• <tr id="yyy80"></tr>
  • <sup id="yyy80"></sup>
  • <tfoot id="yyy80"><noscript id="yyy80"></noscript></tfoot>
  • 99热精品在线国产_美女午夜性视频免费_国产精品国产高清国产av_av欧美777_自拍偷自拍亚洲精品老妇_亚洲熟女精品中文字幕_www日本黄色视频网_国产精品野战在线观看 ?

    Prognostic value of interim18F-FDG PET/CT in diffuse large B-cell lymphoma

    2013-06-12 12:33:29ZhitaoYingXuejuanWangYuqinSongWenZhengXiaopeiWangYanXieNingjingLinMeifengTuLingyanPingWeipingLiuLijuanDengChenZhangZhiYangJunZhu
    Chinese Journal of Cancer Research 2013年1期

    Zhitao Ying, Xuejuan Wang, Yuqin Song, Wen Zheng, Xiaopei Wang, Yan Xie, Ningjing Lin, Meifeng Tu, Lingyan Ping, Weiping Liu, Lijuan Deng, Chen Zhang, Zhi Yang, Jun Zhu

    Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education),1Department of Lymphoma,2Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China

    Prognostic value of interim18F-FDG PET/CT in diffuse large B-cell lymphoma

    Zhitao Ying1, Xuejuan Wang2, Yuqin Song1, Wen Zheng1, Xiaopei Wang1, Yan Xie1, Ningjing Lin1, Meifeng Tu1, Lingyan Ping1, Weiping Liu1, Lijuan Deng1, Chen Zhang1, Zhi Yang2, Jun Zhu1

    Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education),1Department of Lymphoma,2Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China

    Corresponding to:Jun Zhu. Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, 100142, China. Email: zj@bjcancer.org.

    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 interim18F-FDG PET/CT after first-line treatment in patients with DLBCL.

    Methods:Thirty-two patients with DLBCL underwent baseline, interim and post-treatment18F-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 interim18F-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 SUVmaxcut-off value of 2.5 (P=0.039). No significant differences were found in the 2-year PFS rates if SUVmaxcut-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 SUVmaxcut-off value of 2.5, but more clinical data should be concluded to confirm this conclusion.

    Fludeoxyglucose F18; lymphoma; large cell; diffuse; prognosis; standard utility value

    Scan to your mobile device or view this article at:http://www.thecjcr.org/article/view/1380/1956

    Introduction

    Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin’s lymphoma, is clinically heterogeneous. Approximately 30-40% of patients will relapse after first-line treatment (1-3). Currently, the prognosis of patients with DLBCL is estimated by using the clinical parameters of the International Prognostic Index (IPI) (4). And patients with different lymphoma cell origins have different prognosis (5). The 5-year overall survival (OS) for the germina center B cell origin (GCB) group was 76% compared with only 34% for the non-GCB group (P<0.001). However, the treatment outcomes of individual patients within the same IPI risk group or the same cell origin can be considerably different. So we need to find a new factor to value the prognosis of patients with DLBCL.

    Fludeoxyglucose F18 positron emission tomography and computed tomography (18F-FDG PET/CT), providing information about the metabolic activity in patients with lymphoma, is helpful for differentiating viable tumor from post-treatment fibrosis or necrosis. Evidences showed that the post-treatment18F-FDG PET/CT can predict the outcome of patients with DLBCL (6-9). However, the role of interim PET/CT, after a few cycles of treatment, for predicting patients’ outcome is still controversial. In addition, there is still no universal conclusion on SUVmaxcut-off value for interpreting interim PET/CT as positive or negative.

    In this retrospective study, we try to find out the SUVmaxcut-off value for interpreting interim PET/CT as positive or negative, and to discuss the prognostic value of interim PET/CT in DLBCL.

    Materials and methods

    Patients

    Between September 2009 and November 2011, a total of 32 patients with newly diagnosed DLBCL were enrolled at Peking University Cancer Hospital. All patients were diagnosed according to 2008 WHO classification for Tumors of Hematopoietic and Lymphoid Tissue. All patients underwent baseline, interim (after 2-4 cycles of treatment), and post-treatment PET/CT scans. The treatment efficacy and survival time were retrospectively analyzed.

