Discussion document. To review the work performed on conditions and disorders that predispose persons with spinal cord injury (SCI) to an increased risk of coronary heart disease (CHD). Individuals with SCI have an increased prevalence of abnormalities in carbohydrate and lipid metabolism because of immobilization, muscle atrophy and relative adiposity. In those with SCI, an inverse relationship has been reported between serum high-density lipoprotein (HDL) cholesterol values and abdominal circumference, and a direct relationship between serum triglycerides levels and abdominal circumference. Persons with SCI have lower serum HDL cholesterol levels than able-bodied controls. A higher prevalence of insulin resistance and diabetes mellitus, as well as an earlier occurrence of coronary heart disease (CHD), has been reported in persons with SCI than in the general population. Recently, a higher prevalence and greater degree of coronary artery calcification by electron beam computerized tomography has been demonstrated in persons with SCI, even if matched with the able-bodied population for age, gender, ethnicity and conventional risk factors for CHD. Knowledge of relative risk of CHD in persons with SCI is important for appropriate intervention strategies. The conventional risk factors for CHD were determined in veterans with SCI to assign risk to determine target low-density lipoprotein cholesterol levels for therapeutic intervention. Limitations of conventional guidelines when applied to the SCI population should be appreciated. Conventional risk factors for CHD should be identified and treated in individuals with SCI, according to current standards of care.

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Coronary heart disease in individuals with spinal cord injury: assessment of risk factors

While chemotherapy provides useful palliation, advanced lung cancer remains incurable since those tumors that are initially sensitive to therapy rapidly develop acquired resistance. Resistance may arise from impaired drug delivery, extracellular factors, decreased drug uptake into tumor cells, increased drug efflux, drug inactivation by detoxifying factors, decreased drug activation or binding to target, altered target, increased damage repair, tolerance of damage, decreased proapoptotic factors, increased antiapoptotic factors, or altered cell cycling or transcription factors. Factors for which there is now substantial clinical evidence of a link to small cell lung cancer (SCLC) resistance to chemotherapy include MRP (for platinum-based combination chemotherapy) and MDR1/P-gp (for non-platinum agents). SPECT MIBI and Tc-TF scanning appears to predict chemotherapy benefit in SCLC. In non-small cell lung cancer (NSCLC), the strongest clinical evidence is for taxane resistance with elevated expression or mutation of class III β-tubulin (and possibly α tubulin), platinum resistance and expression of ERCC1 or BCRP, gemcitabine resistance and RRM1 expression, and resistance to several agents and COX-2 expression (although COX-2 inhibitors have had minimal impact on drug efficacy clinically). Tumors expressing high BRCA1 may have increased resistance to platinums but increased sensitivity to taxanes. Limited early clinical data suggest that chemotherapy resistance in NSCLC may also be increased with decreased expression of cyclin B1 or of Eg5, or with increased expression of ICAM, matrilysin, osteopontin, DDH, survivin, PCDGF, caveolin-1, p21WAF1/CIP1, or 14-3-3sigma, and that IGF-1R inhibitors may increase efficacy of chemotherapy, particularly in squamous cell carcinomas. Equivocal data (with some positive studies but other negative studies) suggest that NSCLC tumors with some EGFR mutations may have increased sensitivity to chemotherapy, while K-ras mutations and expression of GST-pi, RB or p27kip1 may possibly confer resistance. While limited clinical data suggest that p53 mutations are associated with resistance to platinum-based therapies in NSCLC, data on p53 IHC positivity are equivocal. To date, resistance-modulating strategies have generally not proven clinically useful in lung cancer, although small randomized trials suggest a modest benefit of verapamil and related agents in NSCLC.

