Edward A. Eikman

Quantitative Computed Tomographic Descriptors Associate Tumor Shape Complexity and Intratumor Heterogeneity with Prognosis in Lung Adenocarcinoma

Two CT features were developed to quantitatively describe lung adenocarcinomas by scoring tumor shape complexity (feature 1: convexity) and intratumor density variation (feature 2: entropy ratio) in routinely obtained diagnostic CT scans. The developed quantitative features were analyzed in two independent cohorts (cohort 1: n = 61; cohort 2: n = 47) of patients diagnosed with primary lung adenocarcinoma, retrospectively curated to include imaging and clinical data. Preoperative chest CTs were segmented semi-automatically. Segmented tumor regions were further subdivided into core and boundary sub-regions, to quantify intensity variations across the tumor. Reproducibility of the features was evaluated in an independent test-retest dataset of 32 patients. The proposed metrics showed high degree of reproducibility in a repeated experiment (concordance, CCC≥0.897; dynamic range, DR≥0.92). Association with overall survival was evaluated by Cox proportional hazard regression, Kaplan-Meier survival curves, and the log-rank test. Both features were associated with overall survival (convexity: p = 0.008; entropy ratio: p = 0.04) in Cohort 1 but not in Cohort 2 (convexity: p = 0.7; entropy ratio: p = 0.8). In both cohorts, these features were found to be descriptive and demonstrated the link between imaging characteristics and patient survival in lung adenocarcinoma.

Computed Tomography Response, But Not Positron Emission Tomography Scan Response, Predicts Survival After Neoadjuvant Chemotherapy for Resectable Non–Small-Cell Lung Cancer

PURPOSE Tumor response is considered a surrogate marker of survival. We investigated whether tumor response based on computed tomography (CT) scan or whole-body [(18)F]fluorodeoxyglucose positron emission tomography (PET) scan after neoadjuvant chemotherapy for resectable non-small-cell lung cancer (NSCLC) is prognostic of survival. PATIENTS AND METHODS Two consecutive phase II clinical trials were jointly analyzed. Patients underwent CT and PET scans before and after completion of neoadjuvant chemotherapy, followed by surgery. RESULTS Eighty-nine patients were included. Patients with a partial or complete response based on Response Evaluation Criteria in Solid Tumors categories (n = 33) had a better overall survival than those with stable or progressive disease (n = 56; median survival time, not reached v 36 months, respectively; P = .04). Of all patients, those with response in the highest quartile had 1- and 2-year survival rates of 100% and 81%, respectively, compared with 77% and 61%, respectively, among patients in the lowest quartile. However, on the basis of visual analysis of PET scan, patients with a metabolic response (n = 28) had no significant difference in survival compared with patients without response (n = 61; median survival time, 35.6 months v not reached, respectively; P = .94). In addition, on the basis of a semiquantitative analysis of PET scan, using at least 30% reduction in tumor metabolism as a response (n = 59), we also found no significant difference in survival among those with or without response. CONCLUSION Among patients with resectable NSCLC treated with neoadjuvant chemotherapy, we found no evidence that tumor response by PET scan after chemotherapy is prognostic of survival; however, response by CT scan was associated with better survival.

Asymptomatic pulmonary embolism: a common event in high risk patients

Ventilation and perfusion lung scans were obtained before and at weekly intervals following hip surgery or major amputation in 158 patients. Pulmonary arteriograms were obtained in 21 of 33 patients developing perfusion patterns strongly suggesting embolism; 19 of the 21 arteriograms demonstrated pulmonary embolism. From autopsy and clinical data, 36 patients were diagnosed as having an embolus while under study, and 12 patients were suspected of having had an embolus during their illness but prior to entry into the study. Only four of these 48 patients experienced symptoms suggestive of pulmonary embolism. We conclude that asymptomatic pulmonary embolism is a common event in the populations studied.

Variance of SUVs for FDG-PET/CT is greater in clinical practice than under ideal study settings.