    All patients were treated with R-CHOP regimen [rituximab 375 mg/m2i.v. on day one (D1), cyclophosphamide 750 mg/m2i.v. on D1, vincristine 1.4 mg/m2i.v. on D1, doxorubicin 50 mg/m2i.v. on D1, and prednisone 100 mg p.o. on D1-5] or CHOP regimen. According to National Comprehensive Cancer Network (NCCN) guideline (10), 1 patient received local residual disease radiation after firstline treatment. Five high-risk patients received consolidative autologous stem cell transplantation with BEAM (Carmustine, etoposide, cytarabine, melphalan) as preparative regimen.

    18F-FDG PET/CT scans

    18F-FDG PET scan (Gemini TF 16 PET/CT, Philips, Netherland) was performed according to standard procedures. PET acquisition was performed in 6-hour fasting patients after intravenous injection of 0.1 mCi/kg of18F-FDG. We utilized a low-dose spiral mode CT scan (100 mAs, 120 keV; slice thickness 3 mm), covering the area from the base of the skull to the proximal thighs, which was used for attenuation correction and image fusion. PET data were reconstructed iteratively with attenuation correction based on CT data and reoriented in axial, sagittal, and coronal slices.

    PET/CT images were interpreted on the basis of visual analysis by 2 experienced nuclear medicine physicians. The examination was considered negative when no pathologic FDG uptake was shown. Focal FDG uptake beyond the physiological uptake areas was interpreted as positive. Lymph nodes with a short axis diameter of <1.0 cm was defined as abnormal.

    Statistical analysis

    OS was defined as the time from the date of diagnosis until death as a result of any cause. Progression-free survival (PFS) was measured as the time from diagnosis until lymphoma progression, relapse after response, or death as a result of any cause (9). The Kaplan-Meier method with the log-rank test was performed to estimate the PFS rate and to compare survival differences between groups. P<0.05 was considered statistically significant, and all P values were two-sided. All statistical analyses were performed using SPSS 13.0 for Windows (SPSS Inc., Chicago, IL, USA).

    Results

    Clinical characteristics of patients

    Baseline characteristics of 32 patients are listed inTable 1. Twenty-three patients (71.9%) presented with advanced stage disease and 27 (84.4%) had good performance status. Cases were subclassified using CD10, bcl-6, and MUM1 expression (11), 8 cases (25%) were considered GCB, and 22 cases (68.8%) non-GCB. Two cases cannot determine cell origin because of limited sample or technology reason. Thirty-one patients received R-CHOP regimen, and 1 patient CHOP regimen. Most of the patients (75%) underwent PET/CT scans after 2 cycles of treatment.

    Correlation of interim PET/CT results with PFS

    After a median follow-up period of 16.7 months (9.1-35.5 months), 4 patients showed progressive disease.

    We set 2.0, 2.5 and 3.0 as the SUVmaxcut-off value of interim PET/CT, respectively. PET/CT was defined as negative or positive according to the cut-off value.

    If SUVmax2.0 was applied as the cut-off value, the median SUVmaxof interim PET/CT negative patients was 0.8 (0-1.8,n=15), and 14 patients maintained negative after completion of first-line treatment. The median SUVmaxof interim PET/CT positive patients was 2.7 (2.2-15.3,n=17), 8 patients (41.7%) turned to negative at the end of the treatment, and these 8 patients are still in remission now. There was no difference in 2-year PFS rates between interim PET/CT negative and positive patients (88%vs.82%, P=0.360)(Table 2,Figure 1A).

    Table 1 Clinical characteristics of 32 patients

    If SUVmax2.5 was applied as the cut-off value, the median SUVmaxof interim PET/CT negative patients was 1.5 (0-2.4,n=22), and all of these patients maintained negative after completion of first-line treatment. The median SUVmaxof interim PET/CT positive patients was 3.6 (2.6-15.3,n=10), 5 patients (50%) turned to negative at the end of the treatment, and these 5 patients are still in remission now. The 2-year PFS rates differed between the interim PET/CT negative and positive patients (92%vs.69%, P=0.039) (Table 2,Figure 1B).

