Primary Tumor Maximum Standardized Uptake Research Articles

Impact of definitive radiotherapy on metabolic response measured with 68Ga-PSMA-PET/CT in patients with intermediate-risk prostate cancer.

To assess the early metabolic response of the primary tumor using Gallium-68 (68Ga)-labeled-prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET/CT), as well as the relationship between PSMA change in the primary tumor and PSA response after definitive radiotherapy (RT), either alone or in combination with androgen deprivation therapy (ADT) in intermediate risk prostate cancer (IR-PCa) patients. The clinical data of 71 IR-PCa patients treated with RT alone (36 patients, 50.7%) or RT and ADT (35 patients, 49.3%) were retrospectively analyzed. The difference between pre- and Posttreatment primary tumor PSMA expression and serum PSA values measured 4 months after completion of treatment were compared between treatment arms. Correlation between primary tumor metabolic response and serum PSA changes was analyzed. The median duration between pre- and Posttreatment 68Ga-PSMA-PET/CT for the entire patient population was 6.9 months (range, 5.6-8.4 months), and it was similar in both treatment arms. A decrease in primary tumor maximum standardized uptake value (SUVmax) was seen in 66 patients (93.0%), with a median value of 61.2%, which is significantly lower in patients undergoing RT alone than those undergoing RT and ADT (45.1 ± 30.6% vs. 59.1 ± 24.7%; p = 0.004). The complete metabolic response rate was significantly higher in patients undergoing RT and ADT than those treated with RT alone (40% vs. 0%; p < 0.001). Although moderate and positive correlation between pretreatment SUVmax and oosttreatment SUVmax was observed, there was no significant correlation between SUV change and PSA change. For patients treated with RT and ADT, posttreatment SUVmax was significantly lower and SUV change was significantly higher in patients with PSA nadir than in those without. Our preliminary results show that RT, with or without ADT, significantly reduces primary tumor SUVmax and serum PSA levels. Nonetheless, our findings indicate that early treatment response using 68Ga-PSMA-PET/CT is not feasible for those treated with RT alone, and it may only be useful in better distinguishing patients with and without PSA nadir for those who received both RT and ADT.

Prognostic significance of 18F-Fluorodeoxyglucose positron-emission tomography parameters in patients with biliary tract cancers: a meta-analysis.

Numerous previous studies have assessed the prognostic role of 18F-fluorodeoxyglucose positron-emission tomography (18F FDG PET) in patients with biliary tract cancer (BTC), but those results were inconsistent. The present study aims to determine the predictive value of 18F FDG PET in BTC patients via a meta-analysis. The underlying studies related to 18F FDG PET and BTC patients` outcomes were searched and identified in the online databases. The interested parameters include total lesion glycolysis (TLG), metabolic tumor volume (MTV), primary tumor and metastatic lymph node (LN) maximum standardized uptake value (SUVmax), as well as change of SUVmax (ΔSUVmax) during treatment. Overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were considered as the primary endpoints. Hazard ratio (HR) and corresponding 95% confidence intervals (CIs) were defined as the effective measure and calculated by a pooled analysis. Publication bias was assessed by funnel plot, Bagg's and Egger's tests. Totally, 23 studies involving 1478 patients were included in the present meta-analysis. After a pooled analysis, it revealed that a high SUVmax was significantly associated with a poor OS (HR:2.07, 95%CI: 1.74-2.46, P = 0.000) and DFS (HR: 2.28, 95%CI: 1.53-3.41, P = 0.000). In addition, an increased TLG level contributed to a shorter OS (HR:1.91, 95%CI: 1.26-2.90, P = 0.002) and DFS (HR: 4.34, 95%CI: 1.42-13.27, P = 0.01). Moreover, we confirmed that an elevated MTV was significantly associated with increased mortality (HR:2.04, 95%CI:1.26-3.31, P = 0.004) and disease relapse (HR: 3.88, 95%CI:1.25-12.09, P = 0.019) risks. Besides, the present study uncovered that increased ΔSUVmax could predict poor OS (HR:1.26, 95%CI:1.06-1.50, P = 0.008) instead of PFS (HR: 1.96, 95%CI: 0.82-4.72, P = 0.280). Lastly, we found that LN SUVmax did not link to OS (HR: 1.49, 95%CI: 0.83-2.68, P = 0.178). No obvious publication bias was detected in the present study. 18F FDG PET parameters, including SUVmax, TLG, MTV, and ΔSUVmax, could be applied as convenient and reliable factors for predicting BTC patients` outcomes.

An Innovative Non-Linear Prediction Model for Clinical Benefit in Women with Newly Diagnosed Breast Cancer Using Baseline FDG-PET/CT and Clinical Data.

