Dynamics of patient reported quality of life and symptoms in the acute phase of online adaptive external beam radiation therapy for locally advanced cervical cancer.

OBJECTIVE: For locally advanced cervical cancer patients, treated with External Beam Radiotherapy (EBRT), Quality of Life (QoL) questionnaires arefrequently used to evaluate treatment-related symptoms and functioning scales. Currently, it is unknown how those evolve during the radiation treatment course. In this prospective study we report on weekly-captured patient-reported QoL and symptoms during image-guided adaptive radiotherapy (IGART) of cervical cancer patients. MATERIAL AND METHODS: Between January 2012 and September 2016, all locally advanced cervical cancer patients treated with IGART and brachytherapy with or without chemotherapy or hyperthermia, were eligible. QoL was assessed at baseline; weekly during the first five weeks of treatment; 1week, 1 and 3months after treatment, using the EORTC QLQ-C30 and the QLQ-CX24 questionnaires. Comparisons were made with an age-matched norm population. RESULTS: Among the 138 (70%) responders, most symptoms showed a moderate-to-large increase, reaching a maximum at the end of treatment, or first week after treatment with return to baseline value at 3months after treatment. While most symptoms gradually increased during the first five weeks, diarrhea and bowel cramps already markedly increased within the first three weeks to reach a plateau at the 5th week of treatment. Global health and functioning were temporarily decreased and returned to a plateau at baseline level 3months after treatment, except for cognitive functioning. CONCLUSION: A profound impact on QoL was observed during the radiation treatment course, temporarily affecting functioning. The maximum impaired was reached at the end of EBRT.

Palliative radiotherapy: New prognostic factors for patients with bone metastasis.

PURPOSE: Many cancer patients develop bone metastases, however the prognosis of overall survival differs. To provide an optimal treatment for these patients, especially towards the end of life, a reliable prediction of survival is needed. The goal of this study was to find new clinical factors in relation to overall survival. MATERIALS AND METHODS: Prospectively 22 clinical factors were collected from 734 patients. The Kaplan-Meier and Cox regression models were used. RESULTS: Most patients were diagnosed with lung cancer (29%), followed by prostate (19.8%) and breast cancer (14.7%). Median overall survival was 6.4months. Fourteen clinical factors showed significance in the univariate analyses. In the multivariate analyses 6 factors were found to be significant for the overall survival: Karnofsky performance status, primary tumor, gender, total organs affected, morphine use and systemic treatment options after radiotherapy. CONCLUSION: Morphine use and systemic treatment options after radiotherapy, Karnofsky performance status, primary tumor, gender and total organs affected are strong prediction factors on overall survival after palliative radiotherapy in patients with bone metastasis. These factors are easily applicable in the clinic.

[Evaluation of a two-dimensional scale for the assessment of fear avoidance beliefs in elderly chronic low back pain patients]. / Evaluation einer zweidimensionalen Skala zur Erfassung von Angst-Vermeidungs-Überzeugungen an älteren Patienten mit chronischem Rückenschmerz.

BACKGROUND: There is evidence on the importance of fear avoidance beliefs (FAB) as prognostic risk factors in elderly patients suffering from chronic low back pain (CLBP). However, so far there is no validated German instrument for measuring FAB in elderly CLBP patients. The aim of the study presented was to evaluate the psychometric properties of the Catastrophizing Avoidance Scale D-65+ (CAS-D-65+) within a population of elderly patients with CLBP. METHODS: A cross-sectional study was conducted with measurement repeated after 4 weeks in 68 CLBP patients aged 64 years and older. The CAS-D-65+ was analyzed performing an item analysis and retest reliability. For validation standardized assessment methods (Tampa Scale of Kinesiophobia [TSK], Photography of Daily Activity - Short electronic Version [Phoda-SeV], 5-Item-FAB, pain, disability, well-being and strain) were used. RESULTS: Internal consistency (Cronbach's α) ranged from 0.87 to 0.92 for total scale and from 0.71 to 0.89 for the sub-scales "catastrophizing" and "avoidance", retest reliability (r(tt)) ranged from 0.67 for the sub-scale "catastrophizing" to 0.70 for total scale and sub-scale "avoidance". The CAS-D-65+ showed moderate and strong effect sizes (Cohen's d) with other related FAB scales and external criteria. CONCLUSION: As shown in this study the CAS-D-65+ is a reliable and a valid instrument for the assessment of FAB in older patients with CLBP.

