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Radiotherapy (RT) for head and neck cancer is now guided by cone-beam computed tomography (CBCT). We aim to identify a CBCT radiomic signature predictive of progression to RT. A cohort of 93 patients was split into training (n = 60) and testing (n = 33) sets. A total of 88 features were extracted from the gross tumor volume (GTV) on each CBCT. Receiver operating characteristic (ROC) curves were used to determine the power of each feature at each week of treatment to predict progression to radio(chemo)therapy. Only features with AUC > 0.65 at each week were pre-selected. Absolute differences were calculated between features from each weekly CBCT and baseline CBCT1 images. The smallest detectable change (C = 1.96 × SD, SD being the standard deviation of differences between feature values calculated on CBCT1 and CBCTn) with its confidence interval (95% confidence interval [CI]) was determined for each feature. The features for which the change was larger than C for at least 5% of patients were then selected. A radiomics-based model was built at the time-point that showed the highest AUC and compared with models relying on clinical variables. Seven features had an AUC > 0.65 at each week, and six exhibited a change larger than the predefined CI 95%. After exclusion of inter-correlated features, only one parameter remains, Coarseness. Among clinical variable, only hemoglobin value was significant. AUC for predicting the treatment response were 0.78 (p =.006), 0.85 (p <.001), and 0.99 (p <.001) for clinical, CBCT4-radiomics (Coarseness) and clinical + radiomics based models respectively. The mean AUC of this last model on a 5-fold cross-validation was 0.80 (±0.09). On the testing cohort, the best prediction was given by the combined model (balanced accuracy [BAcc] 0.67 , p <.001). We described a feature selection methodology for delta-radiomics that is able to select reproducible features which are informative due to their change during treatment. A selected delta radiomics feature may improve clinical-based prediction models. [ABSTRACT FROM AUTHOR]

Multicenter studies are needed to demonstrate the clinical potential value of radiomics as a prognostic tool. However, variability in scanner models, acquisition protocols and reconstruction settings are unavoidable and radiomic features are notoriously sensitive to these factors, which hinders pooling them in a statistical analysis. A statistical harmonization method called ComBat was developed to deal with the "batch effect" in gene expression microarray data and was used in radiomics studies to deal with the "center-effect". Our goal was to evaluate modifications in ComBat allowing for more flexibility in choosing a reference and improving robustness of the estimation. Two modified ComBat versions were evaluated: M-ComBat allows to transform all features distributions to a chosen reference, instead of the overall mean, providing more flexibility. B-ComBat adds bootstrap and Monte Carlo for improved robustness in the estimation. BM-ComBat combines both modifications. The four versions were compared regarding their ability to harmonize features in a multicenter context in two different clinical datasets. The first contains 119 locally advanced cervical cancer patients from 3 centers, with magnetic resonance imaging and positron emission tomography imaging. In that case ComBat was applied with 3 labels corresponding to each center. The second one contains 98 locally advanced laryngeal cancer patients from 5 centers with contrast-enhanced computed tomography. In that specific case, because imaging settings were highly heterogeneous even within each of the five centers, unsupervised clustering was used to determine two labels for applying ComBat. The impact of each harmonization was evaluated through three different machine learning pipelines for the modelling step in predicting the clinical outcomes, across two performance metrics (balanced accuracy and Matthews correlation coefficient). Before harmonization, almost all radiomic features had significantly different distributions between labels. These differences were successfully removed with all ComBat versions. The predictive ability of the radiomic models was always improved with harmonization and the improved ComBat provided the best results. This was observed consistently in both datasets, through all machine learning pipelines and performance metrics. The proposed modifications allow for more flexibility and robustness in the estimation. They also slightly but consistently improve the predictive power of resulting radiomic models. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the patient positioning accuracy in radiotherapy using a stereo-time of flight (ToF)-camera system. Methods: A system using two ToF cameras was used to scan the surface of the patients in order to position them daily on the treatment couch. The obtained point clouds were registered to (a) detect translations applied to the table (intrafraction motion) and (b) predict the displacement to be applied in order to place the patient in its reference position (interfraction motion). The measures provided by this system were compared to the effectively applied translations. The authors analyzed 150 fractions including lung, pelvis/prostate, and head and neck cancer patients. Results: The authors obtained small absolute errors for displacement detection: 0.8 ± 0.7, 0.8 ± 0.7, and 0.7 ± 0.6 mm along the vertical, longitudinal, and lateral axes, respectively, and 0.8 ± 0.7 mm for the total norm displacement. Lung cancer patients presented the largest errors with a respective mean of 1.1 ± 0.9, 0.9 ± 0.9, and 0.8 ± 0.7 mm. Conclusions: The proposed stereo-ToF system allows for sufficient accuracy and faster patient repositioning in radiotherapy. Its capability to track the complete patient surface in real time could allow, in the future, not only for an accurate positioning but also a real time tracking of any patient intrafraction motion (translation, involuntary, and breathing). [ABSTRACT FROM AUTHOR]

