Baijiang Zhang

Value of PET/CT versus enhanced CT for locoregional lymph nodes in non-small cell lung cancer ☆

PURPOSE To compare the diagnostic efficacies of integrated (18)F FDG PET/CT images and contrast-enhanced helical CT images in locoregional lymph node metastasis in the patients with non-small cell lung cancer (NSCLC). METHODS From June 2005 to June 2007, 122 potentially operable patients with proven or suspected non-small cell lung cancer underwent integrated PET/CT and contrast-enhanced CT scans followed by surgical nodal staging. The results of reviewing PET/CT and enhanced CT images for the locoregional lymph node metastasis were compared in relation to pathologic findings. RESULTS Preoperative nodal staging was compared with postoperative histopathological staging, 80% (98 of 122) of patients correctly staged, 13% (16 of 122) of patients were overstaged, and 7% (8 of 122) were understaged by PET/CT, while those values for CT were 56% (68 of 122), 26% (32 of 122), and 18% (22 of 122), respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for lymph nodes were 86%, 85%, 85%, 64%, 95%, respectively; compared with 69%, 71%, 70%, 43%, 88% for CT (P=0.000, 0.000, 0.000, 0.001, 0.001, respectively). 81% false-negative interpretations and 72% false-positive interpretations on CT were corrected by PET/CT. 57% false-negative interpretations and 45% false-positive interpretations on PET/CT were corrected by CT. 6 % (9 of 153) positive lymph nodes and 8% (40 of 486) negative nodes at pathology were incorrectly diagnosed both by PET/CT and CT. CONCLUSION Integrated PET/CT improves the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value than enhanced CT in the assessment of locoregional lymph nodes, and provides more efficient and accurate data of nodal staging, with a better effect on diagnosis and therapy in non-small cell lung cancer.

Diagnostic and Prognostic Value of 18F-FDG PET/CT for Patients with Suspected Recurrence from Squamous Cell Carcinoma of the Esophagus

Patients with esophageal squamous cell carcinoma (ESCC) are commonly at high risk of recurrence within 2 y after initial treatment. The aim of this study was to evaluate the role of 18F-FDG PET/CT in patients with possibly recurrent ESCC who underwent definitive treatment. Methods: Fifty-six patients with previously treated ESCC underwent PET/CT scans. The PET/CT findings were validated by histopathology or clinical follow-up of at least 6 mo. The sensitivity, specificity, and accuracy of PET/CT for detecting recurrence were calculated. Comparison of the standardized uptake value (SUV) was performed between patients grouped according to their status at the last follow-up (relapsed or relapse-free, alive or dead). The overall survival rates were estimated by the Kaplan–Meier method. The Cox proportional hazards model was used to evaluate independent prognostic variables for both univariate and multivariate survival analysis. Results: Forty-five (80.4%) patients had recurrence in 72 (66.1%) malignant sites. On PET/CT, there were 9 false-positive and 5 false-negative results. The overall sensitivity, specificity, and accuracy of PET/CT for detecting recurrence at all sites were 93.1% (67/72), 75.7% (28/37), and 87.2% (95/109), respectively. PET/CT was highly sensitive, specific, and accurate at regional and distant sites. At local sites, sensitivity was high, but specificity was lower (50%) because of a high incidence of false-positive findings. Patients who were confirmed with recurrence or who had died at the last follow-up had higher SUVs (P = 0.027 and <0.001, respectively). In multivariate survival analysis, therapeutic modality (hazard ratio = 0.437; P = 0.044), SUV (hazard ratio = 1.071; P = 0.029), and disease status on PET/CT (hazard ratio = 2.430; P = 0.045) were independent significant prognostic predictors for overall survival. The Kaplan–Meier survival curves indicated poor prognostic outcome in subgroup patients with higher SUVs or systemic disease on PET/CT. Conclusion: 18F-FDG PET/CT is highly effective for detecting recurrent ESCC. The relatively low specificity at local sites is associated primarily with a high rate of false-positive interpretations at anastomoses. PET/CT can also provide noninvasive and independent prognostic information using SUV and recurrent disease pattern on PET/CT images for previously treated ESCC.

