Ying-Shi Sun

Apparent Diffusion Coefficient : Potential Imaging Biomarker for Prediction and Early Detection of Response to Chemotherapy in Hepatic Metastases

PURPOSE To evaluate the ability of the apparent diffusion coefficient (ADC) to help predict response to chemotherapy in patients with colorectal and gastric hepatic metastases. MATERIALS AND METHODS Institutional review board approval was obtained; all patients provided informed consent. Standard magnetic resonance (MR) imaging and diffusion-weighted (DW) MR imaging were performed before and 3, 7, and 42 days after initiating chemotherapy for 87 hepatic metastases in 23 colorectal and gastric cancer patients (16 men, seven women; mean age, 55.7 years; range, 33-71 years). Lesions were classified as either responding or nonresponding, according to changes in size at the end of therapy. Linear mixed-effects modeling was applied to analyze change in ADCs and size following treatment. The Pearson correlation test was calculated between those ADC parameters and tumor response. RESULTS Thirty-eight responding and 49 nonresponding metastatic lesions were evaluated. Pretherapy mean ADCs in responding lesions were significantly lower than those of nonresponding lesions (P = .003). An early increase in ADCs (on day 3 or 7) was observed in responding lesions but not in nonresponding lesions (P = .002). Weak but significant correlations were found between final tumor size reduction and both pretreatment ADCs (P = .006) and early ADC changes (day 3, P = .004; day 7, P < .001). CONCLUSION ADC seems to be a promising tool for helping predict and monitor the early response to chemotherapy of hepatic metastases from colorectal and gastric carcinomas.

Locally advanced rectal carcinoma treated with preoperative chemotherapy and radiation therapy: preliminary analysis of diffusion-weighted MR imaging for early detection of tumor histopathologic downstaging.

PURPOSE To determine whether changes in apparent diffusion coefficients (ADCs) of rectal carcinoma obtained 1 week after the beginning of chemotherapy and radiation therapy (CRT) correlate with tumor histopathologic downstaging after preoperative CRT. MATERIALS AND METHODS This prospective study was approved by an institutional review board; informed consent was obtained from all patients. Thirty-seven patients (mean age, 54.7 years; 13 women, 24 men) with primary rectal carcinoma who were undergoing preoperative CRT were recruited for the study. Diffusion-weighted (DW) magnetic resonance (MR) imaging was performed with a 1.5-T MR imager in all patients before therapy, at the end of the 1st and 2nd week of therapy, and before surgery. Tumor ADCs were calculated. Linear mixed-effects modeling was applied to analyze change in ADCs and volumes following treatment. RESULTS Patients were assigned to the tumor downstaged group (n = 17) or the tumor nondownstaged group (n = 20) on the basis of histopathologic examination results following surgery. Before CRT, the mean tumor ADC in the downstaged group was lower than that in the nondownstaged group (1.07 x 10(-3) mm(2)/sec +/- 0.13 [standard deviation] vs 1.19 x 10(-3) mm(2)/sec +/- 0.15, F = 6.91, P = .013). At the end of the 1st week of CRT, the mean tumor ADC increased significantly from 1.07 x 10(-3) mm(2)/sec +/- 0.13 to 1.32 x 10(-3) mm(2)/sec +/- 0.16 (F = 37.63, P <.001) in the downstaged group, but there was no significant ADC increase in the nondownstaged group (F = 1.18, P = .291). The mean percentage of tumor ADC change in the downstaged group was significantly higher than that in the nondownstaged group at each time point (F = 18.39, P < .001). CONCLUSION Early increase of mean tumor ADC and low pretherapy mean ADC in rectal carcinoma correlate with good response to CRT. DW MR imaging is a promising noninvasive technique for helping predict and monitor early therapeutic response in patients with rectal carcinoma who are undergoing CRT.

Early Evaluation of Cancer Response by a New Functional Biomarker: Apparent Diffusion Coefficient

OBJECTIVE The purpose of this article is to investigate whether apparent diffusion coefficient (ADC) might be used as a universal biomarker for response evaluation in different tumors. SUBJECTS AND METHODS Twenty-one patients with lung cancer, 12 patients with esophageal cancer, 19 patients with liver metastases, 24 patients with gastric cancer, and 26 patients with rectal cancer were recruited to the study. Percentage changes in the ADC and changes in the size of responding and nonresponding lesions of different tumors after treatment were analyzed using repeated measures analysis of variance. RESULTS There was no significant difference among the percentage ADC changes of different tumors (F = 1.57; p = 0.192). Clear differences were seen in the percentage ADC changes between responding and nonresponding tumors (F = 21.62; p < 0.001), which were significant at every time point after the start of treatment (early time point, F = 19.75 and p < 0.001; middle time point, F = 11.23 and p = 0.001; and later time point, F = 15.98 and p < 0.001). The percentage size changes after treatment between responding and nonresponding tumors were significantly different (F = 19.38; p < 0.001). However, at the early time point after treatment, the difference was not statistically significant (F = 0.02; p = 0.894). CONCLUSION The ADC changes correlated with treatment response in five types of body tumor but were independent of the tumors location. Early increases in ADC during treatment indicate good response to treatment. ADC change is a promising biomarker for detecting therapeutic responses at an early stage that could be widely used.