    If SUVmax3.0 was applied as the cut-off value, the median SUVmaxof interim PET/CT negative patients was 1.6 (0-2.7,n=25), and 24 patients maintained negative after completion of first-line treatment. The median SUVmaxof interim PET/CT positive patients was 3.9 (3.3-15.3,n=7), 4 patients (57.1%) turned to negative at the end of the treatment, and these 4 patients are still in remission now. There was no difference in 2-year PFS rates between interim PET/CT negative and positive patients (89%vs.70%, P=0.113) (Table 2,Figure 1C).

    Correlation of SUVmaxreduction with PFS

    This study calculated the SUVmaxreduction rate between baseline and interim PET/CT, and we defined a reduction rate of 70% and 90% as cut-off value, respectively. A cut-off of 70% SUVmaxreduction yielded a 2-year PFS rate of 86% in patients with reduction of more than 70%vs.84% with reduction of 70% or less (P=0.885) (Figure 2A). The 2-year PFS rate was 89% in patients with reduction of more than 90%, and 79% in those with reduction of 90% or less (P=0.229) (Figure 2B).

    Correlation of PET/CT results with OS

    There was only 1 patient died until the last follow-up time (August, 2012). We cannot analyze the correlation of interim PET/CT with OS.

    Discussion

    This study aims to determine the prognostic value of interim18F-FDG PET/CT in DLBCL. Actually, there are many controversies until now.

    Multiple studies have proved that interim PET/CT can predict the outcomes of patients with DLBCL (12,13). Yang DHet al.evaluated the prognostic significance of interim PET/CT in the treatment of DLBCL. SUVmax3.0 was defined as the cut-off value of interim PET/CT. Patients who continued to have positive interim PET/CT showed a significantly high relapse rate (62.8%) compared to those

    with a negative PET/CT (12.1%) (P<0.01). After a median follow-up period of 30.8 months, the positivity of interim PET/CT was found to be a prognostic factor for both OS and PFS. This study concluded interim PET/CT scanning had a significant predictive value for disease progression and survival of DLBCL (12). However, other studies have drawn different conclusions (14,15). The study performed by Yoo Cet al.demonstrated that there was no difference in PFS (P=0.07) and OS (P=0.24) between interim PET/CT positive and negative groups (14).

    Table 2 Correlation of interim PET/CT results with PFS according to different SUVmaxcut-off values

    Figure 1 PFS curves of patients with different interim PET/CT results. A. SUVmax2.0 as cut-off value; B. SUVmax2.5 as cut-off value; C. SUVmax3.0 as cut-off value

    Figure 2 PFS curves of patients with different SUVmaxreduction rates. A. SUVmaxreduction rate 70% as cut-off value; B. SUVmaxreduction rate 90% as cut-off value

    In the present study, we also evaluated the correlation of interim PET/CT with the outcomes of patients with DLBCL. PET/CT results were affected by different machines, observers, and interpretation criteria. A more direct index in PET/CT is urgently needed to guide clinical treatment. A study has applied SUVmaxcut-off value to define PET/CT as negative or positive (12), but there is still controversy. In our study, we set SUVmax2.0, 2.5 and 3.0 as cut-off value of interim PET/CT, respectively. If SUVmax2.0 and 3.0 were applied as cut-off value, there was no difference in 2-year PFS rates between interim PET/CT negative and positive patients (P=0.360; P=0.113). However, if we applied SUVmax2.5 as the cut-off value, the 2-year PFS rates differed between the negative and positive patients (P=0.039). Unfortunately, we cannot analyze patients’ OS because of the small sample size and short follow-up time.