Objectives: We aimed to develop a novel non-linear statistical model integrating primary tumor features on baseline [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), molecular subtype, and clinical data for treatment benefit prediction in women with newly diagnosed breast cancer using innovative statistical techniques, as opposed to conventional methodological approaches. Methods: In this single-center retrospective study, we conducted a comprehensive assessment of women newly diagnosed with breast cancer who had undergone a FDG-PET/CT scan for staging prior to treatment. Primary tumor (PT) volume, maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured on PET/CT. Clinical data including clinical staging (TNM) but also PT anatomical site, histology, receptor status, proliferation index, and molecular subtype were obtained from the medical records. Overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) were assessed as endpoints. A logistic generalized additive model was chosen as the statistical approach to assess the impact of all listed variables on CB. Results: 70 women with newly diagnosed breast cancer (mean age 63.3 ± 15.4 years) were included. The most common location of breast cancer was the upper outer quadrant (40.0%) in the left breast (52.9%). An invasive ductal adenocarcinoma (88.6%) with a high tumor proliferation index (mean ki-67 expression 35.1 ± 24.5%) and molecular subtype B (51.4%) was by far the most detected breast tumor. Most PTs displayed on hybrid imaging a greater volume (12.8 ± 30.4 cm3) with hypermetabolism (mean ± SD of PT maximum SUVmax, SUVmean, MTV, and TLG, respectively: 8.1 ± 7.2, 4.9 ± 4.4, 12.7 ± 30.4, and 47.4 ± 80.2). Higher PT volume (p < 0.01), SUVmax (p = 0.04), SUVmean (p = 0.03), and MTV (<0.01) significantly compromised CB. A considerable majority of patients survived throughout this period (92.8%), while five women died (7.2%). In fact, the OS was 31.7 ± 14.2 months and PFS was 30.2 ± 14.1 months. A multivariate prediction model for CB with excellent accuracy could be developed using age, body mass index (BMI), T, M, PT TLG, and PT volume as predictive parameters. PT volume and PT TLG demonstrated a significant influence on CB in lower ranges; however, beyond a specific cutoff value (respectively, 29.52 cm3 for PT volume and 161.95 cm3 for PT TLG), their impact on CB only reached negligible levels. Ultimately, the absence of distant metastasis M displayed a strong positive impact on CB far ahead of the tumor size T (standardized average estimate 0.88 vs. 0.4). Conclusions: Our results emphasized the pivotal role played by FDG-PET/CT prior to treatment in forecasting treatment outcomes in women newly diagnosed with breast cancer. Nevertheless, careful consideration is required when selecting the methodological approach, as our innovative statistical techniques unveiled non-linear influences of predictive biomarkers on treatment benefit, highlighting also the importance of early breast cancer diagnosis.

Simultaneous Integrated Boost for Dose Escalation in Node-Positive Cervical Cancer: 5-Year Experience in a Single Institution.

This study retrospectively evaluates clinical outcomes of dose escalation to involved nodes using volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) for node-positive locally advanced cervical cancer (LACC) at a single institution. Consecutive patients with node-positive LACC (FIGO2018 IIIC1-IVA) who received definitive chemoradiotherapy by VMAT 45 Gy in 25 fractions with SIB to 55-57.5 Gy, followed by magnetic resonance image-guided adaptive brachytherapy (IGABT) between 2018 and 2022 were identified. A standardized strategy regarding nodal boost delivery and elective para-aortic (PAO) irradiation was employed. Primary endpoints were involved nodal control (INC) and regional nodal control (RNC). Secondary endpoints were pelvic control (PC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), failure pattern, and radiotherapy-related toxicities. A total of 234 involved nodes (182 pelvic and 52 PAO) in 54 patients, with a median of 3 involved nodes per patient (range 1-16), were analyzed. After a median follow-up of 19.6 months, excellent INC was achieved, with four (2%) boost-volume failures occurring in three patients. The 2-year actuarial RNC, PC, LRC, DFS, and OS were 93%, 87%, 87%, 78%, and 85%, respectively. Adenocarcinoma histology was associated with worse RNC (p = 0.02) and OS (p = 0.04), whereas the primary tumor maximum standardized uptake value (SUVmax) was associated with worse PC (p = 0.04) and LRC (p = 0.046) on univariate analysis. The incidence of grade ≥3 acute and late radiotherapy-related toxicity were 2% and 4%, respectively. Treatment of node-positive LACC with VMAT with SIB allows safe and effective dose escalation. The 5-year local experience demonstrated excellent treatment outcomes without additional toxicity.

Prognostic Factors in Lung Adenocarcinoma with Brain Metastasis

Introduction: Brain metastasis (BM) is significantly seen in lung adenocarcinoma and adversely affects survival. We aimed to evaluate the factors affecting the prognosis in patients with BM diagnosed with lung adenocarcinoma. Materials and Methods: Patients with BM between 2012 and 2022 were reviewed retrospectively. Demographic characteristics of the patients, primary tumor characteristics, presence of mutation, BM number, localization, size, development time, and treatment characteristics were evaluated. Inflammatory indices at the time of BM were examined. The overall survival time was calculated. Results: About 92.9% of 113 patients were male, the median age was 62 years (54.5–68.5), and follow-up was 8 months (3–18). BM was detected at the time of diagnosis in 62 (54.9%) of the patients, whereas BM developed later in 51 (45.1%) patients. Systemic treatment was applied to 72.5% of the patients. Survival was lower in patients with BM at diagnosis (4 vs. 14 months, P &lt; 0.001). Primary tumor maximum standardized uptake value level was higher on fluorodeoxyglucose-positron emission tomography-computed tomography at diagnosis in patients with late BM (P = 0.004). The development time of BM was 9 months (4–16), and the median survival was 8 months (6.2–9.8). There was no difference between tumor localization or inflammatory indices and the development of BM and prognosis. The presence of BM at diagnosis and lack of systemic treatment were found to be factors that independently reduced survival (P &lt; 0.001, P = 0.007). Conclusion: The presence of BM at diagnosis significantly reduces survival. It has been observed that systemic treatments applied in addition to local treatments have a positive effect on the prognosis.

