[Validation of Quantitative Accuracy and Variability in 177Lu Imaging Using Monte Carlo Simulation].

PURPOSE: To predict side effects and optimize injection doses in the dosimetry of 177Lu imaging, highly accurate quantitative SPECT images are required. Monte Carlo simulations were performed to verify the accuracy and variability of quantitative values for 177Lu imaging under various imaging conditions. METHODS: SPECT data of NEMA body phantom were assumed to simulate intrahepatic tumors 6 h after administration of 7.4 GBq of 177Lu-Dotatate. SPECT data were acquired using the SIMIND program with different combinations of collimators and energy windows. For variability evaluation, 30 SPECT images with Poisson noise were generated for each acquisition time. The relative error was evaluated for accuracy evaluation, and the coefficient of variation was estimated for variability evaluation. RESULTS: The accuracy of BG quantification was less than 10% relative error. The accuracy of hot sphere quantification was highest with the combination of MEGP and an energy window of 208 keV±10%. However, the accuracy of hot sphere quantification decreased significantly with decreasing hot sphere diameter. Variability varied with imaging conditions and improved with longer acquisition time. CONCLUSION: Monte Carlo simulations revealed the accuracy and variability of quantitative values for each SPECT imaging condition for 177Lu imaging.

Correction: Investigation of the new non-invasive semi-quantitative method of 123I-IMP pediatric cerebral perfusion SPECT.

[This corrects the article DOI: 10.1371/journal.pone.0241987.].

Evaluation of two-dimensional total bone uptake (2D-TBU) and bone scan index (BSI) extracted from active bone metastatic burden on the bone scintigraphy in patients with radium-223 treatment.

OBJECTIVE: Radium-223 is a first alpha-emitting radionuclide treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with bone metastases. Although the spread-based bone scan index (BSI) and novel index of the intensity-based two-dimensional total bone uptake (2D-TBU) from bone scintigraphy may provide useful input in radium-223 treatment, they have not been evaluated in detail yet. This study aimed to fill this gap by evaluating BSI and 2D-TBU in patients treated with radium-223. METHODS: Twenty-seven Japanese patients with mCRPC treated with radium-223 were retrospectively analyzed. The patients were evaluated via blood tests and bone scans at baseline and 3 cycles intervals of treatment. BSI and 2D-TBU were analyzed via VSBONE BSI in terms of correlations, response to radium-223 treatment, association with treatment completion, and the Kaplan-Meier survival analysis was performed. RESULTS: Nineteen patients (70.4%) completed six cycles of radium-223 treatment, whereas eight patients (29.6%) did not complete the treatment regimen. A significant difference in baseline BSI and 2D-TBU was observed between these groups of patients. Both BSI and 2D-TBU were highly correlated (r = 0.96, p < 0.001). Univariate analysis showed an association between radium-223 completion in median BSI and 2D-TBU values (p = 0.015) and completion percentage differences (91.7% vs. 45.5%; p = 0.027). The Kaplan-Meier product limit estimator showed that the median overall survival was 25.2 months (95% CI 14.0-33.6 months) in the completion group and 7.5 months (95% CI 3.3-14.2 months) in the without completion group (p < 0.001). The overall survival based on median cutoff levels showed a significant difference in 2D-TBU (p = 0.007), but not in BSI (p = 0.15). CONCLUSIONS: The 2D-TBU may offer advantages over BSI in classifying patients towards radium-223 treatment based on the degree of progression of bone metastases. This study supports the importance of preliminary assessment of bone metastasis status using BSI and 2D-TBU extracted from VSBONE BSI for radium-223 treatment decisions.

Prognostic role of preoperative fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography with an image-based harmonization technique: A multicenter retrospective study.

Objectives: Despite the prognostic impacts of preoperative fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography examination, fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography-based prognosis prediction has not been used clinically because of the disparity in data between institutions. By applying an image-based harmonized approach, we evaluated the prognostic roles of fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters in clinical stage I non-small cell lung cancer. Methods: We retrospectively examined 495 patients with clinical stage I non-small cell lung cancer who underwent fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography examinations before pulmonary resection between 2013 and 2014 at 4 institutions. Three different harmonization techniques were applied, and an image-based harmonization, which showed the best-fit results, was used in the further analyses to evaluate the prognostic roles of fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters. Results: Cutoff values of image-based harmonized fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters, maximum standardized uptake, metabolic tumor volume, and total lesion glycolysis were determined using receiver operating characteristic curves that distinguish pathologic high invasiveness of tumors. Among these parameters, only the maximum standardized uptake was an independent prognostic factor in recurrence-free and overall survivals in univariate and multivariate analyses. High image-based maximum standardized uptake value was associated with squamous histology or lung adenocarcinomas with higher pathologic grades. In subgroup analyses defined by ground-glass opacity status and histology or by clinical stages, the prognostic impact of image-based maximum standardized uptake value was always the highest compared with other fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography parameters. Conclusions: The image-based fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography harmonization was the best fit, and the image-based maximum standardized uptake was the most important prognostic marker in all patients and in subgroups defined by ground-glass opacity status and histology in surgically resected clinical stage I non-small cell lung cancers.

