Strong damped Lyman-α absorption in young star-forming galaxies at redshifts 9 to 11.

Primordial neutral atomic gas, mostly composed of hydrogen, is the raw material for star formation in galaxies. However, there are few direct constraints on the amount of neutral atomic hydrogen (H i) in galaxies at early cosmic times. We analyzed James Webb Space Telescope (JWST) near-infrared spectroscopy of distant galaxies, at redshifts ≳8. From a sample of 12 galaxies, we identified three that show strong damped Lyman-α absorption due to H i in their local surroundings. The galaxies are located at spectroscopic redshifts of 8.8, 10.2, and 11.4, corresponding to 400 to 600 million years after the Big Bang. They have H i column densities ≳1022 cm-2, which is an order of magnitude higher than expected for a fully neutral intergalactic medium, and constitute a gas-rich population of young star-forming galaxies.

Hemibody Irradiation for Bone Metastases: A Systematic Review and Meta-Analysis.

Hemibody irradiation (HBI) is a radiation therapy technique that involves treating one-half of the patient's skeletal system in a single radiation field. It is mostly given as upper hemibody irradiation (UHBI), lower hemibody irradiation (LHBI), or sequential UHBI and LHBI. It is used to treat extensive bone metastases from solid tumors. It was primarily utilized in the 1980s and 1990s and has since fallen out of favor. However, it is a potentially cost-effective treatment for widespread bone metastases. To determine its efficacy, we performed a meta-analysis of all available published articles on the efficacy of HBI to relieve pain from bone metastases. Twenty-seven articles involving 1318 patients were identified and analyzed. Our findings show that 80% of the patients had complete or partial pain relief and 29% had complete pain relief. The trials were of poor quality, but the results showed minimal heterogeneity in the response rates. These response rates are consistent with those seen with focal irradiation of bone metastases and for radionuclide treatment of bone metastases. The toxicity of the treatments decreased when delivered with modern treatment techniques. In light of this, we propose that this technique warrants re-evaluation with modern treatment methods.

A Milky Way-like barred spiral galaxy at a redshift of 3.

The majority of massive disk galaxies in the local Universe show a stellar barred structure in their central regions, including our Milky Way1,2. Bars are supposed to develop in dynamically cold stellar disks at low redshift, as the strong gas turbulence typical of disk galaxies at high redshift suppresses or delays bar formation3,4. Moreover, simulations predict bars to be almost absent beyond z = 1.5 in the progenitors of Milky Way-like galaxies5,6. Here we report observations of ceers-2112, a barred spiral galaxy at redshift zphot ≈ 3, which was already mature when the Universe was only 2 Gyr old. The stellar mass (M★ = 3.9 × 109 M⊙) and barred morphology mean that ceers-2112 can be considered a progenitor of the Milky Way7-9, in terms of both structure and mass-assembly history in the first 2 Gyr of the Universe, and was the closest in mass in the first 4 Gyr. We infer that baryons in galaxies could have already dominated over dark matter at z ≈ 3, that high-redshift bars could form in approximately 400 Myr and that dynamically cold stellar disks could have been in place by redshift z = 4-5 (more than 12 Gyrs ago)10,11.

Confirmation and refutation of very luminous galaxies in the early Universe.

During the first 500 million years of cosmic history, the first stars and galaxies formed, seeding the Universe with heavy elements and eventually reionizing the intergalactic medium1-3. Observations with the James Webb Space Telescope (JWST) have uncovered a surprisingly high abundance of candidates for early star-forming galaxies, with distances (redshifts, z), estimated from multiband photometry, as large as z ≈ 16, far beyond pre-JWST limits4-9. Although such photometric redshifts are generally robust, they can suffer from degeneracies and occasionally catastrophic errors. Spectroscopic measurements are required to validate these sources and to reliably quantify physical properties that can constrain galaxy formation models and cosmology10. Here we present JWST spectroscopy that confirms redshifts for two very luminous galaxies with z > 11, and also demonstrates that another candidate with suggested z ≈ 16 instead has z = 4.9, with an unusual combination of nebular line emission and dust reddening that mimics the colours expected for much more distant objects. These results reinforce evidence for the early, rapid formation of remarkably luminous galaxies while also highlighting the necessity of spectroscopic verification. The large abundance of bright, early galaxies may indicate shortcomings in current galaxy formation models or deviations from physical properties (such as the stellar initial mass function) that are generally believed to hold at later times.

