The Relative Importance of Clinical and Socio-demographic Variables in Prognostic Prediction in Non-Small Cell Lung Cancer: A Variable Importance Approach.

BACKGROUND: Prognostic modeling in health care has been predominantly statistical, despite a rapid growth of literature on machine-learning approaches in biological data analysis. We aim to assess the relative importance of variables in predicting overall survival among patients with non-small cell lung cancer using a Variable Importance (VIMP) approach in a machine-learning Random Survival Forest (RSF) model for posttreatment planning and follow-up. METHODS: A total of 935 non-small cell lung cancer patients were randomly and equally divided into 2 training and testing cohorts in an RFS model. The prognostic variables included age, sex, race, the TNM Classification of Malignant Tumors (TNM) stage, smoking history, Eastern Cooperative Oncology Group performance status, histologic type, treatment category, maximum standard uptake value of whole-body tumor (SUVmaxWB), whole-body metabolic tumor volume (MTVwb), and Charlson Comorbidity Index. The VIMP was calculated using a permutation method in the RSF model. We further compared the VIMP of the RSF model to that of the standard Cox survival model. We examined the order of VIMP with the differential functional forms of the variables. RESULTS: In both the RSF and the standard Cox models, the most important variables are treatment category, TNM stage, and MTVwb. The order of VIMP is more robust in RSF model than in Cox model regarding the differential functional forms of the variables. CONCLUSIONS: The RSF VIMP approach can be applied alongside with the Cox model to further advance the understanding of the roles of prognostic factors, and improve prognostic precision and care efficiency.

Developing and validating a novel metabolic tumor volume risk stratification system for supplementing non-small cell lung cancer staging.

PURPOSE: We hypothesized that whole-body metabolic tumor volume (MTVwb) could be used to supplement non-small cell lung cancer (NSCLC) staging due to its independent prognostic value. The goal of this study was to develop and validate a novel MTVwb risk stratification system to supplement NSCLC staging. METHODS: We performed an IRB-approved retrospective review of 935 patients with NSCLC and FDG-avid tumor divided into modeling and validation cohorts based on the type of PET/CT scanner used for imaging. In addition, sensitivity analysis was conducted by dividing the patient population into two randomized cohorts. Cox regression and Kaplan-Meier survival analyses were performed to determine the prognostic value of the MTVwb risk stratification system. RESULTS: The cut-off values (10.0, 53.4 and 155.0 mL) between the MTVwb quartiles of the modeling cohort were applied to both the modeling and validation cohorts to determine each patient's MTVwb risk stratum. The survival analyses showed that a lower MTVwb risk stratum was associated with better overall survival (all p < 0.01), independent of TNM stage together with other clinical prognostic factors, and the discriminatory power of the MTVwb risk stratification system, as measured by Gönen and Heller's concordance index, was not significantly different from that of TNM stage in both cohorts. Also, the prognostic value of the MTVwb risk stratum was robust in the two randomized cohorts. The discordance rate between the MTVwb risk stratum and TNM stage or substage was 45.1% in the modeling cohort and 50.3% in the validation cohort. CONCLUSION: This study developed and validated a novel MTVwb risk stratification system, which has prognostic value independent of the TNM stage and other clinical prognostic factors in NSCLC, suggesting that it could be used for further NSCLC pretreatment assessment and for refining treatment decisions in individual patients.

Computer-assisted Curie scoring for metaiodobenzylguanidine (MIBG) scans in patients with neuroblastoma.

BACKGROUND: Radiolabeled metaiodobenzylguanidine (MIBG) is sensitive and specific for detecting neuroblastoma. The extent of MIBG-avid disease is assessed using Curie scores. Although Curie scoring is prognostic in patients with high-risk neuroblastoma, there is no standardized method to assess the response of specific sites of disease over time. The goal of this study was to develop approaches for Curie scoring to facilitate the calculation of scores and comparison of specific sites on serial scans. PROCEDURE: We designed three semiautomated methods for determining Curie scores, each with increasing degrees of computer assistance. Method A was based on visual assessment and tallying of MIBG-avid lesions. For method B, scores were tabulated from a schematic that associated anatomic regions to MIBG-positive lesions. For method C, an anatomic mesh was used to mark MIBG-positive lesions with automatic assignment and tallying of scores. Five imaging physicians experienced in MIBG interpretation scored 38 scans using each method, and the feasibility and utility of the methods were assessed using surveys. RESULTS: There was good reliability between methods and observers. The user-interface methods required 57 to 110 seconds longer than the visual method. Imaging physicians indicated that it was useful that methods B and C enabled tracking of lesions. Imaging physicians preferred method B to method C because of its efficiency. CONCLUSIONS: We demonstrate the feasibility of semiautomated approaches for Curie score calculation. Although more time was needed for strategies B and C, the ability to track and document individual MIBG-positive lesions over time is a strength of these methods.

