Initial management of prostate-specific antigen-detected, low-risk prostate cancer and the risk of death from prostate cancer.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The recently published Prostate Cancer Intervention versus Observation Trial (PIVOT) did not identify differences in prostate cancer-specific mortality or all-cause mortality among patients with low-risk disease managed conservatively vs those managed definitively; however, recently published data suggest that older men may harbour more aggressive disease than is identified at biopsy owing to sampling error and undergrading. Whether older men with apparent low-risk disease are placed at risk of prostate cancer-specific mortality when managed conservatively remains unknown. The study used population-level data to show that non-curative approaches for older men with low-risk prostate cancer do result in an increased risk of prostate cancer-specific mortality. Differences between our study and the PIVOT trial include the fact that we included a larger sample size, analysed the data using an 'as-treated' approach, and included a healthier cohort of men as evinced by lower 4-year all-cause mortality estimates in our study than in the PIVOT. Our results suggest that older men with apparent low-risk prostate cancer are at risk of undergrading, which probably explains the differences in prostate cancer-specific mortality observed between men managed conservatively vs those managed definitively. Our study suggests that alternative approaches to excluding occult, high grade prostate cancer are needed in such men. OBJECTIVE: To evaluate whether older age in men with low-risk prostate cancer increases the risk of prostate cancer-specific mortality (PCSM) when non-curative approaches are selected as initial management. PATIENTS AND METHODS: The study cohort consisted of 27 969 men, with a median age of 67 years, with prostate-specific antigen (PSA)-detected, low-risk prostate cancer (clinical category T1c, Gleason score ≤6, and PSA ≤10) identified by the Surveillance, Epidemiology and End Results programme between 2004 and 2007. Fine and Gray's competing risk regression analysis was used to evaluate whether management with non-curative vs curative therapy was associated with an increased risk of PCSM after adjusting for PSA level, age at diagnosis and year of diagnosis. RESULTS: After a median follow-up of 2.75 years, 1121 men died, 60 (5.4%) from prostate cancer. Both older age (adjusted hazard ratio [AHR] 1.05; 95% confidence interval (CI) 1.02-1.08; P < 0.001) and non-curative treatment (AHR 3.34; 95% CI 1.97-5.67; P < 0.001) were significantly associated with an increased risk of PCSM. Men > the median age experienced increased estimates of PCSM when treated with non-curative as opposed to curative intent (P < 0.001); this finding was not seen in men ≤ the median age (P = 0.17). CONCLUSION: Pending prospective validation, our study suggests that non-curative approaches for older men with 'low-risk' prostate cancer result in an increased risk of PCSM, suggesting the need for alternative approaches to exclude occult, high grade prostate cancer in these men.

Frameless single-isocenter intensity modulated stereotactic radiosurgery for simultaneous treatment of multiple intracranial metastases.

PURPOSE: Stereotactic radiosurgery (SRS) is well accepted treatment for patients with intracranial metastases, but the role of frameless radiosurgery is not well defined. Here, we describe our clinical experience applying a novel single-isocenter technique to frameless intensity modulated stereotactic radiosurgery (IMRS) for simultaneous treatment of multiple intracranial metastases. METHODS AND MATERIALS: Between 2006 and 2012, 100 consecutive patients received frameless IMRS for multiple intracranial metastases using a single, centrally-located isocenter. Among these, 29 patients were treated for progressive or recurrent intracranial disease. A total of 465 metastases (median, 4 per patient, range, 2-18) were treated to a median dose of 20 Gy (range, 15-50 Gy). Follow-up including clinical examination and magnetic resonance imaging (MRI) occurred every 3 months. RESULTS: Median follow-up for all patients was 4.3 months (range, 0.2-58.3 months), with 83 patients (83.0%) followed until their death. For the remaining 17 patients alive at the time of analysis, median follow-up was 9.2 months (range, 2.2-58.3 months). Overall survival at 6 months was 49.5% [95% confidence interval (CI), 35.3-63.6%]. Local control at 6 and 12 months was 88.9% (95% CI, 79.1-98.6%) and 81.5% (95% CI, 65.2-97.7%), respectively. Regional failure was observed in 39 patients (39%), and 25 patients (25%) received salvage therapy. Grade 3 or greater treatment-related toxicity was observed in 4 patients (4%) and included intracranial hemorrhage, seizure, and radionecrosis. Median total treatment time was 17.2 minutes (range, 2.8-55.3 minutes). CONCLUSIONS: Single-isocenter IMRS for multiple intracranial metastases can produce clinical outcomes comparable to those of conventional radiosurgery techniques.

