Search

External beam radiation therapy (EBRT) dose escalation has been tested in multiple prospective trials. However, the impact on patient reported outcomes (PROs) associated with higher doses of EBRT remain poorly understood. We sought to assess the differences in PROs between men treated with a dose of 70.2 Gy versus 79.2 Gy of EBRT for prostate cancer.The phase 3 clinical trial RTOG 0126 randomized 1532 patients with prostate cancer between March 2002 and August 2008 to 79.2 Gy over 44 fractions versus 70.2 Gy over 39 fractions. Eligible patients participated in the PRO data collection. PROs completed included the International Index of Erectile Function Questionnaire (IIEF), Functional Alterations due to Changes in Elimination (FACE), and the Spitzer Quality of Life Index (SQLI). The timepoints for the IIEF were collected pre-entry and at 6, 12, and 24 months. The FACE and SQLI were collected pre-entry and at 3, 6, 12, 18, and 24 months. The impact of EBRT dose to normal structures (penile bulb, rectum, and bladder) on PROs was also examined. Mixed effects models were used to analyze trends across time.In total, 1144 patients completed baseline IIEF forms and of these, 56%, 64%, and 61% completed the IIEF at 6, 12, and 24 months, respectively; 1123 patients completed the FACE score at baseline and 50%, 61%, 73%, 61%, and 65% completed all 15 items for the FACE metric at timepoints of 3, 6, 12, 18, and 24 months, respectively. Erectile dysfunction at 12 months based on the single question was not significantly different between arms (38.1% for the standard dose radiation therapy arm vs 49.7% for the dose escalated radiation therapy arm; P = .051). Treatment arm (70.2 vs 79.2) had no significant impact on any PRO metrics measured across all collected domains. Comprehensive dosimetric analyses are presented and reveal multiple significant differences to regional organs at risk.Compliance with PRO data collection was lower than anticipated in this phase 3 trial. Examining the available data, dose escalated EBRT did not appear to be associated with any detriment to PROs across numerous prospectively collected domains. These data, notwithstanding limitations, add to our understanding of the implications of EBRT dose escalation in prostate cancer. Furthermore, these results illustrate challenges associated with PRO data collection.

PURPOSE: To report the long-term outcomes of the RTOG 0424 study of a high-risk, low-grade glioma population treated with concurrent and adjuvant temozolomide (TMZ) and radiation therapy (RT). METHODS AND MATERIALS: For this single-arm, phase 2 study, patients with low-grade gliomas with ≥3 risk factors (age ≥40 years, astrocytoma, bihemispheric tumor, size ≥6 cm, or preoperative neurologic function status >1) received RT (54 Gy in 30 fractions) with TMZ and up to 12 cycles of post-RT TMZ. The initial primary endpoint P was overall survival (OS) at 3 years after registration. Secondary endpoints included progression-free survival (PFS) and the association of survival outcomes with methylation status. The initial 3-year report of this study was published in 2015. RESULTS: The study accrued 136 patients, of whom 129 were analyzable. The median follow-up for surviving patients was 9.0 years. The 3-year OS was 73.5% (95% confidence interval, 65.8%−81.1%), numerically superior to the 3-year OS historical control of 54% (P < .001). The median survival time was 8.2 years (95% confidence interval, 5.6–9.1). Five- and 10-year OS rates were 60.9% and 34.6%, respectively, and 5- and 10-year PFS rates were 46.8% and 25.5%, respectively. CONCLUSIONS: The long-term results confirmed the findings from the initial report for efficacy, suggesting OS and PFS outcomes with the RT-TMZ regimen exceeded historical control groups treated with radiation alone. Toxicity was acceptable.

