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.

Physiological 68Ga-RM2 uptake in patients with biochemically recurrent prostate cancer: an atlas of semi-quantitative measurements.

AIM: 68Ga-RM2 is a bombesin (BBN) analog that targets the gastrin releasing peptide receptors (GRPR) overexpressed in many cancer cells, including prostate cancer (PC). It has been reported to successfully detect primary and recurrent PC. Here, we describe the distribution and range of physiological uptake of 68Ga-RM2 in 95 patients with biochemically recurrent (BCR) PC. MATERIALS AND METHODS: Ninety-five participants had simultaneous PET/MRI for BCR PC and were prospectively enrolled in this study. Maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) were measured in 24 normal anatomical structures for each participant. Three readers evaluated the images independently. Uptake in various normal tissues was classified into 4 different categories: no significant uptake if SUVmean was less than SUVmean of the aortic arch (AA); mild if SUVmean was less or equal to 2.5, but higher than SUVmean of the AA; moderate if SUVmean was higher than 2.5, but less or equal to 5; intense if SUVmean was higher than 5. RESULTS: The most intense uptake was observed in the urinary bladder, due to excretion of the radiotracer. No significant uptake was seen in the brain, salivary glands, lungs, myocardium, skeleton, muscles, and fat. Liver, spleen, and adrenal glands had mostly no significant uptake; the gastrointestinal tract had intense physiological uptake, with pancreas being the organ with the highest SUVmax measurements (average SUVmax 64.91). Mild and moderate uptake was measured in the esophagus (average SUVmax 3.99), while the stomach wall, duodenum, and rectum had mild uptake (average SUVmax 2.49, 3.42, and 3.58, respectively). CONCLUSIONS: 68Ga-RM2 has been mostly evaluated for PC detection, but it can be used for other tumors overexpressing GRPR such as breast cancer. This atlas of normal biodistribution and SUV measurements in healthy tissues will help physicians distinguish between physiological vs. pathological uptake, as well as potentially assist with planning future studies using GRPR targeting radiopharmaceuticals.

Prognostic value of somatostatin receptor expressing tumor volume calculated from 68Ga-DOTATATE PET/CT in patients with well-differentiated neuroendocrine tumors.

PURPOSE: To evaluate the prognostic value of volumetric parameters calculated from 68Ga-1,4,7,10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Thr3-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated neuroendocrine tumor (WD-NET). METHODS: Ninety-two patients (44 men and 48 women, mean age of 59.5-year-old) with pathologically confirmed WD-NET (grades 1 or 2) were enrolled in a prospective expanded access protocol. Selected data was analyzed retrospectively for this project. Maximum standardized uptake value (SUVmax) in the lesion with the highest 68Ga-DOTATATE uptake was measured and recorded for each patient. In addition, two volumetric parameters, namely, somatostatin receptor expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE), were calculated in each 68Ga-DOTATATE-avid lesion. SRETV was defined as tumor volume with higher 68Ga-DOTATATE uptake than the 50% of SUVmax within the volume of interest (VOI) for each lesion. TLSRE was calculated by multiplying SRETV and mean SUV within the same VOI. Thereafter, the sum of SRETV (ΣSRETV) and TLSRE (ΣTLSRE) for all detected lesions per patient were calculated. Progression-free survival (PFS) was set as primary endpoint. Kaplan-Meier survival analysis, log-rank test, and Cox's proportional hazard model were used for statistical analysis. RESULTS: Univariate analyses revealed significant difference of PFS for WHO tumor grade and ΣSRETV (P < 0.05), while there were no significant differences in age, sex, SUVmax, and ΣTLSRE (P > 0.05). Multivariate analysis identified WHO tumor grade and ΣSRETV as independent predictors of PFS. CONCLUSION: ΣSRETV calculated from 68Ga-DOTATATE PET/CT may have prognostic value of PFS in WD-NET patients.

18F-FPPRGD2 PET/CT in patients with metastatic renal cell cancer.

