Machine learning-based diagnostic method of pre-therapeutic 18F-FDG PET/CT for evaluating mediastinal lymph nodes in non-small cell lung cancer.

OBJECTIVES: We aimed to find the best machine learning (ML) model using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for evaluating metastatic mediastinal lymph nodes (MedLNs) in non-small cell lung cancer, and compare the diagnostic results with those of nuclear medicine physicians. METHODS: A total of 1329 MedLNs were reviewed. Boosted decision tree, logistic regression, support vector machine, neural network, and decision forest models were compared. The diagnostic performance of the best ML model was compared with that of physicians. The ML method was divided into ML with quantitative variables only (MLq) and adding clinical information (MLc). We performed an analysis based on the 18F-FDG-avidity of the MedLNs. RESULTS: The boosted decision tree model obtained higher sensitivity and negative predictive values but lower specificity and positive predictive values than the physicians. There was no significant difference between the accuracy of the physicians and MLq (79.8% vs. 76.8%, p = 0.067). The accuracy of MLc was significantly higher than that of the physicians (81.0% vs. 76.8%, p = 0.009). In MedLNs with low 18F-FDG-avidity, ML had significantly higher accuracy than the physicians (70.0% vs. 63.3%, p = 0.018). CONCLUSION: Although there was no significant difference in accuracy between the MLq and physicians, the diagnostic performance of MLc was better than that of MLq or of the physicians. The ML method appeared to be useful for evaluating low metabolic MedLNs. Therefore, adding clinical information to the quantitative variables from 18F-FDG PET/CT can improve the diagnostic results of ML. KEY POINTS: • Machine learning using two-class boosted decision tree model revealed the highest value of area under curve, and it showed higher sensitivity and negative predictive values but lower specificity and positive predictive values than nuclear medicine physicians. • The diagnostic results from machine learning method after adding clinical information to the quantitative variables improved accuracy significantly than nuclear medicine physicians. • Machine learning could improve the diagnostic significance of metastatic mediastinal lymph nodes, especially in mediastinal lymph nodes with low 18F-FDG-avidity.

Prognostic value of LI-RADS category on gadoxetic acid-enhanced MRI and 18F-FDG PET-CT in patients with primary liver carcinomas.

OBJECTIVES: To evaluate the postoperative prognostic value of the Liver Imaging Reporting and Data System (LI-RADS) category on gadoxetic acid-enhanced MRI and 18F-fluorodeoxyglucose PET-CT in patients with primary liver carcinomas (PLCs). METHODS: A total of 189 patients with chronic liver disease and surgically proven single PLC (42 intrahepatic cholangiocarcinomas and 21 combined hepatocellular-cholangiocarcinomas and 126 hepatocellular carcinomas [2:1 matching to non-HCC malignancies]) were retrospectively evaluated with gadoxetic acid-enhanced MRI and PET-CT. Two independent reviewers assigned an LI-RADS category for each observation. The tumor-to-liver standardized uptake value ratio (TLR) was calculated. The overall survival (OS), recurrence-free survival (RFS), and the associated factors were evaluated. RESULTS: In multivariable analysis, LI-RADS category (LR-4 or LR-5 [LR-4/5] vs. LR-M; OS, hazard ratio [HR] 2.24, p = 0.006; RFS, HR 1.61, p = 0.028) and TLR (low, < 2.3 vs. high, ≥ 2.3; OS, HR 2.09, p = 0.014; RFS, HR 2.17, p < 0.001) were the independent factors for OS and RFS. For the LR-M group, the high TLR group showed lower OS and RFS rates than the low TLR group (OS, p = 0.008; RFS, p < 0.001). For the LR-4/5 group, the OS and RFS rates were not significantly different between the high TLR and low TLR groups (both p > 0.05). CONCLUSIONS: Both LI-RADS category on MRI and TLR on PET-CT are associated with the postoperative prognosis of PLCs. The prognosis of PLCs classified as LR-M can be further stratified according to the TLR group, but not for the PLCs classified as LR-4/5. KEY POINTS: • The LI-RADS category (LR-4/5 vs. LR-M) and tumor-to-liver standardized uptake value ratio (TLR, low vs. high) were independent factors for postoperative prognosis of primary liver carcinomas (PLCs). • For PLCs classified as LR-M, the TLR group helps stratify the postoperative prognosis of PLCs, with the high TLR group having a poor prognosis and the low TLR group having a better prognosis (p = 0.008 for OS and p < 0.001 for RFS). • For PLCs classified as LR-4/5, the OS and RFS rates were not significantly different between the high TLR and low TLR groups (both p > 0.05).