Risk-stratifying capacity of PET/CT metabolic tumor volume in stage IIIA non-small cell lung cancer.

OBJECTIVES: Stage IIIA non-small cell lung cancer (NSCLC) is heterogeneous in tumor burden, and its treatment is variable. Whole-body metabolic tumor volume (MTVWB) has been shown to be an independent prognostic index for overall survival (OS). However, the potential of MTVWB to risk-stratify stage IIIA NSCLC has previously been unknown. If we can identify subgroups within the stage exhibiting significant OS differences using MTVWB, MTVWB may lead to adjustments in patients' risk profile evaluations and may, therefore, influence clinical decision making regarding treatment. We estimated the risk-stratifying capacity of MTVWB in stage IIIA by comparing OS of stratified stage IIIA with stage IIB and IIIB NSCLC. METHODS: We performed a retrospective review of 330 patients with clinical stage IIB, IIIA, and IIIB NSCLC diagnosed between 2004 and 2014. The patients' clinical TNM stage, initial MTVWB, and long-term survival data were collected. Patients with TNM stage IIIA disease were stratified by MTVWB. The optimal MTVWB cutoff value for stage IIIA patients was calculated using sequential log-rank tests. Univariate and multivariate cox regression analyses and Kaplan-Meier OS analysis with log-rank tests were performed. RESULTS: The optimal MTVWB cut-point was 29.2 mL for the risk-stratification of stage IIIA. We identified statistically significant differences in OS between stage IIB and IIIA patients (p < 0.01), between IIIA and IIIB patients (p < 0.01), and between the stage IIIA patients with low MTVWB (below 29.2 mL) and the stage IIIA patients with high MTVWB (above 29.2 mL) (p < 0.01). There was no OS difference between the low MTVWB stage IIIA and the cohort of stage IIB patients (p = 0.485), or between the high MTVWB stage IIIA patients and the cohort of stage IIIB patients (p = 0.459). Similar risk-stratification capacity of MTVWB was observed in a large range of cutoff values from 15 to 55 mL in stage IIIA patients. CONCLUSIONS: Using MTVWB cutoff points ranging from 15 to 55 mL with an optimal value of 29.2 mL, stage IIIA NSCLC may be effectively stratified into subgroups with no significant survival difference from stages IIB or IIIB NSCLC. This may result in more accurate survival estimation and more appropriate risk adapted treatment selection in stage IIIA NSCLC.

Relationship between Overall Survival of Patients with Non-Small Cell Lung Cancer and Whole-Body Metabolic Tumor Burden Seen on Postsurgical Fluorodeoxyglucose PET Images.

PURPOSE: To test the hypothesis that whole-body metabolic tumor burden (MTBWB) on postsurgical fluorodeoxyglucose (FDG) positron emission tomographic (PET)/computed tomographic (CT) images in patients with non-small cell lung cancer (NSCLC) is associated with their overall survival (OS). MATERIALS AND METHODS: The institutional review board approved this study and waived the requirement for obtaining informed consent. One hundred forty-two patients with NSCLC (69 men, 73 women; median age, 67.7 years) who underwent postsurgical FDG PET/CT were retrospectively reviewed. The whole-body metabolic tumor volume (MTVWB), whole-body total lesion glycolysis (TLGWB), and whole-body maximum standardized uptake value (SUVWBmax) were measured. OS served as the primary end point of the study. Kaplan-Meier curves and Cox regression were used to assess the association between PET/CT markers and OS. RESULTS: The interobserver variability was low, as demonstrated with intraclass correlation coefficients higher than 0.94 for SUVWBmax, MTVWB, and TLGWB. When compared with those with negative postsurgical FDG PET/CT findings, a significant decrease of OS was found in patients with the presence of FDG-avid tumor on the basis of both a log-rank test (P = .001) and a univariate Cox model (hazard ratio = 2.805, P = .001). In patients with FDG-avid tumor, there was a significant association between OS and ln MTVWB (P < .001), ln TLGWB (P < .001), and ln SUVWBmax (P < .010) in either univariate or multivariate analysis, after adjusting for patient age, sex, TNM restage, and therapy after postsurgical PET/CT studies. The OS differences between the groups dichotomized by the median value of MTVWB (11.54 mL, P = .004), TLGWB (32.38 mL, P < .001), or SUVWBmax (4.93, P = .023) were significant. CONCLUSION: MTBWB and tumor maximum standardized uptake at postsurgical FDG PET/CT are related to the patient's OS in NSCLC, independent of age, sex, TNM restaging, and therapy after postsurgical PET/CT studies.