PURPOSE/OBJECTIVE(S) To validate the association between body composition and all-cause mortality in men treated with radiation therapy for localized prostate cancer (PCa). Secondarily, to integrate body composition as a factor to help classify patients by risk of all-cause mortality. MATERIALS/METHODS All participants of NRG/RTOG 9406 and NRG/RTOG 0126 with archived computed tomography that extended cranially to include the L4-L5 interface were included. Muscle mass and muscle density were estimated by measuring the cross-sectional area and average attenuation of the paired psoas muscles on a single slice at the level of L4-L5. Bone density was estimated by measuring the average attenuation of the vertebral body cancellous bone on a single slice at mid-L5. Adipose tissue density was estimated by measuring the average attenuation of the subcutaneous adipose tissue on a single slice at L4-L5. Survival analyses, including Cox proportional hazards models, were performed to assess the relationship between body composition variables and all-cause mortality. Recursive partitioning (RPA) was utilized to create a classification tree to classify NRG/RTOG 0126 participants by risk of death, and the discriminant ability of the classification model was validated using the NRG/RTOG 9406 data set. RESULTS Data from 2,066 men was included in this study (864 from NRG/RTOG 9406 and 1,202 from NRG/RTOG 0126). A total of 648 men died in the follow-up period and 51 (7.9%) were due to PCa. Psoas area, psoas density, and vertebral body density were individually associated with overall survival. In the final multivariable model, psoas area, comorbidity score, and age were associated with overall survival (Table). The RPA yielded a classification tree with 4 prognostic groups determined by age, comorbidity, and psoas cross-sectional area. When the RPA classification was applied to the NRG/RTOG 9406 validation set the discriminant ability was preserved (P < 0.001 groupwise log-rank). CONCLUSION The results of this study strongly support that body composition is related to all-cause mortality in men with localized PCa, with most deaths due to causes other than PCa. The inclusion of psoas cross-sectional area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction. This study also confirms the feasibility of performing body composition analysis using archived CT scans using NRG Oncology clinical trial data sets. These methods can be applied to other NRG Oncology data sets to further explore how body composition is related to patient outcomes.

Background Long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) is a standard treatment for patients with localized high-risk prostate cancer (HRPC). However, the optimal duration of ADT is not yet defined. Objective The aim of this superiority randomized trial was to compare outcomes of RT combined with either 36 or 18 mo of ADT. Design, setting and participants From October 2000 to January 2008, 630 patients with HRPC were randomized, 310 to pelvic and prostate RT combined with 36 mo (long arm) and 320 to the same RT with 18 mo (short arm) of ADT. Outcome measurements and statistical analysis Overall survival (OS) and quality of life (QoL) were primary end points. OS rates were compared with Cox Regression model and QoL data were analyzed through mixed linear model. Results and limitations With a median follow-up of 9.4 yr, 290 patients had died (147 long arm vs 143 short arm). The 5-yr OS rates (95% confidence interval) were 91% for long arm (88–95%) and 86% for short arm (83–90%), p=0.07. QoL analysis showed a significant difference (p Conclusions In localized HRPC, our results support that 36 mo is not superior to 18 mo of ADT. ADT combined with RT can potentially be reduced to 18 mo in selected men without compromising survival or QoL. Thus, 18 mo of ADT appears to represent a valid option in HRPC. Patient summary In this study, we report outcomes from high-risk prostate cancer patients treated with radiotherapy and either 36 or 18 mo of androgen deprivation therapy. There was no difference in survival between the two groups, with the 18-mo group experiencing a better quality of life.

Purpose The aim of this study was to compare early prostate-specific antigen (PSA) decline patterns and PSA nadirs between low-dose-rate seed prostate brachytherapy (LDR-PB) and different fractionations of external beam radiotherapy (EBRT) and their predictive importance for biochemical failure (bF). Methods and Materials Patients with D'Amico low- or intermediate-risk prostate cancer who underwent a single-modality treatment without androgen deprivation were included in this study. Three different treatment groups were compared: (1) normofractionation EBRT up to 70.2–79.2 Gy/1.8–2.0 Gy, (2) LDR-PB, and (3) EBRT with hypofractionation 60 Gy/3 Gy daily or 5–7.25 Gy once a week over 9–5 weeks, to a total dose of 45–36.25 Gy, respectively. The log-rank test, Cox regression analysis, and nonparametric tests were used. Results We analyzed 892 patients: the median followup for patients without bF was 84 months (interquartile range 60–102 months), with 12% of patients experiencing bF. The PSA decline within the first 15 months was generally exponential. LDR-PB showed a faster early exponential decline compared with EBRT treatments, but whether decline was fast or slow had no influence on recurrence. The only factors that were positive predictive factors in univariate and multivariate analyses were the time to nadir >48 months (median), PSA nadir Conclusions Although there are significant differences in early exponential PSA decline between different treatments, only the PSA nadir and longer time to nadir were predictive factors for bF.

