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Results for “Multivariate Analysis”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 235 records · Page 13
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Lymphopenia Association With Gross Tumor Volume and Lung V5 and Its Effects on Non-Small Cell Lung Cancer Patient Outcomes

Purpose: Radiation therapy (RT) can both suppress and stimulate the immune system. We sought to investigate the mechanisms underlying radiation-induced lymphopenia and its associations with patient outcomes in non-small cell lung cancer (NSCLC). Methods and Materials: Subjects consisted of 711 patients who had received definitive RT for NSCLC. A lymphocyte nadir was calculated as the minimum lymphocyte value measured during definitive RT. Associations between gross tumor volumes (GTVs) and lung dose-volume histogram (DVH) parameters with lymphocyte nadirs were assessed with Spearman correlation coefficients. Relationships between lymphocyte nadirs with overall survival (OS) and event free survival (EFS) were evaluated with Kaplan-Meier analysis and compared with log-rank test results. Multivariate regressions were conducted with linear and Cox regression analyses. All variables were analyzed as continuous if possible. Results: Larger GTVs were correlated with lower lymphocyte nadirs regardless of concurrent chemotherapy receipt (with concurrent: r = −0.26, P<.0001; without: r = −0.48, P<.0001). Analyses of lung DVH parameters revealed significant correlations at lower doses (lung V5-V10: P<.0001) that incrementally decreased and became nonsignificant at higher doses (lung V60-V70: P>.05). Of note, no significant associations were detected between GTV and lung DVH parameters with total leukocyte, neutrophil, or monocyte nadirs during RT or with lymphocyte count prior to RT. Multivariate analysis revealed larger GTV (P<.0001), receipt of concurrent chemotherapy (P<.0001), twice-daily radiation fractionation (P=.02), and stage III disease (P=.05) to be associated with lower lymphocyte nadirs. On univariate analysis, patients with higher lymphocyte nadirs exhibited significantly improved OS (hazard ratio [HR] = 0.51 per 10{sup 3} lymphocytes/μL, P=.01) and EFS (HR = 0.46 per 10{sup 3} lymphocytes/μL, P<.0001). These differences held on multivariate analyses, controlling for common disease and treatment characteristics including GTV. Conclusions: Lower lymphocyte nadirs during definitive RT were associated with larger GTVs and worse patient outcomes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Karnofsky Performance Status and Lactate Dehydrogenase Predict the Benefit of Palliative Whole-Brain Irradiation in Patients With Advanced Intra- and Extracranial Metastases From Malignant Melanoma

Purpose: To determine prognostic factors that allow the selection of melanoma patients with advanced intra- and extracerebral metastatic disease for palliative whole-brain radiation therapy (WBRT) or best supportive care. Methods and Materials: This was a retrospective study of 87 patients who underwent palliative WBRT between 1988 and 2009 for progressive or multiple cerebral metastases at presentation. Uni- and multivariate analysis took into account the following patient- and tumor-associated factors: gender and age, Karnofsky performance status (KPS), neurologic symptoms, serum lactate dehydrogenase (LDH) level, number of intracranial metastases, previous resection or stereotactic radiosurgery of brain metastases, number of extracranial metastasis sites, and local recurrences as well as regional lymph node metastases at the time of WBRT. Results: In univariate analysis, KPS, LDH, number of intracranial metastases, and neurologic symptoms had a significant influence on overall survival. In multivariate survival analysis, KPS and LDH remained as significant prognostic factors, with hazard ratios of 3.3 (95% confidence interval [CI] 1.6-6.5) and 2.8 (95% CI 1.6-4.9), respectively. Patients with KPS ≥70 and LDH ≤240 U/L had a median survival of 191 days; patients with KPS ≥70 and LDH >240 U/L, 96 days; patients with KPS <70 and LDH ≤240 U/L, 47 days; and patients with KPS <70 and LDH >240 U/L, only 34 days. Conclusions: Karnofsky performance status and serum LDH values indicate whether patients with advanced intra- and extracranial tumor manifestations are candidates for palliative WBRT or best supportive care.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Evaluation of Vascular Endothelial Growth Factor as a Prognostic Marker for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast-Conserving Therapy

