Occult nodal metastasis in patients with non‐small cell lung cancer at clinical stage IA by PET/CT

Background and objective: The introduction of ¹⁸F‐FDG PET/CT has enhanced the diagnostic accuracy of nodal staging for non‐small cell lung cancer (NSCLC). We analysed risk factors for occult nodal metastasis in patients with clinical stage IA NSCLC as determined by ¹⁸F‐FDG PET/CT. Methods: Data for 147 patients diagnosed as clinical stage IA NSCLC by PET/CT from 2005 to 2007 were retrospectively reviewed. All study patients underwent ¹⁸F‐FDG PET/CT for lung cancer staging. They also underwent cervical mediastinoscopy or systematic lymph node dissection. Results: Cervical mediastinoscopy was performed in 78 patients (53.1%), and N2 involvement was detected in 3.8% (3/78) of these patients. Thoracotomy with systematic lymph node dissection was done in 144 patients. Four patients (2.8%, 4/144) were diagnosed with N2 disease after systematic lymph node dissection. Total N2 involvement was 4.8% (7/147). As 9.5% (14/147) of study patients had N1 disease, 14.3% (21/147) of patients had occult nodal (N1 or N2) metastasis. In univariate analyses, larger tumour size and a higher primary tumour maximum standardized uptake value >7.3 (SUV_max) were associated with occult nodal metastasis. Multivariate analysis demonstrated that a primary tumour SUV_max >7.3 was an independent predictor of occult nodal metastasis (odds ratio: 7.574; P = 0.001). Conclusions: Preoperative PET/CT scans contribute to reduce the frequency of occult nodal metastasis compared with those reported in the pre‐PET/CT era. The higher SUV_max in primary tumour was an independent predictor of occult nodal metastasis in patients with clinical stage IA NSCLC by PET/CT.     

Geometrical differences in target volumes based on 18F‐fluorodeoxyglucose positron emission tomography/computed tomography and four‐dimensional computed tomography maximum intensity projection images of primary thoracic esophageal cancer

The objective of the study was to compare geometrical differences of target volumes based on four‐dimensional computed tomography (4DCT) maximum intensity projection (MIP) and ¹⁸F‐fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F‐FDG PET/CT) images of primary thoracic esophageal cancer for radiation treatment. Twenty‐one patients with thoracic esophageal cancer sequentially underwent contrast‐enhanced three‐dimensional computed tomography (3DCT), 4DCT, and ¹⁸F‐FDG PET/CT thoracic simulation scans during normal free breathing. The internal gross target volume defined as IGTV_MIP was obtained by contouring on MIP images. The gross target volumes based on PET/CT images (GTV_PET) were determined with nine different standardized uptake value (SUV) thresholds and manual contouring: SUV ≥ 2.0, 2.5, 3.0, 3.5 (SUV_n); ≥20%, 25%, 30%, 35%, 40% of the maximum (percentages of SUV_max, SUV_n%). The differences in volume ratio (VR), conformity index (CI), and degree of inclusion (DI) between IGTV_MIP and GTV_PET were investigated. The mean centroid distance between GTV_PET and IGTV_MIP ranged from 4.98 mm to 6.53 mm. The VR ranged from 0.37 to 1.34, being significantly (P < 0.05) closest to 1 at SUV_2.5 (0.94), SUV_20% (1.07), or manual contouring (1.10). The mean CI ranged from 0.34 to 0.58, being significantly closest to 1 (P < 0.05) at SUV_2.0 (0.55), SUV_2.5 (0.56), SUV_20% (0.56), SUV_25% (0.53), or manual contouring (0.58). The mean DI of GTV_PET in IGTV_MIP ranged from 0.61 to 0.91, and the mean DI of IGTV_MIP in GTV_PET ranged from 0.34 to 0.86. The SUV threshold setting of SUV_2.5, SUV_20% or manual contouring yields the best tumor VR and CI with internal‐gross target volume contoured on MIP of 4DCT dataset, but 3DPET/CT and 4DCT MIP could not replace each other for motion encompassing target volume delineation for radiation treatment.     

