Pretreatment tumor-related leukocytosis misleads positron emission tomography-computed tomography during lymph node staging in gynecological malignancies.
ABSTRACT: The accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) can be influenced by the increased glycolytic activity of inflammatory lesions. Here, using clinical data obtained from gynecological cancer patients, tumor samples and animal models, we investigate the impact of pretreatment tumor-related leukocytosis (TRL) on the diagnostic performance of 18F-FDG-PET/CT in detecting pelvic and paraaortic lymph node metastasis. We demonstrate that pretreatment TRL misleads 18F-FDG-PET/CT during lymph node staging in gynecological malignancies. In the mechanistic investigations, we show that the false-positive 18F-FDG-PET/CT result for detecting nodal metastasis can be reproduced in animal models of TRL-positive cancer bearing G-CSF expressing cervical cancer cells. We also show that increased 18F-FDG uptake in non-metastatic nodes can be explained by the MDSC-mediated premetastatic niche formation in which proinflammatory factors, such as S100A8 or S100A9, are abundantly expressed. Together, our results suggest that the MDSC-mediated premetastatic niche created in the lymph node of TRL-positive patients misleads 18F-FDG-PET/CT for detecting nodal metastasis.
Project description:To evaluate diagnostic accuracy of qualitative analysis and interobserver agreement of single ultrafast-DCE, DWI or 18F-FDG-PET and the combination of modalities for the detection of unknown primary tumor (UPT) in patients presenting with cervical lymph node metastasis from squamous cell carcinoma (SCC). Between 2014-2019, patients with histologically proven cervical lymph node metastasis of UPT SCC were prospectively included and underwent DWI, ultrafast-DCE, and 18F-FDG-PET/CT. Qualitative assessment was performed by two observers per modality. Interobserver agreement was calculated using the proportion specific agreement. Diagnostic accuracy of combined use of DWI, ultrafast-DCE and 18F-FDG-PET/CT was assessed. Twenty-nine patients were included (20 males. [68%], median age 60 years). Nine (31%) primary tumors remained occult. Ultrafast-DCE added reader confidence for suspicious locations (one additional true positive (5%), 2 decisive true malignant (10%). The per-location analysis showed highest specific positive agreement for ultrafast-DCE (77.6%). The per-location rating showed highest sensitivity (95%, 95%CI = 75.1-99.9, YI = 0.814) when either one of all modalities was scored positive, and 97.4% (95%CI = 93.5-99.3, YI = 0.774) specificity when co-detected on all. The per-patient analysis showed highest sensitivity (100%) for 18F-FDG-PET/CT (YI = 0.222) and either DWI or PET (YI = 0.111). Despite highest trends, no significant differences were found. The per-patient analysis showed highest specific positive agreement when co-detected on all modalities (55.6%, 95%CI = 21.2-86.3, YI = 0.456). Ultrafast-DCE showed potential to improve detection of unknown primary tumors in addition to DWI and 18F-FDG-PET/CT in patients with cervical squamous cell carcinoma lymph node metastasis. The combined use of ultrafast-DCE, DWI and 18F-FDG-PET/CT yielded highest sensitivity.
Project description:OBJECTIVES:We had developed a method that can help detect and identify lymph nodes affected by the neoplastic process. Our group evaluated the fractal dimension (FD) and X-ray attenuation (XRA) of lymph nodes in HL and compared to their metabolic activity as measured by 18F-FDG-PET examination. METHODS:The training set included 72 lymph nodes from 31 consecutive patients, and the tested set of 71 lymph nodes from next 19 patients. The measurement of FD of each lymph node was performed before the start of therapy using original software. X-ray attenuation (XRA) expressed in HU (Hounsfield Units) from CT scans was compared with the metabolic activity of the lymphatic nodes, measured by 18F-FDG-PET examination. RESULTS:Significant differences were observed between XRAmax and FDmax values in assessing the PET(+) and PET(-) nodes. All nodes were scored from 0 to 2. The HUFRA test properly qualified 95% with a score of 2 and 0 points as PET(+) or PET(-). CONCLUSION:The HUFRA test can differentiate about 70-80% of lymph nodes as PET(+) or PET(-) based solely on the CT examination. It can be useful in patients who were not subjected to 18FFDG-PET/CT examination before the treatment, or who had an unreliable result of 18F-FDG-PET/CT with further research requirements.
