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At least 1,639 records · Page 91
All sourcesNASA NTRSDOE OSTI
DOE OSTI2011

The insecticide 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (DDT) alters the membrane raft location of the TSH receptor stably expressed in Chinese hamster ovary cells

DDT is a highly lipophilic molecule known to deplete membrane rafts of their phosphoglycolipid and cholesterol contents. However, we have recently shown that DDT can also alter the thyroid homeostasis by inhibiting TSH receptor (TSHr) internalization. The present study was undertaken to verify whether DDT goitrogenic effects are due to the insecticide acting directly on TSHr or via alteration of the membrane rafts hosting the receptor itself. Our results demonstrate that, in CHO-TSHr transfected cells, TSHr is activated in the presence of TSH, while it is inhibited following DDT exposure. DDT can also reduce the endocytic vesicular traffic, alter the extension of multi-branched microvilli along their plasma membranes and induce TSHr shedding in vesicular forms. To verify whether TSHr displacement might depend on DDT altering the raft constitution of CHO-TSHr cell membranes the extent of TSHr and lipid raft co-localization was examined by confocal microscopy. Evidence shows that receptor/raft co-localization increased significantly upon exposure to TSH, while receptors and lipid rafts become dislodged on opposite cell poles in DDT-exposed CHO-TSHr cells. As a control, under similar culturing conditions, diphenylethylene, which is known to be a lipophilic substance that is structurally related to DDT, did not affect the extent of TSHr and lipid raft co-localization in CHO-TSHr cells treated with TSH. These findings corroborate and extend our view that, in CHO cells, the DDT disrupting action on TSHr is primarily due to the insecticide acting on membranes to deplete their raft cholesterol content, and that the resulting inhibition on TSHr internalization is due to receptor dislodgement from altered raft microdomains of the plasma membrane. - Highlights: >DDT is a pesticide with a severe environmental impact >Epidemiologic correlation exists between exposition to DDT and thyroid dysfunction >DDT is a lipophilic molecule that has been shown to inhibit TSH receptor function >DDT depletes membrane raft cholesterol content and by this way inhibits TSH receptor

60 APPLIED LIFE SCIENCES↗
DOE OSTI2010

Combined Adrenal and Ovarian Venous Sampling to Localize an Androgen Producing Tumor

A postmenopausal woman presented with hirsutism and elevated serum testosterone levels. A 1-cm adrenal adenoma was noted on computed tomography. Combined adrenal and ovarian venous sampling was performed to localize an androgen producing tumor to the left ovary. The patient underwent a bilateral salpingo-oophrectomy and was spared an unnecessary adrenalectomy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

The Association Between Biological Subtype and Isolated Regional Nodal Failure After Breast-Conserving Therapy

Purpose: To evaluate the risk of isolated regional nodal failure (RNF) among women with invasive breast cancer treated with breast-conserving surgery (BCS) and radiation therapy (RT) and to determine factors, including biological subtype, associated with RNF. Methods and Materials: We retrospectively studied 1,000 consecutive women with invasive breast cancer who received breast-conserving surgery and RT from 1997 through 2002. Ninety percent of patients received adjuvant systemic therapy; none received trastuzumab. Sentinel lymph node biopsy was done in 617 patients (62%). Of patients with one to three positive nodes, 34% received regional nodal irradiation (RNI). Biological subtype classification into luminal A, luminal B, HER-2, and basal subtypes was based on estrogen receptor status-, progesterone receptor status-, and HER-2-status of the primary tumor. Results: Median follow-up was 77 months. Isolated RNF occurred in 6 patients (0.6%). On univariate analysis, biological subtype (p = 0.0002), lymph node involvement (p = 0.008), lymphovascular invasion (p = 0.02), and Grade 3 histology (p = 0.01) were associated with significantly higher RNF rates. Compared with luminal A, the HER-2 (p = 0.01) and basal (p = 0.08) subtypes were associated with higher RNF rates. The 5-year RNF rate among patients with one to three positive nodes treated with tangents alone was 2.4%; we could not identify a subset of these patients with a substantial risk of RNF. Conclusions: Isolated RNF is a rare occurrence after breast-conserving therapy. Patients with the HER-2 (not treated with trastuzumab) and basal subtypes appear to be at higher risk of developing RNF although this risk is not high enough to justify the addition of RNI. Low rates of RNF in patients with one to three positive nodes suggest that tangential RT without RNI is reasonable in most patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Radiotherapy Can Decrease Locoregional Recurrence and Increase Survival in Mastectomy Patients With T1 to T2 Breast Cancer and One to Three Positive Nodes With Negative Estrogen Receptor and Positive Lymphovascular Invasion Status