Using 18F-Fluorodeoxyglucose Positron Emission Tomography to Estimate the Length of Gross Tumor in Patients With Squamous Cell Carcinoma of the Esophagus

PURPOSE To determine the optimal method of using (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) to estimate gross tumor length in esophageal carcinoma. METHODS AND MATERIALS Thirty-six patients with esophageal squamous cell carcinoma treated with radical surgery were enrolled. Gross tumor volumes (GTVs) were delineated using three different methods: visual interpretation, standardized uptake value (SUV) 2.5, and 40% of maximum standard uptake value (SUV(max)) on FDG-PET imaging. The length of tumors on PET scan were measured and recorded as Length(vis), Length(2.5), and Length(40), respectively, and compared with the length of gross tumor in the resected specimen (Length(gross)). All PET data were reviewed again postoperatively, and the GTV was delineated using various percentages of SUV(max). The optimal-threshold SUV was generated when the length of PET matched the Length(gross). RESULTS The mean (+/-SD) Length(gross) was 5.48 +/- 1.98 cm. The mean Length(vis), Length(2.5), and Length(40) were 5.18 +/- 1.93 cm, 5.49 +/- 1.79 cm, and 4.34 +/- 1.54 cm, respectively. The mean Length(vis) (p = 0.123) and Length(2.5) (p = 0.957) were not significantly different from Length(gross), and Length(2.5) seems more approximate to Length(gross.) The mean Length(40) was significantly shorter than Length(gross) (p < 0.001). The mean optimal threshold was 23.81% +/- 11.29% for all tumors, and it was 19.78% +/- 8.59%, 30.92% +/- 12.28% for tumors >/=5 cm, and <5 cm, respectively (p = 0.009). The correlation coefficients of the optimal threshold were -0.802 and -0.561 with SUV(max) and Length(gross), respectively. CONCLUSIONS The optimal PET method to estimate the length of gross tumor varies with tumor length and SUV(max); an SUV cutoff of 2.5 provided the closest estimation in this study.

Comparison of Tumor Volumes as Determined by Pathologic Examination and FDG-PET/CT Images of Non–Small-Cell Lung Cancer: A Pilot Study

PURPOSE To determine the cut-off standardized uptake value (SUV) on (18)F fluoro-2-deoxy-glucose (FDG) positron emission tomography/computed tomography (FDG-PET/CT) images that generates the best volumetric match to pathologic gross tumor volume (GTV(path)) for non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS Fifteen patients with NSCLC who underwent FDG-PET/CT scans followed by lobectomy were enrolled. The surgical specimen was dissected into 5-7-mum sections at approximately 4-mm intervals and stained with hematoxylin and eosin. The tumor-containing area was outlined slice by slice and the GTV(path) determined by summing over all the slices, taking into account the interslice thickness and fixation-induced volume reduction. The gross tumor volume from the PET images, GTV(PET), was determined as a function of cut-off SUV. The optimal threshold or optimal absolute SUV was defined as the value at which the GTV(PET) was the same as the GTV(path). RESULTS The fixation process induced a volumetric reduction to 82% +/- 10% (range, 62-100%) of the original. The maximal SUV was 10.1 +/- 3.6 (range, 4.2-18.7). The optimal threshold and absolute SUV were 31% +/- 11% and 3.0 +/- 1.6, respectively. The optimal threshold was inversely correlated with GTV(path) and tumor diameter (p < 0.05), but the optimal absolute SUV had no significant correlation with GTV(path) or tumor diameter (p > 0.05). CONCLUSION This study evaluated the use of GTV(path) as a criterion for determining the optimal cut-off SUV for NSCLC target volume delineation. Confirmatory studies including more cases are being performed.

COMPARISON OF 18F-FLUOROTHYMIDINE AND 18F-FLUORODEOXYGLUCOSE PET/CT IN DELINEATING GROSS TUMOR VOLUME BY OPTIMAL THRESHOLD IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THORACIC ESOPHAGUS

