adverse events were observed (grade ≥ 3). The objective response rate and disease control rate were 50.0% and 85.3%, respectively. The mean overall survival (OS), cancer-specific survival (CSS), and relapse-free survival (RFS) times were 7.25, 7.80, and 4.18 months, respectively. Remarkably, the mean OS, CSS, and RFS of patients who achieved a complete response were 17.66, 22.5, and 7.50 months, respectively. Kaplan–Meier analysis identified the optimal BNCT parameters and tumor characteristics of these patients, including a T/N ratio ≥ 4, tumor volume &lt, 20 mL, mean tumor dose ≥ 25 Gy-E, MIB-1 ≤ 40, and a lower recursive partitioning analysis (RPA) class. In conclusion, for malignant brain tumor patients who have exhausted all available treatment options and who are in an immediately life-threatening condition, BNCT may be considered as a therapeutic approach to prolong survival.

To develop a method of estimating surface dose in whole breast irradiation, we used an anthropomorphic phantom with accessories for the simulation of different breast sizes. The surface points, which are measured by TLDs, are set along with two main directions, superior-inferior and medial-lateral. The incident angle between the photon beam and the surface and the doses at 1 cm beneath the surface at every point are assessed by a computerized treatment planning system (cTPS). With the prescription dose of 200 cGy, the average surface doses under tangential irradiation are 97.73 (±14.96) cGy, 99.90 (±10.73) cGy, and 105.26 (±9.21) cGy for large, medium, and small breast volumes, respectively. The surface dose increased in the model of small breast volume without significance (p = 0.39). The linear analysis between surface dose and the incident angle is y = 0.5258x + 69.648, R2 = 0.7131 (x: incident angle and y: surface dose). We develop the percentage of skin surface dose with reference to a depth of 1 cm (PSDR1cm) to normalize the inhomogeneous dose. The relationship between incident angle and PSDR1cm is y = 0.1894x + 36.021, R2 = 0.6536 (x: incident angle and y: PSDR1cm) by linear analysis. In conclusion, the surface dose in whole breast irradiation could be estimated from this linear relationship between PSDR1cm and incident angle in daily clinical practice by cTPS. Further in vivo data should be studied to verify this formula.

Objectives: This study examines the practice of the regulation of Standards for Medical Exposure Quality Assurance (SMEQA) in Taiwan based on on-site quality audit for radiation therapy systems from 2016 to 2019. Methods: 81 radiation therapy departments, 141 linacs, 9 γ knife systems, 34 high dose rate brachytherapy systems, 20 Tomotherapys, and 6 Cyberknives were audited yearly. Data collection and analysis for each institute’s documents including QA procedure, ion chamber and electrometer calibration reports, and a questionnaire relating to machine type and staffing, were requested first and reviewed by auditors. On-site SMEQA core item measurements, including beam output, beam profile and energy constancy for external beam therapy systems, and the source strength, positioning, and timer accuracy for brachytherapy systems were audited second. More than 300 photon beams and more than 400 electron beams were measured each year. Results: There were approximately 8.9 radiotherapy units per million population, and 1.2 medical physicists per unit in Taiwan. For the output measurements, more than 78 and 75% of the photon beams and electron beams, respectively, from linacs were with deviations within ±1.0%. Photon beams have lower beam quality measurement deviations than electron beams. Including in-plane and cross-plane measurements, more than 90 and 85% photon and electron beams, respectively, were with flatness consistency within 1.0%. All audit measurements were within the SMEQA acceptance criteria. Conclusions: According to SMEQA regulations on-site QA audits were successfully carried out from 2016 to 2019 for all Taiwan radiotherapy units. The measurement results showed high quality machine performance in Taiwan. Advances in knowledge: Dosimetry audits with directly acquired measurement readings have lower uncertainties; allow immediate feedback, discussion, and adjustment in a timely manner. In addition to regulation system establishment and education and training implementation, the machine quality is closely related to machine maintenance implementation.