Prognostic value of maximum standardized uptake values from preoperative positron emission tomography in resectable adenocarcinoma of the esophagus treated by surgery alone

Preoperative staging for esophageal adenocarcinoma is suboptimal for predicting outcomes when compared with pathological data. The aim of this study was to assess if the quantitative values obtained by preoperative 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) are independent prognostic indicators for survival in patients with resectable adenocarcinoma of the esophagus undergoing surgical treatment without neoadjuvant therapy. Patients were identified from a prospective database, survival analyses were undertaken using log rank and Cox method. The median follow‐up was 44 months (range 18–61 months). Between November 2002 and November 2005, 45 consecutive patients underwent FDG‐PET followed by surgery. The median age was 72 years (range 38–82 years). On univariate analysis of overall survival and disease‐free survival, preoperative FDG‐PET maximum standardized uptake value (SUV_max; P= 0.008 and P= 0.015, respectively) and postoperative pathological stage (P= 0.001 and P= 0.001, respectively) as well as postoperative histological grade (P= 0.001 and P= 0.001, respectively) were significantly associated with outcome. Multivariate analysis demonstrated that only the postoperative pathological variables were independent predictors of outcome (Wald 11.81, P= 0.001). Preoperative FDG‐PET SUV_max is associated with outcome after esophageal adenocarcinoma resection but remains less accurate than postoperative variables. A high FDG‐PET SUV_max could be used to identify a high‐risk population who would benefit most from neoadjuvant therapies.     

18F-FDG uptake in primary gastric malignant lymphoma correlates with glucose transporter 1 expression and histologic malignant potential

Positron emission tomography (PET) is used for staging and response evaluation in primary gastric lymphoma (PGL). However, the implications of [¹⁸F]-2-fluoro-2-deoxy-d-glucose (¹⁸F-FDG) uptake in PGL at first diagnosis have not been reported. The relationship between ¹⁸F-FDG uptake and the expression of facilitative glucose transporters (GLUTs), hexokinase II (HK II), and Ki67, as well as malignant potential in PGL, was assessed in this study. We analyzed 23 patients with PGL [nine with diffuse large B-cell lymphoma (DLBCL); seven with high-grade mucosa-associated lymphoid tissue (MALT) lymphoma; and seven with low-grade MALT lymphoma]. The expression levels of GLUT1, GLUT3, HK II, and Ki67 were evaluated according to the percentage of positive area determined by immunohistochemistry. Standardized uptake values correlated significantly with pathological malignant potentials (low-grade/high-grade MALT lymphoma and DLBCL: p = 0.001–0.002), Ki67 (p < 0.001), and GLUT1 expression (p = 0.02). We determined that ¹⁸F-FDG uptake is related to GLUT1 expression and tumor histological grade as well as Ki67 in PGL.     

The role of FDG‐PET/CT in the evaluation of residual disease in paediatric non‐Hodgkin lymphoma

¹⁸F‐labelled–fluorodeoxyglucose positron emission tomography (FDG‐PET) findings are challenging to interpret for residual disease versus complete response in paediatric patients with non‐Hodgkin lymphoma (NHL). A biopsy is often warranted to confirm the presence or absence of viable tumour if there is clinical or radiographic evidence of residual disease. In this study, we compared conventional imaging and FDG‐PET/computerized tomography (CT) findings with biopsy results in 18 children with NHL. Our goal was to provide additional data to establish more reliable criteria for response evaluation. Residual disease was suspected after conventional imaging alone in eight patients, after FDG‐PET/CT alone in three and after both modalities in seven patients. Biopsy confirmed the presence of viable tumour in two patients. Two additional patients experienced progressive disease or relapse. The sensitivity and negative predictive value of FDG‐PET/CT using the London criteria to indicate residual tumour detectable by biopsy were 100%, but specificity was low (60%), as was the positive predictive value (25%). Thus, in this study, a negative FDG‐PET/CT finding was a good indicator of complete remission. However, because false‐positive FDG‐PET/CT findings are common, biopsy and close monitoring are required for accurate determination of residual disease in individual patients.     

Ki‐67 expression as a prognostic factor in diffuse large B‐cell lymphoma patients treated with rituximab plus CHOP