    Recently, the role of SUVmaxreduction becomes more important in predicting outcomes of patients with DLBCL (16,17). Casasnovas ROet al.assessed whether SUVmaxcan predict the survival of DLBCL. Eighty-five high-risk patients underwent PET/CT scans at baseline (PET0), after 2 (PET2) and 4 cycles (PET4) chemotherapy, respectively. ΔSUVmaxwas calculated between PET2 and PET0 (ΔSUVmaxPET0-2) or PET4 (ΔSUVmaxPET0-4), ΔSUVmaxPET0-2(>66%vs.≤66%) analysis identified patients with significantly different 2-year PFS and OS rates (P=0.0282; P<0.0001). ΔSUVmaxPET0-4(>70%vs.≤70%) seemed even more predictive for 2-year PFS and OS rates (P<0.0001; P<0.0001) (16). In this study, we also calculated SUVmaxreduction of interim PET/CT scan compared to the baseline result, and applied 70% and 90% as the cutoff value of SUVmaxreduction. But we did not find the correlation of SUVmaxreduction and the outcomes of DLBCL, and this may be attributed to the small sample size and short follow-up time.

    The interim PET/CT cannot predict outcomes of DLBCL accurately, and the reasons are as following:

    Difficulty in determining the exact timing of interim PET/CT scan

    If patients underwent interim PET/CT too early (after 1-2 cycles of treatment), 2/3 interim positive patients will be turned to negative after the following treatment (15), and it has reached agreement that post-treatment PET/ CT negative patients have a good prognosis (6-8). The outcomes of this group of interim PET/CT positive patients are similar to that of interim negative patients (14,15). In this study, about half of the interim PET/CT positive patients turned to negative after the following treatment, and these patients did not relapse till now, indicating the treatment after interim PET/CT can affect the prognosis of patients. If patients underwent interim PET/CT too late (after 4 cycles for patients planning for receiving 6 cycles of treatment, after 6 cycles for the patients planning for receiving 8 cycles of treatment), the interim PET/CT loses its significance for predicting prognosis early.

    High false-positive rate

    FDG as a marker does not have such a high specificity because it is also taken up in infections and inflammatory processes (18-20). Rituximab is a kind of immunotherapy drug, and antibody-mediated cellular cytotoxicity and complement activity are important mechanisms in rituximab’s activity. Both processes are able to attract mediators of inflammation to tumor sites (21,22). Although a study recommended to exclude false-positive cases by biopsy (21), it is hard in a clinical setting to perform biopsies on every lesion showing residual FDG uptake, and these may cause unwanted procedure-related complications or interruptions of treatment.

    Absence of uniform interpretation criteria

    Currently, there are many PET interpretation criteria, but most of these criteria are defined for post-treatment assessment. Recently, Horninget al.reported only a moderate reproducibility among the observer in interim PET interpretation (23). To minimize the affection of immunochemotherapy on the PET result, PET scans should not be performed for at least 3 weeks, and preferably 6-8 weeks, after completion of therapy (9). This is easy for the post-treatment PET scan. However, it is difficult for the interim PET scan, because the time interval of the regimen for lymphoma is 2-3 weeks. To ensure thefollowing treatment on time, the interim PET is always within 3 weeks. So it is inevitable of the affection of immunochemotherapy on the interim PET result.

    In conclusion, using a SUVmaxcut-off value of 2.5, interim PET/CT can predict the 2-year PFS rate of patients with DLBCL. But this is a small retrospective study. We should treat this result cautiously, and cannot adjust the following treatment according to the interim PET/CT. In the future, larger prospective trials are needed to assess the real prognostic value of interim PET/CT in patients with DLBCL.

    Acknowledgements

    Disclosure:The authors declare no conflict of interest.

    1. Pfreundschuh M, Kuhnt E, Trümper L, et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol 2011;12:1013-22.

    2. Pfreundschuh M, Schubert J, Ziepert M, et al. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol 2008;9:105-16.

    3. Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood 2010;116:2040-5.

    4. Sehn LH, Berry B, Chhanabhai M, et al. The revised international prognostic index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood 2007;109:1857-61.

    5. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000;403:503-11.

    6. Thomas A, Gingrich RD, Smith BJ, et al. 18-Fluorodeoxyglucose positron emission tomography report interpretation as predictor of outcome in diffuse large B-cell lymphoma including analysis of ‘indeterminate’reports. Leuk Lymphoma 2010;51:439-46.