Report from the SWOG Radiation Oncology Committee: Research Objectives Workshop 2017.

The Radiation Therapy Committee of SWOG periodically evaluates its strategic plan in an effort to maintain a current and relevant scientific focus, and to provide a standard platform for future development of protocol concepts. Participants in the 2017 Strategic Planning Workshop included leaders in cancer basic sciences, molecular theragnostics, pharmaceutical and technology industries, clinical trial design, oncology practice, and statistical analysis. The committee discussed high-priority research areas, such as optimization of combined modality therapy, radiation oncology-specific drug design, identification of molecular profiles predictive of radiation-induced local or distant tumor responses, and methods for normal tissue-specific mitigation of radiation toxicity. The following concepts emerged as dominant questions ready for national testing: (i) what is the role of radiotherapy in the treatment of oligometastatic, oligorecurrent, and oligoprogressive disease? (ii) How can combined modality therapy be used to enhance systemic and local response? (iii) Can we validate and optimize liquid biopsy and other biomarkers (such as novel imaging) to supplement current response criteria to guide therapy and clinical trial design endpoints? (iv) How can we overcome deficiencies of randomized survival endpoint trials in an era of increasing molecular stratification factors? And (v) how can we mitigate treatment-related side effects and maximize quality of life in cancer survivors? The committee concluded that many aspects of these questions are ready for clinical evaluation and example protocol concepts are provided that could improve rates of cancer cure and quality of survival. Clin Cancer Res; 24(15); 3500-9. ©2018 AACR.

Radiation dose and cardiac risk in breast cancer treatment: An analysis of modern radiation therapy including community settings.

PURPOSE: Adjuvant radiation therapy (RT) for breast cancer improves outcomes, but prior studies have documented substantive cardiac dose and cardiac risk. We assessed the mean heart dose (MHD) of RT and estimated the risk of RT-associated cardiac toxicity in women undergoing adjuvant RT for breast cancer in contemporary (predominantly) community practice. METHODS AND MATERIALS: We identified women with left-sided breast cancer receiving adjuvant RT between 2012 and 2014 from 94 centers across 16 states. We used bivariate analyses and multivariable linear regression to assess associations between RT techniques and MHD. Excess RT-related cardiac risk by age 80 was estimated for women diagnosed at age 60 using the previously reported relationship between MHD and cardiac risk. RESULTS: Among 1161 women, 77.3% were treated in community practice and with breast conservation (77.8%). The most common techniques were free-breathing (92.2%), supine (94.8%), and fixed gantry intensity modulated RT (FG-IMRT; 46.9%). The median MHD was 2.76 Gy (interquartile range, 1.47-5.03). In multivariable analyses, the predicted median MHD with deep inspiration breath hold was 2.41 Gy compared with 3.86 Gy with free-breathing (P < .001). Three-dimensional conformal RT (3D-CRT) was associated with a lower predicted median MHD (2.78 Gy) than FG-IMRT (4.02 Gy) or rotational IMRT, 6.60 Gy, P < .001). For 60-year-old women with the median MHD of the study population (2.76 Gy) and no cardiovascular risk factors, the 20-year predicted excess risk of death from ischemic heart disease attributable to radiation was 3.5 excess events/1000 patients, in contrast to estimates of 8 events/1000 from prior analyses. The predicted risk of cardiac events varied based on radiation technique, with 4 excess events/1000 with 3D-CRT, 5 excess events/1000 with FG-IMRT, and 8 excess events/1000 with rotational IMRT. CONCLUSIONS: MHD varies substantially across patients and is influenced by technique in predominantly community settings. Overall risk of cardiac toxicity is modest.

The Role of Therapeutic Layering in Optimizing Treatment for Patients With Castration-resistant Prostate Cancer (Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence II).

OBJECTIVE: To offer recommendations on identification of disease progression, treatment management strategies, and suggestions on timing of initiating and discontinuing specific castration-resistant prostate cancer (CRPC) treatments. MATERIALS AND METHODS: The Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence II Working Group convened to provide guidance on sequencing, combination, or layering of approved treatments for metastatic CRPC based on available data and clinical experience. RESULTS: A consensus was developed to address important questions on management of patients with metastatic CRPC. CONCLUSION: In the absence of large-scale clinical trials, the Working Group recommends that patients may best be managed with a layered approach of approved therapies with unique or complimentary mechanisms of action.

