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Femoral Fracture in Primary Soft-Tissue Sarcoma of the Thigh and Groin Treated with Intensity-Modulated Radiation Therapy: Observed versus Expected Risk

Purpose: This study was designed to compare the observed risk of femoral fracture in primary soft-tissue sarcoma (STS) of the thigh/groin treated with intensity-modulated radiation therapy (IMRT) to expected risk calculated using the Princess Margaret Hospital (PMH) nomogram. Methods: Expected femoral fracture risk was calculated by using the PMH nomogram. Cumulative risk of fracture was estimated by using Kaplan–Meier statistics. Prognostic factors were assessed with univariate and multivariate analysis using Cox’s stepwise regression. Results: Between February 2002 and December 2010, 92 consecutive eligible patients were assessed. Median follow-up was 73 months (106 months in surviving patients). IMRT was delivered preoperatively (50 Gy) in 13 (14%) patients and postoperatively in 79 (86%) patients (median dose, 63 Gy; range, 59.4–66.6 Gy). The observed crude risk of fractures was 6.5% compared with 25.6% expected risk from the nomogram; the cumulative risk of fracture using IMRT at 5 years was 6.7% (95% CI 2.8–16.0%). The median time to fracture was 23 months (range, 6.9–88.6). Significant predictors of fracture on univariate analysis were age ≥ 60 years (p = 0.03), tumor location in the anterior thigh (p = 0.008), and periosteal stripping to > 20 cm (p < 0.0001). On multivariate analysis, age ≥ 60 years and periosteal stripping > 20 cm retained significance (p = 0.04 and p = 0.009, respectively). Conclusions: In this study, the cumulative risk of femur fracture in patients treated with IMRT (6.7%) is less than the expected risk using the PMH nomogram (25.6%). Established predictors of femur fracture, such as gender, tumor size, and dose of RT, seem to have less impact on fracture risk when using IMRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Anticipated Intraoperative Electron Beam Boost, External Beam Radiation Therapy, and Limb-Sparing Surgical Resection for Patients with Pediatric Soft-Tissue Sarcomas of the Extremity: A Multicentric Pooled Analysis of Long-Term Outcomes

Purpose: To perform a joint analysis of data from 3 contributing centers within the intraoperative electron-beam radiation therapy (IOERT)-Spanish program, to determine the potential of IOERT as an anticipated boost before external beam radiation therapy in the multidisciplinary treatment of pediatric extremity soft-tissue sarcomas. Methods and Materials: From June 1993 to May 2013, 62 patients (aged <21 years) with a histologic diagnosis of primary extremity soft-tissue sarcoma with absence of distant metastases, undergoing limb-sparing grossly resected surgery, external beam radiation therapy (median dose 40 Gy) and IOERT (median dose 10 Gy) were considered eligible for this analysis. Results: After a median follow-up of 66 months (range, 4-235 months), 10-year local control, disease-free survival, and overall survival was 85%, 76%, and 81%, respectively. In multivariate analysis after adjustment for other covariates, tumor size >5 cm (P=.04) and R1 margin status (P=.04) remained significantly associated with local relapse. In regard to overall survival only margin status (P=.04) retained association on multivariate analysis. Ten patients (16%) reported severe chronic toxicity events (all grade 3). Conclusions: An anticipated IOERT boost allowed for external beam radiation therapy dose reduction, with high local control and acceptably low toxicity rates. The combined radiosurgical approach needs to be tested in a prospective trial to confirm these results.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Do Carbamazepine, Gabapentin, or Other Anticonvulsants Exert Sufficient Radioprotective Effects to Alter Responses From Trigeminal Neuralgia Radiosurgery?

Purpose: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. Methods and Materials: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up {>=}6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Results: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age {<=}70 years, and Type 1 typical trigeminal neuralgia pain compared with 25% (7 of 28), 20% (23 of 114), and 33% (4 of 12) of patients taking no anticonvulsants, age >70 years, and partly atypical Type 2 trigeminal neuralgia, respectively. Conclusions: The use of carbamazepine or gabapentin at the time of radiosurgery does not decrease the rates of obtaining partial or complete pain relief after radiosurgery, but gabapentin may reduce the risks of developing post-radiosurgery trigeminal neuropathy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Effectiveness of Radiotherapy for Elderly Patients With Glioblastoma