Purpose Measurement variance affects the clinical effectiveness of PET-based measurement as a semiquantitative imaging biomarker for cancer response in individual patients and for planning clinical trials. In this study, we measured test-retest reproducibility of SUV measurements under clinical practice conditions and recorded recognized deviations from protocol compliance. Methods Instrument performance calibration, display, and analyses conformed to manufacture recommendations. Baseline clinical 18F-FDG PET/CT examinations were performed and then repeated at 1 to 7 days. Intended scan initiation uptake period was to repeat the examinations at the same time for each study after injection of 12 mCi FDG tracer. Avidity of uptake was measured in 62 tumors in 21 patients as SUV for maximum voxel (SUVmax) and for a mean of sampled tumor voxels (SUVmean). Results The range of SUVmax and SUVmean was 1.07 to 21.47 and 0.91 to 14.69, respectively. Intraclass correlation coefficient between log of SUVmax and log of SUVmean was 0.93 (95% confidence interval [CI], 0.88–0.95) and 0.92 (95% CI, 0.87–0.95), respectively. Correlation analysis failed to show an effect on uptake period variation on SUV measurements between the 2 examinations, suggesting additional sources of noise. The threshold criteria for relative difference from baseline for the 95% CI were ±49% or ±44% for SUVmax or SUVmean, respectively. Conclusions Variance of SUV for FDG-PET/CT in current clinical practice in a single institution was greater than expected when compared with benchmarks reported under stringent efficacy study settings. Under comparable clinical practice conditions, interpretation of changes in tumor avidity in individuals and assumptions in planning clinical trials may be affected.

A multicenter prospective evaluation of the clinical utility of F-18 FDG-PET/CT in patients with AJCC stage IIIB or IIIC extremity melanoma

Objective/Background:There is a high risk of relapse in stage IIIB/IIIC melanoma. The utility of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography integrated with computed tomography (FDG-PET/CT) in these patients to evaluate response to treatment or for surveillance after treatment is currently not well defined. Methods:Prospective data from 2 centers identified 97 patients with stage IIIB/IIIC extremity melanoma undergoing isolated limb infusion (ILI) who had whole body FDG-PET/CT scans before and every 3 months after treatment. Clinical response was determined at 3 months by Response Evaluation Criteria In Solid Tumors. Results:Complete response (CR) after ILI occurred in 33% (32/97) of patients. FDG-PET/CT accurately identified 59% of patients who were CRs (19/32), whereas 41% (13/32) had residual metabolic activity in the extremity that was histologically negative for melanoma. The 3-year disease-free rate was 62.2% (95% CI: 40.1%–96.4%) for those patients who were CRs by both clinical/pathologic examination and FDG-PET/CT (n = 19) compared to only 29.4% (95% CI: 9.9%–87.2%) of those CRs who still had residual FDG-PET/CT activity (n = 13). FDG-PET/CT was utilized for surveillance of disease recurrence outside the regional field of treatment. Fifty-two percent (51/97) of patients developed disease outside the extremity at a median time of 212 days from pre-ILI FDG-PET/CT. In 47% (29/62) of these cases, the recurrence was resected. Conclusions:Although FDG-PET/CT does not appear to accurately identify patients who appear to be CRs to ILI, it does appear to identify a subgroup of patients whose regional progression-free survival is markedly worse. However, FDG-PET/CT appears to be an excellent method for surveillance in stage IIIB/IIIC patients after ILI with ability to identify surgically resectable recurrent disease in these high-risk patients.

Failure of low dose heparin to prevent pulmonary embolism after hip surgery or above the knee amputation.

In a randomized, double-blind trial, 5,000 USP units of sodium heparin or saline were give subcutaneously at least two hours before surgery and at 12 hour intervals thereafter to patients requiring total hip replacement, surgical correction of hip fracture, or major lower extremity amputation for vascular insufficiency. Lung perfusion scans were performed before surgery and at weekly intervals during the postoperative period. Pulmonary arteriograms were requested in patients developing new perfusion defects on serial scans. Two hundred twelve patient hospitalizations were analyzed. We diagnosed acute pulmonary embolism by serial lung perfusion scans or at autopsy in 37 patients. The incidence of pulmonary embolism in 40 patients with below the knee amputation was too low to warrant conclusions. The incidence of acute pulmonary embolism in 94 patients undergoing above the knee amputation was 25% in patients receiving heparin and 27% in patients receiving saline. The incidence of acute pulmonary embolism in 78 patients undergoing hip surgery was 13% in patients receiving heparin and 12% in patients receiving saline. We conclude that the regimen used had no significant effect on the incidence of acute pulmonary embolism in patients undergoing hip surgery or above the knee amputation.

Semiquantitative Computed Tomography Characteristics for Lung Adenocarcinoma and Their Association With Lung Cancer Survival.

