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At least 631 records · Page 35

Endovascular Extra-Anatomic Femoro-Popliteal Bypass for Limb Salvage in Chronic Critical Limb Ischemia

Purpose: To report the initial clinical experience with fully endovascular extra-anatomic femoro-popliteal bypass (FPB) for limb salvage in patients with critical limb ischemia (CLI) and no traditional endovascular or surgical revascularization options. Methods: Between June 2013 and May 2018, endovascular procedure was proposed for limb salvage during multidisciplinary team meeting in fifteen hospitalized patients (median age 67 years; 73% men) with CLI and a high risk of major amputation. Primary outcome was amputation-free survival at 1 year. Secondary outcomes included mortality, cardiovascular (CV) events and major limb amputation at 1 year, primary/secondary bypass patency and wound healing at the last follow-up visit. Procedure-related complications (deaths, CV events, hemorrhages) were recorded through 30 days. Results: Technical procedure success rate was 100%. Major peri-procedural outcomes occurred in two patients (13%): One patient died secondary to cardiogenic shock; one patient suffered acute coronary syndrome associated with iliopsoas bleeding. No major amputation occurred through 30 days. Median follow-up period was 21.5 (18.25–45.5) months (last follow-up visits on April 2019). Amputation-free survival at 1-year and at the last follow-up visit was 80% and 53%, respectively. Cumulative mortality at 1-year and at the last follow-up visit was 13% and 33%, respectively. Primary and secondary bypass patency was 27% and 60%, respectively. Complete wound healing was achieved in 11 patients (73%). Conclusion: Endovascular extra-anatomic FPB represents an innovative approach for limb salvage in CLI with no traditional endovascular or surgical revascularization options. Our clinical experience highlights that this technique remains challenging because of frequent comorbidities and fragility of this patient population. Level of Evidence: Level 4, Case series.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Early Experience of Trans-arterial Chemo-Embolisation for Hepatocellular Carcinoma with a Novel Radiopaque Bead

Aims: To evaluate early outcomes of patients with hepatocellular carcinoma (HCC) treated with a novel radiopaque bead, the 75–150 μm DC Bead LUMI™ (Biocompatibles UK Ltd). Materials and Methods: This was a retrospective review of the first 40 consecutive patients at a UK tertiary hepato-biliary centre, treated for HCC with TACE using radiopaque beads, between May 2017 and March 2019. Information regarding complications, mortality, lesion response and subsequent ablation procedures was collected from electronic records and case notes. Intra- and post-operative imaging was reviewed for visibility of the embolised territory. Results: Fifty-five TACE procedures were performed in 40 patients, with a median age of 70 years (range 28–88) and median lesion size of 3.8 cm (range 1.5–7.8). The median follow-up period was 30 weeks (range 6–101). Mean post-procedure hospital stay was 1.2 days. Complications of CIRSE Grade II or above occurred after 4/55 procedures (7.3%). Mortality at 30 days was zero. Objective response rates (mRECIST) at 1, 3 and 6 months were 32/35 (91.4%), 21/24 (87.5%) and 12/15 (80%), respectively. Complete response rates at 1, 3 and 6 months were 16/35 (45.7%), 12/24 (50%) and 9/15 (60%). The embolised territory was visible on intra-operative and follow-up CT imaging in all patients. The radiopaque beads were used as a fiducial marker to guide ablation in 5/40 patients (12.5%). Conclusion: TACE with radiopaque beads shows promising tolerability and efficacy. The radiopaque beads ensure visualisation of the embolised lesion on intra- and post-operative imaging and, in selected cases, can act as a marker for CT-guided ablation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Acute toxicity of copper to the larval stage of three species of ambystomatid salamanders

