Assessing Therapeutic Response to Radium-223 with an Automated Bone Scan Index among Metastatic Castration-Resistant Prostate Cancer Patients: Data from Patients in the J-RAP-BSI Trial.

To evaluate the usefulness of change in the automated bone scan index (aBSI) value derived from bone scintigraphy findings as an imaging biomarker for the assessment of treatment response and survival prediction in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223. This study was a retrospective investigation of a Japanese cohort of 205 mCRPC patients who received Ra-223 in 14 hospitals between July 2016 and August 2020 and for whom bone scintigraphy before and after radium-223 treatment was available. Correlations of aBSI change, with changes in the serum markers alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were evaluated. Additionally, the association of those changes with overall survival (OS) was assessed using the Cox proportional-hazards model and Kaplan-Meier curve results. Of the 205 patients enrolled, 165 (80.5%) completed six cycles of Ra-223. Following treatment, ALP decline (%ALP < 0%) was noted in 72.2% (148/205), aBSI decline (%aBSI < 0%) in 52.7% (108/205), and PSA decline (%PSA < 0%) in 27.8% (57/205). Furthermore, a reduction in both aBSI and ALP was seen in 87 (42.4%), a reduction in only ALP was seen in 61 (29.8%), a reduction in only aBSI was seen in 21 (10.2%), and in both aBSI and ALP increasing/stable (≥0%) was seen in 36 (17.6%) patients. Multiparametric analysis showed changes in PSA [hazard ratio (HR) 4.30, 95% confidence interval (CI) 2.32-8.77, p < 0.0001], aBSI (HR 2.22, 95%CI 1.43-3.59, p = 0.0003), and ALP (HR 2.06, 95%CI 1.35-3.14, p = 0.0008) as significant prognostic factors for OS. For mCRPC patients treated with Ra-223, aBSI change is useful as an imaging biomarker for treatment response assessment and survival prediction.

Prognostic analysis of curatively resected pancreatic cancer using harmonized positron emission tomography radiomic features.

BACKGROUND: Texture features reflecting tumour heterogeneity enable us to investigate prognostic factors. The R package ComBat can harmonize the quantitative texture features among several positron emission tomography (PET) scanners. We aimed to identify prognostic factors among harmonized PET radiomic features and clinical information from pancreatic cancer patients who underwent curative surgery. METHODS: Fifty-eight patients underwent preoperative enhanced dynamic computed tomography (CT) scanning and fluorodeoxyglucose PET/CT using four PET scanners. Using LIFEx software, we measured PET radiomic parameters including texture features with higher order and harmonized these PET parameters. For progression-free survival (PFS) and overall survival (OS), we evaluated clinical information, including age, TNM stage, and neural invasion, and the harmonized PET radiomic features based on univariate Cox proportional hazard regression. Next, we analysed the prognostic indices by multivariate Cox proportional hazard regression (1) by using either significant (p < 0.05) or borderline significant (p = 0.05-0.10) indices in the univariate analysis (first multivariate analysis) or (2) by using the selected features with random forest algorithms (second multivariate analysis). Finally, we checked these multivariate results by log-rank test. RESULTS: Regarding the first multivariate analysis for PFS after univariate analysis, age was the significant prognostic factor (p = 0.020), and MTV and GLCM contrast were borderline significant (p = 0.051 and 0.075, respectively). Regarding the first multivariate analysis of OS, neural invasion, Shape sphericity and GLZLM LZLGE were significant (p = 0.019, 0.042 and 0.0076). In the second multivariate analysis, only MTV was significant (p = 0.046) for PFS, whereas GLZLM LZLGE was significant (p = 0.047), and Shape sphericity was borderline significant (p = 0.088) for OS. In the log-rank test, age, MTV and GLCM contrast were borderline significant for PFS (p = 0.08, 0.06 and 0.07, respectively), whereas neural invasion and Shape sphericity were significant (p = 0.03 and 0.04, respectively), and GLZLM LZLGE was borderline significant for OS (p = 0.08). CONCLUSIONS: Other than the clinical factors, MTV and GLCM contrast for PFS and Shape sphericity and GLZLM LZLGE for OS may be prognostic PET parameters. A prospective multicentre study with a larger sample size may be warranted.

Novel nomogram developed for determining suitability of metastatic castration-resistant prostate cancer patients to receive maximum benefit from radium-223 dichloride treatment-Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial.

