Structural Design of 3D Current Collectors for Lithium Metal Anodes: A Review.

Due to the ultrahigh theoretical specific capacity (3860 mAh g-1) and low redox potential (-3.04 V vs. standard hydrogen electrode), Lithium (Li) metal anode (LMA) received increasing attentions. However, notorious dendrite and volume expansion during the cycling process seriously hinder the development of high energy density Li metal batteries. Constructing three-dimensional (3D) current collectors for Li can fundamentally solve the intrinsic drawback of hostless for Li. Therefore, this review systematically introduces the design and synthesis engineering and the current development status of different 3D collectors in recent years (the current collectors are divided into two major parts: metal-based current collectors and carbon-based current collectors). In the end, some perspectives of the future promotion for LMA application are also presented.

Still equivalent for dose calculation in the Monte Carlo era? A comparison of free breathing and average intensity projection CT datasets for lung SBRT using three generations of dose calculation algorithms.

PURPOSE: Inhomogeneity dose modeling and respiratory motion description are two critical technical challenges for lung stereotactic body radiotherapy, an important treatment modality for small size primary and secondary lung tumors. Recent studies revealed lung density-dependent target dose differences between Monte Carlo (Type-C) algorithm and earlier algorithms. Therefore, this study aimed to investigate the equivalence of the two most popular CT datasets for treatment planning, free breathing (FB) and average intensity projection (AIP) CTs, using Type-C algorithms, and comparing with two older generation algorithms (Type-A and Type-B). METHODS: Twenty patients (twenty-one lesions) were planned using a Type-A algorithm on the FB CT. Lung was contoured separately on FB and AIP CTs and compared. Dose comparison was obtained between the two CTs using four commercial dose algorithms including one Type-A (Pencil Beam Convolution - PBC), one Type-B (Analytical Anisotropic Algorithm - AAA), and two Type-C algorithms (Voxel Monte Carlo - VMC and Acuros External Beam - AXB). For each algorithm, the dosimetric parameters of the target (PTV, Dmin , Dmax , Dmean , D95, and D90) and lung (V5, V10, V20, V30, V35, and V40) were compared between the two CTs using the Wilcoxon signed rank test. Correlation between dosimetric differences and density differences for each algorithm were studied using linear regression and Spearman correlation, in which both global and local density differences were evaluated. RESULTS: Although the lung density differences on FB and AIP CTs were statistically significant (P = 0.003), the magnitude was small at 1.21 ± 1.45%. Correspondingly, for the two Type-C algorithms, target and lung dosimetric differences were small in magnitude and statistically insignificant (P > 0.05) for all but one instance, similar to the findings for the older generation algorithms. Nevertheless, a significant correlation was shown between the dosimetric and density differences for Type-C and Type-B algorithms, but not for the Type-A algorithm. CONCLUSIONS: With the capability to more accurately model inhomogeneity, Monte Carlo (Type-C) algorithms are sensitive to respiration-induced local and global tissue density changes and exhibit a strong correlation between dosimetric and density differences. However, FB and AIP CTs may still be considered equivalent for dose calculation in the Monte Carlo era, due to the small magnitude of lung density differences between these two datasets.

Setup uncertainties in linear accelerator based stereotactic radiosurgery and a derivation of the corresponding setup margin for treatment planning.

PURPOSE: In the present study, clinical stereotactic radiosurgery (SRS) setup uncertainties from image-guidance data are analyzed, and the corresponding setup margin is estimated for treatment planning purposes. METHODS: Patients undergoing single-fraction SRS at our institution were localized using invasive head ring or non-invasive thermoplastic masks. Setup discrepancies were obtained from an in-room x-ray patient position monitoring system. Post treatment re-planning using the measured setup errors was performed in order to estimate the individual target margins sufficient to compensate for the actual setup errors. The formula of setup margin for a general SRS patient population was derived by proposing a correlation between the three-dimensional setup error and the required minimal margin. RESULTS: Setup errors of 104 brain lesions were analyzed, in which 81 lesions were treated using an invasive head ring, and 23 were treated using non-invasive masks. In the mask cases with image guidance, the translational setup uncertainties achieved the same level as those in the head ring cases. Re-planning results showed that the margins for individual patients could be smaller than the clinical three-dimensional setup errors. The derivation of setup margin adequate to address the patient setup errors was demonstrated by using the arbitrary planning goal of treating 95% of the lesions with sufficient doses. CONCLUSIONS: With image guidance, the patient setup accuracy of mask cases can be comparable to that of invasive head rings. The SRS setup margin can be derived for a patient population with the proposed margin formula to compensate for the institution-specific setup errors.