Copper (Cu) appears to be consistently more toxic to anuran species relative to other vertebrate taxa. There are limited Cu toxicity data for salamanders; of the few studies conducted on salamanders, most examined Cu effects on the embryonic, but not the larval, stage. We performed acute toxicity experiments, to quantify LC50s, on Harrison stage 46 larvae (free swimming hatchlings with egg yolk completely absorbed) of three ambystomatid salamander species. Each LC50 experiment used exposure concentrations of 10, 20, 30, 40, 50, and 60 µg/L with 10 replicates per concentration each containing one larva. We found very high toxicity for all species compared to previously published research on the embryo stage. Specifically, the 4-d LC50s for Ambystoma tigrinum and A. opacum were 35.3 and 18.73 µg/L, respectively. The same Cu concentrations caused similar toxicity to A. talpoideum (LC50 = 47.88 µg/L), but exposures required up to 48 d to elicit the same level of mortality. A time-to-event analysis indicated that time to mortality was significantly affected by Cu concentration. Additionally, for A. talpoideum, we observed that elevated levels of Cu decreased growth rate. Finally, comparisons with previously reported Cu toxicity for embryos suggest that, as with fish, Cu may be more toxic to larval salamander stages than for embryos. Further, our data suggest that Cu is an important environmental contaminant that deserves increased scrutiny on the potential for population-level effects where contamination has occurred in wetlands and streams inhabited by salamanders.

59 BASIC BIOLOGICAL SCIENCES↗

Risk factors, clinical outcomes, and natural history of uveal melanoma: a single-institution analysis

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. We describe the characteristics of UM patients at a tertiary referral center in the Mid-Southern United States, and explore associations and predictors of outcomes. This is a retrospective cohort study of patients with UM seen at West Cancer Center, from 07/2006 to 08/2017. Clinical characteristics and their relationship to outcomes (time-to-death and metastasis) were explored using Cox regression analysis. We identified 208 patients, 51% males, 97% Caucasians, 80% were symptomatic, with a median follow-up of 2.34 years, IQR (1.01–3.03), of which 19.2% died during follow-up. Metastases were diagnosed in 19% (4 older patients had metastases at diagnosis), 53% of those by surveillance. Without considering metastases as a time-varying covariate, age (HR = 1.06/year, CI 1.0–1.1; p < 0.001), headaches (HR = 5.7, CI 1.6–20.5; p = 0.03), and tumor stage (T) were significant covariates for time-to-death. Tumor stages T3 versus T1 (HR = 6.4; CI 1.5–27.7; p = 0.01) and T4 versus T1 (HR = 5.98; CI 1.3–27.8; p = 0.02) were associated with worse outcomes. When considering metastases as a time-varying covariate (HR = 35.8, CI 17–75.2; p < 0.001), only age remains in the model (HR = 1.04/year; p < 0.001). However, tumor stage (p < 0.001), headaches (p = 0.008), and age (p < 0.001) are associated with time-to-metastasis. One in five patients developed metastasis which was the most influential factor on mortality. Predictors of mortality were metastasis, age, tumor stage, and headache as a reported symptom. Surveillance successfully diagnosed metastatic disease in most patients. Most patients had symptoms preceding their UM diagnosis highlighting an opportunity for earlier recognition of UM.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Complete revascularization determined by myocardial perfusion imaging could improve the outcomes of patients with stable coronary artery disease, compared with incomplete revascularization and no revascularization