Predictive role of lymphoscintigraphy undergoing lymphovenous anastomosis in patients with lower extremity lymphedema: a preliminary study.

BACKGROUND: We investigated whether preoperative lymphoscintigraphy could predict the treatment response of unilateral lymphovenous anastomosis (LVA) in patients with lower extremity lymphedema. MATERIALS AND METHODS: A total of 17 patients undergoing lymphoscintigraphy subsequent to LVA was included. As qualitative lymphoscintigraphic indicators, ilioinguinal lymph node uptake, main lymphatic vessel, collateral vessel, and four types of dermal backflow patterns (absent; distal only; proximal only; whole lower limb) were evaluated. Lymph node uptake ratio, extremity uptake ratio, and injection site clearance ratio were obtained as quantitative lymphoscintigraphic indicators at 1 and 2-h after injection. To evaluate therapy response, the volume difference ratio of the whole lower limb at 3 months (early response) and 1 year (late response) was measured. Volume difference ratios (continuous variable and binary variable with a cut-off value of zero) were compared according to the lymphoscintigraphic variables. RESULTS: The group with whole lower limb dermal backflow had a greater volume change than the other groups (p = 0.047). The group with dermal backflow in the whole lower limb OR only in the distal part had a higher rate of volume reduction than the group with dermal backflow only in the proximal part OR absent (p = 0.050). The 2-h extremity uptake ratio was the only indicator that positively correlated with early and late volume difference ratio (p = 0.016, p = 0.001). The rate of volume decrease at 1 year was high in patients with high 2-h extremity uptake ratio (p = 0.027). As the amount of dermal backflow increases, the postoperative therapeutic effect increases (p = 0.040). CONCLUSIONS: Preoperative lymphoscintigraphy is useful to predict both early and late therapy response in patients with lower extremity lymphedema undergoing LVA. Both dermal backflow pattern and extremity uptake ratio may be predictive lymphoscintigraphic indicators.

Correction to: Imaging phenotype using 18F-fluorodeoxyglucose positron emission tomography-based radiomics and genetic alterations of pancreatic ductal adenocarcinoma.

After publication of this article we received a request from Dr. Jong Kyun Lee to have his name removed from the author list as he felt he did not fully meet the authorship criteria. The original version of this article was inadvertently published with an incorrect inclusion period of study.

Imaging phenotype using 18F-fluorodeoxyglucose positron emission tomography-based radiomics and genetic alterations of pancreatic ductal adenocarcinoma.

PURPOSE: This study aimed to determine if major gene mutations including in KRAS, SMAD4, TP53, and CDKN2A were related to imaging phenotype using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-based radiomics in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Data on 48 PDAC patients with pretreatment FDG PET/CT who underwent genomic analysis of their tumor tissue were retrospectively analyzed. A total of 35 unique quantitative radiomic features were extracted from PET images, including imaging phenotypes such as pixel intensity, shape, and textural features. Targeted exome sequencing using a customized cancer panel was used for genomic analysis. To assess the predictive performance of genetic alteration using PET-based radiomics, areas under the receiver operating characteristic curve (AUC) were used. RESULTS: Mutation frequencies were KRAS 87.5%, TP53 70.8%, SMAD4 25.0%, and CDKN2A 18.8%. KRAS gene mutations were significantly associated with low-intensity textural features, including long-run emphasis (AUC = 0.806), zone emphasis (AUC = 0.794), and large-zone emphasis (AUC = 0.829). SMAD4 gene mutations showed significant relationships with standardized uptake value skewness (AUC = 0.727), long-run emphasis (AUC = 0.692), and high-intensity textural features such as run emphasis (AUC = 0.775), short-run emphasis (AUC = 0.736), zone emphasis (AUC = 0.750), and short-zone emphasis (AUC = 0.725). No significant associations were seen between the imaging phenotypes and genetic alterations in TP53 and CDKN2A. CONCLUSION: Genetic alterations of KRAS and SMAD4 had significant associations with FDG PET-based radiomic features in PDAC. PET-based radiomics may help clinicians predict genetic alteration status in a noninvasive way.

Serum uric acid in asymptomatic adults is weakly associated with carotid artery FDG uptake but not intima-media thickness.