Prognostic significance of the harmonized maximum standardized uptake value of 18F-FDG-PET/CT in patients with resectable oral tongue squamous cell carcinoma: a multicenter study.

OBJECTIVES: To investigate the usefulness of harmonized 18F-FDG-PET/CT parameters for predicting the postoperative recurrence and prognosis of oral tongue squamous cell carcinoma (OTSCC). METHODS: We retrospectively analyzed the cases of 107 OTSCC patients who underwent surgical resection at four institutions in Japan in 2010-2016 and evaluated the harmonized PET parameters of the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the primary tumor as the pSUVmax, pMTV, and pTLG. For lymph node metastasis, we used harmonized PET parameters of nodal-SUVmax, nodal-total MTV (tMTV), and nodal-total TLG (tTLG). The associations between the harmonized PET parameters and the patients' relapse-free survival (RFS) and overall survival (OS) were evaluated by the Kaplan-Meier method and Cox proportional hazard regression analysis for model 1 (preoperative stage) and model 2 (preoperative + postoperative stages). RESULTS: The harmonized SUVmax values were significantly lower than those before harmonization (p=0.012). The pSUVmax was revealed as a significant preoperative risk factor for RFS and OS. Nodal-SUVmax, nodal-tMTV, and nodal-tTLG were significant preoperative risk factors for OS. The combination of pSUVmax + nodal-SUVmax significantly stratified the patients into a low-risk group (pSUVmax <3.97 + nodal-SUVmax <2.85 or ≥2.85) and a high-risk group (pSUVmax ≥3.97 + nodal-SUVmax <2.85 or pSUVmax ≥3.97 + nodal-SUVmax ≥2.85) for recurrence and prognosis (RFS: p=0.001; OS: p<0.001). CONCLUSIONS: The harmonized pSUVmax is a significant prognostic factor for the survival of OTSCC patients. The combination of pSUVmax and nodal-SUVmax identified OTSCC patients at high risk for recurrence and poor prognosis at the preoperative stage.

Reproducibility of the principal component analysis (PCA)-based data-driven respiratory gating on texture features in non-small cell lung cancer patients with 18 F-FDG PET/CT.

OBJECTIVE: Texture analysis is one of the lung cancer countermeasures in the field of radiomics. Even though image quality affects texture features, the reproducibility of principal component analysis (PCA)-based data-driven respiratory gating (DDG) on texture features remains poorly understood. Hence, this study aimed to clarify the reproducibility of PCA-based DDG on texture features in non-small cell lung cancer (NSCLC) patients with 18 F-Fluorodeoxyglucose (18 F-FDG) Positron emission tomography/computed tomography (PET/CT). METHODS: Twenty patients with NSCLC who underwent 18 F-FDG PET/CT in routine clinical practice were retrospectively analyzed. Each patient's PET data were reconstructed in two PET groups of no gating (NG-PET) and PCA-based DDG gating (DDG-PET). Forty-six image features were analyzed using LIFEx software. Reproducibility was evaluated using Lin's concordance correlation coefficient ( ρ c ${\rho _c}$ ) and percentage difference (%Diff). Non-reproducibility was defined as having unacceptable strength ( ρ c $({\rho _c}$  < 0.8) and a %Diff of >10%. NG-PET and DDG-PET were compared using the Wilcoxon signed-rank test. RESULTS: A total of 3/46 (6.5%) image features had unacceptable strength, and 9/46 (19.6%) image features had a %Diff of >10%. Significant differences between the NG-PET and DDG-PET groups were confirmed in only 4/46 (8.7%) of the high %Diff image features. CONCLUSION: Although the DDG application affected several texture features, most image features had adequate reproducibility. PCA-based DDG-PET can be routinely used as interchangeable images for texture feature extraction from NSCLC patients.