Purpose: To define a subgroup of patients at high risk of locoregional recurrence (LRR) who might be benefit from postmastectomy radiotherapy in invasive breast cancer and tumor size <5 cm with one to three involved axillary lymph nodes (T1-2 N1). Methods and Materials: Between April 1991 and December 2005, 544 patients with T1-2 N1 invasive breast cancer were treated with modified radical mastectomy. Of the 544 patients, 383 patients (70.4%) had no radiotherapy, and 161 patients (29.6%) received radiotherapy. We retrospectively compared these two patient groups. Results: With a median follow-up of 40.3 months, LRR occurred in 40 (7.4%) of 544 patients. On univariate analysis, high nuclear grade (p = 0.04), negative estrogen receptor (ER) status (p = 0.001), presence of lymphovascular invasion (LVI) (p = 0.003), and no radiotherapy (p = 0.0015) were associated with a significantly higher rate of LRR. Negative ER status (hazard ratio = 5.1) and presence of LVI (hazard ratio = 2.5) were the risk factors for LRR with statistical significance in the multivariate analysis. Radiotherapy reduced the LRR in patients with the following characteristics: age <40 years, T2 stage, high nuclear grade, negative ER status, and presence of LVI. For 41 patients with negative ER and positive LVI status, radiotherapy can reduce LRR from 10 of 25 (40%) to 2 of 16 (12.5%) and increase the 5-year overall survival from 43.7% to 87.1%. Conclusion: Radiotherapy can reduce LRR and increase survival in T1-2 N1 breast cancer patients with negative ER status and presence of LVI.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Radiation With or Without 6 Months of Androgen Suppression Therapy in Intermediate- and High-Risk Clinically Localized Prostate Cancer: A Postrandomization Analysis by Risk Group

Purpose: Six months of androgen suppression therapy (AST) plus radiation (RT) prolongs survival vs. RT alone in men with unfavorable risk localized prostate cancer (PCa), but it is unknown if this benefit applies to all risk subgroups and, in particular, the intermediate-risk group. Methods and Materials: Among 206 men with stages T1b to T2b PCa and either a prostate-specific antigen level of >10 or a Gleason score of {>=}7 or MRI evidence of T3 disease randomized to receive 70 Gy of RT with or without 6 months of AST, Cox multivariable analysis was used to assess the impact of AST on overall survival in intermediate- and high-risk localized PCa, adjusting for age, Adult Comorbidity Evaluation 27 comorbidity score, interaction between comorbidity and treatment, and known prognostic factors. Survival estimates were compared using a two-sided log-rank test. Results: After an 8.2-year median follow-up, 74 men died. Compared to treatment with AST plus RT, treatment with RT alone was associated with an increased risk of death in intermediate-risk (adjusted hazard ratio, 3.0 [95% confidence interval, 1.3-7.2]; p = 0.01) and high-risk PCa (adjusted hazard ratio, 3.3 [95% confidence interval, 0.94-11.3]; p = 0.06). The survival benefit of adding AST was restricted to men with no or mild comorbidity in both the intermediate-risk (90.9% vs. 85.8% survival, respectively, at 7 years for AST plus RT vs. RT alone; p = 0.009) and high-risk (88.9% vs. 51.2% survival, respectively, at 7 years for AST plus RT vs. RT alone; p = 0.007) subgroups. Conclusions: In men with localized PCa who have no or mild comorbidity, adding 6 months of AST to RT was associated with improved survival for those with both intermediate-risk and high-risk disease, but in men with moderate to severe comorbidity, no benefit was observed in either risk group.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

