Dianbin Mu

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.

Measuring Tumor Cell Proliferation with 18F-FLT PET During Radiotherapy of Esophageal Squamous Cell Carcinoma: A Pilot Clinical Study

The primary aim of this study was to use serial 18F-3′-deoxy-3′-fluorothymidine (FLT) PET/CT to measure tumor cell proliferation during radiotherapy of squamous cell carcinoma (SCC) of the esophagus. Methods: Twenty-one patients with inoperable locally advanced SCC of the esophagus underwent serial 18F-FLT PET/CT during radiotherapy. Each patient received a pretreatment scan, followed by 1–3 scans after delivery of 2, 6, 10, 20, 30, 40, 50, or 60 Gy to the tumor. Results: Among the 19 patients who completed radiotherapy without interruption, parameters reflecting 18F-FLT uptake in the tumor (i.e., maximum tumor standardized uptake value [SUVmax] and proliferation target volume) decreased steadily. All patients demonstrated an almost complete absence of proliferating esophageal tumor after 30 Gy and a complete absence after 40 Gy. In the 2 patients whose radiotherapy course was interrupted, 18F-FLT uptake in the tumor was greater after the interruption than before the interruption. Marked early reduction of 18F-FLT uptake in irradiated bone marrow was observed in all patients, even after only 2 Gy. All showed a complete absence of proliferating marrow in irradiated regions after 10 Gy. Both patients who underwent scans after completing the entire radiotherapy course showed no tumor uptake on 18F-FLT PET/CT but high uptake on 18F-FDG PET/CT. Pathologic examination of these regions revealed inflammatory infiltrates but no residual tumor. Conclusion: 18F-FLT uptake can be used to monitor the biologic response of esophageal SCC and normal tissue to radiotherapy. Increased uptake of 18F-FLT after treatment interruptions may reflect accelerated repopulation. 18F-FLT PET/CT may have an advantage over 18F-FDG PET/CT in differentiating inflammation from tumor.

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.

Assessment of 11C-labeled-4-N-(3-bromoanilino)-6, 7-dimethoxyquinazoline as a positron emission tomography agent to monitor epidermal growth factor receptor expression

The aim of the present study was to investigate the biodistribution of 11C‐labeled‐4‐N‐(3‐bromoanilino), 6,7‐dimethoxyquinazoline (11C‐PD153035) and the relationship between accumulation of the tracer and epidermal growth factor receptor (EGFR) expression levels. Biodistribution studies of 11C‐PD153035 were performed in tumor‐bearing nude mice. The amount of radioactivity in the lungs was small while concentrations were highest in the liver and intestine. From in vitro studies, the level of 11C‐PD153035 accumulation was detected in MDA‐MB‐468, A549, and MDA‐MB‐231 cells. The uptake of 11C‐PD153035 in cells was closely correlated with the EGFR expression level of cells (r2 = 0.85; P < 0.001), and the results obtained in excised tumors were also significantly correlated (r2 = 0.63; P = 0.003). Binding in MDA‐MB‐468, A549, and MDA‐MB‐231 tumors was reduced to background level at 60 min post injection 11C‐PD153035 by pretreatment with cold PD153035. The present study showed that whether in vitro or ex vivo the uptake of 11C‐PD153035 closely correlated with EGFR expression levels. In contrast, blocking studies revealed specific binding in the three kinds of tumors. Thus 11C‐PD153035 may be used as a positron emission tomography tracer to yield useful information about tumors, particularly for lung cancer with different EGFR expression levels. (Cancer Sci 2007; 98: 1413–1416)

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.

Hypoxia imaging with 18F-fluoroerythronitroimidazole integrated PET/CT and immunohistochemical studies in non-small cell lung cancer.

