A Prospective Comparison of 18F-FDG PET/CT and CT as Diagnostic Tools to Identify the Primary Tumor Site in Patients with Extracervical Carcinoma of Unknown Primary Site

Background. The aim of the present study was to evaluate prospectively the diagnostic value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) and conventional CT regarding the ability to detect the primary tumor site in patients with extracervical metastases from carcinoma of unknown primary (CUP) site. Patients and Methods. From January 2006 to December 2010, 136 newly diagnosed CUP patients with extracervical metastases underwent (18)F-FDG PET/CT. A standard of reference (SR) was established by a multidisciplinary team to ensure that the same set of criteria were used for classification of patients, that is, either as CUP patients or patients with a suggested primary tumor site. The independently obtained suggestions of primary tumor sites using PET/CT and CT were correlated with the SR to reach a consensus regarding true-positive (TP), true-negative, false-negative, and false-positive results. Results. SR identified a primary tumor site in 66 CUP patients (48.9%). PET/CT identified 38 TP primary tumor sites and CT identified 43 TP primary tumor sites. No statistically significant differences were observed between (18)F-FDG PET/CT and CT alone in regard to sensitivity, specificity, and accuracy. Conclusion. In the general CUP population with multiple extracervical metastases (18)F-FDG PET/CT does not represent a clear diagnostic advantage over CT alone regarding the ability to detect the primary tumor site.     

Effectiveness of Breast MRI and 18F-FDG PET/CT for the Preoperative Staging of Invasive Lobular Carcinoma versus Ductal Carcinoma

Purpose

We evaluated the utility of magnetic resonance imaging (MRI) and ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) for the preoperative staging of invasive lobular carcinoma (ILC) of the breast and compared the results with those of invasive ductal carcinoma (IDC).

Methods

The study included pathologically proven 32 ILCs and 73 IDCs. We compared clinical and histopathological characteristics and the diagnostic performances of MRI and ¹⁸F-FDG PET/CT for the primary mass, additional ipsilateral and/or contralateral lesion(s), and axillary lymph node metastasis between the ILC and IDC groups.

Results

Primary ILCs were greater in size, but demonstrated lower maximum standardized uptake values than IDCs. All primary masses were detected on MRI. The detection rate for ILCs (75.0%) was lower than that for IDCs (83.6%) on ¹⁸F-FDG PET/CT, but the difference was not significant. For additional ipsilateral lesion(s), the sensitivities and specificities of MRI were 87.5% and 58.3% for ILC and 100.0% and 66.7% for IDC, respectively; whereas the sensitivities and specificities of ¹⁸F-FDG PET/CT were 0% and 91.7% for ILC and 37.5% and 94.7% for IDC, respectively. The sensitivity of ¹⁸F-FDG PET/CT for ipsilateral lesion(s) was significantly lower in the ILC group than the IDC group. The sensitivity for ipsilateral lesion(s) was significantly higher with MRI; however, specificity was higher with ¹⁸F-FDG PET/CT in both tumor groups. There was no significant difference in the diagnostic performance for additional contralateral lesion(s) or axillary lymph node metastasis on MRI or ¹⁸F-FDG PET/CT for ILC versus IDC.

Conclusion

The MRI and ¹⁸F-FDG PET/CT detection rates for the primary cancer do not differ between the ILC and IDC groups. Although ¹⁸F-FDG PET/CT demonstrates lower sensitivity for primary and additional ipsilateral lesions, it shows higher specificity for additional ipsilateral lesions, and could play a complementary role in the staging of ILC as well as IDC.     

