Monocyte recruitment in venous pulmonary embolism at time of cancer diagnosis in upper gastrointestinal cancer patients.

Upper gastrointestinal cancer is frequently complicated by venous thromboembolisms (VTE), especially pulmonary embolisms (PE) increase the mortality rate. Monocytes are a part of the innate immune system and up-regulation may indicate an ongoing inflammatory response or infectious disease and has lately been associated with a moderate risk of suffering from VTE. This prospectively study aims to compare the incidence of pulmonary embolism with markers of coagulation and compare it to the absolute monocyte count. A consecutive cohort of 250 patients with biopsy proven upper gastrointestinal cancer (i.e. pancreas, biliary tract, esophagus and gastric cancer) where included at the time of cancer diagnosis and before treatment. All patients underwent bilateral compression ultrasonography for detection of deep vein thrombosis (DVT). Of these 143 had an additionally pulmonary angiografi (CTPA) with the staging computer tomography. 13 of 250 patients (5.2%) had a DVT and 11 of 143 (7.7%) had CTPA proven PE. PE was significantly more common among patients with elevated D-dimer (OR 11.62, 95%CI: 1.13-119, P = 0.039) and elevated absolute monocyte count (OR 7.59, 95%CI: 1.37-41.98, P = 0.020). Only patients with pancreatic cancer had a significantly higher risk of DVT (OR 11.03, 95%CI: 1.25-97.43, P = 0.031). The sensitivity of absolute monocyte count was 63.6 (95%CI: 30.8-89.1) and specificity 80.3 (95%CI: 72.5-86.7), with a negative predictive value of 96.4 (95%CI: 91-99) in PE. An increased absolute monocyte count was detected in patients suffering from PE but not DVT, suggesting a possible interaction with the innate immune system.

Frequency and malignancy rate of incidental focal salivary gland lesions identified by 18F-fluorodeoxyglucose-positron emission tomography.

PURPOSE: We aimed to evaluate the frequency and malignancy rate of incidental salivary gland lesions (ISGLs) in patients undergoing 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT). METHODS: Using a predefined algorithm, all descriptions of FDG-PET/CT scans performed in the North Denmark Region at the Department of Nuclear Medicine, Aalborg University Hospital from 1.12 2009 to 31.12 2019 were electronically searched for focal uptake in one or more salivary glands. RESULTS: In total, 28,362 FDG-PET/CT scans were performed in the study period. ISGLs were found in 197 (0.7%). A total of 193 (98%) had parotid gland ISGL, and four (2%) had submandibular ISGL. No sublingual lesions were found. Ultimately, 117 patients (60%) were referred to the Department of Otorhinolaryngology-Head and Neck Surgery for evaluation. Fine needle aspiration biopsy was performed in 97 patients, and the most frequent cytopathology was Warthin's tumour (n = 62). Two patients had verified malignancy: one with histopathologically proven acinic cell carcinoma and one with cytopathologically proven metastasis from an oral squamous cell carcinoma. CONCLUSIONS: Incidental salivary gland findings on FDG-PET/CT are rare, and the risk of malignancy is low. Patients with ISGL may be evaluated secondary to the primary disease, but special attention should be given to patients with prior or known head-and-neck malignancies and patients with symptoms from the salivary glands, including swelling.

Usefulness of Imaging Response Assessment after Irreversible Electroporation of Localized Pancreatic Cancer-Results from a Prospective Cohort.

(1) Background: Irreversible electroporation (IRE) is a nonthermal ablation technique that is being studied in nonmetastatic pancreatic cancer (PC). Most published studies use imaging outcomes as an efficacy endpoint, but imaging interpretation can be difficult and has yet to be correlated with survival. The aim of this study was to examine the correlation of imaging endpoints with survival in a cohort of IRE-treated PC patients. (2) Methods: Several imaging endpoints were examined before and after IRE on 18F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography. Separate analyses were performed at the patient and lesion levels. Mortality rate (MR) ratios for imaging endpoints after IRE were estimated. (3) Results: Forty-one patients were included. Patient-level analysis revealed that progressive disease (PD), as defined by RECIST 1.1, is correlated with a higher MR at all time intervals, but PD, as defined by EORTC PET response criteria, is only correlated with the MR in the longest interval. No correlation was found between PD, as defined by RECIST, and the MR in the lesion-level analysis. (4) Conclusions: Patient-level PD, as defined by RECIST, was correlated with poorer survival after IRE ablation, whereas no correlations were observed in the lesion-level analyses. Several promising lesion-level outcomes were identified.