Risk analysis in peripheral clinical T1 non-small cell lung cancer correlations between tumor-to-blood standardized uptake ratio on 18F-FDG PET-CT and primary tumor pathological invasiveness: a real-world observational study.

Sublobar resection is not suitable for patients with pathological invasiveness [including lymph node metastasis (LNM), visceral pleural invasion (VPI), and lymphovascular invasion (LVI)] of peripheral clinical T1 (cT1) non-small cell lung cancer (NSCLC), while primary tumor maximum standardized uptake value (SUVmax) on 18F-FDG PET-CT is related to pathological invasiveness, the significance differed among different institutions is still challenging. This study explored the relationship between the tumor-to-blood standardized uptake ratio (SUR) of 18F-FDG PET-CT and primary tumor pathological invasiveness in peripheral cT1 NSCLC patients. This retrospective study included 174 patients with suspected lung neoplasms who underwent preoperative 18F-FDG PET-CT. We compared the differences of the clinicopathological variables, metabolic and morphological parameters in the pathological invasiveness and less-invasiveness group. We performed a trend test for these parameters based on the tertiles of SUR. The relationship between SUR and pathological invasiveness was evaluated by univariate and multivariate logistics regression models (included unadjusted, simple adjusted, and fully adjusted models), odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. A smooth fitting curve between SUR and pathological invasiveness was produced by the generalized additive model (GAM). Thirty-eight point five percent of patients had pathological invasiveness and tended to have a higher SUR value than the less-invasiveness group [6.50 (4.82-11.16) vs. 4.12 (2.04-6.61), P<0.001]. The trend of SUVmax, mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), mean CT value (CTmean), size of the primary tumor, neuron-specific enolase (NSE), the incidence of LNM, adenocarcinoma (AC), and poor differentiation in the tertiles of SUR value were statistically significant (P were <0.001, <0.001, 0.010, <0.001, <0.001, 0.002, 0.033, <0.001, 0.002, and <0.001, respectively). Univariate analysis showed that the risk of pathological invasiveness increased significantly with increasing SUR [OR: 1.13 (95% CI: 1.06-1.21), P<0.001], and multivariate analysis demonstrated SUR, as a continuous variable, was still significantly related to pathological invasiveness [OR: 1.09 (95% CI: 1.01-1.18), P=0.032] after adjusting for confounding covariates. GAM revealed that SUR tended to be linearly and positively associated with pathological invasiveness and E-value analysis suggested robustness to unmeasured confounding. SUR is linearly and positively associated with primary tumor pathological invasiveness independent of confounding covariates in peripheral cT1 NSCLC patients and could be used as a supplementary risk maker to assess the risk of pathological invasiveness.

Preoperative imaging with positron emission tomography and computed tomography (18F-FDG PET/CT) or contrast-enhanced computed tomography (CECT) scan in operable cervical cancer: a prospective study

We evaluated the accuracy of preoperative PET/CT and CECT for lymph node staging in cervical cancer, which is relevant in the context of recently revised staging. Patients with International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage IB1–IB2 cervical cancer underwent preoperative 18F-FDG PET/CT and CECT abdomen and pelvis. Lymph nodes in various anatomical stations (paraaortic, various right and left pelvic regions) were scored separately as involved or not involved on both imaging modalities and compared with histopathology. The sensitivity and specificity of PET/CT and CECT were estimated for each lymph node station, and all lymph node stations combined, per patient. The study population comprised 57 patients (stage IB1 37, IB2 19) with median age of 45 (32–64) years, 39 (68.7%) with squamous carcinoma, median tumor size of 3.1 (0.5–9.0) cm, mean (range) lymph node harvest of 23.5 (8–46), and 13 (22.8%) patients with histopathologically positive lymph node(s). The sensitivity and specificity of PET/CT for various pelvic lymph node stations were 22.2–100% and 96.3–100%, respectively, and of CECT were 22.2–100% and 96.2–100%, respectively. At patient level, for all lymph node stations combined, the sensitivity and specificity of PET/CT and CECT were 53.9% (95% confidence interval (CI), 26.8%–80.9%) and 90.5% (95% CI, 81.6%–99.4%), and 69.2% (95% CI, 44.1%–94.3%) and 95.0% (95% CI, 88.3%–100%), respectively. Primary tumor maximum standardized uptake value (SUVmax) was the only independent prognostic factor for overall survival. The sensitivity of PET/CT and CECT for lymph node staging in operable cervical cancer is modest, and these modalities can miss lymph node involvement, but they have high specificity and, when indicative of lymph node involvement, may be clinically useful in triaging patients for primary chemoradiation therapy.

Prognostic significance of volume-based 18F-FDG PET/CT parameters and correlation with PD-L1 expression in patients with surgically resected lung adenocarcinoma.

