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At least 955 records · Page 53

Environmental risk factors associated with low birth weight: The case study of the Haifa Bay Area in Israel

Highlights: • Environmental factors affecting low birth weight (LBW) rate are investigated. • Analysis is conducted by alternative techniques of geo-statistical analysis. • Proximity to petrochemical industries is found to increase LBW rate. • Seashore proximity and elevation above the sea level reduce the LBW rate. • We attribute the latter to climate-moderating effect of elevated seashore locations. Low birth weight (LBW) is known to be associated with infant mortality and postnatal health complications. Previous studies revealed strong relationships between LBW rate and several socio-demographic factors, including ethnicity, maternal age, and family income. However, studies of association between LBW rate and environmental risk factors remain infrequent.

54 ENVIRONMENTAL SCIENCES↗

Assessment of heat- and cold-related emergency department visits in cities of China and Australia: Population vulnerability and attributable burden

Highlights: • The first comparative study on temperature impacts on EDV between different settings. • Significant associations of EDV with heat and cold in both China and Australia. • Higher heat and cold trigger points in Australia than in China. • For heat effects, higher RR in Australia, but similar AF between two countries. • For cold effects, similar RR between two countries, but higher AF in China. Non-optimal ambient temperature has detrimental impacts on mortality worldwide, but little is known about the difference in population vulnerability to non-optimal temperature and temperature-related morbidity burden between developing and developed countries.

54 ENVIRONMENTAL SCIENCES↗

The health benefits of the great outdoors: A systematic review and meta-analysis of greenspace exposure and health outcomes

Highlights: • Greenspace exposure is associated with wide ranging health benefits across 143 included studies. • Meta-analysis showed statistically significant reductions in diastolic blood pressure, salivary cortisol and heart rate. • Meta-analysis found statistically significant decreases in incidence of diabetes, all-cause and cardiovascular mortality. • A number of meta-analyses were limited by poor study quality and high levels of heterogeneity. • Greenspace and street greenery may form part of a multi-faceted approach to improve a wide range of health outcomes. The health benefits of greenspaces have demanded the attention of policymakers since the 1800s. Although much evidence suggests greenspace exposure is beneficial for health, there exists no systematic review and meta-analysis to synthesise and quantify the impact of greenspace on a wide range of health outcomes.

54 ENVIRONMENTAL SCIENCES↗

Excess lung cancer occurrence in poultry plants. Occupational risk factors: Findings for oncogenic viruses exposure and other occupational exposures

Highlights: • Exposure to poultry oncogenic virus was associated with increased lung cancer risk. • Exposure to chemical carcinogens was associated with increased lung cancer risk. • Each of these tobacco smoking-adjusted findings was independent of the other. Certain viruses naturally infect and cause cancer in chickens and turkeys. Humans are widely exposed. The viruses cause cancer in primates, and transform human cells in vitro, but it is not known if they cause cancer in humans, mainly because of the lack of epidemiologic evidence. We conducted cohort mortality studies of workers in poultry slaughtering/processing plants across the United States, because they have the highest human exposures. An excess of lung cancer and other deaths was recorded in the poultry workers. Here, we report on a case-cohort study of the lung cancer deaths nested within these cohorts, that was conducted to provide epidemiologic evidence linking these viruses with human cancer occurrence, while adjusting for possible confounders, including workplace chemical carcinogens. We obtained interviews for 339 lung cancer deaths and 457 controls, selected from our combined cohorts of 30,411 poultry plant workers and 16,405 non-poultry workers, belonging to United Food & Commercial Workers unions. Data was analyzed by both logistic regression and Cox regression, adjusting for smoking and other confounders. Lung cancer risk was independently associated with tasks or work areas indicative of exposure to both poultry oncogenic viruses and to workplace chemical carcinogens. The study provides an incremental piece of evidence (epidemiologic), indirectly linking the oncogenic viruses of poultry with the occurrence of cancer in humans, and thus may have public health implications, but the limitations highlighted must be considered. Confirmatory studies, particularly molecular studies providing definitive proof of poultry oncogenic retrovirus integration in human DNA are needed, before the findings observed in this study can be put into proper perspective.