    7. Vitolo U, Chiappella A, Bellò M, et al. The outcome of patients with diffuse large B-Cell lymphoma (DLBCL) treated with Rituximab-CHOP (R-CHOP) is not predicted by 18-FDG-Positron Emission Tomography/ Computerized Tomography (PET) performed at intermediate in-course evaluation, but only by PET assessed at the end of therapy. Blood (ASH Annual Meeting Abstracts) 2010;116:2819.

    8. Cashen AF, Dehdashti F, Luo J, et al. 18F-FDG PET/ CT for early response assessment in diffuse large B-cell lymphoma: poor predictive value of international harmonization project interpretation. J Nucl Med 2011;52:386-92.

    9. Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol 2007;25:579-86.

    10. National Comprehensive Cancer Network. [EB/OL] Version 2. [2012-02-23] Available online: http://www.nccn. org/index.asp

    11. Hans CP, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004;103:275-82.

    12. Yang DH, Min JJ, Song HC, et al. Prognostic significance of interim18F-FDG PET/CT after three or four cycles of R-CHOP chemotherapy in the treatment of diffuse large B-cell lymphoma. Eur J Cancer 2011;47:1312-8.

    13. Delarue R, Meignan M, Fournier M, et al. Predictive value of interim PET in elderly patients with diffuse large B cell lymphoma (DLBCL): A sub-group analysis of the LNH03-6B GELA Study. Ann Oncol 2011;22:159.

    14. Yoo C, Lee DH, Kim JE, et al. Limited role of interim PET/CT in patients with diffuse large B-cell lymphoma treated with R-CHOP. Ann Hematol 2011;90:797-802.

    15. Gigli F, Gardellini A, Bertazzoni P, et al. Positive interim18F[FDG] positron emission tomography seems not to predict relapse in patients with diffuse large B-Cell lymphoma. Ann Oncol 2011;22:158.

    16. Casasnovas RO, Meignan M, Berriolo-Riedinger A, et al. SUVmaxreduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma. Blood 2011;118:37-43.

    17. Itti E, Lin C, Dupuis J, et al. Prognostic value of interim18F-FDG PET in patients with diffuse large B-cell lymphoma: SUV-based assessment at 4 Cycles of chemotherapy. J Nucl Med 2009;50:527-33.

    18. Inoue Y, Tamaki H, Yamagami T, et al. False positive FDG-PET findings due to bone metastasis from prostatecancer in staging of non-Hodgkin’s lymphoma. Eur J Haematol 2007;79:88-90.

    19. Ford CD, Gabor F, Morgan R, et al. False positive restaging PET scans involving the spleen in two patients with aggressive non-Hodgkin lymphoma. Clin Nucl Med 2006;31:391-3.

    20. Focosi D, Caracciolo F, Galimberti S, et al. False positive PET scanning caused by inactivated influenza virus vaccination during complete remission from anaplastic T-cell lymphoma. Ann Hematol 2008;87:343-4.

    21. Moskowitz CH, Sch?der H, Teruya-Feldtein J, et al. Riskadapted dose-dense immunochemotherapy determined by interim FDG-PET in advanced-stage diffuse large B-cell lymphoma. J Clin Oncol 2010;28:1896-903.

    22. Han HS, Escalón MP, Hsiao B, et al. High incidence of false-positive PET scans in patients with aggressive non-Hodgkin’s lymphoma treated with rituximab-containing regimens. Ann Oncol 2009;20:309-18.

    23. Horning SJ, Juweid ME, Sch?der H, et al. Interim positron emission tomography scans in diffuse large B-cell lymphoma: an independent expert nuclear medicine evaluation of the Eastern Cooperative Oncology Group E3404 study. Blood 2010;115:775-7; quiz 918.