用全身PET/CT寻找转移瘤患者的原发灶

目的:对不明原因转移瘤患者,探讨利用正电子发射计算机断层显像（positron emission tomography/computed tomography,PET/CT）寻找肿瘤原发灶的临床价值。方法:回顾性收集经病理学证实或影像学检查诊断为转移瘤的137例住院患者的临床及PET/CT成像资料,计算全身PET/CT显像对不明原因转移瘤患者肿瘤原发灶的检出率,分析不同部位转移瘤原发灶检出率间的差异。结果:确诊1例淋巴瘤患者被排除,18F-FDG PET/CT正确检出原发病灶89例,检出率为65.4%（89/136）。18F-FDG PET/CT对于淋巴结转移、骨转移、肝转移及脑转移瘤肿瘤原发灶检出率分别为63.2%（36/57）、60.0%（18/30）、86.7%（13/15）和57.1%（8/14）。结论:全身PET/CT显像在不明原因转移瘤寻找肿瘤原发灶方面具有重要临床应用价值。     

A second-generation microRNA-based assay for diagnosing tumor tissue origin

Background.

Cancers of unknown primary origin (CUP) constitute 3%–5% (50,000 to 70,000 cases) of all newly diagnosed cancers per year in the United States. Including cancers of uncertain primary origin, the total number increases to 12%–15% (180,000 to 220,000 cases) of all newly diagnosed cancers per year in the United States. Cancers of unknown/uncertain primary origins present major diagnostic and clinical challenges because the tumor tissue of origin is crucial for selecting optimal treatment. MicroRNAs are a family of noncoding, regulatory RNA genes involved in carcinogenesis. MicroRNAs that are highly stable in clinical samples and tissue specific serve as ideal biomarkers for cancer diagnosis. Our first-generation assay identified the tumor of origin based on 48 microRNAs measured on a quantitative real-time polymerase chain reaction platform and differentiated 25 tumor types.

Methods.

We present here the development and validation of a second-generation assay that identifies 42 tumor types using a custom microarray. A combination of a binary decision-tree and a k-nearest-neighbor classifier was developed to identify the tumor of origin based on the expression of 64 microRNAs.

Results.

Overall assay sensitivity (positive agreement), measured blindly on a validation set of 509 independent samples, was 85%. The sensitivity reached 90% for cases in which the assay reported a single answer (>80% of cases). A clinical validation study on 52 true CUP patients showed 88% concordance with the clinicopathological evaluation of the patients.

Conclusion.

The abilities of the assay to identify 42 tumor types with high accuracy and to maintain the same performance in samples from patients clinically diagnosed with CUP promise improved utility in the diagnosis of cancers of unknown/uncertain primary origins.     

Use of 18F-FDG PET/CT to locate primary malignancies in patients with hepatic cirrhosis and malignant ascites

Objective：Ascites in patients with hepatic cirrhosis is caused by cirrhosis in most cases.For most malignant ascites,the primary malignancy could be readily identified using conventional imaging methods,e.g.,computer tomography （CT） and magnetic resonance imaging （MRI）.However,in a small fraction of the patients,the primary malignancy remains occult even with these examinations.In this retrospective study,we assessed the usefulness of 18F-FDG PET/CT in patients with hepatic cirrhosis and malignant ascites of otherwise unknown origin.Methods：Twenty-eight patients with malignant ascites of unknown primary sites after CT,MRI and ultrasound during the period of five years between January 2008 and December 2012 had received 18F-FDG PET/CT.Medical records of these patients were reviewed and analyzed.Results：Elevated 18F-FDG absorption was found in 23 of 28 cases in the following sites：gastrointestinal tract （n=10,43.5％）,prostate （n=5,21.7％）,peritoneum （n=4,13.3％）,and ovary （n=4,13.3％）.Cancer was confirmed by pathology in 20 cases after open or laparoscopic surgeries.Five patients were found to have benign ascites,among which,3 were found to be false positive due to tuberculosis.SUV values were significantly higher for tumors than for benign lesions （mean values,6.95 vs.2.94; P=0.005）.Conclusions：The 18F-FDG PET/CT can be as a powerful imaging tool in identifying tissue origin in liver cirrhosis patients suspected of cancers or with cancers of unknown primary sites.     

