Lack of dose dependency for radiation pneumonitis after chemoradiotherapy with the use of tomotherapy for lung cancer.

A 71-year-old man with stage IIB (Union for International Cancer Control, 8th edition) non-small cell lung cancer underwent intensity-modulated radiation therapy with a dose of 66 Gy administered in 33 fractions concomitant with carboplatin and paclitaxel therapy. On computed tomography after completion of radiation therapy, ground-glass opacity, which was larger on the contralateral side, was observed, but it was not observed in the high-dose area on the ipsilateral side. Although the adverse event theoretically shows dose dependency, it was finally diagnosed as radiation pneumonitis. The presence of an atypical distribution of radiation pneumonitis should be recognized to improve the diagnosis, and it is suggested that the relative volume of the normal contralateral lung receiving a dose of ≥5 Gy is a possible risk factor for radiation pneumonitis.

Visualizing "featureless" regions on mammograms classified as invasive ductal carcinomas by a deep learning algorithm: the promise of AI support in radiology.

PURPOSE: To demonstrate how artificial intelligence (AI) can expand radiologists' capacity, we visualized the features of invasive ductal carcinomas (IDCs) that our algorithm, developed and validated for basic pathological classification on mammograms, had focused on. MATERIALS AND METHODS: IDC datasets were built using mammograms from patients diagnosed with IDCs from January 2006 to December 2017. The developing dataset was used to train and validate a VGG-16 deep learning (DL) network. The true positives (TPs) and accuracy of the algorithm were externally evaluated using the test dataset. A visualization technique was applied to the algorithm to determine which malignant findings on mammograms were revealed. RESULTS: The datasets were split into a developing dataset (988 images) and a test dataset (131 images). The proposed algorithm diagnosed 62 TPs with an accuracy of 0.61-0.70. The visualization of features on the mammograms revealed that the tubule forming, solid, and scirrhous types of IDCs exhibited visible features on the surroundings, corners of the masses, and architectural distortions, respectively. CONCLUSION: We successfully showed that features isolated by a DL-based algorithm trained to classify IDCs were indeed those known to be associated with each pathology. Thus, using AI can expand the capacity of radiologists through the discovery of previously unknown findings.

Evaluation of the Antifoaming Effect Using Hansen Solubility Parameters.

The appearance of foam in various industrial processes can cause challenges. Antifoaming agents are widely added to suppress foam. To exert a defoaming effect, affinity between the main foam-generating component and the antifoaming agent is an important criterion for selection of an antifoaming agent. The Hansen solubility parameter (HSP) can be used as an index to show the affinity between substances more quantitatively, simply, and accurately. The Hansen solubility sphere method was used to measure the HSPs of antifoaming agents and a foam-forming surfactant. Various antifoaming agents were added to a surfactant solution, and the defoaming effect was evaluated. Correlations of 0.953-0.860 confirmed a relationship between affinity of the antifoaming agents for the surfactant based on HSP theory and the defoaming effect. It is suggested that use of HSP as an indicator can facilitate selection of the most suitable antifoaming agent for the process.

Measurements of the Hansen solubility parameters of mites and cockroaches to improve pest control applications.

Various pests, such as cockroaches and mites, can negatively affect agriculture and human health. Many pesticides have been developed to control these pests. The surfaces of pests are hydrophobic, so an insecticide in an aqueous solution will be repelled by the surface of a pest and therefore will not be effective. Adding a spreading agent (e.g., a surfactant) will improve the ability of a pesticide solution to wet pest surfaces and therefore improve the ability of the active ingredient to permeate and kill pests. Efficiently killing insects requires the insecticidal component to have an affinity for the pest surface. This affinity was assessed here using the Hansen solubility parameter, which is a quantitative measure of the affinity between two substances. We determined HSPs of mites and cockroaches using Hansen solubility sphere method. The HSPs of mites were δ d = 16.4 (MPa)1/2, δ p = 2.6 (MPa)1/2, and δ h = 4.7 (MPa)1/2. The one HSPs of cockroaches were δ d = 15.5 (MPa)1/2, δ p = 20.4 (MPa)1/2, δ h = 20.2 (MPa)1/2, and others were δ d = 17.6 (MPa)1/2, δ p = 2.8 (MPa)1/2, and δ h = 3.8 (MPa)1/2. The HSPs of cockroaches showed two values of hydrophobicity and hydrophilicity. Finally, we proposed new derived guidelines for using Hansen solubility parameters in research into pest control agents.

