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Abdominal Adiposity and Testosterone Levels in Patients with Localized Prostate Cancer
Proceedings of the 52nd Annual ASTRO Meeting associated with grade $2 late rectal (p = 0.7, Pearson chi-square; OR 1.16, 95% CI 0.51 - 2.68) or grade $2 late genitourinary toxicity (p = 0.089, Pearson chi-square; OR 1.89, 95% CI 0.9 - 3.95). To examine the potential confounding effects of fraction size and rectal or bladder dosimetry, we generated BED-corrected estimates of NTCP for rectum (median 0.11, range 0.03 0.31) and bladder (median 0.39, range 0.01 - 0.97). Neither the cohort above or below the median NTCP value showed a significant association between genotype and toxicity. Conclusions: Notwithstanding the limits of this retrospective analysis, within a range of dose fractionation schemes, this analysis failed to show a significant association between TGF-b1 -509 genotype and late rectal or genitourinary toxicity in prostate cancer patients after 3DCRT or IMRT. Author Disclosure: M.B. Parliament, None; M. Blackshaw, None; N. Pervez, None; D. Murray, None; A. Scott, None; B. Warkentin, None; S. Ghosh, None; M. Sia, None; D. Skarsgard, None.
3033
AKR1C3 Expression in Non-small Cell Lung Cancer as a Predictor for Radiotherapeutic Sensitivity
X. Song, L. Xie, X. Wang, L. Wei Shandong Cancer Hospital & Institute, Jinan, China Purpose/Objective(s): It would be of considerable benefit to patients with NSCLC to be able to predict the effect of radiotherapy before therapy, because critical side effects could be avoided and the therapeutic cost of radiotherapy-resistant cases could be reduced. Materials/Methods: We established the radio-resistant subclone cell line A549/R derived from human NSCLC cell line A549 by eight rounds of sublethal ionizing radiation. We found that AKR1C3, a member of a family of 3 alpha-hydroxysteroid dehydrogenase, is significantly up-regulated in the radioresistant A549/R cells by Illumina Human-6 v2 Expression BeadChip and real-time RT-PCR. Furthermore, AKR1C3 expression was specifically suppressed by small interfering RNA transfection and then the sensitivity to ionizing radiation was tested. The apoptosis induced by irradiation was detected using FACS analysis. The expression of AKR1C3 protein in 40 NSCLC tissues and non-carcinoma adjacent tissues was examined. Results: AKR1C3 is highly up-regulated in the radioresistant A549/R cells. Targeted knockdown of AKR1C3 expression in A549/ R resulted in more sensitive to irradiation, and the rate of apoptosis after ionizing radiation was reduced. AKR1C3 was found highly expressed in cancer tissues. Conclusions: Our results help to elucidate the molecular mechanisms of the radioresistance of NSCLC. AKR1C3 may be a potential target to sensitize NSCLC cells to irradiation. Author Disclosure: X. Song, None; L. Xie, None; X. Wang, None; L. Wei, None.
3034
Abdominal Adiposity and Testosterone Levels in Patients with Localized Prostate Cancer
M. Alizadeh, N. Nguyen, T. Zilli, T. Nguyen, J. Guay, J. Bahary, D. Taussky Centre Hospitalier de l’Universite´ de Montre´al, Montreal, QC, Canada Purpose/Objective(s): Several reports suggest that men with low testosterone levels as well as obese men have more aggressive prostate cancers(PCa). We analyzed the relationship between body mass index (BMI), abdominal fat tissue distribution and testosterone levels in men with localized Pca. Materials/Methods: Eligible for this analysis were 243 patients with intermediate-(n = 144, 60.5%) and high-risk (n = 94, 39.5%) PCa treated in two different prospective randomized phase III trials with either exclusive external beam radiotherapy (EBRT) or EBRT and androgen deprivation. Abdominal fat tissue compartments were measured on planning abdominal computed tomography images. Testosterone levels were measured before randomization at different laboratories. Patients were divided into two groups: the first group included patients whose testosterone level was below the normal reference level values; the second included patients whose testosterone was above the lowest reference level. Comparison between the two groups was made using the MannWhitney U non-parametric test. Results: Testosterone measurements were available in 238 (97.9%) patients. 60.5% had intermediate-risk PCa, 39.5% high-risk PCa. Patients with low testosterone levels did not have a higher baseline PSA, Gleason score or clinical T-stage (p = 0.206-0.950) than patients with normal testosterone levels. There was no difference in age between patients with normal and low testosterone (p = 0.632). Patients with intermediate-risk cancers were not more likely (p = 0.101, chi-square test) to have a low testosterone (22.9%) than patients with high risk cancer (33.0%). Normal weighted patients (BMI \ 25 kg/m2) had an odds ratio of 2.74 (95% CI, 1.219 - 6.175) of having normal testosterone levels compared to men with a BMI $ 25 kg/m2 (p = 0.016). The mean difference BMI between patients with normal and low testosterone was 1.8 kg/m2 (p = 0.005). For a patient with a height of 1.75 m, a BMI difference of 1.8 kg/m2 translates in a weight difference of 5.5 kg. Patients with normal testosterone before RT had significantly less visceral fat (mean difference 18%, p = 0.020). Subcutaneous fat (p = 0.351) was not different between both groups. Conclusions: Patients with testosterone lower than normal reference level have more visceral fat and higher BMI. Low testosterone was not associated with more pathologically advanced disease. Our results emphasize the important relationship between testosterone and obesity in patients with localized PCa. Author Disclosure: M. Alizadeh, None; N. Nguyen, None; T. Zilli, None; T. Nguyen, None; J. Guay, None; J. Bahary, None; D. Taussky, None.