Purpose: This study examines the practice of the regulation of Standards for Medical Exposure Quality Assurance (SMEQA) in Taiwan based on on-site quality audit for radiation therapy systems from 2016 to 2019. Methods and Materials: about 81 radiation therapy departments, 141 medical linear accelerators, 9 gamma knifes, 34 high dose rate brachytherapy systems, 20 Tomotherapys and 6 Cyberknives were audited yearly. The inspection was implemented in two stages. Data collection and analysis for each institute’s documents including QA operating procedure, ion chamber and electrometer calibration reports, and a questionnaire relating to machine type and staffing, were requested first and reviewed by specially trained auditors. On-site measurements of SMEQA core items, including beam output, beam profile and energy constancy for external beam therapy systems, and the source strength, positioning and timer accuracy for brachytherapy systems were audited second. More than 300 photon beams were measured from linacs, Gamma knives, Cyberknives and Tomotherapys, and more than 400 electron beams from linacs each year.Results: The radiation treatment resource is about 8.9 therapy machines or 7.5 MV/MeV/ion beam therapy machines per million population, respectively, and there are on average about 1.20 medical physicists per radiation therapy unit in Taiwan. There were more than 78% and 75% of photon and electron beams respectively from linacs with deviations measured to the stated reference-point dose within 1.0%. Photon beams have lower beam quality measurement deviations than electron beams, and more than 90% of photon beams from linacs were within 1.0%. Including in-plane and cross-plane measurements, more than 90% and 85% of photon and electron beams respectively with flatness consistency within 1.0%. Beam symmetry as an absolute value has more than 75% of measurements within 1.0%. All audit measurements in this study were within the SMEQA acceptance criteria.Conclusions: On-site machine QA audits have been implemented from 2016 to 2019 for all radiation therapy units each year. The measurement results have shown a high quality machine performance in Taiwan.

ObjectiveTo evaluate the effects of body mass index (BMI) and weight change during radiotherapy on the development of toxicity in patients with locally advanced cervical cancer (LACC) treated with intensity-modulated radiotherapy (IMRT).MethodsA total of 245 patients were analyzed after undergoing definitive IMRT treatment between 2004 and 2015 for stage IB2 to stage IVA LACC. The patients were divided into 3 groups: underweight (BMI 2), normal weight (BMI 18.5–24.9 kg/m2), and overweight (BMI ≥25.0 kg/m2). The relationships between toxicity, clinical factors, and the bowel dose-volume histogram were analyzed. V45 indicated the bowel volume that received a radiation dose of 45 Gy.ResultsThe median follow-up period was 63 months. The V45 was similar among the 3 groups. The 5-year rates of grade 3 or higher late gastrointestinal toxicities were 18.6%, 4.0%, and 4.2% for the underweight, normal weight, and overweight groups, respectively (P = 0.002). In the multivariable analysis, underweight (hazard ratio, 13.99; 95% confidence interval, 3.22-60.82; P < 0.001) and weight loss (> −5%) (hazard ratio, 5.91; 95% confidence interval, 1.75-19.98; P = 0.004) were significant predictors of grade 3 or higher-grade late gastrointestinal toxicities.ConclusionA BMI of less than 18.5 kg/m2 and weight loss (> −5%) were associated with a higher risk of grade ≥3 or higher late gastrointestinal toxicity in patients with LACC treated with definitive IMRT. Future research on the development of a standardized and structured approach to improve the therapeutic ratio for the supportive care of patients with LACC is needed.

Background and purpose The left anterior descending coronary artery (LAD) and diagonal branches (DBs) are blurred on computed tomography (CT). We aimed to define the LAD region (LADR) with adequate inclusion of the LAD and DBs and contouring consistency. Methods and materials The LADR was defined using coronary CT angiograms. The inclusion ratio was used to assess the LAD and DBs inclusion by the LADR. Four radiation oncologists delineated the LAD and LADR, using contrast-enhanced CT of 15 patients undergoing left breast radiotherapy. The Sorensen–Dice similarity index (DSI), Jaccard similarity index (JSI), and Hausdorff distance (HD) were calculated to assess similarity. The mean dose ( D mean ) and maximum dose ( D max ) to the LAD and LADR were calculated to compare consistency. Correlations were evaluated using Pearson's correlation coefficient. Results The inclusion ratio of the LAD by the LADR was 96%. The mean DSI, JSI, and HD values were respectively 27.9%, 16.7%, and 0.42mm for the LAD, and 83.1%, 73.0%, and 0.18mm for the LADR. The D mean between the LAD and LADR were strongly correlated ( r =0.93). Conclusion Delineation of the LADR significantly improved contouring similarity and consistency for dose reporting. This could optimize dose estimation for breast radiotherapy.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and deadliest cancers in the world. Currently, sorafenib is the only drug that has been approved by the U.S. FDA for patients with advanced HCC. However, its improvement on patient outcomes is modest, and the median survival time is only prolonged 2–3 months. In addition, the application of sorafenib is limited because of its high cost and severe adverse side-effects. Therefore, developing more effective novel agents and reducing the dosage of sorafenib are urgently needed for HCC therapy. Here, a novel benzimidazole derivative (4a) bearing a pyrolidine side chain (9a) was synthesized. The treatments of compounds 4a, 9a and sorafenib either alone or in combination on the inhibition of liver cancer cells proliferation were measured using alamarBlue cell viability and trypan blue staining assay. Intracellular signaling pathway activities were assessed by Western blot, Q-PCR and IHC staining. The HuH7 xenograft model was used to examine antitumor activity in vivo. Adverse effects (e.g., changes in body weight, serum parameters, liver function and pathology) of mice treated with 9a were also evaluated. Compound 9a significantly inhibited HCC cell proliferation compared with 4a. In addition, 9a strongly synergized with a low dose of sorafenib in suppressing HCC cell proliferation. Regarding the activities of the signaling pathways, sorafenib did not suppress AKT signaling; however, 9a inhibited AKT and its downstream phosphorylation of p70S6K. In addition, treatment with either 9a alone or in combination with sorafenib led to the inhibition of JNK phosphorylation. However, there were no effects on the inhibition of apoptosis. The in vivo HuH7 xenograft model showed that the administration of 9a plus a low dose of sorafenib significantly decreased expression of the HCC markers α-fetoprotein, glypican-3 and survivin as well as suppressed tumor growth. Finally, there were no adverse effects in mice treated with 9a. In conclusion, co-treatment with a novel benzimidazole derivative bearing a pyrolidine side chain in combination with a low dose of sorafenib exerted significant antitumor activity in preclinical HCC models, which potentially suggests its use as a novel therapeutic strategy for patients with HCC.