Treatment of two cases with refractory, metastatic intermediate-risk neuroblastoma with isotretenoin alone or observation.

Patients <12 months with favorable biology, metastatic neuroblastoma have >90% overall survival following treatment with chemotherapy and surgery. We report two infants with favorable biology, stage 4 neuroblastoma with refractory disease after standard intermediate-risk chemotherapy and additional retrieval chemotherapy. One patient was treated with six additional cycles of isotretinoin and the other observed. Both remain clinically well with persistent disease but no evidence of tumor progression for 28 and 13 months following completion of cytotoxic treatment. Similar to residual tumor in primary sites, refractory metastatic disease may not portend a poor outcome in patients with favorable biology, intermediate-risk neuroblastoma.

Comparison of Measurement and Prognostic Power of SUV Between High-Definition and Standard PET Imaging in Non-Small Cell Lung Cancer Patients.

This study aimed to evaluate the measurement and prognostic ability of the SUVmax of whole-body tumors (SUVmaxwb) in non-small cell lung cancer (NSCLC) patients, comparing high-definition (HD) PET imaging with standard-definition (SD) PET imaging. Methods: The study included 242 consecutive NSCLC patients who underwent baseline 18F-FDG PET/CT from April 2018 to January 2021. Two imaging techniques were used: HD PET (using ordered-subsets expectation maximization with point-spread function modeling and time-of-flight techniques and smaller voxels) and SD PET (with ordered-subsets expectation maximization and time-of-flight techniques). SUVmaxwb was determined by measuring all the tumor lesions in the whole body, and tumor-to-background ratio (TBR) was calculated using the background SUVmean of various body parts. Results: The patient cohort had an average age of 68.3 y, with 59.1% being female. During a median follow-up of 29.6 mo, 83 deaths occurred. SUVmaxwb was significantly higher in HD PET than SD PET, with respective medians of 17.4 and 11.8. The TBR of 1,125 tumoral lesions was also higher in HD PET. Univariate Cox regression analysis showed that SUVmaxwb from both HD and SD PET were significantly associated with overall survival. However, after adjusting for TNM (tumor, node, metastasis) stage, only SUVmaxwb from SD PET remained significantly associated with survival. Conclusion: HD PET imaging in NSCLC patients yields higher SUVmaxwb and TBR, enhancing tumor visibility. Despite this, its prognostic value is less significant than SD PET after adjusting clinical TNM stage. Thus, consideration should be given to using HD PET reconstruction to increase tumor visibility, and SD PET is recommended for NSCLC patient prognostication and therapeutic evaluation, as well as for the classification of lung nodules.

Optimization of Metabolic Tumor Volume as a Prognostic Marker in CAR T-Cell Therapy for Aggressive Large B-cell NHL.

BACKGROUND: CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has become a standard of care in relapsed/refractory (R/R) aggressive large B-cell non-Hodgkin lymphomas (B-NHL) though the majority of recipients do not receive durable disease benefit, prompting the need to better define risk factors for relapse/progression. OBJECTIVES: We performed a single-center, retrospective analysis of patients treated with commercial CAR T-cell therapy to evaluate the impact of tumor burden, as measured by whole-body metabolic tumor volume (MTV) from 18F fluorodeoxyglucose PET imaging, on treatment outcomes. STUDY DESIGN: Sixty-one patients treated with CAR T-cell therapy for R/R B-NHL between May 2016 and November 2021 were included. RESULTS: Using a receiver operating characteristic curve-based MTV optimization cutoff of 450 mL, 1-year progression-free survival (PFS) was 22% for high MTV versus 54% for low MTV (P < .01), and 1-year overall survival (OS) was 37% and 73%, respectively (P = .01). In a subset of 46 patients, residual MTV of less than 106 mL at the day 30 (D30) disease assessment was associated with significantly improved outcomes (1-year OS 85% vs. 13%, P < .01). Incorporation of pretreatment MTV to the International Prognostic Index (IPI) scoring system significantly distinguished 2-year PFS and OS outcomes by 3 risk groups. CONCLUSIONS: Our findings suggest that both pretreatment and D30 MTV are predictive of outcomes among R/R B-NHL patients treated with CAR T-cell therapy. These data indicate that efforts to reduce pretreatment tumor burden may improve longitudinal clinical outcomes. Furthermore, D30 postinfusion MTV quantification may aid clinicians in optimally identifying patients at high-risk for progression, and in whom closer disease monitoring should be considered. MTV also adds prognostic value to patients with high-risk IPI and holds promise for incorporation in novel risk scoring systems which can identify patients prior to CAR T-cell therapy at highest risk of adverse outcomes.