Purpose: Radiotherapy plays a central role in the definitive treatment of glioblastoma. However, the optimal management of elderly patients with glioblastoma remains controversial, as the relative benefit in this patient population is unclear. To better understand the role that radiation plays in the treatment of glioblastoma in the elderly, we analyzed factors influencing patient survival using a large population-based registry. Methods and Materials: A total of 2,836 patients more than 70 years of age diagnosed with glioblastoma between 1993 and 2005 were identified from the Surveillance, Epidemiology, and End Results (SEER) registry. Demographic and clinical variables used in the analysis included gender, ethnicity, tumor size, age at diagnosis, surgery, and radiotherapy. Cancer-specific survival and overall survival were evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using Cox regression. Results: Radiotherapy was administered in 64% of these patients, and surgery was performed in 68%. Among 2,836 patients, 46% received surgery and radiotherapy, 22% underwent surgery only, 18% underwent radiotherapy only, and 14% did not undergo either treatment. The median survival for patients who underwent surgery and radiotherapy was 8 months. The median survival for patients who underwent radiotherapy only was 4 months, and for patients who underwent surgery only was 3 months. Those who received neither surgery nor radiotherapy had a median survival of 2 months (p < 0.001). Multivariate analysis showed that radiotherapy significantly improved cancer-specific survival (hazard ratio [HR], 0.43, 95% confidence interval [CI] 0.38-0.49) after adjusting for surgery, tumor size, gender, ethnicity, and age at diagnosis. Other factors associated with Cancer-specific survival included surgery, tumor size, age at diagnosis, and ethnicity. Analysis using overall survival as the endpoint yielded very similar results. Conclusions: Elderly patients with glioblastoma who underwent radiotherapy had improved cancer-specific survival and overall survival compared to patients who did not receive radiotherapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Neoadjuvant Chemoradiation Therapy Using Concurrent S-1 and Irinotecan in Rectal Cancer: Impact on Long-Term Clinical Outcomes and Prognostic Factors

Purpose: To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy. Methods and Materials: The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months. Results: Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung. Conclusions: NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Evaluation of the Role of Radiation Therapy in the Management of Malignant Thymoma

Purpose: The management of patients diagnosed with thymoma remains unclear. This report attempts to identify the impact of adjuvant radiotherapy on overall survival (OS) and cause-specific survival (CSS) in patients diagnosed with thymoma. Methods and Materials: Patients diagnosed with thymic malignancy between 1973 and 2003 were retrospectively identified from centers participating in the Surveillance, Epidemiology, and End Results (SEER) program. Those patients classified as having thymic carcinoma were excluded from this analysis. OS and CSS were estimated by the Kaplan-Meier method. Outcomes for patients treated with and without radiation therapy were compared using the log-rank test. Multivariate analysis was performed with the Cox proportional hazards model to analyze factors predictive of OS and CSS. Results: A total of 1,464 patients were identified as having thymic malignancy, and of these, 1,254 patients were identified as having malignant thymoma. The median follow-up time was 41 months (range, 4-337 months). Among patients who did not receive radiotherapy (RT), the 10-year rate of OS was 41% compared to 42% for those who did receive RT (p = 0.06). The median OS for the patients who did not receive RT was 80 months compared to 97 months for those who did receive RT. In patients with Masaoka stage II-III malignancy, OS was significantly improved with RT (p = 0.002), and a trend in improved CSS was observed (p = 0.1). Patients were also analyzed based on resection status. For those patients who had an incomplete excision, the 10-year OS was 63% with RT and 46% without RT (p = 0.38). On multivariate analysis, factors predictive of OS included age, extent of surgery, stage, and number of lymph nodes examined. Conclusions: This study reports treatment results of a large cohort of patients who were diagnosed with malignant thymoma. This study demonstrates that the use of RT following resection for thymoma significantly improves OS for those with regional disease and marginally improves CSS.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