Purpose: Vascular endothelial growth factor (VEGF) is an important protein involved in the process of angiogenesis that has been found to correlate with relapse-free and overall survival in breast cancer, predominantly in locally advanced and metastatic disease. A paucity of data is available on the prognostic implications of VEGF in early-stage breast cancer; specifically, its prognostic value for local relapse after breast-conserving therapy (BCT) is largely unknown. The purpose of our study was to assess VEGF expression in a cohort of early-stage breast cancer patients treated with BCT and to correlate the clinical and pathologic features and outcomes with overexpression of VEGF. Methods and Materials: After obtaining institutional review board approval, the paraffin specimens of 368 patients with early-stage breast cancer treated with BCT between 1975 and 2005 were constructed into tissue microarrays with twofold redundancy. The tissue microarrays were stained for VEGF and read by a trained pathologist, who was unaware of the clinical details, as positive or negative according the standard guidelines. The clinical and pathologic data, long-term outcomes, and results of VEGF staining were analyzed. Results: The median follow-up for the entire cohort was 6.5 years. VEGF expression was positive in 56 (15%) of the 368 patients. Although VEGF expression did not correlate with age at diagnosis, tumor size, nodal status, histologic type, family history, estrogen receptor/progesterone receptor status, or HER-2 status, a trend was seen toward increased VEGF expression in the black cohort (26% black vs. 13% white, p = .068). Within the margin-negative cohort, VEGF did not predict for local relapse-free survival (RFS) (96% vs. 95%), nodal RFS (100% vs. 100%), distant metastasis-free survival (91% vs. 92%), overall survival (92% vs. 97%), respectively (all p >.05). Subset analysis revealed that VEGF was highly predictive of local RFS in node-positive, margin-negative patients (86% vs. 100%, p = .029) on univariate analysis, but it did not retain its significance on multivariate analysis (hazard ratio, 2.52; 95% confidence interval, 0.804-7.920, p = .113). No other subgroups were identified in which a correlation was found between VEGF expression and local relapse. Conclusion: To our knowledge, our study is the first to assess the prognostic value of VEGF with the endpoint of local relapse in early-stage breast cancer treated with BCT, an important question given the recent increased use of targeted antiangiogenic agents in early-stage breast cancer. Our study results suggest that VEGF is not an independent predictor of local RFS after BCT, but additional, larger studies specifically analyzing the endpoint of VEGF and local relapse are warranted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Multi-Institutional Experience of Stereotactic Ablative Radiation Therapy for Stage I Small Cell Lung Cancer

Purpose: For inoperable stage I (T1-T2N0) small cell lung cancer (SCLC), national guidelines recommend chemotherapy with or without conventionally fractionated radiation therapy. The present multi-institutional cohort study investigated the role of stereotactic ablative radiation therapy (SABR) for this population. Methods and Materials: The clinical and treatment characteristics, toxicities, outcomes, and patterns of failure were assessed in patients with histologically confirmed stage T1-T2N0M0 SCLC. Kaplan-Meier analysis was used to evaluate the survival outcomes. Univariate and multivariate analyses identified predictors of outcomes. Results: From 24 institutions, 76 lesions were treated in 74 patients (median follow-up 18 months). The median age and tumor size was 72 years and 2.5 cm, respectively. Chemotherapy and prophylactic cranial irradiation were delivered in 56% and 23% of cases, respectively. The median SABR dose and fractionation was 50 Gy and 5 fractions. The 1- and 3-year local control rate was 97.4% and 96.1%, respectively. The median disease-free survival (DFS) duration was 49.7 months. The DFS rate was 58.3% and 53.2% at 1 and 3 years, respectively. The median, 1-year, and 3-year disease-specific survival was 52.3 months, 84.5%, and 64.4%, respectively. The median, 1-year, and 3-year overall survival (OS) was 17.8 months, 69.9%, and 34.0% respectively. Patients receiving chemotherapy experienced an increased median DFS (61.3 vs 9.0 months; P=.02) and OS (31.4 vs 14.3 months; P=.02). The receipt of chemotherapy independently predicted better outcomes for DFS/OS on multivariate analysis (P=.01). Toxicities were uncommon; 5.2% experienced grade ≥2 pneumonitis. Post-treatment failure was most commonly distant (45.8% of recurrence), followed by nodal (25.0%) and “elsewhere lung” (20.8%). The median time to each was 5 to 7 months. Conclusions: From the findings of the largest report of SABR for stage T1-T2N0 SCLC to date, SABR (≥50 Gy) with chemotherapy should be considered a standard option.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Temporal Evolution and Dose-Volume Histogram Predictors of Visual Acuity After Proton Beam Radiation Therapy of Uveal Melanoma