Project description:OBJECTIVES:To compare the diagnostic accuracy of preoperative 18F-FDG PET/CT and MRI tumor markers for prediction of lymph node metastases (LNM) and aggressive disease in endometrial cancer (EC). METHODS:Preoperative whole-body 18F-FDG PET/CT and pelvic MRI were performed in 215 consecutive patients with histologically confirmed EC. PET/CT-based tumor standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and PET-positive lymph nodes (LNs) (SUVmax >?2.5) were analyzed together with the MRI-based tumor volume (VMRI), mean apparent diffusion coefficient (ADCmean), and MRI-positive LN (maximum short-axis diameter ??10 mm). Imaging parameters were explored in relation to surgicopathological stage and tumor grade. Receiver operating characteristic (ROC) curves were generated yielding optimal cutoff values for imaging parameters, and regression analyses were used to assess their diagnostic performance for prediction of LNM and progression-free survival. RESULTS:For prediction of LNM, MTV yielded the largest area under the ROC curve (AUC) (AUC?=?0.80), whereas VMRI had lower AUC (AUC?=?0.72) (p?=?0.03). Furthermore, MTV >?27 ml yielded significantly higher specificity (74%, p?<?0.001) and accuracy (75%, p?<?0.001) and also higher odds ratio (12.2) for predicting LNM, compared with VMRI >?10 ml (58%, 62%, and 9.7, respectively). MTV >?27 ml also tended to yield higher sensitivity than PET-positive LN (81% vs 50%, p?=?0.13). Both VMRI >?10 ml and MTV >?27 ml were significantly associated with reduced progression-free survival. CONCLUSIONS:Tumor markers from 18F-FDG PET/CT outperform MRI markers for the prediction of LNM. MTV >?27 ml yields a high diagnostic performance for predicting aggressive disease and represents a promising supplement to conventional PET/CT reading in EC. KEY POINTS:• Metabolic tumor volume (MTV) outperforms other 18F-FDG PET/CT and MRI markers for preoperative prediction of lymph node metastases (LNM) in endometrial cancer patients. • Using cutoff values for tumor volume for prediction of LNM, MTV >?27 ml yielded higher specificity and accuracy than VMRI>?10 ml. • MTV represents a promising supplement to conventional PET/CT reading for predicting aggressive disease in EC.
Project description:BACKGROUND:Predicting the aggressive behavior of non-functional pancreatic neuroendocrine tumors (NF-PNET) remains controversial. We wanted to explore, in a prospective setting, whether the diagnostic accuracy can be improved by dual-tracer functional imaging 68Ga-DOTANOC and 18F-FDG-PET/CT in patients with NF-PNETs. METHODS:Thirty-one patients with NF-PNET (90% asymptomatic) underwent PET-imaging with 18F-FDG and 68Ga-DOTANOC, followed by surgery (n = 20), an endoscopic ultrasonography and fine-needle biopsy (n = 2) or follow-up (n = 9). A focal activity on PET/CT greater than the background that could not be identified as physiological activity was considered to indicate tumor tissue. The imaging results were compared to histopathology. The mean follow-up time was 31.3 months. RESULTS:Thirty-one patients presented a total of 53 lesions (40 histologically confirmed) on PET/CT. Thirty patients had a 68Ga-DOTANOC-positive tumor (sensitivity 97%) and 10 patients had an 18F-FDG-positive tumor. In addition, one 68Ga-DOTANOC-negative patient was 18F-FDG-positive. 18F-FDG-PET/CT was positive in 19% (3/16) of the G1 tumors, 63% (5/8) of the G2 tumors and 1/1 of the well-differentiated G3 tumor. 68Ga-DOTANOC-PET/CT was positive in 94% of the G1 tumors, 100% of the G2 tumors and 1/1 of the well-differentiated G3 tumor. Two out of six (33%) of the patients with lymph node metastases (LN+) were 18F-FDG-positive. The 18F-FDG-PET/CT correlated with tumor Ki-67 (P = 0.021). Further, the Krenning score correlated with tumor Ki-67 (P = 0.013). 18F-FDG-positive tumors were significantly larger than the 18F-FDG-negative tumors (P = 0.012). 18F-FDG-PET/CT showed a positive predictive value of 78% in the detection of potentially aggressive tumors (G2, G3, or LN + PNETs); the negative predictive value was 69%. CONCLUSIONS:18F-FDG-PET/CT is useful to predict tumor grade but not the LN+ of NF-PNETs. Patients with 18F-FDG-avid NF-PNETs should be referred for surgery. The 68Ga-DOTANOC-PET/CT also has prognostic value since the Krenning score predicts the histopathological tumor grade. TRIAL REGISTRATION:The study has been registered at ClinicalTrials.gov; Non-functional Pancreatic NET and PET imaging, NCT02621541.