    Cite this article as:Ying Z, Wang X, Song Y, Zheng W, Wang X, Xie Y, Lin N, Tu M, Ping L, Liu W, Deng L, Zhang C, Yang Z, Zhu J. Prognostic value of interim18F-FDG PET/ CT in diffuse large B-cell lymphoma. Chin J Cancer Res 2013;25(1):95-101. doi: 10.3978/j.issn.1000-9604.2013.01.08

    10.3978/j.issn.1000-9604.2013.01.08

    Submitted Nov 11, 2012. Accepted for publication Jan 04, 2013.

    av黄色大香蕉| 中文字幕av在线有码专区| 精品久久久久久久人妻蜜臀av| 亚洲成a人片在线一区二区| 亚洲专区中文字幕在线| 成人高潮视频无遮挡免费网站| 国产成人一区二区在线| 中国美白少妇内射xxxbb| 伦精品一区二区三区| 亚洲色图av天堂| 永久网站在线| 婷婷精品国产亚洲av在线| 亚洲成人中文字幕在线播放| 久久精品国产清高在天天线| 欧美一区二区国产精品久久精品| 最近中文字幕高清免费大全6 | 一个人观看的视频www高清免费观看| 精品久久久久久久末码| 国产精品三级大全| 欧美日韩国产亚洲二区| 老熟妇乱子伦视频在线观看| 欧美日韩综合久久久久久 | 亚洲色图av天堂| 亚洲第一区二区三区不卡| 日韩人妻高清精品专区| 精品人妻视频免费看| 久久久久久久久大av| 精品久久国产蜜桃| 少妇猛男粗大的猛烈进出视频 | 国产探花极品一区二区| 亚洲专区国产一区二区| 成人毛片a级毛片在线播放| 神马国产精品三级电影在线观看| 中文字幕熟女人妻在线| 亚洲一区高清亚洲精品| 国产伦一二天堂av在线观看| 久久精品久久久久久噜噜老黄 | 不卡一级毛片| 国国产精品蜜臀av免费| 国产亚洲欧美98| 国内精品久久久久精免费| 国产亚洲精品久久久久久毛片| 他把我摸到了高潮在线观看| 久久九九热精品免费| 国产综合懂色| 精品人妻偷拍中文字幕| 免费看美女性在线毛片视频| 99热这里只有精品一区| 全区人妻精品视频| 亚洲国产欧美人成| 美女 人体艺术 gogo| 国产在线男女| 日韩欧美精品v在线| 欧美一区二区亚洲| 国产精品久久电影中文字幕| 在线观看66精品国产| 男女做爰动态图高潮gif福利片| 亚洲国产精品成人综合色| 亚洲av电影不卡..在线观看| 婷婷亚洲欧美| 国产精品国产三级国产av玫瑰| 久久久久国内视频| 黄色欧美视频在线观看| 12—13女人毛片做爰片一| 日韩欧美在线二视频| 免费av不卡在线播放| 久久婷婷人人爽人人干人人爱| 欧美成人性av电影在线观看| 乱码一卡2卡4卡精品| 国语自产精品视频在线第100页| 亚洲美女视频黄频| 一边摸一边抽搐一进一小说| 午夜久久久久精精品| 女同久久另类99精品国产91| 美女黄网站色视频| 亚洲成人久久爱视频| 成人精品一区二区免费| 日本色播在线视频| 女人十人毛片免费观看3o分钟| 色av中文字幕| 国产午夜福利久久久久久| 少妇的逼好多水| 18禁黄网站禁片午夜丰满| 波多野结衣巨乳人妻| 人人妻,人人澡人人爽秒播| 亚洲性夜色夜夜综合| 一级av片app| 婷婷亚洲欧美| 亚洲av成人av| 国产单亲对白刺激| 麻豆成人av在线观看| 久久中文看片网| 