Purpose: To perform an in-depth temporal analysis of visual acuity (VA) outcomes after proton beam radiation therapy (PBRT) in a large, uniformly treated cohort of uveal melanoma (UM) patients, to determine trends in VA evolution depending on pretreatment and temporally defined posttreatment VA measurements; and to investigate the relevance of specific patient, tumor and dose-volume parameters to posttreatment vision loss. Methods and Materials: Uveal melanoma patients receiving PBRT were identified from a prospectively maintained database. Included patients (n=645) received 56 GyE in 4 fractions, had pretreatment best corrected VA (BCVA) in the affected eye of count fingers (CF) or better, with posttreatment VA assessment at specified post-PBRT time point(s). Patients were grouped according to the pretreatment BCVA into favorable (≥20/40) or unfavorable (20/50-20/400) and poor (CF) strata. Temporal analysis of BCVA changes was described, and univariate and forward stepwise multivariate logistic regression analyses were performed to identify predictors for VA loss. Results: Median VA follow-up was 53 months (range, 3-213 months). At 60-month follow up, among evaluable treated eyes with favorable pretreatment BCVA, 45% retained BCVA ≥20/40, whereas among evaluable treated eyes with initially unfavorable/poor BCVA, 21% had vision ≥20/100. Among those with a favorable initial BCVA, attaining BCVA of ≥20/40 at any posttreatment time point was associated with subsequent maintenance of excellent BCVA. Multivariate analysis identified volume of the macula receiving 28GyE (P<.0001) and optic nerve (P=.0004) as independent dose-volume histogram predictors of 48-month post-PBRT vision loss among initially favorable treated eyes. Conclusions: Approximately half of PBRT-treated UM eyes with excellent pretreatment BCVA assessed at 5 years after treatment will retain excellent long-term vision. 28GyE macula and optic nerve dose-volume histogram parameters allow for rational treatment planning optimization that may lead to improved visual outcomes. The detailed temporal analysis with intermediate as well as long-term functional prognosis, and the relationship of outcomes with clinical and treatment planning parameters, is critical for informed care of UM patients before and after PBRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Applications of High Resolution Laser Induced Breakdown Spectroscopy for Environmental and Biological Samples

This chapter details the application of LIBS in a number of environmental areas of research such as carbon sequestration and climate change. LIBS has also been shown to be useful in other high resolution environmental applications for example, elemental mapping and detection of metals in plant materials. LIBS has also been used in phytoremediation applications. Other biological research involves a detailed understanding of wood chemistry response to precipitation variations and also to forest fires. A cross-section of Mountain pine (pinceae Pinus pungen Lamb.) was scanned using a translational stage to determine the differences in the chemical features both before and after a fire event. Consequently, by monitoring the elemental composition pattern of a tree and by looking for abrupt changes, one can reconstruct the disturbance history of a tree and a forest. Lastly we have shown that multivariate analysis of the LIBS data is necessary to standardize the analysis and correlate to other standard laboratory techniques. LIBS along with multivariate statistical analysis makes it a very powerful technology that can be transferred from laboratory to field applications with ease.