The Effect of Biologically Effective Dose and Radiation Treatment Schedule on Overall Survival in Stage I Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy.

PURPOSE: To determine the effect of biologically effective dose (BED10) and radiation treatment schedule on overall survival (OS) in patients with early-stage non-small cell lung cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Using data from 65 treatment centers in the United States, we retrospectively reviewed the records of T1-2 N0 NSCLC patients undergoing SBRT alone from 2006 to 2014. Biologically relevant covariates, including dose per fraction, number of fractions, and time between fractions, were used to quantify BED10 and radiation treatment schedule. The linear-quadratic equation was used to calculate BED10 and to generate a dichotomous dose variable of <105 Gy versus ≥105 Gy BED10. The primary outcome was OS. We used the Kaplan-Meier method, the log-rank test, and Cox proportional hazards regression with propensity score matching to determine whether prescription BED10 was associated with OS. RESULTS: We identified 747 patients who met inclusion criteria. The median BED10 was 132 Gy, and 59 (7.7%) had consecutive-day fractions. Median follow-up was 41 months, and 452 patients (60.5%) had died by the conclusion of the study. The 581 patients receiving ≥105 Gy BED10 had a median survival of 28 months, whereas the 166 patients receiving <105 Gy BED10 had a median survival of 22 months (log-rank, P=.01). Radiation treatment schedule was not a significant predictor of OS on univariable analysis. After adjusting for T stage, sex, tumor histology, and Eastern Cooperative Oncology Group performance status, BED10 ≥105 Gy versus <105 Gy remained significantly associated with improved OS (hazard ratio 0.78, 95% confidence interval 0.62-0.98, P=.03). Propensity score matching on imbalanced variables within high- and low-dose cohorts confirmed a survival benefit with higher prescription dose. CONCLUSIONS: We found that dose escalation to 105 Gy BED10 and beyond may improve survival in NSCLC patients treated with SBRT.

Patient-reported quality of life after stereotactic body radiation therapy versus moderate hypofractionation for clinically localized prostate cancer.

BACKGROUND AND PURPOSE: Evaluate changes in bowel, urinary and sexual patient-reported quality of life following treatment with moderately hypofractionated radiotherapy (<5Gray/fraction) or stereotactic body radiation therapy (SBRT;5-10Gray/fraction) for prostate cancer. MATERIALS AND METHODS: In a pooled multi-institutional analysis of men treated with moderate hypofractionation or SBRT, we compared minimally detectable difference in bowel, urinary and sexual quality of life at 1 and 2years using chi-squared analysis and logistic regression. RESULTS: 378 men received moderate hypofractionation compared to 534 men who received SBRT. After 1year, patients receiving moderate hypofractionation were more likely to experience worsening in bowel symptoms (39.5%) compared to SBRT (32.5%; p=.06), with a larger difference at 2years (37.4% versus 25.3%, p=.002). Similarly, patients receiving moderate fractionation had worsening urinary symptom score compared to patients who underwent SBRT at 1 and 2years (34.7% versus 23.1%, p<.001; and 32.8% versus 14.0%, p<.001). There was no difference in sexual symptom score at 1 or 2years. After adjusting for age and cancer characteristics, patients receiving SBRT were less likely to experience worsening urinary symptom scores at 2years (odds ratio: 0.24[95%CI: 0.07-0.79]). CONCLUSIONS: Patients who received SBRT or moderate hypofractionation have similar patient-reported change in bowel and sexual symptoms, although there was worse change in urinary symptoms for patients receiving moderate hypofractionation.

Multinational Prospective Study of Patient-Reported Outcomes After Prostate Radiation Therapy: Detailed Assessment of Rectal Bleeding.