68Ga-PSMA PET/CT compared with MRI/CT and diffusion-weighted MRI for primary lymph node staging prior to definitive radiotherapy in prostate cancer: a prospective diagnostic test accuracy study.

BACKGROUND: The aim was to compare the diagnostic accuracy of 68Ga-PSMA PET/CT with conventional cross-sectional imaging and diffusion-weighted MRI (DW-MRI) for detecting lymph node metastasis (LNM) to stage prostate cancer patients. Twenty consecutive, newly- diagnosed prostate cancer patients were prospectively enrolled and underwent 68Ga-PSMA-11 PET/CT, anatomical MRI or contrast-enhanced CT, and DW-MRI prior to laparoscopic, template-based, extended lymph node dissection. Histopathological findings served as the reference test. RESULTS: Histopathology showed LNM in 13 of 20 patients (19 high-risk, 1 intermediate risk). Five patients had metastasis-suspected lymph nodes on 68Ga-PSMA PET/CT. Patient-based analysis showed that the sensitivity and specificity for detecting LNM were 39% and 100% with 68Ga-PSMA PET/CT, 8% and 100% with MRI/CT, and 36% and 83% with DW-MRI, respectively. The positive and negative predictive values were 100% and 49% with 68Ga-PSMA PET/C, 100% and 37% with MRI/CT, and 80% and 42% with DW-MRI. Of 573 dissected lymph nodes, 33 were LNM from 26 regions. True-positive LNM on 68Ga-PSMA PET/CT was 9-11 mm in diameter, whereas false-negative LNM had a median diameter of 4 mm, with only 3 of 30 lymph nodes being larger than 10 mm. LNM were positive for PSMA by immunostaining. CONCLUSIONS: The sensitivity of 68Ga-PSMA PET/CT was notably better than that of MRI/CT and comparable to that of DW-MRI. Some false positive findings with DW-MRI reduced its specificity and positive predictive value compared with those of 68Ga-PSMA PET/CT and MRI/CT.

The Frequency of Focal Thyroid Incidental Findings and Risk of Malignancy Detected by 18F-Fluorodeoxyglucose Positron Emission Tomography in an Iodine Deficient Population.

Incidental focal uptake of 18F-fluorodeoxyglucose (FDG) in the thyroid on positron emission tomography (PET/CT) is rare but often associated with malignancy. The epidemiology of thyroid incidentalomas has only to some extent been described in countries with iodine deficiency. Here we report data from Denmark, a country with known iodine deficiency and wide access to PET/CT. All FDG PET/CT comprising the head and neck region, during 2014, were retrospectively reviewed, and patients with focal FDG uptake in the thyroid gland were identified. A total of 2451 patients had an FDG PET/CT of which 59 (2.4%) patients presented with FDG-avid focal lesions in the thyroid gland. Among the 59 patients with FDG-avid lesions, 33 patients (56%) received work up with ultrasound, thyroid technetium scintigraphy, fine needle aspiration, and/or histology of which 20 patients had a conclusive pathology report. Ten patients with FDG-avid lesions were identified with thyroid malignancy. The risk of thyroid malignancy was 16.9% among patient with incidental FDG-avid thyroid lesions. Our findings indicated a similar frequency of FDG thyroid incidentalomas and malignancy rates in an iodine deficient population compared to summary data from prior studies, studies mostly performed in geographical areas of normal or excess iodine supplementation.

Prospective comparison of 68Ga-PSMA PET/CT, 18F-sodium fluoride PET/CT and diffusion weighted-MRI at for the detection of bone metastases in biochemically recurrent prostate cancer.