Prognostic value of metabolic tumor burden in lung cancer.

Accurate prognosis in patients with lung cancer is important for clinical decision making and treatment selection. The TNM staging system is currently the main method for establishing prognosis. Using this system, patients are grouped into one of four stages based on primary tumor extent, nodal disease, and distant metastases. However, each stage represents a range of disease extent and may not on its own be the best reflection of individual patient prognosis. (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) can be used to evaluate the metabolic tumor burden affecting the whole body with measures such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG). MTV and TLG have been shown to be significant prognostic factors in patients with lung cancer, independent of TNM stage. These metabolic tumor burden measures have the potential to make lung cancer staging and prognostication more accurate and quantitative, with the goal of optimizing treatment choices and outcome predictions.

Whole-body tumor segmentation from PET/CT images using a two-stage cascaded neural network with camouflaged object detection mechanisms.

BACKGROUND: Whole-body Metabolic Tumor Volume (MTVwb) is an independent prognostic factor for overall survival in lung cancer patients. Automatic segmentation methods have been proposed for MTV calculation. Nevertheless, most of existing methods for patients with lung cancer only segment tumors in the thoracic region. PURPOSE: In this paper, we present a Two-Stage cascaded neural network integrated with Camouflaged Object Detection mEchanisms (TS-Code-Net) for automatic segmenting tumors from whole-body PET/CT images. METHODS: Firstly, tumors are detected from the Maximum Intensity Projection (MIP) images of PET/CT scans, and tumors' approximate localizations along z-axis are identified. Secondly, the segmentations are performed on PET/CT slices that contain tumors identified by the first step. Camouflaged object detection mechanisms are utilized to distinguish the tumors from their surrounding regions that have similar Standard Uptake Values (SUV) and texture appearance. Finally, the TS-Code-Net is trained by minimizing the total loss that incorporates the segmentation accuracy loss and the class imbalance loss. RESULTS: The performance of the TS-Code-Net is tested on a whole-body PET/CT image data-set including 480 Non-Small Cell Lung Cancer (NSCLC) patients with five-fold cross-validation using image segmentation metrics. Our method achieves 0.70, 0.76, and 0.70, for Dice, Sensitivity and Precision, respectively, which demonstrates the superiority of the TS-Code-Net over several existing methods related to metastatic lung cancer segmentation from whole-body PET/CT images. CONCLUSIONS: The proposed TS-Code-Net is effective for whole-body tumor segmentation of PET/CT images. Codes for TS-Code-Net are available at: https://github.com/zyj19/TS-Code-Net.

Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer.