PURPOSE: To develop a novel nomogram for determining radium-223 dichloride (Ra-223) treatment suitability for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: This Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial was a retrospective multicenter investigation enrolled 258 mCRPC patients in Japan with Ra-223 treatment between June 2016 and August 2020, with bone scintigraphy findings before treatment, clinical data, and survival outcome available. A nomogram was constructed using prognostic factors for overall survival (OS) based on a least absolute shrinkage and selection operator Cox regression model. A sub-analysis was also conducted for patients meeting European Medicines Agency (EMA) guidelines. RESULTS: Within a median of 17.4 months after initial Ra-223 treatment, 124 patients (48.1%) died from prostate cancer. Predictive factors included (1) sum of prior treatment history (score 0, never prior novel androgen receptor-targeted agents (ARTA) therapy, never prior taxane-based chemotherapy, and ever prior bisphosphonate/denosumab treatment), (2) Eastern Cooperative Oncology Group (ECOG) performance status, (3) prostate-specific antigen doubling time (PSADT), (4) hemoglobin, (5) lactate dehydrogenase (LDH), and (6) alkaline phosphatase (ALP) levels, and (7) automated bone scan index (aBSI) value based on bone scintigraphy. The nomogram using those factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.748 and 0.734, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.771, 0.818, and 0.771, respectively. In 227 patients meeting EMA recommendation, the nomogram with seven factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.722 and 0.704, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.747, 0.790, and 0.759, respectively. CONCLUSION: This novel nomogram including aBSI to select mCRPC patients to receive Ra-223 with significantly prolonged OS possibility was found suitable for assisting therapeutic decision-making, regardless of EMA recommendation.

Clinical value of FDG-PET for preoperative evaluation of endometrial cancer.

OBJECTIVE: Whole body positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) has been widely used in various malignancies, but the clinical value of FDG-PET for endometrial cancer has not been fully investigated. The purpose of this study was to evaluate the usefulness of FDG-PET for preoperative evaluation of endometrial cancer. METHODS: Forty female patients suspected of having endometrial cancer were included in this study. All patients underwent an FDG-PET or PET/CT scan, and images were interpreted visually. The diagnostic performance in detecting the primary tumor, regional nodal status, and distant metastasis was determined. In addition, the usefulness of PET was assessed in terms of additional information and clinical impact for therapeutic management. RESULTS: Of 40 patients, 30 were histologically confirmed to have endometrial cancer. The patient-based sensitivity and specificity of FDG-PET for primary tumors were 83 and 100%, respectively, and 100 and 100%, respectively, for nodal metastases. There were 12 distant metastases in 6 patients and two second primary cancers in two patients, which were all accurately diagnosed by PET on a patient-basis. PET yielded 12 additional findings in 10 patients, and had a bearing on the therapeutic management of four patients, including one patient with recurrent breast cancer. CONCLUSIONS: FDG-PET had a reasonably high diagnostic accuracy in endometrial cancer. Although the number of cases with clinical impact was limited, additional information by PET was obtained in one-third of the cases.

Prevalence of positive FDG-PET findings in patients with high CEA levels.

OBJECTIVE: The purpose of this study was to evaluate the prevalence of positive findings of positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in patients with high serum CEA levels. METHODS: A total of 303 patients who had undergone an FDG-PET scan in our institution with high serum CEA levels were analyzed. The prevalence of positive PET findings was evaluated with regard to a previous history of malignancy, absolute value of CEA levels, and the time course of CEA levels (an increasing or decreasing pattern, a change divided by time (DeltaCEA) and doubling time of CEA). RESULTS: Of 303 patients, 232 were confirmed to have malignancy, and the patient-based sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of PET were 87, 86, 95, 66, and 86%, respectively. There was no statistically significant difference in positive rates according to the history of previous malignancy. The prevalence of PET-positive cases was higher with an increase in absolute CEA levels, and more than 90% of the patients were positive when CEA levels were more than 20 ng/ml. The DeltaCEA was significantly higher and the doubling time was significantly shorter in patients with positive results than those with negative results. CONCLUSIONS: A high value of serum CEA levels was correlated with a higher prevalence of positive PET findings. FDG-PET scans would be justified in patients with high serum CEA levels, regardless of whether there was or was not a previous history of malignancy.

Inhomogeneous bone marrow uptake caused by G-CSF mimics multiple bone metastases on FDG-PET.