PURPOSE: The usefulness of positron emission tomography/computed tomography (PET/CT) using (18F)-2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid peptide [PEG3-E{c(RGDyk)}2] (18F-FPPRGD2) in patients with metastatic renal cell cancer (mRCC) has not been evaluated; therefore, we were prompted to conduct this pilot study. METHODS: Seven patients with mRCC were enrolled in this prospective study. 18F-FPPRGD2 and 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/CT images were evaluated in a per-lesion analysis. Maximum standardized uptake value (SUVmax) and tumor-to-background ratio (T/B) were measured for all detected lesions, both before and after starting antiangiogenic therapy. RESULTS: Sixty lesions in total were detected in this cohort. SUVmax from 18F-FPPRGD2 PET/CT was lower than that from 18F-FDG PET/CT (4.4 ± 2.9 vs 7.8 ± 5.6, P < 0.001). Both SUVmax and T/B from 18F-FPPRGD2 PET/CT decreased after starting antiangiogenic therapy (SUVmax, 4.2 ± 3.2 vs 2.6 ± 1.4, P = 0.003; T/B, 3.7 ± 3.2 vs 1.5 ± 0.8, P < 0.001). Average changes in SUVmax and T/B were - 29.3 ± 23.6% and - 48.1 ± 28.3%, respectively. CONCLUSIONS: 18F-FPPRGD2 PET/CT may be an useful tool for monitoring early response to antiangiogenic therapy in patients with mRCC. These preliminary results need to be confirmed in larger cohorts.

Clinical usefulness of 2-deoxy-2-[18F] fluoro-d-glucose-positron emission tomography/computed tomography for assessing early oral squamous cell carcinoma (cT1-2N0M0).

BACKGROUND: Positron emission tomography with 2-deoxy-2-[18F] fluoro-d-glucose integrated with computed tomography (FDG-PET/CT) is a useful method to evaluate patients with oral squamous cell carcinoma (OSCC). However, the prognostic significance of FDG-PET/CT for assessing early OSCC remains unclear. METHODS: Pretreatment FDG-PET/CT of 205 consecutive patients (125 men, 80 women, mean age 59.7 year old) with early OSCC (cT1-2N0M0) between June 2010 and December 2014 were retrospectively analyzed. FDG avidity in primary lesions was assessed by visual interpretation. Thereafter, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured in primary lesions. The relationship between each parameter and recurrence free survival (RFS) was assessed using the log-rank test. The performance of FDG-PET/CT for diagnosing metastatic lesions and synchronous cancer was also assessed. RESULTS: During the follow-up period (mean 32.9 months), 43 patients developed recurrences (21.0%). Patients with visually positive FDG uptake in primary lesions showed significantly shorter RFS than the others (63.0 months vs. 52.9 months, P = 0.005). In those patients, greater SUVmax, MTV, and TLG did not significantly predict shorter RFS. The sensitivity and specificity of FDG-PET/CT for cervical nodal metastases detection were 32.3% and 77.6%, respectively. FDG-PET/CT detected eight synchronous cancers (3.9%) and overlooked six synchronous cancers (2.9%). CONCLUSIONS: Although its utility for detecting cervical nodal metastases and synchronous cancers is limited, FDG-PET/CT is a potentially prognostic indicator in early OSCC.

Clinical characteristics of definite or suspected isolated cardiac sarcoidosis: application of cardiac magnetic resonance imaging and 18F-Fluoro-2-deoxyglucose positron-emission tomography/computerized tomography.

BACKGROUND: Isolated cardiac sarcoidosis (iCS) is difficult to diagnose in patients without histologic evidence of sarcoidosis. We aimed to clarify the clinical characteristics of iCS, including imaging features on cardiac magnetic resonance imaging (MRI) and (18)F-fluoro-2-deoxyglucose positron-emission tomography/computerized tomography (FDG-PET/CT) scans. We also reviewed the therapeutic effect of corticosteroids and determined the long-term prognosis. METHODS AND RESULTS: We retrospectively reviewed 83 consecutive patients with suspicious CS from 1997 to 2013. Systemic sarcoidosis with CS (sCS, n = 30) and iCS (n = 11) were diagnosed according to clinical criteria. In iCS cases, sarcoidosis was not detected in any other organs. The clinical features did not significantly differ between sCS and iCS cases, except for ejection fraction, which was lower in iCS (P = .025). Nine sCS and 4 iCS cases showed late gadolinium enhancement, and the lesions tended to be on the epicardial side (76.9% P = .011) and septal wall (52.9% P < .001). The coefficient of variance for the myocardial standardized uptake value of FDG-PET/CT was higher in sCS (0.32 ± 0.13; n = 19) and iCS (0.32 ± 0.09; n = 7) than in control cases (n = 31; P < .001). B-Type natriuretic peptide level was improved after prednisolone treatment in both groups. Kaplan-Meier curve indicated that prognosis was not different between sCS and iCS cases. CONCLUSIONS: The clinical cardiac characteristics of iCS cases were similar to those of sCS. Cardiac MRI and FDG-PET, noninvasive imaging modalities, could be useful modalities to detect myocardial involvement in the cases with definite or suspected iCS.