BACKGROUND: This study investigated the association of serum uric acid (UA) with carotid fluoro-2-deoxyglucose (FDG) uptake as a marker of inflammatory atherosclerosis. METHODS AND RESULTS: In this cross-sectional retrospective study of 970 otherwise healthy adults, subjects in the greater serum UA quartiles had higher triglyceride (P < .001), lower high-density lipoprotein cholesterol (P < .05), and lower estimated GFR (P < .001). Mean and maximum Target-to-background ratios (TBRs) of carotid FDG uptake measured by positron emission tomography were significantly increased across greater serum UA quartiles (1.35 and 1.57 for Q1, 1.38 and 1.60 for Q2, 1.39 and 1.62 for Q3, and 1.39 and 1.61 for Q4; P = .001 and < .001). Carotid intima-media thickness was not different. Serum UA showed weak but significant correlations with estimated GFR (P < .001), and with mean (P < .001) and maximum carotid TBR (P = .004). Serum UA correlated with mean TBR in male (P = .008) and female subjects (P = .011), in high (≥ 70; P = .015) and low estimated GFR (< 70; P = .035), and in normotensive (P = .001) but not in hypertensive subjects. CONCLUSIONS: Elevated serum UA in asymptomatic adults is associated with increased carotid FDG uptake, which suggests a potential role of UA in carotid inflammatory atherosclerosis.

Prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with combined hepatocellular-cholangiocarcinoma.

PURPOSE: The prognostic value of pretreatment 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET/CT) was assessed in patients with combined hepatocellular-cholangiocarcinoma (cHCC-CC). METHODS: A total of 46 patients with cHCC-CC who underwent FDG PET/CT before treatment were retrospectively analysed. Tumour FDG avidity was measured in terms of the tumour-to-normal liver standardized uptake value ratio (TLR) of the primary tumour on FDG PET/CT. The prognostic significance of TLR using the median value of 3.4 as the cut-off value and other clinical variables was assessed using Cox proportional hazards regression models. Differences in progression-free survival (PFS) and overall survival (OS) in relation to TLR were examined by the Kaplan-Meier method. RESULTS: During a median follow-up period of 29 months, 29 patients (63.0%) showed tumour recurrence or progression, and 25 patients (54.4%) died from cancer. Higher TLRs (>3.4) were associated with larger tumour size (p = 0.007) and higher tumour stage (p = 0.030). In a univariable analysis, TLR, tumour stage and CEA were significant prognostic predictors. In a multivariable analysis, TLR was an independent predictor of PFS (HR 5.19, 95% CI 1.80-15.01; p = 0.002) and OS (HR 3.95, 95% CI 1.27-12.24; p = 0.017). Patients with a higher TLR showed significantly worse PFS (2-year survival rate 17.8% vs. 62.9%; p = 0.001) and OS (2-year survival rate, 39.1% vs. 77.3%; p = 0.001) than those with a lower TLR. CONCLUSION: Pretreatment TLR of the primary tumour measured on FDG PET/CT is an independent predictor of survival in patients with cHCC-CC.

Diagnostic value of surveillance 18F-fluorodeoxyglucose PET/CT for detecting recurrent esophageal carcinoma after curative treatment.

PURPOSE: Esophageal carcinoma recurs within two years in approximately half of patients who receive curative treatment and is associated with poor survival. While 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is a reliable method of detecting recurrent esophageal carcinoma, in most previous studies FDG PET/CT scans were performed when recurrence was suspected. The aim of this study was to evaluate FDG PET/CT as a surveillance modality to detect recurrence of esophageal carcinoma after curative treatment where clinical indications of recurrent disease are absent. METHODS: A total of 782 consecutive FDG PET/CT studies from 375 patients with esophageal carcinoma after definitive treatment were reviewed. Abnormal lesions suggestive of recurrence on PET/CT scans were then evaluated. Recurrence was determined by pathologic confirmation or other clinical evidence within two months of the scan. If no clinical evidence for recurrence was found at least 6 months after the scan, the case was considered a true negative for recurrence. RESULTS: The diagnostic sensitivity and specificity of PET/CT for detecting recurrent esophageal carcinomas were 100% (64/64) and 94.0% (675/718), respectively. There were no significant differences in the diagnostic performance of PET/CT for detecting recurrence according to initial stage or time between PET/CT and curative treatments. Unexpected second primary cancers were detected by FDG PET/CT in seven patients. CONCLUSIONS: Surveillance FDG PET/CT is a useful imaging tool for detection of early recurrence or clinically unsuspected early second primary cancer in patients with curatively treated esophageal carcinoma but without clinical suspicion of recurrence.