54 ENVIRONMENTAL SCIENCES↗

Evaluation of Common Angling-Induced Sources of Epithelial Damage for Popular Freshwater Sport Fish using Fluorescein

Angling is a popular recreational activity across the globe and a large proportion of fish captured by anglers are released due to voluntary or mandatory catch-and-release practices. The handling associated with hook removal and return of the fish to their environment can cause physical damage to the epidermal layer of the fish which may affect the condition and survival of released fish. This study investigated possible sources of epithelial damage associated with several different handling methods (i.e. landing net types, interactions with different boat floor surfaces, tournament procedures) commonly used in recreational angling for two popular freshwater sport fish species, largemouth bass (Micropterus salmoides) and northern pike (Esox lucius). Epithelial damage was examined using fluorescein, a non-toxic dye, which has been shown to detect latent epithelial damage. Northern pike exhibited extensive epithelial damage after exposure to several of the induced treatments (i.e., interaction with a carpeted surface, knotted nylon net, and line rolling) but relatively little epithelial damage when exposed to others (i.e., knotless rubber nets, smooth boat surfaces, or lip gripping devices). Largemouth bass did not show significant epithelial damage for any of the treatments, with the exception of fish caught in a semi-professional live release tournament. The detection of latent injuries using fluorescein can be an important management tool as it provides visual examples of potential damage that can be caused by different handling methods. Such visualizations can be used to encourage fish friendly angler behaviour and enhance the survival and welfare of released fish. It can also be used to test new products that are intended to or claim to reduce injury to fish that are to be released. Future research should evaluate the relationship between different levels of epithelial damage and mortality across a range of environmental conditions.

54 ENVIRONMENTAL SCIENCES↗

Long-Term Outcome for Clinically Localized Prostate Cancer Treated With Permanent Interstitial Brachytherapy

Purpose: To present the largest series of prostate cancer brachytherapy patients treated with modern brachytherapy techniques and postimplant day 0 dosimetric evaluation. Methods and Materials: Between April 1995 and July 2006, 1,656 consecutive patients were treated with permanent interstitial brachytherapy. Risk group stratification was carried out according to the Mt. Sinai guidelines. Median follow-up was 7.0 years. The median day 0 minimum dose covering at least 90% of the target volume was 118.8% of the prescription dose. Cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters. Results: At 12 years, biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) for the entire cohort was 95.6%, 98.2%, and 72.6%, respectively. For low-, intermediate-, and high-risk patients, bPFS was 98.6%, 96.5%, and 90.5%; CSS was 99.8%, 99.3%, and 95.2%; and OS was 77.5%, 71.1%, and 69.2%, respectively. For biochemically controlled patients, the median posttreatment prostate-specific antigen (PSA) concentration was 0.02 ng/ml. bPFS was most closely related to percent positive biopsy specimens and risk group, while Gleason score was the strongest predictor of CSS. OS was best predicted by patient age, hypertension, diabetes, and tobacco use. At 12 years, biochemical failure and cause-specific mortality were 1.8% and 0.2%, 5.1% and 2.1%, and 10.4% and 7.1% for Gleason scores 5 to 6 and 7 and {>=}8, respectively. Conclusions: Excellent long-term outcomes are achievable with high-quality brachytherapy for low-, intermediate-, and high-risk patients. These results compare favorably to alternative treatment modalities including radical prostatectomy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients {>=}75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age {>=}75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were {>=}75 years of age and 489 of 655 patients (74.7%) were <75 years of age. Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.

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Salvage Reirradiaton With Stereotactic Body Radiotherapy for Locally Recurrent Head-and-Neck Tumors

Purpose: In this study, we present our results of reirradiation of locally recurrent head-and-neck cancer with image-guided, fractionated, frameless stereotactic body radiotherapy technique. Methods and Materials: From July 2007 to February 2009, 46 patients were treated using the CyberKnife (Accuray, Sunnyvale, CA) at the Department of Radiation Oncology, Hacettepe University, Ankara, Turkey. All patients had recurrent, unresectable, and previously irradiated head-and-neck cancer. The most prominent site was the nasopharynx (32.6%), and the most common histopathology was epidermoid carcinoma. The planning target volume was defined as the gross tumor volume identified on magnetic resonance imaging and computed tomography. There were 22 female and 24 male patients. Median age was 53 years (range, 19-87 years). The median tumor dose with stereotactic body radiotherapy was 30 Gy (range, 18-35 Gy) in a median of five (range, one to five) fractions. Results: Of 37 patients whose response to therapy was evaluated, 10 patients (27%) had complete tumor regression, 11 (29.8%) had partial response, and 10 (27%) had stable disease. Ultimate local disease control was achieved in 31 patients (83.8%). The overall survival was 11.93 months in median (ranged, 11.4 - 17.4 months), and the median progression free survival was 10.5 months. One-year progression-free survival and overall survival were 41% and 46%, respectively. Grade II or greater long-term complications were observed in 6 (13.3%) patients. On follow-up, 8 (17.3%) patients had carotid blow-out syndrome, and 7 (15.2%) patients died of bleeding from carotid arteries. We discovered that this fatal syndrome occurred only in patients with tumor surrounding carotid arteries and carotid arteries receiving all prescribed dose. Conclusions: Stereotactic body radiotherapy is an appealing treatment option for patients with recurrent head-and-neck cancer previously treated with radiation to high doses. Good local control with considerable 1-year survival is achieved with a relatively high rate of morbidity and related mortality.