Density functional theory study on (LiNH2)n (n=1-5) clusters.

Geometrical structures and relative stabilities of (LiNH(2))(n) (n = 1-5) clusters were studied using density functional theory (DFT) at the B3LYP/6-31G* and B3LYP/6-31++G* levels. The electronic structures, vibrational properties, N-H bond dissociation energies (BDE), thermodynamic properties, bond properties and ionization potentials were analyzed for the most stable isomers. The calculated results show that the Li-N and Li-Li bonds can be formed more easily than those of the Li-H or N-H bonds in the clusters, in which NH(2) is bound to the framework of Li atomic clusters with fused rings. The average binding energies for each LiNH(2) unit increase gradually from 142 kJ mol(-1) up to about 180 kJ mol(-1) with increasing n. Natural bond orbital (NBO) analysis suggests that the bonds between Li and NH(2) are of strong ionicity. Three-center-two-electron Li-N-Li bonding exists in the (LiNH(2))(2) dimer. The N-H BDE values indicate that the change in N-H BDE values from the monomer a1 to the singlet-state clusters is small. The N-H bonds in singlet state clusters are stable, while the N-H bonds in triplet clusters dissociate easily. A study of their thermodynamic properties suggests that monomer a1 forms clusters (b1, c1, d2 and e1) easily at low temperature, and clusters with fewer numbers of rings tend to transfer to ones with more rings at low temperature. E(g), E(HOMO) and E(av) decrease gradually, and become constant. Ring-like (LiNH(2))(3,4) clusters possess higher ionization energy (VIE) and E(g), but lower values of E(HOMO). Ring-like (LiNH(2))(3,4) clusters are more stable than other types. A comparison of structures and spectra between clusters and crystal showed that the NH(2) moiety in clusters has a structure and spectral features similar to those of the crystal.

[Nifedipine attenuates vascular inflammation via inhibin NF-κB activity].

OBJECTIVE: To explore the effects and related mechanism of nifedipine on vascular inflammation induced by cuff placement. METHODS: Adult male C57BL/6J mice (10 to 12 weeks of age) were assigned to control (no cuff placement without nifedipine), cuff placement (cuff placement without nifedipine) and treatment (cuff placement with nifedipine 1 or 5 mg×kg(-1)×d(-1)) groups. Activity of NF-κB in injured artery was measured 5 days after operation. MCP-1 expression and nuclear translocation of NF-κB were examined in injured artery 7 days after operation. RESULTS: DNA-binding activity of NF-κB was significantly increased in the injured artery 5 days after cuff placement which could be downregulated by nifedipine 5 mg×kg(-1)×d(-1). MCP-1 mRNA expression in the injured arteries was increased 7 days after cuff placement and which could be significantly attenuated by nifedipine 5 mg×kg(-1)×d(-1). Cuff placement decreased the cytoplasmic level of p50, IκBα, IκBß, and increased the nuclear level of p50. Nifedipine 5 mg×kg(-1)×d(-1) significantly attenuated these changes. CONCLUSION: Our results suggest that high dose nifedipine could suppresses expression of MCP-1 induced by injured arteries via the inhibin NF-κB DNA binding activity, thereby attenuating vascular inflammation.

Synthesis, crystal structure and quantum chemical study on 3-phenylamino-4-phenyl-1,2,4-triazole-5-thione.

3-Phenylamino-4-phenyl-1,2,4-triazole-5-thione was synthesized and characterized by elemental analysis, IR and X-ray single crystal diffraction. Density functional theory calculations of the structure, natural bond orbitals, atomic charge distributions and thermodynamic functions of the title compound were performed at B3LYP/ 6-311G** and PBE1PBE/6-311G**levels of theory, respectively. NPA atomic charge distributions indicate that the title compound can be used as a potential multi-dentate ligand to coordinate with various metallic ions. Calculation of the second order optical nonlinearity was also carried out. The thermodynamic properties of C(0)(p,m), S(0)(m) and H(0)(m) were calculated and correlative equations between the thermodynamic properties and temperatures were also obtained.