PURPOSE: The objective of this study was to assess the prognostic value of metabolic tumor burden on 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) positron emission tomography (PET)/CT measured with metabolic tumor volume (MTV) and total lesion glycolysis (TLG), independent of Union Internationale Contra la Cancrum (UICC)/American Joint Committee on Cancer (AJCC) tumor, node, and metastasis (TNM) stage, in comparison with that of standardized uptake value (SUV) in nonsurgical patients with non-small cell lung cancer (NSCLC). METHODS: This study retrospectively reviewed 169 consecutive nonsurgical patients (78 men, 91 women, median age of 68 years) with newly diagnosed NSCLC who had pretreatment (18)F-FDG PET/CT scans. The (18)F-FDG PET/CT scans were performed in accordance with National Cancer Institute guidelines. The MTV of whole-body tumor (MTV(WB)), of primary tumor (MTV(T)), of nodal metastases (MTV(N)), and of distant metastases (MTV(M)); the TLG of whole-body tumor (TLG(WB)), of primary tumor (TLG(T)), of nodal metastases (TLG(N)), and of distant metastases (TLG(M)); the SUV(max) of whole-body tumor (SUV(maxWB)), of primary tumor (SUV(maxT)), of nodal metastases (SUV(maxN)), and of distant metastases (SUV(maxM)) as well as the SUV(mean) of whole-body tumor (SUV(meanWB)), of primary tumor (SUV(meanT)), of nodal metastases (SUV(meanN)), and of distant metastases (SUV(meanM)) were measured with the PETedge tool on a MIMvista workstation with manual adjustment. The median follow-up among survivors was 35 months from the PET/CT (range 2-82 months). Statistical methods included Kaplan-Meier curves, Cox regression, and C-statistics. RESULTS: There were a total of 139 deaths during follow-up. Median overall survival (OS) was 10.9 months [95% confidence interval (CI) 9.0-13.2 months]. The MTV was statistically associated with OS. The hazard ratios (HR) for 1 unit increase of ln(MTV(WB)), √(MTV(T)), √(MTV(N)), and √(MTV(M)) before/after adjusting for stage were: 1.47/1.43 (p < 0.001/<0.001), 1.06/1.05 (p < 0.001/<0.001), 1.11/1.10 (p < 0.001/<0.001), and 1.04/1.03 (p = 0.007/0.043), respectively. TLG had statistically significant associations with OS with the HRs for 1 unit increase in ln(TLG(WB)), √(TLG(T)), √(TLG(N)), and √(TLG(M)) before/after adjusting for stage being 1.36/1.33 (p < 0.001/<0.001), 1.02/1.02 (p = 0.001/0.002), 1.05/1.04 (p < 0.001/<0.001), and 1.02/1.02 (p = 0.003/0.024), respectively. The ln(SUV(maxWB)) and √(SUV(maxN)) were statistically associated with OS with the corresponding HRs for a 1 unit increase before/after adjusting for stage being 1.46/1.43 (p = 0.013/0.024) and 1.22/1.16 (p = 0.002/0.040). The √(SUV(meanN)) was statistically associated with OS before and after adjusting for stage with HRs for a 1 unit increase of 1.32 (p < 0.001) and 1.24 (p = 0.015), respectively. The √(SUV(meanM)) and √(SUV(maxM)) were statistically associated with OS before adjusting for stage with HRs for a 1 unit increase of 1.26 (p = 0.017) and 1.18 (p = 0.007), respectively, but not after adjusting for stage (p = 0.127 and 0.056). There was no statistically significant association between OS and √(SUV(maxT)), ln(SUV(meanWB)), or √(SUV(meanT)). There was low interobserver variability among three radiologists with intraclass correlation coefficients (ICC) greater than 0.94 for SUV(maxWB), ln(MTV(WB)), and ln(TLG(WB)). Interobserver variability was higher for SUV(meanWB) with an ICC of 0.806. CONCLUSION: Baseline metabolic tumor burdens at the level of whole-body tumor, primary tumor, nodal metastasis, and distant metastasis as measured with MTV and TLG on FDG PET are prognostic measures independent of clinical stage with low inter-observer variability and may be used to further stratify nonsurgical patients with NSCLC. This study also suggests MTV and TLG are better prognostic measures than SUV(max) and SUV(mean). These results will need to be validated in larger cohorts in a prospective study.

Prognostic value of tumor burden measurement using the number of tumors in non-surgical patients with non-small cell lung cancer.

BACKGROUND: No study to test the feasibility and prognostic value of the number of primary tumors, the number of positive lymph nodes, and the total number of tumors in the whole body as tumor burden measurements on FDG PET/CT imaging has been reported. PURPOSE: To determine whether the number of tumors seen in 18F-FDG PET scans can be a prognostic factor in non-surgical patients with non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: One hundred and forty patients with histologically proven NSCLC and baseline 18F-FDG PET scan before therapy were identified in this retrospective analysis. The total number of tumors (TTn) in the whole body, the number of primary tumors (Tn), positive lymph nodes (Nn), and distant metastases (Mn), along with the maximum standardized uptake values (SUV(max)) of the tumors were measured. Inter-observer variability of the total number of tumors, counted by two radiologists, was assessed. Survival analyses were performed to determine the prognostic value of the number of tumors. RESULTS: Concordance correlation coefficients for the TTn, Tn, Nn, and Mn were all greater than 0.85. TTn and Nn were strong prognostic factors of NSCLC patients' overall survival (OS). In univariate Cox regression models, gender, stage, TTn, Nn, and Mn were statistically significant factors (P = 0.016, 0.032, <0.001, <0.001, and 0.006, respectively). In multivariate Cox regression models, TTn and Nn remained as statistically significant predictors for survival with hazard ratios (HR) of 1.06 (P = 0.001) and 1.11 (P = 0.002), respectively, after adjusting for clinical stage based 7th edition of TNM staging system, age, gender, and SUV(max). Patients with a TTn ≤4 (cutpoint based on median value) had a median OS of 15.2 months compared with 9.0 months for those with TTn >4. CONCLUSION: Measuring the number of tumors on FDG PET imaging is easy to perform with minimal inter-observer variability. The total number of tumors and number of nodal metastases, as metabolic tumor burden measurements in 18F-FDG PET/CT, are prognostic markers independent of clinical stage, age, gender, and SUV measurement in non-surgical patients with NSCLC.