Background: Assessment of tumor cell proliferation based on Ki‐67 expression yielded conflicting prognostic predictions of patients with diffuse large B‐cell lymphoma (DLBCL). The introduction of rituximab to the DLBCL treatment regime has led to alterations in the significance of previous prognostic factors. Methods: We analyzed Ki‐67 expression and its correlation with prognosis in 144 patients with DLBCL treated with rituximab plus CHOP (R‐CHOP) between July 2003 and January 2008. Results: The complete response (CR) rates following R‐CHOP administration were not significantly different, based on Ki‐67 expression status (P = 0.104). However, higher rates of relapse were observed in the high Ki‐67 expression group (Ki‐67 ≥ 85%, n = 46) with 25.0%, compared to 10.0% in the low Ki‐67 expression group (Ki‐67 < 85%, n = 88) (P = 0.040). The 2‐yr event‐free survival (EFS) rates were 44.3% and 74.1% in the high and low Ki‐67 expression groups, respectively (P = 0.011). The 2‐yr overall survival (OS) rate was 66.4% in the high Ki‐67 expression group and 82.2% in the low Ki‐67 expression group (P = 0.016). In multivariate analysis, Ki‐67 expression was a significant prognostic factor for EFS [hazard ratio (HR) = 2.909; 95% confidence interval (CI) 1.261–6.708; P = 0.012]. Ki‐67 was associated with OS but with borderline significance (HR = 2.876; 95% CI, 0.972–8.508; P = 0.056). Conclusion: Elevated Ki‐67 expression seems to be associated with higher relapse after CR and inferior EFS in patients with DLBCL treated with R‐CHOP.     

18F‐Fluorodeoxyglucose (FDG)‐PET features of focal nodular hyperplasia (FNH) of the liver

Abstract: Aim: The aim of this paper is to describe the imaging pattern of focal nodular hyperplasia (FNH) by ¹⁸F‐fluorodeoxyglucose (18F‐FDG) positron emission tomography (PET). Methods: Eight consecutive asymptomatic patients with histologic proof of FNH underwent 18F‐FDG PET imaging. The lesions were found incidentally. The 18F‐FDG PET imaging was performed with a dedicated PET tomograph after intravenous injection of 300–370 MBq 18F‐FDG. The 18F‐FDG accumulation in the lesions was (semi)quantified by calculating the standardized uptake value (SUV) and SUV has been corrected for the lean body mass (LBM). Eight patients with liver metastases spread from melanoma (n=2) and colorectal carcinoma (n=6) served as controls. The size of the FNH lesions and of the control group ranged from 2.0 to 8.5 cm (mean 4.83 cm±2.37) and from 1.5 to 6 cm (mean 3.28±1.52), respectively. Results: While in malignant liver lesions the accumulation of 18F‐FDG was significantly increased, all FNH lesions showed normal or even decreased accumulation of 18F‐FDG. In FNH lesions, SUV ranged between 1.5 and 2.6 (mean 2.12±0.38), whereas all liver metastases showed an increased SUV ranging between 6.20 and 16.00 (mean 10.07±3.79). The SUV corrected for LMB (SUV_LBM) was similar to the SUV and ranged between 0.9 and 2.2 (mean 1.81±0.41) for FNH and between 5.9 and 16.3 (mean 9.15±4.03), respectively. Conclusion: In contrast to liver metastases, there is no increased glucose metabolism in FNH in vivo. The imaging feature of FNH by 18F‐FDG‐PET imaging is not specific for FNH; however, it may be helpful to differentiate FNH from liver metastases in cancer patients if radiological methods are not diagnostic.     

Measuring tumor hypoxia with 18F‐FETNIM PET in esophageal squamous cell carcinoma: a pilot clinical study

The purpose of this study was to evaluate hypoxia in esophageal squamous cell carcinoma (SCC) with ¹⁸F‐fluoroerythronitroimidazole positron emission tomography/computed tomography (¹⁸F‐FETNIM PET/CT). We determined an imaging threshold for hypoxia, quantified the spatiotemporal variability of hypoxia in untreated tumor, and evaluated the ability of ¹⁸F‐FETNIM PET to predict clinical response following concurrent chemoradiotherapy (CCRT). Twenty‐eight consecutive patients with inoperable SCC of the esophagus were consecutively accrued between April 2007 and June 2010. The first 10 patients received two pretreatment ¹⁸F‐FETNIM PET/CT scans on separate days. The remaining 18 patients only underwent ¹⁸F‐FETNIM PET/CT once before CCRT. The ratio of the maximum standardized uptake value (SUV_max) of 336 normal tissue regions (i.e. heart, lung, brain, or muscle) to the mean standardized uptake value (SUV_mean) of the respective patient's spleen was calculated, and the imaging threshold for hypoxia defined as the level of uptake demonstrated by less than 5% of tissue regions. Among the patients with two pretreatment scans, each pair of scans was compared with respect to location and intensity of uptake to assess for baseline spatiotemporal variability. Logistic regression analysis was used to determine whether pretreatment imaging characteristics are predictive of clinical response. The mean and median ratios of the SUV_max of tissue : SUV_mean of spleen were nearly identical, and 95% of the ratios fell below 1.3. The mean Dice similarity coefficient for the hypoxic volumes on pretreatment PET scans acquired in the same patient on different days was 0.12 (range, 0.05–0.21). Individuals' tumor SUV_max and SUV_mean did not vary significantly, but on average, the geometric centers of hypoxic regions shifted 15 mm (range, 8–20 mm) from the first pretreatment scan to the second. SUV_max was the imaging characteristic most predictive of treatment response (P= 0.041), with high SUVmax associated with poor clinical response. ¹⁸F‐FETNIM PET/CT can depict hypoxia in esophageal SCC. Prior to CCRT, tumor hypoxia demonstrates spatial variability on different days, although overall ¹⁸F‐FETNIM uptake remains similar. Baseline SUV_max may be predictive of treatment response.     

