Interim response in diffuse large B cell lymphoma on CT: what is the optimal size reduction (ΔSPD) for predicting outcome?

OBJECTIVES: To investigate whether there was an optimal interim size reduction (iΔSPD) cutoff value that could discriminate diffuse large B cell lymphoma (DLBCL) patients with poor prognosis. METHODS: This retrospective study enrolled 265 newly diagnosed DLBCL patients with baseline and interim (after 3 cycles) contrast-enhanced computed tomographic scan (CECT) available. Two radiologists evaluated CECT images and selected target lesions according to the Lugano Response Criteria. Lymph nodes greater than 15 mm in longest diameter (LDi) and extra-nodal lesions with LDi greater than 10 mm could be chosen as target lesions and used to calculate iΔSPD. A software tool, X-Tile, was used to calculate the optimal iΔSPD cutoff value to differentiate patients with good vs. poor prognosis. Receiver operating characteristic curve analysis, Cox regression analysis, and Kaplan-Meier analyses were further used to validate the optimal cutoff value. RESULTS: The optimal cutoff value of iΔSPD calculated by X-tile was 80%. Compared with 50% and 100%, 80% cutoff value had the intermediate sensitivity and specificity (57.75% and 86.69% for overall survival (OS), 48.98% and 92.22% for progression-free survival (PFS), respectively), but the maximal Youden index (0.4744 for OS, 0.4120 for PFS, respectively) and areas under the curve (0.737 [0.680, 0.789] for OS). Cox regression analysis also revealed that iΔSPD < 80% could independently predict an inferior OS and PFS (both p < 0.001) while neither iΔSPD < 50% nor iΔSPD = 100% could. CONCLUSIONS: iΔSPD with the cutoff value 80% is an independent predictor of PFS and OS for patients with DLBCL. Results suggest that treatment should be modified for patients with iΔSPD < 80%. KEY POINTS: • The aim of interim response assessment is to identify patients whose disease has not responded to or has progressed on induction therapy. • A cutoff value of 80% in size reduction (ΔSPD) is an independent predictor of PFS and OS for DLBCL patients and is better than 50%. • In DLBCL patients with interim ΔSPD < 80%, a change to a more efficient therapy should be considered.

Prognostic Value of Baseline and Interim Total Metabolic Tumor Volume and Total Lesion Glycolysis Measured on 18F-FDG PET-CT in Patients with Follicular Lymphoma.

PURPOSE: The purpose of this study was to investigate the prognostic significance of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) in patients with follicular lymphoma (FL) at baseline and mid-treatment with 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans. METHODS: The study analyzed data from 48 patients with FL who were treated in Jiangsu Province Hospital and reviewed their baseline PET-CT scans. TMTV and TLG were computed by using the absolute value of 2.0, 2.5, and 3.0 thresholding method, respectively. RESULTS: Median age was 53 years, 75.0% of patients had stage III to IV disease, 43.8% had a Follicular Lymphoma International Prognostic Index 1 (FLIPI1) score of 3 to 5 and 20.8% had a FLIPI2 score of 3 to 5. Receiver operating characteristic (ROC) curve analysis showed the optimal cut-off values for TMTV3.0 and TLG3.0 were 476.4 (sensitivity, 85.7%; specificity, 78.0%; area under the curve [AUC], 0.760; p=0.003) and 2,676.9 (sensitivity, 71.4%; specificity, 78.0%; AUC, 0.760; p=0.003). On multivariable analysis, TMTV3.0 and TLG3.0 were independent predictors of both progression-free survival (PFS) (hazard ratio [HR], 5.406; 95% confidence interval [CI], 1.326 to 22.040; p=0.019 and HR, 6.502; 95% CI, 1.079 to 39.182; p=0.042) and overall survival (OS) (HR, 4.111; 95% CI, 1.125 to 15.027; p=0.033 and HR, 5.885; 95% CI, 1.014 to 34.148; p=0.049). ROC curve analysis showed the optimal cut-off values for ΔTMTV3.0 and ΔTLG3.0 were 66.3% (sensitivity, 85.7%; specificity, 63.4%; AUC, 0.774; p < 0.001) and 64.5% (sensitivity, 85.7%; specificity, 65.9%; AUC, 0.777; p < 0.001). CONCLUSION: Baseline TMTV and TLG are strong predictors of PFS and OS in FL. Furthermore, interim TMTV (ΔTMTV > 66.3%) and TLG (ΔTLG > 64.5%) reduction are valuable tools for early treatment response assessment in FL patients.