Project description:OBJECTIVE:The objective of this study was to assess the clinical value of 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) after the first cycle of induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head and neck (LASCCHN). METHODS AND FINDINGS:A prospective, single-arm, single center study was performed, with patients enrolled between February 2010 and July 2013.Patients (n = 49) with stage III/IVA-B LASCCHN who underwent IC with taxanes, cisplatin, and fluorouracil were recruited. Staging procedures included loco-regional and chest imaging, endoscopic examination, and PET/CT scan. On day 14 of the first cycle, a second PET/CT scan was performed. Patients with no early increase in regional lymph node maximum 18F-FDG standard uptake value (SUV), detected using 18F-FDG PET/CT after first IC had better progression-free survival (hazard ratio (HR) = 0.18, 95%, confidence interval (CI) 0.056-0.585; p = 0.004) and overall survival (HR = 0.14, 95% CI 0.040-0.498; p = 0.002), and were considered responders. In this subgroup, patients who achieved a reduction of ? 45% maximum primary tumor SUV experienced improved progression-free (HR = 0.23, 95% CI 0.062-0.854; p = 0.028) and overall (HR = 0.11, 95% CI 0.013-0.96; p = 0.046) survival. CONCLUSIONS:These results suggest a potential role for early response evaluation with PET/CT examination in patients with LASCCHN undergoing IC. Increased regional lymph node maximum SUV and insufficient decrease in primary tumor uptake predict poorer outcomes.
Project description:OBJECTIVE:To compare the apparent diffusion coefficient (ADC) in lymph node metastases of non-small cell lung cancer (NSCLC) patients with standardized uptake values (SUV) derived from combined 18F-fluoro-deoxy-glucose-positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). MATERIAL AND METHODS:38 patients with histopathologically proven NSCLC (mean age 60.1 ± 9.5 y) received whole-body PET/CT (Siemens mCT™) 60 min after injection of a mean dose of 280 ± 50 MBq 18F-FDG and subsequent PET/MRI (mean time after tracer injection: 139 ± 26 min, Siemens Biograph mMR). During PET acquisition, simultaneous diffusion-weighted imaging (DWI, b values: 0, 500, 1000 s/mm²) was performed. A maximum of 10 lymph nodes per patient suspicious for malignancy were analyzed. Regions of interest (ROI) were drawn covering the entire lymph node on the attenuation-corrected PET-image and the monoexponential ADC-map. According to histopathology or radiological follow-up, lymph nodes were classified as benign or malignant. Pearson's correlation coefficients were calculated for all lymph node metastases correlating SUVmax and SUVmean with ADCmean. RESULTS:A total of 146 suspicious lymph nodes were found in 25 patients. One hundred lymph nodes were eligible for final analysis. Ninety-one lymph nodes were classified as malignant and 9 as benign according to the reference standard. In malignant lesions, mean SUVmax was 9.1 ± 3.8 and mean SUVmean was 6.0 ± 2.5 while mean ADCmean was 877.0 ± 128.6 x10(-5) mm²/s in PET/MRI. For all malignant lymph nodes, a weak, inverse correlation between SUVmax and ADCmean as well as SUVmean and ADCmean (r = -0.30, p<0.05 and r = -0.36, p<0.05) existed. CONCLUSION:The present data show a weak inverse correlation between increased glucose-metabolism and cellularity in lymph node metastases of NSCLC patients. 18F-FDG-PET and DWI thus may offer complementary information for the evaluation of treatment response in lymph node metastases of NSCLC.
