scholarly journals Genomic Profile of Fatigued Men Receiving Localized Radiation Therapy

2015 ◽  
Vol 18 (3) ◽  
pp. 281-289 ◽  
Author(s):  
Chao-Pin Hsiao ◽  
Swarnalatha Y. Reddy ◽  
Mei-Kuang Chen ◽  
Leorey N. Saligan

Purpose: The purpose of this study was to explore gene expression changes in fatigued men with nonmetastatic prostate cancer receiving localized external beam radiation therapy (EBRT). Methods: Fatigue was measured in 40 men with prostate cancer (20 receiving EBRT and 20 controls on active surveillance) using the Functional Assessment of Cancer Therapy–Fatigue (FACT-F). EBRT subjects were followed from baseline to midpoint and end point of EBRT, while controls were seen at one time point. EBRT subjects were categorized into high- and low-fatigue groups based on change in FACT-F scores from baseline to EBRT completion. Full genome microarray was performed from peripheral leukocyte RNA to determine gene expression changes related to fatigue phenotypes. Real-time polymerase chain reaction and enzyme-linked immunosorbent assay confirmed the most differentially expressed gene in the microarray experiment. Results: At baseline, mean FACT-F scores were not different between EBRT subjects (44.3 ± 7.16) and controls (46.7 ± 4.32, p = .24). Fatigue scores of EBRT subjects decreased at treatment midpoint (38.6 ± 9.17, p = .01) and completion (37.6 ± 9.9, p = .06), indicating worsening fatigue. Differential expression of 42 genes was observed between fatigue groups when EBRT time points were controlled. Membrane-spanning four domains, subfamily A, member ( MS4A1) was the most differentially expressed gene and was associated with fatigue at treatment end point ( r = −.46, p = .04). Conclusion: Fatigue intensification was associated with MS4A1 downregulation, suggesting that fatigue during EBRT may be related to impairment in B-cell immune response. The 42 differentially expressed fatigue-related genes are associated with glutathione biosynthesis, γ-glutamyl cycle, and antigen presentation pathways.

2015 ◽  
Vol 18 (3) ◽  
pp. 274-280 ◽  
Author(s):  
Kristin Filler ◽  
Debra Lyon ◽  
Nancy McCain ◽  
James Bennett ◽  
Juan Luis Fernández-Martínez ◽  
...  

Purpose: Mitochondrial dysfunction is a plausible biological mechanism for cancer-related fatigue. Specific aims of this study were to (1) describe the levels of mitochondrial oxidative phosphorylation complex (MOPC) enzymes, fatigue, and health-related quality of life (HRQOL) before and at completion of external beam radiation therapy (EBRT) in men with nonmetastatic prostate cancer (PC); (2) examine relationships over time among levels of MOPC enzymes, fatigue, and HRQOL; and (3) compare levels of MOPC enzymes in men with clinically significant and nonsignificant fatigue intensification during EBRT. Methods: Fatigue was measured by the revised Piper Fatigue Scale and the Functional Assessment of Cancer Therapy–Fatigue subscale (FACT-F). MOPC enzymes (Complexes I–V) and mitochondrial antioxidant superoxide dismutase 2 were measured in peripheral blood using enzyme-linked immunosorbent assay at baseline and completion of EBRT. Participants were categorized into high or low fatigue (HF vs. LF) intensification groups based on amount of change in FACT-F scores during EBRT. Results: Fatigue reported by the 22 participants with PC significantly worsened and HRQOL significantly declined from baseline to EBRT completion. The HF group comprised 12 men with clinically significant change in fatigue (HF) during EBRT. Although no significant changes were observed in MOPC enzymes from baseline to EBRT completion, there were important differences in the patterns in the levels of MOPC enzymes between HF and LF groups. Conclusion: Distinct patterns of changes in the absorbance of MOPC enzymes delineated fatigue intensification among participants. Further investigation using a larger sample is warranted.


Author(s):  
Daryoush Khoramian ◽  
Soroush Sistani ◽  
Bagher Farhood

Abstract Aim: In radiation therapy, accurate dose distribution in target volume requires accurate treatment setup. The set-up errors are unwanted and inherent in the treatment process. By achieving these errors, a set-up margin (SM) of clinical target volume (CTV) to planning target volume (PTV) can be determined. In the current study, systematic and random set-up errors that occurred during prostate cancer radiotherapy were measured by an electronic portal imaging device (EPID). The obtained values were used to propose the optimum CTV-to-PTV margin in prostate cancer radiotherapy. Materials and methods: A total of 21 patients with prostate cancer treated with external beam radiation therapy (EBRT) participated in this study. A total of 280 portal images were acquired during 12 months. Gross, population systematic (Σ) and random (σ) errors were obtained based on the portal images in Anterior–Posterior (AP), Medio-Lateral (ML) and Superior–Inferior (SI) directions. The SM of CTV to PTV were then calculated and compared by using the formulas presented by the International Commission on Radiation Units and Measurements (ICRU) 62, Stroom and Heijmen and Van Herk et al. Results: The findings showed that the population systematic errors during prostate cancer radiotherapy in AP, ML and SI directions were 1·40, 1·95 and 1·94 mm, respectively. The population random errors in AP, ML and SI directions were 2·09, 1·85 and 2·29 mm, respectively. The SM of CTV to PTV calculated in accordance with the formula of ICRU 62 in AP, ML and SI directions were 2·51, 2·68 and 3·00 mm, respectively. And according to Stroom and Heijmen, formula were 4·23, 5·19 and 5·48 mm, respectively. And Van Herk et al. formula were 4·96, 6·17 and 6·45 mm, respectively. Findings: The SM of CTV to PTV in all directions, based on the formulas of ICRU 62, Stroom and Heijmen and van Herk et al., were equal to 2·73, 4·98 and 5·86 mm, respectively; these values were obtained by averaging the margins in all directions.


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