Ectopic insulinomas in the pelvis secondary to rectum neuroendocrine tumour.

We describe a middle-aged woman with recurrent hypoglycaemia, who confirmed with rectum G1 neuroendocrine tumour (NET) 6 years ago. Biochemical assay showed high concentration of serum insulin and C-peptide associated with hypoglycaemia. Because of recurrent hypoglycaemia in June 2015, she underwent a resection of the tail of the pancreas. However, hypoglycaemia attack happened more frequently and severely. 68Ga-DOTA-NOC positron emission tomography/CT revealed five foci in the pelvis with intense uptake. Immediately after excision of the pelvic lesions, insulin and C-peptide decreased to normal levels promptly, and therefore, serum glucose increased significantly. Hypoglycaemia was disappeared, and insulin and C-peptide were normal at 2 years follow-up after surgery. Immunohistochemistry validated the primary rectum NET and pelvic tumours expressed with higher insulin, somatostatin receptor and glucagon-like peptide-1. This is the first reported ectopic pelvic insulinomas secondary to rectum NET, which may originate both from neuroendocrine cells in the rectum and pelvic tissues.

[Clinical Value of 18F-FDG PET/CT for Patients with B Cell Lymphoma-Associated Hemophagocytic Syndrome].

OBJECTIVE: To investigate the clinical value of 18F-FDG PET/CT for patients with B cell lymphoma-associated hemophagocytic syndrome. METHODS: The clinical characteristics, laboratory parameters and 18F-FDG PET/CT data of 23 newly diagnosed patients sufferred from B cell lymphoma-associated hemophagocytic syndrome were retrospectively analyzed. The correlation between PET and laboratory parameters were determined using Spearman correlation test. The prognostic factors were analyzed by the Kaplan-Meier method. RESULTS: 23 patients were all examined by 18F-FDG PET/CT before chemotherapy, the 18F-FDG uptake of spleen positively correlated with neutrophil count and hemoglobin content (r=0.588, P=0.035;r=0.699, P=0.008), respectively, and the 18F-FDG uptake of bone marrow positively correlated with neutrophil count only (r=0.691, P=0.009). Among all the clinical or laboratorial parameters and 18F-FDG PET/CT, only PET parameter was poor factor affecting prognosis of patients with B cell lymphoma-associated hemophagocytic syndrome. Out of 6 patients received PET/CT scans after 6 cycles of treatment, the 5 patients with negative PET/CT survived, and one patient with positive result died. CONCLUSION: Baseline 18F-FDG PET/CT may provide prognostic information for the management of patients with B cell lymphoma-associated hemophagocytic syndrome, and the data of 18F-FDG PET/CT before chemotherapy may predict the pregnosis of the patients with negative results, and the negative PET/CT results after chemotherapy betokens a better prognosis of patients.

68Ga-PSMA-11 PET/CT for prostate cancer staging and risk stratification in Chinese patients.