Maximum standard uptake value of 18F-fluorodeoxyglucose positron emission tomography is a prognostic factor for progression-free survival of newly diagnosed patients with diffuse large B cell lymphoma

The treatment of patients with diffuse large B cell lymphoma (DLBCL) would be greatly facilitated with a rapid method for determining prognosis that can be performed more easily and earlier than cytological or specific pathological examinations. It has been suggested that newly diagnosed patients with DLBCL who have low maximum standard uptake value (SUV_max) on ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) are more likely to be successfully treated and remain in remission compared with patients with high SUV_max, but this concept has been poorly studied. We retrospectively analyzed 50 patients with de novo DLBCL to evaluate the relationship between the SUV_max and disease progression. For patients with low SUV_max (n?=?10) and high SUV_max (n?=?40) (P?=?0.255), respectively, the 3-year overall survival rates were 90 and 72 %, and the progression-free survival (PFS) rates were 90 and 39 % (P?=?0.012). By multivariate analysis, the revised International Prognostics Index (R-IPI) and SUV_max at diagnosis were shown to predict longer PFS. The 3-year PFS for patients with low SUV_max classified into the good prognosis group by R-IPI was 100 vs. 62 % for those with high SUV_max (P?=?0.161), and patients with low SUV_max classified into the poor prognosis group by R-IPI was 80 vs. 18 % for those with high SUV_max (P?=?0.050). We conclude that the SUV_max on FDG-PET for newly diagnosed patients with DLBCL is an important predictor of disease progression, especially for patients with poor prognosis by R-IPI.     

Bone marrow 18F‐fluoro‐2‐deoxy‐d‐glucose positron emission tomography/computed tomography cannot replace bone marrow biopsy in diffuse large B‐cell lymphoma

This study aimed to investigate whether visual and quantitative ¹⁸F‐fluoro‐2‐deoxy‐d ‐glucose positron emission tomography/computed tomography (FDG‐PET/CT)‐based bone marrow assessment can replace blind bone marrow biopsy (BMB) in newly diagnosed diffuse large B‐cell lymphoma (DLBCL). This retrospective study included 78 patients with newly diagnosed DLBCL who had undergone both FDG‐PET/CT and BMB. FDG‐PET/CT images were visually evaluated for bone marrow involvement. Patient‐based sensitivity of visual FDG‐PET/CT assessment was calculated using BMB as the reference standard. Metabolically active volume, maximum standardized uptake value, 3D partial volume corrected mean standardized uptake value, and 3D partial volume corrected mean metabolic volume product (cMVP_mean) of FDG‐avid bone marrow lesions were measured. Cox regression analysis was used to determine the influence of (potential) prognostic factors (BMB status, visual [dichotomous] FDG‐PET/CT bone marrow status, metabolically active volume, maximum standardized uptake value, 3D partial volume corrected mean standardized uptake value, 3D partial volume corrected mean metabolic volume product, and International Prognostic Index score) on progression‐free survival and overall survival. FDG‐PET/CT detected bone marrow involvement in 34 (43.6%) cases and BMB in 16 (20.5%) of 78 cases, of whom 11 were also detected by FDG‐PET/CT, resulting in a patient‐based sensitivity of 68.8% (95% confidence interval = 44.2%–86.1%) for FDG‐PET/CT. In the multivariate Cox proportional hazards model, only BMB status was an independent predictive factor of progression‐free survival (P = 0.016) and overall survival (P = 0.004). In conclusion, FDG‐PET/CT misses bone marrow involvement that has been detected by BMB in a non‐negligible proportion of patients. Furthermore, both visual and quantitative FDG‐PET/CT‐based bone marrow assessments are prognostically inferior to BMB. Therefore, FDG‐PET/CT cannot replace BMB in newly diagnosed DLBCL. Am. J. Hematol. 89:726–731, 2014. © 2014 Wiley Periodicals, Inc.     