PET imaging of patients with non-small cell lung cancer employing an EGF receptor targeting drug as tracer

Background:

We have previously developed ¹¹C-erlotinib as a new positron emission tomography (PET) tracer and shown that it accumulates in epidermal growth factor receptor (EGFR)-positive lung cancer xenografts in mice. Here, we present a study in patients with non-small cell lung cancer (NSCLC) investigating the feasibility of ¹¹C-erlotinib PET as a potential method for the identification of lung tumours accumulating erlotinib.

Methods:

Thirteen patients with NSCLC destined for erlotinib treatment were examined by contrast-enhanced computed tomography (CT), ¹¹C-erlotinib PET/low-dose CT and ¹⁸F-fluoro-2-deoxy--glucose (¹⁸F-FDG) PET/low-dose CT before start of the erlotinib treatment. After 12 weeks treatment, they were examined by ¹⁸F-FDG PET/contrast-enhanced CT for the assessment of clinical response.

Results:

Of the 13 patients included, 4 accumulated ¹¹C-erlotinib in one or more of their lung tumours or lymph-node metastases. Moreover, ¹¹C-erlotinib PET/CT identified lesions that were not visible on ¹⁸F-FDG PET/CT. Of the four patients with accumulation of ¹¹C-erlotinib, one died before follow-up, whereas the other three showed a positive response to erlotinib treatment. Three of the nine patients with no accumulation died before follow-up, four showed progressive disease while two had stable disease after 12 weeks of treatment.

Conclusion:

Our data show a potential for ¹¹C-erlotinib PET/CT for visualizing NSCLC lung tumours, including lymph nodes not identified by ¹⁸F-FDG PET/CT. Large clinical studies are now needed to explore to which extent pre-treatment ¹¹C-erlotinib PET/CT can predict erlotinib treatment response.     

Prognostic value of interim 18F-FDG PET/CT in diffuse large B-cell lymphoma

Objective: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. The prognostic factor currently used is not accurate enough to predict the outcomes of patients with DLBCL. The prognostic significance of interim PET/CT in DLBCL remains controversial. The aim of this study is to determine the predictive value of interim 18F-FDG PET/CT after first-line treatment in patients with DLBCL. Methods: Thirty-two patients with DLBCL underwent baseline, interim and post-treatment 18F-FDG PET/CT scans. Imaging results were analyzed for the survival of patients via software SPSS 13.0, retrospectively. Results: Thirty-one of the 32 patients were treated with R-CHOP regimen, and interim 18F-FDG PET/CT of 24 patients was performed after 2 cycles of treatment. After a median follow-up period of 16.7 months, the 2-year progression-free survival (PFS) rates were significantly different between the groups above and below SUV max cut-off value of 2.5 (P=0.039). No significant differences were found in the 2-year PFS rates if SUV max cut-off values were set as 2.0 and 3.0, respectively (P=0.360; P=0.113). Conclusions: Interim PET/CT could predict the prognosis of DLBCL patients with the SUV max cut-off value of 2.5, but more clinical data should be concluded to confirm this conclusion.     

Cancer of unknown primary: a population-based analysis of temporal change and socioeconomic disparities

Background:

Cancer of unknown primary (CUP) is the fourth most common cause of cancer death. With advanced diagnostics and treatments, we investigated the proportion of cancers diagnosed as CUP, treatment outcomes and association with socioeconomic disparities.

Methods:

We analysed trends in CUP diagnosis and outcome within the Surveillance, Epidemiology, and End Results registry between 1973 and 2008.

Results:

The percentage of all cancers diagnosed as CUP has decreased over time comprising <2% of cancers since 2007. A higher proportion of CUP was diagnosed in the elderly, females, blacks and residents of less affluent or less educated counties. Median survival of all CUP patients was 3 months, with no improvement over time. The 5-year survival significantly improved in those with squamous histology (squamous cell carcinoma; SCC) but only marginally in non-SCC. Factors associated with a longer survival on multivariate analysis included white race; female; <65 years old; most recent decade at diagnosis; SCC; married; a histological diagnosis; and treatment with radiotherapy (all P<0.001). Despite the improvement in survival with radiotherapy, its use was less frequent in females and blacks.