A review of harmonization strategies for quantitative PET.

PET can reveal in vivo biological processes at the molecular level. PET-derived quantitative values have been used as a surrogate marker for clinical decision-making in numerous clinical studies and trials. However, quantitative values in PET are variable depending on technical, biological, and physical factors. The variability may have a significant impact on a study outcome. Appropriate scanner calibration and quality control, standardization of imaging protocols, and any necessary harmonization strategies are essential to make use of PET as a biomarker with low bias and variability. This review summarizes benefits, limitations, and remaining challenges for harmonization of quantitative PET, including whole-body PET in oncology, brain PET in neurology, PET/MR, and non-18F PET imaging. This review is expected to facilitate harmonization of quantitative PET and to promote the contribution of PET-derived biomarkers to research and development in medicine.

[Three-dimensional Quantitative Evaluation Method in 123I-MIBG Myocardial SPECT-CT].

PURPOSE: To distinguish neurodegenerative diseases using 123I-metaiodobenzylguanidine (MIBG). This study proposes a method to evaluate myocardial standardized uptake value (SUV) and assess its accuracy. METHODS: We created a 17-segment polar map of the myocardial region from single-photon emission computed tomography-computed tomography (SPECT-CT) images using a cardioliver phantom simulating the standard uptake of MIBG. We clarified the optimal reconstruction conditions with good repeatability and accuracy of quantitative values and compared them with the H/M ratio. Myocardial SUVs were evaluated from eight normal cases using our method established from the phantom experiment and compared with the H/M ratio. RESULTS: The optimal numbers of iterations and subsets in OSEM reconstruction were both 10. The optimal full width at half maximum (FWHM) value of the Gaussian filter was 4 pixels. The RCs and %CV of (1) maximum SUVmax (MaxSUVmax) and (2) average SUVmax (AveSUVmax) were (1) 36.5% and 4.99%, and (2) 33.6% and 4.84%, respectively. The RC and %CV of the H/M ratio was 15.0% and 1.50%, respectively. In clinical cases, average MaxSUVmax and AveSUVmax were 8.27 and 7.58, respectively. CONCLUSION: Myocardial SUV can provide quantitative values slightly closer to theoretical values than the H/M ratios. Besides, using the optimal reconstruction parameters makes it feasible to quantitatively assess myocardial uptake with good repeatability.

Evaluation of data-driven respiratory gating for subcentimeter lesions using digital PET/CT system and three-axis motion phantom.

Introduction.The application of data-driven respiratory gating (DDG) for subcentimeter lesions with respiratory movement remains poorly understood. Hence, this study aimed to clarify DDG application for subcentimeter lesions and the ability of digital Positron emission tomography/computed tomography (PET/CT) system combined with DDG to detect these lesions under three-axis respiration.Methods.Discovery MI PET/CT system and National Electrical Manufacturers Association (NEMA) body phantom with Micro Hollow Sphere (4, 5, 6, 8, 10, and 13 mm) were used. The NEMA phantom was filled with18F-FDG solutions of 42.4 and 5.3 kBq/ml for each hot sphere and background region. The 3.6 s cycles of three-axis respiratory motion were reproduced using the motion platform UniTraQ. The PET data acquisition was performed in stationary and respiratory-moving states. The data were reconstructed in three PET groups: stationary (NM-PET), no gating with respiratory movement (NG-PET), and DDG gating with respiratory movement (DDG-PET) groups. For image quality, percent contrast (QH); maximum, peak, and mean standardized uptake value (SUV); background region; and detectability index (DI) were evaluated in each PET group. Visual assessment was also conducted.Results.The groups with respiratory movement had deteriorated QHand SUVs compared with NM-PET. Compared with NG-PET, DDG-PET has significantly improved QHand SUVs in spheres above 6 mm. The background region showed no significant difference between groups. The SUVmax, SUVpeak, and QHvalues of 8 mm sphere were highest in NM-PET, followed by DDG-PET and NG-PET. In visual assessment, the spheres above 6 mm were detected in all PET groups. DDG application did not detect new lesions, but it increased DI and visual score.Conclusions. The application of principal component analysis (PCA)-based DDG algorithm improves both image quality and quantitative SUVs in subcentimeter lesions measuring above 6 mm. Although DDG application cannot detect new subcentimeter lesions, it increases the visual indices.

Dopamine dysfunction in depression: application of texture analysis to dopamine transporter single-photon emission computed tomography imaging.