Cost effectiveness of proton therapy compared with photon therapy in the management of pediatric medulloblastoma.

BACKGROUND: Proton therapy has been a hotly contested issue in both scientific publications and lay media. Proponents cite the modality's ability to spare healthy tissue, but critics claim the benefit gained from its use does not validate its cost compared with photon therapy. The objective of this study was to evaluate the cost effectiveness of proton therapy versus photon therapy in the management of pediatric medulloblastoma. METHODS: A cost-effective analysis was performed from the societal perspective using a Monte Carlo simulation model. A population of pediatric medulloblastoma survivors aged 18 years was studied who had received treatment at age 5 years and who were at risk of developing 10 adverse events, such as growth hormone deficiency, coronary artery disease, ototoxicity, secondary malignant neoplasm, and death. Costing data included the cost of investment and the costs of diagnosis and management of adverse health states from institutional and Medicare data. Longitudinal outcomes data and recent modeling studies informed risk parameters for the model. Incremental cost-effectiveness ratios were used to measure outcomes. RESULTS: Results from the base case demonstrated that proton therapy was associated with higher quality-adjusted life years and lower costs; therefore, it dominated photon therapy. In 1-way sensitivity analyses, proton therapy remained the more attractive strategy, either dominating photon therapy or having a very low cost per quality-adjust life year gained. Probabilistic sensitivity analysis illustrated the domination of proton therapy over photon therapy in 96.4% of simulations. CONCLUSIONS: By using current risk estimates and data on required capital investments, the current study indicated that proton therapy is a cost-effective strategy for the management of pediatric patients with medulloblastoma compared with standard of care photon therapy.

Advancing age within established Gleason score categories and the risk of prostate cancer-specific mortality (PCSM).

UNLABELLED: Study Type - Prognosis (case series) Level of Evidence 4. What's known on the subject? and What does the study add? There is limited data that suggests that men aged >70 years have a higher proportion of Gleason 8-10 prostate cancer than men aged <70 years, as well as a higher risk of PSA recurrence, distant metastases, and disease-specific death on univariate analysis. The present study shows that older as compared with younger men with Gleason score 6 and 7 prostate cancer have an increased risk of prostate cancer-specific mortality. This may be due to the presence of occult high-grade disease and suggests further diagnostic studies, e.g. multiparametric MRI, may be indicated in these men to reduce biopsy sampling error. OBJECTIVE: To determine if advancing age is a risk factor for high-grade prostate cancer due to occult high-grade disease in elderly men with Gleason score 6 or 7 prostate cancer. We investigated whether advancing age is associated with the risk of prostate cancer-specific mortality (PCSM) within established Gleason score categories adjusting for known predictors of PCSM. PATIENTS AND METHODS: Using data from the Surveillance, Epidemiology and End Results database between 1 January 2004 to 31 December 2007, 166 104 men with non-metastatic prostate cancer were identified and formed the study cohort. • Within established Gleason score categories, Fine and Gray's multivariable competing risk regressions were used to evaluate whether increasing age at diagnosis was significantly associated with an increased risk of PCSM, adjusting for prostate-specific antigen level and T-category at diagnosis and whether treatment was curative or non-curative. RESULTS: After adjusting for treatment and prognostic factors, Gleason score 8-10 and 7 as compared with ≤6 was associated with an increased risk of PCSM (P < 0.001). • Increasing age was associated with an increased risk of PCSM only in Gleason score 6 (adjusted hazard ratio [AHR] 1.06, 95% confidence interval [CI] 1.04-1.08, P < 0.001) and 7 (AHR 1.02, 95% CI 1.01-1.03, P < 0.001), but not with Gleason score 8-10 (AHR 0.999, 95% CI 0.995-1.003, P= 0.61). • These risks were highest in men aged >70 years having Gleason score 6 (AHR 1.10, 95% CI 1.07-1.13, P < 0.001) and Gleason score 7 prostate cancer (AHR 1.04, 95% CI 1.02-1.06, P < 0.001). CONCLUSIONS: PCSM increases with advancing age in men with Gleason score 6 and 7 but not 8-10 prostate cancer. • Techniques to reduce biopsy sampling error in men, particularly those aged >70 years and healthy with Gleason score 6 and 7 disease deserve further study.