Conclusion:

The percentage of cancers diagnosed as CUP is decreasing but prognosis remains poor, particularly in non-SCC CUP. However, significant socioeconomic disparities exist in diagnosis and survival, suggesting inequalities in access to diagnostic investigations and treatment.     

Prognostic value of post-treatment 18F-FDG PET/CT for advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy简

Objective：To clarify the prognostic value of post-treatment 18F-fluorodeoxyglucose （FDG） positron emission tomography （PET）/computed tomography （CT） in patients with advanced head and neck squamous cell carcinoma （HNSCC） after combined intra-arterial chemotherapy and radiotherapy （IACR）.Methods：Thirty-six patients with HNSCC who underwent IACR were recruited.The period from the end of IACR to the last post-treatment 18F-FDG PET/CT examination was 8-12 weeks.Both patient-based and lesion-based analyses were used to evaluate the PET/CT images.For lesion-based analysis,36 regions （12 lesions of recurrences and 24 scars at primary sites） were selected.The Kaplan-Meier method was used to assess the overall survival （OS） stratified by 18F-FDG uptake or visual interpretation results.Results：Twelve patients with recurrence were identified by six months after IACR.The sensitivity and specificity in the patient-based analysis were 67％ （8/12） and 88％ （21/24）,respectively.The mean OS was estimated to be 12.1 months （95％ CI,6.3-18.0 months） for the higher maximum standardized uptake value （SUVmax） group （n=7） and 44.6 months （95％ CI,39.9-49.3 months） for the lower SUVmax group （n=29）.OS in the higher SUVmax group （cut-off point,6.1） or positive visual interpretation group was significantly shorter than that in the lower SUVmax or negative visual interpretation group （P＜0.001 and P＜0.05,respectively）.Conclusions：The SUVmax and visual interpretation of HNSCC on post-IACR 18F-FDG PET/CT can provide prognostic survival estimates.     

18F-FDG PET/CT surveillance at 3–6 and 12 months for detection of recurrence and second primary cancer in patients with head and neck squamous cell carcinoma

Background:

Early detection of recurrence of head and neck squamous cell carcinoma (HNSCC), which is often obscured by surgical or radiotherapy-induced tissue distortion, is essential for proper patient management.

Methods:

A total of 143 consecutive patients with previously untreated HNSCC were evaluated by whole-body fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and regular clinical follow-up after curative treatment. The ¹⁸F-FDG PET/CT was performed ∼3–6 and 12 months after treatment and findings suspicious for recurrence or SPC were confirmed using histopathology.

Results:

The sensitivities of 3–6- and 12-month PET/CT scans at patient level were 96% and 93%, respectively, and those of regular clinical follow-up were 11% and 19%, respectively (McNemar test, P<0.001). In patients with no clinical suspicion, PET/CT detected 95% and 91% of recurrent patients at 3–6 and 12 months, respectively. The sensitivity of PET/CT for the identification of SPC was 29% and 80% at 3–6 and 12 months, respectively. A positive interpretation of PET/CT was significantly associated with poor overall survival (log-rank test, P<0.001).

Conclusion:

The ¹⁸F-FDG PET/CT surveillance is beneficial for the detection of recurrence that may be missed by regular follow-up physical and endoscopic examinations of the head and neck area after curative treatment for HNSCC.     

Inflammation as a validated prognostic determinant in carcinoma of unknown primary site

Background:

Carcinoma of unknown primary (CUP) is a clinical presentation with a poor prognosis. Inflammation-based prognostic systems are stage-independent prognostic predictors in various malignancies. We aimed to assess the accuracy of the modified Glasgow Prognostic Score (mGPS), neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) as objective prognostic models in CUP.

