NRG Oncology/RTOG1205: A Randomized Phase II Trial of Concurrent Bevacizumab and Reirradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma.

PURPOSE: To assess whether reirradiation (re-RT) and concurrent bevacizumab (BEV) improve overall survival (OS) and/or progression-free survival (PFS), compared with BEV alone in recurrent glioblastoma (GBM). The primary objective was OS, and secondary objectives included PFS, response rate, and treatment adverse events (AEs) including delayed CNS toxicities. METHODS: NRG Oncology/RTOG1205 is a prospective, phase II, randomized trial of re-RT and BEV versus BEV alone. Stratification factors included age, resection, and Karnofsky performance status (KPS). Patients with recurrent GBM with imaging evidence of tumor progression ≥ 6 months from completion of prior chemo-RT were eligible. Patients were randomly assigned 1:1 to re-RT, 35 Gy in 10 fractions, with concurrent BEV IV 10 mg/kg once in every 2 weeks or BEV alone until progression. RESULTS: From December 2012 to April 2016, 182 patients were randomly assigned, of whom 170 were eligible. Patient characteristics were well balanced between arms. The median follow-up for censored patients was 12.8 months. There was no improvement in OS for BEV + RT, hazard ratio, 0.98; 80% CI, 0.79 to 1.23; P = .46; the median survival time was 10.1 versus 9.7 months for BEV + RT versus BEV alone. The median PFS for BEV + RT was 7.1 versus 3.8 months for BEV, hazard ratio, 0.73; 95% CI, 0.53 to 1.0; P = .05. The 6-month PFS rate improved from 29.1% (95% CI, 19.1 to 39.1) for BEV to 54.3% (95% CI, 43.5 to 65.1) for BEV + RT, P = .001. Treatment was well tolerated. There were a 5% rate of acute grade 3+ treatment-related AEs and no delayed high-grade AEs. Most patients died of recurrent GBM. CONCLUSION: To our knowledge, NRG Oncology/RTOG1205 is the first prospective, randomized multi-institutional study to evaluate the safety and efficacy of re-RT in recurrent GBM using modern RT techniques. Overall, re-RT was shown to be safe and well tolerated. BEV + RT demonstrated a clinically meaningful improvement in PFS, specifically the 6-month PFS rate but no difference in OS.

Prospective International Pilot Study Evaluating the Efficacy of a Self-Guided Contouring Teaching Module With Integrated Feedback for Transitioning From 2D to 3D Treatment Planning.

PURPOSE: Transitioning from two-dimensional to three-dimensional treatment planning requires developing contouring skills. Contouring atlases are excellent resources, but they do not provide users active feedback. Developing countries may not have many radiation oncologists experienced in three-dimensional planning to provide training. We sought to develop a standardized self-guided educational module with integrated feedback to teach contouring skills. METHODS AND MATERIALS: All 18 oncology residents at Black Lion Hospital/Addis Ababa University in Ethiopia were trained to contour the level II lymph node station. Residents took a baseline pretest quiz, survey, and contouring evaluation. Residents then watched an instructional contouring lecture and performed three additional cases with integrated feedback by comparing their contours to gold-standard contours. Residents then took a post-training quiz, survey, and contouring evaluation. Paired t tests and analysis of variance were used for analysis. RESULTS: Before training, the average number of total cases ever contoured was 2.4 and the average number of head and neck cases contoured was 0.5. Comfort with contouring improved from being "not at all comfortable" to "quite comfortable" after the 3-hour training (P < .001). The standard deviation between the resident contours and gold standard improved from 72.6 cm3 (pretest) to 7.4 cm3 (post-test). The average percentage overlap with the gold-standard contours and Dice similarity coefficient improved with each case performed, from 27.7% and 0.26 (pretest) to 80.1% and 0.77 (post-test), respectively (P < .001). After training, 16 of 18 (88.9%) residents produced a Dice similarity coefficient greater than 0.7, the threshold generally accepted for excellent agreement. CONCLUSION: This self-guided teaching module was an effective tool for developing level II lymph node contouring skills by providing active feedback and resulted in improved user confidence and accuracy compared with a gold standard. This module can be expanded to other disease sites and countries to further facilitate transitioning to three-dimensional treatment planning in developing countries.