Developing a clinical and PET/CT volumetric prognostic index for risk assessment and management of NSCLC patients after initial therapy.

BACKGROUND: Currently, individual clinical prognostic variables are used sequentially with risk-stratification after TNM staging in clinical practice for the prognostic assessment of patients with NSCLC, which is not effective for estimating the collective impact of multiple individual variables on patient outcomes. Here, we developed a clinical and PET/CT volumetric prognostic (CPVP) index that integrates the prognostic power of multiple clinical variables and metabolic tumor volume from baseline FDG-PET, for use immediately after definitive therapy. PATIENTS AND METHODS: This retrospective cohort study included 998 NSCLC patients diagnosed between 2004 and 2017, randomly assigned to two cohorts for modeling the CPVP index using Cox regression models examining overall survival (OS) and subsequent validation. RESULTS: The CPVP index generated from the model cohort included pretreatment variables (whole-body metabolic tumor volume [MTVwb], clinical TNM stage, tumor histology, performance status, age, race, gender, smoking history) and treatment type. A clinical variable (CV) index without MTVwb and PET/CT volumetric prognostic (PVP) index without clinical variables were also generated for comparison. In the validation cohort, univariate Cox modeling showed a significant association of the index with overall survival (OS; Hazard Ratio [HR] 3.14; 95% confidence interval [95% CI] = 2.71 to 3.65, p < 0.001). Multivariate Cox regression analysis demonstrated a significant association of the index with OS (HR = 3.13, 95% CI = 2.66 to 3.67, p < 0.001). The index showed greater prognostic power (C-statistic = 0.72) than any of its independent variables including clinical TNM stage (C-statistic ranged from 0.50 to 0.69, all p < 0.003), CV index (C-statistic = 0.68, p < 0.001) and PVP index (C-statistic = 0.70, p = 0.006). CONCLUSIONS: The CPVP index for NSCLC patients has moderately strong prognostic power and is more prognostic than its individual prognostic variables and other indices. It provides a practical tool for quantitative prognostic assessment after initial treatment and therefore may be helpful for the development of individualized treatment and monitoring strategy for NSCLC patients.

Clinical utility of temporal subtraction images in successive whole-body bone scans: evaluation in a prospective clinical study.

In order to aid radiologists' routine work for interpreting bone scan images, we developed a computerized method for temporal subtraction (TS) images which can highlight interval changes between successive whole-body bone scans, and we performed a prospective clinical study for evaluating the clinical utility of the TS images. We developed a TS image server which includes an automated image-retrieval system, an automated image-conversion system, an automated TS image-producing system, a computer interface for displaying and evaluating TS images with five subjective scales, and an automated data-archiving system. In this study, the radiologist could revise his/her report after reviewing the TS images if the findings on the TS image were confirmed retrospectively on our clinical picture archiving and communication system. We had 256 consenting patients of whom 143 had two or more whole-body bone scans available for TS images. In total, we obtained TS images successfully in 292 (96.1%) pairs and failed to produce TS images in 12 pairs. Among the 292 TS studies used for diagnosis, TS images were considered as "extremely beneficial" or "somewhat beneficial" in 247 (84.6%) pairs, as "no utility" in 44 pairs, and as "somewhat detrimental" in only one pair. There was no TS image for any pairs that was considered "extremely detrimental." In addition, the radiologists changed their initial reported impression in 18 pairs (6.2%). The benefit to the radiologist of using TS images in the routine interpretation of successive whole-body bone scans was significant, with negligible detrimental effects.

Interobserver variability among measurements of the maximum and mean standardized uptake values on (18)F-FDG PET/CT and measurements of tumor size on diagnostic CT in patients with pulmonary tumors.