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Comparison of Treatment Outcome Between Breast-Conservation Surgery With Radiation and Total Mastectomy Without Radiation in Patients With One to Three Positive Axillary Lymph Nodes

Purpose: To test the difference in treatment outcome between breast-conservation surgery with radiation and total mastectomy without radiation, to evaluate the benefits of adjuvant radiotherapy in patients with one to three positive axillary lymph nodes. Methods and Materials: Using the Severance Hospital Breast Cancer Registry, we divided the study population of T1, T2 and one to three axillary node-positive patients into two groups: breast-conservation surgery with radiation (BCS/RT) and total mastectomy without radiation (TM/no-RT). Data related to locoregional recurrence, distant recurrence, and death were collected, and survival rates were calculated. Results: The study population consisted of 125 patients treated with BCS/RT and 365 patients treated with TM/no-RT. With a median follow-up of 68.4 months, the 10-year locoregional recurrence-free survival rate with BCS/RT and TM/no-RT was 90.5% and 79.2%, respectively (p = 0.056). The 10-year distant recurrence-free survival rate was 78.8% for patients treated with BCS/RT vs. 68.0% for those treated with TM/no-RT (p = 0.012). The 10-years overall survival rate for patients treated with BCT/RT and TM/no-RT was 87.5% and 73.9%, respectively (p = 0.035). After multivariate analysis, patients treated with BCT/RT had better distant recurrence-free survival (hazard ratio [HR], 0.527; 95% confidence interval [CI], 0.297-0.934; p = 0.028), with improving locoregional recurrence-free survival (HR, 0.491; 95% CI, 0.231-1.041; p = 0.064) and overall survival trend (HR, 0.544; 95% CI, 0.277-1.067; p = 0.076). Conclusions: This study provides additional evidence that adjuvant radiation substantially reduces local recurrence, distant recurrence, and mortality for patients with one to three involved nodes.

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Preoperative Versus Postoperative Radiotherapy in Soft-Tissue Sarcoma: Multi-Institutional Analysis of 821 Patients

Purpose: To assess the impact of radiotherapy (RT) sequencing with surgery on overall survival (OS), cause-specific survival (CSS), local failure, and distant failure in soft-tissue sarcoma (STS). Methods and Materials: A retrospective analysis was conducted using the National Oncology Database, a proprietary database of aggregated tumor registries owned by IMPAC Medical Systems (Sunnyvale, CA). Patients with STS of all major anatomic sites who received definitive surgery and either preoperative (preop) or postoperative (postop) RT were included. Patients were also required to have known stage and grade. Prognostic factors for survival were identified using multivariate techniques. Survival was calculated using the Kaplan-Meier method, and compared for statistical significance (p < 0.05) using the log-rank test. Results: A total of 821 patients met inclusion criteria. The median follow-up time was 63 months. Age, stage, histology, gender, tumor size, and RT sequence were independent predictors for OS (p < 0.05). Preop RT was associated with significantly improved OS and CSS compared with postop RT (hazard ratio [HR] = 0.72, 95% confidence interval [CI] 0.56-0.91, p < 0.01, and HR = 0.64, 95% CI 0.46-0.88, p < 0.01, respectively). The 5-year CSS was 79% and 74%, in favor of preop RT (log-rank, p < 0.05). Preop RT was also significantly associated with a reduced risk for local and distant relapse compared with postop RT. Conclusion: Preoperative RT is associated with a reduced cancer-specific mortality compared with postoperative RT in STS. The results of this study may serve as motivation to conduct future prospective studies with larger patient numbers.