A randomised phase II trial of S-1 plus cisplatin versus vinorelbine plus cisplatin with concurrent thoracic radiotherapy for unresectable, locally advanced non-small cell lung cancer: WJOG5008L.

BACKGROUND: Cisplatin-based chemoradiotherapy is the standard treatment for unresectable, locally advanced non-small-cell lung cancer (NSCLC). This trial evaluated two experimental regimens that combine chemotherapy with concurrent radiotherapy. METHODS: Eligible patients with unresectable stage III NSCLC were randomised to either the SP arm (S-1 and cisplatin) or VP arm (vinorelbine and cisplatin), with early concurrent thoracic radiotherapy of 60 Gy, comprising 2 Gy per daily fraction. The primary endpoint was the overall survival rate at 2 years (2-year overall survival (OS)) (Study ID: UMIN000002420). RESULTS: From September 2009 to September 2012, 112 patients were enroled. Of the 108 eligible patients, the 2-year OS was 75.6% (80% confidence interval (CI), 67-82%) in the SP arm and 68.5% (80% CI: 60-76%) in the VP arm. The hazard ratio (HR) for death between the two arms was 0.85 (0.48-1.49). The median progression-free survival was 14.8 months for the SP arm and 12.3 months for the VP arm with an HR of 0.92 (0.58-1.44). There were four treatment-related deaths in the SP arm and five in the VP arm. CONCLUSIONS: The null hypotheses for 2-year OS were rejected in both arms. The West Japan Oncology Group will employ the SP arm as the investigational arm in a future phase III study.

Three-dimensional conformal radiotherapy for locally advanced hepatocellular carcinoma with portal vein tumour thrombosis: evaluating effectiveness of the model for end-stage liver disease (MELD) score compared with the Child-Pugh classification.

OBJECTIVE: The purpose of this study was to retrospectively evaluate the effectiveness of the model for end-stage liver disease (MELD) score compared with the Child-Pugh classification in patients who received three-dimensional conformal radiotherapy (3D CRT) for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) by analyzing toxicity and prognostic factors. METHODS: 56 consecutive patients who had locally advanced HCC with PVTT treated by 3D CRT between September 2007 and April 2013 were retrospectively reviewed. RESULTS: The median survival time of all patients was 6.4 months. Receiver-operating characteristic (ROC) analysis identified MELD score = 7.5 [area under the curve (AUC) 0.81] and Child-Pugh score = 6.5 (AUC 0.86) as the best cut-off values for predicting the incidence of complications over Common Terminology Criteria for Adverse Events grade 2. There was no significant difference in the discrimination power between the MELD score and the Child-Pugh score on comparison of the two ROC curves (p = 0.17). On multivariate analysis, age, MELD score and radiotherapy dose were significant prognostic factors for overall survival (p = 0.021, 0.038 and 0.006, respectively). In contrast, the Child-Pugh classification, tumour response, PVTT response and the number of prior interventional radiologic treatments were not significant on multivariate analysis. CONCLUSION: This study showed that the best MELD score cut-off value is 7.5 and that the MELD score is a better prognostic factor than the Child-Pugh classification in 3D CRT for HCC with PVTT. ADVANCES IN KNOWLEDGE: The MELD score is useful for predicting the risk of severe toxicities and the prognosis of patients treated with 3D CRT for PVTT.

Results of surgery plus postoperative radiotherapy for patients with malignant parotid tumor.

PURPOSE: The latest version of the World Health Organization (WHO) histologic classification of salivary gland malignancies was published in 2005. To contribute to data accumulation on the basis of this latest version, a retrospective study was performed. MATERIALS AND METHODS: Participants comprised 27 patients who underwent postoperative radiotherapy between 2000 and 2013. Two, eight, and 17 patients were allocated to low, intermediate, and high-grade groups, respectively, in accordance with the latest WHO classification. The radiation field included the tumor bed and ipsilateral regional lymph nodes for 25 patients. The radiation dose was 46-60 Gy (median 56 Gy). RESULTS: Median duration of follow-up was 41 months. Five-year locoregional control was 89 %. Two patients experienced local recurrence and 7 patients developed distant metastases. No patients in the low or intermediate-grade groups developed distant metastases. Overall 3 and 5-year survival for all patients were 81 and 75 %, respectively. Five-year overall survival for patients in the low and intermediate-grade groups was 100 %, compared with 59 % for patients in the high-grade group (p = 0.03). CONCLUSION: Favorable locoregional control was achieved for patients with malignant parotid tumors who underwent surgery plus postoperative radiotherapy. Patients with high-grade tumors frequently experienced distant metastases and prognosis was poor.