PURPOSE: The new short Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) patient-reported health-related quality of life (HRQOL) tool has removed the rectal bleeding question from the previous much longer version, EPIC-26. Herein, we assess the impact of losing the dedicated rectal bleeding question in 2 independent prospective multicenter cohorts. METHODS AND MATERIALS: In a prospective multicenter test cohort (n=865), EPIC-26 patient-reported HRQOL data were collected for 2 years after treatment from patients treated with prostate radiation therapy from 2003 to 2011. A second prospective multicenter cohort (n=442) was used for independent validation. A repeated-effects model was used to predict the change from baseline in bowel summary scores from longer EPIC instruments using the change in EPIC-CP bowel summary scores with and without rectal bleeding scores. RESULTS: Two years after radiation therapy, 91% of patients were free of bleeding, and only 2.6% reported bothersome bleeding problems. Correlations between EPIC-26 and EPIC-CP bowel scores were very high (r2=0.90-0.96) and were statistically improved with the addition of rectal bleeding information (r2=0.94-0.98). Considering all patients, only 0.2% of patients in the test cohort and 0.7% in the validation cohort reported bothersome bleeding and had clinically relevant HRQOL changes missed with EPIC-CP. However, of the 2.6% (n=17) of men with bothersome rectal bleeding in the test cohort, EPIC-CP failed to capture 1 patient (6%) as experiencing meaningful declines in bowel HRQOL. CONCLUSIONS: Modern prostate radiation therapy results in exceptionally low rates of bothersome rectal bleeding, and <1% of patients experience bothersome bleeding and are not captured by EPIC-CP as having meaningful HRQOL declines after radiation therapy. However, in the small subset of patients with bothersome rectal bleeding, the longer EPIC-26 should strongly be considered, given its superior performance in this patient subset.

Development and Validation of Consensus Contouring Guidelines for Adjuvant Radiation Therapy for Bladder Cancer After Radical Cystectomy.

PURPOSE: To develop multi-institutional consensus clinical target volumes (CTVs) and organs at risk (OARs) for male and female bladder cancer patients undergoing adjuvant radiation therapy (RT) in clinical trials. METHODS AND MATERIALS: We convened a multidisciplinary group of bladder cancer specialists from 15 centers and 5 countries. Six radiation oncologists and 7 urologists participated in the development of the initial contours. The group proposed initial language for the CTVs and OARs, and each radiation oncologist contoured them on computed tomography scans of a male and female cystectomy patient with input from ≥1 urologist. On the basis of the initial contouring, the group updated its CTV and OAR descriptions. The cystectomy bed, the area of greatest controversy, was contoured by another 6 radiation oncologists, and the cystectomy bed contouring language was again updated. To determine whether the revised language produced consistent contours, CTVs and OARs were redrawn by 6 additional radiation oncologists. We evaluated their contours for level of agreement using the Landis-Koch interpretation of the κ statistic. RESULTS: The group proposed that patients at elevated risk for local-regional failure with negative margins should be treated to the pelvic nodes alone (internal/external iliac, distal common iliac, obturator, and presacral), whereas patients with positive margins should be treated to the pelvic nodes and cystectomy bed. Proposed OARs included the rectum, bowel space, bone marrow, and urinary diversion. Consensus language describing the CTVs and OARs was developed and externally validated. The revised instructions were found to produce consistent contours. CONCLUSIONS: Consensus descriptions of CTVs and OARs were successfully developed and can be used in clinical trials of adjuvant radiation therapy for bladder cancer.

Strut-based accelerated partial breast irradiation: Report of treatment results for 250 consecutive patients at 5 years from a multicenter retrospective study.

PURPOSE: This registry trial studied the long-term outcomes of women receiving accelerated partial breast irradiation (APBI) using strut-based applicators and reports on the local control, toxicity, and survival for the first 250 patients treated with this device. METHODS AND MATERIALS: Patients were treated using the strut-based brachytherapy device with conventional dose and fractionation of 34 Gy in 10 twice-daily fractions. Planning goals for the planning target volume were V90 > 90%, V150 < 50 cc, and V200 < 20 cc. Toxicity was graded based on the Common Terminology Criteria for Adverse Events v3.0. Recurrence rates were also calculated. RESULTS: Median followup was 59.5 months for the 250 patients. Grade 2 or higher adverse events at any time for hyperpigmentation, induration, erythema, telangiectasia, breast pain, seroma, and fat necrosis were 0.4%, 3.0%, 3.0%, 3.0%, 3.9%, 4.8%, and 1.3%, respectively. The median V90 was 97%, V95 was 95.1%, V150 was 28.7 cc, and V200 was 14.2 cc. For those patients with a less than a 5-mm or 3-mm-skin bridge, the median skin max doses were 272 and 289 cGy, respectively. The 4-year actuarial recurrence rates for true recurrence/marginal miss and ipsilateral breast tumor recurrence were 2.3% and 3.6%, respectively. The 4-year actuarial rates for overall survival, cause-specific survival, and disease-free survival were 97%, 98%, and 92%, respectively. CONCLUSIONS: The strut-based applicator was designed to simplify APBI compared to interstitial brachytherapy. This report confirms excellent tumor control and survival with low toxicity and supports the evidence that brachytherapy has less normal tissue toxicity than APBI with external beam irradiation.