Comparison of prognostic values of primary tumor and nodal 18F-fluorodeoxyglucose uptake in non-small cell lung cancer with N1 disease.

INTRODUCTION: We hypothesized that, in non-small cell lung cancer (NSCLC) with N1 metastasis, N1 nodal 18F-fluorodeoxyglucose (FDG) status offers independent and incremental prognostic value. METHODS: We enrolled 106 NSCLC patients with pathology-confirmed N1 metastasis. N1 node FDG positivity, primary tumor maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. Kaplan-Meier method and Cox regression analyses were performed for cancer-specific survival (CSS) and disease-free survival (DFS). RESULTS: Subjects were 67 males and 39 females (61.9 ± 9.4 years). Eighty-one (76.4%) and 25 (23.6%) had pathologic stage IIB and IIIA NSCLC, respectively. All underwent complete tumor resection. FDG-positive N1 nodes were larger and had higher primary tumor SUVmax. During a follow-up of 42 months, there were 56 recurrences and 31 cancer deaths. Significant univariate predictors were stage, no adjuvant therapy, and FDG-positive nodes for DFS, and stage, no adjuvant therapy, node size, tumor MTV, TLG, and SUVmax, and FDG-positive nodes for CSS. Independent predictors on multivariate analyses were FDG-positive nodes (HR = 3.071, p = 0.003), greater tumor TLG (HR = 3.224, p = 0.002), and no adjuvant therapy (HR = 3.631, p < 0.001) for poor CSS, and FDG-positive nodes (HR = 1.771, p = 0.040) and no adjuvant therapy (HR = 2.666, p = 0.002) for poor DFS. Harrell's concordance and net reclassification improvement tests showed that CSS prediction was significantly improved by the addition of N1 FDG status to a model containing tumor TLG. CONCLUSION: N1 node FDG status can be useful for predicting the outcome of NSCLC patients with N1 metastasis beyond that provided by other prognostic variables. KEY POINTS: • In NSCLC with N1 disease, N1 node FDG status is useful as a prognostic predictor. • FDG-positive N1 nodes provide additional prognostic value beyond TLG of primary tumor. • Combining TLG of primary tumor and N1 node uptake can stratify the survival of patients.

Preoperative prediction of microvascular invasion of hepatocellular carcinoma using 18F-FDG PET/CT: a multicenter retrospective cohort study.

PURPOSE: The aim of this study was to assess the potential of tumor 18F-fluorodeoxyglucose (FDG) avidity as a preoperative imaging biomarker for the prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC). METHODS: One hundred and fifty-eight patients diagnosed with Barcelona Clinic Liver Cancer stages 0 or A HCC (median age, 57 years; interquartile range, 50-64 years) who underwent 18F-FDG positron emission tomography with computed tomography (PET/CT) before curative surgery at seven university hospitals were included. Tumor FDG avidity was measured by tumor-to-normal liver standardized uptake value ratio (TLR) of the primary tumor on FDG PET/CT imaging. Logistic regression analysis was performed to identify significant parameters associated with MVI. The predictive performance of TLR and other clinical variables was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: MVI was present in 76 of 158 patients with HCCs (48.1%). Multivariable logistic regression analysis revealed that TLR, serum alpha-fetoprotein (AFP) level, and tumor size were significantly associated with the presence of MVI (P < 0.001). Multinodularity was not significantly associated with MVI (P = 0.563). The area under the ROC curve (AUC) for predicting the presence of MVI was best with TLR (AUC = 0.704), followed by tumor size (AUC = 0.685) and AFP (AUC = 0.670). We were able to build an improved prediction model combining TLR, tumor size, and AFP by using multivariable logistic regression modeling (AUC = 0.756). CONCLUSIONS: Tumor FDG avidity measured by TLR on FDG PET/CT is a preoperative imaging biomarker for the prediction of MVI in patients with HCC.

Strong association of epidermal growth factor receptor status with breast cancer FDG uptake.