The aim of this study was to retrospectively analyze 18F-FDG positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic variables, programmed death-ligand 1 (PD-L1) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) tumor expression, and other factors as predictors of disease-free survival (DFS) in patients with lung adenocarcinoma (LUAD) (stage IA–IIIA) who underwent surgical resection. We still lack predictor of immune checkpoint (programmed cell death-1 [PD-1]/PD-L1) inhibitors. Herein, we investigated the correlation between metabolic parameters from 18F-FDG PET/CT and PD-L1 expression in patients with surgically resected LUAD.Seventy-four patients who underwent 18F-FDG PET/CT prior to treatment were consecutively enrolled. The main 18F-FDG PET/CT-derived variables were primary tumor maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Surgical tumor specimens were analyzed for PD-L1 and p-STAT3 expression using immunohistochemistry. Correlations between immunohistochemistry results and 18F-FDG PET/CT-derived variables were compared. Associations of PD-L1 and p-STAT3 tumor expression, 18F-FDG PET/CT-derived variables, and other factors with DFS in resected LUAD were evaluated.All tumors were FDG-avid. The cutoff values of low and high SUVmax, MTV, and TLG were 12.60, 14.87, and 90.85, respectively. The results indicated that TNM stage, PD-L1 positivity, and high 18F-FDG PET/CT metabolic volume parameters (TLG ≥90.85 or MTV ≥14.87) were independent predictors of worse DFS in resected LUAD. No 18F-FDG metabolic parameters associated with PD-L1 expression were observed (chi-square test), but we found that patients with positive PD-L1 expression have significantly higher SUVmax (P = .01), MTV (P = .00), and TLG (P = .00) than patients with negative PD-L1 expression.18F-FDG PET/CT metabolic volume parameters (TLG ≥90.85 or MTV ≥14.87) were more helpful in prognostication than the conventional parameter (SUVmax), PD-L1 expression was an independent predictor of DFS in patients with resected LUAD. Metabolic parameters on 18F-FDG PET/CT have a potential role for 18F-FDG PET/CT in selecting candidate LUAD for treatment with checkpoint inhibitors.

2-[18F]FDG PET/CT parameters associated with WHO/ISUP grade in clear cell renal cell carcinoma.

To explore the potential parameters from preoperative 2-[18F]FDG PET/CT that might associate with the World Health Organization/the International Society of Urological Pathology (WHO/ISUP) grade in clear cell renal cell carcinoma (ccRCC). One hundred twenty-five patients with newly diagnosed ccRCC who underwent 2-[18F]FDG PET/CT prior to surgery or biopsy were retrospectively reviewed. The metabolic parameters and imaging features obtained from 2-[18F]FDG PET/CT examinations were analyzed in combination with clinical characteristics. Univariate and multivariate logistic regression analyses were performed to identify the predictive factors of WHO/ISUP grade. Metabolic parameters of primary tumor maximum standardized uptake value (SUVmax), tumor-to-liver SUV ratio (TLR), and tumor-to-kidney SUV ratio (TKR) were significantly different between any two of the four different WHO/ISUP grades, except those between the WHO/ISUP grade 3 and grade 4. The optimal cutoff values to predict high WHO/ISUP grade for SUVmax, TLR, and TKR were 4.15, 1.63, and 1.59, respectively. TLR (AUC: 0.841) was superior to TKR (AUC: 0.810) in distinguishing high and low WHO/ISUP grades (P= 0.0042). In univariate analysis, SUVmax, TLR, TKR, primary tumor size, tumor thrombus, distant metastases, and clinical symptoms could discriminate between the high and low WHO/ISUP grades (P< 0.05). In multivariate analysis, TLR (P< 0.001; OR: 1.732; 95%CI: 1.289-2.328) and tumor thrombus (P< 0.001; OR: 6.199; 95%CI: 2.499-15.375) were significant factors for differentiating WHO/ISUP grades. Elevated TLR (> 1.63) and presence of tumor thrombus from preoperative 2-[18F]FDG PET/CT can distinguish high WHO/ISUP grade ccRCC effectively. 2-[18F]FDG PET/CT may be a feasible method for noninvasive assessment of WHO/ISUP grade.

Value of Intratumoral Metabolic Heterogeneity and Quantitative 18F-FDG PET/CT Parameters in Predicting Prognosis for Patients With Cervical Cancer.