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Stereotactic Body Radiotherapy Versus Surgery for Medically Operable Stage I Non-Small-Cell Lung Cancer: A Markov Model-Based Decision Analysis

Purpose: To compare the quality-adjusted life expectancy and overall survival in patients with Stage I non-small-cell lung cancer (NSCLC) treated with either stereotactic body radiation therapy (SBRT) or surgery. Methods and Materials: We constructed a Markov model to describe health states after either SBRT or lobectomy for Stage I NSCLC for a 5-year time frame. We report various treatment strategy survival outcomes stratified by age, sex, and pack-year history of smoking, and compared these with an external outcome prediction tool (Adjuvant{exclamation_point} Online). Results: Overall survival, cancer-specific survival, and other causes of death as predicted by our model correlated closely with those predicted by the external prediction tool. Overall survival at 5 years as predicted by baseline analysis of our model is in favor of surgery, with a benefit ranging from 2.2% to 3.0% for all cohorts. Mean quality-adjusted life expectancy ranged from 3.28 to 3.78 years after surgery and from 3.35 to 3.87 years for SBRT. The utility threshold for preferring SBRT over surgery was 0.90. Outcomes were sensitive to quality of life, the proportion of local and regional recurrences treated with standard vs. palliative treatments, and the surgery- and SBRT-related mortalities. Conclusions: The role of SBRT in the medically operable patient is yet to be defined. Our model indicates that SBRT may offer comparable overall survival and quality-adjusted life expectancy as compared with surgical resection. Well-powered prospective studies comparing surgery vs. SBRT in early-stage lung cancer are warranted to further investigate the relative survival, quality of life, and cost characteristics of both treatment paradigms.

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Long-Term Outcomes of Stereotactic Radiosurgery for Treatment of Cavernous Sinus Meningiomas

Purpose: Patients with cavernous sinus meningiomas (CSM) have an elevated risk of surgical morbidity and mortality. Recurrence is often observed after partial resection. Stereotactic radiosurgery (SRS), either alone or combined with surgery, represents an important advance in CSM management, but long-term results are lacking. Methods and Materials: A total of 88 CSM patients, treated from January 1991 to December 2005, were retrospectively reviewed. The mean follow-up was 86.8 months (range, 17.1-179.4 months). Among the patients, 22 were followed for more than 10 years. There was a female predominance (84.1%). The age varied from 16 to 90 years (mean, 51.6). In all, 47 patients (53.4%) received SRS alone, and 41 patients (46.6%) had undergone surgery before SRS. A dose of 14 Gy was prescribed to isodose curves from 50% to 90%. In 25 patients (28.4%), as a result of the proximity to organs at risk, the prescribed dose did not completely cover the target. Results: After SRS, 65 (73.8%) patients presented with tumor volume reduction; 14 (15.9%) remained stable, and 9 (10.2%) had tumor progression. The progression-free survival was 92.5% at 5 years, and 82.5% at 10 years. Age, sex, maximal diameter of the treated tumor, previous surgery, and complete target coverage did not show significant associations with prognosis. Among the 88 treated patients, 17 experienced morbidity that was related to SRS, and 6 of these patients spontaneously recovered. Conclusions: SRS is an effective and safe treatment for CSM, feasible either in the primary or the postsurgical setting. Incomplete coverage of the target did not worsen outcomes. More than 80% of the patients remained free of disease progression during long-term follow-up.

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Risk of Carotid Blowout After Reirradiation of the Head and Neck: A Systematic Review