PURPOSE: To prospectively compare diagnostic accuracies for detection of bone metastases by 68Ga-PSMA PET/CT, 18F-NaF PET/CT and diffusion-weighted MRI (DW600-MRI) in prostate cancer (PCa) patients with biochemical recurrence (BCR). METHODS: Sixty-eight PCa patients with BCR participated in this prospective study. The patients underwent 68Ga-PSMA PET/CT, a 18F-NaF PET/CT and a DW600-MRI (performed in accordance with European Society of Urogenital Radiology guidelines, with b values of 0 and 600 s/mm2). Bone lesions were categorized using a three-point scale (benign, malignant or equivocal for metastases) and a dichotomous scale (benign or metastatic) for each imaging modality by at least two experienced observers. A best valuable comparator was defined for each patient based on study-specific imaging, at least 12 months of clinical follow-up and any imaging prior to the study and during follow-up. Diagnostic performance was assessed using a sensitivity analysis where equivocal lesions were handled as non-metastatic and then as metastatic. RESULTS: Ten of the 68 patients were diagnosed with bone metastases. On a patient level, sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic analysis were, respectively, 0.80, 0.98-1.00 and 0.89-0.90 for 68Ga-PSMA PET/CT (n = 68 patients); 0.90, 0.90-0.98 and 0.90-0.94 for 18NaF PET/CT (n = 67 patients); and 0.25-0.38, 0.87-0.92 and 0.59-0.62 for DW600-MRI (n = 60 patients). The diagnostic performance of DW600-MRI was significantly lower than that of 68Ga-PSMA PET/CT and 18NaF PET/CT for diagnosing bone metastases (p < 0.01), and no significant difference in the AUC was seen between 68Ga-PSMA PET/CT and 18NaF PET/CT (p = 0.65). CONCLUSION: 68Ga-PSMA PET/CT and 18F-NaF PET/CT showed comparable and high diagnostic accuracies for detecting bone metastases in PCa patients with BCR. Both methods performed significantly better than DW600-MRI, which was inadequate for diagnosing bone metastases when conducted in accordance with European Society of Urogenital Radiology guidelines.

68Ga-PSMA PET/CT for the detection of bone metastasis in recurrent prostate cancer and a PSA level <2 ng/ml: Two case reports and a literature review.

Localization of prostate cancer recurrence, particularly in the bones, is a major challenge with standard of care imaging in patients with biochemical recurrence following curatively intended treatment. Gallium-68-labeled prostate specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) is a novel and promising method for imaging in prostate cancer. The present study reports two cases of patients with prostate cancer with biochemical recurrence, with evidence of bone metastases on 68Ga-PSMA PET/CT images and low prostate specific antigen PSA levels (<2 ng/ml) and PSA doubling time >6 months. The bone metastases were verified by supplementary imaging with 18F-sodium fluoride PET/CT and magnetic resonance imaging as well as biochemical responses to androgen deprivation therapy. Therefore, 68Ga-PSMA PET/CT is promising for the restaging of patients with prostate cancer with biochemical recurrence, including patients with low PSA levels and low PSA kinetics.

Diagnostic value of (18)F-FDG PET/CT as first choice in the detection of recurrent colorectal cancer due to rising CEA.

BACKGROUND: The diagnostic value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) as the first imaging approach in the evaluation of rising carcinoembryonic antigen (CEA) is not clear. The objective of this study was to investigate the value of (18)F-FDG PET/CT in patients with colorectal cancer (CRC) and suspected recurrence based on rising CEA. METHODS: A total of 73 patients with CRC were referred to PET/CT after radical surgery. Generally, all patients were scheduled to follow a CT-based post-surgical follow-up regimen. In the case of rising CEA, (18)F-FDG PET/CT was performed in most patients with contrast-enhanced CT. The PET/CT images were independently reviewed by two readers. The presence or absence of recurrence was based on histology and/or standardized clinical follow-up. RESULTS: Among 35 patients who had confirmed recurrence of CRC, PET/CT demonstrated recurrence with a sensitivity of 85.7 %, a specificity of 94.7 %, a positive predictive value of 93.8 %, and a negative predictive value of 87.8 %. The SUVmax ranged from 1.3 to 19.9. The mean time since the last postoperative imaging and PET/CT was 8 months (median 4 months). CEA values at referral ranged from 1.5 to 164.0 µg/L (median 5.6 µg/L). The diagnostic properties of PET/CT were analyzed in subgroups of patients with a single rising CEA sample (30 patients, 41 %), 31 patients (43 %) with two or more consecutive increases, and 12 patients (16 %) with persistently elevated values. CONCLUSIONS: (18)F-FDG PET/contrast-enhanced CT has high diagnostic accuracy in the diagnosis of recurrent CRC, even in patients in a conventional CT-based follow-up program.