OBJECTIVE. The purpose of this study is to evaluate the prognostic value of quantitative metabolic parameters from pretreatment PET/CT scans of patients with squamous cell cervical cancer. MATERIALS AND METHODS. This retrospective study included 120 patients with biopsy-proven squamous cell carcinoma of the cervix who underwent FDG PET/CT for initial tumor staging. The primary tumor maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean), tumor glycolytic activity, metabolic tumor volume (MTV), and metabolic intratumoral heterogeneity index (calculated as the AUC for the cumulative standardized uptake value [SUV]-volume histogram [CSH] index) were obtained. Information on patient demographic characteristics and tumor staging were collected. Median follow-up was 27.5 months. Overall survival (OS) and progression-free survival (PFS) were calculated using a multivariate Cox proportional hazards regression model and log-rank (Mantel-Cox) test to generate Kaplan-Meier survival plots. RESULTS. The mean (± SD) age of the patients was 54.4 ± 13.1 years. Twenty-two patients had stage I disease; 58, stage II; 23, stage III; and 17, stage IV. Thirty-three patients died, 82 were living, and five were lost to follow-up and were censored; 29 patients had disease progression. The median survival was 74.9 months (95% CI, 63.6-86.9 months). A higher MTV was significantly associated with reduced OS in multivariate analysis (hazard ratio, 1.085; 95% CI, 1.036-1.136; p = 0.0005). A higher AUC-CSH index (denoting lower tumor heterogeneity) was significantly associated with increased OS (hazard ratio, 0.662; 95% CI, 0.448-0.979; p = 0.04) and PFS (hazard ratio, 0.683; 95% CI, 0.471-0.991; p = 0.045) in multivariate analysis. Kaplan-Meier survival analysis using the median value for MTV (61 mL) significantly predicted OS (p = 0.0009). CONCLUSION. Tumor heterogeneity on pretreatment PET/CT is associated with OS and PFS in patients with cervical cancer. MTV is significantly associated with OS.

Performances de la TEP au 18F-FDG dans la caractérisation initiale de la lésion primitive du cancer du sein

Objective18F-FDG PET/CT is for the moment not recommended for stage T of the TNM classification of breast cancer. The aim of our study was to evaluate the performance of 18F-FDG PET/CT in the initial staging of breast tumors. Tumor size, skin involvement and inflammation as well as the relationship between primary tumor maximum standardized uptake value (SUVmax) and histopathological grade (SBR), molecular tumor subtypes (luminal A and B, Her2 enriched, triple negative), estrogen receptors (ER), progesterone receptors (PR) and focality were evaluated. MethodsHistological reports of patients operated for breast cancer, without neoadjuvant chemotherapy, were compared to preoperative 18F-FDG PET/CT. ResultsSeventy-four patients who underwent surgery in 2016 were included. 18F-FDG PET/CT was able to visualize primary tumors in 91% and to correctly classify the T stage of the TNM classification in 81% of the cases, to detect multifocality in 73% and cutaneous and inflammatory breast cancers in 100%. The uptake intensity of 18F-FDG (SUVmax) was significantly correlated with histo-prognostic factors such as SBR grade (P=0.02), lack of expression of estrogen receptors (ER) (P=0.01) and progesterone (PR) (P=0.02), positive HER2 status (P=0.01) or triple negative subtype tumors (P=0.02). Conclusion18F-FDG PET/CT provides relevant elements for local assessment, in particular, tumor focality and inflammatory character in addition to ensuring the regional and extension assessment.

Bone Marrow and Tumor Radiomics at 18F-FDG PET/CT: Impact on Outcome Prediction in Non-Small Cell Lung Cancer.

Background Primary tumor maximum standardized uptake value is a prognostic marker for non-small cell lung cancer. In the setting of malignancy, bone marrow activity from fluorine 18-fluorodeoxyglucose (FDG) PET may be informative for clinical risk stratification. Purpose To determine whether integrating FDG PET radiomic features of the primary tumor, tumor penumbra, and bone marrow identifies lung cancer disease-free survival more accurately than clinical features alone. Materials and Methods Patients were retrospectively analyzed from two distinct cohorts collected between 2008 and 2016. Each tumor, its surrounding penumbra, and bone marrow from the L3-L5 vertebral bodies was contoured on pretreatment FDG PET/CT images. There were 156 bone marrow and 512 tumor and penumbra radiomic features computed from the PET series. Randomized sparse Cox regression by least absolute shrinkage and selection operator identified features that predicted disease-free survival in the training cohort. Cox proportional hazards models were built and locked in the training cohort, then evaluated in an independent cohort for temporal validation. Results There were 227 patients analyzed; 136 for training (mean age, 69 years ± 9 [standard deviation]; 101 men) and 91 for temporal validation (mean age, 72 years ± 10; 91 men). The top clinical model included stage; adding tumor region features alone improved outcome prediction (log likelihood, -158 vs -152; P = .007). Adding bone marrow features continued to improve performance (log likelihood, -158 vs -145; P = .001). The top model integrated stage, two bone marrow texture features, one tumor with penumbra texture feature, and two penumbra texture features (concordance, 0.78; 95% confidence interval: 0.70, 0.85; P < .001). This fully integrated model was a predictor of poor outcome in the independent cohort (concordance, 0.72; 95% confidence interval: 0.64, 0.80; P < .001) and a binary score stratified patients into high and low risk of poor outcome (P < .001). Conclusion A model that includes pretreatment fluorine 18-fluorodeoxyglucose PET texture features from the primary tumor, tumor penumbra, and bone marrow predicts disease-free survival of patients with non-small cell lung cancer more accurately than clinical features alone. © RSNA, 2019 Online supplemental material is available for this article.

