Imaging hypoxia to improve radiotherapy outcome Horsman, Michael R; Mortensen, Lise Saksø; Petersen, Jørgen B ...
Nature reviews. Clinical oncology,
12/2012, Letnik:
9, Številka:
12
Journal Article
Recenzirano
Reduced oxygen levels (hypoxia) is one of the most important factors influencing clinical outcome after radiotherapy. This is primarily because hypoxic cells are resistant to radiation treatment; ...hence, the greater the number of clonogenic cancer stem cells that exist under hypoxia, the lower the local tumour control. Reduced local control will influence overall survival, as may the hypoxic conditions by increasing malignant progression; however, to fight hypoxia, we should first be able to see it. We need noninvasive approaches that can accurately and reliably image hypoxia in tumours, especially using techniques that are routinely available in the clinic, such as PET, MRI and CT. All these imaging methods are already under clinical evaluation in this context. Such data should allow us to identify those patients on an individual basis who have hypoxic tumours and, thus, at the very least should receive some form of hypoxic modifier in conjunction with radiotherapy. Alternatively, the radiation dose could be either increased to the whole tumour or, if the imaging is accurate enough, only to the hypoxic subvolumes. The aim of this Review is to critically assess the potential use of imaging to help improve clinical outcome to radiotherapy.
In this work we report the effects of continuous UV-light (276 nm, ~2.20 W.m(-2)) excitation of human insulin on its absorption and fluorescence properties, structure and functionality. Continuous ...UV-excitation of the peptide hormone in solution leads to the progressive formation of tyrosine photo-product dityrosine, formed upon tyrosine radical cross-linkage. Absorbance, fluorescence emission and excitation data confirm dityrosine formation, leading to covalent insulin dimerization. Furthermore, UV-excitation of insulin induces disulphide bridge breakage. Near- and far-UV-CD spectroscopy shows that UV-excitation of insulin induces secondary and tertiary structure losses. In native insulin, the A and B chains are held together by two disulphide bridges. Disruption of either of these bonds is likely to affect insulin's structure. The UV-light induced structural changes impair its antibody binding capability and in vitro hormonal function. After 1.5 and 3.5 h of 276 nm excitation there is a 33.7% and 62.1% decrease in concentration of insulin recognized by guinea pig anti-insulin antibodies, respectively. Glucose uptake by human skeletal muscle cells decreases 61.7% when the cells are incubated with pre UV-illuminated insulin during 1.5 h. The observations presented in this work highlight the importance of protecting insulin and other drugs from UV-light exposure, which is of outmost relevance to the pharmaceutical industry. Several drug formulations containing insulin in hexameric, dimeric and monomeric forms can be exposed to natural and artificial UV-light during their production, packaging, storage or administration phases. We can estimate that direct long-term exposure of insulin to sunlight and common light sources for indoors lighting and UV-sterilization in industries can be sufficient to induce irreversible changes to human insulin structure. Routine fluorescence and absorption measurements in laboratory experiments may also induce changes in protein structure. Structural damage includes insulin dimerization via dityrosine cross-linking or disulphide bond disruption, which affects the hormone's structure and bioactivity.
Vibrational sum-frequency generation spectroscopy (SFG) is a powerful tool for studying noncentrosymmetric environments, particularly interfaces. Conventional homodyne-detected SFG inherently detects ...the intensity of the emitted light and thus forfeits the ability to directly measure the complex components, that is, phase, of the second-order nonlinear susceptibility, which contains the molecular response of interest. Heterodyne-detected SFG (HD-SFG) has recently been employed to recover this lost information, but has not been broadly adopted due to restrictions in the technical implementation. Presented in this Article is a HD-SFG geometry that fills a need for ease of use and increased versatility; our flexible and convenient design provides the capability to probe any interface in any polarization combination with exceptional phase stability. We demonstrate this ability by collecting the SFG signal from an octadecyltrichlorosilane monolayer on the front of a solid fused silica substrate and determine, for the first time with broadband HD-SFG, the complex spectrum of buried dry and solvated interfaces, collected in both ppp and ssp polarization combinations. This experimental design does not display any appreciable phase shift for over 10 h, which is a necessity for inclusion in more advanced methods such as time-resolved HD-SFG and 2D-HD-SFG.
Objective
The objective was to investigate prevalence, estimate risk factors, and antenatal suspicion of abnormally invasive placenta (AIP) associated with laparotomy in women in the Nordic ...countries.
Design
Population‐based cohort study.
Setting and population
A 3‐year Nordic collaboration among obstetricians to identify and report on uterine rupture, peripartum hysterectomy, excessive blood loss, and AIP from 2009 to 2012 The Nordic Obstetric Surveillance Study (NOSS).