Comparison of cerebral blood flow in oral somatic delusion in patients with and without a history of depression: a comparative case series.

BACKGROUND: A significant number of patients visit dental clinics because of unusual oral sensations for which no physical cause can be found. Such patients are recognized as having oral somatic delusion (OSD). OSD may be either primary (monosymptomatic) or secondary to another disease, such as depression or cerebral infarction. Although the presenting complaints of patients with primary and secondary OSD are nearly indistinguishable, symptoms in patients with secondary OSD seem to be resistant to treatment compared with those in patients with primary OSD. Moreover, right dominant cerebral blood flow (CBF) has been reported in patients with primary OSD, but the difference in CBF between patients with primary and secondary OSD remains unclear. The aim of this study was to assess the differences in clinical characteristics and CBF distribution between patients with monosymptomatic OSD (non-depression group) and OSD in conjunction with remitted depression (depression group). METHODS: Participants were 27 patients of a psychosomatic dentistry clinic, all diagnosed with OSD. They were categorized into either the non-depression group (17 patients) or the depression group (10 patients) on the basis of assessments by their personal medical providers. CBF was examined using single-photon emission computed tomography. RESULTS: There was no difference in clinical presentation between the two groups. A significant right dominant asymmetry in the temporal and posterior cerebral regions was observed in both groups. In the central region, a right dominance was seen in the non-depression group, while a left dominance was seen in the depression group. Moreover, the mean regional CBF values for patients in the depression group were significantly lower in several regions (including bilateral callosomarginal, precentral, angular, temporal, posterior cerebral, pericallosal, lenticular nucleus, thalamus, and hippocampus; and right central and cerebellum) than for patients in the non-depression group. CONCLUSION: These results suggest that the temporal and posterior cerebral regions are involved in in the pathophysiology of OSD, regardless of depression history, and that widespread CBF reduction is a characteristic of remitted depression.

Oral Dysesthesia Rating Scale: a tool for assessing psychosomatic symptoms in oral regions.

BACKGROUND: The concept of cenesthopathy was first introduced by Dupré and Camus in 1907 to describe clinically unexplainable bodily sensations mainly attributed to psychiatric pathology. If it occurs in oral regions, it is termed oral cenesthopathy and it has been of special interest to psychiatrists and dentists. While there is no independently defined criteria for this condition, which is classified as either a delusional or a somatoform disorder, clinical practice and research require a standard scale to measure and rate its symptoms. In this study, we included any types of psychosomatic symptoms in oral regions as oral dysesthesia, and developed an Oral Dysesthesia Rating Scale (Oral DRS) and evaluated its validity and reliability as an assessment tool. METHODS: The scale was developed based on literature review and extensive clinical experience. Twelve reviewers assessed relevancy of each item to oral dysesthesia symptoms by 1-4 scoring scale and item content validity index was computed. To evaluate the inter-rater reliability of Oral DRS, pairs of raters administered the scale to 40 randomly selected patients with complaints of oral dysesthesia symptoms and Cohen's weighted kappa coefficient was determined for each item. RESULTS: The scale assesses the severity of feelings of foreign body [A1], exudation [A2], squeezing-pulling [A3], movement [A4], misalignment [A5], pain [A6], and spontaneous thermal sensation or tastes [A7], and the degree of impairment in eating [B1], articulation [B2], work [B3], and social activities [B4] on a scale of 0-5. Items A1, A2, A3, A4, B3, and B4 demonstrated acceptable content validity. Inter-rater reliabilities were good or excellent for all items evaluated. CONCLUSION: The Oral DRS can help define the nosography of clinically unexplainable oral dysesthesia through further case evaluation and clinical research and facilitate devising of treatment modalities.