Treatment-related frequency of venous thrombosis in lower esophageal, gastro-esophageal and gastric cancer--a clinical prospective study of outcome and prognostic factors.

INTRODUCTION: Prospective studies of chemotherapy-associated VTE in cancer patients undergoing neoadjuvant chemotherapy in combination with curative intended surgery have not been reported for upper gastrointestinal cancer. In this clinical prospective study, we sought to estimate the incidence of VTE in esophagogastric cancer (OEC) patients scheduled for a specific perioperative chemotherapy regime: oxaliplatin, capecitabine, and epirubicin, (EXE) and curative intended surgery. MATERIAL AND METHODS: A total of 129 consecutive OEC patients were examined using state-of-the-art bilateral compression ultrasound (biCUS) for deep vein thrombosis (DVT) before undergoing preoperative chemotherapy, surgery, and postoperative chemotherapy. In addition 79 were also consecutively scanned at baseline for pulmonary embolism (PE) using state-of-the-art computer tomography pulmonary angiography (CTPA). RESULTS: There were 21 VTE cases throughout the course of treatment (16%, 95% confidence interval [95% CI]: 10 - 24%) among the patients examined using both biCUS and CTPA. Fourteen of 21 VTE was incidental (68%, 95% CI: 43 -85) and 7 VTE events was symptomatic (33%, 15 - 57). The median overall survival was 18months (95% CI: 13 - 24) in patients without any VTE and 14months (95% CI: 7 -30, P = 0.820) in patients with VTE. The cancer stage (adjusted odds ratio [OR]: 5.2, 95% CI: 1 - 21, p=0.002) and gastric cancer (OR 6.4, 95% CI: 2 - 21, P = 0.002) was a significant predictor of VTE. CONCLUSION: The incidence of VTE in patients undergoing EXE neoadjuvant chemotherapy was high, particularly among patients with initial stage III and IV cancers. In addition, a substantial number of chemotherapy-related VTE cases were asymptomatic.

Mazabraud's syndrome: case report and literature review.

Mazabraud's syndrome is a rare disorder characterized by the association of single or multiple intramuscular myxomas with fibrous dysplasia. Here, we present the first case of Mazabraud's syndrome visualized on 18F-FDG PET/CT with histopathological confirmation of the myxoma. Our case demonstrates a slightly increased FDG uptake (SUVmax 2.1) within the myxomas and a moderately to highly increased tracer uptake (SUVmax 7.0) within the fibrous dysplastic lesions. The typical histological appearance of the intramuscular myxoma confirmed the radiological diagnosis. Further, we discuss the imaging findings and the histopathological features of this rare case with a review of the related literature.

SUVmax of 18FDG PET/CT as a predictor of high-risk endometrial cancer patients.