Heart period sensitivity to forced oscillations in ventilatory pressure.

Heart rate variability analysis is a dynamic method to estimate the autonomic control over the cardiac cycle. Although dysfunction in this control system may appear spontaneously, other deficits may require provocation of the system. In this article we describe a non-invasive method to perturb the autonomic influences on the cardiac cycle. We recorded the ECG and respiratory pressure of ten healthy volunteers while introducing a random forced oscillation pressure wave onto spontaneous respiration. The heart period time series was determined and the power spectra for the 0.05-0.15, 0.15-0.3 and 0.05-0.4 Hz bands were calculated. The random input did not alter mean heart rate. However, the segments with the forced oscillation input demonstrated, on average, a tenfold increase in spectral power averaged across all subjects, with a maximum observed effect of 100-fold increase in power. This increase in power correlated with the respiratory frequency. This study demonstrates that random noise ventilation, such as used in respiratory forced oscillation impedance estimates, significantly alters the autonomic input to cardiac cycle variability in wake subjects.

Enzymatic epoxidation of cyclohexene by peroxidase immobilization on a textile and an adapted reactor design.

A textile-based reaction system for new peroxidase reactions in non-native media was implemented. The epoxidation of cyclohexene by the commercial peroxidase MaxiBright® was realized with the textile-immobilized enzyme in an adapted liquid-liquid two-phase reactor. A commercially available polyester felt was used as low-price carrier and functionalized with polyvinyl amine. The covalent immobilization with glutardialdehyde lead to an enzyme loading of 0.10 genzyme/gtextile. The textile-based peroxidase shows a high activity retention in the presence of organic media. This catalyst is shown to enable the epoxidation of cyclohexene in various solvents as well as under neat conditions. A model reactor was produced by 3D printing which places the textile catalyst at the interphase between the liquid reaction phase and the product extracting solvent.

Improved signal recovery for flow cytometry based on 'spatially modulated emission'.

Recently, the technique of 'spatially modulated emission' has been introduced (Baßler et al 2008 US Patent 0080181827A1; Kiesel et al 2009 Appl. Phys. Lett. 94 041107; Kiesel et al 2011 Cytometry A 79A 317-24) improving the signal-to-noise ratio (SNR) for detecting bio-particles in the field of flow cytometry. Based on this concept, we developed two advanced signal processing methods which further enhance the SNR and selectivity for cell detection. The improvements are achieved by adapting digital filtering methods from RADAR technology and mainly address inherent offset elimination, increased signal dynamics and moreover reduction of erroneous detections due to processing artifacts. We present a comprehensive theory on SNR gain and provide experimental results of our concepts.

What is the optimal number of library plans in ART for locally advanced cervical cancer?

PURPOSE: Library-of-plans ART is used to manage daily anatomy changes in locally advanced cervical cancer. In our institute, the library contains 2 VMAT plans for patients with large cervix-uterus motion. Increasing this number could be beneficial for tissue sparing, but is burdensome while the dosimetric gain is yet unclear. This study's aim is to determine the optimal number of plans at an individual patient level. MATERIAL AND METHODS: Data of 14 treated patients were analyzed. Plan libraries were created containing 1-4 VMAT plans. Pre-treatment extent of uterus motion was defined by the 99th percentile of the Hausdorff distance (HD99). For dosimetric evaluations, OARs were contoured in daily CBCT scans, plan selection was simulated, and the V45Gy and V40Gy parameters were recorded. RESULTS: Moderate to strong correlations were found between HD99 and the volume of spared OARs. All patients benefitted from adding a 2nd plan, as is the clinical practice. For patients with a HD99 between 30 and 50mm, a 3-plan library reduced the composite V40Gy with 11-21ml compared to a 2-plan library. CONCLUSION: Patients with large uterus motion (HD99>30mm) would benefit from an extension of the plan library to 3. HD99 is an easy-to-implement criteria to select those patients pre-treatment.