Can dual-time-point 18F-FDG PET/CT differentiate malignant salivary gland tumors from benign tumors?

OBJECTIVE: The purpose of this study is to evaluate the usefulness of dual-time-point 18F-FDG PET/CT for discriminating between benign and malignant salivary gland tumors. MATERIALS AND METHODS: Dual-time-point FDG PET/CT images of 40 salivary gland tumors (20 benign and 20 malignant) were evaluated retrospectively. The maximum standardized uptake values (SUVmax) in the early and delayed phases and the retention index of each tumor were calculated and compared between benign and malignant tumors by the Mann-Whitney U test. Receiver operating characteristic (ROC) analysis was used to determine the diagnostic accuracy for malignant salivary gland tumors. The correlation between the delayed SUVmax and retention index was analyzed by calculation of the Spearman correlation coefficient. RESULTS: There were no significant differences in the mean early phase SUVmax or mean delayed phase SUVmax between benign and malignant tumors. The mean (±SD) retention index of the malignant tumors was significantly higher than that of the benign tumors (20.1%±10.2% vs 8.5%±12.3%; p=0.006). When the cutoff value of retention index (15.0%) was used, the sensitivity, specificity, and accuracy each was determined to be 75.0%. ROC analysis did not reveal a significant difference in the diagnostic accuracy between the delayed phase SUVmax and retention index (p=0.139). A significant correlation between the delayed phase SUVmax and retention index was observed for the benign salivary gland tumors (r=0.839; p<0.001). CONCLUSION: Dual-time-point FDG PET/CT is not useful for discriminating between benign and malignant salivary gland tumors, because benign tumors also show high FDG uptake, which increases in the delayed phase.

Brain perfusion asymmetry in patients with oral somatic delusions.

Oral cenesthopathy is a somatic delusion or hallucination involving the oral area and is categorized as a delusional disorder, somatic type. The pathophysiology of this intractable condition remains obscure. In this study, we clarified the pathophysiology of oral cenesthopathy by evaluating regional brain perfusion. We performed single photon emission computed tomography (SPECT) using (99m)Tc-ethylcysteinate dimer in 16 subjects (cenesthopathy:control = 8:8). The SPECT images were visually assessed qualitatively, and quantitative analyses were also performed using a three-dimensional stereotactic region-of-interest template. The visual assessment revealed a right > left perfusion asymmetry in broad areas of the brain among the patients. The quantitative analysis confirmed that the regional cerebral blood flow values on the right side were significantly larger than those on the left side for most areas of the brain in the patients. A comparison of the R/(R + L) ratios in both groups confirmed the significant brain perfusion asymmetry between the two sides in the callosomarginal, precentral, and temporal regions in the patients. Qualitative evaluation of the SPECT images revealed right > left brain perfusion asymmetry in broad regions of the brain. Moreover, the quantitative analyses confirmed the perfusion asymmetry between the two sides in the frontal and temporal areas. Those may provide the key for elucidation of the pathophysiology of oral cenesthopathy.

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.

Prevalence of esophageal cancer during the pretreatment of hypopharyngeal cancer patients: routinely performed esophagogastroduodenoscopy and FDG-PET/CT findings.