Objectives: To compare the outcomes among patients treated by complete coronary revascularization (CCR) or incomplete coronary revascularization (ICR) and no coronary revascularization (NCR) by myocardial perfusion imaging (MPI), as well as to evaluate the impact of severity of ischemia on patients with coronary artery disease (CAD) by different therapy strategies. Background: Using myocardial ischemia severity determined by MPI guiding treatment strategies for CAD patients still lacks strong clinical evidences. Methods: Consecutive patients (N = 286) underwent clinical stress-rest SPECT MPI and were retrospectively followed-up. For assessment of outcome of treatment, all patients were classified into three groups (CCR, ICR, and NCR), and further divided into two subgroups as mild ischemia (< 10% ischemic myocardium) and moderate-severe ischemia (≥ 10% ischemic myocardium). All-cause death was defined as the primary endpoint, and the composite of deaths, nonfatal myocardial infarction, and repeat revascularization (MACE) as the secondary endpoint. Results: Two-hundred eighty-six patients were followed-up for 46 ± 21 months. Thirty deaths and 65 MACEs were recorded. Patients treated by revascularization had significantly lower MACE (P < .001) but not mortality (P = .158) than patients treated by NCR. Outcomes of CCR related to mortality rate were greater than ICR and NCR (death: P = .019, MACE: P < .001). In patients with moderate-severe ischemia, CCR showed improved outcomes than ICR and NCR (death: P = .034; and MACE: P < .001). In patients with mild ischemia, the outcomes of CCR, ICR, and NCR had no significant difference (P > .05). Multivariate regression Cox analysis revealed that summed difference score [death: HR 1.09 (1.03, 1.15), P = .004] was an independent risk factor and CCR was an independent negative predictor [death: HR 0.31 (0.12, 0.81), P = .017; MACE: HR 0.30 (0.16, 0.57), P < .001]. Conclusions: Outcomes of patients treated by CCR were most likely more promising in comparison with treatment of ICR and NCR, especially when patients had over 10% ischemic myocardium.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Impaired lipid accumulation in the liver of Tsc2-heterozygous mice during liver regeneration

Highlights: •Tuberin phosphorylation correlated with mTOR activation in early liver regeneration. •Liver regeneration in the Tsc2+/− mice was not enhanced. •The Tsc2+/− livers failed to accumulate lipid bodies during liver regeneration. •Mortality rate increased in Tsc2+/− mice after partial hepatectomy. •Tuberin plays a critical role in hepatic lipid accumulation to support regeneration. -- Abstract: Tuberin is a negative regulator of mTOR pathway. To investigate the function of tuberin during liver regeneration, we performed 70% hepatectomy on wild-type and Tsc2+/− mice. We found the tuberin phosphorylation correlated with mTOR activation during early liver regeneration in wild-type mice. However, liver regeneration in the Tsc2+/− mice was not enhanced. Instead, the Tsc2+/− livers failed to accumulate lipid bodies, and this was accompanied by increased mortality. These findings suggest that tuberin plays a critical role in liver energy balance by regulating hepatocellular lipid accumulation during early liver regeneration. These effects may influence the role of mTORC1 on cell growth and proliferation.

60 APPLIED LIFE SCIENCES↗

Approaching population thresholds in presence of uncertainty: Assessing displacement of seabirds from offshore wind farms

Assessment of the displacement impacts of offshore wind farms on seabirds is impeded by a lack of evidence regarding species-specific reactions to developed sites and the potential ecological consequences faced by displaced individuals. In this study, we present a method that makes best use of the currently limited understanding of displacement impacts. The combination of a matrix table displaying the full range of potential displacement and mortality levels together with seasonal potential biological removal (PBR) assessments provides a tool that increases confidence in the conclusions of impact assessments. If unrealistic displacement levels and/or mortality rates are required to equal or approach seasonal PBRs, this gives an indication of the likeliness of adverse impacts on the assessed population. This approach is demonstrated by assessing the displacement impacts of an offshore wind farm cluster in the German North Sea on the local common guillemot (Uria aalge) population. - Highlights: • A novel approach for assessing displacement impacts of offshore wind farms on seabirds is presented making best use of limited data • A displacement matrix approach is linked with PBR analysis to increased confidence in assessment conclusions drawn • A case example demonstrates the applicability of the methods described in practice.