OBJECTIVEOne- and two-level cervical disc arthroplasty (CDA) has been compared to anterior cervical discectomy and fusion (ACDF) in several large-scale, prospective, randomized trials that have demonstrated similar clinical outcomes. However, whether these results would be similar when treating 3-level disc herniation and/or spondylosis has remained unanswered. This study aimed to investigate the differences between 3-level CDA and ACDF.METHODSA series of 50 patients who underwent 3-level CDA at C3–7 was retrospectively reviewed and compared with another series of 50 patients (age- and sex-matched controls) who underwent ACDF at C3–7. Clinical outcomes were measured using the visual analog scale (VAS) for neck and arm pain, the modified Japanese Orthopaedic Association (mJOA) scale, and the Neck Disability Index (NDI). Radiological outcomes included range of motion (ROM) at the index levels. Every patient was evaluated by CT for the presence of fusion in the ACDF group. Also, complication profiles were investigated.RESULTSThe demographics and levels of distribution in both groups were very similar. During the follow-up period of 24 months, clinical outcomes improved (overall and respectively in each group) for both the CDA and ACDF patients when compared with the patients’ preoperative condition. There were essentially few differences between the two groups in terms of neck and arm pain VAS scores, mJOA scores, and NDI scores preoperatively and at 3, 6, 12, and 24 months postoperatively. After the 3-level surgery, the CDA group had an increased mean ROM of approximately 3.4°, at 25.2° ± 8.84°, compared to their preoperative ROM (21.8° ± 7.20°) (p = 0.001), whereas the ACDF group had little mobility (22.8° ± 5.90° before and 1.0° ± 1.28° after surgery; p < 0.001). The mean operative time, estimated blood loss, and complication profiles were similar for both groups.CONCLUSIONSIn this selectively matched retrospective study, clinical outcomes after 3-level CDA and ACDF were similar during the 2-year follow-up period. CDA not only successfully preserved but slightly increased the mobility at the 3 index levels. However, the safety and efficacy of 3-level CDA requires more long-term data for validatation.

Radiation therapy plays an important role in standard cancer treatment. However, patients who are resistant to traditional radiation therapy or who have relapsed after conventional radiation therapy are often encountered in clinical practice...

Purpose: Primary hepatocellular carcinoma and metastatic liver tumors are highly malignant tumors in Asia. The incidence of fatal liver cancer is also increasing in the United States. The aim of this study was to establish a spherical tumor model and determine its accuracy in predicting the absorbed dose in yttrium-90 (Y-90) microsphere therapy for liver cancer. Methods: Liver morphology can be approximated by a spherical model comprising three concentric regions representing necrotic, tumor, and normal liver tissues. The volumes of these three regions represent those in the actual liver. A spherical tumor model was proposed to calculate the absorbed fractions in the spherical tumor, necrotic, and normal tissue regions. The THORplan treatment planning system and Monte Carlo N-particle extended codes were used for this spherical tumor model. Using the volume-equivalent method, a spherical tumor model was created to calculate the total absorbed fraction [under different tumor-to-healthy-liver ratios (TLRs)]. The patient-specific model (THORplan) results were used to verify the spherical tumor model results. Results: The results for both the Y-90 spectrum and the Y-90 mean energy indicated that the absorbed fraction was a function of the tumor radius and mass. The absorbed fraction increased with tumor radius. The total absorbed fractions calculated using the spherical tumor model for necrotic, liver tumor, and normal liver tissues were in good agreement with the THORplan results, with differences of less than 3% for TLRs of 2–5. The results for the effect of TLR indicate that for the same tumor configuration, the total absorbed fraction decreased with increasing TLR; for the same shell tumor thickness and TLR, the total absorbed fraction was approximately constant; and for tumors with the same radius, the total fraction absorbed by the tumor increased with the shell thickness. Conclusions: The results from spherical tumor models with different tumor-to-healthy-liver ratios were highly consistent with the reference results (THORplan). These findings indicate that a spherical tumor model can provide good estimates of Y-90 doses in microsphere therapy and can be considered a first approximation for dose estimation in Y-90 microsphere therapy.