Activating therapy modalities in older individuals with chronic non-specific low back pain: a systematic review.

BACKGROUND: Although there are many special exercise-based therapy approaches for the working population suffering chronic low back pain, similar programmes for older individuals are rare. OBJECTIVES: To summarise all evaluated physical therapy approaches, and assess the effects on older people with chronic low back pain. DATA SOURCES: Medline, CINAHL, Cochrane, Embase, PEDro, PsychINFO and Psyndex. STUDY SELECTION/ELIGIBILITY: Age≥65 years, subacute or chronic non-specific low back pain of ≥6weeks' duration, and a physical therapy approach. STUDY APPRAISAL AND SYNTHESIS METHODS: Study selection, data extraction, and assessment of methodological quality and clinical relevance were performed independently by two reviewers. As there were only a few controlled trials and wide heterogeneity in observation periods and outcome measures, pooling of data was not feasible. Therefore, the results are presented descriptively. RESULTS: In total, nine studies were included; six related to mixed physiotherapy modalities, one related to strength training, and two related to endurance training. Low-quality evidence suggests that physical therapy modalities are associated with a small-to-moderate reduction in pain and a small improvement in function. LIMITATIONS: The results must be interpreted with caution due to poor methodological quality. CONCLUSION AND IMPLICATIONS OF KEY FINDINGS: Few studies have been performed in this highly relevant and growing age group. It is not possible to recommend one particular modality or programme; as such, prescriptions should reflect patients' preferences and local conditions. Further research of higher methodological quality is needed urgently.

Transit dosimetry with an electronic portal imaging device (EPID) for 115 prostate cancer patients.

PURPOSE: Comparison of predicted portal dose images (PDIs) with PDIs measured with an electronic portal imaging device (EPID) may be used to detect errors in the dose delivery to patients. However, these comparisons cannot reveal errors in the MU calculation of a beam, since the calculated number of MU is used both for treatment (and thus affects the PDI measurement) and for PDI prediction. In this paper a method is presented that enables "in vivo" verification of the MU calculation of the treatment beams. The method is based on comparison of the intended on-axis patient dose at 5 cm depth for each treatment beam, D5, with D5 as derived from the portal dose Dp measured with an EPID. The developed method has been evaluated clinically for a group of 115 prostate cancer patients. METHODS AND MATERIALS: The patient dose D5 was derived from the portal dose measured with a fluoroscopic EPID using (i) the predicted beam transmission (i.e., the ratio of the portal dose with and without the patient in the beam) calculated with the planning CT data of the patient, and (ii) an empirical relation between portal doses Dp and patient doses D5. For each beam separately, the derived patient dose D5 was compared with the intended dose as determined from the relative dose distribution as calculated by the treatment planning system and the prescribed isocenter dose (2 Gy). For interpretation of observed deviating patient doses D5, the corresponding on-axis measured portal doses Dp were also compared with predicted portal doses. RESULTS: For three beams, a total of 7828 images were analyzed. The mean difference between the predicted patient dose and the patient dose derived from the average measured portal dose was: 0.4+/-3.4% (1 SD) for the anterior-posterior (AP) beam and -1.5+/-2.4% (1 SD) for the lateral beams. For 7 patients the difference between the predicted portal dose and the average measured portal dose for the AP beam and the corresponding difference in patient dose were both greater than 5%. All these patients had relatively large gas pockets (3-3.5 cm in AP direction) in the rectum during acquisition of the planning CT, which were not present during (most) treatments. CONCLUSIONS: An accurate method for verification of the MU calculation of an x-ray beam using EPID measurements has been developed. The method allows the discrimination of errors that are due to changes in patient anatomy related to appearance or disappearance of gas pockets in the rectum and errors due to a deviating cGy/MU-value.

On-line set-up corrections during radiotherapy of patients with gynecologic tumors.