Methods
In the NOSS study, clinicians reported AIP cases from maternity wards and the data were validated against National health registries.
Main outcome measures
Prevalence, risk factors, antenatal suspicion, birth complications, and risk estimations using aggregated national data.
Results
A total of 205 cases of AIP in association with laparotomy were identified, representing 3.4 per 10 000 deliveries. The single most important risk factor, which was reported in 49% of all cases of AIP, was placenta praevia. The risk of AIP increased seven‐fold after one prior caesarean section (CS) to 56‐fold after three or more CS. Prior postpartum haemorrhage was associated with six‐fold increased risk of AIP (95% confidence interval 3.7–10.9). Approximately 70% of all cases were not diagnosed antepartum. Of these, 39% had prior CS and 33% had placenta praevia.
Conclusion
Our findings indicate that a lower CS rate in the population may be the most effective way to lower the incidence of AIP. Focused ultrasound assessment of women at high risk will likely strengthen antenatal suspicion. Prior PPH is a novel risk factor associated with an increased prevalence of AIP.
Tweetable
An ultrasound assessment in women with placenta praevia or prior CS may double the awareness for AIP.
Tweetable
An ultrasound assessment in women with placenta praevia or prior CS may double the awareness for AIP.
This article includes Author Insights, a video available at https://vimeo.com/rcog/authorinsights13547
Background. Invasive aspergillosis (IA) is an important cause of morbidity and mortality among immunocompromised patients. Echinocandins are novel antifungal molecules with in vitro and in vivo ...activity against Aspergillus species. Methods. We investigated the efficacy and safety of caspofungin in the treatment of IA. Ninety patients with IA who were refractory to or intolerant of amphotericin B, lipid formulations of amphotericin B, or triazoles were enrolled to receive caspofungin. Results. Efficacy was assessed for 83 patients who had infection consistent with definitions of IA and who received ⩾1 dose of study drug. Common underlying conditions included hematologic malignancy (48% of patients), allogeneic blood and marrow transplantation (25% of patients), and solid-organ transplantation (11% of patients). Seventy-one patients (86%) were refractory to and 12 patients (14%) were intolerant of previous therapy. A favorable response to caspofungin therapy was observed in 37 (45%) of 83 patients, including 32 (50%) of 64 with pulmonary aspergillosis and 3 (23%) of 13 with disseminated aspergillosis. Two patients discontinued caspofungin therapy because of drug-related adverse events. Drug-related nephrotoxicity and hepatotoxicity occurred infrequently. Conclusion. Caspofungin demonstrated usefulness in the salvage treatment of IA.
Introduction
Noninvasive prenatal testing (NIPT) using cell‐free fetal DNA has increasingly been adopted as a screening tool for fetal aneuploidies. Several studies have discussed benefits and ...limitations of NIPT compared with both ultrasound and invasive procedures, but in spite of some shortcomings NIPT has become extensively used within the last 5 years. This study aims to describe the current use of NIPT in Europe, Australia and the USA.
Material and methods
We conducted a survey to describe the current use of NIPT. Colleagues filled in a simple email‐based questionnaire on NIPT in their own country, providing information on (a) access to NIPT, (b) NIPT’s chromosomal coverage, (c) financial coverage of NIPT for the patient and (d) the proportion of women using NIPT in pregnancy. Some data are best clinical estimates, due to a lack of national data.
Results
In Europe, 14 countries have adopted NIPT into a national policy/program. Two countries (Belgium and the Netherlands) offer NIPT for all pregnant women, whereas most other European countries have implemented NIPT as an offer for higher risk women after first trimester screening. In Australia, either combined first trimester screening (cFTS) or NIPT is used as a primary prenatal screening test. In the USA, there are no national consensus policies on the use of NIPT; however, NIPT is widely implemented. In most European countries offering NIPT, the proportion of women using NIPT is well below 25%. In the Netherlands, Austria, Italy, Spain and most Australian and American States, 25%‐50% of women have NIPT performed and in Belgium testing is above 75%. In most countries, NIPT reports on trisomy 13, 18 and 21, and often also on sex chromosome aneuploidies. Only in Belgium, the Netherlands, Lithuania, Greece, Cyprus and Italy is NIPT offered predominantly as a genome‐wide test (including some microdeletions or a whole genome coverage).
Conclusions
Noninvasive prenatal testing has been widely adopted throughout Europe, Australia and the USA, but only a few countries/states have a national policy on the use of NIPT. The variation in NIPT utilization is considerable.