PURPOSE To determine the optimal method of using (18)F-fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) simulation to delineate the gross tumor volume (GTV) in esophageal squamous cell carcinoma verified by pathologic examination and compare the results with those using (18)F-fluorodeoxyglucose (FDG) PET/CT. METHODS AND MATERIALS A total of 22 patients were enrolled and underwent both FLT and FDG PET/CT. The GTVs with biologic information were delineated using seven different methods in FLT PET/CT and three different methods in FDG PET/CT. The results were compared with the pathologic gross tumor length, and the optimal threshold was obtained. Next, we compared the simulation plans using the optimal threshold of FLT and FDG PET/CT. The radiation dose was prescribed as 60 Gy in 30 fractions with a precise radiotherapy technique. RESULTS The mean +/- standard deviation pathologic gross tumor length was 4.94 +/- 2.21 cm. On FLT PET/CT, the length of the standardized uptake value 1.4 was 4.91 +/- 2.43 cm. On FDG PET/CT, the length of the standardized uptake value 2.5 was 5.10 +/- 2.18 cm, both of which seemed more approximate to the pathologic gross tumor length. The differences in the bilateral lung volume receiving > or =20 Gy, heart volume receiving > or =40 Gy, and the maximal dose received by spinal cord between FLT and FDG were not significant. However, the values for mean lung dose, bilateral lung volume receiving > or =5, > or =10, > or =30, > or =40, and > or =50 Gy, mean heart dose, and heart volume receiving > or =30 Gy using FLT PET/CT-based planning were significant lower than those using FDG PET/CT. CONCLUSION A standardized uptake value cutoff of 1.4 on FLT PET/CT and one of 2.5 on FDG PET/CT provided the closest estimation of GTV length. Finally, FLT PET/CT-based treatment planning provided potential benefits to the lungs and heart.

NONINVASIVE EVALUATION OF MICROSCOPIC TUMOR EXTENSIONS USING STANDARDIZED UPTAKE VALUE AND METABOLIC TUMOR VOLUME IN NON-SMALL-CELL LUNG CANCER

PURPOSE To prospectively evaluate whether maximal microscopic extensions (MEmax) correlate with maximal standardized uptake value (SUVmax) and metabolic tumor volume (MTV) at 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images in non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS Thirty-nine patients with Stage I-IIIA NSCLC underwent surgery after FDG-PET/CT scanning. SUVmax and MTV were calculated on the PET/CT images. The maximum linear distance from the tumor margin to the farthest extent of the tumor in every dimension was measured at the tumor section. The correlations among MEmax, SUVmax, MTV and other clinical pathologic parameters were analyzed. RESULTS MEmax for all patients had a significant correlation with SUVmax (r = 0.777, p = 0.008) and MTV (r = 0.724, p < 0.001). When expressed in terms of the probability of covering ME with respect to a given margin, we suggested that margins of 1.93 mm, 3.90 mm, and 9.60 mm for SUVmax ≤ 5, 5-10, and >10 added to the gross tumor volume would be adequate to cover 95% of ME. CONCLUSIONS This study demonstrated that tumors with high SUVmax and MTV have more MEmax and would therefore require more margin expansion from gross tumor volume to clinical target volume. FDG-PET/CT, especially for SUVmax, is promising and effective and merits additional study in noninvasive delimiting of the clinical target volume margin for NSCLC.

Rapid on-site evaluation during endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis of hilar and mediastinal lymphadenopathy in patients with lung cancer.

The purpose of this study was to assess the usefulness of rapid on-site evaluation (ROSE) during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and the interpretation of its results. Based on the criterion of using ROSE or not, 236 patients with known or suspected lung cancer undergoing EBUS-TBNA were allocated into the ROSE group (122 patients with 252 lymph nodes) and non-ROSE group (114 patients with 260 lymph nodes). In the ROSE group, the percentages of the suspicious specimens on cytology and non-diagnostic specimens on pathology were both significantly lower than that in the non-ROSE group (8.7% vs. 14.6%, p = 0.038; and 0.9% vs. 4.4%, p = 0.018, respectively), and 13 out of 22 suspicious lesions on ROSE were confirmed with definite diagnoses on TBNA pathology. The diagnostic yield stratified by pathology was significantly higher in the ROSE group than that in the non-ROSE group (90.5% vs. 81.2%, p = 0.003). These results suggest that ROSE during EBUS-TBNA allows for a low rate of suspicious results and therefore improves the diagnostic yield stratified by pathology when sampling hilar or mediastinal lymphadenopathy in patients with lung cancer.