Efficacy and Safety of Radium-223 Dichloride in Symptomatic Castration-resistant Prostate Cancer Patients With or Without Baseline Opioid Use From the Phase 3 ALSYMPCA Trial.

BACKGROUND: The phase 3 ALSYMPCA trial enrolled metastatic castration-resistant prostate cancer patients with or without baseline opioid use. OBJECTIVE: To assess the efficacy and safety of radium-223 dichloride (radium-223) versus placebo in ALSYMPCA patients by baseline opioid use. DESIGN, SETTING, AND PARTICIPANTS: Nine hundred and twenty one patients enrolled at 136 centers globally. INTERVENTION: Radium-223 (50 kBq/kg, intravenous injection) every 4 wk for six cycles or matching placebo, each plus best standard of care. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint (overall survival [OS]), main secondary efficacy endpoints, and safety were evaluated by baseline opioid use. Additional analyses included time to first opioid use, time to first external beam radiation therapy for bone pain, and safety of concomitant external beam radiation therapy. RESULTS AND LIMITATIONS: At baseline, 408 (44%) patients had no pain and no analgesic use or mild pain with nonopioid therapy (World Health Organization ladder pain score 0-1 [nonopioid subgroup]), and 513 (56%) had moderate pain with occasional opioids or severe pain with regular daily opioids (World Health Organization ladder pain score 2-3 [opioid subgroup]). Radium-223 significantly prolonged OS versus placebo in nonopioid (hazard ratio [HR]=0.70; 95% confidence interval [CI]: 0.52-0.93; p=0.013) and opioid (HR=0.68; 95% CI: 0.54-0.86; p=0.001) subgroups, and significantly reduced risk of symptomatic skeletal events versus placebo, regardless of baseline opioid use (nonopioid subgroup: HR=0.56, 95% CI: 0.39-0.82, p=0.002; opioid subgroup: HR=0.72, 95% CI: 0.53-0.98, p=0.038). Time to first opioid use for bone pain was significantly delayed with radium-223 versus placebo (HR=0.62, 95% CI: 0.46-0.85, p=0.002). Adverse event incidences were similar between opioid subgroups. CONCLUSIONS: Radium-223 versus placebo significantly prolonged OS and reduced symptomatic skeletal event risk with a favorable safety profile in castration-resistant prostate cancer patients with symptomatic bone metastases, regardless of baseline opioid use. PATIENT SUMMARY: In this ALSYMPCA opioid subgroup analysis, baseline symptom levels did not appear to impact radium-223 dichloride efficacy or safety.

Abscopal Benefits of Localized Radiotherapy Depend on Activated T-cell Trafficking and Distribution between Metastatic Lesions.

It remains unclear how localized radiotherapy for cancer metastases can occasionally elicit a systemic antitumor effect, known as the abscopal effect, but historically, it has been speculated to reflect the generation of a host immunotherapeutic response. The ability to purposefully and reliably induce abscopal effects in metastatic tumors could meet many unmet clinical needs. Here, we describe a mathematical model that incorporates physiologic information about T-cell trafficking to estimate the distribution of focal therapy-activated T cells between metastatic lesions. We integrated a dynamic model of tumor-immune interactions with systemic T-cell trafficking patterns to simulate the development of metastases. In virtual case studies, we found that the dissemination of activated T cells among multiple metastatic sites is complex and not intuitively predictable. Furthermore, we show that not all metastatic sites participate in systemic immune surveillance equally, and therefore the success in triggering the abscopal effect depends, at least in part, on which metastatic site is selected for localized therapy. Moreover, simulations revealed that seeding new metastatic sites may accelerate the growth of the primary tumor, because T-cell responses are partially diverted to the developing metastases, but the removal of the primary tumor can also favor the rapid growth of preexisting metastatic lesions. Collectively, our work provides the framework to prospectively identify anatomically defined focal therapy targets that are most likely to trigger an immune-mediated abscopal response and therefore may inform personalized treatment strategies in patients with metastatic disease.