Gastrointestinal Stromal Tumors Treated with Imatinib Mesylate: Apparent Diffusion Coefficient in the Evaluation of Therapy Response in Patients

PURPOSE To prospectively investigate the use of the apparent diffusion coefficient (ADC) as an early response indicator in patients with gastrointestinal stromal tumors (GISTs) treated with imatinib mesylate. MATERIALS AND METHODS This study was approved by the institutional review board and written informed consent was obtained from all patients. Diffusion-weighted magnetic resonance (MR) imaging was performed in 32 patients with GISTs before and 1, 4, and 12 weeks after treatment with a tyrosine kinase inhibitor, imatinib mesylate. The measurable lesions were classified as having responded well or poorly according to size alterations at clinical evaluation following the first round of treatment (3 months). A linear mixed-effects model was applied to analyze changes in the ADCs of tumors during treatment and to compare the variation and slopes of the time-dependent ADC curves between the good- and poor-response groups. RESULTS There were 56 lesions in the good-response group and 35 in the poor-response group. An early (1 week after therapy) noticeable and statistically significant (P < .001) increase in the ADC was observed in the good-response group (median ADC increase, 44.8%) but not in the poor-response group (median ADC increase, 1.5%). The time-dependent ADC variation was significantly different between the good- and poor-response groups, with a sharper median ADC increase displayed in the former (week 1: 44.8% vs 1.5%; week 4: 80.4% vs 7.8%; week 12: 89.6% vs 16.7%; F = 25.78, P < .001). The largest difference in the weekly percentage increase in ADC between the good- and poor-response groups was observed at 1 week after therapy (week 0-1: 44.8% vs 1.5%; week 1-4: 7.0% vs 2.8%; week 4-12: 1.6% vs 0.7%). The pretherapy mean ADC (± standard deviation) of lesions in the good-response group (1.06 [×10(-3) mm(2)/sec] ± 0.27) was significantly lower than that in the poor-response group (1.24 [×10(-3) mm(2)/sec] ± 0.32) (F = 8.34, P = .005). CONCLUSION Comparatively low pretherapy ADC and marked ADC increase at 1 week after therapy is associated with good response to imatinib mesylate in patients with GISTs.

Effect of multidisciplinary team treatment on outcomes of patients with gastrointestinal malignancy

AIM To evaluate the effect of multidisciplinary team (MDT) treatment modality on outcomes of patients with gastrointestinal malignancy in China. METHODS Data about patients with gastric and colorectal cancer treated in our center during the past 10 years were collected and divided into two parts. Part 1 consisted of the data collected from 516 consecutive complicated cases discussed at MDT meetings in Peking University School of Oncology (PKUSO) from December 2005 to July 2009. Part 2 consisted of the data collected from 263 consecutive cases of resectable locally advanced rectal cancer from January 2001 to January 2005. These 263 patients were divided into neoadjuvant therapy (NT) group and control group. Patients in NT group received MDT treatment, namely neoadjuvant therapy + surgery + postoperative adjuvant therapy. Patients in control group underwent direct surgery + postoperative adjuvant therapy. The outcomes in two groups were compared. RESULTS The treatment strategy was altered after discussed at MDT meeting in 76.81% of gastric cancer patients and in 58.33% of colorectal cancer patients before operation. The sphincter-preservation and local control of tumor were better in NT group than in control group. The 5-year overall survival rate was also higher in NT group than in control group (77.23% vs 69.75%, P = 0.049). CONCLUSION MDT treatment modality can significantly improve the outcomes of patients with gastrointestinal malignancy in China.

Apparent diffusion coefficient of diffusion weighted MRI in endometrial carcinoma—Relationship with local invasiveness

OBJECTIVE To evaluate the relationship between apparent diffusion coefficient (ADC) value and the local invasiveness of endometrial carcinoma. METHODS AND MATERIALS The MR imaging of seventy-three patients with endometrial carcinoma proved by post-operative pathology and sixty-four patients with healthy uteri were retrospectively reviewed. All MR examinations included axial T2WI and T1WI, sagittal T2WI and diffusion-weighted sequences (b=0 and b=1000s/mm(2)). Tumor size, mean ADC value (ADCm) and quartile ADC (ADCq) were acquired on post-processing workstation using voxel-analysis software. Differences between the ADC values among three layers of normal uterine body and endometrial carcinomas were compared by ANOVA test. Groups were divided according to pathologic type, histologic grade, depth of myometrial infiltration, presence of cervical invasion and lymphovascular space invasion, and lymph node metastasis. Tumor size and ADC values were compared and analyzed. RESULTS ADC values were different in three zones of uterine body (P<0.001), with the lowest in junctional zone [(1.126±0.190)×10(-3)mm(2)/s] and highest in outer myometrium [(1.496±0.196)×10(-3)mm(2)/s]. Mean ADC value of endometrial carcinomas [(1.011±0.121)×10(-3)mm(2)/s] was lower than the normal uterine body. Quartile ADC and tumor size were greater in groups with more invasive pathologic factors (P<0.05). Deep myometrial infiltration, cervical invasion, lymphovascular space invasion and lymph node metastasis were more common as quartile ADC values and tumor sizes increased. CONCLUSION Mean ADC value was lower in endometrial carcinoma was lower than the normal uterus. Quartile ADC, representing the intra-tumor heterogeneity of water movement, had a profound relationship with invasiveness of endometrial carcinomas, while mean ADC value did not. ADC values may serve as a quantitative indicator to complement routine sequences.