PURPOSE: Positioning of patients with gynecologic tumors for radiotherapy has proven to be relatively inaccurate. To improve the accuracy and reduce the margins from clinical target volume (CTV) to planning target volume (PTV), on-line set-up corrections were investigated. METHODS AND MATERIALS: Anterior-posterior portal images of 14 patients were acquired using the first six monitor units (MU) of each irradiation fraction. The set-up deviation was established by matching three user-defined landmarks in portal and simulator image. If the two-dimensional deviation exceeded 4 mm, the table position was corrected. A second portal image was acquired using 30 MU of the remaining dose. This image was analyzed off-line using a semiautomatic contour match to obtain the final set-up accuracy. To verify the landmark match accuracy, the contour match was retrospectively performed on the six MU images as well. RESULTS: The standard deviation (SD) of the distribution of systematic set-up deviations after correction was < 1 mm in left-right and cranio-caudal directions. The average random deviation was < 2 mm in these directions (1 SD). Before correction, all standard deviations were 2 to 3 mm. The landmark match procedure was sufficiently accurate and added on average 3 min to the treatment time. The application of on-line corrections justifies a CTV-to-PTV margin reduction to about 5 mm. CONCLUSIONS: On-line set-up corrections significantly improve the positioning accuracy. The procedure increases treatment time but might be used effectively in combination with off-line corrections.

In vivo dosimetry for prostate cancer patients using an electronic portal imaging device (EPID); demonstration of internal organ motion.

PURPOSE: To investigate the use of a commercially available video-based EPID for in vivo dosimetry during treatment of prostate cancer patients. METHODS: For 10 prostate cancer patients, the inter-fraction variation within measured portal dose images (PDIs) was assessed and measured PDIs were compared with corresponding predicted PDIs based on the planning CT scan of the patient. RESULTS: For the lateral fields, the average standard deviation in the measured on-axis portal doses during the course of a treatment was 0.9%; for the anterior fields this standard deviation was 2.2%. The difference between the average on-axis measured portal dose and the predicted portal dose was 0.3+/-2.1% (1 SD) for the lateral fields and 0.7+/-3.4% (1 SD) for the anterior fields. Off-axis differences between measured and predicted portal doses were regularly much larger (up to 15%) and were caused by frequently occurring gas pockets inside the rectum of the patients during treatment or during acquisition of the planning CT scan. The detected gas pockets did sometimes extend into the gross tumour volume (GTV) area as outlined in the planning CT scans, implying a shift of the anterior rectum wall and prostate in the anterior direction (internal organ motion). CONCLUSIONS: The developed procedures for measurement and prediction of PDIs allow accurate dosimetric quality control of the treatment of prostate cancer patients. Comparing measured PDIs with predicted PDIs can reveal internal organ motion.

Set-up verification of cervix cancer patients treated with long treatment fields; implications of a non-rigid bony anatomy.

BACKGROUND AND PURPOSE: For cervix cancer patients, treatment fields may extend up to vertebra L1. In clinical practice, set-up verification is based on measured displacements of the pelvic rim as visible in the caudal part of the treatment fields. The implications of this procedure for the positions of bony structures in the cranial part of the fields were investigated. MATERIALS AND METHODS: Twelve patients had four repeat simulator sessions. Both during treatment simulation (the reference) and the repeat sessions, anterior radiographs were acquired covering the whole treatment field. The films were used to investigate differences between the cranial and the caudal parts of the treatment field in day-to-day bony anatomy displacements. RESULTS: Both in the transversal and the longitudinal directions, these differences were significant (3.5 mm, 1 SD). Indications were found that large differences in the cranio-caudal direction may be correlated with (non-rigid) internal pelvic rim rotations around a lateral axis. In the longitudinal direction, the position of L1 correlated much better with the position of vertebra S1 than with the position of the pelvic rim, which is usually used for set-up verification. CONCLUSIONS: Due to the non-rigid bony anatomy of the studied patients, the usual set-up verification and correction procedure can result in set-up errors of 10 mm and more for structures in the cranial part of the treatment field, even in the case of a perfect set-up of the pelvic rim. Possibly, other patient set-up and immobilization procedures may result in a better day-to-day reproducibility of the 3D bony anatomy shape. (Remaining) Differences in anatomy position changes between the caudal and cranial field ends may be accounted for by using non-uniform clinical target volume-to-planning target volume margins, or by an adapted patient set-up verification and correction protocol.