OBJECTIVE: To evaluate SUVmax in the assessment of endometrial cancer preoperatively with particular focus on myometrial invasion (MI), cervical invasion (CI), FIGO stage, risk-stratification and lymph node metastases (LNM). METHODS: A total of 268 women with endometrial cancer or atypical endometrial hyperplasia underwent FDG PET/CT imaging before surgical treatment. SUVmax of the primary tumour was compared with histological prognostic factors. RESULTS: SUVmax was significantly higher in patients with high FIGO stages (p<0.0001), deep MI (p=0.002), CI (p=0.04), LNM (p=0.04) and high risk tumours (p=0.003). Linear regression found that SUVmax was dependent of MI (p=0.001, 95% CI 2.863-11.098), CI (p=0.001, 95% CI 2.896-11.499), risk (p=0.004, 95% CI 0.077-0.397), LNM (p=0.04, 95% CI 0.011-0.482) and FIGO stage (p<0.0001, 95% CI 0.158-0.473). CONCLUSIONS: Preoperative PET/CT scanning and SUVmax measurements of the primary tumour may provide additional clinical and prognostic information about MI, CI, LNM and high risk disease in patients with endometrial cancer and allow for individualization of patient care. However, the sensitivity and specificity of the SUVmax in staging endometrial cancer is not high enough to reliably replace surgical staging.

MRI, PET/CT and ultrasound in the preoperative staging of endometrial cancer - a multicenter prospective comparative study.

OBJECTIVES: The aim of this prospective multicenter study was to evaluate and compare the diagnostic performance of PET/CT, MRI and transvaginal two-dimensional ultrasound (2DUS) in the preoperative assessment of endometrial cancer (EC). METHODS: 318 consecutive women with EC were included when referred to three Danish tertiary gynecological centers for surgical treatment. Preoperatively they were PET/CT-, MRI-, and 2DUS scanned. The imaging results were compared to the final pathological findings. This study was approved by the National Committee on Health Research Ethics. RESULTS: For predicting myometrial invasion, we found sensitivity, specificity, PPV, NPV, and accuracy for PET/CT to be 93%, 49%, 41%, 95% and 61%, for MRI to be 87%, 57%, 44%, 92%, and 66% and for 2DUS to be 71%, 72%, 51%, 86% and 72%. For predicting cervical invasion, the values were 43%, 94%, 69%, 85% and 83%, respectively, for PET/CT, 33%, 95%, 60%, 85%, and 82%, respectively, for MRI, and 29%, 92%, 48%, 82% and 78% for 2DUS. Finally, for lymph node metastases, the values were 74%, 93%, 59%, 96%, and 91% for PET/CT and 59%, 93%, 40%, 97% and 90% for MRI. When comparing the diagnostic performance we found PET/CT, MRI and 2DUS to be comparable in predicting myometrial invasion. For cervical invasion and lymph node metastases, however, PET/CT was the best. CONCLUSIONS: None of the modalities can yet replace surgical staging. However, they all contributed to important knowledge and were, furthermore, able to upstage low-risk patients who would not have been recommended lymph node resection based on histology and grade alone.

Clinical results from first use of prostate stent as fiducial for radiotherapy of prostate cancer.

PURPOSE: A clinical feasibility study using a removable prostate stent as fiducial for image-guided radiotherapy (IGRT) of localized prostate cancer (PC). MATERIAL AND METHODS: The study included patients with local or locally advanced PC. The clinical target volume (CTV) was outlined on magnetic resonance (MR) images co-registered to planning computer tomography (CT) images. Daily online IGRT was delivered using the stent as fiducial. Risk of migration was estimated using multiple MR. Acute urinary toxicity was scored using the international prostate symptom score (IPSS). Late gastro-intestinal (GI) and genito-urinary (GU) toxicity was scored using the Radio Therapy Oncology Group (RTOG) score, biochemical failure (BF) was defined as an elevation of prostate specific antigen (PSA) above nadir plus 2 ng/ml after radiotherapy. RESULTS: One hundred men were enrolled in the study. Ninety completed radiotherapy with the stent as fiducial. No migration of the stent was seen, but three cases of dislocation of the stent to the bladder were observed. Acute urinary toxicity based on IPSS was comparable to toxicity in patients who had gold markers (GM) as fiducials. Removal of the stent was associated with a high frequency of urinary retention. Late GI and GU toxicity and BF were comparable to those of other studies, but longer observation time is needed. CONCLUSIONS: This study reports the first clinical results of using a prostate stent as fiducial. No migration of the stent observed. Dislocation of the stent to the urinary bladder was observed in three cases, requiring removal of the stent and insertion of a new fiducial. Acute toxicity during radiotherapy evaluated from IPSS was comparable to toxicity in patients with GM. Removal of the stent was associated with a high frequency of post procedural urinary retention. Late toxicity and BF were comparable to those of other studies, though longer observation time is needed.