UNCOVERING THE FORMATION OF ULTRACOMPACT DWARF GALAXIES BY MULTIVARIATE STATISTICAL ANALYSIS

We present a statistical analysis of the properties of a large sample of dynamically hot old stellar systems, from globular clusters (GCs) to giant ellipticals, which was performed in order to investigate the origin of ultracompact dwarf galaxies (UCDs). The data were mostly drawn from Forbes et al. We recalculated some of the effective radii, computed mean surface brightnesses and mass-to-light ratios, and estimated ages and metallicities. We completed the sample with GCs of M31. We used a multivariate statistical technique (K-Means clustering), together with a new algorithm (Gap Statistics) for finding the optimum number of homogeneous sub-groups in the sample, using a total of six parameters (absolute magnitude, effective radius, virial mass-to-light ratio, stellar mass-to-light ratio, and metallicity). We found six groups. FK1 and FK5 are composed of high- and low-mass elliptical galaxies, respectively. FK3 and FK6 are composed of high-metallicity and low-metallicity objects, respectively, and both include GCs and UCDs. Two very small groups, FK2 and FK4, are composed of Local Group dwarf spheroidals. Our groups differ in their mean masses and virial mass-to-light ratios. The relations between these two parameters are also different for the various groups. The probability density distributions of metallicity for the four groups of galaxies are similar to those of the GCs and UCDs. The brightest low-metallicity GCs and UCDs tend to follow the mass-metallicity relation like elliptical galaxies. The objects of FK3 are more metal-rich per unit effective luminosity density than high-mass ellipticals.

79 ASTRONOMY AND ASTROPHYSICS↗

PSA Response to Neoadjuvant Androgen Deprivation Therapy Is a Strong Independent Predictor of Survival in High-Risk Prostate Cancer in the Dose-Escalated Radiation Therapy Era

Purpose: The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. Methods and Materials: We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specific mortality (PCSM) and overall survival (OS) were examined. Results: A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs {>=}0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. Conclusions: For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level {>=}0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level {>=}0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The Significance of Tumoral ERCC1 Status in Patients With Locally Advanced Cervical Cancer Treated With Chemoradiation Therapy: A Multicenter Clinicopathologic Analysis

Purpose: ERCC1 (excision repair cross-complementation group 1) expression has been shown to be a molecular marker of cisplatin resistance in many tumor sites, but has not been well studied in cervical cancer patients. The purpose of this study was to measure tumoral ERCC1 in patients with locally advanced cervical cancer treated with chemoradiation therapy (CRT) in a large multicenter cohort, and to correlate expression with clinical outcome parameters. Methods and Materials: A total of 264 patients with locally advanced cervical cancer, treated with curative-intent radical CRT from 3 major Canadian cancer centers were evaluated. Pretreatment formalin-fixed, paraffin-embedded tumor specimens were retrieved, and tissue microarrays were constructed. Tumoral ERCC1 (FL297 antibody) was measured using AQUA (R) technology. Statistical analysis was performed to determine the significance of clinical factors and ERCC1 status with progression-free survival (PFS) and overall survival (OS) at 5 years. Results: The majority of patients had International Federation of Gynecology and Obstetrics (FIGO) stage II disease (n=119, 45%); median tumor size was 5 cm. OS was associated with tumor size (HR 1.16, P=.018), pretreatment hemoglobin status (HR 2.33, P=.00027), and FIGO stage. In addition, tumoral ERCC1 status (nuclear to cytoplasmic ratio) was associated with PFS (HR 2.33 [1.05-5.18], P=.038) and OS (HR 3.13 [1.27-7.71], P=.013). ERCC1 status was not significant on multivariate analysis when the model was adjusted for the clinical factors: for PFS (HR 1.49 [0.61-3.6], P=.38); for OS (HR 2.42 [0.94-6.24] P=.067). Conclusions: In this large multicenter cohort of locally advanced cervical cancer patients treated with radical CRT, stage, tumor size, and pretreatment hemoglobin status were significantly associated with PFS and OS. ERCC1 status appears to have prognostic impact on univariate analysis in these patients, but was not independently associated with outcome on multivariate analysis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Impact of Neoadjuvant Prostate-Specific Antigen Kinetics on Biochemical Failure and Prostate Cancer Mortality: Results From a Prospective Patient Database