Hepatocellular carcinoma (HCC) is a common cause of cancer death worldwide. Sorafenib, a multikinase inhibitor, is the first-line drug approved by the Food and Drug Administration (FDA) for the treatment of patients with advanced HCC. However, most patients who continuously receive sorafenib may acquire resistance to this drug. Therefore, it is important to develop a new compound to treat liver cancer and sorafenib-resistant liver cancer. Barbituric acid derivatives have been used as antiasthmatic drugs in the clinic. We previously reported that a novel barbituric acid derivative inhibited carbon tetrachloride-induced liver fibrosis in mice, but its effects on liver cancer remain unknown. Thus, the purpose of this study was to investigate the antitumor effect of barbituric acid derivatives on HCC cells and sorafenib-resistant HCC cells (HCC-SRs). Our findings reveal that one of the barbituric acid derivatives, BA-5, significantly inhibited HCC and HCC-SR cell viability in a dose- and time-dependent manner. Therefore, compound BA-5 was selected for further experiments. Western blot data revealed that BA-5 treatment decreased the phosphorylation of AKT/p70s6k without affecting the MAPK pathway and increased cleaved PARP and cleaved caspase-7 in both HCC and HCC-SR cells. Since epithelial-mesenchymal transition plays a significant role in regulating cancer invasion and migration, we used the wound healing assay to evaluate the antimigratory effect of compound BA-5. The results showed that BA-5 treatment inhibited HCC and HCC-SR cell migration and reduced Vimentin protein expression. These results were confirmed by microarray analysis showing that BA-5 treatment influenced cancer cell motility and growth-related pathways. In the xenograft mouse model experiment, BA-5 administration significantly inhibited HCC cancer cell growth in mice. Furthermore, the combination of BA-5 with a low dose of regorafenib synergistically inhibited HCC-SR cell proliferation. In conclusion, our study showed that the barbituric acid derivative BA-5 is a new candidate for HCC and sorafenib-resistant HCC therapy.

This paper describes the methodology of an ongoing project of constructing an East Asian climate database REACHES based on Chinese historical documents. The record source is Compendium of Meteorological Records of China in the Last 3000 Years which collects meteorology and climate related records from mainly official and local chronicles along with a small number of other documents. We report the digitization of the records covering the period 1644–1795. An example of the original records is translated to illustrate the typical contents which contain time, location and type of events. Chinese historical times and location names are converted into Gregorian calendar and latitudes and longitudes. A hierarchical database system is developed that consists of the hierarchies of domains, main categories, subcategories, and further details. Historical events are then digitized and categorized into such a system. Code systems are developed at all levels such that the original descriptive entries are converted into digitized records suitable for treatment by computers. Statistics and characteristics of the digitized records in the database are described. Machine-accessible metadata file describing the reported data (ISA-Tab format)

Purpose: This study investigates the association between body composition change during concurrent chemoradiotherapy (CCRT) and outcome in patients with locally advanced cervical cancer (LACC). Experimental Design: Pre- and posttreatment CT images of 245 patients with LACC who were treated between 2004 and 2015 were analyzed. Skeletal muscle index (SMI) and density (SMD), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured from two sets of CT images at the level of the L3 vertebra. Sarcopenia and a low SMD were defined using published cut-off points. Predictors of overall survival (OS) and cancer-specific survival (CSS) were analyzed using Cox regression models. Results: The median follow-up was 62.7 (range, 7.3–152.3) months. Among the 245 patients, 127 (51.8%) had pretreatment sarcopenia, and 154 (62.9%) had a low SMD. SMI did not decrease significantly during CCRT, 0.6%/150 days [95% confidence interval (CI), −1.8–0.6; P = 0.35]. However, SMI loss during CCRT of >10.0%/150 days was independently associated with poorer OS (HR, 6.02; 95% CI, 3.04–11.93; P < 0.001) and CSS (HR, 3.49; 95% CI, 1.44–8.42; P = 0.006) when adjusted for FIGO stage, pathology, and treatment. Pretreatment sarcopenia and change of SMD, SATI, and VATI during CCRT were not associated with survival. Conclusions: Skeletal muscle measurements could be imaging biomarkers to predict outcomes for patients with LACC in clinical practice. Further studies are needed to determine whether multimodal interventions can preserve skeletal muscle mass and thereby improve survival. Clin Cancer Res; 24(20); 5028–36. ©2018 AACR.