Dose-dependent effects of radiation therapy on cerebral blood flow, metabolism, and neurocognitive dysfunction.

PURPOSE: A prospective study was performed to formally relate dose-dependent radiologically defined changes in normal brain induced by radiotherapy (RT) to neurocognitive dysfunction in subjects with primary brain tumors. METHODS AND MATERIALS: Adult patients receiving three-dimensional RT for central nervous system (CNS) tumors were enrolled. Positron emission tomography (PET) scanning and neuropsychological testing were performed before RT and 3 weeks and 6 months after treatment. Analyses were performed for correlations between changes in 2-deoxy-2-[(18)F]-fluoro-d-glucose (FDG)-PET (metabolism), (15)O-PET (relative blood flow), regional radiation dose, follow-up time, and neuropsychological test scores. RESULTS: Eleven subjects were enrolled and 6 completed follow-up studies. The PET data showed reduced FDG uptake, with average decreases of 2-6% in regions of the brain receiving greater than 40 Gy at 3 weeks' and 6 months' follow-up. The (15)O-H(2)O PET showed increases (<10%) at 3 weeks in relative regional blood flow in brain receiving greater than 30 Gy, but less at the 6-month follow-up studies. There were significant correlations between decreases in FDG uptake and increased scores from the Symptom Checklist-90-R, with an average increase in T score of 2 (p < 0.0001). The Wisconsin Card Sorting Test showed a significant correlation of decreased FDG uptake with increased errors and perseveration in test performance, with an average decrease in T score of 11 (p = 0.037). CONCLUSIONS: A dose-dependent response of CNS tissue was detected using FDG PET in this small number of patients. Decreases in CNS metabolism correlated with decreased performance on neuropsychological tests for problem solving, cognitive flexibility, and global measures of psychopathology. Additional research is needed to verify and define these findings.

A novel digital tomosynthesis (DTS) reconstruction method using a deformation field map.

We developed a novel digital tomosynthesis (DTS) reconstruction method using a deformation field map to optimally estimate volumetric information in DTS images. The deformation field map is solved by using prior information, a deformation model, and new projection data. Patients' previous cone-beam CT (CBCT) or planning CT data are used as the prior information, and the new patient volume to be reconstructed is considered as a deformation of the prior patient volume. The deformation field is solved by minimizing bending energy and maintaining new projection data fidelity using a nonlinear conjugate gradient method. The new patient DTS volume is then obtained by deforming the prior patient CBCT or CT volume according to the solution to the deformation field. This method is novel because it is the first method to combine deformable registration with limited angle image reconstruction. The method was tested in 2D cases using simulated projections of a Shepp-Logan phantom, liver, and head-and-neck patient data. The accuracy of the reconstruction was evaluated by comparing both organ volume and pixel value differences between DTS and CBCT images. In the Shepp-Logan phantom study, the reconstructed pixel signal-to-noise ratio (PSNR) for the 60 degrees DTS image reached 34.3 dB. In the liver patient study, the relative error of the liver volume reconstructed using 60 degrees projections was 3.4%. The reconstructed PSNR for the 60 degrees DTS image reached 23.5 dB. In the head-and-neck patient study, the new method using 60 degrees projections was able to reconstruct the 8.1 degrees rotation of the bony structure with 0.0 degrees error. The reconstructed PSNR for the 60 degrees DTS image reached 24.2 dB. In summary, the new reconstruction method can optimally estimate the volumetric information in DTS images using 60 degrees projections. Preliminary validation of the algorithm showed that it is both technically and clinically feasible for image guidance in radiation therapy.

A genetic algorithm for variable selection in logistic regression analysis of radiotherapy treatment outcomes.

A given outcome of radiotherapy treatment can be modeled by analyzing its correlation with a combination of dosimetric, physiological, biological, and clinical factors, through a logistic regression fit of a large patient population. The quality of the fit is measured by the combination of the predictive power of this particular set of factors and the statistical significance of the individual factors in the model. We developed a genetic algorithm (GA), in which a small sample of all the possible combinations of variables are fitted to the patient data. New models are derived from the best models, through crossover and mutation operations, and are in turn fitted. The process is repeated until the sample converges to the combination of factors that best predicts the outcome. The GA was tested on a data set that investigated the incidence of lung injury in NSCLC patients treated with 3DCRT. The GA identified a model with two variables as the best predictor of radiation pneumonitis: the V30 (p=0.048) and the ongoing use of tobacco at the time of referral (p=0.074). This two-variable model was confirmed as the best model by analyzing all possible combinations of factors. In conclusion, genetic algorithms provide a reliable and fast way to select significant factors in logistic regression analysis of large clinical studies.