Project description:BACKGROUND:Postoperative pathologic risk factors (PRFs) could increase the recurrence rate in early-stage uterine cervical squamous cancer (ECSC). Our study intended to explore the efficiency of 18F-FDG PET/CT for assessing the pathologic risk status (PRS) in ECSC patients. METHODS:This retrospective study was performed in 240 ECSC patients with stage IA2-IIA2 (FIGO 2009), who underwent preoperative PET/CT scans and subsequent radical surgery between January 2010 and July 2015. Intermediate-risk (tumour diameter???4?cm, stromal invasion depth???1/2, lymphovascular space invasion (LVSI)), and high-risk factors (parametria involvement, positive surgery margin, pelvic lymph node metastasis) were confirmed by postoperative pathology. Patients with none of these PRFs were at a low risk for relapse. One of these PRFs was defined as positive risk. The relationship between each PRF and 18F-FDG uptake was analysed by t-test. Chi-square tests and logistic regression analyses were used to determine the efficiency of PET/CT parameters for assessing the PRS. The area under the curve (AUC) was used as an indicator for predictive efficiency. RESULTS:Patients with higher SUVmax (p?<?0.001), MTV (p?<?0.001) and TLG (p?<?0.001) had larger tumour sizes and deeper stromal invasion. Further multivariate analyses showed SUVmax and TLG were independent predictors for positive- and intermediate-risk status. In high-risk group, MTV and TLG were associated with pelvic lymph node metastasis and parametria involvement. However, only MTV was a significant indicator. CONCLUSIONS:Preoperative 18F-FDG PET/CT had an independent predictive value for PRS in ECSC.
Project description:Positron lymphography using 18F-FDG followed by Cerenkov-guided resection of lymph nodes in healthy mice has previously been introduced by our group. Our aim in this study was to further assess the technique's potential beyond merely localizing sentinel lymph nodes. We now aimed to evaluate the potential of positron lymphography to characterize the nodes with respect to their tumor status in order to identify metastatic lymph nodes. We explored whether metastatic nodes could be distinguished from normal nodes via dynamic 18F-FDG lymphography, to then be resected under Cerenkov imaging guidance. Methods: A murine melanoma cell line highly metastatic to lymph nodes (B16F10) was implanted subcutaneously on the dorsal hind paw of C57 mice while the tumor-free contralateral leg served as an intraindividual control. A model of reactive lymph nodes after concanavalin A challenge served as an additional control to provide nonmalignant inflammatory lymphadenopathy. Dynamic PET/CT imaging was performed immediately after injection of 18F-FDG around the tumor or intracutaneously in the contralateral footpad. Furthermore, PET/CT and Cerenkov studies were performed repeatedly over time to follow the course of metastatic spread. In selected mice, popliteal lymph nodes underwent Cerenkov luminescence imaging. Hematoxylin and eosin staining was done to verify the presence of lymphatic melanoma infiltration. Results: Positron lymphography using 18F-FDG was successfully performed on tumor-bearing and non-tumor-bearing mice, as well as on controls bearing sites of inflammation; the results clearly identified the sentinel lymph node basin and delineated the lymphatic drainage. Significantly prolonged retention of activity was evident in metastatic nodes as compared with controls without tumor. On the basis of these results, the contrast in detection and identification of metastatic lymph nodes was distinct and could be used for guided lymph node resection, such as by using Cerenkov luminescence imaging. However, retention after 18F-FDG lymphography was also seen in acute inflammatory lymphadenopathy. Conclusion: In a tumor model, significantly longer retention of the radiotracer during 18F-FDG lymphography was seen in metastatic than nonmetastatic lymph nodes, allowing for differentiation between the two and for selective resection of tumor-bearing nodes using Cerenkov imaging. Inflammation can be better differentiated in a subacute state.