春色校园在线视频观看| 99久久精品一区二区三区| 嫩草影视91久久| 国产精品自产拍在线观看55亚洲| 欧洲精品卡2卡3卡4卡5卡区| 两个人的视频大全免费| 国产精品精品国产色婷婷| 啦啦啦啦在线视频资源| 国产老妇女一区| 亚州av有码| 能在线免费观看的黄片| 国产精品乱码一区二三区的特点| 少妇丰满av| 中国美女看黄片| 国产精品一区二区免费欧美| 欧美又色又爽又黄视频| 两个人视频免费观看高清| 蜜桃久久精品国产亚洲av| 又紧又爽又黄一区二区| 国产精品自产拍在线观看55亚洲| 久久久久精品国产欧美久久久| 全区人妻精品视频| 18禁在线播放成人免费| 中文字幕人妻熟人妻熟丝袜美| 国产极品精品免费视频能看的| 亚洲熟妇熟女久久| 亚洲欧美精品综合久久99| 精品福利观看| 色哟哟·www| xxxwww97欧美| 国产精品久久久久久久电影| av在线天堂中文字幕| 18禁黄网站禁片午夜丰满| 中文在线观看免费www的网站| 国产一区二区激情短视频| 日本免费a在线| 日本一二三区视频观看| 无人区码免费观看不卡| 国产探花极品一区二区| 免费高清视频大片| 国产精品久久久久久久久免| 亚洲国产高清在线一区二区三| 天堂√8在线中文| 三级毛片av免费| 中文字幕av在线有码专区| 久久久午夜欧美精品| 一个人免费在线观看电影| 精品日产1卡2卡| 亚洲最大成人中文| www日本黄色视频网| 久久天躁狠狠躁夜夜2o2o| 久久久久精品国产欧美久久久| 在线观看舔阴道视频| 午夜福利在线在线| 免费搜索国产男女视频| 99精品在免费线老司机午夜| 国产精品福利在线免费观看| 俺也久久电影网| 99久久精品一区二区三区| 少妇人妻一区二区三区视频| 精品一区二区三区视频在线| 欧美激情国产日韩精品一区| 天堂动漫精品| 亚洲欧美精品综合久久99| 全区人妻精品视频| 久久久久久国产a免费观看| 国产日本99.免费观看| 日韩,欧美,国产一区二区三区 | 国产精品永久免费网站| 日韩精品青青久久久久久| 天美传媒精品一区二区| 日日摸夜夜添夜夜添小说| 村上凉子中文字幕在线| 高清毛片免费观看视频网站| 内射极品少妇av片p| 久久婷婷人人爽人人干人人爱| 国产真实乱freesex| 熟妇人妻久久中文字幕3abv| 亚洲av成人av| 少妇人妻精品综合一区二区 | 欧美极品一区二区三区四区| 三级国产精品欧美在线观看| 欧美激情在线99| 亚洲av成人精品一区久久| 亚洲精品一区av在线观看| 亚洲av熟女| 国产精品一区二区免费欧美| 最新中文字幕久久久久| 在线看三级毛片| 亚洲精品一卡2卡三卡4卡5卡| 久久人人爽人人爽人人片va| 亚洲图色成人| 国产av在哪里看| 国产精品久久视频播放| 成人欧美大片| 久久99热这里只有精品18| 禁无遮挡网站| 欧美+日韩+精品| 国产精品一及| 一卡2卡三卡四卡精品乱码亚洲| 身体一侧抽搐| 夜夜爽天天搞| 国产精品电影一区二区三区| 国产精品久久久久久精品电影| 三级毛片av免费| 亚洲av二区三区四区| 久久久久久国产a免费观看| 午夜福利成人在线免费观看| 国产av在哪里看| 一本久久中文字幕| 国产毛片a区久久久久| 变态另类丝袜制服| 国产精品久久久久久久久免| 男人舔奶头视频| 一个人观看的视频www高清免费观看| 成人欧美大片| 九九爱精品视频在线观看| 老熟妇仑乱视频hdxx| av视频在线观看入口| 亚洲在线观看片| 18禁黄网站禁片免费观看直播| 亚洲最大成人手机在线| 日韩国内少妇激情av| 国产欧美日韩精品亚洲av| 99久国产av精品| 国内精品美女久久久久久| 日本爱情动作片www.