Prospective assessment of radiotherapy-associated cardiac toxicity in breast cancer patients: analysis of data 3 to 6 years after treatment.

BACKGROUND: Radiation therapy (RT) to the left breast/chest wall has been linked with cardiac dysfunction. Previously, the authors identified cardiac perfusion defects in approximately 50% to 60% of patients 0.5 to 2 years post-RT. In the current study, they assessed the persistence of these defects 3 to 6 years post-RT. METHODS: From 1998 to 2006, 160 patients with left-sided breast cancer were enrolled onto an Institutional Review Board-approved, prospective study. All patients received tangential photons to the left breast/chest wall. Patients had pre-RT and serial post-RT single-photon emission computed tomography (SPECT) scans to assess changes in regional cardiac perfusion, wall motion, and ejection fraction (EF). Forty-four patients had SPECT scans 3 to 6 years post-RT and were evaluable for the current analysis. RESULTS: The overall incidence of perfusion defects at 3 years, 4 years, 5 years, and 6 years was 52% (11 of 21 patients), 71% (17 of 24 patients), 67% (12 of 18 patients), and 57% (4 of 7 patients), respectively. The rate of abnormal SPECT scans 3 to 6 years post-RT in patients who had scans at 0.5 to 2 years that were either all abnormal, intermittently abnormal, or all normal was 80%, 67%, and 63%, respectively. The incidence of wall motion abnormalities in patients with or without perfusion defects 3 to 6 years post-RT was low and did not differ statistically (17% vs 7.1%, respectively; P = .65), as was the incidence of reductions in EF of >/=5% (27% vs 36%, respectively; P = .72). CONCLUSIONS: The results from this study indicated that RT-induced perfusion defects may persist or initially may appear 3 to 6 years post-RT in a high percentage of patients. However, these defects were not associated with changes in regional wall motion or EF. Additional study will be needed to determine the clinical relevance of these defects. In the meantime, the authors believe that every effort should be made to minimize incidental irradiation of the heart while maintaining adequate coverage of target volumes.

Self-consistent tumor control probability and normal tissue complication probability models based on generalized EUD.

Traditional methods to compute the tumor control probability (TCP) or normal tissue complication probability (NTCP) typically require a heterogeneous radiation dose distribution to be converted into a simple uniform dose distribution with an equivalent biological effect. Several power-law type dose-volume-histogram reduction schemes, particularly Niemierko's generalized equivalent uniform dose model [Med. Phys. 26, 1000 (1999)], have been proposed to achieve this goal. In this study, we carefully examine the mathematical outcome of these schemes. We demonstrate that (1) for tumors, with each tumor cell independently responding to local radiation dose, a closed-form analytical solution for tumor survival fraction and TCP can be obtained; (2) for serial structured normal tissues, an exponential power-law form relating survival to functional sub-unit (FSU) radiation is required, and a closed-form analytical solution for the related NTCP is provided; (3) in the case of a parallel structured normal tissue, when NTCP is determined solely by the number of the surviving FSUs, a mathematical solution is available only when there is a non-zero threshold dose and/or a finite critical dose defining the radiotherapy response. Some discussion is offered for the partial irradiation effect on normal tissues in this category; (4) for normal tissues with alternative architectures, where the radiation response of FSU is inhomogeneous, there is no exact global mathematical solution for SF or NTCP within the available schemes. Finally, numerical fits of our models to some experimental data are also presented.

The role of functional imaging in the diagnosis and management of late normal tissue injury.