Early detection of high-grade prostate cancer using digital rectal examination (DRE) in men with a prostate-specific antigen level of <2.5 ng/mL and the risk of death.

UNLABELLED: Study Type--Prognosis (inception cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? There is little data on the utility of digital rectal examination (DRE) as a diagnostic tool in the era of prostate-specific antigen (PSA) testing. Using a population-based database, we found that detection of prostate cancer while still localized among men with high-grade PSA-occult disease may result in survival benefit. OBJECTIVE: • To determine whether detection of high-grade prostate cancer while still clinically localised on digital rectal examination (DRE) can improve survival in men with a normal prostate-specific antigen (PSA) level. PATIENTS AND METHODS: • From the Surveillance, Epidemiology and End Results database, 166,104 men with prostate cancer diagnosed between 2004 and 2007 were identified. • Logistic regression was used to identify factors associated with the occurrence of palpable, PSA-occult (PSA level of <2.5 ng/mL), Gleason score 8-10 prostate cancer. • Fine and Gray's and Cox multivariable regressions were used to analyse whether demographic, treatment, and clinicopathological factors were associated with the risk of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM), respectively. RESULTS: • Both increasing age (adjusted odds ratio [aOR] 1.02, 95% confidence interval (CI) 1.01-1.03; P < 0.001) and White race (aOR 1.26, 95% CI 1.03-1.54; P = 0.027) were associated with palpable, Gleason 8-10 prostate cancer. Of 166,104 men, 685 (0.4%) had this subset of prostate cancer. • Significant factors associated with risk of PCSM included PSA level (adjusted hazard ratio [aHR] 0.71, 95% CI 0.51-0.99; P = 0.04), higher Gleason score (aHR 2.20, 95% CI 1.25-3.87; P = 0.006), and T3-T4 vs T2 disease (aHR 3.11, 95% CI 1.79-5.41; P < 0.001). • Significant factors associated with risk of ACM included age (aHR 1.03, 95% CI 1.01-1.06; P = 0.006), higher Gleason score (aHR 2.05, 95% CI 1.36-3.09; P < 0.001), and T3-T4 vs T2 disease (aHR 2.11, 95% CI 1.38-3.25, P < 0.001) CONCLUSIONS: • Clinically localised disease on DRE among men with PSA-occult high-grade prostate cancer was associated with improved PCSM and ACM, suggesting that DRE in this cohort (older age and White race) may have the potential to improve survival.

US Food and Drug Administration Regulation of Medical Devices and Radiation Oncology: Can Reform Improve Safety?

Although radiation therapy is highly safe and effective in treating cancer, recent reports of dangerous radiation-related errors have focused a national spotlight on the field of radiation oncology and, more specifically, on the rapidly evolving and complex nature of radiation devices and how they are regulated. The purpose of this review is to explore the issues involved in medical device regulation in radiation oncology. We start with a general review of federal medical device regulation, including explanations of the legal and regulatory framework, and then discuss issues specific to radiation oncology with real-world examples. We also provide our thoughts on potential solutions and reforms to the current system, including better reporting of radiation-related errors in a centralized database, well-defined criteria for establishing substantial equivalence of a new device, and standard postmarket surveillance of radiation devices. Modern radiation therapy is a powerful tool that can help cure many patients' cancers and alleviate others' suffering with limited adverse effects. We must ensure that this promise is never compromised by avoidable mistakes.

Radiation recall myositis in pediatric Ewing sarcoma.

Radiation recall is a rare and poorly understood phenomenon, characterized by an acute inflammatory reaction within the previously irradiated area, triggered by a precipitating systemic agent. This reaction typically affects the skin, and radiation recall myositis in the absence of cutaneous involvement has rarely been described in the literature. In this report, we present two cases of radiation recall in pediatric Ewing sarcoma patients receiving successive proton radiotherapy and chemotherapy, with magnetic resonance imaging (MRI) of muscle edema within the prior radiation fields.

Proton radiotherapy for high-risk pediatric neuroblastoma: early outcomes and dose comparison.

PURPOSE: To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed. METHODS AND MATERIALS: All patients with high-risk (International Neuroblastoma Staging System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our institution were included. All patients received induction chemotherapy, surgical resection of residual disease, high-dose chemotherapy with stem cell rescue, and adjuvant 3D-CPT to the primary tumor sites. The patients were followed with clinical examinations, imaging, and laboratory testing every 6 months to monitor disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT plans were generated and compared for a representative case of adjuvant RT to the primary tumor bed followed by a boost. RESULTS: Nine patients were treated with 3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and all patients had Stage IV disease. All patients had unfavorable histologic characteristics (poorly differentiated histologic features in 8, N-Myc amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median follow-up of 38 months (range 11-70), there were no local failures. Four patients developed distant failure, and, of these, two died of disease. Acute side effects included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients. Although comparable target coverage was achieved with all three modalities, proton therapy achieved substantial normal tissue sparing compared with IMRT. Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs, and heart. CONCLUSIONS: Preliminary outcomes reveal excellent local control with proton therapy for high-risk neuroblastoma, although distant failures continu to occur. Dosimetric comparisons demonstrate the advantage of proton RT compared with IMRT in this setting, allowing more conformal treatment and better normal tissue sparing.

Accelerated partial breast irradiation using brachytherapy for breast cancer: patterns in utilization and guideline concordance.

BACKGROUND: Accelerated partial breast irradiation using brachytherapy (APBIb) is an alternative to whole-breast irradiation (WBI) after breast-conserving surgery. We evaluated patterns of APBIb use with respect to 2009 American Society for Radiation Oncology consensus guidelines (ASTRO-G) in a population-based cohort. METHODS: From Surveillance, Epidemiology, and End Results data, we identified 138 815 American women with breast cancer diagnosed between January 1, 2000, and December 31, 2007, who underwent WBI or APBIb after breast-conserving surgery and classified them as suitable, cautionary, or unsuitable for APBIb according to ASTRO-G criteria. Logistic regression was applied to study APBIb use overall and within each guideline category. All P values are from two-sided tests. RESULTS: Overall, 2.6% of patients received APBIb, and 65.8% of them were classified as cautionary or unsuitable. APBIb was used by 5% of suitable, 3.4% of cautionary, and 1.6% of unsuitable patients by ASTRO-G criteria (P < .001). APBIb use increased from 0.4% in 2000 to 6.6% in 2007 and varied widely (0%-7%) between localities. Variables associated with APBIb use among suitable patients included other vs white race (odds ratio [OR] = 0.51, P < .001), region (OR = 2.60-8.62, P < .001), and more recent year (OR = 20.3, P < .001). Among cautionary patients, variables associated with APBIb use included black vs white race (OR = 0.76, P = .027), other vs white race (OR = 0.57, P < .001), Hispanic ethnicity (OR = 0.75, P = .036), region (OR = 3.10-10.2, P < .001), nonmetropolitan or rural location (OR = 0.53, P = .012), and more recent year (OR = 17.6, P < .001). Among unsuitable patients, black vs white race (OR = 0.77, P = .008), other vs white race (OR = 0.46, P < .001), region (OR = 3.33-21.6, P < .001), and more recent year (OR = 12.7, P < .001) were associated with APBIb use. CONCLUSIONS: APBIb after breast-conserving surgery has been rapidly adopted in the United States. Use varied by race, ethnicity, and widely by region, especially among patients who may not be suitable for this radiation technique.