/pdf/tumor-and-host-factors-that-may-limit-efficacy-of-3724xy0twt.pdf

Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer

The use of radiochromic film (RCF) dosimetry in radiation therapy is extensive due to its high level of achievable accuracy for a wide range of dose values and its suitability under a variety of measurement conditions. However, since the publication of the 1998 AAPM Task Group 55, Report No. 63 on RCF dosimetry, the chemistry, composition, and readout systems for RCFs have evolved steadily. There are several challenges in using the new RCFs, readout systems and validation of the results depending on their applications. Accurate RCF dosimetry requires understanding of RCF selection, handling and calibration methods, calibration curves, dose conversion methods, correction methodologies as well as selection, operation and quality assurance (QA) programs of the readout systems. Acquiring this level of knowledge is not straight forward, even for some experienced users. This Task Group report addresses these issues and provides a basic understanding of available RCF models, dosimetric characteristics and properties, advantages and limitations, configurations, and overall elemental compositions of the RCFs that have changed over the past 20 yr. In addition, this report provides specific guidelines for data processing and analysis schemes and correction methodologies for clinical applications in radiation therapy.

https://aapm.onlinelibrary.wiley.com/doi/pdf/10.1002/mp.14497

Report of AAPM Task Group 235 Radiochromic Film Dosimetry: An Update to TG-55.

Sedation practices for gastrointestinal endoscopic (GIE) procedures vary widely in different countries depending on health system regulations and local circumstances. The goal of procedural sedation is the safe and effective control of pain and anxiety, as well as to provide an appropriate degree of memory loss or decreased awareness. Sedation-related complications in gastrointestinal endoscopy, once occurred, can lead to significant morbidity and occasional mortality in patients. The risk factors of these complications include the type, dose and mode of administration of sedative agents, as well as the patient's age and underlying medical diseases. Complications attributed to moderate and deep sedation levels are more often associated with cardiovascular and respiratory systems. However, sedation-related complications during GIE procedures are commonly transient and of a mild degree. The risk for these complications while providing any level of sedation is greatest when caring for patients already medically compromised. Significant unwanted complications can generally be prevented by careful pre-procedure assessment and preparation, appropriate monitoring and support, as well as post-procedure management. Additionally, physicians must be prepared to manage these complications. This article will review sedation-related complications during moderate and deep sedation for GIE procedures and also address their appropriate management.

Sedation-related complications in gastrointestinal endoscopy

X-ray film has been used for the dosimetry of intensity modulated radiation therapy (IMRT). However, the over-response of the film to low-energy photons is a significant problem in photon beam dosimetry, especially in regions outside penumbra. In IMRT, the radiation field consists of multiple small fields and their outside-penumbra regions; thus, the film dosimetry, for it involves the source of over-response in its radiation field. In this study we aim to verify and possibly improve film dosimetry for IMRT. Two types of modulated beams were constructed by combining five to seven different static radiation fields using 6 MV x rays. For verifying film dosimetry, x-ray films and an ion chamber were used to measure dose profiles at various depths in a phantom. The film setups include both parallel and perpendicular arrangements against the beam incident direction. In addition, to reduce an over-response, we placed 0.01 in. (0.25 mm) thick lead filters on both sides of the film. Compared with ion-chamber measurement, measured dose profiles showed the film over-response at outside-penumbra and low-dose regions. The error increased with depths and approached 15% as a maximum for the field size of 15 cm x 15 cm at 10 cm depth. The use of filters reduced the error down to 3%. In this study we demonstrated that film dosimetry for IMRT involves sources of error due to its over-response to low-energy photons, with the error most transparent in the low-dose region. The use of filters could enhance the accuracy in film dosimetry for IMRT. In this regard, the use of an optimal filter condition is recommended.

Film Dosimetry for Intensity Modulated Radiation Therapy: Dosimetric Evaluation.