Normal tissue injury after radiation therapy (RT) can be defined based on either clinical symptoms or laboratory/radiologic tests. In the research setting, functional imaging (eg, single-photon emission computed tomography [SPECT], positron-emission tomography [PET], and magnetic resonance imaging [MRI]) is useful because it provides objective quantitative data such as metabolic activity, perfusion, and soft-tissue contrast within tissues and organs. For RT-induced lung, heart, and parotid gland injury, pre- and post-RT SPECT images can be compared with the dose- and volume-dependent nature of regional injury. In the brain, SPECT can detect changes in perfusion and blood flow post-RT, and PET can detect metabolic changes, particularly to regions of the brain that have received doses above 40 to 50 Gy. On MRI, changes in contrast-enhanced images, T(1) and T(2) relaxation times, and pulmonary vascular resistance at different intervals pre- and post-RT show its ability to detect and distinguish different phases of radiation pneumonitis. Similarly, conventional and diffusion-weighted MRI can be used to differentiate between normal tissue edema, necrosis, and tumor in the irradiated brain, and magnetic resonance spectroscopy can measure changes in compounds, indicative of membrane and neuron disruption. The use of functional imaging is a powerful tool for early detection of RT-induced normal tissue injury, which may be related to long-term clinically significant injury.

Impact of patient-specific factors, irradiated left ventricular volume, and treatment set-up errors on the development of myocardial perfusion defects after radiation therapy for left-sided breast cancer.

PURPOSE: The aim of this study was to assess the impact of patient-specific factors, left ventricle (LV) volume, and treatment set-up errors on the rate of perfusion defects 6 to 60 months post-radiation therapy (RT) in patients receiving tangential RT for left-sided breast cancer. METHODS AND MATERIALS: Between 1998 and 2005, a total of 153 patients were enrolled onto an institutional review board-approved prospective study and had pre- and serial post-RT (6-60 months) cardiac perfusion scans to assess for perfusion defects. Of the patients, 108 had normal pre-RT perfusion scans and available follow-up data. The impact of patient-specific factors on the rate of perfusion defects was assessed at various time points using univariate and multivariate analysis. The impact of set-up errors on the rate of perfusion defects was also analyzed using a one-tailed Fisher's Exact test. RESULTS: Consistent with our prior results, the volume of LV in the RT field was the most significant predictor of perfusion defects on both univariate (p = 0.0005 to 0.0058) and multivariate analysis (p = 0.0026 to 0.0029). Body mass index (BMI) was the only significant patient-specific factor on both univariate (p = 0.0005 to 0.022) and multivariate analysis (p = 0.0091 to 0.05). In patients with very small volumes of LV in the planned RT fields, the rate of perfusion defects was significantly higher when the fields set-up "too deep" (83% vs. 30%, p = 0.059). The frequency of deep set-up errors was significantly higher among patients with BMI > or =25 kg/m2 compared with patients of normal weight (47% vs. 28%, p = 0.068). CONCLUSIONS: BMI > or =25 kg/m2 may be a significant risk factor for cardiac toxicity after RT for left-sided breast cancer, possibly because of more frequent deep set-up errors resulting in the inclusion of additional heart in the RT fields. Further study is necessary to better understand the impact of patient-specific factors and set-up errors on the development of RT-induced perfusion defects.

Does transforming growth factor-beta1 predict for radiation-induced pneumonitis in patients treated for lung cancer?

The purpose of the study was to reassess the utility of transforming growth factor-beta-1 (TGF-beta1) together with dosimetric and tumor parameters as a predictor for radiation pneumonitis (RP). Of the 121 patients studied, 32 (26.4%) developed grade > or =1 RP, and 27 (22.3%) developed grade > or =2 RP. For the endpoint of grade > or =1 RP, those with V30>30% and an end-RT/baseline TGF-beta1 ratio> or =1 had a significantly higher incidence of RP than did those with V30>30% and an end-RT/baseline TGF-beta1 ratio<1. For most other patient groups, there were no clear associations between TGF-beta1 values and rates of RP. These findings suggest that TGF-beta1 is generally not predictive for RP except for the group of patients with a high V30.

Physics and imaging for targeting of oligometastases.