Purpose 18F-fluoroerythronitroimidazole (18F-FETNIM) PET/CT allows a noninvasive assessment of tumor hypoxia. The purpose of this study was to evaluate a noninvasive and simplicity parameter for quantization of 18F-FETNIM uptake with expectations to predict survival in non–small cell lung cancer surgical patients and investigate the relationship between 18F-FETNIM uptake and molecular markers related to hypoxia, glucose metabolism, and angiogenesis. Patients and Methods Thirty-two patients with biopsy-proven non–small cell lung cancer for surgical treatment were enrolled from March 2007 to February 2011. All patients had PET/CT studies with 18F-FETNIM and subsequently underwent surgery. Twenty-five patients had stage II disease of surgical staging only for statistical analysis. The tumor-to-mediastinum (T/Me) ratio was calculated and correlated with survival and immunohistochemical staining of hypoxia inducible factor 1&agr; (HIF-1&agr;), glucose transporter 1 (GLUT-1), and vascular endothelial growth factor (VEGF). Results The actuarial survival was worse for patients showing a high T/Me ratio, the best discriminative cutoff value being 1.9. A statistically significant worse survival was noted in patients having a tumor with a T/Me ratio of 1.9 or greater, compared with patients showing a tumor with a T/Me ratio of less than 1.9, a 3-year survival of 43.8% and 88.9%, respectively (P = 0.034). There was a positive correlation between T/Me ratio and HIF-1&agr; (P = 0.023), GLUT-1 (P = 0.035), and VEGF (P = 0.042). Conclusions T/Me ratio provides a noninvasive parameter for quantization of 18F-FETNIM uptake on PET/CT. T/Me ratio is correlated with a worse outcome and with the expression of HIF-1&agr;, GLUT-1, and VEGF, all up-regulated under hypoxic conditions.

Expression of Human Epidermal Growth Factor Receptor-2 in Resected Rectal Cancer.

AbstractThe addition of trastuzumab to chemotherapy was demonstrated to be beneficial for advanced human epidermal growth factor receptor-2 (HER-2) positive gastric cancer. However, the HER-2 status of rectal cancer remains uncertain. This study aimed to determine the HER-2 expression in a large multicenter cohort of rectal cancer patients. The clinical and pathological features of 717 patients were retrospectively reviewed. All the patients were diagnosed with primary rectal adenocarcinoma without distant metastasis and took surgery directly without any preoperative anticancer treatment. HER-2 status was assessed on resected samples. A total of 99 cases with IHC3+ and 16 cases with IHC 2+ plus gene amplification were determined as HER-2 positive. 22.6% of HER-2 positive patients had local recurrence, whereas 16.9% of HER-2 negative patients did (P = 0.146). HER-2 positive tumors were more likely to have distant metastasis (P = 0.007). Univariate analysis revealed that pathological tumor stage, pathological node stage, positive margin, and lymphovascular invasion were significantly correlated with 5-year disease-free survival (DFS) and 5-year overall survival (OS). The patients with >10 dissected lymph nodes showed significantly longer OS (P = 0.045) but not DFS (P = 0.054). HER-2 negative patients had significantly better 5-year DFS (P < 0.001) and 5-year OS (P = 0.013) than those of the HER-2 positive patients. In the subgroup analysis for the early rectal cancer and locally advanced rectal cancer, HER-2 was also a poor predictor for survival. Multivariate analysis revealed that HER-2 was an independent prognostic factor for 5-year DFS (hazard ratio [HR] = 1.919, 95% confidence interval [CI] 1.415–2.605, P < 0.001) and for 5-year OS (HR = 1.549, 95% CI 1.097–2.186, P = 0.013). When the treatment was included in the analysis for locally advanced patients, HER-2 was a prognostic factor for 5-year DFS (P = 0.001) but not for 5-year OS (P = 0.106). This study confirmed that HER-2 was expressed in a part of patients with rectal cancers and might be used as a negative predictor. The results may support the trials to assess the efficacy of trastuzumab in treating HER-2 positive rectal cancer patients.

HIF-1α and EGFR as progonostic factors for therapy response and 1-year locoregional recurrence not for distant metastasis and 2-year OS in unresectable stage IIIA NSCLC treated with combined chemoradiotherapy.

10640 Background: The purpose is to evaluated the effect of prognosis of HIF-1α and EGFR in unresectable stage IIIA NSCLC treated with chemoradiotherapy. Methods: A retrospective review of 44 patients with unresectable stage IIIA NSCLC treated with chemoradiotherapy (CRT) in 2007 was performed. Stage diagnosis data including PET/CT and CT guided primary tumor biopsy tissue could be obtained. HIF-1α and EGFR expression were inspected by IHC method. Definitive combined CRT schemes were vinorelbine or gemcita plus cisplatin and irradiation with a total dose of 60 to 65 Gy. 36 patients were underwent follow-up (median time 31 ± 2.7 months, range 25-36 months). Results: HIF-1α expression was diffused in cytoplasma and nuclear, EGFR expresssion in cell membrane. Of 44 patients, the cut-off value for HIF-1α positive expression was 72%, 60% for EGFR. HIF-1α and EGFR expression were only correlated with histological type (70% and 33.% for SCC and ADC). HIF-1α, EGFR expression and SUVmax value were significantly co...