Fractionated Radiotherapy Is Associated with Lower Rates of Treatment-Related Edema than Stereotactic Radiosurgery in Magnetic Resonance Imaging-Defined Meningiomas.

OBJECTIVE: Both stereotactic radiosurgery (SRS) and fractionated radiation therapy (FRT) techniques are used for treatment of intracranial meningiomas with excellent local control (LC) rates. Although SRS techniques are convenient, toxicity including treatment-related edema can significantly impact patient quality of life. The long-term clinical outcomes of patients with magnetic resonance imaging (MRI)-defined meningiomas treated with radiation therapy (RT) alone are reported. METHODS: The charts of 211 patients with meningiomas diagnosed by contrast-enhanced MRI treated with either SRS or FRT between 1991 and 2012 at a single institution were reviewed. Actuarial rates for LC and development of treatment-related radiographic edema (TRE) were determined by the Kaplan-Meier method. RESULTS: There were 211 patients who received radiation therapy for 223 lesions. Median follow-up was 5.7 years. Eleven patients experienced a local failure; of these, 2 were ultimately found to have pathologically proven metastatic carcinoma. Two- and 5-year LC was 97.8% and 94.6%, respectively, with no significant difference based on modality of therapy. Actuarial rate for development of TRE at 1 and 2 years was 30.1% and 34.6% for the SRS group and 1.6% and 2.5% for the FRT group, respectively (P < 0.001). CONCLUSIONS: RT alone using a limited margin is an effective treatment option for MRI-defined meningiomas and should be considered even without biopsy if surgery will present significant morbidity. Although LC with SRS versus FRT was comparable, FRT was associated with a significantly decreased risk of TRE.

NRG oncology RTOG 9006: a phase III randomized trial of hyperfractionated radiotherapy (RT) and BCNU versus standard RT and BCNU for malignant glioma patients.

From 1990 to 1994, patients with newly diagnosed malignant gliomas were enrolled and randomized between hyperfractionated radiation (HFX) of 72.0 Gy in 60 fractions given twice daily and 60.0 Gy in 30 fractions given once daily. All patients received 80 mg/m2 of 1,3 bis(2 chloroethyl)-1 nitrosourea on days 1-3 q8 weeks for 1 year. Patients were stratified by age, KPS, and histology. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and toxicity. Out of the 712 patients accrued, 694 (97.5%) were analyzable cases (350 HFX, 344 standard arm). There was no significant difference between the arms on overall acute or late treatment-related toxicity. No statistically significant effect for HFX, as compared to standard therapy, was found on either OS, with a median survival time (MST) of 11.3 versus 13.1 months (p = 0.20) or PFS, with a median PFS time of 5.7 versus 6.9 months (p = 0.18). The treatment effect on OS remained insignificant based on the multivariate analysis (hazard ratio 1.16; p = 0.0682). When OS was analyzed by histology subgroup there was also no significant difference between the two arms for patients with glioblastoma multiforme (MST: 10.3 vs. 11.2 months; p = 0.34), anaplastic astrocytoma (MST: 69.8 vs. 50.0 months; p = 0.91) or anaplastic oligodendroglioma (MST: 92.1 vs. 66.5 months; p = 0.33). Though this trial provided many invaluable secondary analyses, there was no trend or indication of a benefit to HFX radiation to 72.0 Gy in any subset of malignant glioma patients.

Matrix metalloproteinases: their functional role in lung cancer.

Lung malignancy is the foremost cause of cancer-related deaths globally and is frequently related to long-term tobacco smoking. Recent studies reveal that the expression of matrix metalloproteinases (MMPs) is extremely high in lung tumors compared with non-malignant lung tissue. MMPs are zinc-dependent proteases and are involved in the degradation of extracellular matrix (ECM). Several investigations have shown that MMPs manipulate the activity of non-ECM molecules, including cytokines, growth factors and receptors that control the tumor microenvironment. In this review, we have summarized and critically reviewed the published works on the role of MMPs in non-small-cell lung cancer. We have also explored the structure of MMPs, their various types and roles in lung cancer metastasis including invasion, migration and angiogenesis.