Reduction of irradiated small bowel volume and accurate patient positioning by use of a bellyboard device in pelvic radiotherapy of gynecological cancer patients.

PURPOSE: To reduce the volume of small bowel within pelvic treatment fields for gynecological cancer using a bellyboard device and to determine the accuracy of the prone treatment position. MATERIALS AND METHODS: Fifteen consecutive patients with a gynecologic malignancy who were treated with postoperative pelvic radiotherapy were selected for this study. The volume of small bowel within the treatment fields was calculated for both the supine and prone treatment positions. The patients were treated in the prone position in a so-called bellyboard device. During treatment sessions electronic portal images were obtained. An off-line setup verification and correction protocol was used and the setup accuracy of the positioning in the bellyboard was determined. RESULTS: The average volume of small bowel within the treatment fields was 229 cm(3) and 66 cm(3) in the supine and prone treatment, respectively, which means an average volume reduction in the prone position of 64% (95% CI 56-72%), as compared with the supine position. For the position of the patient in the field, the systematic error defined by the standard deviation (SD) of the mean difference per patient between simulation and treatment images was 1.7 mm in the lateral direction, 2.1 mm in the craniocaudal direction and 1.7 mm in the ventrodorsal direction. On average, only 0.4 setup correction per patient was required to achieve this accuracy. The random day-to-day variations were 1.9 (1SD), 2.6 and 2.3 mm, respectively. Standard deviations of the systematic differences between patient positioning relative to the bellyboard were 6.2 mm in lateral direction and 9.1 mm in craniocaudal direction. CONCLUSIONS: Treatment of gynecological cancer patients in the prone position using a bellyboard reduces the volume of irradiated small bowel. An off-line verification and correction protocol ensures accurate patient positioning. Daily setup variations using the bellyboard were small (1 SD<3 mm). Therefore for pelvic radiotherapy in patients with a gynecological malignancy, the use of a bellyboard is recommended.

Definition and validation of a reference target volume in early stage node-positive cervical carcinoma, based on lymphangiograms and CT-scans.

PURPOSE: To establish a reference planning target volume for postoperative radiotherapy in stage Ib and IIa N+ cervical carcinoma, based on 47 lymphangiograms and 15 CT-scans. METHODS: Radiation oncologists (n=17) from all radiotherapy institutes in The Netherlands were asked to define the clinical target volume (CTV) and planning target volume (PTV), and to delineate (on simulation films) the radiotherapy treatment portals following a radical hysterectomy with lymph node dissection for an early stage cervical carcinoma with positive iliac lymph nodes. A reference PTV was defined by using 47 normal lymphangiograms and CT-data of the pelvis from 15 patients who underwent surgery for cervical carcinoma. The simulation films were digitized and evaluated for adequacy in covering the PTV, previously individually determined by the radiation oncologists. Subsequently, the simulation films were also evaluated for adequacy in covering the reference PTV. RESULTS: Large variations were observed in the portals used and in treatment techniques. From the digitized films, it appeared that in 50% of the cases the defined PTV was not covered adequately. Furthermore, 71% of the treatment plans would not cover the lateral borders of the reference PTV sufficiently. CONCLUSIONS: There appears to be no consensus on the target volumes to be irradiated in postoperative radiotherapy of early stage cervical carcinoma. When a PTV defined on the basis of lymphangiograms and CT-data is taken as a reference, 71% of the treatment plans would not cover this PTV adequately. These findings indicate the need for a consensus in the design of standardized treatment volumes.

Response of medullary neurons to step changes in carotid sinus pressure.