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3033
AKR1C3 Expression in Non-small Cell Lung Cancer as a Predictor for Radiotherapeutic Sensitivity
X. Song, L. Xie, X. Wang, L. Wei Shandong Cancer Hospital & Institute, Jinan, China Purpose/Objective(s): It would be of considerable benefit to patients with NSCLC to be able to predict the effect of radiotherapy before therapy, because critical side effects could be avoided and the therapeutic cost of radiotherapy-resistant cases could be reduced. Materials/Methods: We established the radio-resistant subclone cell line A549/R derived from human NSCLC cell line A549 by eight rounds of sublethal ionizing radiation. We found that AKR1C3, a member of a family of 3 alpha-hydroxysteroid dehydrogenase, is significantly up-regulated in the radioresistant A549/R cells by Illumina Human-6 v2 Expression BeadChip and real-time RT-PCR. Furthermore, AKR1C3 expression was specifically suppressed by small interfering RNA transfection and then the sensitivity to ionizing radiation was tested. The apoptosis induced by irradiation was detected using FACS analysis. The expression of AKR1C3 protein in 40 NSCLC tissues and non-carcinoma adjacent tissues was examined. Results: AKR1C3 is highly up-regulated in the radioresistant A549/R cells. Targeted knockdown of AKR1C3 expression in A549/ R resulted in more sensitive to irradiation, and the rate of apoptosis after ionizing radiation was reduced. AKR1C3 was found highly expressed in cancer tissues. Conclusions: Our results help to elucidate the molecular mechanisms of the radioresistance of NSCLC. AKR1C3 may be a potential target to sensitize NSCLC cells to irradiation. Author Disclosure: X. Song, None; L. Xie, None; X. Wang, None; L. Wei, None.
3034
Abdominal Adiposity and Testosterone Levels in Patients with Localized Prostate Cancer
M. Alizadeh, N. Nguyen, T. Zilli, T. Nguyen, J. Guay, J. Bahary, D. Taussky Centre Hospitalier de l’Universite´ de Montre´al, Montreal, QC, Canada Purpose/Objective(s): Several reports suggest that men with low testosterone levels as well as obese men have more aggressive prostate cancers(PCa). We analyzed the relationship between body mass index (BMI), abdominal fat tissue distribution and testosterone levels in men with localized Pca. Materials/Methods: Eligible for this analysis were 243 patients with intermediate-(n = 144, 60.5%) and high-risk (n = 94, 39.5%) PCa treated in two different prospective randomized phase III trials with either exclusive external beam radiotherapy (EBRT) or EBRT and androgen deprivation. Abdominal fat tissue compartments were measured on planning abdominal computed tomography images. Testosterone levels were measured before randomization at different laboratories. Patients were divided into two groups: the first group included patients whose testosterone level was below the normal reference level values; the second included patients whose testosterone was above the lowest reference level. Comparison between the two groups was made using the MannWhitney U non-parametric test. Results: Testosterone measurements were available in 238 (97.9%) patients. 60.5% had intermediate-risk PCa, 39.5% high-risk PCa. Patients with low testosterone levels did not have a higher baseline PSA, Gleason score or clinical T-stage (p = 0.206-0.950) than patients with normal testosterone levels. There was no difference in age between patients with normal and low testosterone (p = 0.632). Patients with intermediate-risk cancers were not more likely (p = 0.101, chi-square test) to have a low testosterone (22.9%) than patients with high risk cancer (33.0%). Normal weighted patients (BMI \ 25 kg/m2) had an odds ratio of 2.74 (95% CI, 1.219 - 6.175) of having normal testosterone levels compared to men with a BMI $ 25 kg/m2 (p = 0.016). The mean difference BMI between patients with normal and low testosterone was 1.8 kg/m2 (p = 0.005). For a patient with a height of 1.75 m, a BMI difference of 1.8 kg/m2 translates in a weight difference of 5.5 kg. Patients with normal testosterone before RT had significantly less visceral fat (mean difference 18%, p = 0.020). Subcutaneous fat (p = 0.351) was not different between both groups. Conclusions: Patients with testosterone lower than normal reference level have more visceral fat and higher BMI. Low testosterone was not associated with more pathologically advanced disease. Our results emphasize the important relationship between testosterone and obesity in patients with localized PCa. Author Disclosure: M. Alizadeh, None; N. Nguyen, None; T. Zilli, None; T. Nguyen, None; J. Guay, None; J. Bahary, None; D. Taussky, None.
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