Use of positron emission tomography with methyl‐11C‐choline and 2‐18F‐fluoro‐2‐deoxy‐D‐glucose in comparison with magnetic resonance imaging for the assessment of inflammatory proliferation of synovium

Objective

To compare positron emission tomography (PET) and magnetic resonance imaging (MRI) in the evaluation of inflammatory proliferation of synovium.

Methods

Ten patients (mean ± SD age 36 ± 13 years) with inflammatory joint disease and with clinical signs of inflammation of the joint were studied. A new tracer for cellular proliferation, methyl‐¹¹C‐choline (¹¹C‐choline), and a widely used tracer for the detection of inflammation and cancer, 2‐¹⁸F‐fluoro‐2‐deoxy‐D ‐glucose (¹⁸F‐FDG), were applied for PET imaging, and the results were compared with the findings from gadolinium diethylenetriaminepentaacetic acid–enhanced MR images. The uptake of ¹¹C‐choline and ¹⁸F‐FDG in the inflamed synovium was measured and expressed as the standardized uptake value (SUV) and the kinetic influx constant (K_i) obtained from graphic analysis, and these values were compared with quantitative values on MRI. Synovial volumes were measured on the coronal contrast‐enhanced T1‐weighted MR images using the standard software of the MR imager.

Results

All patients showed high accumulation of both ¹¹C‐choline and ¹⁸F‐FDG at the site of arthritic changes, where quantification of the tracer uptake was performed. The SUV of ¹¹C‐choline was 1.5 ± 0.9 gm/ml (mean ± SD; n = 10) and the SUV of ¹⁸F‐FDG was 1.9 ± 0.9 gm/ml (n = 10) (P = 0.017). The K_i of ¹¹C‐choline (mean ± SD 0.048 ± 0.042 minute⁻¹) was 8‐fold higher than the K_i of ¹⁸F‐FDG (0.006 ± 0.003 minute⁻¹) (P = 0.009). Both the uptake of ¹¹C‐choline and the uptake of ¹⁸F‐FDG correlated highly with the volume of synovium; the highest correlation was observed with the K_i of ¹¹C‐choline (r = 0.954, P < 0.0001).

Conclusion

In the use of PET scans,¹¹C‐choline can be regarded as a promising tracer for quantitative imaging of proliferative arthritis changes. Nevertheless, subsequent prospective studies with larger numbers of patients are necessary to further characterize the relationship between the findings on PET imaging and the clinical and functional measures of inflammation.

     

Prognostic value of complete remission status at end‐of‐treatment FDG‐PET in R‐CHOP‐treated diffuse large B‐cell lymphoma: systematic review and meta‐analysis

This study systematically reviewed and meta‐analysed the prognostic value of complete remission status at end‐of‐treatment ¹⁸F‐fluoro‐2‐deoxy‐d ‐glucose positron emission tomography (FDG‐PET) in diffuse large B‐cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP). The systematic PubMed/MEDLINE search yielded seven suitable studies comprising a total of 737 R‐CHOP‐treated DLBCL patients who were in complete remission at end‐of‐treatment FDG‐PET. Overall, the methodological quality of included studies was reasonable. The disease relapse rate among all patients with complete remission status according to end‐of‐treatment FDG‐PET ranged from 7·0% to 20·0%, with a weighted summary proportion of 13·7%. Five of seven studies reported progression‐free survival (PFS) of these patients at various specific time points, i.e., 2‐year PFS (n = 1), estimated 3‐year PFS (n = 3) and 5‐year PFS (n = 1), which was 83%, 85–86·4% and 75%, respectively. Three of seven studies reported overall survival (OS) of these patients at various specific time points, i.e., estimated 3‐year OS (n = 2) and estimated 5‐year OS (n = 1), which were 90%, 93·6% and 83%, respectively. In conclusion, a non‐negligible proportion of R‐CHOP‐treated DLBCL patients who achieve complete remission according to end‐of‐treatment FDG‐PET experiences disease relapse during follow‐up.     