Radiation Therapy Oncology Group (RTOG) 0424 was a phase 2 study of a high-risk low-grade glioma (LGG) population who were treated with temozolomide (TMZ) and radiation therapy (RT), and outcomes were compared to those of historical controls. This study was designed to detect a 43% increase in median survival time (MST) from 40.5 to 57.9 months and a 20% improvement in 3-year overall survival (OS) rate from 54% to 65% at a 10% significance level (1-sided) and 96% power.Patients with LGGs with 3 or more risk factors for recurrence (age ≥40 years, astrocytoma histology, bihemispherical tumor, preoperative tumor diameter of ≥6 cm, or a preoperative neurological function status of1) were treated with RT (54 Gy in 30 fractions) and concurrent and adjuvant TMZ.From 2005 to 2009, 129 evaluable patients (75 males and 54 females) were accrued. Median age was 49 years; 91% had a Zubrod score of 0 or 1; and 69%, 25%, and 6% of patients had 3, 4, and 5 risk factors, respectively. Patients had median and minimum follow-up examinations of 4.1 years and 3 years, respectively. The 3-year OS rate was 73.1% (95% confidence interval: 65.3%-80.8%), which was significantly improved compared to that of prespecified historical control values (P.001). Median survival time has not yet been reached. Three-year progression-free survival was 59.2%. Grades 3 and 4 adverse events occurred in 43% and 10% of patients, respectively. One patient died of herpes encephalitis.The 3-year OS rate of 73.1% for RTOG 0424 high-risk LGG patients is higher than that reported for historical controls (P.001) and the study-hypothesized rate of 65%.

Purpose: Radiation Therapy Oncology Group (RTOG) 9508 showed a survival advantage for patients with 1 but not 2 or 3 brain metastasis (BM) treated with whole-brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) versus WBRT alone. An improved prognostic index, the graded prognostic assessment (GPA) has been developed. Our hypothesis was that if the data from RTOG 9508 were poststratified by the GPA, the conclusions may vary. Methods and Materials: In this analysis, 252 of the 331 patients were evaluable by GPA. Of those, 211 had lung cancer. Breast cancer patients were excluded because the components of the breast GPA are not in the RTOG database. Multiple Cox regression was used to compare survival between treatment groups, adjusting for GPA. Treatment comparisons within subgroups were performed with the log-rank test. A free online tool ( (brainmetgpa.com)) simplified GPA use. Results: The fundamental conclusions of the primary analysis were confirmed in that there was no survival benefit overall for patients with 1 to 3 metastases; however, there was a benefit for the subset of patients with GPA 3.5 to 4.0 (median survival time [MST] for WBRT + SRS vs WBRT alone was 21.0 versus 10.3 months, P=.05) regardless of the numbermore » of metastases. Among patients with GPA 3.5 to 4.0 treated with WBRT and SRS, the MST for patients with 1 versus 2 to 3 metastases was 21 and 14.1 months, respectively. Conclusions: This secondary analysis of predominantly lung cancer patients, consistent with the original analysis, shows no survival advantage for the group overall when treated with WBRT and SRS; however, in patients with high GPA (3.5-4), there is a survival advantage regardless of whether they have 1, 2, or 3 BM. This benefit did not extend to patients with lower GPA. Prospective validation of this survival benefit for patients with multiple BM and high GPA when treated with WBRT and SRS is warranted.« less

Purpose To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial. Methods and Materials The trial was initiated with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects. Results Of 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P P =.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity ( P =.099). Acute G2+ toxicity was associated with late G3+ toxicity ( P =.005). With dose–volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race ( P =.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity ( P =.034). Conclusions Intensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a clinically meaningful reduction in late G2+ GI toxicity with IMRT. The occurrence of acute GI toxicity and large (>15%) volumes of rectum >70 Gy are associated with late rectal toxicity.