We evaluated the clinical utility of 68Ga-PSMA-11 PET/CT for staging and risk stratification of treatment-naïve prostate cancer (PCa) and metastatic castrate-resistant prostate cancer (mCRPC). Twenty-two consecutive patients with treatment-naïve PCa and 18 with mCRPC were enrolled. 68Ga-PSMA-11 PET/CT and magnetic resonance imaging (MRI) were performed for the evaluation of primary prostatic lesions, and bone scans were used for evaluation bone metastasis. Among the 40 patients, 37 (92.5% [22 treatment-naïve PCa, 15 mCRPC]) showed PSMA-avid lesions on 68Ga-PSMA-11 images. Only 3 patients with stable mCRPC after chemotherapy were negative for PSMA. The sensitivity, specificity and accuracy of 68Ga-PSMA-11 imaging were 97.3%, 100.0% and 97.5%, respectively. The maximum standardized uptake (SUVmax) of prostatic lesions was 17.09 ± 11.08 and 13.33 ± 12.31 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 revealed 105 metastatic lymph nodes in 15 patients; the SUVmax was 16.85 ± 9.70 and 7.54 ± 5.20 in treatment-naïve PCa and mCRPC, respectively. 68Ga-PSMA-11 PET/CT also newly detected visceral metastasis in 9 patients (22.5%) and bone metastasis in 29 patients (72.5%). 68Ga-PSMA-11 PET/CT exhibits potential for staging and risk stratification in naïve PCa, as well as improved sensitivity for detection of lymph node and remote metastasis.

Prognostic significance of bone marrow infiltration detected by PET-CT in newly diagnosed diffuse large B cell lymphoma.

The aim of this study was to examine the prognostic value of bone marrow involvement (BMI) assessed by baseline PET-CT (PET(0)-BMI) in treatment-naïve patients with diffuse large B-cell lymphoma (DLBCL). All patients from a single centre diagnosed as DLBCL between 2005 and 2014 had data extracted from staging PET-CT (PET(0)-CT), bone marrow biopsy (BMB), and treatment records. The PET(3)-CT (PET-CT scan after cycle 3 of immunochemotherapy) was performed on all the patients with PET(0)-BMI positivity (PET(0)-BMI(+)). Of 169 patients, 20 (11.8%) had BMI on BMB, whereas 35 (20.7%) were PET(0)-BMI positive. Among PET(0)-BMI(+) patients, patients with maximum of standard uptake value (SUVmax) of bone marrow (SUVmax(BM)) more than 8.6 were significantly associated with high IPI score (3-5) (P=0.002), worse progression-free survival (PFS) and overall survival (OS) (P=0.025 and P=0.002, respectively). In the 68 stage IV cases, 3-year OS was higher in the patients with negative PET(0)-BMI (PET(0)-BMI(-)) than that with PET(0)-BMI(+) (84.2%±6.5% vs. 44.1%±8.6%; P=0.003), while 3-year PFS only shown a trend of statistic significance (P=0.077) between the two groups. Among the 69 patients of inter-risk of IPI (2-3), patients with PET(0)-BMI(+) had significantly inferior PFS and OS than that with PET(0)-BMI(-) (P=0.009 and P<0.001, respectively). The cut-off value of the decreased percentage of SUVmax(BM) between PET(0)-CT and PET(3)-CT (ΔSUVmax(BM)) was 70.0%, which can predict PFS (P=0.003) and OS (P=0.023). These data confirmed that along with the increased sensitivity and accuracy of identifying bone marrow by PET-CT, novel prognostic values of marrow involvement were found in patients with DLBCL.

The Neural Basis of Postural Instability Gait Disorder Subtype of Parkinson's Disease: A PET and fMRI Study.

AIMS: The aim of this study is to further uncover the neural basis of postural instability gait disorder (PIGD) subtype of Parkinson's disease. METHODS: With F-18 fluorodeoxyglucose PET (FDG-PET), brain glucose metabolism of patients with PIGD (n = 15) was compared with healthy controls (n = 17) and tremor-dominant (TD) patients (n = 15), and the correlation between metabolism and PIGD symptoms was also assessed. Within PIGD symptom-correlated hypometabolic areas, the relationship of functional connectivity (FC) with motor and cognitive symptoms was examined by using functional MRI. RESULTS: Compared with controls, patients with PIGD displayed a distributed pattern of brain hypometabolism including striatal, frontal, and parietal areas. Relative to the pattern of TD patients, the pattern of patients with PIGD had additional metabolic decreases in caudate and inferior parietal lobule (IPL, Brodmann area [BA] 40). In PIGD group, the metabolic reductions in IPL (BA 40), middle frontal gyrus (MFG, BA 9) and fusiform gyrus (FG, BA 20) were associated with severe PIGD symptoms. Regions showing such correlation were chosen for further seed-based FC analysis. Decreased FC within the prefrontal-parietal network (between the MFG and IPL) was associated with severe PIGD symptoms. CONCLUSION: The involvement of the caudate, FG, and prefrontal-parietal network may be associated with the prominent gait impairments of PIGD subtype. Our findings expand the pathophysiological knowledge of PIGD subtype and provide valuable information for potential neuromodulation therapies alleviating gait disorders.