Ultraviolet luminosity density of the universe during the epoch of reionization.

The spatial fluctuations of the extragalactic background light trace the total emission from all stars and galaxies in the Universe. A multiwavelength study can be used to measure the integrated emission from first galaxies during reionization when the Universe was about 500 million years old. Here we report arcmin-scale spatial fluctuations in one of the deepest sky surveys with the Hubble Space Telescope in five wavebands between 0.6 and 1.6 µm. We model-fit the angular power spectra of intensity fluctuation measurements to find the ultraviolet luminosity density of galaxies at redshifts greater than 8 to be log ρ(UV) = 27.4(+0.2)(-1.2) ergs(-1) Hz(-1) Mpc(-3) (1σ). This level of integrated light emission allows for a significant surface density of fainter primeval galaxies that are below the point-source detection level in current surveys.

Patient-reported quality of life after stereotactic body radiotherapy (SBRT), intensity modulated radiotherapy (IMRT), and brachytherapy.

BACKGROUND AND PURPOSE: Stereotactic body radiotherapy (SBRT) is being used for prostate cancer, but concerns persist about toxicity compared to other radiotherapy options. MATERIALS AND METHODS: We conducted a multi-institutional pooled cohort analysis of patient-reported quality of life (QOL) [EPIC-26] before and after intensity-modulated radiotherapy (IMRT), brachytherapy, or SBRT for localized prostate cancer. Data were analyzed by mean domain score, minimal clinically detectable difference (MCD) in domain score, and multivariate analyses to determine factors associated with domain scores at 2-years. RESULTS: Data were analyzed from 803 patients at baseline and 645 at 2-years. Mean declines at 2-years across all patients were -1.9, -4.8, -4.9, and -13.3 points for urinary obstructive, urinary incontinence, bowel, and sexual symptom domains, respectively, corresponding to MCD in 29%, 20%, and 28% of patients. On multivariate analysis (vs. IMRT), brachytherapy had worse urinary irritation at 2-years (-6.8 points, p<0.0001) but no differences in other domains (p>0.15). QOL after SBRT was similar for urinary (p>0.5) and sexual domains (p=0.57), but was associated with better bowel score (+6.7 points, p<0.0002). CONCLUSIONS: QOL 2-years after brachytherapy, IMRT, or SBRT is very good and largely similar, with small differences in urinary and bowel QOL that are likely minimized by modern techniques.

Annual Fecal Occult Blood Testing can be Safely Suspended for up to 5 Years After a Negative Colonoscopy in Asymptomatic Average-Risk Patients.

OBJECTIVES: Annual fecal occult blood testing (FOBT) is often continued in patients who have had a recent negative colonoscopy, despite recommendations to the contrary. This prospective study aimed to determine the proportion of patients with a positive FOBT who had adenomas and cancers on colonoscopy stratified according to the duration of time since the last negative colonoscopy. METHODS: A total of 1,119 asymptomatic average-risk patients ≥50 years of age referred for a positive FOBT were prospectively identified and stratified by the duration of time since the last colonoscopy (never, >10 years, 5-10 years, or <5 years). The proportion of patients in each category with adenomas of any size, adenomas ≥10 mm, advanced neoplasms, and cancers was assessed. RESULTS: The mean age (68.9±9.6 years), sex (95.2% male), and race (48.1% white, 32.1% black, 15.6% Hispanic, and 4.2% other) did not differ between the four groups. Overall, adenomas of any size were detected in 42.8% of patients, adenomas ≥10 mm in 14.7%, advanced neoplasms in 20.7%, and cancers in 7.3%. Advanced neoplasms were detected in 30.4% of patients who have never had a colonoscopy, 27% in those who have had one greater than 10 years prior, 10.0% in 5-10 years prior, and 1.1% in less than 5 years prior. CONCLUSIONS: In asymptomatic average-risk patients with a negative colonoscopy within the last 5 years, the prevalence of adenomas is low, and no patient was diagnosed with cancer. These findings support the CDC recommendations to suspend annual FOBT for up to 5 years after a negative colonoscopy.

Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists.

PURPOSE: The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. METHODS AND MATERIALS: Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. RESULTS: Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. CONCLUSIONS: For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed.