Neutrophil-Lymphocyte Ratio Is a Prognostic Marker in Patients with Locally Advanced (Stage IIIA and IIIB) Non-Small Cell Lung Cancer Treated with Combined Modality Therapy.

BACKGROUND: Neutrophil-lymphocyte ratio (NLR) is a measure of systemic inflammation that appears prognostic in localized and advanced non-small cell lung cancer (NSCLC). Increased systemic inflammation portends a poorer prognosis in cancer patients. We hypothesized that low NLR at diagnosis is associated with improved overall survival (OS) in locally advanced NSCLC (LANSCLC) patients. PATIENTS AND METHODS: Records from 276 patients with stage IIIA and IIIB NSCLC treated with definitive chemoradiation with or without surgery between 2000 and 2010 with adequate data were retrospectively reviewed. Baseline demographic data and pretreatment peripheral blood absolute neutrophil and lymphocyte counts were collected. Patients were grouped into quartiles based on NLR. OS was estimated using the Kaplan-Meier method. The log-rank test was used to compare mortality between groups. A linear test-for-trend was used for the NLR quartile groups. The Cox proportional hazards model was used for multivariable analysis. RESULTS: The NLR was prognostic for OS (p < .0001). Median survival in months (95% confidence interval) for the first, second, third, and fourth quartile groups of the population distribution of NLR were 27 (19-36), 28 (22-34), 22 (12-31), and 10 (8-12), respectively. NLR remained prognostic for OS after adjusting for race, sex, stage, performance status, and chemoradiotherapy approach (p = .004). CONCLUSION: To our knowledge, our series is the largest to demonstrate that baseline NLR is a significant prognostic indicator in LANSCLC patients who received definitive chemoradiation with or without surgery. As an indicator of inflammatory response, it should be explored as a potential predictive marker in the context of immunotherapy and radiation therapy. IMPLICATIONS FOR PRACTICE: Neutrophil-lymphocyte ratio measured at the time of diagnosis was associated with improved overall survival in 276 patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) treated with definitive chemoradiation with or without surgery. To our knowledge, our series is the largest to demonstrate that baseline neutrophil-lymphocyte ratio is a significant prognostic indicator in locally advanced NSCLC patients who received definitive chemoradiation with or without surgery. Neutrophil-lymphocyte ratio is an inexpensive biomarker that may be easily utilized by clinicians at the time of locally advanced NSCLC diagnosis to help predict life expectancy.

Potential of computer-aided diagnosis of high spectral and spatial resolution (HiSS) MRI in the classification of breast lesions.

PURPOSE: To compare the performance of computer-aided diagnosis (CADx) analysis of precontrast high spectral and spatial resolution (HiSS) MRI to that of clinical dynamic contrast-enhanced MRI (DCE-MRI) in the diagnostic classification of breast lesions. MATERIALS AND METHODS: Thirty-four malignant and seven benign lesions were scanned using two-dimensional (2D) HiSS and clinical 4D DCE-MRI protocols. Lesions were automatically segmented. Morphological features were calculated for HiSS, whereas both morphological and kinetic features were calculated for DCE-MRI. After stepwise feature selection, Bayesian artificial neural networks merged selected features, and receiver operating characteristic (ROC) analysis evaluated the performance with leave-one-lesion-out validation. RESULTS: AUC (area under the ROC curve) values of 0.92 ± 0.06 and 0.90 ± 0.05 were obtained using CADx on HiSS and DCE-MRI, respectively, in the task of classifying benign and malignant lesions. While we failed to show that the higher HiSS performance was significantly better than DCE-MRI, noninferiority testing confirmed that HiSS was not worse than DCE-MRI. CONCLUSION: CADx of HiSS (without contrast) performed similarly to CADx on clinical DCE-MRI; thus, computerized analysis of HiSS may provide sufficient information for diagnostic classification. The results are clinically important for patients in whom contrast agent is contra-indicated. Even in the limited acquisition mode of 2D single slice HiSS, by using quantitative image analysis to extract characteristics from the HiSS images, similar performance levels were obtained as compared with those from current clinical 4D DCE-MRI. As HiSS acquisitions become possible in 3D, CADx methods can also be applied. Because HiSS and DCE-MRI are based on different contrast mechanisms, the use of the two protocols in combination may increase diagnostic accuracy.

Evaluation of clinical breast MR imaging performed with prototype computer-aided diagnosis breast MR imaging workstation: reader study.

PURPOSE: To evaluate a computer-aided diagnosis (CADx) system for dynamic contrast material-enhanced magnetic resonance (MR) imaging and compare it with a currently used clinical method of interpreting breast MR image findings that includes the use of commercially available automated software for kinetic image data processing and visualization. MATERIALS AND METHODS: In this HIPAA-compliant, institutional review board-approved study, a training set of 121 breast lesions (77 malignant, 44 benign) was used to train the CADx system. After practicing with 10 training cases, six breast imaging radiologists assessed the likelihood of malignancy and the need for biopsy with a separate test set of 60 lesions (30 malignant, 30 benign). Their performances in differentiating between benign and malignant breast lesions both without (conventional lesion viewing, output from commercially available breast MR imaging analysis software) and with the aid of the CADx workstation (with classification yielding an estimation of the probability of malignancy for each lesion) were evaluated with receiver operating characteristic analysis. RESULTS: When CADx was used, the average performance of the radiologists was significantly improved, as indicated by increases in mean area under the receiver operating characteristic curve (from 0.80 to 0.84, P = .007), mean sensitivity (from 83% to 88%, P = .001), and average number of biopsy recommendations for malignant cases (1.7 more biopsies for malignant lesions with use of CADx, P = .032). Although the mean specificity improved (from 50% to 53%), the improvement was not significant (P = .2). CONCLUSION: Use of the CADx system improved the radiologists' performance in differentiating between malignant and benign MR imaging-depicted breast lesions.

Combined use of T2-weighted MRI and T1-weighted dynamic contrast-enhanced MRI in the automated analysis of breast lesions.

A multiparametric computer-aided diagnosis scheme that combines information from T1-weighted dynamic contrast-enhanced (DCE)-MRI and T2-weighted MRI was investigated using a database of 110 malignant and 86 benign breast lesions. Automatic lesion segmentation was performed, and three categories of lesion features (geometric, T1-weighted DCE, and T2-weighted) were automatically extracted. Stepwise feature selection was performed considering only geometric features, only T1-weighted DCE features, only T2-weighted features, and all features. Features were merged with Bayesian artificial neural networks, and diagnostic performance was evaluated by ROC analysis. With leave-one-lesion-out cross-validation, an area under the ROC curve value of 0.77±0.03 was achieved with T2-weighted-only features, indicating high diagnostic value of information in T2-weighted images. Area under the ROC curve values of 0.79±0.03 and 0.80 ± 0.03 were obtained for geometric-only features and T1-weighted DCE-only features, respectively. When all features were considered, an area under the ROC curve value of 0.85±0.03 was achieved. We observed P values of 0.006, 0.023, and 0.0014 between the geometric-only, T1-weighted DCE-only, and T2-weighted-only features and all features conditions, respectively. When ranked, the P values satisfied the Holm-Bonferroni multiple-comparison test; thus, the improvement of multiparametric computer-aided diagnosis was statistically significant. A computer-aided diagnosis scheme that combines information from T1-weighted DCE and T2-weighted MRI may be advantageous over conventional T1-weighted DCE-MRI computer-aided diagnosis.

Cancerous breast lesions on dynamic contrast-enhanced MR images: computerized characterization for image-based prognostic markers.

PURPOSE: To assess the performance of computer-extracted dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging kinetic and morphologic features in the differentiation of invasive versus noninvasive breast lesions and metastatic versus nonmetastatic breast lesions. MATERIALS AND METHODS: In this institutional review board-approved HIPAA-compliant study, in which the requirement for informed patient consent was waived, breast MR images were retrospectively collected. The images had been obtained with a 1.5-T MR unit by using a gadodiamide-enhanced T1-weighted spoiled gradient-recalled acquisition in the steady state sequence. The breast MR imaging database contained 132 benign, 71 ductal carcinoma in situ (DCIS), and 150 invasive ductal carcinoma (IDC) lesions. Fifty-four IDC lesions were associated with metastasis-positive lymph nodes (LNs), and 64 IDC lesions were associated with negative LNs. Lesion segmentation and extraction of morphologic and kinetic features were automatically performed by a laboratory-developed computer workstation. Features were first selected by using stepwise linear discriminant analysis and then merged by using Bayesian neural networks. Lesion classification performance was assessed with receiver operating characteristic analysis. RESULTS: Differentiation of DCIS from IDC lesions yielded an area under the receiver operating characteristic curve (AUC) of 0.83 +/- 0.03 (standard error). AUCs were 0.85 +/- 0.02 for differentiation between IDC and benign lesions and 0.79 +/- 0.03 for differentiation between DCIS and benign lesions. Differentiation between IDC lesions associated with positive LNs and IDC lesions associated with negative LNs yielded an AUC of 0.82 +/- 0.04. AUCs were 0.86 +/- 0.03 for differentiation between IDC lesions associated with positive LNs and benign lesions and 0.83 +/- 0.03 for differentiation between IDC lesions associated with negative LNs and benign lesions. CONCLUSION: Computer-aided diagnosis of breast DCE MR imaging-depicted lesions was extended from the task of discriminating between malignant and benign lesions to the prognostic tasks of distinguishing between noninvasive and invasive lesions and discriminating between metastatic and nonmetastatic lesions, yielding MR imaging-based prognostic markers. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09090838/-/DC1.

Exploring nonlinear feature space dimension reduction and data representation in breast Cadx with Laplacian eigenmaps and t-SNE.

PURPOSE: In this preliminary study, recently developed unsupervised nonlinear dimension reduction (DR) and data representation techniques were applied to computer-extracted breast lesion feature spaces across three separate imaging modalities: Ultrasound (U.S.) with 1126 cases, dynamic contrast enhanced magnetic resonance imaging with 356 cases, and full-field digital mammography with 245 cases. Two methods for nonlinear DR were explored: Laplacian eigenmaps [M. Belkin and P. Niyogi, "Laplacian eigenmaps for dimensionality reduction and data representation," Neural Comput. 15, 1373-1396 (2003)] and t-distributed stochastic neighbor embedding (t-SNE) [L. van der Maaten and G. Hinton, "Visualizing data using t-SNE," J. Mach. Learn. Res. 9, 2579-2605 (2008)]. METHODS: These methods attempt to map originally high dimensional feature spaces to more human interpretable lower dimensional spaces while preserving both local and global information. The properties of these methods as applied to breast computer-aided diagnosis (CADx) were evaluated in the context of malignancy classification performance as well as in the visual inspection of the sparseness within the two-dimensional and three-dimensional mappings. Classification performance was estimated by using the reduced dimension mapped feature output as input into both linear and nonlinear classifiers: Markov chain Monte Carlo based Bayesian artificial neural network (MCMC-BANN) and linear discriminant analysis. The new techniques were compared to previously developed breast CADx methodologies, including automatic relevance determination and linear stepwise (LSW) feature selection, as well as a linear DR method based on principal component analysis. Using ROC analysis and 0.632+bootstrap validation, 95% empirical confidence intervals were computed for the each classifier's AUC performance. RESULTS: In the large U.S. data set, sample high performance results include, AUC0.632+ = 0.88 with 95% empirical bootstrap interval [0.787;0.895] for 13 ARD selected features and AUC0.632+ = 0.87 with interval [0.817;0.906] for four LSW selected features compared to 4D t-SNE mapping (from the original 81D feature space) giving AUC0.632+ = 0.90 with interval [0.847;0.919], all using the MCMC-BANN. CONCLUSIONS: Preliminary results appear to indicate capability for the new methods to match or exceed classification performance of current advanced breast lesion CADx algorithms. While not appropriate as a complete replacement of feature selection in CADx problems, DR techniques offer a complementary approach, which can aid elucidation of additional properties associated with the data. Specifically, the new techniques were shown to possess the added benefit of delivering sparse lower dimensional representations for visual interpretation, revealing intricate data structure of the feature space.

Insurance Status is an Independent Predictor of Overall Survival in Patients With Stage III Non-small-cell Lung Cancer Treated With Curative Intent.

INTRODUCTION: Population studies suggest an impact of insurance status on oncologic outcomes. We sought to explore this in a large single-institution cohort of patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively analyzed 342 consecutive patients (January 2000 to December 2013) curatively treated for stage III NSCLC. Patients were categorized by insurance status as uninsured (U), Medicare/Medicaid + Veterans Affairs (M/M + VA), or Private (P). The χ2 test was utilized to compare categorical variables. The Kaplan-Meier approach and the Cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence (FFR). RESULTS: Compared with M/M + VA patients, P insurance patients were more likely to be younger (P < .001), married (P < .001), Caucasian (P = .001), reside in higher median income zip codes (P < .001), have higher performance status (P < .001), and undergo consolidation chemotherapy (P < .001) and trimodality therapy (P < .001). Diagnosis to treatment was delayed > 30 days in U (67.3%), M/M + VA (68.1%), and P (52.6%) patients (P = .017). Compared with the M/M + VA and U cohorts, P insurance patients had improved OS (median/5-year: 30.7 months/34.2%, 19 months/17%, and 16.9 months/3.8%; P < .001) and FFR (median/5-year: 18.4 months/27.3%, 15.2 months/23.2%, and 11.4 months/4.8%; P = .012), respectively. On multivariate analysis, insurance status was an independent predictor for OS (P = .017) but not FFR. CONCLUSION: Compared with U or M/M + VA patients, P insurance patients with stage III NSCLC were more likely to be optimally diagnosed and treated, resulting in a doubling of median OS for P versus U patients. Improved access to affordable health insurance is critical to combat inequities in access to care and has potential for improvements in cancer outcomes.

Correlation of radiation dose and activity with clinical outcomes in metastatic colorectal cancer after selective internal radiation therapy using yttrium-90 resin microspheres.

PURPOSE: Yttrium-90 (Y)-resin microspheres are prescribed using activity. We evaluated overall survival (OS) and radiographic tumor response after selective internal radiation therapy (SIRT) with resin microspheres in patients with liver metastases from colorectal cancer. PATIENTS AND METHODS: We retrospectively reviewed 60 metastatic colorectal cancer patients treated at our institution with SIRT using Y-resin microspheres. Each patient underwent pre-SIRT MRI or computed tomography imaging of the liver with intravenous contrast. Patients underwent post-treatment imaging at 2-3-month intervals with response assessed according to unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) criteria as well as published three-dimensional volumetric criteria. We then related the prescribed activity established by the body surface area method and the corresponding prescribed dose to radiographic treatment response and OS. RESULTS: The median follow-up after the first SIRT treatment was 8.9 months. The mean prescribed activity and the prescribed dose were 26.6 mCi and 52.8 Gy, respectively. OS was not significantly associated with either prescribed activity or prescribed dose. Prescribed dose was also not related to response. However, a significant relationship was found between a higher prescribed activity and an improved radiographic response by RECIST (P=0.04) at the second follow-up. CONCLUSION: The prescribed activity of Y-resin microspheres may be correlated with radiographic response by RECIST criteria at 4-6 months post-treatment. For a more accurate prediction of response, a valid dose calculation model based on post-Y PET dosimetry is likely needed given the heterogeneous dose delivery seen in SIRT.

Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer.

PURPOSE: To determine, in a retrospective analysis of a large cohort of stage III non-small cell lung cancer patients treated with curative intent at our institution, whether having a pathologic complete response (pCR) influenced overall survival (OS) or freedom from recurrence (FFR) in patients who underwent definitive (≥60 Gy) neoadjuvant doses of chemoradiation (CRT). METHODS AND MATERIALS: At our institution, 355 patients with locally advanced non-small cell lung cancer were treated with curative intent with definitive CRT (January 2000-December 2013), of whom 111 underwent mediastinal reassessment for possible surgical resection. Ultimately 88 patients received trimodality therapy. Chi-squared analysis was used to compare categorical variables. The Kaplan-Meier analysis was performed to estimate OS and FFR, with Cox regression used to determine the absolute hazards. RESULTS: Using high-dose neoadjuvant CRT, we observed a mediastinal nodal clearance (MNC) rate of 74% (82 of 111 patients) and pCR rate of 48% (37 of 77 patients). With a median follow-up of 34.2 months (range, 3-177 months), MNC resulted in improved OS and FFR on both univariate (OS: hazard ratio [HR] 0.455, 95% confidence interval [CI] 0.272-0.763, P = .004; FFR: HR 0.426, 95% CI 0.250-0.726, P = .002) and multivariate analysis (OS: HR 0.460, 95% CI 0.239-0.699, P = .001; FFR: HR 0.455, 95% CI 0.266-0.778, P = .004). However, pCR did not independently impact OS (P = .918) or FFR (P = .474). CONCLUSIONS: Mediastinal nodal clearance after CRT continues to be predictive of improved survival for patients undergoing trimodality therapy. However, a pCR at both the primary and mediastinum did not further improve survival outcomes. Future therapies should focus on improving MNC to encourage more frequent use of surgery and might justify use of preoperative CRT over chemotherapy alone.

Obesity is associated with long-term improved survival in definitively treated locally advanced non-small cell lung cancer (NSCLC).

OBJECTIVES: To determine the prognostic effect of Body Mass Index (BMI) in definitively treated locally advanced NSCLC patients. MATERIALS AND METHODS: In this single institution retrospective cohort study, we evaluated 291 patients who were treated for locally advanced NSCLC from 2000 to 2010. They were stratified into four BMI groups based on World Health Organization criteria: underweight (<18.5kg/m2), normal weight (18.5 to <25kg/m2), overweight (25 to <30kg/m2), and obese (≧30kg/m2). Overall survival was analyzed by BMI group. RESULTS: Baseline patient characteristics and treatment parameters were similar between obese and normal weight patients. Increasing BMI was associated with improved overall survival (P=0.011), even when underweight cases were excluded. There was a sustained 31%-58% reduction in mortality of obese relative to normal weight patients (HR 0.68±0.21, 0.61±0.19, and 0.42±0.19, for each year post-treatment respectively). Statin use after diagnosis was highly associated with increasing BMI (P<0.001) and predicted improved survival in a multivariate analysis (HR 0.60, 95% CI 0.41-0.89, P=0.011). CONCLUSION: Obese patients in this retrospective study had significantly improved survival relative to normal weight patients. Our data suggest that the protective effect of obesity in locally advanced NSCLC is not solely due to short-term treatment effects, decreased smoking exposure, or poor prognostic factors from underweight patients. Notably, statin use was also associated with improved survival. Additional studies are needed to clarify the mechanisms and possible concomitant factors underlying the obesity paradox in NSCLC.

Clinical outcomes of black vs. non-black patients with locally advanced non-small cell lung cancer.

OBJECTIVES: The black population remains underrepresented in clinical trials despite reports suggesting greater incidence and deaths from locally advanced non-small cell lung cancer (NSCLC). We determined outcomes for black and non-black patients in a well-annotated cohort treated with either definitive chemoradiation (CRT; bimodality) or CRT followed by surgery (trimodality therapy). MATERIALS AND METHODS: A retrospective analysis of 355 stage III NSCLC patients treated with curative intent at the University of Maryland, Medical Center, between January 2000-December 2013 was performed. The Kaplan-Meier approach and the Cox proportional hazards models were used to analyze overall survival (OS) and freedom-from-recurrence (FFR) in black and non-black patients. The chi-square test was used to compare categorical variables. RESULTS: Black patients comprised 42% of the cohort and were more likely to be younger (p<0.0001), male (p=0.030), single (p<0.0001), reside in lower household income zipcodes (p<0.0001), have an Eastern Cooperative Oncology Group (ECOG) performance status >0 (p<0.001), and less likely to undergo surgery (p<0.0001). With a median follow-up of 15 months for all patients and 89 months for surviving patients (range:1-186 months), median OS times for black and non-black patients were 22 and 24 months, respectively (p=0.698). FFR rates were also comparable between the two groups (p=0.468). Surgery improved OS in both cohorts. Race was not a significant predictor for OS or FFR even when adjusted for other factors. CONCLUSIONS: We found similar oncologic outcomes in black and non-black NSCLC patients when treated with curative intent in a comprehensive cancer center setting, despite epidemiologic differences in presentation and receipt of care. Future efforts to improve outcomes in black patients could focus on addressing modifiable social disparities.

Oncological outcomes from trimodality therapy receiving definitive doses of neoadjuvant chemoradiation (≥60 Gy) and factors influencing consideration for surgery in stage III non-small cell lung cancer.

PURPOSE: Guidelines for locally advanced non-small cell lung cancer (LA-NSCLC) recommend definitive chemoradiation therapy (CRT) for cN2-N3 disease, reserving surgery for patients with minimal nodal involvement at presentation. The current literature suggests that surgery after CRT for stage III NSCLC can improve freedom-from-recurrence (FFR) but has not consistently demonstrated an improvement in overall survival, perhaps partly due to the low (45-50.4 Gy) preoperative doses delivered that result in low rates of mediastinal nodal clearance. We therefore analyzed factors associated with trimodality therapy receipt and determined outcomes in patients with LA-NSCLC who were treated with definitive doses (≥60 Gy) of neoadjuvant CRT prior to surgery. METHODS AND MATERIALS: We retrospectively analyzed 355 consecutive patients with LA-NSCLC who were treated with curative intent between January 2000 and December 2013. The Kaplan-Meier method was used to estimate the overall survival and FFR of patients who were initially planned to receive trimodality treatment but never underwent surgery (unplanned bimodality) compared with those who were never considered to be surgical candidates (planned bimodality) and those who underwent surgical resection after CRT (trimodality). Cox proportional hazards regression with forward selection was used for multivariate analyses, and the Fisher exact test was used to test contingency tables. RESULTS: Patients who received trimodality therapy had a longer median survival than those with unplanned or planned bimodality therapy at 59.9, 20.1, and 17.3 months, respectively (P < .001). The survival benefit with surgery persisted in patients with stage IIIB (P < .001) and N3 (P = .010) nodal disease when mediastinal nodal clearance was achieved. FFR was also improved with surgical resection (P = .001). Race (P < .001), stage (P < .001), performance status (P < .001), age (P < .001), and diagnosis of chronic obstructive pulmonary disease (P = .009) were significant indicators that influenced both the decision to initially choose trimodality therapy at consultation and to actually perform surgical resection. CONCLUSIONS: Trimodality treatment significantly improves survival and FFR in patients with LA-NSCLC when definitive doses of radiation with neoadjuvant chemotherapy are employed. We identified important demographic features that predict the use of surgical intervention in patients with stage III NSCLC.

A Multi-institutional Analysis of Trimodality Therapy for Esophageal Cancer in Elderly Patients.

PURPOSE: The therapeutic gains of neoadjuvant chemoradiation therapy (nCRT) followed by esophagectomy may be offset by increased incidences of morbidity and mortality in elderly patients. This study aimed to determine the impact of age on the risks and benefits of trimodality therapy for esophageal cancer. METHODS AND MATERIALS: We evaluated 571 patients treated with trimodality therapy at 3 high-volume tertiary cancer centers in the United States from 2007 to 2013. Two hundred two of 571 (35%) patients were 65 years or older at diagnosis and were classified as elderly. Toxicity and treatment parameters for the elderly cohort were compared with the younger cohort (ages 22-64) by the use of univariate (UVA) and multivariable (MVA) logistic analyses. Age was analyzed as a continuous hazard for cardiac and pulmonary toxicities. Survival was assessed by the Kaplan-Meier method. RESULTS: Elderly patients had a higher risk for postoperative cardiac toxicities (UVA: odds ratio [OR] 2.2, P<.001; MVA: OR 2.07, P=.004) and pulmonary toxicities (UVA: OR 2.0, P<.001; MVA: OR 2.03, P<.001) and a higher 90-day postoperative mortality (5.4% vs 2.2%, P=.049). Of the elderly patients, 6.9% experienced acute respiratory distress syndrome compared with 3.8% of younger patients (P=.11). Cardiac toxicity was linearly associated with age, and the relative risk increased by 61% for every additional decade of age. There was no difference in postoperative gastrointestinal or wound adverse events or in length of hospital stay. Grade 3+ acute toxicities from nCRT were infrequent and were clinically similar regardless of age. Freedom from esophageal cancer and disease-free survival were similar, but overall survival was significantly shorter in the elderly cohort. CONCLUSIONS: Elderly patients experienced more postoperative cardiopulmonary toxicities and mortality than did younger patients after nCRT. Compared with contemporary outcomes for trimodality therapy, both cohorts had acceptable rates for adverse events and disease control. For appropriately selected elderly patients, trimodality therapy for esophageal cancer is a reasonable treatment option.

Multi-institutional analysis of radiation modality use and postoperative outcomes of neoadjuvant chemoradiation for esophageal cancer.

PURPOSE: Relative radiation dose exposure to vital organs in the thorax could influence clinical outcomes in esophageal cancer (EC). We assessed whether the type of radiation therapy (RT) modality used was associated with postoperative outcomes after neoadjuvant chemoradiation (nCRT). PATIENTS AND METHODS: Contemporary data from 580 EC patients treated with nCRT at 3 academic institutions from 2007 to 2013 were reviewed. 3D conformal RT (3D), intensity modulated RT (IMRT) and proton beam therapy (PBT) were used for 214 (37%), 255 (44%), and 111 (19%) patients, respectively. Postoperative outcomes included pulmonary, GI, cardiac, wound healing complications, length of in-hospital stay (LOS), and 90-day postoperative mortality. Cox model fits, and log-rank tests both with and without Inverse Probability of treatment Weighting (IPW) were used to correct for bias due to non-randomization. RESULTS: RT modality was significantly associated with the incidence of pulmonary, cardiac and wound complications, which also bore out on multivariate analysis. Mean LOS was also significantly associated with treatment modality (13.2days for 3D (95%CI 11.7-14.7), 11.6days for IMRT (95%CI 10.9-12.7), and 9.3days for PBT (95%CI 8.2-10.3) (p<0.0001)). The 90day postoperative mortality rates were 4.2%, 4.3%, and 0.9%, respectively, for 3D, IMRT and PBT (p=0.264). CONCLUSIONS: Advanced RT technologies (IMRT and PBT) were associated with significantly reduced rate of postoperative complications and LOS compared to 3D, with PBT displaying the greatest benefit in a number of clinical endpoints. Ongoing prospective randomized trial will be needed to validate these results.

Prostaglandin E Receptor EP4 expression, survival and pattern of recurrence in locally advanced NSCLC.

BACKGROUND: Elevated COX-2 expression has been correlated with inferior outcome in NSCLC. COX-2 catalyzes the transformation of arachidonate to PGE2. We and others have demonstrated that PGE2 induces proliferation and metastatic spread and immunosuppression through the G protein-coupled EP4 receptor. We hypothesized that EP4 expression on malignant cells would correlate with outcome and patterns of relapse after treatment of LANSCLC stage IIIA (7th edition, N2+). METHODS: Tissue specimens from 41 pts treated for LANSC at UMGCC were obtained. A tissue microarray was prepared and examined for EP4 expression. Intensity of staining was scored semi-quantitatively as 0-4 in both the nuclear and cytoplasmic compartments by a pathologist blinded to the clinical data. RESULTS: EP4 nuclear staining 0-1 vs. 2+ was associated with overall survival, (OS) (44.3 vs. 18 mo; HR=0.41, p=0.024) and numerically superior progression free survival (PFS) (16.4 vs. 10.2 mo, p=0.16). EP4 cytoplasmic staining did not correlate with OS (0-1 vs. 2+, 23.8 vs. 28.8 mo; HR=1.2, p=0.81). Relapse pattern (no relapse or local vs. systemic) did not correlate with EP nuclear staining (p=1.0, X2). CONCLUSIONS: This is the first clinical study of EP4 expression in lung cancer. There was a significant correlation between OS and nuclear EP4 expression, indicating that this is a potential therapeutic target. Studies with AT-007, a specific inhibitor of EP4, are planned to commence this year.

Pretreatment tumor volume as a prognostic factor in metastatic colorectal cancer treated with selective internal radiation to the liver using yttrium-90 resin microspheres.