External Beam Radiation Therapy After Transurethral Resection of the Prostate: A Report on Acute and Late Genitourinary Toxicity

Purpose: To describe genitourinary (GU) toxicity in men with a history of transurethral resection of the prostate (TURP) treated with external beam radiation therapy (EBRT) for prostate cancer. Methods and Materials: Seventy-one men with a history of TURP were treated with EBRT for prostate cancer. The median time from TURP to EBRT was 15 months. The median EBRT dose was 70 Gy, and 21 men (30%) received androgen deprivation therapy (ADT). Acute GU toxicity and late GU toxicity were scored by Radiation Therapy Oncology Group criteria and compared with a cohort of 538 men without prior TURP. The median follow-up for men with TURP and men without TURP was 40 months and 50 months, respectively (p = 0.7605). Results: The rate of acute Grade 2 GU toxicity or higher was 41%, and was increased with a history of more than 1 TURP (73% vs. 31%, p = 0.0036). The 4-year rate of freedom from late Grade 3 GU toxicity or higher was 84%, and was decreased with ADT (45% vs. 95% without ADT, p = 0.0024). By last follow-up, maximal GU toxicity tended to resolve (p < 0.0001) and there was no worsening of urinary symptom scores (p = 0.6911). Compared to men without a prior TURP, TURP patients had a lower rate of freedom from late Grade 3 toxicity or higher (84% vs. 96%, p = 0.0483). Multivariate analysis suggested a higher rate of late Grade 3 toxicity or higher with TURP (risk ratio, 2.87; p = 0.0612) and EBRT dose of 74 Gy or greater (risk ratio, 2.26; p = 0.0521). Conclusions: Men treated for prostate cancer with EBRT after TURP have a higher risk of severe GU toxicity; however, the overall incidence is low, and toxicity tends not to persist.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Expression of Bcl-2, p53, and MDM2 in Localized Prostate Cancer With Respect to the Outcome of Radical Radiotherapy Dose Escalation

Purpose: Established prognostic factors in localized prostate cancer explain only a moderate proportion of variation in outcome. We analyzed tumor expression of apoptotic markers with respect to outcome in men with localized prostate cancer in two randomized controlled trials of radiotherapy dose escalation. Methods and Materials: Between 1995 and 2001, 308 patients with localized prostate cancer received neoadjuvant androgen deprivation and radical radiotherapy at our institution in one of two dose-escalation trials. The biopsy specimens in 201 cases were used to make a biopsy tissue microarray. We evaluated tumor expression of Bcl-2, p53, and MDM2 by immunohistochemistry with respect to outcome. Results: Median follow-up was 7 years, and 5-year freedom from biochemical failure (FFBF) was 70.4% (95% CI, 63.5-76.3%). On univariate analysis, expression of Bcl-2 (p < 0.001) and p53 (p = 0.017), but not MDM2 (p = 0.224), was significantly associated with FFBF. Expression of Bcl-2 remained significantly associated with FFBF (p = 0.001) on multivariate analysis, independently of T stage, Gleason score, initial prostate-specific antigen level, and radiotherapy dose. Seven-year biochemical control was 61% vs. 41% (p = 0.0122) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-positive tumors and 87% vs. 81% (p = 0.423) for 74 Gy vs. 64 Gy, respectively, among patients with Bcl-2-negative tumors. There was no statistically significant interaction between dose and Bcl-2 expression. Conclusions: Bcl-2 expression was a significant, independent determinant of biochemical control after neoadjuvant androgen deprivation and radical radiotherapy for prostate cancer. These data generate the hypothesis that Bcl-2 expression could be used to inform the choice of radiotherapy dose in individual patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