To evaluate the prevalence of coronary artery disease (CAD) in patients with spinal cord injury (SCI), 47 clinically asymptomatic SCI patients received thallium-201 myocardial perfusion single photon emission computed tomography (Tl-201 SPECT) after dipyridamole administration for the diagnosis of CAD. There were 4 groups as follows; group 1: 13 patients with quadriplegia and complete SCI, group 2: 11 patients with quadriplegia and incomplete SCI, group 3: 11 patients with paraplegia and complete SCI, and group 4: 12 patients with paraplegia and incomplete SCI. There were no significant differences in sex distribution, ages, SCI duration, or CAD risk factors among the SCI patients in the 4 groups. All Tl-201 SPECT images were interpreted by the agreement of 2 experienced nuclear medicine physicians without prior knowledge of the patients' histories. A total of 30 of 47 (63.8%) SCI patients had abnormal Tl-201 SPECT findings. Among the 4 groups of SCI patients, those in groups 1 and 4 had the significantly highest and lowest prevalences of abnormal Tl-201 SPECT findings, respectively. We concluded that combined quadriplegia and complete SCI is an important CAD risk factor in SCI patients based on the objective evidence of intravenous dipyridamole cardiac stress testing with Tl-201 SPECT.

Evaluating the prevalence of silent coronary artery disease in asymptomatic patients with spinal cord injury.

The EBT2 film together with a flatbed scanner is a convenient dosimetry QA tool for verification of clinical radiotherapy treatments. However, it suffers from a relatively high degree of uncertainty and a tedious film calibration process for every new lot of films, including cutting the films into several small pieces, exposing with different doses, restoring them back and selecting the proper region of interest (ROI) for each piece for curve fitting. In this work, we present a percentage depth dose (PDD) method that can accurately calibrate the EBT2 film together with the scanner non-uniformity correction and provide an easy way to perform film dosimetry. All films were scanned before and after the irradiation in one of the two homemade 2 mm thick acrylic frames (one portrait and the other landscape), which was located at a fixed position on the scan bed of an Epson 10 000XL scanner. After the pre-irradiated scan, the film was placed parallel to the beam central axis and sandwiched between six polystyrene plates (5 cm thick each), followed by irradiation of a 20 × 20 cm2 6 MV photon beam. Two different beams on times were used on two different films to deliver a dose to the film ranging from 32 to 320 cGy. After the post-irradiated scan, the net optical densities for a total of 235 points on the beam central axis on the films were auto-extracted and compared with the corresponding depth doses that were calculated through the measurement of a 0.6 cc farmer chamber and the related PDD table to perform the curve fitting. The portrait film location was selected for routine calibration, since the central beam axis on the film is parallel to the scanning direction, where non-uniformity correction is not needed (Ferreira et al 2009 Phys. Med. Biol. 54 1073–85). To perform the scanner non-uniformity calibration, the cross-beam profiles of the film were analysed by referencing the measured profiles from a Profiler™. Finally, to verify our method, the films were exposed to 60° physical wedge fields and the compositive fields, and their relative dose profiles were compared with those from the water phantom measurement. The fitting uncertainty was less than 0.5% due to the many calibration points, and the overall calibration uncertainty was within 3% for doses above 50 cGy, when the average of four films were used for the calibration. According to our study, the non-uniformity calibration factor was found to be independent of the given dose for the EBT2 film and the relative dose differences between the profiles measured by the film and the Profiler were within 1.5% after applying the non-uniformity correction. For the verification tests, the relative dose differences between the measurements by films and in the water phantom, when the average of three films were used, were generally within 3% for the 60° wedge fields and compositive fields, respectively. In conclusion, our method is convenient, time-saving and cost-effective, since no film cutting is needed and only two films with two exposures are needed.

https://iopscience.iop.org/article/10.1088/0031-9155/57/18/5875/pdf

Calibration of EBT2 film by the PDD method with scanner non-uniformity correction