BACKGROUND: Yttrium-90 (90Y)-resin microspheres can prolong intrahepatic disease control and improve overall survival (OS) in patients with metastatic colorectal cancer (CRC). Prognostic factors for improved outcomes in patients undergoing selective internal radiation therapy (SIRT) have been studied, but the relationship between pre-SIRT liver tumor volume and outcomes has not well described. METHODS: We retrospectively reviewed the records of patients with metastatic CRC who were treated at our institution with 90Y-resin microspheres. Each patient underwent either MR or CT imaging of the liver with intravenous (IV) contrast before and within ~2-3 months after SIRT. Imaging data were transferred into our treatment planning system. Each metastatic liver lesion was contoured, and the volume of each lesion was summed to determine the total liver tumor volume at a given time point. We evaluated whether pretreatment liver tumor volume was related to OS. We also evaluated the relationship between pre-SIRT tumor volume and radiographic treatment response by either unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) or three-dimensional volumetric criteria. RESULTS: We included 60 patients with a median age of 59 years (range, 38-97 years); 60% of patients received sequential lobar treatment. The median number of chemotherapy cycles received prior to SIRT was 2. Median follow-up from first SIRT was 8.9 months. Pre- and post-SIRT tumor volumes were primarily calculated on CT (87%). The median pre-SIRT tumor volume was 77 cc (range, 4.5-2,170.4 cc). The median intervals between the first SIRT and the first, second, and third follow-up scans were 2.2, 4.4, and 7.7 months, respectively. No patient experienced a radiographic complete response. Pretreatment volume was a significant predictor for estimating the odds of a patient having stable disease or partial response using volumetric response criteria at first (P=0.016), second (P=0.023), and third (P=0.015) follow-ups. For each unit increase in log volume, a patient's odds of having a stable or partial response were 0.57, 0.63, and 0.61 times as likely at first, second, and third follow-up, respectively. OS was not significantly associated with pretreatment tumor volume. CONCLUSIONS: Patients with metastatic CRC with larger overall pretreatment liver tumor volumes, regardless of number of individual liver lesions, are less likely to have radiographic evidence of stable disease or partial response following SIRT using volumetric response criteria. However, pretreatment volume was not significantly associated with OS, and thus SIRT should be considered for patients with larger pretreatment volumetric tumor burden.

Computerized three-class classification of MRI-based prognostic markers for breast cancer.

The purpose of this study is to investigate whether computerized analysis using three-class Bayesian artificial neural network (BANN) feature selection and classification can characterize tumor grades (grade 1, grade 2 and grade 3) of breast lesions for prognostic classification on DCE-MRI. A database of 26 IDC grade 1 lesions, 86 IDC grade 2 lesions and 58 IDC grade 3 lesions was collected. The computer automatically segmented the lesions, and kinetic and morphological lesion features were automatically extracted. The discrimination tasks-grade 1 versus grade 3, grade 2 versus grade 3, and grade 1 versus grade 2 lesions-were investigated. Step-wise feature selection was conducted by three-class BANNs. Classification was performed with three-class BANNs using leave-one-lesion-out cross-validation to yield computer-estimated probabilities of being grade 3 lesion, grade 2 lesion and grade 1 lesion. Two-class ROC analysis was used to evaluate the performances. We achieved AUC values of 0.80 ± 0.05, 0.78 ± 0.05 and 0.62 ± 0.05 for grade 1 versus grade 3, grade 1 versus grade 2, and grade 2 versus grade 3, respectively. This study shows the potential for (1) applying three-class BANN feature selection and classification to CADx and (2) expanding the role of DCE-MRI CADx from diagnostic to prognostic classification in distinguishing tumor grades.

Multimodality computer-aided breast cancer diagnosis with FFDM and DCE-MRI.

RATIONALE AND OBJECTIVES: To investigate a multimodality computer-aided diagnosis (CAD) scheme that combines image information from full-field digital mammography (FFDM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for computerized breast cancer classification. MATERIALS AND METHODS: From a retrospective FFDM database with 432 lesions (255 malignant, 177 benign) and a retrospective DCE-MRI database including 476 lesions (347 malignant, 129 benign), we constructed a multimodality dataset of 213 lesions (168 malignant, 45 benign). Each lesion was present on both FFDM and DCE-MRI images and deemed to be a difficult case given the necessity of having both clinical imaging exams. Using a manually indicated lesion location (ie, a seed point on FFDM images or a region of interest on DCE-MRI images, the computer automatically segmented the mass lesions and extracted lesion features). A subset of features was selected using linear stepwise feature selection and merged by a Bayesian artificial neural network to yield an estimate of the probability of malignancy. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of the selected features in distinguishing between malignant and benign lesions. RESULTS: With leave-one-lesion-out cross-validation on the multimodality dataset, the mammography-only features yielded an area under the ROC curve (AUC) of 0.74 +/- 0.04, and the DCE-MRI-only features yielded an AUC of 0.78 +/- 0.04. The combination of these two modalities, which included a spiculation feature from mammography and two kinetic features from DCE-MRI, yielded an AUC of 0.87 +/- 0.03. The improvement of combining multimodality information was statistically significant as compared to the use of single modality information alone. CONCLUSIONS: A CAD scheme that combines features extracted from FFDM and DCE-MRI images may be advantageous to single-modality CAD in the task of differentiating between malignant and benign lesions.