Neoadjuvant capecitabine, bevacizumab and radiotherapy for locally advanced rectal cancer: results of a single-institute Phase I study.

The aim of this Phase I clinical trial was to assess the feasibility and safety of capecitabine-based preoperative chemoradiotherapy (CRT) combined with bevacizumab and to determine the optimal capecitabine dose for Japanese patients with locally advanced rectal cancer. Patients with cT3/T4 rectal cancer were eligible. Bevacizumab was administered at 5 mg/kg intravenously on Days 1, 15 and 29. Capecitabine was administered on weekdays concurrently with pelvic radiotherapy at a daily dose of 1.8 Gy, totally to 50.4 Gy. Capecitabine was initiated at 825 mg/m(2) twice daily at Dose Level 1, with a planned escalation to 900 mg/m(2) twice daily at Dose Level 2. Within 6.1-10.3 (median, 9.4) weeks after the completion of the CRT, surgery was performed. Three patients were enrolled at each dose level. Regarding the CRT-related acute toxicities, all of the adverse events were limited to Grade 1. There was no Grade 2 or greater toxicity. No patient needed attenuation or interruption of bevacizumab, capecitabine or radiation. All of the patients received the scheduled dose of CRT. All of the patients underwent R0 resection. Two (33.3%) of the six patients had a pathological complete response, and five (83.3%) patients experienced downstaging. In total, three patients (50%) developed postoperative complications. One patient developed an intrapelvic abscess and healed with incisional drainage. The other two patients healed following conservative treatment. This regimen was safely performed as preoperative CRT for Japanese patients with locally advanced rectal cancer. The recommended capecitabine dose is 900 mg/m(2) twice daily.

Lung cancer: a 6-field technique using lateral beams in conformal radiotherapy for bilateral supraclavicular lymph node metastases.

A 6-field technique using lateral beams in conformal radiotherapy was developed for patients with bilateral supraclavicular lymph node metastasis of lung cancer. The possibility of using this technique in practice was evaluated. Six fields with the same isocenter point (IP) were arranged. Two fields using anterior-posterior opposed beams involved all of the planning target volume (PTV). The next 2 fields using off-cord oblique beams involved the PTV inferior to the IP. The remaining 2 fields using lateral opposed beams, that shielded the spinal cord, involved the PTV superior to the IP. The oblique 2 fields and lateral 2 fields were connected using a half-beam technique. In 6 patients with non-small-cell lung cancer (NSCLC, n = 4) or small-cell lung cancer (SCLC, n = 2), treatment re-planning based on this technique was performed. This technique was applicable in 4 patients with NSCLC, in whom the general criteria of radiotherapy for lung cancer were met. In 2 patients with SCLC, the cumulative volume of lung that received more than 20 Gy exceeded 37% of the total lung volume. This technique was usable in 67% of the patients and was not necessarily contraindicated in the other 33%.

Delivery parameter variations and early clinical outcomes of volumetric modulated arc therapy for 31 prostate cancer patients: an intercomparison of three treatment planning systems.

We created volumetric modulated arc therapy (VMAT) plans for 31 prostate cancer patients using one of three treatment planning systems (TPSs)--ERGO++, Monaco, or Pinnacle--and then treated those patients. A dose of 74 Gy was prescribed to the planning target volume (PTV). The rectum, bladder, and femur were chosen as organs at risk (OARs) with specified dose-volume constraints. Dose volume histograms (DVHs), the mean dose rate, the beam-on time, and early treatment outcomes were evaluated and compared. The DVHs calculated for the three TPSs were comparable. The mean dose rates and beam-on times for Ergo++, Monaco, and SmartArc were, respectively, 174.3 ± 17.7, 149.7 ± 8.4, and 185.8 ± 15.6 MU/min and 132.7 ± 8.4, 217.6 ± 13.1, and 127.5 ± 27.1 sec. During a follow-up period of 486.2 ± 289.9 days, local recurrence was not observed, but distant metastasis was observed in a single patient. Adverse events of grade 3 to grade 4 were not observed. The mean dose rate for Monaco was significantly lower than that for ERGO++ and SmartArc (P < 0.0001), and the beam-on time for Monaco was significantly longer than that for ERGO++ and SmartArc (P < 0.0001). Each TPS was successfully used for prostate VMAT planning without significant differences in early clinical outcomes despite significant TPS-specific delivery parameter variations.

A dose-volume intercomparison of volumetric-modulated arc therapy, 3D static conformal, and rotational conformal techniques for portal vein tumor thrombus in hepatocellular carcinoma.