Final Trial Results of Repeated Diffusion-Weighted MRI and FDG-PET Imaging for the Prediction of Response to Chemoradiation Therapy in Esophageal Cancer

To present the final results of a prospective study to evaluate imaging predictors for pathologic complete response (pathCR) to chemoradiation therapy (CRT) in esophageal cancer using repeated diffusion-weighted magnetic resonance imaging (DW-MRI) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging before, during, and after CRT. Between January 2014 and July 2017, 60 patients with stage II-III esophageal cancer were prospectively enrolled. DW-MRI and FDG-PET imaging were acquired before treatment (baseline), 12-14 days after initiation of CRT (interim, IM), and at first follow-up 4-6 weeks after completing CRT. The primary outcome was pathCR as assessed after subsequent surgery, with secondary outcomes evaluating locoregional and distant progression-free survival (LPFS and DPFS), and overall survival (OS) according to the imaging parameters. Logistic regression analysis was used to evaluate the association of primary tumor apparent diffusion coefficient (ADC) values, maximum and mean standardized uptake value (SUV), metabolic tumor volume (MTV), and tumor lesion glycolysis (TLG) at baseline and their relative changes (Δ) at interim and follow-up scans with pathCR. Survival analyses applied to evaluate the association of the imaging parameters with LPFS, DPFS, and OS. Surgery after CRT was performed in 29 (48%) of 60 included patients. Imaging data was eligible for analysis in 28 patients in whom pathCR was observed in 7 (25%). The change in tumor mean ADC from the baseline to the interim DW-MRI scan, at a threshold of +27.7%, was best predictive for pathCR (c-statistic=0.98). The change in TLG from the baseline to interim FDG-PET scan, at a threshold of 58% decrease, was the best FDG-PET-based predictor of pathCR (c-statistic=0.77). Multivariable logistic regression suggested no significant added value of ΔTLGIM to ΔADCIM for the prediction of pathCR. Median follow-up was 29 months (range: 5-59) overall and 36 months (range: 24-59) for survivors. In surgical patients no locoregional progression was seen, and studied DW-MRI and FDG-PET parameters were not significantly associated with DPFS or OS. For non-surgical patients with ΔADCIM above vs below +27.7%, observed locoregional recurrence rates were 1/5 (20%) vs 7/25 (28%) (NS), and distant recurrence rates were 1/5 (20%) vs 15/25 (60%) (NS). For non-surgical patients with ΔTLGIM below vs above -58%, observed locoregional recurrence rates were 2/11 (18%) vs 5/17 (29%) (NS), and distant recurrence rates were 3/11 (27%) vs 12/17 (71%) (log-rank test, p=0.04). No association between imaging parameters and OS was observed. ΔADC on DW-MRI after 2 weeks of CRT strongly predicts pathologic complete response in esophageal cancer, with superior performance to repeated FDG-PET imaging. Early response assessment using DW-MRI is potentially useful for stratification of esophageal cancer patients to treatment intensification or organ-preserving strategies.

Role of 18F-FDG PET/CT in evaluating molecular subtypes and clinicopathological features of primary breast cancer.

In this study, primary tumors' fluorine-18-fluorodeoxyglucose (F-FDG) uptake in luminal A, luminal B, triple-negative, and human epidermal growth factor receptor type-2 subtypes of breast cancer was evaluated. In addition, the relationship between the primary tumor maximum standardized uptake value (SUVmax) value and the presence of distant metastasis and axillary involvement was evaluated. Whole-body F-FDG PET/computed tomography (CT) imaging of 493 patients (mean age; 54.6±13.2 years) diagnosed with primary breast cancer were analyzed retrospectively. PET/CT imaging was obtained 60 min after the intravenous administration of F-FDG. F-FDG uptake of the lesions was assessed by calculating the SUVmax. Histopathological analyses were carried out on the basis of biopsy samples before PET/CT. For histopathological staging, the Scarff Bloom Richardson classification system was utilized, and patients were classified into luminal A, luminal B, triple-negative, and human epidermal growth factor receptor type-2 molecular subtypes. 82.9% of the patients had invasive ductal carcinoma, 5.8% had invasive lobular carcinoma, 4.2% had apocrine carcinoma, 3.8% had mucinous carcinoma, and 3.4% has mixed carcinoma. Although the highest mean SUVmax was calculated in apocrine tumors (12.4±7.2), the lowest mean SUVmax was calculated in lobular carcinoma (6.8±4.6), and a statistically significant difference was found between the histological groups (P<0.001). F-FDG uptake was reported to be significantly higher in the triple-negative subtype than the luminal types, and in the luminal B subtype than the luminal A subtype. A statistically significant relation was found between primary tumor SUVmax and distant nodal, organ metastasis (P=0.003 and <0.001, respectively). Increased primary tumor F-FDG uptake was associated with aggressive molecular subtypes in this study. The relationship of distant nodal and organ metastasis with primary tumor SUVmax showed that increased F-FDG uptake is important in terms of management of therapy and prognosis.

Correlation of 18F-FDG PET/CT with pathological features and survival in primary breast cancer.