Exploring the role of bone marrow increased FDG uptake on PET/CT in patients with lymphoma-associated hemophagocytic lymphohistiocytosis: a reflection of bone marrow involvement or cytokine storm?

The role of 18F-2-fluoro-2-deoxy-D-glucose (FDG) uptake of bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) in patients with lymphoma-associated hemophagocytic lymphohistiocytosis (LA-HLH) remains uncertain. This retrospective study included 34 LA-HLH patients who underwent both PET/CT and comprehensive BM examinations prior to treatment. Comparison between PET/CT and BM examinations for the assessment of bone marrow involvement (BMI) indicated statistical difference (p = 0.039). The specificity of PET/CT in detecting BMI was 11.1% compared to BM examinations. However, a significant correlation was found between PET parameters of BM and laboratory parameters associated with HLH, such as C-reactive protein, ferritin, fibrinogen and soluble CD25. By multivariate analysis, PET parameters of marrow were significantly associated with overall survival. The findings suggest that FDG uptake of marrow might fail to detect lymphomatous BMI, but reflected the level of cytokine storm to a certain extent and might be a prognostic factor in patients with LA-HLH.

[Prognostic Value of Maximum Standard Uptake on Pretreatment ¹8F-FDG PET/CT Scan in Newly Diagnosed Follicular Lymphoma].

OBJECTIVE: To determine the prognostic value of maximum standard uptake (SUV(max)) of pretreatment ¹8F-FDG PET/CT scan in newly diagnosed follicular lymphoma (FL). METHODS: The clinical data and detection results of ¹8F-FDG PET/CT scan of 30 patients with FL before treatment from November 2005 to October 2013 were analyzed retrospectively. The relation of SUV(max) with prognostic factors, therapeutic efficacy and survival time was evaluated in term of pathologic grade, FLIPI2 absence and presence of bulky disease and bone marrow involvement, clinical indicators and outcome of treatment. RESULTS: There was significant differences of SUV(max) among pathological grade 1, grade 2 and grade 3 (P = 0.040), but no significant difference was found among FLIPI 2 low risk group, intermediate risk group and high risk groups (P = 0.431). No difference of SUV(max) was observed in patients with and without bulky disease, or with and without bone marrow involvement (both P > 0.05). SUV(max) was not related with such patient characteristics as stage, ß2-microglobulin level, hemoglobin content, lactate dehydrogenase and Ki-67 (both P > 0.05). And the difference of SUV(max) was no significant for patients with complete remission (CR) and non-CR, or with efficacy and no efficacy (both P > 0.05). With the cutoff values of 10 and 15, the CR rate, overall response rate, 3-year progression-free survival (PFS) rate and 2-year overall survival (OS) rate were not different between the patients with SUV(max) below and above cut-off value (both P > 0.05). CONCLUSION: In our study the prognostic value of SUV(max) on PET/CT is indeterminate, and it can not be used to predict the FL patients prognosis.

[Value of PET/CT after Chemotherapy for Evaluating Therapentic Efficacy of Patients with Diffuse Large B-cell Lymphoma].