Oligometastases refer to metastases that are limited in number and location and are amenable to regional treatment. The majority of these metastases appear in the brain, lung, liver, and bone. Although the focus of interest in the past within radiation oncology has been on the treatment of intracranial metastases, there has been growing interest in extracranial sites such as the liver and lung. This is largely because of the rapid development of targeting techniques for oligometastases such as intensity-modulated and image-guided radiation therapy, which has made it possible to deliver single or a few fractions of high-dose radiation treatments, highly conformal to the target. The clinical decision to use radiation to treat oligometastases is based on both radiobiological and physics considerations. The radiobiological considerations involve improvement of treatment schema for time, dose, and volume. Areas of interests are hypofractionation, tumor and normal tissue tolerance, and hypoxia. The physics considerations for oligometastases treatment are focused mainly on ensuring treatment accuracy and precision. This article discusses the physics and imaging aspects involved in each step of the radiation treatment process for oligometastases, including target definition, treatment simulation, treatment planning, pretreatment target localization, radiation delivery, treatment verification, and treatment evaluation.

Radiation-induced narrowing of the tracheobronchial tree: an in-depth analysis.

PURPOSE: Symptomatic narrowing of the tracheobronchial tree is not a common clinical problem after conventional-dose external beam radiation therapy but has been described when higher doses are utilized. This in-depth study quantifies changes in the caliber of the trachea and mainstem bronchi after high-dose external beam radiation therapy (EBRT). METHODS AND MATERIALS: As part of an IRB-approved prospective clinical trial to assess for radiation-induced lung injury, patients with thoracic malignancies had pre- and serial post-RT CT scans in the radiation oncology department. This report focuses on 18 enrolled patients who received high-dose (> or = 73.6 Gy) EBRT for NSCLC. The caliber of the trachea, right mainstem bronchus, and left mainstem bronchus were measured utilizing three-dimensional coordinates in axial and coronal planes such that multiple measurements were made of each structure. The decrease in airway caliber was tested for significance using a one-sided Wilcoxon matched-pairs signed-ranks test. The correlation between airway caliber changes, dose, and follow-up interval was tested using the Spearman rank correlation coefficient and the effect of chemotherapy on airway narrowing was evaluated with a one-sided exact Wilcoxon rank sum test. RESULTS: There was no significant narrowing of the trachea for all dose and time points. There were significant decreases in the caliber of both mainstem bronchi on axial measurements (p = 0.07 and 0.005 for right and left mainstem bronchi, respectively). Decrease in airway caliber ranged from 6 to 57% and appeared to be dose dependent (p = 0.08), progressed with increasing time post-RT (p = 0.04), and was worse in patients who also received chemotherapy (p = 0.04). CONCLUSION: High-dose EBRT (> or = 73.6 Gy) appears to cause narrowing of the mainstem bronchi as early as 3 months post radiation therapy. Additional study is needed to assess the impact of such narrowing on RT-induced pulmonary symptoms.

Body mass index predicts the incidence of radiation pneumonitis in breast cancer patients.

In patients receiving breast radiotherapy, the risk of radiation pneumonitis has been associated with the volume of irradiated lung, and concomitant methotrexate, paclitaxel, and tamoxifen therapy. Many of the studies of radiation pneumonitis are based on estimates of pulmonary risk using central lung distance that is calculated using two-dimensional techniques. With the treatment of internal mammary nodes and three-dimensional treatment planning for breast cancer becoming increasingly more common, there is a need to further consider the impact of dose-volume metrics in assessing radiation pneumonitis risk. We herein present a case control study assessing the impact of clinical and dose-volume metrics on the development of radiation pneumonitis in patients receiving sequential chemotherapy and local-regional radiotherapy.

The incidence and functional consequences of RT-associated cardiac perfusion defects.

PURPOSE: Radiation therapy (RT) for left-sided breast cancer has been associated with cardiac dysfunction. We herein assess the temporal nature and volume dependence of RT-induced left ventricular perfusion defects and whether these perfusion defects are related to changes in cardiac wall motion or alterations in ejection fraction. METHODS: From 1998 to 2001, 114 patients were enrolled onto an IRB-approved prospective clinical study to assess changes in regional and global cardiac function after RT for left-sided breast cancer. Patients were imaged 30 to 60 minutes after injection of technetium 99m sestamibi or tetrofosmin. Post-RT perfusion scans were compared with the pre-RT studies to assess for RT-induced perfusion defects as well as functional changes in wall motion and ejection fraction. Two-tailed Fisher's exact test and the Cochran-Armitage test for linear trends were used for statistical analysis. RESULTS: The incidence of new perfusion defects 6, 12, 18, and 24 months after RT was 27%, 29%, 38%, and 42%, respectively. New defects occurred in approximately 10% to 20% and 50% to 60% of patients with less than 5%, and greater than 5%, of their left ventricle included within the RT fields, respectively (p = 0.33 to 0.00008). The rates of wall motion abnormalities in patients with and without perfusion defects were 12% to 40% versus 0% to 9%, respectively; p values were 0.007 to 0.16, depending on the post-RT interval. CONCLUSIONS: Radiation therapy causes volume-dependent perfusion defects in approximately 40% of patients within 2 years of RT. These perfusion defects are associated with corresponding wall-motion abnormalities. Additional study is necessary to better define the long-term functional consequences of RT-induced perfusion defects.