Evaluating the Special Needs of The Military for Radiation Biodosimetry for Tactical Warfare Against Deployed Troops: Comparing Military to Civilian Needs for Biodosimetry Methods.

The aim of this paper is to delineate characteristics of biodosimetry most suitable for assessing individuals who have potentially been exposed to significant radiation from a nuclear device explosion when the primary population targeted by the explosion and needing rapid assessment for triage is civilians vs. deployed military personnel. The authors first carry out a systematic analysis of the requirements for biodosimetry to meet the military's needs to assess deployed troops in a warfare situation, which include accomplishing the military mission. Then the military's special capabilities to respond and carry out biodosimetry for deployed troops in warfare are compared and contrasted systematically, in contrast to those available to respond and conduct biodosimetry for civilians who have been targeted by terrorists, for example. Then the effectiveness of different biodosimetry methods to address military vs. civilian needs and capabilities in these scenarios was compared and, using five representative types of biodosimetry with sufficient published data to be useful for the simulations, the number of individuals are estimated who could be assessed by military vs. civilian responders within the timeframe needed for triage decisions. Analyses based on these scenarios indicate that, in comparison to responses for a civilian population, a wartime military response for deployed troops has both more complex requirements for and greater capabilities to use different types of biodosimetry to evaluate radiation exposure in a very short timeframe after the exposure occurs. Greater complexity for the deployed military is based on factors such as a greater likelihood of partial or whole body exposure, conditions that include exposure to neutrons, and a greater likelihood of combined injury. These simulations showed, for both the military and civilian response, that a very fast rate of initiating the processing (24,000 d) is needed to have at least some methods capable of completing the assessment of 50,000 people within a 2- or 6-d timeframe following exposure. This in turn suggests a very high capacity (i.e., laboratories, devices, supplies and expertise) would be necessary to achieve these rates. These simulations also demonstrated the practical importance of the military's superior capacity to minimize time to transport samples to offsite facilities and use the results to carry out triage quickly. Assuming sufficient resources and the fastest daily rate to initiate processing victims, the military scenario revealed that two biodosimetry methods could achieve the necessary throughput to triage 50,000 victims in 2 d (i.e., the timeframe needed for injured victims), and all five achieved the targeted throughput within 6 d. In contrast, simulations based on the civilian scenario revealed that no method could process 50,000 people in 2 d and only two could succeed within 6 d.

Emesis as a Screening Diagnostic for Low Dose Rate (LDR) Total Body Radiation Exposure.

Current radiation disaster manuals list the time-to-emesis (TE) as the key triage indicator of radiation dose. The data used to support TE recommendations were derived primarily from nearly instantaneous, high dose-rate exposures as part of variable condition accident databases. To date, there has not been a systematic differentiation between triage dose estimates associated with high and low dose rate (LDR) exposures, even though it is likely that after a nuclear detonation or radiologic disaster, many surviving casualties would have received a significant portion of their total exposure from fallout (LDR exposure) rather than from the initial nuclear detonation or criticality event (high dose rate exposure). This commentary discusses the issues surrounding the use of emesis as a screening diagnostic for radiation dose after LDR exposure. As part of this discussion, previously published clinical data on emesis after LDR total body irradiation (TBI) is statistically re-analyzed as an illustration of the complexity of the issue and confounding factors. This previously published data includes 107 patients who underwent TBI up to 10.5 Gy in a single fraction delivered over several hours at 0.02 to 0.04 Gy min. Estimates based on these data for the sensitivity of emesis as a screening diagnostic for the low dose rate radiation exposure range from 57.1% to 76.6%, and the estimates for specificity range from 87.5% to 99.4%. Though the original data contain multiple confounding factors, the evidence regarding sensitivity suggests that emesis appears to be quite poor as a medical screening diagnostic for LDR exposures.

Bevacizumab-induced hypertension is a predictive marker for improved outcomes in patients with recurrent glioblastoma treated with bevacizumab.