Moderate amplitude step changes in carotid sinus pressure were found, in an open-loop baroreflex preparation, to produce equivalent step changes in the firing rate of a majority of the medullary neurons tested. The average firing rate remained constant so long as the pressure was held constant (up to 24 sec). No rate sensitivity was observed in 32 out of 33 neurons; however, a single neuron showed mean firing rate changes only during pressure transitions. The variety in the activity patterns of cells which, on the average exhibited stereotyped responses to a simple repetitive stimulus, suggests that afferent information may undergo considerable integration and restructuring within the sensory nucleus, rather than being 'relayed' intact to other regions.

[Balint syndrome as a result of a biparietal infarct. Neuropsychological analysis]. / Syndrome de Balint par infarctus biparietal analyse neuropsychologique.

A case of Balint syndrome with bilateral parietal infarction is presented. Analysis shows the tight intrication of visual inattention and psychic gaze palsy. The deficit of visuo-manual adjustment is characterized by a fixed divergence between the target and the point where the patient places his hand, either in ballistic movements (classical optic ataxia), either in pursuit movements; for this reason, a simple disconnexion should not explain the classic optic ataxia. The discretion of aphasia allows the individualization of an anterograde and partially retrograde amnesia.

A comparison of the noise sensitivity of nine QRS detection algorithms.

The noise sensitivities for nine different QRS detection algorithms were measured for a normal, single-channel lead II, synthesized ECG corrupted with five different types of synthesized noise. The noise types were electromyographic interference, 60 Hz powerline interference, baseline drift due to respiration, abrupt baseline shift, and a composite noise constructed from all of the other noise types. The percentage of QRS complexes detected, the number of false positives, and the detection delay were measured. None of the algorithms were able to detect all QRS complexes without any false positives for all of the noise types at the highest noise level. Algorithms based on amplitude and slope had the highest performance for EMG-corrupted ECG. An algorithm using a digital filter had the best performance for the composite noise corrupted data.

Heart period variability during vagal nerve stimulation.

Vagal nerve stimulation is an emerging therapy for epilepsy, yet little is known regarding the effects of this stimulation on heart period variability. We selected 10 patients (two female, eight male) who were receiving high-frequency, high-intensity left vagal nerve stimulation for intractable epilepsy. Electrocardiogram data were recorded for a 7 min baseline, 2.5 min of stimulation and a 7 min post-stimulation period. We found no significant changes in average heart period, instantaneous changes of successive R-to-R intervals greater than 50 ms or fractal dimension. We also found no significant changes in the total power in the 0.0-0.04 Hz, 0.04-0.12 Hz and 0.2-0.4 Hz bands with stimulation of the left vagus nerve. This study suggests that left vagal nerve stimulation has little acute effect on the cardiac rhythm or heart period variability.

Picture confrontation oral naming: performance differences between aphasics and normals.

Oral confrontation naming was compared in 108 normal subjects controlled for education, age, and gender and in 18 aphasic patients for the same set of 115 pictures. Demographic variables influenced both normals' and aphasics' performance. However, the nature of aphasics' misnamings on the one hand and the differential effects of characteristics of pictures and words on normals' and aphasics' responses on the other indicated specific deficits in patients. The classical hypothesis that aphasics' misnamings and the production of word associations by normals should rely on similar mechanisms (Rinnert & Whitaker, 1973) is questioned. Nondominant responses observed in normals accounted for a larger proportion of verbal errors than associates to target words.

Automated data acquisition and analysis of neural evoked potentials.

A software system to collect, analyze and store trains of neural evoked potentials is presented. Real-time waveform capture permits sampling of a variable-duration data window of 6 to 399.6 ms with a sample delay accurately adjustable up to 1 001 ms (20 microseconds resolution). The digitized representation of each waveform is stored for individual analysis. Off-line processing determines 17 parameters of each waveform, including an arrow-selected amplitude and time. Individual processing of waveforms preserves all degrees of freedom for statistical analysis across waveforms. Ensemble averages may optionally be formed from the individual waveforms with processing performed on the averaged responses. The software provides MENU-selectable support functions including stimulus-to-artifact timing, storage and retrieval of data and calculated parameters, digital display of waveforms, data calibration and gain modification, table referenced data editing, file management, simple statistics, hardcopy output, and optional database interfacing with output formatted for compatibility with a statistics package (SAS).