PURPOSE: Imaging tumor FDG uptake could complement breast cancer biomarkers of risk and treatment response. Although breast cancer FDG uptake is reputedly influenced by major biomarker states, the role of epidermal growth factor receptor (EGFR) expression remains largely unexplored. METHODS: This is a retrospective study that included 499 patients with primary breast cancer at initial presentation. Tumor FDG uptake was measured on pretreatment PET/CT as maximum standardized uptake value (SUVmax), and biomarkers were assessed by immunohistochemistry of tumor tissue. Regression analysis was performed for predictors of high tumor FDG uptake (SUVmax ≥ 8.6). RESULTS: SUVmax was higher in ER- (36.5%; 11.2 ± 6.0 vs. 8.3 ± 5.3), PR- (42.3%; 10.9 ± 6.0 vs. 8.2 ± 5.2), and triple-negative tumors (19.8%; 12.0 ± 6.9 vs. 8.7 ± 5.2; all p < 0.0001). EGFR expression (28.5%) was more frequent in ER-, PR-, triple-negative, cytokeratin 5/6 (CK5/6) + and mutant P53 (mP53) + tumors (all p < 0.0001). EGFR+ was associated with higher SUVmax among all tumors (11.9 ± 6.0 vs. 8.3 ± 5.3), ER- tumors (p < 0.0001), PR- and + tumors (p < 0.0001 and 0.027), hormone receptor- and + tumors (p < 0.0001 and 0.004), human epidermal growth factor receptor 2 (HER2)- and + tumors (p < 0.0001 and 0.006), non-triple negative tumors (p < 0.0001), CK5/6- and + tumors (p = 0.021 and <0.0001), and mP53- and + tumors (p < 0.0001 and 0.008). Tumors had high FDG uptake in 73.2% of EGFR+ and 40.6% of EGFR- tumors. On regression analysis, significant multivariate predictors of high tumor FDG uptake were large size, EGFR+ and CK5/6+ for the entire subjects, and EGFR+ and CK5/6+ for ER- and hormone receptor negative subgroups. High FDG uptake was able to sub-stratify EGFR+ tumors that were more likely to be ER- and CK5/6+, and EGFR- tumors more likely to be mP53 +. CONCLUSIONS: Primary breast tumor FDG uptake is strongly influenced by EGFR status beyond that by other major biomarkers including hormone receptor and HER2 status, and EGFR expression is a strong independent predictor of high breast tumor FDG uptake.

Prognostic value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with Barcelona Clinic Liver Cancer stages 0 and A hepatocellular carcinomas: a multicenter retrospective cohort study.

PURPOSE: We evaluated the prognostic value of pretreatment (18)F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET/CT) in patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A hepatocellular carcinoma (HCC) who had received curative treatment or transarterial chemoembolization (TACE). METHODS: Between 2009 and 2010, 317 patients diagnosed with HCC at seven hospitals were enrolled. Among these, 195 patients underwent curative treatments including resection, liver transplantation, and radiofrequency ablation. TACE was performed in 122 patients. The tumor-to-normal liver standardized uptake value ratio (TLR) of the primary tumor was measured using pretreatment FDG PET/CT. The prognostic significance of TLR and other clinical variables was assessed using Cox regression models. Differences in the overall survival (OS) associated with TLR or other significant clinical factors were examined using the Kaplan-Meier method. RESULTS: Over a median follow-up period of 46 months, 77 patients died from cancer. In the curative cohort, higher TLR (≥2) was significantly associated with death (hazard ratio [HR] = 2.68; 95 % CI, 1.16-6.15; P = 0.020) in multivariable analysis. Patients with a higher TLR had significantly worse OS than patients with a lower TLR (5-year overall survival, 61 % vs. 79.4 %; P = 0.006). In the TACE cohort, the Model for End-Stage Liver Disease (MELD) score (≥8) was a significant independent prognostic factor for OS (HR = 3.34; 95 % CI, 1.49-7.48; P = 0.003), whereas TLR was not associated with OS. The Kaplan-Meier curves showed significantly poorer OS in patients with higher MELD scores (≥8) than in those with lower MELD scores (5-year survival rate, 33.1 % vs. 79.6 %; P < 0.001). CONCLUSIONS: Pretreatment TLR measured using FDG PET/CT was an independent prognostic factor for OS in patients with BCLC stage 0 or A HCC undergoing curative treatment. In contrast, underlying liver function appeared to be important in predicting the prognosis of patients undergoing TACE.

Intratumoral heterogeneity of (18)F-FDG uptake predicts survival in patients with pancreatic ductal adenocarcinoma.