BACKGROUND: Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor and is approved for the treatment of patients with recurrent glioblastoma (GBM). Previous authors have reported differential response to bevacizumab on an individual basis. Bevacizumab-induced hypertension is a well-documented side effect, and some reports have suggested this occurrence to be related to treatment outcome in other cancers. In the current study, the authors analyzed patients with recurrent GBM who were treated with bevacizumab based on whether the patients developed drug-induced hypertension. METHODS: All patients with GBM treated within the Emory Healthcare system from 2007 through 2012 were reviewed. A total of 82 patients were identified who received bevacizumab for the treatment of recurrent GBM and were included in the current study. Patients were classified as normotensive or hypertensive depending on whether hypertension developed that was attributable to therapy. Progression-free survival (PFS) and overall survival (OS) were graphed by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards method. RESULTS: The median follow-up was 19.7 months. Of the 82 patients with recurrent GBM who were treated with bevacizumab, 30 developed drug-induced hypertension. The median time to the development of hypertension was 21 days. The median PFS for the normotensive and hypertensive groups were 2.5 months (95% confidence interval [95% CI], 1.6-3.0 months) and 6.7 months (95% CI, 4.6-10.0 months), respectively (P<.001). The median OS times for the normotensive and hypertensive groups were 4.9 months (95% CI, 4.4-6.8 months) and 11.7 months (95% CI, 9.0-20.5 months), respectively (P<.001). CONCLUSIONS: Patients with recurrent GBM who developed bevacizumab-induced hypertension demonstrated significantly better PFS and OS compared with normotensive individuals. Bevacizumab-induced hypertension may be a physiologic marker of outcome in patients with recurrent GBM.

A model and nomogram to predict tumor site origin for squamous cell cancer confined to cervical lymph nodes.

BACKGROUND: The current study was conducted to develop a multifactorial statistical model to predict the specific head and neck (H&N) tumor site origin in cases of squamous cell carcinoma confined to the cervical lymph nodes ("unknown primaries"). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was analyzed for patients with an H&N tumor site who were diagnosed between 2004 and 2011. The SEER patients were identified according to their H&N primary tumor site and clinically positive cervical lymph node levels at the time of presentation. The SEER patient data set was randomly divided into 2 data sets for the purposes of internal split-sample validation. The effects of cervical lymph node levels, age, race, and sex on H&N primary tumor site were examined using univariate and multivariate analyses. Multivariate logistic regression models and an associated set of nomograms were developed based on relevant factors to provide probabilities of tumor site origin. RESULTS: Analysis of the SEER database identified 20,011 patients with H&N disease with both site-level and lymph node-level data. Sex, race, age, and lymph node levels were associated with primary H&N tumor site (nasopharynx, hypopharynx, oropharynx, and larynx) in the multivariate models. Internal validation techniques affirmed the accuracy of these models on separate data. CONCLUSIONS: The incorporation of epidemiologic and lymph node data into a predictive model has the potential to provide valuable guidance to clinicians in the treatment of patients with squamous cell carcinoma confined to the cervical lymph nodes.

Improved hippocampal dose with reduced margin radiotherapy for glioblastoma multiforme.

BACKGROUND: To dosimetrically evaluate the effect of reduced margin radiotherapy on hippocampal dose for glioblastoma multiforme (GBM) patients. METHODS: GBM patients enrolled on the Radiation Therapy Oncology Group (RTOG) 0825 trial at our institution were identified. Standard RTOG 0825 expansions were 2 cm + 3-5 mm from the gross tumor volume (GTV) to the clinical tumor volume (CTV) and from the CTV to the planning tumor volume (PTV), respectively. These same patients also had reduced margin tumor volumes generated with 8 mm (GTV to CTV) + 3 mm (CTV to PTV) expansions. Individual plans were created for both standard and reduced margin structures. The dose-volume histograms were statistically compared with a paired, two-tailed Student's t-test with a significance level of p < 0.05. RESULTS: A total of 16 patients were enrolled on RTOG 0825. The reduced margins resulted in statistically significant reductions in hippocampal dose at all evaluated endpoints. The hippocampal Dmax was reduced from a mean of 61.4 Gy to 56.1 Gy (8.7%), D40% was reduced from 49.9 Gy to 36.5 Gy (26.9%), D60% was reduced from 32.7 Gy to 18.7 Gy (42.9%) and the D80% was reduced from 27.3 Gy to 15.3 Gy (44%). CONCLUSIONS: The use of reduced margin PTV expansions in the treatment of GBM patients results in significant reductions in hippocampal dose. Though the exact clinical benefit of this reduction is currently unclear, this study does provide support for a future prospective trial evaluating the neurocognitive benefits of reduced margin tumor volumes in the treatment of GBM patients.