Dopamine dysfunction has been associated with depression. However, results of recent neuroimaging studies on dopamine transporter (DAT), which reflect the function of the dopaminergic system, are inconclusive. The aim of this study was to apply texture analysis, a novel method to extract information about the textural properties of images (e.g., coarseness), to single-photon emission computed tomography (SPECT) imaging in depression. We performed SPECT using 123I-ioflupane to measure DAT binding in 150 patients with major depressive disorder (N = 112) and bipolar disorder (N = 38). The texture features of DAT binding in subregions of the striatum were calculated. We evaluated the relationship between the texture feature values (coarseness, contrast, and busyness) and severity of depression, and then examined the effects of medication and diagnosis on such relationship. Furthermore, using the data from 40 healthy subjects, we examined the effects of age and sex on the texture feature values. The degree of busyness of the limbic region in the left striatum linked to the severity of depression (p = 0.0025). The post-hoc analysis revealed that this texture feature value was significantly higher in both the severe and non-severe depression groups than in the remission group (p = 0.001 and p = 0.028, respectively). This finding remained consistent after considering the effect of medication. The effects of age and sex in healthy individuals were not evident in this texture feature value. Our findings imply that the application of texture analysis to DAT-SPECT may provide a state-marker of depression.

Impact of patient body habitus on image quality and quantitative value in bone SPECT/CT.

OBJECTIVE: The first edition of guidelines for standardization of bone single photon emission computed tomography (SPECT) imaging was published in 2017, and the optimization and standardization are widely promoted. To the purpose, clarification of the factors related to image quality and quantitative values and their influence are required. The present study aimed to clarify and optimize the influence of patient body habitus on image quality and quantitative values in bone SPECT/CT. METHODS: National Electrical Manufacturers Association body phantom (S-size) and custom-made large body phantoms (M-size and L-size) that simulate the abdomens of Japanese patients weighing 60, 80, and 100 kg, were used. Each phantom was filled with 99mTc-solutions of 108 and 18 kBq/mL for the hot spheres and background, respectively. Dynamic SPECT acquisition was performed for 6000 s (150 s /rotation × 40 rotation). The data were divided into six projection data and reconstructed each acquisition time (150, 300, 450, 600, 750, 900 s, and single projection 6000 s). Image quality was evaluated for contrast (QH, 17 mm), background noise (NB, 17 mm), contrast-to-noise ratio (CNR), maximum standardized uptake value (SUVmax, 17 mm), and visual assessment for a 17 mm hot sphere. RESULTS: Image quality in the 300 s acquisition showed that values of QH, 17 mm, CNR, and SUVmax, 17 mm decreased (-16.7%, -11.8%, and -11.3%) for M-size and (-28.2%, -30.1%, and -21.7%) for L-size compared with S-size, respectively. No significant difference was observed in NB, 17 mm values. M-size and L-size required 1.2 and 2.3 times longer acquisition, to achieve same CNR as S-size. In visual assessment, 17 mm hot sphere could not be detected only in the L-size. When the Japanese bone SPECT guidelines criteria were applied in 600 s, the sphere could be detected between all phantoms. CONCLUSIONS: Patient body habitus significantly affects image quality and decreases the quantitative value in bone SPECT/CT. For the optimization, extend acquisition time according to the patient body habitus is effective for image quality. And for the standardization, it is important to achieve imaging conditions that meet the Japanese bone SPECT guidelines criteria to ensure adequate detectability.

New standards for phantom image quality and SUV harmonization range for multicenter oncology PET studies.