Purpose: Carotid blowout (CB) is a rare but frequently fatal complication of head-and-neck (H and N) cancer or its treatment. We sought to determine the reported rate of CB in patients receiving salvage reirradiation for H and N cancer. Methods and Materials: A literature search identified 27 published articles on H and N reirradiation involving 1554 patients, and a pooled analysis was performed to determine the rate of CB. Treatment parameters, including prior radiation dose, interval from prior radiation, dose and fractionation of reirradiation, use of salvage surgery, and chemotherapy, were abstracted and summarized. The cumulative risk of CB was compared between groups using Fisher's exact test. Results: Among 1554 patients receiving salvage H and N reirradiation, there were 41 reported CBs, for a rate of 2.6%; 76% were fatal. In patients treated in a continuous course with 1.8-2-Gy daily fractions or 1.2-Gy twice-daily fractions, 36% of whom received concurrent chemotherapy, the rate of CB was 1.3%, compared with 4.5% in patients treated with 1.5 Gy twice daily in alternating weeks or with delayed accelerated hyperfractionation, all of whom received concurrent chemotherapy (p = 0.002). There was no statistically significant difference in the rate of CB between patients treated with or without concurrent chemotherapy, or between patients treated with or without salvage surgery before reirradiation. Conclusion: Carotid blowout is an infrequent but serious complication of salvage reirradiation for H and N cancer. The rate of CB was lower among patients treated with conventional or hyperfractionated schedules compared with regimens of accelerated hyperfractionation, though heterogeneous patient populations and treatment parameters preclude definite conclusions. Given the high mortality rate of CB, discussion of the risk of CB is an important component of informed consent for salvage reirradiation.

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Race and Survival Following Brachytherapy-Based Treatment for Men With Localized or Locally Advanced Adenocarcinoma of the Prostate

Purpose: We investigated whether race was associated with risk of death following brachytherapy-based treatment for localized prostate cancer, adjusting for age, cardiovascular comorbidity, treatment, and established prostate cancer prognostic factors. Methods: The study cohort was composed of 5,360 men with clinical stage T1-3N0M0 prostate cancer who underwent brachytherapy-based treatment at 20 centers within the 21st Century Oncology consortium. Cox regression multivariable analysis was used to evaluate the risk of death in African-American and Hispanic men compared to that in Caucasian men, adjusting for age, pretreatment prostate-specific antigen (PSA) level, Gleason score, clinical T stage, year and type of treatment, median income, and cardiovascular comorbidities. Results: After a median follow-up of 3 years, there were 673 deaths. African-American and Hispanic races were significantly associated with an increased risk of all-cause mortality (ACM) (adjusted hazard ratio, 1.77 and 1.79; 95% confidence intervals, 1.3-2.5 and 1.2-2.7; p < 0.001 and p = 0.005, respectively). Other factors significantly associated with an increased risk of death included age (p < 0.001), Gleason score of 8 to 10 (p = 0.04), year of brachytherapy (p < 0.001), and history of myocardial infarction treated with stent or coronary artery bypass graft (p < 0.001). Conclusions: After adjustment for prostate cancer prognostic factors, age, income level, and revascularized cardiovascular comorbidities, African-American and Hispanic races were associated with higher ACM in men with prostate cancer. Additional causative factors need to be identified.

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Long-Term Outcomes After Maximal Surgical Resection and Intraoperative Electron Radiotherapy for Locoregionally Recurrent or Locoregionally Advanced Primary Renal Cell Carcinoma

Purpose: To report outcomes of a multimodality therapy combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) for patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. Methods and Materials: From 1989 through 2005, a total of 22 patients with LR recurrent (n = 19) or LR advanced primary (n = 3) RCC were treated with this multimodality approach. The median patient age was 63 years (range 46-78). Twenty-one patients (95%) received perioperative external beam radiotherapy (EBRT) with a median dose of 4,500 cGy (range, 4,140-5,500). Surgical resection was R0 (negative margins) in 5 patients (23%) and R1 (residual microscopic disease) in 17 patients (77%). The median IOERT dose delivered was 1,250 cGy (range, 1,000-2,000). Overall survival (OS) and disease-free survival (DFS) and relapse patterns were estimated using the Kaplan-Meier method. Results: The median follow-up for surviving patients was 9.9 years (range, 3.6-20 years). The OS and DFS at 1, 5, and 10 years were 91%, 40%, and 35% and 64%, 31%, and 31%, respectively. Central recurrence (within the IOERT field), LR relapse (tumor bed or regional lymph nodes), and distant metastases at 5 years were 9%, 27%, and 64%, respectively. Mortality within 30 days of surgery and IOERT was 0%. Five patients (23%) experienced acute or late National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) Version 4 Grade 3 to 5 toxicities. Conclusions: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach of perioperative EBRT, maximal surgical resection, and IOERT yielded encouraging results. This regimen warrants further investigation.