Tumor size on abdominal MRI versus pathologic specimen in resected pancreatic adenocarcinoma: implications for radiation treatment planning.

PURPOSE: We assessed the accuracy of abdominal magnetic resonance imaging (MRI) for determining tumor size by comparing the preoperative contrast-enhanced T1-weighted gradient echo (3-dimensional [3D] volumetric interpolated breath-hold [VIBE]) MRI tumor size with pathologic specimen size. METHODS AND MATERIALS: The records of 92 patients who had both preoperative contrast-enhanced 3D VIBE MRI images and detailed pathologic specimen measurements were available for review. Primary tumor size from the MRI was independently measured by a single diagnostic radiologist (P.M.) who was blinded to the pathology reports. Pathologic tumor measurements from gross specimens were obtained from the pathology reports. The maximum dimensions of tumor measured in any plane on the MRI and the gross specimen were compared. The median difference between the pathology sample and the MRI measurements was calculated. A paired t test was conducted to test for differences between the MRI and pathology measurements. The Pearson correlation coefficient was used to measure the association of disparity between the MRI and pathology sizes with the pathology size. Disparities relative to pathology size were also examined and tested for significance using a 1-sample t test. RESULTS: The median patient age was 64.5 years. The primary site was pancreatic head in 81 patients, body in 4, and tail in 7. Three patients were American Joint Commission on Cancer stage IA, 7 stage IB, 21 stage IIA, 58 stage IIB, and 3 stage III. The 3D VIBE MRI underestimated tumor size by a median difference of 4 mm (range, -34-22 mm). The median largest tumor dimensions on MRI and pathology specimen were 2.65 cm (range, 1.5-9.5 cm) and 3.2 cm (range, 1.3-10 cm), respectively. CONCLUSIONS: Contrast-enhanced 3D VIBE MRI underestimates tumor size by 4 mm when compared with pathologic specimen. Advanced abdominal MRI sequences warrant further investigation for radiation therapy planning in pancreatic adenocarcinoma before routine integration into the treatment planning process.

Impact of magnetic resonance imaging on computed tomography-based treatment planning and acute toxicity for prostate cancer patients treated with intensity modulated radiation therapy.

PURPOSE: To evaluate rectal and bladder dosimetric and clinical acute toxicity endpoints for prostate patients treated with intensity modulated radiation therapy (IMRT) using magnetic resonance images (MRI) registered to computed tomographic (CT) simulation images versus CT alone. MATERIALS AND METHODS: The charts of 155 consecutive prostate cancer patients at our institution from 2004 to 2008 were reviewed. A cohort of 15 IMRT treatment plans was created to compare dosimetric endpoints for CT-MRI vs CT alone. A subsequent clinical comparison involved 81 patients (CT-MRI [n = 28] vs CT alone [n = 53]). Acute genitourinary and rectal toxicity rates for the CT-MRI and CT cohorts were compared; also, univariate and multivariate regression analyses were performed using all major demographic, disease, and treatment factors as covariates. RESULTS: Contoured prostate volumes were 43.0 vs 55.7 cm(3) (P < .001, n = 15) for CT-MRI vs CT definition, with significant reductions in all bladder dose endpoints and rectal V20, V30, and V70. Grades 0, 1, and 2 toxicity rates for CT-MRI (n = 28) vs CT (n = 53) were, respectively, 25%, 25%, and 50% vs 8%, 21%, and 72% (acute genitourinary [GU], P = .024) and 39%, 29%, and 32% vs 32%, 28%, and 40% (acute rectal, P = .495). On univariate regression, only MRI use and International Prostate Symptom Scores reached significance for acute GU toxicity. On multivariate regression, age, prostate volume, and MRI use reached statistical significance for acute GU toxicity. No factor reached significance for rectal toxicity. CONCLUSIONS: This study demonstrates a statistically significant reduction in clinical acute GU toxicity with the clinical implementation of MRI in the treatment planning process.