Preliminary report of the 6-minute walk test as a predictor of radiation-induced pulmonary toxicity.

PURPOSE: To assess the 6-minute walk test (6MWT) as a predictor of radiation therapy-induced lung injury (RTLI). METHODS AND MATERIALS: The 6MWT is a simple, economical, and reproducible test that measures both how far a person can walk in 6 min and any associated changes in vital signs. As part of a prospective trial to study RTLI, a pre-RT 6MWT was performed in 41 patients. The predictive capacities of pre-RT 6MWT, forced expiratory volume in 1 s (FEV1), and single-breath diffusing capacity for carbon monoxide (DLCO) for the development of RTLI were assessed with receiver operating curve (ROC) techniques. To evaluate the 6MWT, alone or with mean lung dose (MLD) of radiation, as a predictor of RTLI, the rates of RTLI in patient subgroups defined by 6MWT results were compared by using Fisher's exact test. RESULTS: Thirty-one patients with > or =3 months' follow-up were evaluable. The median baseline 6MWT result was 1400 ft. Of 31 patients, 7 developed Grade > or =2 RTLI. Of 15 patients with an MLD >18 Gy (the median), 5 developed RTLI, compared with 2 of 16 with MLD < or =18 Gy (p = 0.22). Among those with an MLD < or =18 Gy, the RTLI rates were 0 of 8 and 2 of 8 for 6MWT results > or =1400 ft or <1400 ft, respectively, p = 0.46. The ROC area under the curve for individual metrics was as follows: FEV1 0.66, MLD 0.70, DLCO 0.61, and 6MWT 0.47. Combining FEV1 with 6MWT increased the ROC to 0.71, suggesting that the ratio might be a better predictor than the individual values. Patients with a high 6MWT/FEV1 ratio had a lower rate of RTLI than those with a relatively low ratio. CONCLUSIONS: The 6MWT might provide prognostic information beyond pulmonary function tests and dosimetric parameters in predicting RTLI. Additional work is needed to better assess the utility of these functional metrics.

Challenges in defining radiation pneumonitis in patients with lung cancer.

PURPOSE: To assess the difficulty of assigning a definitive clinical diagnosis of radiation (RT)-induced lung injury in patients irradiated for lung cancer. METHODS: Between 1991 and 2003, 318 patients were enrolled in a prospective study to evaluate RT-induced lung injury. Only patients with lung cancer who had a longer than 6-month follow-up (251 patients) were considered in the current analysis. Of these, 47 of 251 patients had Grade >/=2 (treated with steroids) increasing shortness of breath after RT, thought possibly consistent with pneumonitis/fibrosis. The treating physician, and one to three additional reviewing physicians, evaluated the patients or their medical records, or both. The presence or absence of confounding clinical factors that made the diagnosis of RT-induced uncertain lung injury were recorded. RESULTS: Thirty-one of 47 patients (66%) with shortness of breath had "classic" pneumonitis, i.e., they responded to steroids and had a definitive diagnosis of pneumonitis. In 13 of 47 patients (28%), the diagnosis of RT-induced toxicity was confounded by possible infection; exacerbation of preexisting lung disease (chronic obstructive pulmonary disease); tumor regrowth/progression; and cardiac disease in 6, 8, 5, and 1 patients, respectively (some of the patients had multiple confounding factors and were counted more than once). An additional 3 patients (6%) had progressive shortness of breath and an overall clinical course more consistent with fibrosis. All 3 had evidence of bronchial stenosis by bronchoscopy. CONCLUSIONS: Scoring of radiation pneumonitis was challenging in 28% of patients treated for lung cancer owing to confounding medical conditions. Recognition of this uncertainty is needed and may limit our ability to understand RT-induced lung injury.