Administration of granulocyte colony stimulating factor can cause homogeneous hypermetabolic activity of bone marrow in positron emission tomography using F-18-fluorodeoxyglucose. We report a case in which positron emission tomography demonstrated multiple foci of hypermetabolic activity in the bone marrow, which was considered an early effect of granulocyte colony stimulating factor, and not multiple osseous metastases.

FDG PET as a prognostic predictor in the early post-therapeutic evaluation for unresectable hepatocellular carcinoma.

PURPOSE: To elucidate the prognostic role of post-therapeutic (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET), we conducted a retrospective cohort study analysing the clinical factors that affect overall survival after non-operative therapy for unresectable hepatocellular carcinoma (HCC). METHODS: Sixty-seven cases with unresectable HCC who received non-operative therapy (transcatheter arterial chemoembolization: n = 24, transcatheter arterial infusion chemotherapy: n = 31, radiofrequency ablation: n = 5 or systemic chemotherapy: n = 7) and had received FDG PET for the evaluation of the therapeutic effect within 1 month after the end of the therapy were evaluated. Overall survival rate was evaluated using the univariate and multivariate analyses of relevant clinical and laboratory parameters before and after therapy, including visual PET analysis and quantitative analysis using maximum standardized uptake value (SUV). RESULTS: Visual PET diagnosis of post-therapeutic lesions was a good predictor of overall survival of unresectable HCC patients. The low FDG group showed significantly longer survival (average: 608 days) than that (average: 328 days) of the high FDG group (p < 0.0001). Multivariate analysis showed four significant prognostic factors for the survival: post-therapeutic alpha-fetoprotein (alphaFP) level (=400 ng/ml, p = 0.004), post-therapeutic visual PET diagnosis (p = 0.006), post-therapeutic clinical stage (UICC stage IV, p = 0.04) and post-therapeutic Milan criteria (p = 0.03), while pre-therapeutic clinical factors, SUV by post-therapeutic FDG PET (5.0 or more) or others did not show significance. CONCLUSION: The present study suggests that post-therapeutic PET performed within 1 month after non-operative therapy can be a good predictor of overall survival in unresectable HCC patients, while pre-therapeutic evaluation including PET, tumour markers and clinical staging may not be useful.

Clinical impact of whole body FDG-PET for recurrent biliary cancer: a multicenter study.

OBJECTIVE: To evaluate the clinical usefulness of positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) in patients with follow-up or suspected recurrent biliary cancer in a multicenter study. METHODS: We performed a retrospective review of 50 patients who underwent FDG-PET (either integrated PET/CT or manual fusion of dedicated PET and CT) scans for post-treatment surveillance of biliary cancer. Recurrence was suspected in 40 of these patients on the basis of tumor marker levels, and/or findings of conventional imaging (group A). Clinical findings in the remaining 10 patients showed them to be disease-free (group B). The diagnostic performance and clinical impact of PET were analyzed. RESULTS: Recurrence was confirmed in 28 out of the 40 patients in group A, and 1 of the 10 patients in group B. Patient-based analysis showed that the sensitivity, specificity, and accuracy of PET for detecting recurrence were 86% (25/29), 91% (19/21), and 88% (44/50), respectively. The one patient with recurrence in group B was correctly interpreted by PET. Positive test likelihood ratio and negative test likelihood ratio were increased from 1.69 to 9.05, and 0.08 to 0.32, respectively, after PET study. The findings of PET resulted in a change of management for 10 out of the 50 patients (20%) by initiating an unplanned treatment strategy (n = 7), by obviating the need for planned diagnostic procedures (n = 2), or by changing the treatment plan (n = 1). CONCLUSION: FDG-PET/CT or PET with CT yielded helpful information in patients with suspected recurrent biliary cancer.

Significance of chronic marked hyperglycemia on FDG-PET: is it really problematic for clinical oncologic imaging?