Dosimetric and cost comparison of first fraction imaging versus fractional re-imaging on critical organ dose in vaginal cuff brachytherapy.

PURPOSE: Vaginal cylinder high-dose-rate (HDR) brachytherapy is currently one of the most common procedures performed in the treatment of early-stage endometrial cancer. However, current recommendations by the American Brachytherapy Society regarding fractional re-imaging and dose calculation for organs at risk for HDR vaginal cuff brachytherapy are not well defined. In this study, we aim to compare a fractional re-imaging approach using computed tomographic (CT) scans prior to each fraction with a first fraction imaging-only approach with respect to bladder, rectal, and bowel dosimetry. METHODS AND MATERIALS: Nineteen endometrial cancer patients undergoing vaginal cuff brachytherapy for endometrial cancer were imaged with CT scanning prior to every HDR fraction (fractional re-imaging [FRI]). Dose to the bowel, bladder, and rectum were calculated and compared with the estimated dose if imaging and planning were done only on the first fraction (first fraction imaging [FFI]). RESULTS: In the analysis of FFI versus FRI, we observed mean bladder doses of 8.34 Gy vs 8.33 Gy (P = .98), mean rectal doses of 12.19 Gy versus 12.14 Gy (P = .81), and mean bowel doses of 2.82 Gy versus 2.76 Gy (P = .81). The FFI approach underestimated the FRI doses to the bladder, rectum, and bowel by 20% or more in 11%, 5%, and 29% of patients, respectively. Cost analysis revealed an estimated $663.06, or a 35% savings per patient treated with FFI. CONCLUSIONS: There is no statistically significant difference in the mean dose to the bladder, rectum, or bowel in patients undergoing HDR vaginal cuff brachytherapy with a first fraction imaging scheme versus a fractional re-imaging scheme. These results indicate that fractional re-imaging is not necessary except in patients whose estimated dose to critical organs is near the maximum limit.

Comparing central nervous system (CNS) and extra-CNS hemangiopericytomas in the Surveillance, Epidemiology, and End Results program: analysis of 655 patients and review of current literature.

BACKGROUND: Hemangiopericytomas (HPCs) are rare tumors in the central nervous system (CNS) and in extra-CNS sites. The authors of this report used the Surveillance, Epidemiology, and End Results (SEER) Program to study prognostic factors in patients with HPC. METHODS: The SEER database was analyzed for patients who were diagnosed with HPC tumors from 1973 to 2007. Patients were stratified into CNS and extra-CNS groups. Univariate and multivariate analyses were performed for the overall survival (OS) endpoint using major demographic factors (age, race, and sex) and disease factors (tumor site). RESULTS: In total, 655 patients with HPC were stratified into a CNS group (n = 199) and an extra-CNS group (n = 456). The patients with extra-CNS HPC were statistically older (mean age, 53 years vs 49 years; P = .008) and were more likely to have larger tumors (median greatest dimension, 7.0 cm vs 5.2 cm; P < .001). Patients who had CNS tumors had better OS and cause-specific survival (CSS) compared with patients who had extra-CNS tumors (P < .001 for both). Negative predictors of OS on multivariate analysis included extra-CNS tumor site (hazard ratio [HR], 1.6; P = .005) and older age (ages 40-59 years: HR, 2.08; P = .032; ages 60-79 years: HR, 3.9; P < .001; aged ≥80 years: HR, 7.7; P < .001). CONCLUSIONS: The current analysis demonstrated that patients with extra-CNS HPCs had worse OS and CSS than patients with CNS HPCs.

A Surveillance, Epidemiology and End Results (SEER) program comparison of adult and pediatric Wilms' tumor.