54 ENVIRONMENTAL SCIENCES↗

The impact of climate change and emissions control on future ozone levels: Implications for human health

Overwhelming evidence has shown that, from the Industrial Revolution to the present, human activities influence ground-level ozone (O 3 ) concentrations. Past studies demonstrate links between O 3 exposure and health. However, knowledge gaps remain in our understanding concerning the impacts of climate change mitigation policies on O 3 concentrations and health. Using a hybrid downscaling approach, we evaluated the separate impact of climate change and emission control policies on O 3 levels and associated excess mortality in the US in the 2050s under two Representative Concentration Pathways (RCPs). We show that, by the 2050s, under RCP4.5, increased O 3 levels due to combined climate change and emission control policies, could contribute to an increase of approximately 50 premature deaths annually nationwide in the US. The biggest impact, however, is seen under RCP8.5, where rises in O 3 concentrations are expected to result in over 2,200 additional premature deaths annually. Here, the largest increases in O 3 are seen in RCP8.5 in the Northeast, the Southeast, the Central, and the West regions of the US. Additionally, when O 3 increases are examined by climate change and emissions contributions separately, the benefits of emissions mitigation efforts may significantly outweigh the effects of climate change mitigation policies on O 3 -related mortality.

54 ENVIRONMENTAL SCIENCES↗

Cadmium and atherosclerosis: A review of toxicological mechanisms and a meta-analysis of epidemiologic studies

Cadmium has been proposed to be the one of the factors of atherosclerosis development, although the existing data are still controversial. The primary objective of the present study is the review and the meta-analysis of studies demonstrating the association between Cd exposure and atherosclerosis as well as review of the potential mechanisms of such association. We performed a systematic search in the PubMed-Medline database using the MeSH terms cadmium, cardiovascular disease, atherosclerosis, coronary artery disease, myocardial infarction, stroke, mortality and humans up through December 20, 2017. Elevated urinary Cd levels were associated with increased mortality for cardiovascular disease (HR = 1.34, 95% CI: 1.07–1.67) as well as elevated blood Cd levels (HR = 1.78, 95% CI: 1.24–2.56). Analysis restricted to never smokers showed similar, though more imprecise, results. Consistently, we also observed an association between Cd exposure markers (blood and urine) and coronary heart disease, stroke, and peripheral artery disease. Moreover, Cd exposure was associated with atherogenic changes in lipid profile. High Cd exposure was associated with higher TC levels (OR = 1.48, 95% CI: 1.10–2.01), higher LDL-C levels (OR = 1.31, 95% CI 0.99–1.73) and lower HDL-C levels (OR = 1.96, 95% CI: 1.09–3.55). The mechanisms of atherogenic effect of cadmium may involve oxidative stress, inflammation, endothelial dysfunction, enhanced lipid synthesis, up-regulation of adhesion molecules, prostanoid dysbalance, as well as altered glycosaminoglycan synthesis.

54 ENVIRONMENTAL SCIENCES↗

Effects of exposure estimation errors on estimated exposure-response relations for PM2.5

Highlights: • Recent literature has identified associations between concentrations of fine particulate matter (PM2.5) in ambient air and adverse health effects at estimated exposure concentrations below current air ambient quality standards. • The models and analyses used do not usually quantify uncertainty about exposure estimates. • Realistic errors in exposure estimates can be estimated from available air quality monitoring stations by predicting concentrations at each station from concentrations at neighboring stations. • Exposure estimation errors are large enough to obscure low-dose nonlinearities or thresholds in the true concentration-response (C-R) function, artificially making them appear to be linear at low doses. • Better estimates of C-R functions will require modeling exposure distributions and estimation errors, rather than just estimating average exposure concentrations. Associations between fine particulate matter (PM2.5) exposure concentrations and a wide variety of undesirable outcomes, from autism and auto theft to elderly mortality, suicide, and violent crime, have been widely reported. Influential articles have argued that reducing National Ambient Air Quality Standards for PM2.5 is desirable to reduce these outcomes. Yet, other studies have found that reducing black smoke and other particulate matter by as much as 70% and dozens of micrograms per cubic meter has not detectably affected all-cause mortality rates even after decades, despite strong, statistically significant positive exposure concentration-response (C-R) associations between them. This paper examines whether this disconnect between association and causation might be explained in part by ignored estimation errors in estimated exposure concentrations. We use EPA air quality monitor data from the Los Angeles area of California to examine the shapes of estimated C-R functions for PM2.5 when the true C-R functions are assumed to be step functions with well-defined response thresholds. The estimated C-R functions mistakenly show risk as smoothly increasing with concentrations even well below the response thresholds, thus incorrectly predicting substantial risk reductions from reductions in concentrations that do not affect health risks. We conclude that ignored estimation errors obscure the shapes of true C-R functions, including possible thresholds, possibly leading to unrealistic predictions of the changes in risk caused by changing exposures. Instead of estimating improvements in public health per unit reduction (e.g., per 10 µg/m{sup 3} decrease) in average PM2.5 concentrations, it may be essential to consider how interventions change the distributions of exposure concentrations.