Purpose: The Ashland Inc. product EBT2 film model is a widely used quality assurance tool, especially for verification of 2-dimensional dose distributions. In general, the calibration film and the dose measurement film are irradiated, scanned, and calibrated at the same postirradiation time (PIT), 1-2 days after the films are irradiated. However, for a busy clinic or in some special situations, the PIT for the dose measurement film may be different from that of the calibration film. In this case, the measured dose will be incorrect. This paper proposed a film calibration method that includes the effect of PIT. Methods: The dose versus film optical density was fitted to a power function with three parameters. One of these parameters was PIT dependent, while the other two were found to be almost constant with a standard deviation of the mean less than 4%. The PIT-dependent parameter was fitted to another power function of PIT. The EBT2 film model was calibrated using the PDD method with 14 different PITs ranging from 1 h to 2 months. Ten of the fourteen PITs were used for finding the fitting parameters, and the other four were used for testing the model. Results: The verification test showsmore » that the differences between the delivered doses and the film doses calculated with this modeling were mainly within 2% for delivered doses above 60 cGy, and the total uncertainties were generally under 5%. The errors and total uncertainties of film dose calculation were independent of the PIT using the proposed calibration procedure. However, the fitting uncertainty increased with decreasing dose or PIT, but stayed below 1.3% for this study. Conclusions: The EBT2 film dose can be modeled as a function of PIT. For the ease of routine calibration, five PITs were suggested to be used. It is recommended that two PITs be located in the fast developing period (1∼6 h), one in 1 ∼ 2 days, one around a week, and one around a month.« less

Dependency of EBT2 film calibration curve on postirradiation time.

Purpose: Ashland Inc. EBT2 and EBT3 films are widely used in quality assurance for radiation therapy; however, there remains a relatively high degree of uncertainty [B. Hartmann, M. Martisikova, and O. Jakel, “Homogeneity of Gafchromic EBT2 film,” Med. Phys. 37, 1753–1756 (2010)]. Micke et al. (2011) recently improved the spatial homogeneity using all color channels of a flatbed scanner; however, van Hoof et al. (2012) pointed out that the corrected nonuniformity still requires further investigation for larger fields. To reduce the calibration errors and the uncertainty, the authors propose a new red-channel percentage-depth-dose method in combination with a modified three-channel technique. Methods: For the ease of comparison, the EBT2 film image used in the authors’ previous study (2012) was reanalyzed using different approaches. Photon beams of 6-MV were delivered to two different films at two different beam on times, resulting in the absorption doses of ranging from approximately 30 to 300 cGy at the vertical midline of the film, which was set to be coincident with the central axis of the beam. The film was tightly sandwiched in a 303-cm3 polystyrene phantom, and the pixel values for red, green, and blue channels were extracted from 234 points on the central axis of the beam and compared with the corresponding depth doses. The film was first calibrated using the multichannel method proposed by Micke et al. (2010), accounting for nonuniformities in the scanner. After eliminating the scanner and dose-independent nonuniformities, the film was recalibrated via the dose-dependent optical density of the red channel and fitted to a power function. This calibration was verified via comparisons of the dose profiles extracted from the films, where three were exposed to a 60° physical wedge field and three were exposed to composite fields, and all of which were measured in a water phantom. A correction for optical attenuation was implemented, and treatment plans of intensity modulated radiation therapy and volumetric modulated arc therapy were evaluated. Results: The method described here demonstrated improved accuracy with reduced uncertainty. The relative error compared with the measurements of a water phantom was less than 1%, and the overall calibration uncertainty was less than 2%. Verification tests revealed that the results were close to those of the authors’ previous study, and all differences were within 3%, except those with a high-dose gradient. The gamma pass rates (2%/2 mm) of the treatment plan evaluated using the method described here were greater than 99%, and no obvious stripe patterns were observed in the dose-difference maps. Conclusions: Spatial homogeneity was significantly improved via the calibration method described here. This technique is both convenient and time-efficient because it does not require cutting the film, and only two exposures are necessary.

Calibration of EBT2 film using a red-channel PDD method in combination with a modified three-channel technique.

Clinically unrecognized pulmonary aspiration during gastrointestinal endoscopy with sedation: a potential pitfall interfering the performance of 18F-FDG PET for cancer screening.

Hueisch-Jy Ding

Papers

Evaluating the prevalence of silent coronary artery disease in asymptomatic patients with spinal cord injury.

Calibration of EBT2 film by the PDD method with scanner non-uniformity correction

Dependency of EBT2 film calibration curve on postirradiation time.

Calibration of EBT2 film using a red-channel PDD method in combination with a modified three-channel technique.

Clinically unrecognized pulmonary aspiration during gastrointestinal endoscopy with sedation: a potential pitfall interfering the performance of 18F-FDG PET for cancer screening.