PSA Decrease During Combined-Modality Radiotherapy Predicts for Treatment Outcome

Purpose: Prostate-specific antigen (PSA) is the well-used marker in the diagnosis, prognosis, and follow-up for prostate cancer patients. Although reports have focused on the importance of pretreatment PSA levels, doubling time, and posttreatment nadirs, there is little information on the value of PSA during the course of radiotherapy. Methods and Materials: Retrospective review of PSA values obtained midway through a course of radiotherapy treatment for prostate cancer. Patients had a PSA (midPSA) measured after a course of external beam radiation (EBRT) before planned transperineal low-dose-rate brachytherapy implant (LDR). Results: A total of 717 patients were analyzed with a median follow-up of 5.8 years, all censored patients had a minimum follow-up of 2 years. A total of 277 patients had low-risk disease, 267 patients had intermediate risk, and 173 patients had high-risk disease. Androgen blockade was used in 512 patients. A total of 653 patients had a midPSA decrease after EBRT, the median decrease was 6.2 ng/mL. Patients who had a midPSA decrease {>=}25% compared with pretreatment PSA had improved overall survival of 10.0 vs. 7.4 years (p < 0.0004) and improved disease-free survival of 9.8 vs. 7.3 years (p < 0.01). When stratified by use of androgen blockade, midPSA remained significant for both androgen and non-androgen patients. Conclusions: PSA response after EBRT before brachytherapy predicts for long-term outcome; this may allow for risk stratification and intervention with higher LDR doses to improve outcomes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Results With Accelerated Partial Breast Irradiation in Terms of Estrogen Receptor, Progesterone Receptor, and Human Growth Factor Receptor 2 Status

Purpose: To report our results with accelerated partial breast irradiation (APBI) in terms of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2/neu) status. Methods and Materials: Between February 2003 and June 2009, 209 women with early-stage breast carcinomas were treated with APBI using multicatheter, MammoSite, or Contura brachytherapy to 34 Gy in 10 fractions twice daily over 5-7 days. Three patient groups were defined by receptor status: Group 1: ER or PR (+) and HER-2/neu (-) (n = 180), Group 2: ER and PR (-) and HER-2/neu (+) (n = 10), and Group 3: ER, PR, and HER-2/neu (-) (triple negative breast cancer, n = 19). Median follow-up was 22 months. Results: Group 3 patients had significantly higher Scarff-Bloom-Richardson scores (p < 0.001). The 3-year ipsilateral breast tumor control rates for Groups 1, 2, and 3 were 99%, 100%, and 100%, respectively (p = 0.15). Group 3 patients tended to experience relapse in distant sites earlier than did non-Group 3 patients. The 3-year relapse-free survival rates for Groups 1, 2, and 3 were 100%, 100%, and 81%, respectively (p = 0.046). The 3-year cause-specific and overall survival rates for Groups 1, 2, and 3 were 100%, 100%, and 89%, respectively (p = 0.002). Conclusions: Triple negative breast cancer patients typically have high-grade tumors with significantly worse relapse-free, cause-specific, and overall survival. Longer follow-up will help to determine whether these patients also have a higher risk of ipsilateral breast tumor relapse.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Baseline Serum Testosterone in Men Treated With Androgen Deprivation Therapy and Radiotherapy for Localized Prostate Cancer