PURPOSE: To assess whether intratumoral heterogeneity measured by (18)F-FDG PET texture analysis has potential as a prognostic imaging biomarker in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We evaluated a cohort of 137 patients with newly diagnosed PDAC who underwent pretreatment (18)F-FDG PET/CT from January 2008 to December 2010. First-order (histogram indices) and higher-order (grey-level run length, difference, size zone matrices) textural features of primary tumours were extracted by PET texture analysis. Conventional PET parameters including metabolic tumour volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) were also measured. To assess and compare the predictive performance of imaging biomarkers, time-dependent receiver operating characteristic (ROC) curves for censored survival data and areas under the ROC curve (AUC) at 2 years after diagnosis were used. Associations between imaging biomarkers and overall survival were assessed using Cox proportional hazards regression models. RESULTS: The best imaging biomarker for overall survival prediction was first-order entropy (AUC = 0.720), followed by TLG (AUC = 0.697), MTV (AUC = 0.692), and maximum SUV (AUC = 0.625). After adjusting for age, sex, clinical stage, tumour size and serum CA19-9 level, multivariable Cox analysis demonstrated that higher entropy (hazard ratio, HR, 5.59; P = 0.028) was independently associated with worse survival, whereas TLG (HR 0.98; P = 0.875) was not an independent prognostic factor. CONCLUSION: Intratumoral heterogeneity of (18)F-FDG uptake measured by PET texture analysis is an independent predictor of survival along with tumour stage and serum CA19-9 level in patients with PDAC. In addition, first-order entropy as a measure of intratumoral metabolic heterogeneity is a better quantitative imaging biomarker of prognosis than conventional PET parameters.

Prognostic significance of clinical and 18 F-FDG PET/CT parameters for post-distant metastasis survival in head and neck squamous cell carcinoma patients.

INTRODUCTION: Distant metastasis (M1) to vital organs remains a major cause of death in patients with head and neck squamous cell carcinomas (HNSCC). Clinically the survival periods vary in individual M1 HNSCC patients and a prognostic indicator has not been fully studied. Here, we evaluated the prognostic factors for survival including 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) parameters in M1 HNSCC patients. METHODS: The study included 108 patients with newly diagnosed M1 HNSCC (68 during clinical courses, 40 at presentation) who underwent FDG PET/CT. Maximum standardized uptake value (SUVmax) of metastatic tumors was measured by FDG PET/CT. Associations of primary tumor or metastatic tumor variables with overall survival were assessed with Cox regression models. RESULTS: Multivariate analyses demonstrated that nasopharynx primary and incomplete response of loco-regional disease to treatment were significant prognostic factors. In addition, adverse prognostic factors included short distant metastasis-free period (<10 months), high number (≥5), and high PET SUVmax (≥6.3) of metastatic lesions. The patients with at least one of these adverse features had a median survival <14 months. CONCLUSION: PET SUVmax of the metastatic tumors in M1 HNSCC patients can be a good predictor for survival. J. Surg. Oncol. 2016;114:888-894. © 2016 2016 Wiley Periodicals, Inc.

Volume-based metabolic tumor response to neoadjuvant chemotherapy is associated with an increased risk of recurrence in breast cancer.

PURPOSE: To evaluate the prognostic value of a volume-based metabolic tumor response to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MATERIALS AND METHODS: This study was approved by the institutional review board, with waivers of informed consent. One hundred sixty-seven patients (mean age, 44 years; range, 22-68 years) with clinical stage II or III breast cancer who underwent fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography scans at baseline and after completion of neoadjuvant chemotherapy between July 2006 and June 2013 were selected. The association between the metabolic response parameters and the disease-free survival was assessed by using a Cox proportional hazards regression model and time-dependent receiver operating characteristic curve analysis. Metabolic response parameters included the maximum standardized uptake value (SUVmax), the total metabolic tumor volume (MTVtotal), and the relative decrease in SUVmax and MTVtotal. RESULTS: In the Cox model, posttreatment SUVmax (P = .029) and MTVtotal (P = .028) and relative decreases in SUVmax (P = .032) and MTVtotal (P = .005) after neoadjuvant chemotherapy were significantly associated with disease-free survival after adjusting for pretreatment clinical stage, yp stage, and tumor subtype. In the time-dependent receiver operating characteristic curve analysis, MTVtotal after neoadjuvant chemotherapy had the highest association with outcome compared with the other parameters (P < .001). MTVtotal of up to 0.2 cm(3) after neoadjuvant chemotherapy was significantly associated with a favorable outcome in patients who did not achieve pathologic complete response after neoadjuvant chemotherapy. CONCLUSION: The volume-based metabolic tumor response to neoadjuvant chemotherapy is associated with an increased risk of recurrence, regardless of tumor subtype and pathologic tumor response.