Accelerated partial breast irradiation with low-dose-rate interstitial implant brachytherapy after wide local excision: 12-year outcomes from a prospective trial.

PURPOSE: To evaluate the long-term toxicity, cosmesis, and local control of accelerated partial breast irradiation with implant brachytherapy after wide local excision for Stage T1N0 breast cancer (BCa). MATERIALS AND METHODS: Between 1997 and 2001, 50 patients with Stage T1N0M0 BCa were treated in a Phase I-II protocol using low-dose-rate accelerated partial breast irradiation with implant brachytherapy after wide local excision and lymph node surgery. The total dose was escalated in three groups: 50 Gy (n = 20), 55 Gy (n = 17), and 60 Gy (n = 13). Patient- and physician-assessed breast cosmesis, patient satisfaction, toxicity, mammographic abnormalities, repeat biopsies, and disease status were prospectively evaluated at each visit. Kendall's tau (τ(ß)) and logistic regression analyses were used to correlate outcomes with dose, implant volume, patient age, and systemic therapy. RESULTS: The median follow-up period was 11.2 years (range, 4-14). The patient satisfaction rate was 67%, 67% reported good-excellent cosmesis, and 54% had moderate-severe fibrosis. Higher dose was correlated with worse cosmetic outcome (τ(ß) 0.6, p < .0001), lower patient satisfaction (τ(ß) 0.5, p < .001), and worse fibrosis (τ(ß) 0.4, p = .0024). Of the 50 patients, 35% had fat necrosis and 34% developed telangiectasias ≥1 cm(2). Grade 3-4 late skin and subcutaneous toxicities were seen in 4 patients (9%) and 6 patients (13%), respectively, and both correlated with higher dose (τ(ß) 0.3-0.5, p ≤ .01). One patient had Grade 4 skin ulceration and fat necrosis requiring surgery. Mammographic abnormalities were seen in 32% of the patients, and 30% underwent repeat biopsy, of which 73% were benign. Six patients had ipsilateral breast recurrence: five elsewhere in the breast, and one at the implant site. One patient died of metastatic BCa after recurrence. The 12-year actuarial local control, recurrence-free survival, and overall survival rate was 85% (95% confidence interval, 70-97%), 72% (95% confidence interval, 54-86%), and 87% (95% confidence interval, 73-99%), respectively. CONCLUSION: Low-dose-rate accelerated partial breast irradiation with implant brachytherapy provides acceptable local control in select early-stage BCa patients. However, treatment-related toxicity and cosmetic complications were significant with longer follow-up and at higher doses.

Planned two-fraction proton beam stereotactic radiosurgery for high-risk inoperable cerebral arteriovenous malformations.