OBJECTIVES: The purpose of this study was to evaluate the adverse effects of chronic marked hyperglycemia on clinical diagnostic performance of positron emission tomography (PET) using (18)F-fuorodeoxyglucose (FDG). METHODS: Fifty-seven scans of 54 patients, who received FDG-PET for the diagnosis of various cancer(s), and who showed high plasma glucose level of more than 200 mg/dl at the time of administration of FDG in spite of at least 4-h fasting, were retrospectively analyzed. In the clinical follow-up, this high plasma glucose was confirmed as chronic hyperglycemia derived from uncontrolled diabetes (n = 32) and untreated diabetes (n = 25). Based on the final diagnosis of malignancy obtained by histopathology or clinical follow-up for at least 6 months, the diagnostic performance of visual PET analysis was evaluated. RESULTS: Excluding nine scans of nine patients without sufficient follow-up, final diagnosis was obtained in 48 scans of 45 patients. In 36 scans of 36 patients, at least one malignant lesion was finally confirmed, and true-positive and false-negative results were obtained in 30 and six cases, respectively. Six cases showed false-negative results due to low FDG-avid pathological characteristics (hepatocellular carcinoma, etc.), chemotherapeutic effect or small tumor size. Overall, the patient-based sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 83, 83, 94, 63 and 83%, respectively. In lesion-based diagnosis, 56 of 75 lesions (74%) were depicted by PET, while 19 lesions were negative on PET, also due to low FDG-avid characteristics or small size (less than 15 mm). CONCLUSIONS: At the time of chronic hyperglycemia (not acute hyperglycemia), the adverse effect caused by high plasma glucose level was minimum. The FDG uptake of the tumor maintained a sufficiently high level for visual clinical diagnosis in most cases, except in the cases of low FDG-avid tumors or small lesions (15 mm in size).

Comparative study of FDG PET/CT and conventional imaging in the staging of rhabdomyosarcoma.

OBJECTIVE: The current study was conducted to compare the diagnostic accuracy between (18)F-fluoro-2-deoxy-D: -glucose (FDG) positron emission tomography (PET)/computed tomography (CT), and conventional imaging (CI) for the staging and re-staging of patients with rhabdomyosarcomas. METHODS: Thirty-five patients who underwent FDG PET/CT prior to treatment were evaluated retrospectively. CI methods consisted of (99m)Tc-hydroxymethylene diphosphonate bone scintigraphy, chest radiograph, whole body CT, and magnetic resonance imaging of the primary site. The images were reviewed and two boardcertified radiologists reached a diagnostic consensus. Tumor stage was confirmed by histological examination and/or follow-up examinations. RESULTS: Interpretation on the basis of FDG PET/CT, and CI, diagnostic accuracies of the T and N stages were similar. Using FDG PET/CT, the M stage was correctly assigned in 31 patients (89%), whereas the accuracy of CI in M stage was 63%. TNM stage was correctly assessed with FDG PET/CT in 30 of 35 patients (86%) and with CI in 19 of 35 patients (54%). The overall TNM staging and M staging accuracies of FDG PET/CT were significantly higher than that of CI (P < 0.01). CONCLUSIONS: FDG PET/CT is more accurate than CI regarding clinical staging and re-staging of patients with rhabdomyosarcomas.

Clinical value of image fusion from MR and PET in patients with head and neck cancer.

PURPOSE: This study aimed to evaluate the clinical value of image fusion from magnetic resonance (MR) combined with positron emission tomography (PET) imaging, using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) in head and neck cancer. METHODS: Sixty-five consecutive patients underwent MR and FDG-PET scans before or after the treatment of known or suspected head and neck cancer. T1-weighted and T2-weighted images were first assessed by MR interpretation, and then, the fused images of T2-weighted images from MR and PET were evaluated in a blind manner. Diagnostic performance was compared. PROCEDURES: For initial staging, in 48 patients, malignant tumors were histologically confirmed in 45 patients. The interpretation sensitivities of MR alone and fused images for primary tumors were 98% and 100%, respectively. For lymph node metastasis, the sensitivity and specificity of both methods were 85% and 92%, respectively. Of 15 patients with suspected recurrence, ten patients had recurrent tumors, three patients developed second malignant tumors, and two patients had no recurrence. For these patients, the overall sensitivity of MR alone was 67%, whereas that of the fused images was 92%. Eight additional lesions were accurately diagnosed by image fusion only. In two patients with lymph node metastasis from unknown origin, the primary site was not detected in one patient, while tonsilar cancer was identified only by image fusion interpretation. CONCLUSION: Image fusion from MR with PET might be useful in evaluating head and neck cancer, especially in suspected recurrent cases rather than in fresh cases.

Characterization of atherosclerotic plaque of carotid arteries with histopathological correlation: vascular wall MR imaging vs. color Doppler ultrasonography (US).