Methods:

We derived inflammatory scores in 60 consecutive CUP referrals to the Imperial College oncology unit between 1996 and 2011. Patient demographics, treatment and staging data and full blood profiles were collected. An independent cohort of 179 patients presenting to the Taipei Veterens Hospital between 2000 and 2009 were used as a ‘validation'' data set. Uni- and multivariate survival analysis was used to predict the overall survival (OS).

Results:

Sixty patients were included: median age 61 (range: 33–86); 51% men; median OS 5.9 months (0.7–42.9); 88% with distant metastases. On univariate analysis NLR >5 (P=0.04) and mGPS (score 1–2) (P=0.03) correlated with OS. Multivariate analysis demonstrated significant hazard ratios for NLR; 2.02 (CI 1.0–4.1) (P=0.04) and mGPS; 1.52 (CI 1.0–2.3) (P=0.03). These findings were reinforced by analysis of the validation data.

Conclusion:

NLR and mGPS are independent, externally validated prognostic markers in CUP, with superior objectivity compared with performance status.     

Italian Multicenter Study on Accuracy of 18F-FDG PET/CT in Assessing Bone Marrow Involvement in Pediatric Hodgkin Lymphoma

Introduction

The present study investigated the utility of fluorine-18 (¹⁸F) fluoro-2-deoxy-d-glucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared with bone marrow biopsy (BMB) in newly diagnosed pediatric Hodgkin lymphoma (HL).

Whole Body 18F-FDG PET/CT Imaging in the Detection of Primary Tumours in Patients with a Metastatic Carcinoma of Unknown Origin

Purpose: The aim of this study was to evaluate the role of whole body 18F-FDG PET/CT imaging in thedetection of primary tumors in patients with a metastatic cancer from an unknown primary site. Methods: Thestudy population consisted of 43 patients with a biopsy proven metastatic disease, negative conventional diagnosticprocedures (including CT/MRI/endoscopic procedures) and a whole body 18F-FDG PET/CT examination.Patients’ records were retrospectively analyzed. According to the final pathologic diagnoses, rate of detection ofthe primary tumor site was determined. Additionally, overall patient survival was calculated to evaluate theprognostic value of 18F-FDG PET/CT findings. Results: A primary tumor site was shown by 18F-FDG PET/CTin 24 patients (24/43; 55.8%). In 18 patients 18F-FDG PET/CT scans were negative (18/43; 41.8%). In a patientwith an adenocarcinoma metastasis 18F-FDG PET/CT was falsely positive for an inflammatory lesion in thelung. Among the 18F-FDG PET/CT positive and negative groups median overall survival was not significantlydifferent (log-rank p=0.573). Conclusion: Whole body 18F-FDG PET/CT imaging has a high rate of detectionof a primary tumor in patients with a carcinoma of unknown origin.     

The diagnostic performance of 18F-FDG PET/CT,CT and MRI in the treatment evaluation of ablation therapy for colorectal liver metastases: A systematic review and meta-analysis

Purpose

Uncertainty exists regarding the optimal imaging modality for timely detection of disease progression (DP) after ablation therapy for colorectal liver metastases. We evaluated the diagnostic accuracy of ¹⁸F-FDG PET(/CT), CT and MRI for detection of DP following ablation therapy.

Biological significance of fluorine-18-α-methyltyrosine (FAMT) uptake on PET in patients with oesophageal cancer

Purpose:

¹⁸F-FAMT as an amino-acid tracer for positron emission tomography (PET) is useful for detecting human neoplasms. ¹⁸F-FAMT is accumulated in tumour cells solely via L-type amino-acid transporter 1 (LAT1). This study was conducted to investigate the biological significance of ¹⁸F-FAMT uptake in patients with oesophageal cancer.

Methods:

From April 2008 to December 2011, 42 patients with oesophageal cancer underwent both ¹⁸F-FAMT PET/CT and ¹⁸F-FDG PET/CT before surgical treatment. The immunohistochemical analysis of LAT1, CD98, Ki-67, CD34, p53, p-Akt and p-mTOR was performed on the primary lesions. In vitro experiments were performed to examine the mechanism of ¹⁸F-FAMT uptake.