BACKGROUND: The prevalence of esophageal cancer accompanied by hypopharyngeal cancer (HPC) is high and increasing rapidly in Asia. The purpose of this prospective study was to evaluate the prevalence of esophageal cancer during the pretreatment of HPC patients who were routinely examined using esophagogastroduodenoscopy (EGD) and 18F-fluorodeoxyglucose/computed tomography (FDG-PET/CT) and to discuss the utility of these examinations. MATERIAL AND METHODS: Between September 2005 and September 2010, 33 patients with newly diagnosed HPC (all with squamous cell carcinoma) underwent EGD (after a conventional endoscopy, iodine staining was performed) and FDG-PET/CT examinations. We evaluated the prevalence of esophageal cancer among HPC patients according to the EGD findings and determined the sensitivity of FDG-PET/CT for the detection of esophageal primary tumors for each clinical T classification. RESULTS: In 17 of the 33 patients (51.5%), 29 biopsy-proven esophageal squamous cell carcinomas were diagnosed using EGD. In eight of the 17 (47.1%) patients, two or more esophageal cancer lesions were diagnosed. Twenty-four of the 29 (82.8%) lesions were superficial esophageal cancers, and the remaining five (17.2%) lesions were advanced esophageal cancers. In six of the 29 (20.7%) esophageal cancer lesions that were detected using FDG-PET/CT, only one of the 29 (3.4%) lesions was evaluated as being equivocal; the remaining 22 (75.9%) lesions were not detected. The distribution of the clinical T classifications detected using FDG-PET/CT was as follows: T1a, 0/21 (0%); T1b, 1/3 (33%); and T3, 5/5 (100%). CONCLUSIONS: The prevalence of esophageal cancer during the pretreatment of HPC patients was 51.5%; this prevalence was higher than that in previous reports. We believe that the increasing proportion of superficial lesions (82.8%) detected using iodine staining and EGD may have led to the relatively high prevalence. FDG-PET/CT detected only 20.7% of the esophageal cancers, although FDG-PET/CT is capable of detecting unexpected primary malignant tumors other than esophageal cancer.

Improvement of asymmetrical temporal blood flow in refractory oral somatic delusion after successful electroconvulsive therapy.

Oral cenesthopathy is a somatic delusion in the oral area and categorized as delusional disorder, somatic type. Patients experience unusual and annoying sensations in the mouth such as pulling on the teeth, moving teeth, overly secreting mucus, tingling and pain, and so on, without a somatic base. The condition is usually treatment-resistant and impairs patients' quality of life. We report a case of oral cenesthopathy successfully treated with the modified electroconvulsive therapy, who demonstrated altered regional cerebral blood flow before and after the treatment detected by single-photon emission computed tomography.

Recent topics of the clinical utility of PET/MRI in oncology and neuroscience.

Since the inline positron emission tomography (PET)/magnetic resonance imaging (MRI) system appeared in clinical, more than a decade has passed. In this article, we have reviewed recently-published articles about PET/MRI. There have been articles about staging in rectal and breast cancers by PET/MRI using fluorodeoxyglucose (FDG) with higher diagnostic performance in oncology. Assessing possible metastatic bone lesions is considered a proper target by FDG PET/MRI. Other than FDG, PET/MRI with prostate specific membrane antigen (PSMA)-targeted tracers or fibroblast activation protein inhibitor have been reported. Especially, PSMA PET/MRI has been reported to be a promising tool for determining appropriate sites in biopsy. Independent of tracers, the clinical application of artificial intelligence (AI) for images obtained by PET/MRI is one of the current topics in this field, suggesting clinical usefulness for differentiating breast lesions or grading prostate cancer. In addition, AI has been reported to be helpful for noise reduction for reconstructing images, which would be promising for reducing radiation exposure. Furthermore, PET/MRI has a clinical role in neuroscience, including localization of the epileptogenic zone. PET/MRI with new PET tracers could be useful for differentiation among neurological disorders. Clinical applications of integrated PET/MRI in various fields are expected to be reported in the future.

The standardized uptake value calculated from 111In-ibritumomab tiuxetan single-photon emission computed tomography/computed tomography is a useful predictor of the clinical response in patients treated by 90Y- ibritumomab tiuxetan therapy.

90Y-Ibritumomab tiuxetan (IT) therapy is a radioimmunotherapy for indolent B-cell lymphoma. Several predictors of insufficient therapeutic effects have been reported. We performed a retrospective study at a single institute to investigate whether 111In SPECT/CT can predict the therapeutic effects and grade of cytopenia due to 90Y-IT therapy. We enrolled 16 consecutive patients who underwent 90Y-IT therapy, including 15 who underwent 111In-IT SPECT/CT. After 90Y-IT therapy, there were 4 patients in complete remission in whom the lesion SUVmax on 111In-IT SPECT/CT and soluble IL-2 receptor were significantly lower than those of the other patients (P<0.05 and P<0.05, respectively). Based on the log-rank test of factors associated with the progression-free survival (PFS), ≥2 previous treatment regimens was significantly associated with a poor prognosis (P<0.05). The SUV on 111In-IT SPECT/CT may be a good predictor of the clinical response to 90Y-IT therapy.