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Time-of-flight (ToF) camera technology provides a real-time depth map of a scene with adequate frequency for the monitoring of physiological patient motion. However, dynamic surface motion estimation using a ToF camera is limited by issues such as the raw measurement accuracy and the absence of fixed anatomical landmarks. In this work we propose to overcome these limitations using surface modeling through B-splines. This approach was assessed in terms of both motion estimation accuracy and associated variability improvements using acquisitions of an anthropomorphic surface phantom for a range of observation distances (0.6-1.4 m). In addition, feasibility was demonstrated on patient acquisitions. Using the proposed B-spline modeling, the mean motion estimation error and associated repeatability with respect to the raw measurements decreased by a factor of 3. Significant correlation was found between patients' surfaces motion extracted using the proposed B-spline approach applied to the ToF data and the one extracted from synchronized 4D-CT acquisitions as the ground truth. ToF cameras represent a promising alternative for contact-less patient surface monitoring for respiratory motion synchronization or modeling in imaging and/or radiotherapy applications. [ABSTRACT FROM AUTHOR]

Copyright of Oncologie (Tech Science Press) is the property of Tech Science Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Although the prognosis of patients with esophageal cancer has been improved by extended dissection, the incidence of recurrence still remains high. In esophageal cancer, positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) already demonstrated to be useful for initial staging and monitoring response to therapy. This prospective study compared the ability of FDG-PET and conventional imaging to detect early recurrence of esophageal cancer after initial surgery in asymptomatic patients.Materials and Methods: Between October 2003 and September 2006, 41 patients with esophageal cancer were included in a prospective study after initial radical esophagectomy. FDG-PET, thoracoabdominal computed tomography (CT), abdominal ultrasonography, and endoscopy were performed every 6 months after initial treatment.Results and Discussion: Twenty-three patients had recurrent disease (56%), mostly within the first 6 months after surgery (70%). Despite two false-positive scans due to postoperative changes, FDG-PET was more accurate than CT (91% vs. 81%, p = 0.02) for the detection of recurrence with a sensitivity of 100% (vs. 65%), a specificity of 85% (vs. 91%), and a negative predictive value of 100% on a patient-by-patient-based analysis. For the detection of locoregional recurrence, FDG-PET was more accurate than CT (96.2% vs. 88.9%). FDG-PET was also more accurate than CT for the detection of distant metastases (92.5% vs. 84.9%), especially when involving either bones (100%) or liver (98.1%). A lower sensitivity of FDG-PET (57%) for the early detection of small lung metastases did not affect patient management (accuracy = 92.5%).Conclusion: FDG-PET appears to be very useful for the systematic follow-up of asymptomatic patients after esophagectomy with an initial scan performed 6 months after surgery. [ABSTRACT FROM AUTHOR]