A new fiducial marker for Image-guided radiotherapy of prostate cancer: clinical experience.

BACKGROUND: A new fiducial marker for image guided radiotherapy (IGRT) based on a removable prostate stent made of Ni Ti has been developed during two previous clinical feasibility studies. The marker is currently being evaluated for IGRT treatment in a third clinical study. METHOD: The new marker is used to co-register MR and planning CT scans with high accuracy in the region around the prostate. The co-registered MR-CT volumes are used for delineation of GTV before planning. In each treatment session the IGRT system is used to position the patient before treatment. The IGRT system use a stereo pair of kV images matched to corresponding Digital Reconstructed Radiograms (DRR) from the planning CT scan. The match is done using mutual gray scale information. The pair of DRR's for positioning is created in the IGRT system with a threshold in the Look Up Table (LUT). The resulting match provides the necessary shift in couch coordinates to position the stent with an accuracy of 1-2 mm within the planned position. RESULTS: At the present time 39 patients have received the new marker. Of the 39 one has migrated to the bladder. Deviations of more than 5 mm between CTV outlined on CT and MR are seen in several cases and in anterior-posterior (AP), left-right (LR) and cranial-caudal (CC) directions. Intra-fraction translation movements up to +/- 3 mm are seen as well. As the stent is also clearly visible on images taken with high voltage x-rays using electronic portal images devices (EPID), the positioning has been verified independently of the IGRT system. DISCUSSION: The preliminary result of an on going clinical study of a Ni Ti prostate stent, potentially a new fiducial marker for image guided radiotherapy, looks promising. The risk of migration appears to be much lower compared to previous designs.

Leukocyte orchestration in blood and tumour tissue following interleukin-2 based immunotherapy in metastatic renal cell carcinoma.

With the objective of evaluating leukocyte orchestration in situ, serial blood samples and tumour tissue core needle biopsies were obtained at baseline and repeated after 1 month of therapy, among 49 consecutive single-institution patients with metastatic renal cell carcinoma (mRCC). Patients were treated with outpatient low-dose subcutaneous interleukin 2 (IL-2) and interferon alpha (IFN-alpha) alone (n = 23) or in combination with histamine dihydrochloride (n = 26). Objective responses were achieved in ten of 49 patients (20%) with an overall median survival of 14 months and an estimated 1- to 4-year survival rate of 57, 35, 24 and 22%, respectively. Toxicity was mild to moderate with no treatment-related deaths. High numbers of blood monocytes and neutrophils were significantly correlated to short survival. By contrast, high numbers of intratumoural CD3+, CD4+, CD8+ and CD57+ lymphocytes were positively correlated to objective response and/or long-term survival. Intratumoural lymphocytes showed low zeta expression, whereas blood lymphocytes showed almost normal levels of zeta expression. Neutrophils, the most frequent peripheral blood leukocyte subset, were scarce within the tumour tissue. Intratumoural eosinophils were not observed. In progressing patients, both the absolute number and the relative composition of leukocyte subsets in blood and tumour tissue remained unaffected by cytokine therapy. However, in responding patients, cytokine therapy was followed by an absolute and relative increase in T cells in blood as well as tumour tissue, an absolute and relative reduction in neutrophils in peripheral blood and a relative reduction of intratumoural macrophages. Histamine did not influence levels of intratumoural or blood leukocyte numbers, zeta-chain expression or cytotoxicity. In conclusion, the present regimen of outpatient low-dose subcutaneous IL-2 and IFN-alpha in mRCC should attract interest based on response, survival and toxicity. In responding patients, cytokine therapy was followed by substantial changes in the blood and tumour tissue leukocyte composition, correlated to response and survival. No discernable differences in immunologic parameters studied could be detected between histamine- and nonhistamine-treated patients.