Not only visual interpretation for lesion detection, staging, and characterization, but also quantitative treatment response assessment are key roles for 18F-FDG PET in oncology. In multicenter oncology PET studies, image quality standardization and SUV harmonization are essential to obtain reliable study outcomes. Standards for image quality and SUV harmonization range should be regularly updated according to progress in scanner performance. Accordingly, the first aim of this study was to propose new image quality reference levels to ensure small lesion detectability. The second aim was to propose a new SUV harmonization range and an image noise criterion to minimize the inter-scanner and intra-scanner SUV variabilities. We collected a total of 37 patterns of images from 23 recent PET/CT scanner models using the NEMA NU2 image quality phantom. PET images with various acquisition durations of 30-300 s and 1800 s were analyzed visually and quantitatively to derive visual detectability scores of the 10-mm-diameter hot sphere, noise-equivalent count (NECphantom), 10-mm sphere contrast (QH,10 mm), background variability (N10 mm), contrast-to-noise ratio (QH,10 mm/N10 mm), image noise level (CVBG), and SUVmax and SUVpeak for hot spheres (10-37 mm diameters). We calculated a reference level for each image quality metric, so that the 10-mm sphere can be visually detected. The SUV harmonization range and the image noise criterion were proposed with consideration of overshoot due to point-spread function (PSF) reconstruction. We proposed image quality reference levels as follows: QH,10 mm/N10 mm ≥ 2.5 and CVBG ≤ 14.1%. The 10th-90th percentiles in the SUV distributions were defined as the new SUV harmonization range. CVBG ≤ 10% was proposed as the image noise criterion, because the intra-scanner SUV variability significantly depended on CVBG. We proposed new image quality reference levels to ensure small lesion detectability. A new SUV harmonization range (in which PSF reconstruction is applicable) and the image noise criterion were also proposed for minimizing the SUV variabilities. Our proposed new standards will facilitate image quality standardization and SUV harmonization of multicenter oncology PET studies. The reliability of multicenter oncology PET studies will be improved by satisfying the new standards.

Tumor response evaluation in patients with malignant melanoma undergoing immune checkpoint inhibitor therapy and prognosis prediction using 18F-FDG PET/CT: multicenter study for comparison of EORTC, PERCIST, and imPERCIST.

OBJECTIVE: In malignant melanoma patients treated with immune checkpoint inhibitor (ICI) therapy, three different FDG-PET criteria, European Organization for Research and Treatment of Cancer (EORTC), PET Response Criteria in Solid Tumors (PERCIST), immunotherapy-modified PERCIST (imPERCIST), were compared regarding response evaluation and prognosis prediction using standardized uptake value (SUV) harmonization of results obtained with various PET/CT scanners installed at different centers. MATERIALS AND METHODS: Malignant melanoma patients (n = 27) underwent FDG-PET/CT examinations before and again 3 to 9 months after therapy initiation (nivolumab, n = 21; pembrolizumab, n = 6) with different PET scanners at five hospitals. EORTC, PERCIST, and imPERCIST criteria were used to evaluate therapeutic response, then concordance of the results was assessed using Cohen's κ coefficient. Log-rank and Cox methods were employed to determine progression-free (PFS) and overall (OS) survival. RESULTS: Complete metabolic response (CMR)/partial metabolic response (PMR)/stable metabolic disease (SMD)/progressive metabolic disease (PMD) with harmonized EORTC, PERCIST, and imPERCIST was seen in 3/5/4/15, 4/5/3/15, and 4/5/5/13 patients, respectively. Nearly perfect concordance between each pair of criteria was noted (κ = 0.939-0.972). Twenty patients showed progression and 14 died from malignant melanoma after a median 19.2 months. Responders (CMR/PMR) showed significantly longer PFS and OS than non-responders (SMD/PMD) (harmonized EORTC: p < 0.0001 and p = 0.011; harmonized PERCIST: p < 0.0001 and p = 0.0012; harmonized imPERCIST: p < 0.0001 and p = 0.0012, respectively). CONCLUSIONS: All harmonized FDG-PET criteria (EORTC, PERCIST, imPERCIST) showed accuracy for response evaluation of ICI therapy and prediction of malignant melanoma patient prognosis. Additional studies to determine their value in larger study populations will be necessary.

Image quality and quantification accuracy dependence on patient body mass in 89Zr PET/CT imaging.

BACKGROUND: This study was conducted to clarify how patient body mass affects the image quality and quantification accuracy of images obtained using 89Zr PET/CT. 89Zr PET/CT images from time-of-flight (TOF) PET/CT and semiconductor (SC) PET/CT were obtained using three types (M, L, LL; corresponding to increasing patient body weight) of custom-made body phantoms designed similarly to the National Electrical Manufacturers Association (NEMA) IEC body phantom. The phantom data were analyzed visually and quantitatively to derive image quality metrics, namely detectability of the 10-mm-diameter hot sphere, percent contrast for the 10-mm-diameter hot sphere (QH,10 mm), percent background variability (N10mm), contrast-to-noise ratio (QH,10 mm/N10mm), and coefficient of variation of the background area (CVBG). RESULTS: Visual assessment revealed that all the 10-mm-diameter hot spheres of the three types of phantoms were identifiable on both SC and TOF PET/CT images. The N10mm and CVBG values were within the proposed reference levels, and decreased with acquisition duration for both PET/CT types. At 10-min acquisition, the QH,10 mm/N10mm of SC PET/CT was greater than the proposed reference level in all phantoms. However, the QH,10 mm/N10mm of TOF PET/CT was greater than the proposed reference level in M-type phantom alone. All the SUVBG values were within 1.00 ± 0.05 for both PET/CT types. CONCLUSIONS: This study showed that the image quality and quantification accuracy depend on the patient's body mass, suggesting that acquisition time on 89Zr PET/CT should be changed according to the patient's body mass.