The association of Ki-67 staining index (Ki67-SI) with overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), and biochemical failure (BF) was examined in men with favorable- to intermediate-risk prostate cancer receiving radiation therapy (RT) alone or with short-term androgen deprivation (ADT) in Radiation Therapy Oncology Group (RTOG) 94-08.468 patients (23.6%) on RTOG 94-08 had sufficient tissue for Ki67-SI analysis. The median follow-up time was 7.9 years. Ki67-SI was determined by immunohistochemistry and quantified manually and by image analysis. Correlative analysis versus clinical outcome was performed using the third quartile (≥Q3) cutpoint. A proportional hazards multivariable analysis (MVA) dichotomized covariates in accordance with trial stratification and randomization criteria.In MVAs adjusted for all treatment covariates, high Ki67-SI (≥Q3) was correlated with increased DSM (hazard ratio [HR] 2.48, P=.03), DM (HR 3.5, P=.002), and BF (HR 3.55, P.0001). MVA revealed similar Ki67-associated hazard ratios in each separate treatment arm for DSM, DM, and BF; these reached significance only for DM in the RT-alone arm and for BF in both arms. Ki67-SI was not a significant predictor of intraprostatic recurrence assessed by repeated biopsy 2 years after treatment. Patients with a high or low Ki67-SI seemed to experience a similar relative benefit from the addition of ADT to radiation.High Ki67-SI independently predicts for increased DSM, DM, and protocol BF in primarily intermediate-risk prostate cancer patients treated with RT with or without ADT on RTOG 94-08 but does not predict for local recurrence or for increased relative benefit from ADT. This and prior studies lend support for the use of Ki67-SI as a stratification factor in future trials.

To study the influence of an exponential prostate-specific antigen (PSA) decline on biochemical failure after external-beam radiotherapy (EBRT).We analyzed 114 patients with intermediate risk prostate cancer (Gleason≤6 and PSA 10-20 or Gleason 7 and PSA10). Patients were randomized between EBRT doses of either 70.2 Gy or 79.2 Gy (1.8 Gy per day). All patients had a follow up of at least six PSA measurements post-EBRT. Exponential decline and PSA half life were included in a Cox regression analysis for factors associated with biochemical failure.A total of 80/114 (70.2%) patterns were classified as having an exponential PSA decline. Both exponential decline (HR 0.115, 95%CI 0.03-0.44, p=0.0016) and PSA half life ratio were statistically significant predictors (HR 1.03 (95% CI 1.01-1.06)) of biochemical failure. In the model predicting for exponential decline, none of the factors were significant.Patients with an exponential PSA decline show a better biochemical outcome in the long term.

OBJECTIVES We conducted a secondary analysis of the Radiation Therapy Oncology Group protocol 9413 to compare whether the timing of antiandrogen therapy (concomitant versus adjuvant) and testosterone levels influences the incidence of rectal and urinary toxicity in whole pelvic radiotherapy. METHODS We analyzed two of four study arms, in which all patients received radiotherapy to the whole pelvis followed by a boost to the prostate. The two arms differed solely in the timing of the total of 4 months of total androgen deprivation: arm I (320 patients, given concomitantly) and arm III (319 patients, given as adjuvant therapy). The influence of testosterone levels (measured at baseline and yearly thereafter) and its recovery on late rectal and urinary toxicity were modeled by multivariate logistic regression analysis and Fine and Gray's regression models. RESULTS The occurrence of late rectal toxicity (grade 0-1 versus 2-5, P = 0.16) and late urinary toxicity (grade 0-1 versus 2-5, P = 0.52) was not significantly different statistically between the two arms. The time to testosterone recovery was significantly lower in the adjuvant arm (mean difference of 3.2 months, P = 0.0103). Age and radiation field size are statistically significant risk factors for late urinary toxicity (P = 0.01 and P = 0.02). Baseline testosterone levels, before beginning total androgen deprivation, were a statistically significant predictive factor for late urinary toxicity (P = 0.03). CONCLUSIONS Older patients and patients with low testosterone levels at baseline are risk factors for late urinary and rectal toxicities, possibly through impaired tissue repair.