PURPOSE: To investigate whether the vessel wall MRI of carotid arteries would differentiate at-risk soft plaque from solid fibrous plaque by identifying liquid components more accurately than color Doppler ultrasonography (US). MATERIALS AND METHODS: This study included 54 carotid arteries in 54 consecutive patients who underwent carotid endarterectomy. MRI was performed using black-blood fat-suppressed (FS) T1-and FS T2-weighted TSE sequences. A total of 68 major segments of the 54 carotid plaques were grouped into four MR categories based on signal intensity index (SII). MR criteria used for the diagnosis of plaque vulnerability were: at-risk soft plaque including a segment of liquid component (category A or B), solid fibrous plaque (category C or D). The MR and US findings were compared with histopathological findings of endarterectomy specimens. RESULTS: Intraoperative findings and microscopic examination of endarterectomy specimens revealed 24 at-risk soft plaques and 30 solid fibrous plaques. The sensitivity, specificity, and accuracy for diagnosing at-risk soft plaque are 96%, 93%, and 94% for MR, and 75%, 63%, and 69% for color Doppler US, respectively. The slice-by-slice MR evaluation of carotid wall also revealed detailed information of plaque segments and correlated well with the features of corresponding histologic sections. CONCLUSION: Vessel wall MRI with MRI category could have a potential to more accurately diagnose an at-risk soft plaque predominantly composed of liquid components in comparison with color Doppler US.

MR imaging of testicular torsion: features of testicular hemorrhagic necrosis and clinical outcomes.

PURPOSE: To determine whether emergency subtraction dynamic contrast-enhanced MR imaging (DCE-MRI) in combination with T2- and T2*-weighted imaging of the testis is useful in the evaluation of patients with testicular torsion. MATERIALS AND METHODS: Fourteen patients with surgically proven testicular torsion were examined using preoperative emergency MRI, including T2-weighted, T2*-weighted, and DCE-MRI. The affected testis was examined histologically in eight patients who underwent orchiectomy, and by postoperative follow-up MRI in six patients who underwent orchiopexy. The diagnostic criteria for testicular torsion and detection of hemorrhagic necrosis in the affected testis in emergency MRI were decreased or no perfusion in DCE-MRI and a spotty and/or streaky pattern of low or very low signal intensity in T2- and T2*-weighted images. The intraoperative findings and clinical outcomes were also compared. RESULTS: The histological findings and follow-up MR images revealed total or partial necrosis of the affected testis in 10 of the 14 patients. In the diagnosis of complete torsion, the sensitivities were 100% for DCE-MRI and 75% for T2- and T2*-weighted imaging. In the detection of testicular necrosis, T2- and T2*-weighted imaging showed the highest accuracy (100%), followed by 12-hour time from onset (93%), intraoperative findings (79%), and DCE-MRI (71%). CONCLUSION: Emergency MRI can help diagnose testicular torsion and detect testicular necrosis when DCE-MRI is used in combination with T2- and T2*-weighted images.

MR imaging of acute biliary disorders.

In patients with acute right-sided epigastric pain, jaundice, and a high fever, it is essential to accurately diagnose the cause of the symptoms, differentiate acute biliary disorders from nonbiliary disorders, and evaluate the severity of the disease. Gray-scale ultrasonography (US) and computed tomography (CT) are useful primary imaging modalities, but their results are not always conclusive. Magnetic resonance (MR) imaging, including MR cholangiopancreatography, can be a valuable complement to US and CT when additional information is needed. MR images have excellent tissue contrast and can provide more specific information, allowing diagnosis of complications that arise from acute cholecystitis, such as empyema, gangrenous cholecystitis, gallbladder perforation, enterocholecystic fistula, emphysematous cholecystitis, and hemorrhagic cholecystitis. In addition, causes of obstructive jaundice, acute suppurative cholangitis, and hemobilia can be clearly demonstrated with multisequence MR imaging. Single-section MR cholangiopancreatography and heavily T2-weighted imaging, in combination with fat-suppressed T1- and T2-weighted imaging, provide comprehensive and detailed information about the biliary system around the obstruction site, biliary calculi, inflammatory processes, purulent material, abscesses, gas, and hemorrhage. Contrast-enhanced MR imaging is useful for evaluation of the gallbladder wall; lack of enhancement and disruption of the wall may be findings specific for gangrenous cholecystitis and gallbladder perforation, respectively.