PURPOSE: To compare the characteristics and outcome of adults and children diagnosed with Wilms' tumor. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was analyzed for patients diagnosed with Wilms' tumor between 1973 and 2007. Patients were stratified into pediatric (<16 years) or adult (≥16 years) groups. Overall survival was the primary endpoint. RESULTS: A total of 2342 patients (2190 pediatric and 152 adult) with Wilms' tumor were identified. Adult patients were statistically more likely to be staged as localized than pediatric patients (62.5% vs 44.7%), to not receive any lymph node sampling (57.9% vs 16.2%), and to not receive any radiation treatment (74.3% vs 53.9%). Adults had a statistically worse overall survival (OS) than pediatric patients (5-year OS, 69% vs 88%, P<.001) despite the earlier tumor stage. When stratified by treatment era, the OS of all patients treated after 1981 was statistically higher than those treated before (5-year OS, 75% vs 89%, P<.001). Significant predictors of OS on univariate analysis for adults included treatment era, SEER stage, surgery, and radiation treatment. Significant predictors of OS on multivariate analysis of all patients included adult status (hazard ratio, 4.14; P<.001), treatment era, SEER stage, and surgery. CONCLUSION: Adults in the SEER database had statistically worse OS than pediatric patients despite previous studies showing comparable outcome when treated on protocol. The worse outcome of SEER adults likely stems from incorrect diagnosis, inadequate staging and undertreatment. We recommend lymph node samplings for all adult Wilms' tumor patients and collaboration with pediatric oncologists.

Dosimetric comparison of volumetric modulated arc therapy and intensity-modulated radiation therapy for pancreatic malignancies.

Volumetric-modulated arc therapy (VMAT) has been previously evaluated for several tumor sites and has been shown to provide significant dosimetric and delivery benefits when compared with intensity-modulated radiation therapy (IMRT). To date, there have been no published full reports on the benefits of VMAT use in pancreatic patients compared with IMRT. Ten patients with pancreatic malignancies treated with either IMRT or VMAT were retrospectively identified. Both a double-arc VMAT and a 7-field IMRT plan were generated for each of the 10 patients using the same defined tumor volumes, organs at risk (OAR) volumes, dose, fractionation, and optimization constraints. The planning tumor volume (PTV) maximum dose (55.8 Gy vs. 54.4 Gy), PTV mean dose (53.9 Gy vs. 52.1 Gy), and conformality index (1.11 vs. 0.99) were statistically similar between the IMRT and VMAT plans, respectively. The VMAT plans had a statistically significant reduction in monitor units compared with the IMRT plans (1109 vs. 498, p < 0.001). In addition, the doses to the liver, small bowel, and spinal cord were comparable between the IMRT and VMAT plans. However, the VMAT plans demonstrated a statistically significant reduction in the mean left kidney V(25) (9.4 Gy vs. 2.3 Gy, p = 0.018), mean right kidney V(15) (53.4 Gy vs. 45.9 Gy, p = 0.035), V(20) (32.2 Gy vs. 25.5 Gy, p = 0.016), and V(25) (21.7 Gy vs. 14.9 Gy, p = 0.001). VMAT was investigated in patients with pancreatic malignancies and compared with the current standard of IMRT. VMAT was found to have similar or improved dosimetric parameters for all endpoints considered. Specifically, VMAT provided reduced monitor units and improved bilateral kidney normal tissue dose. The clinical relevance of these benefits in the context of pancreatic cancer patients, however, is currently unclear and requires further investigation.

Radiation-induced tumor neoantigens: imaging and therapeutic implications.

Exposure of tumor cells to ionizing radiation (IR) is widely known to induce a number of cellular changes. One way that IR can affect tumor cells is through the development of neoantigens which are new molecules that tumor cells express at the cell membrane following some insult or change to the cell. There have been numerous reports in the literature of changes in both tumor and tumor vasculature cell surface molecule expression following treatment with IR. The usefulness of neoantigens for imaging and therapeutic applications lies in the fact that they are differentially expressed on the surface of irradiated tumor cells to a greater extent than on normal tissues. This differential expression provides a mechanism by which tumor cells can be "marked" by radiation for further targeting. Drug delivery vehicles or imaging agents conjugated to ligands that recognize and interact with the neoantigens can help to improve tumor-specific targeting and reduce systemic toxicity with cancer drugs. This article provides a review of the molecules that have been reported to be expressed on the surface of tumor cells in response to IR either in vivo or in vitro. Additionally, we provide a discussion of some of the methods used in the identification of these antigens and applications for their use in drug delivery and imaging.