The aim of this study was to determine the correlation between the primary tumor (PT) maximum standardized uptake value (SUVmax) and breast cancer prognostic factors, overall survival, and relapse-free survival on the basis of histopathological and molecular characteristics. In this retrospective study, 436 female patients with breast cancer were evaluated following a pretreatment F-FDG PET/CT scan. The PT SUVmax and histopathological/molecular characteristics were determined from primary tumor tissues and analyzed using the Mann-Whitney U and Kruskal-Wallis tests. The median SUVmax of 436 PT was 10.1 (1.7-72). The PT SUVmax values were higher in ER- versus ER+ (P=0.001), PR- versus PR+ (P=0.001), Her2+ versus Her2- (P=0.01), Ki-67% of at least 20 versus Ki-67% of less than 20 (P<0.001), histological grade 3 versus grade 1-2 (P<0.001), nuclear pleomorphism score 3 versus score 1-2 (P<0.001), and mitotic score 3 versus score 1-2 patients (P<0.001). The lowest SUVmax levels were observed in the LumA group and the highest SUVmax levels were observed in the Her2 group (P<0.001). LumA patients with PR values greater than 20% had lower PT SUVmax values than the patients with PR values of 20% or less (P=0.023). The PT SUVmax was higher in patients with recurrence (P=0.03) and died related to disease (P<0.001) independent of time. The PT SUVmax showed a significant correlation with most of the prognostic factors and histopathological subtypes as a noninvasive tool. It is also usable in the prediction of tumor-related deaths or relapse independent of time. Our results could guide future studies to provide new histopathologic subtype definitions on the basis of new PR criteria.

18F-fluorodeoxyglucose uptake predicts PKM2 expression in lung adenocarcinoma.

Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) is widely used in the management of lung adenocarcinoma. Pyruvate kinase M2 (PKM2) plays a key role in glycolysis. We therefore investigated whether PKM2 expression affects 18F-FDG uptake in a retrospective analysis of 76 patients who underwent 18F-FDG PET/computed tomography (CT) scans for staging before surgical resection. We found that PKM2 expression was higher in tumors than peritumoral tissue (p < 0.05). Patients with high PKM2 expression had reduced overall (p < 0.05) and disease-free (p < 0.05) survival as compared to those with low PKM2 expression. Comparison of the primary tumor maximum standardized uptake value (SUVmax) between patients with high and low PKM2 expression revealed that the SUVmax was higher in primary tumors with high PKM2 expression than low PKM2 expression (p < 0.05). Multivariate analysis confirmed the association between SUVmax and PKM2 expression (p < 0.05). PKM2 status was predicted with 81.6% accuracy when the SUVmax cutoff value of 6.4. Thus,18F-FDG PET/CT is predictive of the PKM2 status in lung adenocarcinoma patients and could aid in determining therapeutic strategies.

Predictive Value of 18F-FDG PET/CT for Axillary Lymph Node Metastasis in Invasive Ductal Breast Cancer.

This study assessed whether primary tumor maximum standardized uptake value (pSUVmax) measured by 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) could improve the prediction of axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC). In this study, 128 IDC patients who underwent pretreatment 18F-FDG PET/CT and surgical resection of primary tumor with sentinel lymph node biopsy, ALN dissection, or both were analyzed. All the patients were classified as five molecular subtypes. The optimal cutoff values of pSUVmax for all the patients and each molecular subtype for the prediction of ALN metastasis were determined using receiver operating characteristic (ROC) analysis. Furthermore, the prognostic accuracy of ALN metastasis was assessed using c-statistics. The findings showed ALN metastasis in 52 patients (40.6%). The 18F-FDG PET/CT procedure had a sensitivity of 48.1% and a specificity of 94.7% for ALN metastasis. In the ROC analysis of pSUVmax for ALN metastasis, the optimal cutoff value was 3.9 for all the patients, 2.8 for the luminal A subtype, 3.3 for the luminal B (human epidermal growth factor receptor 2 [HER2]-negative) subtype, 5.3 for the luminal B (HER2-positive) subtype, 12.7 for the HER2-positive subtype, and 11.5 for the triple-negative subtype. A predictive ALN metastasis model using nodal 18F-FDG uptake finding gave a c-statistic of 0.714, and a model combination of nodal 18F-FDG uptake finding with pSUVmax of all the patients gave a c-statistic of 0.736 (P=0.3926). However, the combination of nodal the 18F-FDG uptake finding with the pSUVmax of each molecular subtype gave a c-statistic of 0.791 (P=0.0047). Combining the pSUVmax of each molecular subtype with the nodal 18F-FDG uptake finding can improve the prediction of ALN metastasis in IDC.

Evaluation of the association between HIF-1α and HER-2 expression, hormone receptor status, Ki-67 expression, histology and tumor FDG uptake in breast cancer.