Purpose Because of the low alpha/beta value of prostate cancer, a therapeutic gain may be possible with a hypofractionated radiation scheme, and this gain may be further increased with the adjunct of hormone therapy. A Phase II study was undertaken to study the toxicity of such a treatment. Methods and Materials Forty-two patients with intermediate-risk prostate cancer were recruited for this study. Neoadjuvant and concomitant hormone therapy consisted of one injection of leuprolide acetate (4-month preparation) and 1 month of oral nonsteroidal, anti-androgen medication starting on the day of the injection. Radiation treatment was started 8 weeks after the injection and patients received 57 Gy in 19 fractions. Results Median follow-up was 46 months. The treatment was well tolerated and no interruptions occurred. The majority (59%) had Grade 0 or 1 acute genitourinary (GU) toxicity, whereas 36% had Grade 2 and 5% had Grade 3 acute GU toxicity. Only Grade 1 or 2 gastrointestinal toxicity was seen. All chronic toxicity was of Grade 1 or 2 except for 3 patients (8%) with Grade 3 toxicity. Sixty-eight percent (68%) of patients had no long-term side effects from the treatment. At time of analysis, 79% showed no sign of treatment failure. Conclusions Hypofractionated radiation with neoadjuvant and concomitant hormone therapy is well tolerated with no significant short- or long-term morbidity. Control for this risk group is good, and comparative Phase III studies should be undertaken to determine whether this treatment is superior to new evolving treatments.

Introduction: Glioblastoma multiforme's (GBM) aggressiveness is potentiated in radioresistant tumor cells. The combination of radiotherapy and chemotherapy has been envisioned as a therapeutic approach for GBM. The goal of this study is to determine if epigallocatechin-3-gallate (EGCg), a green tea-derived anti-cancer molecule, can modulate GBMs' response to ionizing radiation (IR) and whether this involves mediators of intracellular signaling and inhibitors of apoptosis proteins. Material and methods: U-87 human GBM cells were cultured and transfected with cDNAs encoding for Survivin, RhoA or Caveolin-1. Mock and transfected cells were irradiated at sublethal single doses. Cell proliferation was analyzed by nuclear cell counting. Apoptosis was detected using a fluorometric caspase-3 assay. Analysis of protein expression was accomplished by Western immunoblotting. Results: IR (10 Gy) reduced control U-87 cell proliferation by 40% through a caspase-independent mechanism. The overexpression of Survivin induced a cytoprotective effect against IR, while the overexpression of RhoA conferred a cytosensitizing effect upon IR. Control U-87 cells pretreated with EGCg exhibited a dose-dependent decrease in their proliferation rate. The growth inhibitory effect of EGCg was not antagonized by overexpressed Survivin. However, Survivin -transfected cells pretreated with EGCg became sensitive to IR, and their RhoA expression was downregulated. A potential therapeutic effect of EGCg targeting the prosurvival intracellular pathways of cancer cells is suggested to act synergistically with IR. Conclusion: The radioresistance of GBM is possibly mediated by a mechanism dependent on Survivin in conjunction with RhoA. The combination of natural anti-cancerous molecules such as EGCg with radiotherapy could improve the efficacy of IR treatments.