Application of recombinant and non-recombinant peptides in the determination of tumor response to cancer therapy.

An early and reliable assessment of therapeutic efficacy during the treatment of cancer is essential to achieve an optimal treatment regimen and patient outcome. The use of labeled peptides to monitor tumor response is associated with several advantages. For example, peptides are very stable, non-immunogenic, are easy to label for imaging, they undergo rapid clearance from the circulation, can penetrate tumor tissue, and are inexpensive to synthesize. In this review, studies using recombinant and non-recombinant peptides to monitor the response of glioblastoma multiforme, lung, breast, pancreas, colon, prostate, and skin carcinomas to radiation and/or chemotherapeutics such as camptothecin, doxorubicin, etoposide, 5-fluorouracil, paclitaxel, AG3340, sunitinib, and dasatinib, are presented. A consideration of the imaging techniques available to monitor peptide localization, including near-infrared (NIR) fluorescence, magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasonography, is also included. Peptides that have been successfully used to monitor various tumor types and therapies have been shown to target proteins that undergo changes in expression in response to treatment, endothelial cells that respond to radiation, or mediators of apoptosis. Peptides that are able to selectively bind responsive versus unresponsive tumors have also been identified. Therefore, the advantages associated with the use of peptides, combined with the capacity for selected peptides to assess tumor response as demonstrated in various studies, support the use of labeled peptides to evaluate the effectiveness of a given cancer therapy.

Magnetic resonance imaging identifies multifocal and multicentric disease in breast cancer patients who are eligible for partial breast irradiation.

BACKGROUND: In this retrospective study, the authors hypothesized that magnetic resonance imaging (MRI) would alter partial breast irradiation (PBI) eligibility by identifying cancers outside the PBI volume compared with mammography alone. METHODS: Since 2002, MRI was used nonselectively at the authors' institution for the staging of patients with nonmetastatic breast cancer. Of 450 consecutive patients with invasive breast cancer, 110 patients who were eligible for PBI were identified by using criteria outlined by National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Oncology Group trial 0413 based on mammography, ultrasonography, and initial pathology. In that trial, patients were randomized (stage I/II invasive cancers that measured

Formative evaluation of standardized training for CT colonographic image interpretation by novice readers.

PURPOSE: To introduce an educational intervention-specifically, a specialized training course-and perform a formative evaluation of the effect of the intervention on novice reader interpretation of computed tomography (CT) colonographic data. MATERIALS AND METHODS: The study was institutional review board approved. Ten normal and 50 abnormal cases, those of 60 patients with 93 polyps-61 polyps 6-9 mm in diameter and 32 polyps 10 mm or larger-were selected from a previously published trial. Seven novice readers underwent initial training that consisted of a 1-day course, reading assignments, a self-study computer module (with 61 limited data sets), observation of an expert interpreting three cases, and full interpretation of 10 cases with unblinding after each case. After training, the observers independently interpreted 60 cases by means of primary two-dimensional reading with unblinding after each case. For each case, the reading time and the location and maximal diameter of the polyp(s) were recorded. A t test was used to evaluate the observers' improvements, and empirical receiver operating characteristic (ROC) curves were constructed. RESULTS: By-patient sensitivities and specificities were determined for each observer. The lowest by-patient sensitivity at the 6 mm or larger polyp threshold was 86%, with 90% specificity. Four observers had 100% by-patient sensitivity at the 10 mm or larger polyp threshold, with 82%-97% specificity. For polyps 10 mm or larger, mean sensitivity and specificity were 98% and 92%, respectively. For the last 20 cases, the average interpretation time per case was 25 minutes. The range of areas under the ROC curve across observers was low: 0.86-0.95. CONCLUSION: In the described polyp-enriched cohort, novice CT colonographic data readers achieved high sensitivity and good specificity at formative evaluation of a comprehensive training program. Use of a similar comprehensive training method might reduce interreader variability in interpretation accuracy and be useful for reader certification.