BACKGROUND: (18)F-fluoro-2-deoxyglucose positron emission tomography ((18)F-FDG PET) imaging has been shown to be an accurate method for diagnosing pulmonary lesions, and the standardized uptake value (SUV) has been shown to be useful in differentiating benign from malignant lesions. PURPOSE: To survey the interobserver variability of SUV(max) and SUV(mean) measurements on (18)F-FDG PET/CT scans and compare them with tumor size measurements on diagnostic CT scans in the same group of patients with focal pulmonary lesions. MATERIAL AND METHODS: Forty-three pulmonary nodules were measured on both (18)F-FDG PET/CT and diagnostic chest CT examinations. Four independent readers measured the SUV(max) and SUV(mean) of the (18)F-FDG PET images, and the unidimensional nodule size of the diagnostic CT scans (UD(CT)) in all nodules. The region of interest (ROI) for the SUV measurements was drawn manually around each tumor on all consecutive slices that contained the nodule. The interobserver reliability and variability, represented by the intraclass correlation coefficient (ICC) and coefficient of variation (COV), respectively, were compared among the three parameters. The correlation between the SUV(max) and SUV(mean) was also analyzed. RESULTS: There was 100% agreement in the SUV(max) measurements among the 4 readers in the 43 pulmonary tumors. The ICCs for the SUV(max), SUV(mean), and UD(CT) by the four readers were 1.00, 0.97, and 0.97, respectively. The root-mean-square values of the COVs for the SUV(max), SUV(mean), and UD(CT) by the four readers were 0%, 13.56%, and 11.03%, respectively. There was a high correlation observed between the SUV(max) and SUV(mean) (Pearson's r=0.958; P <0.01). CONCLUSION: This study has shown that the SUV(max) of lung nodules can be calculated without any interobserver variation. These findings indicate that SUV(max) is a more valuable parameter than the SUV(mean) or UD(CT) for the evaluation of therapeutic effects of chemotherapy or radiation therapy on serial studies.

An updated and validated PET/CT volumetric prognostic index for non-small cell lung cancer.

OBJECTIVES: Whole-body metabolic tumor volume (MTVWB) and TNM staging are independent prognostic factors for overall survival (OS) in non-small cell lung cancer (NSCLC). We aimed to update and validate the PET/CT volumetric prognostic index (PVP index) using the new 8th edition TNM staging system to evaluate its prognostic power versus TNM staging and MTVWB alone. MATERIALS AND METHODS: This study was a retrospective analysis of 949 non-small cell lung cancer (NSCLC) patients diagnosed between 2004 and 2014. Clinical TNM stage, MTVWB, age and gender, tumor histology type at the initial staging PET/CT exam, as well as treatment history and long-term survival data were obtained. Patients were randomly assigned to modeling or validation group. Univariate and multivariate Cox regression analyses were performed to compare PVP index, TNM stage, and MTVWB in the validation group. RESULTS: The updated PVP index included the 3 variables TNM stage, and MTVWB and age. Univariate Cox models showed significant association of PVP index with overall survival (OS) in patients with NSCLC (with Hazard ratio HR = 2.88 in the validation group, p < 0.001). The C-statistic of the PVP index (C-statistic = 0.71 in the validation group) was significantly greater than that of 8th edition TNM staging (C-statistic = 0.68, p = 0.029), MTVWB (C-statistic = 0.68, p = 0.001), and patient age (C-statistic = 0.53, p < 0.001). Multivariate Cox regression analyses demonstrated significant association of PVP index with OS (with HR = 2.80, p < 0.001) after adjusting patient's gender and tumor histology. CONCLUSIONS: The updated PVP index provides a quantitative risk assessment for NSCLC patients using 8th edition TNM staging, MTVWB, and age. The index provides a simple and practical way for the care team to incorporate the independent prognostic value of both the TNM stage and MTVWB. This approach can further improve the accuracy of overall survival prognosis.

An experimental rabbit model of symptomatic cerebral vasospasm with in vivo neuroimaging assessment and ex vivo histological validation.