Patient-Reported Outcomes in NRG Oncology/RTOG 0938, a Randomized Phase 2 Study Evaluating 2 Ultrahypofractionated Regimens (UHRs) for Prostate Cancer H. Lukka, P. Stephanie, D. Bruner, J.P. Bahary, C.A.F. Lawton, J.A. Efstathiou, R. Kudchadker, L. Ponsky, S.A. Seaward, I.S. Dayes, D.D. Gopaul, J.M. Michalski, G. Delouya, I.D. Kaplan, E.M. Horwitz, M. Roach, III, W.H. Pinover, D.C. Beyer, H.M. Sandler, and L.A. Kachnic; Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON, Canada, NRG Oncology Statistics and Data Management Center, Philadelphia, PA, Emory University, Atlanta, GA, Hopital Notre-Dame du CHUM, Montreal, QC, Canada, Medical College of Wisconsin, Milwaukee, WI, Massachusetts General Hospital, Harvard Medical School, Boston, MA, MD Anderson Cancer Center, Houston, TX, United States, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, OH, Kaiser Permanente Northern California, Santa Clara, CA, United States, McMaster University, Hamilton, ON, Canada, Grand River Regional Cancer Centre, Kitchener, ON, Canada, Washington University School of Medicine, St. Louis, MO, Centre Hospitalier de l’Universite de Montreal, Montreal, QC, Canada, Beth Israel Deaconess Medical Center, Boston, MA, Fox Chase Cancer Center, Philadelphia, PA, University of California, San Francisco, San Francisco, CA, Abington Memorial Hospital, Abington, PA, United States, Foundation for Cancer Research and Education, Phoenix, AZ, Cedars-Sinai Medical Center, Los Angeles, CA, Boston Medical Center, Boston, MA

Hospitalization final 90 days of life 48.3% 64.0% .0004 Hospitalization final 30 days of life 31.5% 61.5%

Purpose/Objective(s): To report the long-term survival and toxicity outcomes with the use of ultra-high-dose intensity modulated radiation therapy (IMRT) to a dose of 86.4 Gy for patients with localized prostate cancer. Materials/Methods: Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5-7 field IMRT technique. Patients were stratified into prognostic risk groups based on the National Comprehensive Cancer Network risk-grouping system. Five hundred eighty-seven patients (59%) were treated with neoadjuvant and concurrent androgen-deprivation therapy. The median follow-up for the entire cohort was 5.5 years (range 1-14 years). Results: The 5and 10-year actuarial prostate-specific antigen (PSA) relapse-free survival outcomes for low-, intermediate-, and high-risk groups were 98.8 and 96.3%, 89.1 and 75.4%, and 76.1 and 65.8% (p < 0.001), respectively. On multivariate analysis, T stage (p Z 0.002), Gleason score (p < 0.001), and pretreatment PSA (iPSA) (p Z 0.008) were predictors for biochemical relapse. The 5and 10-year actuarial DMFS for low-, intermediate-, and high-risk groups was 99.4 and 96.8%, 97.4 and 93.6%, and 90.1 and 74.4% (p < 0.001), respectively. On multivariate analysis, T stage (p < 0.001), Gleason score (p < 0.001), and iPSA (p < 0.033) were predictive for DM. No prostate cancer-related deaths were observed in the low-risk group. The 5and 10-year actuarial CSS for intermediateand high-risk groups was 99.4 and 93.8%, and 96.6 and 82.2% (p Z 0.008), respectively. On multivariate analysis, only T stage (p Z 0.016) and Gleason score (p Z 0.003) were predictive for prostate cancer-related death. The incidence of grade 2 or higher late gastrointestinal (GI) and genitourinary (GU) toxicities were 4.4% and 17.1%, respectively. Late grade 3 GI and GU toxicity was experienced in 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions: This represents the largest cohort of patients treated with ultra-high-dose radiation to 86.4 Gy using IMRT for localized prostate cancer with the longest follow-up to date. Our findings indicate that this treatment results in excellent clinical outcomes and is well tolerated with acceptable toxicity. Author Disclosure: D. Spratt: None. X. Pei: None. J. Yamada: None. M.A. Kollmeier: None. B. Cox: None. Z. Zhang: None. M.J. Zelefsky: None.