Purpose: To confirm findings from an earlier report showing that neoadjuvant (NA) prostate-specific antigen (PSA) halving time (PSAHT) impacts biochemical failure (BF) rates, and to examine its association with prostate cancer-specific survival (PCSS), in a large prospective cohort of patients. Methods and Materials: A total of 502 patients were selected from a prospective database, who had localized prostate adenocarcinoma treated with 2-12 months of neoadjuvant androgen deprivation therapy (N-ADT) followed by external beam radiation therapy (EBRT) between 1994 and 2000, and had at least 2 NA PSA values. Seventy-four percent of patients had high-risk prostate cancer. Median initial PSA value, N-ADT duration, total ADT duration, and radiation therapy dose were 14 ng/mL, 6.9 months, 10.8 months, and 68 Gy, respectively. Results: At a median follow-up of 9.9 years, 210 patients have had a BF. Median PSAHT was 18 days. On univariate analysis, PSAHT was not shown to predict for BF (P=.69) or PCSS (P=.28). However, NA nadir PSA (nanPSA) and post-therapy nadir PSA (ptnPSA), when analyzed as continuous or categoric variables, predicted for BF (P<.001) and PCSS (P<.001). On multivariate analysis, nanPSA (P=.037) and ptnPSA (P<.001) continued to be significantly associated with BF. However, N-ADT duration lost significance (P=.67), and PSAHT remained a nonsignificant predictor (P=.97). For PCSS, multivariate analysis showed nanPSA (P=.049) and ptnPSA (P<.001) to be significant. Again PSAHT (P=.49) remained nonsignificant. Conclusions: In this large, prospective cohort of patients, NA PSA kinetics, expressed as PSAHT, did not predict BF or PCSS. However, nadir PSAs, in both the NA and post-therapy settings, were significant predictors of BF and PCSS. Optimization of therapy could potentially be based on early PSA response, with shorter durations of ADT for those predicted to do favorably, and intensification of therapy for those likely to have poorer outcomes.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Hemobilia after CT-guided radiofrequency ablation of liver tumors: frequency, risk factors, and clinical significance

Purpose: The purpose of the study is to evaluate the frequency, risk factors, and clinical significance of hemobilia after percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) of liver tumors. Materials and methods: From January 2013 to September 2016, 195 patients received 267 sessions of CT-guided RFA for liver tumors at our institution. The CT images during and immediately after the RFA were retrospectively reviewed. The frequency of hemobilia development and clinical outcome of patients with hemobilia were studied. Risk factors were identified by comparison between the hemobilia and non-hemobilia groups using univariate and multivariate analysis. The clinical courses of patients with hemobilia were also reviewed. Results: The frequency of CT detected hemobilia after RFA was 8.2% (22/267). The majority of the clinical courses were self-limited. Univariate analysis showed that the tumor numbers (p = 0.015), the central type puncture track (p < 0.001), the length of the puncture track (p = 0.033), and the platelet count (p = 0.026) were significantly associated with the development of hemobilia. Multivariate analysis demonstrated that the central type puncture track (p < 0.024) and the platelet count (p = 0.023) were significant independent risk factors. Conclusion: Detection of hemobilia on CT images immediately after percutaneous RFA for liver tumors was not rare. Low platelet count and central type puncture track are independent risk factors. In most cases, hemobilia presented as a minor complication with favorable prognosis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Prediction of Chest Wall Toxicity From Lung Stereotactic Body Radiotherapy (SBRT)

Purpose: To determine patient, tumor, and treatment factors related to the development of late chest wall toxicity after lung stereotactic body radiotherapy (SBRT). Methods and Materials: We reviewed a registry of 134 patients treated with lung SBRT to 60 Gy in 3 fractions who had greater than 1 year of clinical follow-up and no history of multiple treatments to the same lobe (n = 48). Patients were treated as per Radiation Therapy Oncology Group Protocol 0236 without specific chest wall avoidance criteria. The chest wall was retrospectively contoured. Thirty-two lesions measured less than 3 cm, and sixteen measured 3 to 5 cm. The median planning target volume was 29 cm{sup 3}. Results: With a median follow-up of 18.8 months, 10 patients had late symptomatic chest wall toxicity (4 Grade 1 and 6 Grade 2) at a median of 8.8 months after SBRT. No patient characteristics (age, diabetes, hypertension, peripheral vascular disease, or body mass index) were predictive for toxicity, whereas there was a trend for continued smoking (p = 0.066; odds ratio [OR], 4.4). Greatest single tumor dimension (p = 0.047; OR, 2.63) and planning target volume (p = 0.040; OR, 1.04) were correlated with toxicity, whereas distance from tumor edge to chest wall and gross tumor volume did not reach statistical significance. Volumes of chest wall receiving 30 Gy (V30) through 70 Gy (V70) were all highly significant, although this correlation weakened for V65 and V70 and maximum chest wall point dose only trended to significance (p = 0.06). On multivariate analysis, tumor volume was no longer correlated with toxicity and only V30 through V60 remained statistically significant. Conclusions: Tumor size and chest wall dosimetry are correlated to late chest wall toxicity. Only chest wall V30 through V60 remained significant on multivariate analysis. Restricting V30 to 30 cm{sup 3} or less and V60 to 3 cm{sup 3} or less should result in a 10% to 15% risk of late chest wall toxicity or lower.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Dark Photon Search at BABAR