Objective. The Belgian national External Quality Assessment Scheme (EQAS) for haematology organized a survey to assess the reliability of haemoglobin (Hb) measurements with the blood gas analysers (BGAs) currently available in Belgian hospitals. Material and methods. All hospital laboratories received two specimens of fresh EDTA anticoagulated whole blood and were asked to determine the Hb concentration using both the conventional haematology analyser (HA) and all BGAs in the hospital. Ninety-seven hospital laboratories participated in the study and a total of 166 results were reported. The BGAs used (grouped according to technology) were Rapidlab 845, 855, 865 (Bayer 1, n = 41), Rapidlab 1245, 1265, Rapidpoint 405 (Bayer 2, n = 19), GEM Premier 3000 (Instrumentation Laboratory, IL, n = 13), ABL 500 and 600 series (Radiometer 1, n = 13), ABL 700 and 800 series (Radiometer 2, n = 35), Omni C, S5 (Roche 1, n = 7), Omni 3, 6, 9, S2, S4, S6 (Roche 2, n = 21). Results. For the BGAs from Bayer, Radiometer and Roche, interlaboratory variation ranged from 0.6 % to 4.1 %, indicating good precision and close agreement between centres. A significant negative bias observed on the GEM Premier 3000 using the EDTA anticoagulated blood samples did not appear to be present in fresh heparinized whole blood samples. There was no significant difference in imprecision and bias between Hb measurements on BGA situated in and outside the central laboratory. [ABSTRACT FROM AUTHOR]

The early loss of beta cells after islet cell transplantation has been attributed in part to blood coagulation at the implant site. Tissue factor expressed by beta cells and contaminating duct cells is considered to activate this process. Here, we investigated the ability of N-acetyl- l-cysteine to suppress the in vitro procoagulant activity of duct cells and human islet cell preparations. The effects of Nacystelyn, a salt derivative of N-acetyl- l-cysteine, were first assessed on procoagulant activity induced in human plasma by recombinant tissue factor, human primary duct cells or human islet cell preparations. The influence of Nacystelyn on clot formation, platelet counts and d-dimers were measured in a whole blood tubing loop model. Human beta cell viability and insulin synthesis after Nacystelyn treatment were assessed to exclude cytotoxicity of Nacystelyn. Nacystelyn efficiently inhibited the procoagulant activity of human recombinant tissue factor, primary duct cells and human islet cell preparations at clinically relevant concentrations without cellular toxicity. Nacystelyn is a pharmaceutical candidate to reduce early beta cell loss related to tissue factor-dependent coagulation after islet transplantation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of concurrent radiochemotherapy in patients with stage III non-small cell lung cancer (NSCLC), and to examine the effect of hemoglobin levels on survival of those patients. The negative impact of anemia on survival has been noticed for other cancer sites including the head and neck, and the uterine cervix, but it has been rarely described in NSCLC cancer patients treated with radiotherapy. Methods: From April 1995 through March 2002, 56 patients with inoperable stage III non-small lung cancer were treated with radiotherapy consisting of 60 Gy (50 Gy+10 Gy boost) given in 30 fractions of 2 Gy daily, 5 days a week, over a period of 6 weeks, and concurrent low-dose daily chemotherapy (CHT) consisting of 6 mg/m2 of cisplatin given Mondays-Fridays during weeks 1–2 and 5–6. All patients had stage III disease and ages ranged from 39 to 81 years old (median 63.9 years). Results: The 2-year and 3-year survival rates were 34% and 16%, respectively. Patients with a pretreatment hemoglobin level superior or equal to 11.6 g/dl had a 2-year survival rate of 52% as compared to 15.5% for patients with a pretreatment hemoglobin level inferior to 11.6 g/dl (p=0.0075). Patients with higher KI (>70%) showed better survival rates than those with lower KI. Surprisingly, patients in stage IIIA did not survive significantly longer than those in stage IIIB. Hematological toxicity (grade ≥2) prevailed (25%), followed by esophageal (5.4%) and bronchopulmonary (2%) toxicity. Only three patients experienced acute grade 3 hematological toxicity. Because of acute toxic effects, irradiation was interrupted in 8 patients (14.3%) for 7–13 days (median 7.5 days). Late highgrade (≥3) toxicity was not found. No grade 4 toxicity or treatment-related deaths were observed during this study. Conclusion: Our data show that concurrent radiotherapy with daily low dose cisplatin is well tolerated, and shows survival rates comparable to more aggressive treatment regimens. A combination of this chemotherapy with accelerated hyperfractionated radiotherapy might improve the results in the future. Furthermore, we could show that the hemoglobin levels prior to therapy have an influence on the prognosis, where lower levels were associated with worse outcome. Further trials should consider supplementation with erythropoietin. [ABSTRACT FROM AUTHOR]