Introduction: It is believed that men diagnosed with prostate cancer and a low baseline serum testosterone (BST) may have more aggressive disease, and it is frequently recommended they forgo testosterone replacement therapy. We used two large Phase III trials involving androgen deprivation therapy and external beam radiation therapy to assess the significance of a BST. Methods and Materials: All patients with a BST and complete data (n = 2,478) were included in this analysis and divided into four categories: 'Very Low BST' (VLBST) {<=}16.5th percentile of BST ({<=}248 ng/dL; n = 408); 'Low BST' (LBST) >16.5th percentile and {<=}33rd percentile (>248 ng/dL but {<=}314 ng/dL; n = 415); 'Average BST' (ABST) >33rd percentile and {<=}67th percentile (314-437 ng/dL; n = 845); and 'High BST' (HBST) >67th percentile (>437 ng/dL; n = 810). Outcomes included overall survival, distant metastasis, biochemical failure, and cause-specific survival. All outcomes were adjusted for the following covariates: treatment arm, BST, age (<70 vs. {>=}70), prostate-specific antigen (PSA; <10 vs. 10 {<=} PSA <20 vs. 20 {<=}), Gleason score (2-6 vs. 7 vs. 8-10); T stage (T1-T2 vs. T3-T4), and Karnofsky Performance Status (60-90 vs. 100). Results: On multivariable analysis age, Gleason score, and PSA were independently associated with an increased risk of biochemical failure, distant metastasis and a reduced cause-specific and overall survival (p < 0.05), but BST was not. Conclusions: BST does not affect outcomes in men treated with external beam radiation therapy and androgen deprivation therapy for prostate cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

A Comparison of the Prognostic Value of Early PSA Test-Based Variables Following External Beam Radiotherapy, With or Without Preceding Androgen Deprivation: Analysis of Data From the TROG 96.01 Randomized Trial

Purpose: We sought to compare the prognostic value of early prostate-specific antigen (PSA) test-based variables for the 802 eligible patients treated in the Trans-Tasman Radiation Oncology Group 96.01 randomized trial. Methods and Materials: Patients in this trial had T2b, T2c, T3, and T4 N0 prostate cancer and were randomized to 0, 3, or 6 months of neoadjuvant androgen deprivation therapy (NADT) prior to and during radiation treatment at 66 Gy to the prostate and seminal vesicles. The early PSA test-based variables evaluated were the pretreatment initial PSA (iPSA) value, PSA values at 2 and 4 months into NADT, the PSA nadir (nPSA) value after radiation in all patients, and PSA response signatures in men receiving radiation. Comparisons of endpoints were made using Cox models of local progression-free survival, distant failure-free survival, biochemical failure-free survival, and prostate cancer-specific survival. Results: The nPSA value was a powerful predictor of all endpoints regardless of whether NADT was given before radiation. PSA response signatures also predicted all endpoints in men treated by radiation alone. iPSA and PSA results at 2 and 4 months into NADT predicted biochemical failure-free survival but not any of the clinical endpoints. nPSA values correlated with those of iPSA, Gleason grade, and T stage and were significantly higher in men receiving radiation alone than in those receiving NADT. Conclusions: The postradiation nPSA value is the strongest prognostic indicator of all early PSA-based variables. However, its use as a surrogate endpoint needs to take into account its dependence on pretreatment variables and treatment method.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Mitigation Effect of an FGF-2 Peptide on Acute Gastrointestinal Syndrome After High-Dose Ionizing Radiation