Volume-Based Assessment With 18F-FDG PET/CT Improves Outcome Prediction for Patients With Stage IIIA-N2 Non-Small Cell Lung Cancer.

OBJECTIVE: We evaluated the prognostic impact of volume-based assessment by pretreatment (18)F-FDG PET/CT in patients who had clinical stage IIIA-N2 non-small cell lung cancer (NSCLC) treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgical resection. MATERIALS AND METHODS: We reviewed 161 consecutive patients who had stage IIIA-N2 NSCLC treated with neoadjuvant CCRT followed by surgery. In all cases, N2 disease was pathologically confirmed by mediastinoscopic biopsy, endobronchial ultrasound-guided transbronchial needle aspiration, or video-assisted thoracoscopic surgery. We measured the total metabolic tumor volume (total MTV) and the maximum standardized uptake value (SUVmax), including a primary tumor and metastatic nodes on the pretreatment scan. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method. The association of PET parameters with OS and DFS was determined by univariable and multivariable analyses performed using the Cox regression model. RESULTS: A higher total MTV was significantly associated with poor DFS (hazard ratio [HR], 1.82; p = 0.036) and OS (HR = 2.97; p = 0.012) in the multivariable analysis. In contrast, a higher SUVmax was not significantly associated with poor DFS and OS. Patients with a high total MTV (> 22 cm(3)) had a median survival time that was significantly shorter than that of patients with a low total MTV (median DFS, 11.3 vs 42.0 months, respectively [p < 0.001]; median OS, 38.3 months vs not reached [p < 0.001]). Kaplan-Meier curves showed significant differences on the basis of total MTV in patients with or without mediastinal downstaging after CCRT. Patients with a high total MTV had significantly worse DFS when they had post-neoadjuvant pathologic (yp) stage 0-II disease (p = 0.020) or yp stage III disease (p = 0.036). Higher total MTV was also associated with worse OS in patients with yp stage 0-II disease (p = 0.013) or yp stage III disease (p = 0.007). CONCLUSION: A higher pretreatment total MTV is associated with worse outcome, independent of yp stage, in patients with stage IIIA-N2 NSCLC treated with neoadjuvant CCRT followed by surgery.

Volume-based assessment by (18)F-FDG PET/CT predicts survival in patients with stage III non-small-cell lung cancer.

PURPOSE: We evaluated the prognostic impact of volume-based assessment by (18)F-FDG PET/CT in patients with stage III non-small-cell lung cancer (NSCLC). METHODS: We reviewed 194 consecutive patients with stage IIIA NSCLC treated with surgical resection (surgical group) and 115 patients treated with nonsurgical therapy (nonsurgical group: 50 stage IIIA, 65 stage IIIB). Metabolic tumour volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) of primary tumours were measured using pretreatment (18)F-FDG PET/CT. Overall survival was assessed using the Kaplan-Meier method. The prognostic significance of PET parameters and other clinical variables was assessed using Cox proportional hazards regression analyses. To evaluate and compare the predictive performance of PET parameters, time-dependent receiver operating characteristic (ROC) curve analysis was used. RESULTS: In the Cox proportional hazards models, MTV (HR=1.27 for a doubling of MTV, P=0.008) and TLG (HR=1.22 for a doubling of TLG, P=0.035) were significantly associated with an increased risk of death after adjusting for age, gender, histological cell type, T stage, N stage, and treatment variables in the surgical group. SUVmax was not a significant prognostic factor in either the surgical or nonsurgical group. In the time-dependent ROC curve analysis, volume-based PET parameters predicted survival better than SUVmax. CONCLUSION: The volume-based PET parameters (MTV and TLG) are significant prognostic factors for survival independent of tumour stage and better prognostic imaging biomarkers than SUVmax in patients with stage IIIA NSCLC after surgical resection.

Neovascularization precedes occlusion in moyamoya disease: angiographic findings in 172 pediatric patients.