Purpose: The effect of recombinant human keratinocyte growth factor (rHuKGF) on the proliferation, clonogenic capacity and colony size of low-passage human epithelial tumour cells was tested in vitro. Materials and methods: Five tumour cell cultures derived from head and neck squamous cell carcinomas, three cultures derived from pleural effusions of carcinomas of different origin and normal human nasal epithelial cells were analysed in passages 2-4. Expression of FGF7 and its receptor (FGFR2) were determined by the RNase protection assay. Cells were incubated with rHuKGF (10-200 ng ml[sup -1]) 3 days before or immediately after plating for clonal growth in serum-depleted media. To determine cellular radiosensitivity, single doses of 1-8 Gy X-rays were applied. Colony formation as well as colony size, reflecting the number of cell divisions, was determined after 10-15 days of growth in rHuKGF-treated and control cells. Results: Normal nasal epithelial cells showed a two- to threefold increase in the number of cell divisions due to rHuKGFtreatment. In tumour cell cultures, significant stimulation of proliferation occurred in only one of eight samples. Tumour cells expressed FGF7 mRNA and protein, and low levels of FGFR2 mRNA. The addition of rHuKGF to the medium of the tumour cell cultures influenced neither radiation-induced impairment of proliferation nor clonogenic cell survival. Conclusion: rHuKGF has been shown to ameliorate the radiation tolerance of normal epithelia. The minimum in vitro tumour cell response to rHuKGF compared with normal epithelial cells suggests a potential for selective protection of normal epithelia during radiotherapy. The low FGFR2 expression as well as the FGF7 expression in the tumour cells may contribute to their resistance to rHuKGF treatment. [ABSTRACT FROM AUTHOR]

Purpose: To analyse the relationship between radiation-induced clonogenic cell death, chromosome aberrations and markers of proliferative senescence or differentiation. Materials and methods: Plateau-phase human dermal fibroblasts from 18 donors were irradiated with graded doses of 1-6 Gy 200kV X-rays. Cell survival was determined by a colony-forming assay. Markers of differentiation or senescence were: spontaneous and radiation-induced clonal differentiation, which was determined morphologically and by the cellular potential to proliferate in clonal culture, also single-cell β-galactosidase (β-gal) staining at pH 6.0; and the secretion of transforming growth factor-β (TGF-β1) into the culture medium. Chromosome aberrations were determined as genomic yields of dicentric chromosomes and the excess acentric fragments, scored in Giemsa-stained metaphases, and as partial yields of reciprocal translocations for chromosomes 4, 7 and 9 using the FISH method. Results: A broad spread was found in the shapes of the survival curves, with SF2 ranging from 0.041±0.015 to 0.63±0.05. Radiation-induced clonal differentiation as well as the secretion of TGF-β1 was elevated in radiosensitive samples. With respect to chromosome aberrations, a significant correlation was found between clonogenic survival and radiation-induced excess acentric fragments. Conclusions: In the fibroblast cell system, in vitro radiosensitivity is determined not only by processes directly involved in DNA-damage recognition and repair, but also by intracellular signalling cascades, which will lead to differentiation processes. [ABSTRACT FROM AUTHOR]

Bernard Soulier Syndrome (BSS) is a rare inherited bleeding disorder caused by a defect in the glycoprotein (GP)Ib/IX/V complex. A patient with a bleeding problem was diagnosed as having BSS based on the prolonged bleeding time, the absence of ristocetin induced platelet aggregations, thrombocytopenia and the presence of giant platelets. Analysis of the platelets of the propositus, a 39-year-old Belgian female, by flow cytometry revealed a decreased expression of the GPIb/IX polypeptides. Western blotting confirmed these results and showed moreover that there was a decreased disulfide bridge formation between GPIbα and GPIbβ. After sequence analysis of the GPIbα, GPIbβ and GPIX genes, only a mutation in the GPIX gene at position 1826 (A→G) was identified, changing Asn45→Ser. Restriction analysis with Fnu4H1 demonstrated that the patient was homozygous for this mutation. As this Asn45→Ser mutation in the GPIX gene was already found in four unrelated families, i.e. in a British, Austrian, Swedish and Finnish one, the occurrence of this mutation in a Belgian patient supports the hypothesis of Koskela et al. (1999) that the Asn45Ser mutation in GPIX appears to be an ancient mutation shared by northern and central European populations. Our present observation of a decreased disulfide bridge formation between GPIbα and GPIbβ shows that GPIX is not only needed for the correct assembly of the complex but might also be needed for the disulfide bridge formation between GPIbα and GPIbβ. [ABSTRACT FROM AUTHOR]