Improved survival for relapsed diffuse large B cell lymphoma is predicted by a negative pre‐transplant FDG‐PET scan following salvage chemotherapy

The utility of ^[18F]fluoro‐2‐deoxy‐ d ‐glucose positron‐emission tomography (FDG‐PET) for predicting outcome after autologous stem cell transplantation (ASCT) for diffuse large B cell lymphoma (DLBCL) is uncertain – existing studies include a range of histological subtypes or have a limited duration of follow‐up. Thirty‐nine patients with primary‐refractory or relapsed DLBCL with pre‐ASCT PET scans were analysed. The median follow‐up was 3 years. The 3‐year progression‐free survival (PFS) for patients with positive PET scans pre‐ASCT was 35% vs. 81% for those who had negative PET scans (P = 0·003). The overall survival (OS) in these groups was 39% and 81% (P = 0·01), respectively. In a multivariate analysis, PET result, number of salvage cycles and the presence of relapsed or refractory disease were shown to predict a longer PFS; PET negativity (P = 0·04) was predictive of a longer OS. PET is useful for defining those with an excellent prognosis post‐ASCT. Although those with positive scans can still be salvaged with current treatments, PET may useful for selecting patients eligible for novel consolidation strategies after salvage therapies.     

Role and prognostic significance of the Ki‐67 index in non‐Hodgkin's lymphoma

Expression of Ki‐67, a nuclear antigen protein present in all cycling cells, is used to determine the growth fraction of tumors. The aim of this study was to evaluate the role and prognostic significance of the Ki‐67 proliferation index (PI) in non‐Hodgkin's lymphoma. Ki‐67 was assayed immunohistochemically in tissue samples of 319 patients with newly‐diagnosed non‐Hodgkin's lymphoma. In 268 patients, the Ki‐67 PI was correlated with clinical course and outcome. The mean Ki‐67 PI ranged from 26.6% in indolent lymphomas to 97.6% in very aggressive lymphomas (P < 0.001). The index was <45% in 82.8% of indolent lymphomas and >45% in 85% of aggressive lymphomas (AUC = 0.877, P < 0.001). In patients with diffuse large B‐cell lymphoma (n = 141), a Ki‐67 PI of 70% was found to significantly discriminate patients with good or bad prognosis (AUC = 0.65, P = 0.004). Three‐year survival was 75% ± 5.6% in patients with a low Ki‐67 index compared with 55.9% ± 6% in patients with a high index (P = 0.015). In patients with a low IPI (≤2), 3‐year survival was 94% ± 4% in those with a Ki‐67 index ≤70% and 64% ± 8.1% in those with a higher index (P = 0.002); in patients with bulky disease (>10 cm), the corresponding 3‐year survival by Ki‐67 index was 100% and 25% ± 12% (P = 0.012). Our results suggest that the mean Ki‐67 PI differs by type of lymphoma. A cut‐off value of 45% can help differentiate indolent from aggressive disease. In diffuse large B‐cell lymphoma, a cut‐off value of 70% can distinguish patients with a good and bad prognosis when combined with other prognostic factors of low IPI score and bulky disease. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.     

Usefulness of 18F-fluorodeoxyglucose positron emission tomography in differential diagnosis and staging of cholangiocarcinomas

Background and Aim: ¹⁸F‐Fluoro‐2‐deoxy‐d ‐glucose positron emission tomography (¹⁸FDG‐PET) is promising for diagnosis and treatment of various malignancies. The aim of this study was to evaluate the clinical usefulness of ¹⁸FDG‐PET in differential diagnosis and staging of cholangiocarcinomas according to the intrahepatic, perihilar and common bile duct lesions and to compare with computerized tomography (CT) scan. Methods: From January 2000 to September 2003, 54 patients with suspected cholangiocarcinoma underwent abdominal CT scan and ¹⁸FDG‐PET within a 2‐week period. The PET images were analyzed visually and semiquantitatively. Results: The overall accuracy of ¹⁸FDG‐PET for discriminating malignant diseases of bile duct from benign conditions was slightly higher than that of CT scan (88.9% vs 81.5%). The sensitivity of ¹⁸FDG‐PET in perihilar cholangiocarcinoma was lower than the value of intrahepatic and common bile duct cancers (83.3% vs 91.3%, 90.9%); moreover, in cases of perihilar cancer, the sensitivity of ¹⁸FDG‐PET was lower than that of CT scans (83.3% vs 91.7%). ¹⁸FDG‐PET detected nine distant metastatic lesions not found by other imaging studies and excluded two patients who potentially had resectable condition in other imaging studies from unnecessary laparotomy. Conclusion: The clinical usefulness of ¹⁸FDG‐PET in differential diagnosis of bile duct cancers is related to the site of primary disease. Although it is a helpful method for differential diagnosis especially in cases of intrahepatic and common bile duct cancers, ¹⁸FDG‐PET can not provide confirmative clues in perihilar cholangiocarcinoma. ¹⁸FDG‐PET may hold promise in the detection of hidden distant metastasis and can play an additional role in the evaluation of resectability. ¹⁸FDG‐PET can be complementary to CT scan in diagnosing and staging of cholangiocarcinoma.     