PURPOSE: To evaluate patients with high-risk cerebral arteriovenous malformations (AVMs), based on eloquent brain location or large size, who underwent planned two-fraction proton stereotactic radiosurgery (PSRS). METHODS AND MATERIALS: From 1991 to 2009, 59 patients with high-risk cerebral AVMs received two-fraction PSRS. Median nidus volume was 23 cc (range, 1.4-58.1 cc), 70% of cases had nidus volume ≥ 14 cc, and 34% were in critical locations (brainstem, basal ganglia). Median AVM score based on age, AVM size, and location was 3.19 (range, 0.9-6.9). Many patients had prior surgery or embolization (40%) or prior PSRS (12%). The most common prescription was 16 Gy radiobiologic equivalent (RBE) in two fractions, prescribed to the 90% isodose. RESULTS: At a median follow-up of 56.1 months, 9 patients (15%) had total and 20 patients (34%) had partial obliteration. Patients with total obliteration received higher total dose than those with partial or no obliteration (mean dose, 17.6 vs. 15.5 Gy (RBE), p = 0.01). Median time to total obliteration was 62 months (range, 23-109 months), and 5-year actuarial rate of partial or total obliteration was 33%. Five-year actuarial rate of hemorrhage was 22% (95% confidence interval, 12.5%-36.8%) and 14% (n = 8) suffered fatal hemorrhage. Lesions with higher AVM scores were more likely to hemorrhage (p = 0.024) and less responsive to radiation (p = 0.026). The most common complication was Grade 1 headache acutely (14%) and long term (12%). One patient developed a Grade 2 generalized seizure disorder, and two had mild neurologic deficits. CONCLUSIONS: High-risk AVMs can be safely treated with two-fraction PSRS, although total obliteration rate is low and patients remain at risk for future hemorrhage. Future studies should include higher doses or a multistaged PSRS approach for lesions more resistant to obliteration with radiation.

Predictors of the use of supplemental androgen suppression therapy and external beam radiation in men with high-risk prostate cancer undergoing brachytherapy in community practice.

PURPOSE: We assessed clinical- and practice-related variables associated with the use of trimodality treatment (androgen suppression therapy, external beam radiation therapy, and brachytherapy) in a community-based cohort of men with high-risk prostate cancer. METHODS AND MATERIALS: The study cohort was composed of 1342 men with a prostate-specific antigen level >20ng/mL, clinical tumor stage T3 or T4, and/or Gleason score 8-10 disease at two community radiation facilities, Chicago Prostate Cancer Center (Chicago PCC) and 21st Century Oncology (21C). Logistic regression multivariable analysis was performed to identify factors associated with trimodality treatment. RESULTS: Of 1342 men treated from 1991 to 2005, 650 (48%) received trimodality therapy. Factors associated with trimodality use include younger age (adjusted odds ratio [AOR] 0.95, p<0.0001), increasing prostate-specific antigen (AOR 1.54, p<0.0001), Gleason score 7 (AOR 2.88, p<0.0001), Gleason score 8-10 (AOR 4.28, p<0.0001), clinical category T2 (AOR 1.40, p=0.012), clinical category T3 (AOR 4.84, p<0.0001), and year of brachytherapy (AOR 1.13, p<0.0001). Patients treated at 21C were 4.6 times more likely to receive trimodality therapy (p<0.0001) than Chicago PCC. There was a significant interaction between cardiovascular comorbidity status and site (comorbidity×21C, AOR 1.74, p=0.025), indicating that less healthy patients were more likely to receive trimodality treatment at 21C than healthy patients and vice versa at Chicago PCC. CONCLUSIONS: Younger men and those with more aggressive pretreatment clinical factors were more likely to receive trimodality treatment in this community cohort of men with high-risk prostate cancer. Selection for trimodality use varied significantly by site indicating a need for treatment standardization in the community.

Results and patterns of failure in patients treated with adjuvant combined chemoradiation therapy for resected pancreatic adenocarcinoma.