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N-Terminal Pro-B-Type Natriuretic Peptide Plasma Levels as a Potential Biomarker for Cardiac Damage After Radiotherapy in Patients With Left-Sided Breast Cancer

Purpose: Adjuvant radiotherapy (RT) after breast-conserving surgery has been associated with increased cardiovascular mortality. Cardiac biomarkers may aid in identifying patients with radiation-mediated cardiac dysfunction. We evaluated the correlation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin (TnI) and the dose of radiation to the heart in patients with left-sided breast cancer. Methods and Materials: NT-proBNP and TnI plasma concentrations were measured in 30 left-sided breast cancer patients (median age, 55.0 years) 5 to 22 months after RT (Group I) and in 30 left-sided breast cancer patients (median age, 57.0 years) before RT as control group (Group II). Dosimetric and geometric parameters of heart and left ventricle were determined in all patients of Group I. Seventeen patients underwent complete two-dimensional echocardiography. Results: NT-proBNP levels were significantly higher (p = 0.03) in Group I (median, 90.0 pg/ml; range, 16.7-333.1 pg/ml) than in Group II (median, 63.2 pg/ml; range, 11.0-172.5 pg/ml). TnI levels remained below the cutoff threshold of 0.07 ng/ml in both groups. In patients with NT-proBNP values above the upper limit of 125 pg/ml, there were significant correlations between plasma levels and V{sub 3Gy}(%) (p = 0.001), the ratios D{sub 15cm{sup 3}}(Gy)/D{sub mean}(Gy) (p = 0.01), the ratios D{sub 15cm}{sup 3}/D{sub 50%} (Gy) (p = 0.008) for the heart and correlations between plasma levels and V{sub 2Gy} (%) (p = 0.002), the ratios D{sub 1cm{sup 3}}(Gy)/D{sub mean}(Gy) (p = 0.03), and the ratios D{sub 0.5cm{sup 3}}(Gy)/D{sub 50%}(Gy) (p = 0.05) for the ventricle. Conclusions: Patients with left-sided breast cancer show higher values of NT-pro BNP after RT when compared with non-RT-treated matched patients, increasing in correlation with high doses in small volumes of heart and ventricle. The findings of this study show that the most important parameters are not the mean doses but instead the small percentage of organ volumes (heart or ventricle) receiving high dose levels, supporting the notion that the heart behaves as a serial organ.

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Retrospective Analysis of Outcome Differences in Preoperative Concurrent Chemoradiation With or Without Elective Nodal Irradiation for Esophageal Squamous Cell Carcinoma

Purpose: To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. Methods and Materials: We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-free survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. Results: The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. Conclusions: ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for esophageal SCC. Pathological nodal metastasis predicted poor outcome.

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Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated With Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease

Purpose: To analyze prognostic factors in patients with high-risk prostate cancer treated with dose-escalated external-beam radiation therapy (EBRT) and androgen deprivation (ADT). Methods and Materials: Between 1998 and 2008 at University of Michigan Medical Center, 718 men were consecutively treated with EBRT to at least 75 Gy. Seven definitions of high-risk prostate cancer, applying to 11-33% of patients, were evaluated. Biochemical failure (BF), salvage ADT use, metastatic progression, and prostate cancer-specific mortality (PCSM) were estimated by the Kaplan-Meier method and Cox proportional hazards regression. Results: Each high-risk definition was associated with increased BF (hazard ratio [HR] 2.8-3.9, p < 0.0001), salvage ADT use (HR 3.9-6.3, p < 0.0001), metastasis (HR 3.7-6.6, p < 0.0001), and PCSM (HR 3.7-16.2, p < 0.0001). Furthermore, an increasing number of high-risk features predicted worse outcome. Adjuvant ADT yielded significant reductions in both metastases (HR 0.19-0.38, p < 0.001) and PCSM (HR 0.38-0.50, p < 0.05) for all high-risk definitions (with the exception of clinical Stage T3-4 disease) but improved BF only for those with elevated Gleason scores (p < 0.03, HR 0.25-0.48). When treated with ADT and dose-escalated EBRT, patients with Gleason scores 8 to 10, without other high-risk features, had 8-year freedom from BF of 74%, freedom from distant metastases of 93%, and cause-specific survival of 92%, with salvage ADT used in 16% of patients. Conclusion: Adjuvant ADT results in a significant improvement in clinical progression and PCSM across multiple definitions of high-risk disease even with dose-escalated EBRT. There is a subset of patients, characterized by multiple high-risk features or the presence of Gleason Pattern 5, who remain at significant risk for metastasis and PCSM despite current treatment.

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