54 ENVIRONMENTAL SCIENCES↗

Lung function association with outdoor temperature and relative humidity and its interaction with air pollution in the elderly

Highlights: • We studied pulmonary effects of temperature and relative humidity in elderly. • Temperature and relative humidity were associated with decreased FEV1 and FVC. • The lag structure suggested that acute effects may last several days. • Effects of temperature and relative humidity were stronger on FVC than on FEV1. • Effects of temperature and relative humidity were amplified by black carbon exposure. While the effects of weather variability on cardio-respiratory mortality are well described, research examining the effects on morbidity, especially for vulnerable populations, is warranted. We investigated the associations between lung function and outdoor temperature (T in Celsius degrees (°C)) and relative humidity (RH), in a cohort of elderly men, the Normative Aging Study. Our study included 1103 participants whose forced vital capacity (FVC), forced expiratory volume in one second (FEV{sub 1}), and weather exposures were assessed one to five times during the period 1995–2011 (i.e. 3162 observations). Temperature and relative humidity were measured at one location 4 h to 7 days before lung function tests. We used linear mixed-effects models to examine the associations with outdoor T and RH. A 5-degree increase in the 3-day moving average T was associated with a significant 0.7% decrease (95%CI: −1.24, −0.20) in FVC and a 5% increase in the 7-day moving average RH was associated with a significant 0.2% decrease (95%CI: −0.40, −0.02) in FVC and FEV{sub 1}. The associations with T were greater when combined with higher exposures of black carbon with a 1.6% decrease (95%CI −2.2; −0.9) in FVC and a 1% decrease (95%CI −1.7; −0.4) in FEV{sub 1}. The relationships between T and RH and lung function were linear. No synergistic effect of T and RH was found. Heat and lung function are two predictors of mortality. Our findings suggest that increases in temperature and relative humidity are related to decreases in lung function, and such observations might be amplified by high black carbon levels.

54 ENVIRONMENTAL SCIENCES↗

Does the air pollution model influence the evidence of socio-economic disparities in exposure and susceptibility?

Highlights: • Daily exposure to ozone may vary across air pollution models, considerably. • The exposure model influenced disparity of exposure across socio-economic strata. • The air pollution model does not affect disparity of susceptibility. • Multiple air pollution models should be used to assess socio-economic disparities. Studies assessing socio-economic disparities in air pollution exposure and susceptibility are usually based on a single air pollution model. A time stratified case-crossover study was designed to assess the impact of the type of model on differential exposure and on the differential susceptibility in the relationship between ozone exposure and daily mortality by socio-economic strata (SES) in Montreal. Non-accidental deaths along with deaths from cardiovascular and respiratory causes on the island of Montreal for the period 1991–2002 were included as cases. Daily ozone concentration estimates at partictaipants’ residence were obtained from the five following air pollution models: Average value (AV), Nearest station model (NS), Inverse-distance weighting interpolation (IDW), Land-use regression model with back-extrapolation (LUR-BE) and Bayesian maximum entropy model combined with a land-use regression (BME-LUR). The prevalence of a low household income (< 20,000/year) was used as socio-economic variable, divided into two categories as a proxy for deprivation. Multivariable conditional logistic regressions were used considering 3-day average concentrations. Multiplicative and additive interactions (using Relative Excess Risk due to Interaction) as well as Cochran's tests were calculated and results were compared across the different air pollution models. Heterogeneity of susceptibility and exposure according to socio-economic status (SES) were found. Ratio of exposure across SES groups means ranged from 0.75 [0.74–0.76] to 1.01 [1.00–1.02], respectively for the LUR-BE and the BME-LUR models. Ratio of mortality odds ratios ranged from 1.01 [0.96–1.05] to 1.02 [0.97–1.08], respectively for the IDW and LUR-BE models. Cochran's test of heterogeneity between the air pollution models showed important heterogeneity regarding the differential exposure by SES, but the air pollution model was not found to influence heterogeneity regarding the differential susceptibility. The study showed air pollution models can influence the assessment of disparities in exposure according to SES in Montreal but not that of disparities in susceptibility.