Extraction of metastasis hotspots in a whole-body bone scintigram based on bilateral asymmetry.

PURPOSE: A hotspot of bone metastatic lesion in a whole-body bone scintigram is often observed as left-right asymmetry. The purpose of this study is to present a network to evaluate bilateral difference of a whole-body bone scintigram, and to subsequently integrate it with our previous network that extracts the hotspot from a pair of anterior and posterior images. METHODS: Input of the proposed network is a pair of scintigrams that are the original one and the flipped version with respect to body axis. The paired scintigrams are processed by a butterfly-type network (BtrflyNet). Subsequently, the output of the network is combined with the output of another BtrflyNet for a pair of anterior and posterior scintigrams by employing a convolutional layer optimized using training images. RESULTS: We evaluated the performance of the combined networks, which comprised two BtrflyNets followed by a convolutional layer for integration, in terms of accuracy of hotspot extraction using 1330 bone scintigrams of 665 patients with prostate cancer. A threefold cross-validation experiment showed that the number of false positive regions was reduced from 4.30 to 2.13 for anterior and 4.71 to 2.62 for posterior scintigrams on average compared with our previous model. CONCLUSIONS: This study presented a network for hotspot extraction of bone metastatic lesion that evaluates bilateral difference of a whole-body bone scintigram. When combining the network with the previous network that extracts the hotspot from a pair of anterior and posterior scintigrams, the false positives were reduced by nearly half compared to our previous model.

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.

[Report in 2018 April ～ 2020 March].

To establish a feasible and practical methodology for harmonization of FDG-PET, we have investigated quantitative physical performance of recent clinical PET scanners (23 scanners) using the NEMA image quality phantom. Compared with the previous phantom data (13 scanners) acquired in the early 2000s, the current phantom data showed better contrasts of small spheres even with a smaller number of coincidence counts. This result suggests that clinical PET image quality and small lesion detectability might have been significantly improved in the past 10 years. Based on the data acquired in this working group, we are planning to update the standard phantom test methodology and harmonizing criteria for FDG-PET.

Harmonized pretreatment quantitative volume-based FDG-PET/CT parameters for prognosis of stage I-III breast cancer: Multicenter study.

OBJECTIVES: This study investigated harmonized pretreatment volume-based quantitative FDG-PET/CT parameters in breast cancer patients for prognostic value. RESULTS: During a median overall follow-up period of 5.3 years, 91 patients had recurrence and 40 died. Multivariate analysis of ER-positive/HER2-negative patients showed high maximum standardized uptake value (SUVmax) (p = 0.018), high total lesion glycolysis (TLG) (p = 0.010), and clinical N-classification (p = 0.0027) as independent negative predictors of RFS, while high maximum SUVmax (p = 0.037), advanced clinical T-classification (p = 0.030), and advanced TNM stage (p = 0.0067) were independent negative predictors of OS. For recurrence and death in HER2-positive patients, high total TLG (p = 0.037, p = 0.0048, respectively) and advanced TNM stage (p = 0.048, p = 0.046, respectively) were independent prediction factors. In the triple-negative group, independent factors related to recurrence and death were high maximum SUVmax (p = 0.0014, p = 0.0003, respectively) and advanced TNM stage (p < 0.0001, p < 0.0001, respectively). MATERIALS AND METHODS: Records of 546 stage I-III invasive breast cancer patients, including 344 estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, 110 HER2-positive, and 92 triple-negative cases, treated at four institutions were reviewed retrospectively. Harmonized primary tumor and nodal maximum SUVmax, metabolic tumor volume (MTV), and TLG indicated in pretreatment FDG-PET/CT results were analyzed. Evaluations of relationships of clinicopathological factors, volume-based quantitative parameters, recurrence-free survival (RFS), and overall survival (OS) for each subtype were performed with a Cox proportional hazards model and log-rank test. CONCLUSIONS: The results indicated that potential surrogate markers for prognosis in patients with the three main subtypes of operable breast cancer include harmonized pretreatment quantitative volume-based FDG-PET/CT parameters, particularly whole-lesion SUVmax and TLG.