Purpose: Acute gastrointestinal syndrome (AGS) resulting from ionizing radiation causes death within 7 days. Currently, no satisfactory agent exists for mitigation of AGS. A peptide derived from the receptor binding domain of fibroblast growth factor 2 (FGF-P) was synthesized and its mitigation effect on AGS was examined. Methods and Materials: A subtotal body irradiation (sub-TBI) model was created to induce gastrointestinal (GI) death while avoiding bone marrow death. After 10.5 to 16 Gy sub-TBI, mice received an intramuscular injection of FGF-P (10 mg/kg/day) or saline (0.2 ml/day) for 5 days; survival (frequency and duration) was measured. Crypt cells and their proliferation were assessed by hematoxylin, eosin, and BrdU staining. In addition, GI hemoccult score, stool formation, and plasma levels of endotoxin, insulin, amylase, interleukin (IL)-6, keratinocyte-derived chemokine (KC) monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor (TNF)-alpha were evaluated. Results: Treatment with FGF-P rescued a significant fraction of four strains of mice (33-50%) exposed to a lethal dose of sub-TBI. Use of FGF-P improved crypt survival and repopulation and partially preserved or restored GI function. Furthermore, whereas sub-TBI increased plasma endotoxin levels and several pro-inflammation cytokines (IL-6, KC, MCP-1, and TNF-alpha), FGF-P reduced these adverse responses. Conclusions: The study data support pursuing FGF-P as a mitigator for AGS.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Predictors of Androgen Deprivation Therapy Efficacy Combined With Prostatic Irradiation: The Central Role of Tumor Stage and Radiation Dose

Purpose: To evaluate the response of clinically localized prostate cancer to various durations of planned androgen deprivation therapy (ADT) and to investigate subgroups predicting response. Methods and Materials: Data of 3,666 prostate cancer patients treated with either combined ADT and external beam radiotherapy (EBRT) or EBRT alone at four institutions were examined. ADT consisted of neoadjuvant, concurrent, or adjuvant ADT or combinations of these regimens. The primary endpoint was time to biochemical failure (nadir plus 2 ng/ml), assessed from the end of therapy. Factors predictive for the need for ADT were examined with interaction analyses. Results: The impact of increasing ADT duration was nonlinear with, on average, 6 months of adjuvant ADT resulting in a reduction of the risk of biochemical failure by 38% (95% confidence interval [CI], 29%-46%), while 12, 24, and 36 months of ADT resulted in a 58% (95% CI, 47%-67%), 66% (95% CI, 55%-75%), and 66% (95% CI, 51%-77%) relative failure reduction, respectively. Patients with higher T stage cancers and those treated with lower radiation doses had a significantly greater benefit for increasing ADT duration (interaction, p = 0.016 and p = 0.007, respectively). Pretreatment prostate-specific antigen values, Gleason score, age, and risk group did not modify the response to ADT. Conclusions: The known ADT efficacy derived from randomized studies can be generalized to patients with different features, and individual predictions of potential benefit from ADT use and duration may be calculated to aid patient and physician decision making. Tumor stage and radiation dose variations were related to significantly different ADT duration effects. The validity of these predictive factors requires prospective evaluation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2010

Estrogen/Progesterone Receptor Negativity and HER2 Positivity Predict Locoregional Recurrence in Patients With T1a,bN0 Breast Cancer

Purpose: Data have suggested that the molecular features of breast cancer are important determinants of outcome; however, few studies have correlated these features with locoregional recurrence (LRR). In the present study, we evaluated estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) as predictors of LRR in patients with lymph node-negative disease and tumors {<=}1 cm, because these patients often do not receive adjuvant chemotherapy or trastuzumab. Methods and Materials: The data from 911 patients with stage T1a,bN0 breast cancer who had received definitive treatment at our institution between 1997 and 2002 were retrospectively reviewed. We prospectively analyzed ER/PR/HER2 expression from the archival tissue blocks of 756 patients. These 756 patients represented the cohort for the present study. Results: With a median follow-up of 6.0 years, the 5- and 8-year Kaplan-Meier LRR rate was 1.6% and 5.9%, respectively, with no difference noted in those who underwent breast conservation therapy vs. mastectomy (p = .347). The 8-year LRR rates were greater in the patients with ER-negative (10.6% vs. 4.2%, p = .016), PR-negative (9.0% vs. 4.2%, p = .009), or HER2-positive (17.5% vs. 3.9%, p = 0.009) tumors. On multivariate analysis, ER-negative and PR-negative disease (hazard ratio, 2.37; p = .046) and HER2-positive disease (hazard ratio, 3.13, p = .016) independently predicted for LRR. Conclusion: Patients with ER/PR-negative or HER2-positive T1a,bN0 breast cancer had a greater risk of LRR. Therapeutic strategies, such as the use of chemotherapy and/or anti-HER2 therapies, should be considered for future clinical trials for these patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Prostate-Specific Antigen Halving Time While on Neoadjuvant Androgen Deprivation Therapy Is Associated With Biochemical Control in Men Treated With Radiation Therapy for Localized Prostate Cancer