54 ENVIRONMENTAL SCIENCES↗

The effect of rapid and sustained decompression on barotrauma in juvenile brook lamprey and Pacific lamprey: implications for passage at hydroelectric facilities

Fish passing downstream through hydroelectric facilities may pass through hydroturbines where they experience a rapid decrease in barometric pressure as they pass by turbine blades, which can lead to barotraumas including swim bladder rupture, exopthalmia, emboli, and hemorrhaging. In juvenile Chinook salmon, the main mechanism for injury is thought to be expansion of existing gases (particularly those present in the swim bladder) and the rupture of the swim bladder ultimately leading to exopthalmia, emboli and hemorrhaging. In fish that lack a swim bladder, such as lamprey, the rate and severity of barotraumas due to rapid decompression may be reduced however; this has yet to be extensively studied. Another mechanism for barotrauma can be gases coming out of solution and the rate of this occurrence may vary among species. In this study, juvenile brook and Pacific lamprey acclimated to 146.2 kPa (equivalent to a depth of 4.6 m) were subjected to rapid (<1 sec; brook lamprey only) or sustained decompression (17 minutes) to a very low pressure (13.8 kPa) using a protocol previously applied to juvenile Chinook salmon. No mortality or evidence of barotraumas, as indicated by the presence of hemorrhages, emboli or exopthalmia, were observed during rapid or sustained decompression, nor following recovery for up to 120 h following sustained decompression. In contrast, mortality or injury would be expected for 97.5% of juvenile Chinook salmon exposed to a similar rapid decompression to these very low pressures. Additionally, juvenile Chinook salmon experiencing sustained decompression died within 7 minutes, accompanied by emboli in the fins and gills and hemorrhaging in the tissues. Thus, juvenile lamprey may not be susceptible to barotraumas associated with hydroturbine passage to the same degree as juvenile salmonids, and management of these species should be tailored to their specific morphological and physiological characteristics.

13 HYDRO ENERGY↗

Profiling overstory survival trends following varying thinning and burning disturbance regimes in a mixed pine-hardwood forest in the US South

Prescribed burning as a silvicultural tool may be effective for achieving various management objectives, yet some practitioners have concerns about inadvertently increasing overstory tree mortality. Using extensive data from a long-term, ongoing study in northcentral Alabama, USA, that systematically applies a variety of thinning and prescribed burning disturbances on mixed pine-hardwood stands, we assess survival trends for different groups of trees. The primary research question is whether more frequent prescribed burns adversely affects overstory survival versus infrequent or no burns; secondary questions explore whether overstory survival trends differ based on thinning level, species group, or size class. Interest is in broad groups of trees, not individual tree survival or mortality; consequently, survival analysis methods are used, including nonparametric Kaplan-Meier (KM) techniques for examining single grouping factors, and parametric accelerated failure time models for analyzing simultaneous effects of multiple covariates. Leveraging relatively recent methodological advances, the statistical techniques are adjusted for interval censored data. KM survival curves showed that more frequent prescribed fires did not result in differing survival trends. Also, trees in unthinned stands had the lowest 14-year survival compared to thinned stands, oaks had the highest survival compared to pines and the others species group, and the smallest size class of overstory trees had the lowest survival. In conclusion, these results support managing transitional mixed pine-hardwoods using thinning and multiple prescribed fires to restore specific species composition and structure.