BACKGROUND: Although adjuvant chemoradiation is used commonly in the United States for the treatment of resected pancreatic cancer, there is no consensus on the benefit of this therapy, because the results from randomized trials are conflicting. The authors of this report reviewed their experience in a consecutive, unselected series of patients who received adjuvant 5-fluorouracil (5-FU) and radiation therapy (RT) for resected pancreatic adenocarcinoma. METHODS: Eighty-six patients with resected pancreatic adenocarcinoma who received adjuvant therapy from 1998 to 2005 were identified, and their medical records were reviewed. Ninety-three percent of patients were treated with external beam RT to > or =50.4 grays, and 91% of patients received concurrent 5-FU by continuous infusion. Forty-five percent of patients went on to receive adjuvant gemcitabine. RESULTS: The median follow-up was 31 months (range, 21-62 months) among the 20 patients who remained alive. Less than half of patients had positive (33%) or close (<1 mm; 15%) resection margins, 81% of tumors were classified as T3, and 66% of patients had involved lymph nodes. The median overall survival (OS) for all patients was 22 months. Negative lymph node status (P = .016) was a significant prognostic factor for improved OS, whereas treatment with gemcitabine trended toward improved OS (P = .080). The median disease-free survival (DFS) for all patients was 10 months: Treatment with gemcitabine (P = .044) and the receipt of any chemotherapy (P = .047) were significant predictors of DFS. Seventy-five patients (87%) had disease recurrence, and the majority recurred with peritoneal metastases (55%) or liver metastases (53%). Patients who had negative lymph nodes trended toward a lower rate of distant failure (P = .060). CONCLUSIONS: The median survival of the current cohort was greater than that of the chemoradiation arms of European Organization for Research and Treatment of Cancer trials and European Study Group for Pancreatic Cancer 1 trials and was comparable to the survival observed on the Gastrointestinal Tumor Study Group chemoradiation arm. Lymph node status and treatment with adjuvant chemotherapy were significant predictors of OS and DFS, respectively. Future survival improvements should be directed at reducing peritoneal and liver metastases. Further randomized trials will be required to define the role of adjuvant therapy for pancreatic adenocarcinoma.

Breast stromal enhancement on MRI is associated with response to neoadjuvant chemotherapy.

OBJECTIVE: Cancerous neovascular changes in histologically normal-appearing breast tissue have been shown to increase risk for local recurrence after breast-conserving therapy. However, the imaging characteristics of this tissue have not been well studied. We hypothesized that signal enhancement ratios from dynamic contrast-enhanced breast MRI could be used to analyze the contrast kinetics of microvasculature in breast stroma beyond the tumor margin and that this information can be developed to improve local treatment options. MATERIALS AND METHODS: Signal enhancement ratio analysis of nontumor breast stroma was performed on dynamic contrast-enhanced MRI scans of 42 patients who received neoadjuvant chemotherapy for invasive breast cancer performed before chemotherapy (scan 1) and after one cycle of chemotherapy (scan 2). Stromal signal enhancement ratio values were then correlated to several clinical parameters and to clinical outcome using univariate and multivariate analyses. Median follow-up for the group was 52.1 months. RESULTS: On univariate analysis, factors that were significantly associated (p < 0.05) with disease-free survival included the mean stromal signal enhancement ratio at scan 2 (hazard ratio [HR] = 0.11, 95% CI = 0.013-0.88, p = 0.03), pretreatment tumor size (HR = 1.33, 95% CI = 1.07-1.66, p = 0.012), pretreatment tumor volume (HR = 1.04, 95% CI = 1.01-1.07, p = 0.006), and number of involved axillary lymph nodes (HR = 1.18, 95% CI = 1.05-1.32, p = 0.005). These factors were then analyzed in a multivariate Cox proportional hazards model. The only factor that was associated with disease-free survival was mean stromal signal enhancement ratio at scan 2 (HR = 0.11, 95% CI = 0.012-0.95, p < 0.045). CONCLUSION: These findings indicate that breast stroma tissue outside the incident tumor can be quantified using signal enhancement ratio analysis on dynamic contrast-enhanced MRI. Stromal signal enhancement ratio is a potential indicator for response to treatment and for overall outcome in patients with breast cancer; however, these results should be validated in a prospective study.