Project description:Background:The use of molecular imaging in staging of prostate cancer (PC) is debated. In patients with newly diagnosed PC we investigated the diagnostic value of 18F-flouromethylcholine positron emission tomography/computed tomography (18F-FCH-PET/CT) for the detection of bone and lymph node metastases compared to whole-body bone scintigraphy (WBS) with technetium-99-methylene diphosphonate (99mTc-MDP) and results of extended pelvic lymph node dissection, respectively. Materials and methods:Between January 2013 and April 2016, 143 patients, aged 49-83, mean 69, years with newly diagnosed PC and disease characteristics necessitating WBS underwent both WBS and 18F-FCH-PET/CT using magnetic resonance imaging as standard. Eighty of these patients underwent pelvic lymph node dissection as part of radical prostatectomy or prior to external beam radiation and in these results of 18F-FCH-PET/CT were compared to histologic findings. Results:Bone metastases were detected in 8/143 patients and sensitivity and specificity of WBS were 37.5% and 85.2% versus 100.0% and 96.3% with 18F-FCH-PET/CT, P=0.63 and 0.002, respectively. Histologically confirmed metastases to regional lymph nodes were found in 25/80 patients. Suspicious choline uptake on PET/CT in pelvic lymph nodes was found in 35 patients. Sensitivity, specificity, PPV, NPV and accuracy of 18F-FCH-PET/CT in detection of lymph node metastases were 62.5%, 69.6%, 46.9%, 81.3% and 67.5%, respectively. Conclusions:Findings in this study suggested that 18F-FCH-PET/CT is a more sensitive and specific method for detection of bone metastases from PC than WBS and could potentially reduce the need for confirmatory imaging if used instead of WBS. However, 18F-FCH-PET/CT performs sub-optimally in pre-operative staging of lymph node metastases in patients undergoing extended pelvic lymph node dissection.
Project description:BACKGROUND:18F-FDG PET/CT metabolic parameters have been applied as prognostic factors in multi-malignancies. However, the role in locally advanced pancreatic cancer (LAPC) was not confirmed. In this study, we investigated the prognostic value of 18F-FDG PET/CT metabolic parameters in LAPC patients treated with stereotactic body radiation therapy (SBRT). METHODS:Seventy three LAPC patients who received SBRT therapy and pre-treatment 18F-FDG PET/CT imaging from January 2012 to January 2016 were included in this retrospective study. The study aim was to evaluate the relationship between metabolic parameters with clinical factors, and the value of metabolic parameters in the prognosis of LAPC. The median of parameters was set as the cut-off value for statistical analysis. Univariate survival analysis was performed by the Kaplan Meier method and log-rank test, and multivariate analysis was carried out by a Cox proportional hazards model. RESULTS:Patients with lymph node metastasis or longer tumor diameters were associated with higher TLG (P?<?0.05). Univariate analysis showed MTV, TLG, radiotherapy dose and chemotherapy were significantly associated with disease progression-free survival (PFS) and overall survival (OS) (P < 0.05). Lymph node metastasis and tumor longest diameter were associated with OS. Multivariate analysis demonstrated TLG, radiotherapy dose, and chemotherapy were independent factors of PFS and OS (HR: 2.307, 0.591, 0.572 and 2.145, 0.480, 0.471, P < 0.05). CONCLUSIONS:TLG was found to be the independent prognostic factor of OS and PFS. Among clinical factors, radiotherapy dose and chemotherapy were independent prognostic factors of OS and PFS.