Acquired Hemophilia A Presenting with Infectious Aortic Aneurysms Due to an Underlying Helicobacter cinaedi Infection.

Acquired hemophilia A (AHA) is a bleeding disorder caused by the acquired appearance of inhibitor for factor VIII. Approximately half of all patients with AHA have some type of underlying disease. We herein report the case of a 72-year-old Japanese man with AHA who presented with infectious aortic aneurysms due to an underlying Helicobacter cinaedi infection. To our knowledge, this is the first report of AHA triggered by a bacterial infection; however, there may be similar cases that remain undiagnosed because this pathogen is difficult to identify. Clinicians should consider the possibility of H. cinaedi as a causative pathogen in patients presenting with a fever of unknown origin.

Results of a Prospective Trial to Compare 68Ga-DOTA-TATE with SiPM-Based PET/CT vs. Conventional PET/CT in Patients with Neuroendocrine Tumors.

We prospectively enrolled patients with neuroendocrine tumors (NETs). They underwent a single 68Ga-DOTA-TATE injection followed by dual imaging and were randomly scanned using first either the conventional or the silicon photomultiplier (SiPM) positron emission tomography/computed tomography (PET/CT), followed by imaging using the other system. A total of 94 patients, 44 men and 50 women, between 35 and 91 years old (mean ± SD: 63 ± 11.2), were enrolled. Fifty-two out of ninety-four participants underwent SiPM PET/CT first and a total of 162 lesions were detected using both scanners. Forty-two out of ninety-four participants underwent conventional PET/CT first and a total of 108 lesions were detected using both scanners. Regardless of whether SiPM-based PET/CT was used first or second, maximum standardized uptake value (SUVmax) of lesions measured on SiPM was on average 20% higher when comparing two scanners with all enrolled patients, and the difference was statistically significant. SiPM-based PET/CT detected 19 more lesions in 13 patients compared with conventional PET/CT. No lesions were only identified by conventional PET/CT. In conclusion, we observed higher SUVmax for lesions measured from SiPM PET/CT compared with conventional PET/CT regardless of the order of the scans. SiPM PET/CT allowed for identification of more lesions than conventional PET/CT. While delayed imaging can lead to higher SUVmax in cancer lesions, in the series of lesions identified when SiPM PET/CT was used first, this was not the case; therefore, the data suggest superior performance of the SiPM PET/CT scanner in visualizing and quantifying lesions.

18F-FDG PET/CT for monitoring anti-PD-1 therapy in patients with non-small cell lung cancer using SUV harmonization of results obtained with various types of PET/CT scanners used at different centers.

OBJECTIVE: The prognostic value of treatment response in patients with non-small cell lung cancer (NSCLC) treated with immune-checkpoint inhibitors (ICIs) shown by 18F-fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) results obtained with multiple types of PET scanners using standardized uptake value (SUV) harmonization was evaluated. METHODS: Fifty-eight patients treated with ICIs who underwent 18F-FDG PET/CT examinations with nine types of PET scanners at six hospitals were enrolled. SUV harmonization of multiple PET scanner results was performed using the dedicated software packages "RAVAT" and "RC Tool for Harmonization". Tumor response was assessed by change in sum of harmonized SUVmax, according to the European Organization for Research and Treatment of Cancer (EORTC5) or the SUV of up to five lesions normalized to lean body mass, according to the PET Response Criteria in Solid Tumors (PERCIST5) and immunotherapy-modified PERCIST (imPERCIST5) criteria. The correlation between tumor response according to those three definitions and overall survival (OS) was evaluated and compared to known prognostic factors. RESULTS: One-year OS in responders and non-responders for harmonized EROTC5 was 86 and 32%, for harmonized PERCIST5 was 86 and 32%, and for harmonized imPERCIST5 was 80 and 30%, respectively (each p = 0.001). Univariate analysis showed that all response criteria remained as prognostic factors. However, there was an overlap for the categories stable metabolic disease (SMD) and progression metabolic disease (PMD) in survival curves using the PET treatment response criteria. CONCLUSION: In patients with NSCLC treated with ICIs, tumor response based on the harmonized response criteria was associated with OS. PET response criteria using harmonized metabolic parameters may be difficult to routinely employ in daily practice due to overlapping SMD and PMD, although may have a supporting role for determining prognosis.