Results:

High uptake of ¹⁸F-FAMT was significantly associated with advanced stage, lymph node metastasis and the expression of LAT1, CD98, Ki-67 and CD34. LAT1 expression yielded a statistically significant correlation with CD98 expression, cell proliferation, angiogenesis and glucose metabolism. In vitro experiments revealed that ¹⁸F-FAMT was specifically transported by LAT1.

Conclusions:

The uptake of ¹⁸F-FAMT within tumour cells is determined by the LAT1 expression and correlated with cell proliferation and angiogenesis in oesophageal cancer. The present experiments also confirmed the presence of LAT1 as an underlying mechanism of ¹⁸F-FAMT accumulation.     

Fluorine‐18‐Fluorodeoxyglucose Positron Emission Tomography in Response Assessment Before High‐Dose Chemotherapy for Lymphoma: A Systematic Review and Meta‐Analysis

Background.

We conducted a systematic review and meta-analysis to better define the prognostic ability of fluorine-18-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) following salvage chemotherapy for relapsed or refractory Hodgkin''s lymphoma (HL) and aggressive non-Hodgkin''s lymphoma.

Methods.

We searched PubMed (from inception to January 31, 2010), bibliographies, and review articles without language restriction. Two assessors independently assessed study characteristics, quality, and results. We performed a meta-analysis to determine prognostic accuracy.

Results.

Twelve studies including 630 patients were eligible. The most commonly evaluated histologies were diffuse large B-cell lymphoma (n = 313) and HL (n = 187), which were typically treated with various salvage and high-dose chemotherapy regimens. Studies typically employed nonstandardized protocols and diagnostic criteria. The prognostic accuracy was heterogeneous across the included studies. ¹⁸F-FDG PET had a summary sensitivity of 0.69 (95% confidence interval [CI], 0.56–0.81) and specificity of 0.81 (95% CI, 0.73–0.87). The summary estimates were stable in sensitivity analyses. In four studies that performed direct comparisons between PET and conventional restaging modalities, PET had a superior accuracy for predicting treatment outcomes. Subgroup and metaregression analyses did not identify any particular factor to explain the observed heterogeneity.

Conclusion.

¹⁸F-FDG PET performed after salvage therapy appears to be an appropriate test to predict treatment failure in patients with refractory or relapsed lymphoma who receive high-dose chemotherapy. Some evidence suggests PET is superior to conventional restaging for this purpose. Given the methodological limitations in the primary studies, prospective studies with standardized methodologies are needed to confirm and refine these promising results.     

The role of Fluorine-18-Fluorodeoxyglucose positron emission tomography in staging and restaging of patients with osteosarcoma

Background

The objective of this study is to systematically review the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) with Fluorine-18-Fluorodeoxyglucose (FDG) in patients with osteosarcoma (OS).

Methods

A comprehensive literature search of published studies through October 10^th, 2012 in PubMed/MEDLINE, Embase and Scopus databases regarding whole-body FDG-PET and FDG-PET/CT in patients with OS was performed.

Results

We identified 13 studies including 289 patients with OS. With regard to the staging and restaging of OS, the diagnostic performance of FDG-PET and PET/CT seem to be high; FDG-PET and PET/CT seem to be superior to bone scintigraphy and conventional imaging methods in detecting bone metastases; conversely, spiral CT seems to be superior to FDG-PET in detecting pulmonary metastases from OS

Conclusions

Metabolic imaging may provide additional information in the evaluation of OS patients. The combination of FDG-PET or FDG-PET/CT with conventional imaging methods seems to be a valuable tool in the staging and restaging of OS and may have a relevant impact on the treatment planning.     

Clinical Value of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Response Evaluation after Primary Treatment of Advanced Epithelial Ovarian Cancer

Aims

To prospectively evaluate the use of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) in the definition of the treatment response after primary treatment of advanced epithelial ovarian cancer (EOC).