OBJECTIVE: To investigate the value of PET/CT after chemotherapy for evaluating therapeutic efficacy of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: (18)F-FDG PET/CT was performed before and after 6-8 cycles of chemotherapy in 73 newly diagnosed patients with DLBCL from September 2005 to January 2012. The results of pre-treatment PET/CT was compared with results of post-treatment PET/CT. These patients were divided into 3 groups: complete response group, partial response group and no response group. The post-treatment PET/CT results was used to assess its ability to predict progression-free survival (PFS) and overall survival (OS). RESULTS: The comparison of PET/CT results before and after chemotherapy showed that 2-year PFS rates of complete response group, partial response group and no response group were 82% (41/50), 45.5% (5/11) and 8.3% (1/12), respectively; and the 3-year OS rates of 3 groups were 88% (44/50), 54.5% (6/11) and 8.3% (1/12) respectively (both P < 0.01). The 2-year PFS rate and the 3-year OS rate of the complete response group and partial response group were significantly higher than those of no response group (both P < 0.05), and there was also significant statistical difference between partial response group and complete response group in 2-year PFS rate and 3-year OS rate (both P < 0.05). CONCLUSION: The post-treatment PET/CT can be accurately used to evaluate the curative efficacy of chemotherapy and prognosis of patients with DLBCL.

Thymic hyperplasia following chemotherapy in adults with lymphoma: (18)F-fluorodeoxyglucose positron emission tomography/computed tomography findings and correlation with T cell repopulation.

Thymic hyperplasia (TH) after chemotherapy is an infrequent phenomenon in adults. This study analyzed the incidence and metabolic activity of TH on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in this population. By reviewing 471 PET/CT recordings of 211 adults with lymphoma, increased FDG uptake within an enlarged thymus regarded as TH was observed in 27 patients aged 18-53 years. FDG uptake in hyperplastic thymus was mild and diffuse, with a maximum standard uptake value (SUVmax) of 2.6±0.9. Its intensity varied with different occurrence times following chemotherapy. In addition, by comparing the recovery of T cell subsets in patients with TH (n=20) and without TH (n=28), no impact of the presence of TH was found on the repopulation of total CD4+and CD8+T cells within the first year after treatment. These data may be helpful to avoid misinterpretation of increased thymic uptake in adults.

Role of nesfatin-1 in a rat model of visceral hypersensitivity.

AIM: To explore the role of nesfatin-1 on irritable bowel syndrome (IBS)-like visceral hypersensitivity. METHODS: The animal model of IBS-like visceral hypersensitivity was induced by intracolonic infusion of 0.5% acetic acid (AA) in saline once daily from postnatal days 8-21. Experiments were performed when rats became adults. The visceral sensitivity of rats was evaluated by abdominal withdrawal reflex (AWR) and electromyographic (EMG) activity of the external oblique muscle to graded colorectal distension. The content of nesfatin-1 in serum was determined using enzyme-linked immunosorbent assay. After implantation of an intracerebroventricular (ICV) cannula and two electrodes into the external oblique muscle, model rats were randomly divided into four groups. Animals then received ICV injection of 8 µg of anti-nesfatin-1/nucleobindin-2 (NUCB2), 50 µg of α-helical corticotropin releasing factor (CRF) 9-41 (non-selective CRF receptor antagonist), 50 µg of NBI-27914 (selective CRF1 receptor antagonist) or 5 µL of vehicle. After 1 h of ICV administration, visceral sensitivity of each group was measured again, and comparisons between groups were made. RESULTS: Rats treated with AA showed higher mean AWR scores and EMG activity at all distension pressures compared with controls (P < 0.05). On histopathologic examination, no evidence of inflammation or abnormalities in structure were noted in the colon of either control or AA-treated groups. Myeloperoxidase values were not significantly different between the two groups. The level of nesfatin-1 in serum was significantly higher in the AA-treated group than in the control group (5.34 ± 0.37 ng/mL vs 4.81 ± 0.42 ng/mL, P < 0.01). Compared with rats injected with vehicle, rats which received ICV anti-nesfatin-1/NUCB2, α-helical CRF9-41 or NBI-27914 showed decreased mean AWR scores and EMG activity at all distension pressures (P < 0.05). CONCLUSION: Nesfatin-1 may be associated with IBS-like visceral hypersensitivity, which may be implicated in brain CRF/CRF1 signaling pathways.