Cerebral vasospasm (CVS) is a severe complication that occurs following aneurysmal subarachnoid hemorrhage (SAH). Magnetic resonance angiography (MRA) has been used to evaluate brain injury following SAH in humans. The present study was designed to assess a rabbit model of symptomatic CVS (SCVS) and the utility of MRA in evaluating SCVS in rabbits. Japanese white rabbits (n=24) were randomly divided into 2 equal groups: A sham group and a SAH group. Neurological scores were evaluated for 7 days following SAH. Basilar artery (BA) diameters were measured using MRA preoperatively and 7 days postoperatively. Rabbits were sacrificed 7 days following SAH and the BA diameter of each rabbit was determined using histological evaluation. Compared with the Sham group, neurological function was significantly reduced in the SAH group at all time points (P<0.05). Furthermore, the BA diameter was significantly smaller in the SAH group on day 7 compared with the baseline measurement (P<0.05). No significant difference was observed between histological and MRA findings in either group at day 7. Histological changes in the hippocampus consistent with ischemia were observed in the SAH group. Hippocampal ischemia was also identified in the SAH group via MRA and there was no difference in detection rates following the use of MRA and histochemistry. MRA appears to be an effective method for assessing vasospasms of the BA and ischemic changes to the hippocampus in a rabbit model of SCVS. Furthermore, the animal model used in the present study may be beneficial for the future study of SCVS.

Development of a computer-aided diagnostic scheme for detection of interval changes in successive whole-body bone scans.

Bone scintigraphy is the most frequent examination among various diagnostic nuclear medicine procedures. It is a well-established imaging modality for the diagnosis of osseous metastasis and for monitoring osseous tumor response to chemotherapy and radiation therapy. Although the sensitivity of bone scan examinations for detection of bone abnormalities has been considered to be relatively high, it is time consuming to identify multiple lesions such as bone metastases of prostate and breast cancers. In addition, it is very difficult to detect subtle interval changes between two successive abnormal bone scans, because of variations in patient conditions, the accumulation of radioisotopes during each examination, and the image quality of gamma cameras. Therefore, we developed a new computer-aided diagnostic (CAD) scheme for the detection of interval changes in successive whole-body bone scans by use of a temporal subtraction image which was obtained with a nonlinear image-warping technique. We carried out 58 pairs of successive bone scans in which each scan included both posterior and anterior views. We determined 107 "gold-standard" interval changes among the 58 pairs based on the consensus of three radiologists. Our computerized scheme consisted of seven steps, i.e., initial image density normalization on each image, image matching for the paired images, temporal subtraction by use of the nonlinear image-warping technique, initial detection of interval changes by use of temporal-subtraction images, image feature extraction of candidates of interval changes, rule-based tests by use of 16 image features for removing some false positives, and display of the computer output for identified interval changes. One hundred seven gold standard interval changes included 71 hot lesions (uptake was increased compared with the previous scan, or there was new uptake in the current scan) and 36 cold lesions (uptake was decreased or disappeared) for anterior and posterior views. The overall sensitivity in the detection of interval changes, including both hot and cold lesions evaluated by use of the resubstitution and the leave-one-case-out methods, were 95.3%, with 5.97 false positives per view, and 83.2% with 6.02, respectively. The temporal subtraction image for successive whole-body bone scans has the potential to enhance the interval changes between two images, which also can be quantified. Furthermore, the CAD scheme for the detection of interval changes by use of temporal subtraction images would be useful in assisting radiologists' interpretation on successive bone scan images.

Usefulness of temporal subtraction images for identification of interval changes in successive whole-body bone scans: JAFROC analysis of radiologists' performance.

RATIONALE AND OBJECTIVES: We evaluated the usefulness of temporal subtraction images obtained from two successive whole-body bone scans, in terms of improvement in radiologists' diagnostic accuracy in detecting interval changes and of a reduction in reading time, by use of a jackknife free-response receiver operating characteristic (JAFROC) analysis method. MATERIALS AND METHODS: Twenty pairs of successive whole-body bone scans (72 consented interval changes) and their temporal subtraction images were used for an observer performance study. Our institutional review board approved the use of this database and the participation of radiologists in this study. In the first session of the observer study, without temporal subtraction images, the previous and current images were shown to five radiologists independently for their marking of the locations on current images and confidence ratings on potential interval changes from previous images. In the second session, temporal subtraction images were shown together with the modified previous and current images. JAFROC analysis was used for assessing the statistical significance of differences between radiologists' performance without and with temporal subtraction images. RESULTS: The average sensitivity for detecting interval changes was improved from 58.6% to 73.2% at a false-positive rate of two per case by use of temporal subtraction images, and the difference was statistically significant by use of JAFROC analysis (P = .035). In addition, the mean reading time per case was reduced considerably from 134 seconds to 91 seconds (P < .01). CONCLUSIONS: Temporal subtraction imaging for successive whole-body bone scans has the potential greatly to assist radiologists by increasing both their accuracy and productivity.