54 ENVIRONMENTAL SCIENCES↗

Evaluation of Biologic Effective Dose and Schedule of Fractionation for Preoperative Radiotherapy for Rectal Cancer: Meta-Analyses and Meta-Regression;Rectal cancer; Preoperative radiotherapy; Biologic effective dose; Meta-analysis

Purpose: To evaluate whether the risk of local recurrence depends on the biologic effective dose (BED) or fractionation dose in patients with resectable rectal cancer undergoing preoperative radiotherapy (RT) compared with surgery alone. Methods and Materials: A meta-analysis of randomized controlled trials (RCTs) was performed. The MEDLINE, Embase, CancerLit, and Cochrane Library databases were systematically searched for evidence. To evaluate the dose-response relationship, we conducted a meta-regression analysis. Four subgroups were created: Group 1, RCTs with a BED >30 Gy{sub 10} and a short RT schedule; Group 2, RCTs with BED >30 Gy{sub 10} and a long RT schedule; Group 3, RCTs with BED {<=}30 Gy{sub 10} and a short RT schedule; and Group 4, RCTs with BED {<=}30 Gy{sub 10} and a long RT schedule. Results: Our review identified 21 RCTs, yielding 9,097 patients. The pooled results from these 21 randomized trials of preoperative RT showed a significant reduction in mortality for groups 1 (p = .004) and 2 (p = .03). For local recurrence, the results were also significant in groups 1 (p = .00001) and 2 (p = .00001).The only subgroup that showed a greater sphincter preservation (SP) rate than surgery was group 2 (p = .03). The dose-response curve was linear (p = .006), and RT decreased the risk of local recurrence by about 1.7% for each Gy{sub 10} of BED. Conclusion: Our data have shown that RT with a BED of >30 Gy{sub 10} is more efficient in reducing local recurrence and mortality rates than a BED of {<=}30 Gy{sub 10}, independent of the schedule of fractionation used. A long RT schedule with a BED of >30 Gy{sub 10} should be recommended for sphincter preservation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Curative Treatment of Stage I Non-Small-Cell Lung Cancer in Patients With Severe COPD: Stereotactic Radiotherapy Outcomes and Systematic Review

Objectives: Patients with severe chronic obstructive pulmonary disease (COPD) have a high risk of lung cancer and of postsurgical complications. We studied outcomes after stereotactic body radiotherapy (SBRT) in patients with severe COPD, as defined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, and performed a systematic review of the literature on outcomes after SBRT or surgery in these patients. Methods: A single-institution cohort of 176 patients with COPD GOLD III-IV and Stage I non-small-cell lung cancer (NSCLC) treated with SBRT was evaluated. A systematic review identified studies reporting outcomes after SBRT or surgery for Stage I NSCLC in patients with GOLD III-IV or a predicted postoperative forced expiratory volume in 1 second (FEV1) of {<=}40%. Results: In the single-institution cohort, median follow-up was 21 months and median overall survival (OS) was 32 months. Actuarial 3-year local control was 89%, and 1- and 3-year OS were 79% and 47%, respectively. COPD severity correlated with OS (p = 0.01). The systematic review identified four other studies (two surgical, two SBRT, n = 196 patients). SBRT studies were published more recently and included older patients than surgical studies. Mean 30-day mortality was 0% post-SBRT and 10% after surgery. Local or locoregional control was high ({>=}89%) after both treatments. Post-SBRT, actuarial OS was 79-95% at 1 year and 43-70% at 3 years. Postsurgical actuarial OS was 45-86% at 1 year and 31-66% at 3 years. Conclusions: SBRT and surgery differ in risk of 30-day mortality in patients with severe COPD. Despite the negative selection of SBRT patients, survival at 1 and 3 years is comparable between the two treatments.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Outcomes of Stereotactic Ablative Radiotherapy in Patients With Potentially Operable Stage I Non-Small Cell Lung Cancer