We created volumetric-modulated arc therapy (VMAT) plans for portal vein tumor thrombus (PVTT) in hepatocellular carcinoma, and compared the results with those from three-dimensional conformal radiotherapy (3D-CRT) and rotational conformal radiotherapy (R-CRT) plans. CT scan data from 10 consecutive patients with PVTT treated with 3D-CRT between January 2008 and January 2010 were utilized in the analysis. We analyzed the dosimetric properties of the plans for the 10 patients using the three different techniques with three different isocenter doses of 50, 56 and 60 Gy in 2-Gy fractions. The D95, Dmean, homogeneity index and conformity index were compared for the planning target volume (PTV). The Dmean, V20 and V30 were also compared for normal livers. The monitor units (MUs) and the treatment time were also evaluated. The normal liver V30 for VMAT was significantly less than that for 3D-CRT for the prescribed doses of 56 and 60 Gy (P < 0.05). It was also found that the normal liver V30 resulting from 3D-CRT was prohibitively increased when the prescribed dose was increased in two steps. For PTV D95, we found no significant differences between the three techniques for the 50- and 56-Gy prescriptions, or between VMAT and the other techniques for the 60-Gy prescription. The differences in the MUs and treatment times were not statistically significant between VMAT and 3D-CRT. We have demonstrated that VMAT may be a more advantageous technique for dose escalation reaching 60 Gy in the treatment of PVTT due to the reduced normal liver V30.

Minimum requirements for commissioning and long-term quality assurance of Elekta multi-leaf collimator for volumetric modulated arc therapy.

We have proposed minimum requirements for commissioning and long-term quality assurance (QA) of an Elekta multi-leaf collimator (MLC) for volumetric modulated arc therapy (VMAT). The MLC leaf position accuracy during VMAT delivery was evaluated with the use of three different QA test plans: (1) a leaf gap-width test between opposing leaves by measurement of the isocenter dose during constant-gap sliding-window delivery with varied dose rates, MLC leaf speeds, and gantry angles; (2) a leaf position test by picket-fence delivery with and without gantry rotation; and (3) a leaf-bank symmetry test by measurement of the field geometry with different collimator angles at a fixed gantry position. All the QA test plans were created using an ERGO++ treatment-planning system. The leaf gap-width deviation was within 0.2 mm, the leaf position deviation was within 0.5 mm, and the leaf-bank symmetry error was within 0.5 mm under all the test conditions. MLC leaf position accuracy and long-term stability were confirmed by the proposed procedures.

[Mechanical accuracy of a stereotactic irradiation system using a micro multi-leaf collimator].

Mechanical accuracy of a stereotactic irradiation system using a micro multi-leaf collimator (mMLC), Elekta DMLC, has been evaluated. Measurements were made to obtain transmission, leakage, penumbra, and positioning accuracy of the DMLC leaf for a 6 MV photon beam. Mechanical accuracy and long term stability of a linac isocenter was also evaluated. The resulting transmission, along a line perpendicular to the leaf movement, was 0.31±0.01%, and the leakage from the closed opposing leaf pairs was 0.39±0.01%. The measured penumbra, at a depth incurring maximum dose, was 2.37±0.16 mm toward the leaf end and 2.14±0.18 mm toward the leaf side for various field sizes. The leaf gap width error, of 0.10±0.08 mm, was obtained by analyzing picket fence test results. The maximum leaf positioning error, of 0.14±0.06 mm, was obtained by analyzing the log file for a various gantry angles during an arc delivery. The isocenter accuracy was within a radius of 1 mm, without any recalibration for two years. In conclusion, our stereotactic irradiation system using DMLC was capable of providing accurate stereotactic treatment.

Limited-stage small cell lung cancer: local failure after concurrent chemoradiotherapy with use of accelerated hyperfractionation.

PURPOSE: The aim of this study was to update data of radiation therapy regimens for improvement in local control in patients with limited-stage small cell lung cancer, a retrospective study was conducted. MATERIALS AND METHODS: Results of early concurrent chemoradiotherapy with accelerated hyperfractionation in 30 patients between 1998 and 2005 were retrospectively reviewed. The prescribed dose was 45 Gy in 30 fractions in all patients. RESULTS: All patients received a full dose of radiation therapy; however, interruptions for >or=5 days, mainly due to hematologic toxicity, were required in 18 patients (60%). The 5-year Kaplan-Meier survival rate and the median survival time were 26% and 26 months, respectively. The 4-year in-field control rate was 56%. Sites of relapse were local relapse in 9 patients (6 for in-field relapse, 3 for marginal relapse) and distant metastases in 16 patients (11 for distant metastases only, 5 for distant metastases with local relapse). The sites of marginal relapse were the upper margin in two patients and the peripheral margin in one patient. Grade 3 radiation esophagitis was observed in only three patients. CONCLUSION: Because in-field control was insufficient, a more effective approach should be sought to provide better local control.