The present study aimed to examine hypoxia-inducible factor (HIF)-1α expression and its association with glucose uptake in invasive breast cancer. In addition, connections between glucose uptake and several other prognostic parameters of breast cancer were studied. Between August 2013 and April 2015, 92 patients with biopsy-diagnosed breast cancer were subjected to 18F-fluorodeoxyglucose positron emission tomography/computed tomography. The primary tumor and nodal maximum standardized uptake values (SUVmax) were recorded, and HIF-1α expression and clinical parameters, including tumor mass, estrogen receptor (ER) and progesterone receptor (PgR) levels, human epidermal growth factor receptor-2 (HER-2), Ki-67 index, grade and histology, were analyzed. SUVmax was compared with clinicopathological parameters and HIF-1α expression. The median SUVmax values of the ER-negative and PgR-negative tumors were significantly increased compared with ER and PgR-positive tumors, respectively (P=0.004 and P=0.008). SUVmax differed significantly between the T2 and T3 tumors and the T1 tumors. The median SUVmax levels were higher in the Ki-67 expression >10% group than the Ki-67 index <10% group (P=0.001). Although the median SUVmax values in HER-2-positive and -negative tumors were similar, triple-negative tumors demonstrated significantly higher values (P=0.04). With regard to tumor grade, the median SUVmax was greater in the high-grade tumors compared with the low-grade tumors. SUVmax did not exhibit a significant correlation with HIF-1α expression; however, HIF-1α expression was associated with tumor size and PgR expression. HIF-1α expression increased with a larger tumor size (r=0.27; P=0.008) and decreased PgR expression (r=−0.26; P=0.0002). The axillary nodal SUVmax of the N1 tumors was significantly lower than the N2 and N3 tumors (P<0.0001). In the multivariate analysis, tumor size, Ki-67 expression and ER Allred score were independent factors that impacted SUVmax. The results of the present study indicated strong associations between tumor size, tumor grade, Ki-67 expression, triple-negativity, downregulated hormone receptor expression and SUVmax values. Conversely, there was no association observed between glucose uptake and levels of HIF-1α. Based on these results, it is suggested that the lack of assiocation between hypoxia and glucose uptake indicates phenotypic independence.

Prognostic Value of Baseline 18F-FDG PET/CT Functional Parameters in Patients with Advanced Lung Adenocarcinoma Stratified by EGFR Mutation Status.

The study objective was to retrospectively analyze the metabolic variables derived from 18 F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) as predictors of progression-free survival (PFS) and overall survival (OS) in advanced lung adenocarcinoma stratified by epidermal growth factor receptor (EGFR) mutation status. A total of 176 patients (91, EGFR mutation; 85, wild-type EGFR) who underwent 18F-FDG PET/CT before treatment were enrolled. The main 18F-FDG PET/CT-derived variables: primary tumor maximum standardized uptake value (SUVmaxT), primary tumor total lesion glycolysis (TLGT), the maximum SUVmax of all selected lesions in whole body determined using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria (SUVmaxWBR), and whole-body total TLG determined using the RECIST 1.1 criteria (TLGWBR) were measured. Survival analysis regarding TLGWBR, and other factors in advanced lung adenocarcinoma patients stratified using EGFR mutation status, were evaluated. The results indicated that high TLGWBR (≥259.85), EGFR wild-type, and high serum LDH were independent predictors of worse PFS and OS in all patients with advanced lung adenocarcinoma. Among patients with wild-type EGFR, only TLGWBR retained significance as an independent predictor of both PFS and OS. Among patients with the EGFR mutation, high serum LDH level was an independent predictor of worse PFS and OS, and high TLGWBR (≥259.85) was an independent predictor of worse PFS but not worse OS. In conclusion, TLGWBR is a promising parameter for prognostic stratification of patients with advanced lung adenocarcinoma and EGFR status; however, it cannot be used to further stratify the risk of worse OS for patients with the EGFR mutation. Further prospective studies are needed to validate our findings.

Preoperative Lymph Node Staging by FDG PET/CT With Contrast Enhancement for Thyroid Cancer: A Multicenter Study and Comparison With Neck CT.

ObjectivesThe purpose of this study was to compare lymph node (LN) staging using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) with contrast-enhancement (CE) PET/CT and contrast-enhanced neck CT (neck CT) in patients with thyroid cancer with level-by-level comparison with various factors.MethodsThis was a retrospective multicenter study. A total of 85 patients were enrolled. Patients who underwent a preoperative evaluation by CE PET/CT and neck CT for thyroid cancer were enrolled. The gold standard for LN was the combination of surgical pathology and clinical follow-up. We compared CE PET/CT with neck CT using a level-by-level method. Factors, including age, sex, camera, arm position, tumor size, extra-thyroidal extension, tumor location, number of primary tumors, primary tumor maximum standardized uptake value, and the interval from scan to operation were also analyzed.ResultsOverall accuracy was 81.2% for CE PET/CT and 68.2% for neck CT. CE PET/CT was more sensitive than neck CT (65.8% vs. 44.7%). Also, CE PET/CT showed higher negative predictive value (77.2% vs. 66.1%). CE PET/CT showed good agreement with the gold standard (weighted kappa [κ], 0.7) for differentiating N0, N1a, and N1b, whereas neck CT showed moderate agreement (weighted κ, 0.5). CE PET/CT showed better agreement for the number of levels involved with the gold standard (weighted κ, 0.7) than that of neck CT with the gold standard (weighted κ, 0.5). The accuracies for differentiating N0, N1a, and N1b were 81.2% for CE PET/CT and 68.2% for neck CT. Level-by-level analysis showed that CE PET/CT was more sensitive and has higher negative predictive value for detecting ipsilateral level IV and level VI LNs than neck CT. Other analyzed factors were not related to accuracies of both modalities.ConclusionCE PET/CT was more sensitive and reliable than neck CT for preoperative LN staging in patients with thyroid cancer.