Purpose: To assess whether the PSA response to neoadjuvant androgen deprivation therapy (ADT) is associated with biochemical control in men treated with radiation therapy (RT) for prostate cancer. Methods and Materials: In a cohort of men treated with curative-intent RT for localized prostate cancer between 1988 and 2005, 117 men had PSA values after the first and second months of neoadjuvant ADT. Most men had intermediate-risk (45%) or high-risk (44%) disease. PSA halving time (PSAHT) was calculated by first order kinetics. Median RT dose was 76 Gy and median total duration of ADT was 4 months. Freedom from biochemical failure (FFBF, nadir + 2 definition) was analyzed by PSAHT and absolute PSA nadir before the start of RT. Results: Median follow-up was 45 months. Four-year FFBF was 89%. Median PSAHT was 2 weeks. A faster PSA decline (PSAHT {<=}2 weeks) was associated with greater FFBF (96% vs. 81% for a PSAHT >2 weeks, p = 0.0110). Those within the fastest quartile of PSAHTs ({<=} 10 days) achieved a FFBF of 100%. Among high-risk patients, a PSAHT {<=}2 weeks achieved a 4-yr FFBF of 93% vs. 70% for those with PSAHT >2 weeks (p = 0.0508). Absolute PSA nadir was not associated with FFBF. On multivariable analysis, PSAHT (p = 0.0093) and Gleason score (p = 0.0320) were associated with FFBF, whereas T-stage (p = 0.7363) and initial PSA level (p = 0.9614) were not. Conclusions: For men treated with combined ADT and RT, PSA response to the first month of ADT may be a useful criterion for prognosis and treatment modification.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Acute and Late Toxicity in a Randomized Trial of Conventional Versus Hypofractionated Three-Dimensional Conformal Radiotherapy for Prostate Cancer

Purpose: To compare the toxicity between hypofractionation vs. conventional fractionation schedules in patients with high-risk prostate cancer. Methods and Materials: Between January 2003 and December 2007, 168 patients were randomized to receive either hypofractionated (62 Gy in 20 fractions within 5 weeks, 4 fractions/wk) or conventionally fractionated (80 Gy in 40 fractions within 8 weeks) three-dimensional conformal radiotherapy to the prostate and seminal vesicles. All patients had undergone a 9-month course of total androgen deprivation, with radiotherapy starting 2 months after initiation of the total androgen deprivation. Results: The median follow-up was 32 and 35 months in the hypofractionation and conventional fractionation arms, respectively. For the patients developing acute toxicity, no difference between the two fractionation groups was found in either severity or duration of gastrointestinal or genitourinary toxicity. Also, no difference was found in the incidence and severity of late gastrointestinal and genitourinary toxicity between the two treatment schedules, with a 3-year rate of Grade 2 or greater toxicity of 17% and 16% for the hypofractionation arm and 14% and 11% for the conventional fractionation arm, respectively. A statistically significant correlation between acute and late gastrointestinal toxicity was found only in the conventional fractionation group. Conclusion: Our findings suggest that the hypofractionation regimen used in our study is safe, with only a slight, nonsignificant increase in tolerable and temporary acute toxicity compared with the conventional fractionation schedule. The severity and frequency of late complications was equivalent between the two treatment groups.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Acupuncture for the Alleviation of Hot Flashes in Men Treated With Androgen Ablation Therapy