BACKGROUND: Both basal collaterals (BC) and cortical microvascularization (CM) on angiography have been suggested as moyamoya disease (MMD)-specific findings; however, it is unknown whether the vascular network represents compensatory mechanisms for vascular occlusion or aberrant active neovascularization. METHODS: We investigated the grade of antegrade MCA flow, the degree of BC, and the presence of CM on conventional angiography in relation to disease severity in pediatric MMD. CM was defined as enlarged and winding distal cortical arteries and categorized into anterior or posterior CM depending on their sources. Findings from basal and acetazolamide stress brain perfusion SPECT studies were also evaluated. RESULTS: A total of 172 pediatric patients with MMD were enrolled in this study. As the severity of MMD increased, the grade of antegrade MCA flow gradually diminished. While the degree of BC peaked at Suzuki stage 3-4, CM was frequently observed at early MMD stages. About two-thirds of hemispheres with normal antegrade MCA flow on angiography and normal perfusion status on SPECT had anterior and/or posterior CM. Both anterior and posterior CM gradually decreased with the advancement of MMD. CONCLUSION: Our findings from a large cohort of angiographically confirmed pediatric MMD patients indicate that neovascularization may occur before significant hemodynamic impairment in MMD.

Prognostic Significance of 18F-FDG PET/CT Radiomics in Patients With Resectable Pancreatic Ductal Adenocarcinoma Undergoing Curative Surgery.

PURPOSE: This study aimed to investigate the prognostic significance of PET/CT radiomics to predict overall survival (OS) in patients with resectable pancreatic ductal adenocarcinoma (PDAC). METHODS: We enrolled 627 patients with resectable PDAC who underwent preoperative 18F-FDG PET/CT and subsequent curative surgery. Radiomics analysis of the PET/CT images for the primary tumor was performed using the Chang-Gung Image Texture Analysis toolbox. Radiomics features were subjected to least absolute shrinkage and selection operator (LASSO) regression to select the most valuable imaging features of OS. The prognostic significance was evaluated by Cox proportional hazards regression analysis. Conventional PET parameters and LASSO score were assessed as predictive factors for OS by time-dependent receiver operating characteristic curve analysis. RESULTS: During a mean follow-up of 28.8 months, 378 patients (60.3%) died. In the multivariable Cox regression analysis, tumor differentiation, resection margin status, tumor stage, and LASSO score were independent prognostic factors for OS (HR, 1.753, 1.669, 2.655, and 2.946; all P < 0.001, respectively). The time-dependent receiver operating characteristic curve analysis showed that the LASSO score had better predictive performance for OS than conventional PET parameters. CONCLUSION: The LASSO score using the 18F-FDG PET/CT radiomics of the primary tumor was the independent prognostic factor for predicting OS in patients with resectable PDAC and may be helpful in determining therapeutic and follow-up plans for these patients.

Volume-based parameters of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography improve outcome prediction in early-stage non-small cell lung cancer after surgical resection.

OBJECTIVE: To evaluate the prognostic significance and predictive performance of volume-based parameters of F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in early-stage non-small cell lung cancer (NSCLC). BACKGROUND: Although surgical resection remains the optimal treatment for early-stage NSCLC, approximately 40% of patients with stage I and 60% of patients with stage II NSCLC relapse and die within 5 years after curative resection. Therefore, identification of additional prognostic biomarkers is needed to develop risk-adapted treatment strategies. METHODS: We retrospectively reviewed 529 consecutive patients with pathologically proven early-stage NSCLC who underwent preoperative F-FDG PET/CT. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the primary tumors were measured. Overall survival (OS) and disease-free survival (DFS) were assessed by the Kaplan-Meier method. The prognostic significance of PET parameters and other clinicopathological variables was assessed by Cox proportional hazards regression analysis. To evaluate and compare the predictive performance of PET parameters, time-dependent receiver operating characteristic (ROC) curve analysis was used. RESULTS: In the multivariate analyses, volume-based parameters of PET (MTV and TLG) that were analyzed as continuous variables were significantly associated with an increased risk of recurrence (P = 0.001 for MTV, P < 0.001 for TLG) and death (P = 0.009 for MTV, P = 0.007 for TLG), after adjusting for age, sex, histology, tumor stage, and type of surgery. SUVmax analyzed as a continuous variable was not a significant prognostic factor for both DFS (P = 0.056) and OS (P = 0.525). In the time-dependent ROC curve analysis, the volume-based parameter of PET showed better predictive performance than SUVmax (P < 0.001). CONCLUSIONS: The volume-based parameter of PET is an independent prognostic factor for survival in addition to pathological tumor-node-metastasis stage and a promising tool for better prediction of outcome in patients with early-stage NSCLC.