Presented is the current progress of a search for the signature of a dark photon or new particle using the BaBar data set. We search for the processes e + e - → γ ISR A', A' → e + e - and e + e - → γ ISR γ,γ → A', A' → e + e - , where γ ISR is an initial state radiated photon of energy E γ >= 1 GeV. Twenty-five sets of Monte Carlo, simulating e + e - collisions at an energy of 10.58 GeV, were produced with different values of the A' mass ranging from 100 MeV to 9.5 GeV. The mass resolution is calculated based on Monte Carlo simulations. We implement ROOT's Toolkit for Multivariate Analysis (TMVA), a machine learning tool that allows us to evaluate the signal character of events based on many of discriminating variables. TMVA training is conducted with samples of Monte Carlo as signal and a small portion of Run 6 as background. The multivariate analysis produces additional cuts to separate signal and background. The signal efficiency and sensitivity are calculated. The analysis will move forward to fit the background and scan the residuals for the narrow resonance peak of a new particle.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Proton Beam Therapy for Hepatocellular Carcinoma: A Comparison of Three Treatment Protocols

Background: Our previous results for treatment of hepatocellular carcinoma (HCC) with proton beam therapy revealed excellent local control with low toxicity. Three protocols were used to avoid late complications such as gastrointestinal ulceration and bile duct stenosis. In this study, we examined the efficacy of these protocols. Methods and Materials: The subjects were 266 patients (273 HCCs) treated by proton beam therapy at University of Tsukuba between January 2001 and December 2007. Three treatment protocols (A, 66 GyE in 10 fractions; B, 72.6 GyE in 22 fractions; and C, 77 GyE in 35 fractions) were used, depending on the tumor location. Results: Of the 266 patients, 104, 95, and 60 patients were treated with protocols A, B, and C, respectively. Seven patients with double lesions underwent two different protocols. The overall survival rates after 1, 3 and 5 years were 87%, 61%, and 48%, respectively (median survival, 4.2 years). Multivariate analysis showed that better liver function, small clinical target volume, and no prior treatment (outside the irradiated field) were associated with good survival. The local control rates after 1, 3, and 5 years were 98%, 87%, and 81%, respectively. Multivariate analysis did not identify any factors associated with good local control. Conclusions: This study showed that proton beam therapy achieved good local control for HCC using each of three treatment protocols. This suggests that selection of treatment schedules based on tumor location may be used to reduce the risk of late toxicity and maintain good treatment efficacy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64 months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Which Criteria Applied in Multi-Phasic CT Can Predict Early Tumor Response in Patients with Hepatocellular Carcinoma Treated Using Conventional TACE: RECIST, mRECIST, EASL or qEASL?

PurposeOur study aimed to evaluate quantitative tumor response assessment (quantitative EASL-[qEASL]) on computed tomography (CT) images in patients with hepatocellular carcinoma (HCC) treated using conventional transarterial chemoembolization (cTACE), compared to existing 1-dimensional and 2-dimensional methods (RECIST, mRECIST, EASL).Materials and MethodsIn this IRB-approved, single-institution retrospective cohort study, 52 consecutive patients with intermediate-stage HCC were consecutively included. All patients underwent contrast-enhanced CT scan at baseline and 4 weeks after cTACE.ResultsMedian follow-up period was 13.5 months (range 1.2–54.1). RECIST, mRECIST and EASL identified progression in 2 (4%), 1 (2%) and 1 (2%) patients, respectively, whereas qEASL identified 10 (19%) patients. qEASL was the only tumor response method able to predict survival among different tumor response groups (P < 0.05), whereas RECIST, mRECIST and EASL did not (P > 0.05). Both EASL and qEASL were able to identify responders and non-responders and were predictive of survival (P < 0.05). Multivariate analysis showed that progression was an independent predictor of overall survival with hazard ratio of 1.9 (P = 0.025). Patients who demonstrated progression with qEASL had significantly shorter survival than those with non-progression (7.6 vs. 20.4 months, P = 0.012). Similar multivariate analysis using RECIST, mRECIST and EASL could not be performed because too few patients were categorized as progressive disease.ConclusionqEASL could be applied on CT images to assess tumor response following cTACE and is a more sensitive biomarker to predict survival and identify tumor progression than RECIST, mRECIST and EASL at an early time point.Level of EvidenceLevel 2a, retrospective cohort study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma

Purpose: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). Patients and Methods: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse–free survival (LRFS) and distant metastasis–free survival (DMFS). Results: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels after NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). Conclusion: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