Tissue microarray analysis of multiple gene expression in intestinal metaplasia, dysplasia and carcinoma of the stomach.

Aims : To study multiple gene expression patterns and their roles in the process of gastric carcinogenesis.

Sandwich sign of Borrmann type 4 gastric cancer on diffusion-weighted magnetic resonance imaging

OBJECTIVE To assess the appearance of Borrmann type 4 (BT-4) gastric cancer on diffusion-weighted magnetic resonance imaging (DWI) and to investigate the potential of qualitative and quantitative DW images analysis to differentiate BT-4 gastric cancer from poorly distended normal stomach wall. MATERIALS AND METHODS DWI was performed on 23 patients with BT-4 gastric cancer and 23 healthy volunteers. The signal characteristics and correlated histopathological basis of the cancers on DWI were investigated. The contrast-to-noise ratios (CNR) of cancer were compared between DWI and T1WI/T2WI(.) The thickness and apparent diffusion coefficient (ADC) of cancer and normal stomach wall were compared. RESULTS All of the gastric cancers displayed hyperintensity compared to the nearby normal gastric wall on DWI. A three-layer sandwich sign that demonstrated high signal intensity in the inner and outer layer, and low signal intensity in the intermediate layer was observed in 69.6% of cancers on DWI. The low signal intensity represents the muscularis propria through the comparison with pathology, and it is postulated that scattering distribution of the cancer cells in this layer causes less damage and subsequently less restriction of water movement, which causes the low signal intensity on DWI. The CNR obtained with DWI was higher than that with T1WI and T2WI (P<0.001). The mean ADC value of BT-4 gastric cancer was significantly lower than the poorly distended normal stomach wall (1.12 ± 0.23 × 10(-3)mm(2)/s vs. 1.9 3 ± 0.22 × 10(-3)mm(2)/s, P<0.01). CONCLUSION DWI can highlight the signals of BT-4 gastric cancer which may present a characteristic three-layer sandwich sign, and ADC values are helpful in the discrimination of gastric cancer from poorly distended stomach wall.

Evaluating local lymph node metastasis with magnetic resonance imaging, endoluminal ultrasound and computed tomography in rectal cancer: a meta-analysis.

Magnetic resonance imaging (MRI), endorectal ultrasound (EUS) and computed tomography (CT) are commonly used to evaluate lymph node (LN) metastasis for rectal cancer, but there is no agreement on which form of imaging is most accurate. The study aimed to review systematically the diagnostic performance of the three imaging modalities.

Support vector machine model for diagnosis of lymph node metastasis in gastric cancer with multidetector computed tomography: a preliminary study

BackgroundLymph node metastasis (LNM) of gastric cancer is an important prognostic factor regarding long-term survival. But several imaging techniques which are commonly used in stomach cannot satisfactorily assess the gastric cancer lymph node status. They can not achieve both high sensitivity and specificity. As a kind of machine-learning methods, Support Vector Machine has the potential to solve this complex issue.MethodsThe institutional review board approved this retrospective study. 175 consecutive patients with gastric cancer who underwent MDCT before surgery were included. We evaluated the tumor and lymph node indicators on CT images including serosal invasion, tumor classification, tumor maximum diameter, number of lymph nodes, maximum lymph node size and lymph nodes station, which reflected the biological behavior of gastric cancer. Univariate analysis was used to analyze the relationship between the six image indicators with LNM. A SVM model was built with these indicators above as input index. The output index was that lymph node metastasis of the patient was positive or negative. It was confirmed by the surgery and histopathology. A standard machine-learning technique called k-fold cross-validation (5-fold in our study) was used to train and test SVM models. We evaluated the diagnostic capability of the SVM models in lymph node metastasis with the receiver operating characteristic (ROC) curves. And the radiologist classified the lymph node metastasis of patients by using maximum lymph node size on CT images as criterion. We compared the areas under ROC curves (AUC) of the radiologist and SVM models.ResultsIn 175 cases, the cases of lymph node metastasis were 134 and 41 cases were not. The six image indicators all had statistically significant differences between the LNM negative and positive groups. The means of the sensitivity, specificity and AUC of SVM models with 5-fold cross-validation were 88.5%, 78.5% and 0.876, respectively. While the diagnostic power of the radiologist classifying lymph node metastasis by maximum lymph node size were only 63.4%, 75.6% and 0.757. Each SVM model of the 5-fold cross-validation performed significantly better than the radiologist.ConclusionsBased on biological behavior information of gastric cancer on MDCT images, SVM model can help diagnose the lymph node metastasis preoperatively.