Dendritic cell (DC)-based vaccine is a promising approach for cancer therapy. Pioneer trials have been conducted using DC generated in research conditions. There is now a need for generating DC in clinical grade conditions, including the use of closed systems, avoidance of FCS and respect of good manufacturing practices (GMP). Methods DC were generated from 84 leukapheresis products of 27 cancer patients enrolled in two Phase I/II trials of vaccination of either MAGE+tumors (n = 24) or prostate cancer (n = 3). Monocytes were seeded in culture bags in a serum-free medium supplemented with IL-4 and GM-CSF. After a 7 day culture, DC were collected and most were pulsed with various MAGE-derived peptides. Results After a short leukapheresis (mean time: 66 min; mean processed blood: 5 L), a mean of 6 × 10 9 WBC were collected, from which 2.25 × 10 9 were seeded. The culture procedure yielded a large number of DC (mean: 62 × 10 6 DC) harboring the expected phenotype of immature DC (CD1a + CD14 - HLA-DR + CD80 + CD86 + CD83 - ). This phenotype was not altered by peptide loading. These DC, either fresh or thawed, were functionally effective invitro. Their s.c. and i.v. injections were devoid of any short-term side effect and associated with the induction of immune responses in the patients. Discussion Large numbers of functional immature clinical grade DC can be generated in a closed system from leukapheresis products in cancer patients. These results provide the basis for large-scale studies of cancer immunotherapy under improved safety conditions. [ABSTRACT FROM AUTHOR]

A particular case of marginal zone B-cell lymphoma (MZBCL) presenting with leukemic lymphocytes is reported. In the present observation, the leukemic cells not only displayed a remarkable morphological fluctuation but also had an unusual phenotype, changing with time. These phenotypic features, which have been functionaly investigated by in vitro assays, might simply reflect an activation state depending on the microenvironment. Because of its disconcerting similarities with hairy cell leukemia (HCL) and splenic lymphoma with villous lymphocytes (SLVL), this case relaunches the debate about whether close relationships might exist between the splenic marginal zone, SLVL and HCL. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to evaluate and validate the use of the Geant4 application for emission tomography (GATE) Monte Carlo simulation platform for clinical intensity modulated radiotherapy (IMRT) dosimetry studies. Methods: The first step consisted of modeling a 6 MV photon beam linear accelerator (LINAC), with its corresponding validation carried out using percent depth dose evaluation, transverse profiles, tissue phantom ratio, and output factor on water phantom. The IMRT evaluation was performed by comparing simulation and measurements in terms of absolute and relative doses using IMRT dedicated quality assurance phantoms considering seven different patient datasets. Results: Concerning the LINAC simulated model validation tissue phantom ratios at 20 and 10 cm in water TPR1020 obtained from GATE and measurements were 0.672 ± 0.063 and 0.675, respectively. In terms of percent depth dose and transverse profiles, error ranges were, respectively: 1.472% ± 0.285% and 4.827% ± 1.323% for field size of 4 × 4, 5 × 5, 10 × 10, 15 × 15, 20 × 20, 25 × 25, 30 × 30, and 40 × 40 cm2. Most errors were observed at the edge of radiation fields because of higher dose gradient in these areas. Output factors showed good agreement between simulation and measurements with a maximum error of 1.22%. Finally, for IMRT simulations considering seven patient datasets, GATE provided good results with a relative error of 0.43% ± 0.25% on absolute dose between simulated and measured beams (measurements at the isocenter, volume 0.125 cm3). Planar dose comparisons were also performed using gamma-index analysis. For the whole set of beams considered the mean gamma-index value was 0.497 ± 0.152 and 90.8% ± 3.6% of the evaluated dose points satisfied the 5% / 4 mm criterion. Conclusions: These results show that GATE allows reliable simulation of complex beams in radiotherapy after an accurate LINAC modeling is validated. A simple cross-calibration procedure proposed in this work allows obtaining absolute dose values even in complex fields. [ABSTRACT FROM AUTHOR]