Background: Approximately two-thirds of patients with early-stage non-small-cell lung cancer (NSCLC) in The Netherlands currently undergo surgical resection. As an increasing number of fit patients have elected to undergo stereotactic ablative radiotherapy (SABR) in recent years, we studied outcomes after SABR in patients with potentially operable stage I NSCLC. Methods and Materials: In an institutional prospective database collected since 2003, 25% of lung SABR cases (n = 177 patients) were found to be potentially operable when the following patients were excluded: those with (1) synchronous lung tumors or other malignancy, (2) prior high-dose radiotherapy/pneumonectomy, (3) chronic obstructive pulmonary disease with a severity score of 3-4 according to the Global initiative for Obstructive Lung Disease classification. (4) a performance score of {>=}3, and (5) other comorbidity precluding surgery. Study patients included 101 males and 76 females, with a median age of 76 years old, 60% of whom were staged as T1 and 40% of whom were T2. Median Charlson comorbidity score was 2 (range, 0-5). A SABR dose of 60 Gy was delivered using a risk-adapted scheme in 3, 5, or 8 fractions, depending on tumor size and location. Follow-up chest computed tomography scans were obtained at 3, 6, and 12 months and yearly thereafter. Results: Median follow-up was 31.5 months; and median overall survival (OS) was 61.5 months, with 1- and 3-year survival rates of 94.7% and 84.7%, respectively. OS rates at 3 years in patients with (n = 59) and without (n = 118) histological diagnosis did not differ significantly (96% versus 81%, respectively, p = 0.39). Post-SABR 30-day mortality was 0%, while predicted 30-day mortality for a lobectomy, derived using the Thoracoscore predictive model (Falcoz PE et al. J Thorac Cardiovasc Surg 2007;133:325-332), would have been 2.6%. Local control rates at 1 and 3 years were 98% and 93%, respectively. Regional and distant failure rates at 3 years were each 9.7%. Toxicity was mild, with grade {>=}3 radiation pneumonitis and rib fractures in 2% and 3%, respectively. Conclusions: Patients with potentially operable disease who underwent primary SABR had a median OS that exceeded 5 years. This finding supports ongoing randomized clinical trials comparing surgery and SABR in cases of operable stage I NSCLC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Prognostic Importance of Small Prostate Size in Men Receiving Definitive Prostate Brachytherapy

Purpose: To assess whether small prostate size is an adverse prognostic factor in men undergoing brachytherapy in the same manner in which it seems to be for men undergoing radical prostatectomy. Methods and Materials: From April 1995 to June 2008, 2024 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.4 years. The role of small prostate size ({<=}20 cm{sup 3}) as a prognostic factor for biochemical progression-free survival, cause-specific survival, and all-cause mortality was investigated. The differences in survival between men with small and larger prostates were compared using Kaplan-Meier curves and log-rank tests. Results: Median prostate size for the entire cohort was 32.7 cm{sup 3}. For the 167 men with small prostates, median prostate size was 17.4 cm{sup 3}. There was no difference in biochemical progression-free survival (95.2% vs 96.2%, P=.603), cause-specific survival (97.7% vs 98.3%, P=.546), or all-cause mortality (78.0% vs 77.2%, P=.838) at 10 years for men with small prostates compared with men with larger prostates. On univariate and multivariate analysis, small prostate size was not associated with any of the primary outcome measures. Conclusion: Men with small prostates treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men with larger glands. High-quality implants with adequate margins seem sufficient to address the increased adverse risk factors associated with small prostate size.

62 RADIOLOGY AND NUCLEAR MEDICINE↗