Martin, Madhavi Z↗
DOE OSTI2017

Prognostic significance of high YY1AP1 and PCNA expression in colon adenocarcinoma

Highlights: • YY1AP1 expression might play an important role in the tumorgenesis of colon adenocarcinoma. • YY1AP1 expression is related with colon adenocarcinoma patient M-class/distant metastasis. • High YY1AP1 indicates poor overall survival of colon adenocarcinoma patients. • Cox proportional-hazards model analysis indicated YY1AP1 as an independent predictor for overall survival. To investigate the relationship between YY1AP1 and various clinicopathological features of colon adenocarcinoma (COAD), we conducted immunohistochemical (IHC) analyses of human tissue microarrays. We found that YY1AP1 protein expression was significantly higher in tumor tissue of the colon and liver, and was significantly lower in tumor tissue of the kidney. An analysis that employed the SurvExpress database indicated that increased expression of YY1AP1 mRNA was significantly associated with the overall survival of COAD patients. To clarify the validity of YY1AP1 or PCNA as determined by the IHC analysis was performed on 59 paired samples from COAD and adjacent normal tissue. Statistically significant differences of immunoreactivity for YY1AP1 or PCNA protein expression was observed between COAD tissue and adjacent normal tissue. High protein expression levels of YY1AP1 and PCNA were also found to be significantly correlated with M-class and distant metastasis. We also determined that YY1AP1 was correlated with PCNA expression in COAD samples, and Kaplan-Meier survival curves indicated that YY1AP1 protein expression was significantly associated with poor survival. Finally, a univariate analysis demonstrated that YY1AP1 protein expression was related to YY1AP1 score, and multivariate analysis revealed that the YY1AP1 protein expression level was an independent risk factor of overall COAD survival. Taken together, our findings indicate that YY1AP1 expression plays an important role in the tumorigenesis and progression of COAD and could serve as a clinical prognostic indicator for COAD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

TROP2 overexpression promotes proliferation and invasion of lung adenocarcinoma cells

Recent studies suggest that the human trophoblast cell-surface antigen TROP2 is highly expressed in a number of tumours and is correlated with poor prognosis. However, its role in non-small cell lung carcinoma (NSCLC) remains largely unknown. Here we examined TROP2 expression by immunohistochemistry in a series of 68 patients with adenocarcinoma (ADC). We found significantly elevated TROP2 expression in ADC tissues compared with normal lung tissues (P < 0.05), and TROP2 overexpression was significantly associated with TNM (tumour, node, metastasis) stage (P = 0.012), lymph node metastasis (P = 0.038), and histologic grade (P = 0.013). Kaplan–Meier survival analysis revealed that high TROP2 expression correlated with poor prognosis (P = 0.046). Multivariate analysis revealed that TROP2 expression was an independent prognostic marker for overall survival of ADC patients. Moreover, TROP2 overexpression enhanced cell proliferation, migration, and invasion in the NSCLC cell line A549, whereas knockdown of TROP2 induced apoptosis and impaired proliferation, migration, and invasion in the PC-9 cells. Altogether, our data suggest that TROP2 plays an important role in promoting ADC and may represent a novel prognostic biomarker and therapeutic target for the disease.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Baseline Serum Lactate Dehydrogenase Levels for Patients Treated With Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: A Predictor of Poor Prognosis and Subsequent Liver Metastasis

Purpose: To evaluate the prognostic value of baseline serum lactate dehydrogenase (LDH) levels in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: Cases of NPC (n = 465) that involved treatment with IMRT with or without chemotherapy were retrospectively analyzed. Results: The mean ({+-}SD) and median baseline serum LDH levels for this cohort were 172.77 {+-} 2.28 and 164.00 IU/L, respectively. Levels of LDH were significantly elevated in patients with locoregionally advanced disease (p = 0.016). Elevated LDH levels were identified as a prognostic factor for rates of overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS), with p values <0.001 in the univariate analysis and p < 0.001, p = 0.004, and p = 0.003, respectively, in the multivariate analysis. Correspondingly, the prognostic impact of patient LDH levels was found to be statistically significant for rates of OS, DFS, and DMFS (p = 0.028, 0.024, and 0.020, respectively). For patients who experienced subsequent liver failure after treatment, markedly higher pretreatment serum LDH levels were detected compared with patients experiencing distant metastasis events at other sites (p = 0.032). Conclusions: Elevated baseline LDH levels are associated with clinically advanced disease and are a poor prognosticator for OS, DFS, and DMFS for NPC patients. These results suggest that elevated serum levels of LDH should be considered when evaluating treatment options.

62 RADIOLOGY AND NUCLEAR MEDICINE↗