A Pilot Study of 18 F-Alfatide PET/CT Imaging for Detecting Lymph Node Metastases in Patients with Non-Small Cell Lung Cancer

Angiogenesis plays a key role in tumor development and αvβ3 integrin are overexpressed on the endothelial cell surface of newly forming vessels. 18F-Alfatide has favorable properties for αvβ3 integrin targeting and showed potential for imaging angiogenesis with Positron Emission Tomography (PET)/computed tomography (CT). In this study, 13 patients with non-small cell lung cancer (NSCLC) who underwent 18F-Alfatide PET/CT before surgery were enrolled. The uptake of all dissected lymph nodes (LNs) of 18F-Alfatide were assessed visually and analyzed with a maximum and mean standard uptake value (SUVmax, SUVmean) and SUV ratios. LN metastases were pathologically confirmed and 20 of 196 LNs were malignant. All malignant LNs were successfully visualized on 18F-Alfatide PET/CT in patients and the sensitivity, specificity and accuracy was 100.0%, 94.9% and 95.4%, respectively. SUVmax, SUVmean and SUV ratios in malignant LNs were significantly higher than in benign LNs for NSCLC patients (P < 0.001). The same result was observed in patients with adenocarcinoma and squamous cell carcinoma (P < 0.001). The 18F-Alfatide parameter shows high sensitivity (83.9–100%), specificity (78.6–96.7%) and accuracy (81.7–96.9%) according to thresholds calculated from receiver operating characteristic curve. Our results suggest that 18F-Alfatide PET/CT is valuable in the diagnosis of metastatic LNs for NSCLC patients.

Potential impact of 18 FDG-PET/CT on surgical approach for operable squamous cell cancer of middle-to-lower esophagus

Background Fluorodeoxyglucose-positron emission tomography (PET)/computed tomography (CT) is reported to have a significant advantage over CT for staging esophageal cancer (EC). However, whether PET/CT may play a useful role in guiding surgical approach remains undetermined. Methods Patients with potentially resectable squamous cell EC were randomized into either PET/CT group or CT group. The surgical data and survival outcomes were compared. Results Compared to the CT group, the right-sided approach was more frequently used (42.6% versus 25.5%, P=0.065) in the PET/CT group in order to allow surgical access to radiographically suspicious lymph nodes inaccessible from the left, thus enabling the removal of more involved lymph nodes (2.83 versus 1.76; P=0.039) as well as their stations (1.65 versus 1.08; P=0.042). Although the overall survival between the two groups was similar, the PET/CT group had a longer disease-free survival (DFS) than the CT group (27.1 months versus 18.9 months; P=0.019), especially in the subgroup of node-positive patients (22.5 months versus 13.5 months; P=0.02). Preoperative imaging arm was the only prognostic factor found to independently influence DFS. Conclusion For patients with middle-to-lower EC, surgical approaches directed by PET/CT may increase the likelihood of complete resection and affect DFS.

The clinical features, treatment, and prognosis of primary mediastinal malignant melanoma: A case report

Rationale: Primary malignant melanoma (MM) of the mediastinum is exceedingly rare; a review of the English-language literature reveals only a small number of case reports. In this paper, we discuss a case of primary mediastinal MM and present a review of the relevant literature on its clinical features and treatment. Patient concerns: A 52-year-old male presenting with back pain was admitted to our hospital for treatment. Imaging examination revealed an anterior mediastinal mass and no evidence of other metastatic or primary lesions. Diagnoses: After complete resection by video-assisted thoracoscopic surgery (VATS), histopathologic examination showed evidence of brown melanin pigment in the tumor cells, which were immunohistochemically positive for antimelanoma antibodies (HMB-45, Melan-A, S-100, and Ki67). Interventions: Given the diagnosis of MM after surgery, the tumor was tested for the mutation in the BRAF gene (which encodes the serine/threonine-protein kinase B-raf) that leads to a V600E amino acid substitution, and the tumor was found to be wild type. Then the patient has been given immunotherapy. Outcomes: The patient completed 4 cycles of immunotherapy, and no recurrence or metastasis has been detected to date. Lessons: In such cases, it is difficult to prove the primary nature of the intrathoracic melanoma. Moreover, preoperative identification of this disease is challenging, making misdiagnosis likely. Due to fast progression and poor prognosis, timely and effective systemic treatment is necessary to improve the outcomes for patients with primary mediastinal MM.