Purpose:
In this study the authors present a new method for estimation of proton stopping power ratios (SPRs) using dual energy CT (DECT), which is robust toward CT noise. The authors propose a ...parametrization for SPR based directly on the CT numbers in a DECT image set, whereby the intermediate steps of estimating the relative electron density, ρe
, and mean excitation energy, I, are avoided.
Methods:
The SPR parametrization proposed in this study is a purely empirical fit based on the theoretical SPR values for a list of 34 reference human tissues. To investigate the SPR estimation made with this new method the authors performed a calibration and an evaluation with the method. The authors initially calculated CT numbers using CT energy spectrum characterization parameters obtained from calibration based on a Gammex 467 electron density calibration phantom. These CT numbers were fitted to the theoretical SPR for the reference human tissues using the new SPR parametrization presented in this study. The method was evaluated based on theoretical CT numbers for the reference human tissues. The root-mean-square error (RMSE) of the SPR and the proton range error from the continuous slowing down approximation were calculated for the reference human tissues. To test the stability of the parametrization the authors varied the density and elemental composition of the reference human tissues and calculated their new SPR estimates. Further, clinically realistic noise values were added to the theoretical CT numbers to investigate how CT noise affected the estimated water equivalent range through 10 cm of the reference human tissues. All results for the new SPR parametrization were compared to the results obtained using two previously published DECT methods for SPR estimation. Comparisons were also made to a single energy CT (SECT) SPR estimation method, the stoichiometric method, which is commonly used in clinical practise for proton therapy treatment planning.
Results:
The RMSE for the SPR of the 34 reference human tissues using the new SPR parametrization was 0.12%, compared to 0.19% and 0.28% for the two previously published DECT methods. The SPR parametrization was more stable toward variations of the calcium content in the reference human tissues, but less stable toward density variations and changes to the hydrogen content than the two other DECT methods. When adding noise to the theoretical CT numbers the SPR parametrization gave the lowest water equivalent range errors of all four tested SPR estimation methods (maximum error reduced to 0.4 mm). In all cases tested, the new SPR parametrization outperformed the SECT stoichiometric method.
Conclusions:
The new SPR parametrization gave lower RMSEs than the two other published DECT methods, and was in particular more robust against added noise. The method has potential for reducing range uncertainty margins in treatment planning of proton therapy.
An efficient arylation of carboxylic acids with diaryliodonium salts has been developed, giving aryl esters in high yields within short reaction times for both aromatic and aliphatic substrates. The ...transition-metal-free conditions are compatible with a range of functional groups, and good chemoselectivity is observed with unsymmetric diaryliodonium salts. Furthermore, steric hindrance in the ortho positions is well tolerated both in the carboxylic acid and in the diaryliodonium salt, yielding aryl esters that cannot be obtained via other esterification protocols.
Abstract
Background and purpose. Daily organ motion occurring during the course of radiotherapy in the pelvic region leads to uncertainties in the doses delivered to the tumour and the organs at ...risk. Motion patterns include both volume and shape changes, calling for deformable image registration (DIR), in approaches involving dose accumulation and adaptation. In this study, we tested the performance of a DIR application for contour propagation from the treatment planning computed tomography (pCT) to repeat cone-beam CTs (CBCTs) for a set of prostate cancer patients. Material and methods. The prostate, rectum and bladder were delineated in the pCT and in six to eight repeat CBCTs for each of five patients. The pCT contours were propagated onto the corresponding CBCT using the Multi-modality Image Registration and Segmentation application, resulting in 36 registrations. Prior to the DIR, a rigid registration was performed. The algorithm used for the DIR was based on a 'demons' algorithm and the performance of it was examined quantitatively using the Dice similarity coefficient (DSC) and qualitatively as visual slice-by-slice scoring by a radiation oncologist grading the deviations in shape and/or distance relative to the anatomy. Results. The average DSC (range) for the DIR over all scans and patients was 0.80 (0.65-0.87) for prostate, 0.77 (0.63-0.87) for rectum and 0.73 (0.34-0.91) for bladder, while the corresponding DSCs for the rigid registrations were 0.77 (0.65-0.86), 0.71 (0.55-0.82) and 0.64 (0.33-0.87). The percentage of propagated contours of good/acceptable quality was 45% for prostate; 20% for rectum and 33% for bladder. For the bladder, there was an association between the average DSC and the different scores of the qualitative evaluation. Conclusions. DIR improved the performance of pelvic organ contour propagation from the pCT to CBCTs as compared to rigid registration only. Still, a large fraction of the propagated rectum and bladder contours were unacceptable. The image quality of the CBCTs was sub-optimal and the usability of CBCTs for dose accumulation and adaptation purposes is therefore likely to benefit from improved image quality and improvements of the DIR algorithm.
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