Prognostic value of dual-time-point 18F-fluorodeoxyglucose positron emission tomography in patients with pulmonary sarcoidosis

Background and objective: The value of dual‐time‐ point ¹⁸F‐FDG PET was investigated to predict the prognosis of patients with pulmonary sarcoidosis. Methods: Twenty‐one patients with pulmonary sarcoidosis underwent ¹⁸F‐FDG PET examinations at two time points: an early scan at 60 min and a delayed scan at 180 min after injection of ¹⁸F‐FDG. Standardized uptake values (SUVs) at the two time points and the retention index (RI‐SUV) calculated from these were evaluated. To evaluate disease progression, all patients underwent chest CT 1 year after ¹⁸F‐FDG PET. Using these results, the accuracy of ¹⁸F‐FDG PET parameters and ⁶⁷Ga uptake for predicting disease persistence were compared, and the correlations between those parameters and serum markers were assessed. Results: RI‐SUV was significantly higher in patients with increased or unchanged pulmonary lesions at follow‐up CT (persistent group; 21.3 ± 9.6%) than in patients with improved pulmonary lesions (improved group; ?9.2 ± 28.6%, P = 0.0075). The diagnostic accuracy of RI‐SUV in the persistent group was significantly greater than that of early SUV or ⁶⁷Ga uptake, and serum soluble IL‐2 receptor showed a significant correlation with RI‐SUV. Conclusions: RI‐SUV showed better diagnostic accuracy compared with early SUV or ⁶⁷Ga uptake, in patients with persistent lung involvement at 1 year. It may be a useful measure of persistent inflammation in patients with pulmonary sarcoidosis.     

Telomeric 1p36.3 deletion and Ki‐67 expression in B‐Non‐Hodgkin's Lymphoma patients associated with chronic hepatitis C virus infection

The hepatitis C virus (HCV) core protein is able to accumulate genetic p53 mutations and may be considered co‐oncogenic. This study investigates 1p36.3 telomere deletion in B‐non‐Hodgkin's lymphoma (NHL) patients with chronic HCV infection using fluorescence in situ hybridization (FISH) in relation to survival to assess Ki‐67 antigen expression. A study group and a control group of 100 patients with B‐NHL (50 HCV positive and 50 HCV negative) and 60 control bone marrow biopsies were subjected to FISH for the detection of 1P36.3 deletion and to immunohistochemical staining with Ki‐67 antigens. 1p36.3 deletion by FISH was detected in 40% of the study group, and Ki‐67 was expressed in approximately 74% of patients. A significant difference was found between positive and negative HCV patients in their overall survival, the qualitative expression of Ki‐67 and the quantitative detection of 1p36.3 deletion by FISH. The overall survival was shorter with the presence of an 1p36 deletion by FISH and HCV positive. We concluded that the coexistence of Ki‐67 positivity, HCV positivity and 1p36.3 deletion may contribute to infection‐related cancers at the 1p36.3 locus.     

Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B‐cell non‐Hodgkin lymphomas,ANRS HC‐13 lympho‐C study

Hepatitis C virus (HCV) infection increases the risk of B‐cell non‐Hodgkin lymphomas (B‐NHL). Antiviral treatment (AT) can induce hematological responses in patients with marginal zone lymphomas (MZL). The ANRS HC‐13 Lympho‐C study aimed at a better understanding of the impact of AT on HCV associated B‐NHL. This multicentric study enrolled 116 HCV‐positive patients with B‐NHL between 2006 and 2012. Cytological and histological samples were collected for centralized review. At lymphoma diagnosis, median age was 61 years and gender ratio M/F was 1. Cytohistological distribution was marginal zone lymphoma (MZL) n = 45 (39%), diffuse large B‐cell lymphoma (DLBCL) n = 45 (39%), and other types n = 26 (22%). MZL patients had more frequent detection of rheumatoid factor (68% vs. 35%; P = 0.001) and more frequently mixed cryoglobulinemia (74% vs. 44%; P = 0.021) than patients with DLBCL. Among patients receiving AT, a sustained virologic response was achieved in 23 of 38 (61%) patients with MZL and in 9 of 17 (53%) with DLBCL (P = 0.42). Three‐year overall survival (OS) and progression‐free survival were 78% 95%CI [63–88] and 64% [48–76], respectively, without difference between cytohistological groups. Outcome analysis showed a favorable association between OS and AT in all patients (P = 0.05) and in the subgroup of MZL patients only (P = 0.04). Our data support that AT improves the outcomes of HCV‐associated NHLs. The impact of new AT regimen with protease inhibitor needs to be investigated in this setting. [ clinicalTrials.gov Identification number NCT01545544] Am. J. Hematol. 90:197–203, 2015. © 2014 Wiley Periodicals, Inc.     

Clinical value of 18F-fluoro-dexoxyglucose positron emission tomography/computed tomography in patients with adult-onset Still's disease: A seven-case series and review of the literature

Abstract

Objectives. While there are a few reports describing 18F-fluoro-dexoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) findings in patients with adult-onset Still's disease (AOSD), no summary report has yet been published. In this study, we evaluated the usefulness of FDG-PET/CT for diagnosis and activity evaluation in patients with AOSD by summarizing the findings of our patients and those reported in the literature.

Methods. Seven consecutive AOSD patients who had undergone PET/CT at our department between 2007 and 2012 were included. We evaluated FDG uptake for characteristic findings in patients with AOSD. In addition, we reviewed the literature on seven previously reported AOSD patients who had undergone PET/CT.

Results. FDG accumulation was positive mainly in the bone marrow (100%), spleen (90.9%), lymph nodes (80.0%) and joints (75.0%). In addition, FDG uptake was positive in the pericardium, pleura, salivary glands, eyelids, muscle and major blood vessels. Six patients underwent follow-up FDG PET/CT for evaluation of treatment efficacy. Follow-up PET/CT showed diminished FDG accumulation in the bone marrow, spleen and lymph nodes, with maximum standardized uptake value (SUV_max) being substantially reduced from 4.03 ± 0.95 to 2.20 ± 0.75 (p = 0.04), 4.04 ± 1.10 to 2.55 ± 1.13 (p = 0.04) and 5.63 ± 4.99 to 2.10 ± 1.91 (p = 0.11), respectively. No significant correlation was found between SUV_max in each lesion and the laboratory data, except for a significant correlation between lactate dehydrogenase (LDH) and spleen SUV.

Conclusions. FDG-PET/CT is useful for long-term assessments of AOSD activity in individual patients. However, PET/CT findings alone are not sufficient to make a differential diagnosis of AOSD versus malignant lymphoma.     

Controversies on the prognostic value of interim FDG‐PET in advanced‐stage Hodgkin lymphoma

Hodgkin lymphoma, even in advanced‐stage, is a highly curable malignancy, but treatment is associated with short‐term toxicity and long‐term side effects. Early predictive markers are required to identify those patients who do not require the full‐length standard therapy (and thus qualify for therapy de‐escalation) and those patients who will not be cured by standard therapy (and thus qualify for therapy escalation). Multiple trials have assessed the value of ¹⁸F‐fluoro‐2‐deoxy‐d ‐glucose positron emission tomography (FDG‐PET) after a few cycles of chemotherapy (also known as ‘interim FDG‐PET’) in predicting outcome in advanced‐stage Hodgkin lymphoma. Furthermore, multiple interim FDG‐PET‐adapted trials, in which patients with positive interim FDG‐PET scans are assigned to escalated therapies, and patients with negative interim FDG‐PET scans are assigned to de‐escalated therapies, have recently been published or are currently ongoing, with generally heterogeneous results. The present article reports the currently available evidence (and controversies) on the prognostic value of interim FDG‐PET in advanced‐stage Hodgkin lymphoma in patients with positive and negative interim FDG‐PET findings following continuation of standard chemotherapy or escalated/de‐escalated therapy.