Usefulness of semi-automatic harmonization strategy of standardized uptake values for multicenter PET studies.

This study assessed the possibility of semi-automatic harmonization of standardized uptake values (SUVs) in multicenter studies. Phantom data were acquired using 16 PET/CT scanners (including 3 PET/CT scanners with a silicon photomultiplier detector). PET images obtained using 30-min/bed scans for optimum harmonization filter calculations and using 90-180-s/bed scans for SUV validation under clinical conditions were obtained. Time of flight and a reconstruction method with point-spread function correction were allowed. The optimal full width at half maximum of the 3D-Gaussian filter that minimizes the root mean square error with the median value of the JSNM harmonization range was calculated semi-automatically. The SUVmax and the SUVpeak of the hot spheres were measured, and the inter-scanner coefficient of variation (COV) was calculated before and after harmonization. The harmonization filter was applied to 11 of the 15 PET/CT scanners in which the SUV calibration accuracy had been verified, but not in the remaining 4 scanners. Under noiseless conditions before harmonization, the inter-scanner COVs of the SUVmax and the SUVpeak were as high as 21.57% and 12.20%, respectively, decreasing to 8.79% and 5.73% after harmonization, respectively. Harmonization brought the SUVmax of all the hot spheres to within the harmonization range. Even under clinical conditions affected by image noise, the inter-scanner COVs for the SUVmax and SUVpeak were as high as 8.83% and 5.18% after harmonization, respectively. By applying an optimal harmonization filter that is calculated semi-automatically, the harmonization of SUVs according to the JSNM strategy is possible in multicenter studies, thereby reducing inter-scanner COVs.

A pilot study on EORTC or PERCIST for the prediction of progression-free survival with nivolumab therapy in advanced or metastatic gastric cancers: A STROBE-compliant article.

ABSTRACT: Recent breakthrough results from immune checkpoint inhibitors (ICIs) have paved the way to a new era of cancer immunotherapy, and have thus led to a paradigm shift of cancer treatment. In particular, inhibition of the antiprogrammed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis with ICI, including nivolumab and pembrolizumab, has been emerging as a novel treatment strategy for advanced gastric cancers. An accurate noninvasive assessment of the response to ICI is important for the management of patients with advanced or metastatic gastric cancer.To examine whether the European Organization for Research and Treatment of Cancer (EORTC) and PET Response Criteria in Solid Tumors (PERCIST) are valuable for predicting progression-free survival (PFS) in patients with advanced or metastatic gastric cancers treated with nivolumab.Six patients with advanced or metastatic gastric cancers who underwent 18F-FDG-PET/computed tomography (CT) scans before, and from 2 to 6 months after initiation of nivolumab therapy between September 2017 and August 2019, were evaluated retrospectively. The correlation between tumor progression and EORTC or PERCIST was assessed with the Fisher's exact test. The PFS was assessed with the Kaplan-Meier method.Two patients were alive without progression, and the remaining 4 patients exhibited tumor progression. Two patients without progression were classified as partial metabolic response (PMR) patients based on EORTC or PERCIST, while the other 4 patients with progression were classified as progressive metabolic disease (PMD) patients based on EORTC (P = .067), or stable metabolic disease (SMD) patients, or PMD patients based on PERCIST (P = .067).The mean and median PFS of all patients was 12.7 months (95% confidence interval [CI], 4.9-20.4 months) and 5 months (95%CI, 4.0-11.0 months). Two EORTC or PERCIST PMR patients showed significantly longer median PFS compared with 4 non-PMR patients (not reached vs 4.0 months, P = .044). Three PERCIST PMR or SMD patients also showed significantly longer median PFS compared with 3 PMD patients (not reached vs 4.0 months, P = .022). These results suggest that EORTC or PERCIST has the potential to predict PFS of patients with advanced or metastatic gastric cancers treated by nivolumab and further studies are needed to determine its value in larger study populations.