UNLABELLED In this study we developed 25 computed tomography descriptors among 117 patients with lung adenocarcinoma to semiquantitatively assess their association with overall survival. Pleural attachment was significantly associated with an increased risk of death and texture was most important for distinguishing histological subtypes. This approach has the potential to support automated analyses and develop decision-support clinical tools. BACKGROUND Computed tomography (CT) characteristics derived from noninvasive images that represent the entire tumor might have diagnostic and prognostic value. The purpose of this study was to assess the association of a standardized set of semiquantitative CT characteristics of lung adenocarcinoma with overall survival. PATIENTS AND METHODS An initial set of CT descriptors was developed to semiquantitatively assess lung adenocarcinoma in patients (n = 117) who underwent resection. Survival analyses were used to determine the association between each characteristic and overall survival. Principle component analysis (PCA) was used to determine characteristics that might differentiate histological subtypes. RESULTS Characteristics significantly associated with overall survival included pleural attachment (P < .001), air bronchogram (P = .03), and lymphadenopathy (P = .02). Multivariate analyses revealed pleural attachment was significantly associated with an increased risk of death overall (hazard ratio [HR], 3.21; 95% confidence interval [CI], 1.53-6.70) and among patients with lepidic predominant adenocarcinomas (HR, 5.85; 95% CI, 1.75-19.59), and lymphadenopathy was significantly associated with an increased risk of death among patients with adenocarcinomas without a predominant lepidic component (HR, 3.07; 95% CI, 1.09-8.70). A PCA model showed that texture (ground-glass opacity component) was most important for separating the 2 subtypes. CONCLUSION A subset of the semiquantitative characteristics described herein has prognostic importance and provides the ability to distinguish between different histological subtypes of lung adenocarcinoma.

Metabolic Activity by 18F-FDG-PET/CT Is Prognostic for Stage I and II Pancreatic Cancer.

Purpose Metabolic activity, as defined by 18F-FDG uptake on PET, is a prognostic marker for multiple malignancies; however, no study has examined the prognostic value of imaging with FDG PET in stage I and II pancreatic cancer. We examined the value of PET FDG uptake in early-stage pancreatic cancer patients. Methods We identified patients with early-stage pancreatic cancer (I-II) who had FDG PET scan performed as part of their preoperative evaluation. The patients were divided into either high or low FDG uptake according to the median primary tumor standard uptake value (SUVmax). Our primary end points were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier estimate was used for survival analysis. Pathologic data were compared using the Fisher exact and &khgr;2 tests. Results One hundred five patients were identified: 51 patients with low FDG uptake and 54 patients with high FDG uptake. Eighty-five patients (81%) had PET avid tumors, whereas 20 (19%) patients did not. High FDG uptake correlated with pathologic stage (P = 0.012). Patients with low FDG uptake had significantly better median OS than patients with high FDG uptake (28 vs. 16 months; P = 0.036). Patients with low-FDG uptake had significantly longer median RFS than patients with high FDG uptake (14 vs. 12 months; P = 0.049). Conclusions Low FDG uptake in PET scans in patients with stage I and II pancreatic cancer correlates with improved OS and RFS. This supports the concept that glucose metabolic pathways are important in pancreatic cancer biology and that PET scan activity can be used as a prognostic biomarker after pancreatectomy.

Technology integration performance assessment using lean principles in health care.

This study assesses the impact of an automated infusion system (AIS) integration at a positron emission tomography (PET) center based on “lean thinking” principles. The authors propose a systematic measurement system that evaluates improvement in terms of the “8 wastes.” This adaptation to the health care context consisted of performance measurement before and after integration of AIS in terms of time, utilization of resources, amount of materials wasted/saved, system variability, distances traveled, and worker strain. The authors’ observations indicate that AIS stands to be very effective in a busy PET department, such as the one in Moffitt Cancer Center, owing to its accuracy, pace, and reliability, especially after the necessary adjustments are made to reduce or eliminate the source of errors. This integration must be accompanied by a process reengineering exercise to realize the full potential of AIS in reducing waste and improving patient care and worker satisfaction.

Automatic Analysis of Diagnostic Features from Digitized Radiocolloid Liver Images

In radiocolloid liver imaging, increased liver mass, and patchiness of the radiocolloid image are difficult for the physician to evaluate subjectively. We devised an automatic, computer-assisted method that aids in objective measurement and interpretation of these two image features, and summarize our methods in this paper. Our estimate of liver mass, and a texture index of image patchiness designated T2: D2, are calculated from a preprocessed gamma camera image of the right lateral projection of the liver. At the operating point of liver mass estimate >2.0 kg or T2: D2 > 0.54, the specificity was > 0.95 and sensitivity 0.5 for detection of liver disease in a population of male patients with independent histologic liver diagnoses or normal volunteers.