Purpose: Hot flashes are common side effect due to androgen ablation therapy (AAT). The utility of acupuncture for hot flashes in men has not been thoroughly studied. We prospectively studied the effect of acupuncture in men with hot flashes. Methods and Materials: The study was approved by internal review board. Seventeen men with hot flashes and history of AAT for prostate cancer were enrolled. Three men declined participation before receiving any treatment. A hot flash score (HFS) was used to measure daily hot flashes. The composite daily score was calculated as the product of frequency x severity. The baseline daily scores were compared with scores taken at 2 and 6 weeks and at 8-month average follow-up. Results: No side effects were encountered during, immediately after treatment, or at 8 months. The mean initial HFS was 28.3; it dropped to 10.3 (p = 0.0001) at 2 weeks posttreatment, 7.5 (p = 0.0001) at 6 weeks, and 7.0 (p = 0.001) at 8 months. Clinical improvement for each patient is defined as the percent decrease in the mean HFS at each time point. The mean improvement at Weeks 2 and 6 was 68.4% (mean HFS decreased from 37.409 to 11.836, p = 0.001) and 89.2% (mean HFS decreased from 37.409 to 4.05, p = 0.0078) respectively. The improvement at 8 months was 80.3% (mean HFS decreased from 37.409 to 7.385, p = 0.002). Conclusions: Acupuncture provides excellent control of hot flashes in men with a history of AAT. The absence of side effects and the durable response at 8 months are likely to be appealing to patients. Prospective randomized study is warranted to further evaluate this modality against medical therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2011

Prognostic Impact of Erythropoietin Expression and Erythropoietin Receptor Expression on Locoregional Control and Survival of Patients Irradiated for Stage II/III Non-Small-Cell Lung Cancer

Purpose: Prognostic factors can guide the physician in selecting the optimal treatment for an individual patient. This study investigates the prognostic value of erythropoietin (EPO) and EPO receptor (EPO-R) expression of tumor cells for locoregional control and survival in non-small-cell lung cancer (NSCLC) patients. Methods and Materials: Fourteen factors were investigated in 62 patients irradiated for stage II/III NSCLC, as follows: age, gender, Karnofsky performance score (KPS), histology, grading, TNM/American Joint Committee on Cancer (AJCC) stage, surgery, chemotherapy, pack years (average number of packages of cigarettes smoked per day multiplied by the number of years smoked), smoking during radiotherapy, hemoglobin levels during radiotherapy, EPO expression, and EPO-R expression. Additionally, patients with tumors expressing both EPO and EPO-R were compared to those expressing either EPO or EPO-R and to those expressing neither EPO nor EPO-R. Results: On univariate analysis, improved locoregional control was associated with AJCC stage II cancer (p < 0.048), surgery (p < 0.042), no smoking during radiotherapy (p = 0.024), and no EPO expression (p = 0.001). A trend was observed for a KPS of >70 (p = 0.08), an N stage of 0 to 1 (p = 0.07), and no EPO-R expression (p = 0.10). On multivariate analysis, AJCC stage II and no EPO expression remained significant. No smoking during radiotherapy was almost significant. On univariate analysis, improved survival was associated with N stage 0 to 1 (p = 0.009), surgery (p = 0.039), hemoglobin levels of {>=}12 g/d (p = 0.016), and no EPO expression (p = 0.001). On multivariate analysis, N stage 0 to 1 and no EPO expression maintained significance. Hemoglobin levels of {>=}12 g/d were almost significant. On subgroup analyses, patients with tumors expressing both EPO and EPO-R had worse outcomes than those expressing either EPO or EPO-R and those expressing neither EPO nor RPO-R. Conclusions: EPO expression of tumor cells was an independent prognostic factor for locoregional control and survival in patients irradiated for NSCLC. EPO-R expression showed a trend. Patients with tumors expressing both EPO and EPO-R have an unfavorable prognosis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