Evaluation of posterolateral spinal fusion using mesenchymal stem cells: differences with or without osteogenic differentiation.

STUDY DESIGN: An animal study to achieve posterolateral intertransverse process spine fusion using mesenchymal stem cell (MSC). OBJECTIVE: We investigated the effectiveness of graft material for spinal fusion using a rabbit model by examining the MSC with or without osteogenic differentiation. SUMMARY OF BACKGROUND DATA: Posterolateral spinal fusion is commonly performed. Autogenous bone graft is the gold standard, although various problems are reported. Recently, MSCs from bone marrow have been studied in various fields. Thus, we supposed that MSCs have the ability to spinal fusion. METHODS: Twenty-four mature male Japanese white rabbits (weight, 3.0-4.0 kg) were divided into 4 groups: 1) autologous bone (AG), 2) hydroxyapatite (HA), 3) MSC, and 4) osteogenic MSC (OMSC). Each group underwent fusion of the intertransverse processes. The lumbar spine was harvested en bloc, and the fusion mass was evaluated radiographically, by manual palpation test, and by histologic analysis at 6 weeks after surgery. RESULTS: Fusion success or failure was assumed based on the results from manual palpation of the harvested spine. Four of 5 rabbits in the OMSC group, 4 of 6 rabbits in the AB group, 2 of 6 rabbits in the MSC group, and none of 6 rabbits in the HA group achieved fusion. In the OMSC group and AG group, new bone formation was observed histologically. In the HA group, fibrous tissue and cartilage were observed and there was no new bone. In the MSC group, less mature bone formation was present in the grafted fragments. CONCLUSION: The present study suggested that MSCs that have been cultured with osteogenic differentiation medium may induce the formation of new bone in experimental spinal fusion. Further studies are needed to determine the suitable level of osteogenic differentiate of MSC as well as the most appropriate carrier for MSC.

Rhythmic expression of DEC1 and DEC2 in peripheral tissues: DEC2 is a potent suppressor for hepatic cytochrome P450s opposing DBP.

The mammalian master molecular clock consisting of several clock gene products in the suprachiasmatic nucleus (SCN) drives circadian rhythms in behaviour and physiology. Molecular clocks consisting of the same components also exist in various peripheral organs. DEC1 and DEC2, basic helix-loop-helix transcription factors, were recently reported to be involved in the central clock in the SCN. We examined the expression profile of DEC1 and DEC2 in the periphery and their roles in the regulation of oscillating target genes in the liver. Levels of DEC1 and DEC2 mRNA exhibited a day-night variation in various peripheral tissues of rats. In the liver, their expression was high during the subjective night. Transfection assays showed that DEC2, but not DEC1, suppressed the transcription of the cholesterol 7alpha-hydroxylase gene (CYP7A), overwhelming the potent enhancement by D-site binding protein (DBP). Electrophoretic mobility shift assays indicated that DEC2 binds to the E-box (CACATG) at the -219/-214 region of CYP7A. The transcriptional activities of the other sterol metabolizing cytochrome P450s (Cyps), CYP8B and CYP51, were also suppressed by DEC2 but not DEC1. DEC2, but not DEC1, works as a direct output mediator that transmits the circadian signals to the hepatic functions, including the CYP7A, CYP8B, and CYP51 expression.

A new technique to expand human mesenchymal stem cells using basement membrane extracellular matrix.

Mesenchymal stem cells (MSC) show a very short proliferative life span and readily lose the differentiation potential in culture. However, the growth rate and the proliferative life span of the stem cells markedly increased using tissue culture dishes coated with a basement membrane-like extracellular matrix, which was produced by PYS-2 cells or primary endothelial cells. Furthermore, the stem cells expanded on the extracellular matrix, but not those on plastic tissue culture dishes, retained the osteogenic, chondrogenic, and adipogenic potential throughout many mitotic divisions. The extracellular matrix had greater effects on the proliferation of MSC and the maintenance of the multi-lineage differentiation potential than basic fibroblast growth factor. Mesenchymal stem cells expanded on the extracellular matrix should be useful for regeneration of large tissue defects and repeated cell therapies, which require a large number of stem or progenitor cells.