在线观看 | 国产午夜福利久久久久久| 制服丝袜大香蕉在线| 中文字幕久久专区| 他把我摸到了高潮在线观看| 欧美极品一区二区三区四区| 日本五十路高清| 国产亚洲av嫩草精品影院| 搞女人的毛片| 综合色av麻豆| 久久人妻av系列| 午夜福利18| 日韩亚洲欧美综合| 女同久久另类99精品国产91| 在线观看美女被高潮喷水网站| 亚洲人成网站高清观看| 国产精品久久久久久精品电影| 久久99热6这里只有精品| 亚洲中文字幕日韩| 嫩草影院入口| 欧美日韩瑟瑟在线播放| 男女边吃奶边做爰视频| 国产成人a区在线观看| eeuss影院久久| 国产精品美女特级片免费视频播放器| 动漫黄色视频在线观看| 在线观看午夜福利视频| 成人国产综合亚洲| 亚洲av第一区精品v没综合| 中文字幕久久专区| 88av欧美| 中文在线观看免费www的网站| 精品久久久久久,| 久9热在线精品视频| 少妇高潮的动态图| 日本爱情动作片www.在线观看 | 日本五十路高清| 国内精品宾馆在线| 国产亚洲精品久久久久久毛片| 日本爱情动作片www.在线观看 | av天堂在线播放| 免费观看的影片在线观看| 婷婷亚洲欧美| 欧美成人性av电影在线观看| 亚洲,欧美,日韩| АⅤ资源中文在线天堂| 精品一区二区三区av网在线观看| 日韩欧美一区二区三区在线观看| 中文字幕免费在线视频6| av在线观看视频网站免费| 真人一进一出gif抽搐免费| 国产精品98久久久久久宅男小说| 亚洲av一区综合| 日日夜夜操网爽| 色综合亚洲欧美另类图片| 老司机午夜福利在线观看视频| 久久精品人妻少妇| 可以在线观看的亚洲视频| 在线观看免费视频日本深夜| 男女视频在线观看网站免费| 国内精品一区二区在线观看| 男女之事视频高清在线观看| 亚洲无线观看免费| a级毛片a级免费在线| 国产高清三级在线| 国产私拍福利视频在线观看| 亚洲av电影不卡..在线观看| 欧美日韩精品成人综合77777| 亚洲欧美激情综合另类| 波多野结衣高清无吗| 成年人黄色毛片网站| 波野结衣二区三区在线| 99国产精品一区二区蜜桃av| 一个人看视频在线观看www免费| 欧美日韩中文字幕国产精品一区二区三区| 精品久久久久久久久久免费视频| 91久久精品电影网| 亚洲熟妇中文字幕五十中出| 97人妻精品一区二区三区麻豆| 国产不卡一卡二| 欧美xxxx黑人xx丫x性爽| 小蜜桃在线观看免费完整版高清| 一区福利在线观看| 久久精品国产亚洲网站| 国产黄片美女视频| 国产高清视频在线观看网站| 男女之事视频高清在线观看| 人妻丰满熟妇av一区二区三区| 久久久午夜欧美精品| 国产一区二区激情短视频| 成年女人毛片免费观看观看9| 婷婷精品国产亚洲av| 亚洲av日韩精品久久久久久密| 久久久国产成人精品二区| 亚洲国产高清在线一区二区三| 免费观看人在逋| 岛国在线免费视频观看| 亚洲第一电影网av| 永久网站在线| 日韩欧美免费精品| 婷婷丁香在线五月| 久久久久久久久久成人| 日韩精品青青久久久久久| 精品久久久久久久末码| 日韩欧美在线乱码| 97超视频在线观看视频| 免费看av在线观看网站| 99视频精品全部免费 在线| 男女之事视频高清在线观看| 99热这里只有精品一区| 久久欧美精品欧美久久欧美| 亚洲精品影视一区二区三区av| 男女那种视频在线观看| 亚洲真实伦在线观看| 免费观看人在逋| 蜜桃亚洲精品一区二区三区| 欧美不卡视频在线免费观看| 搡老妇女老女人老熟妇| 特级一级黄色大片| 天美传媒精品一区二区| 亚洲国产精品合色在线| 91久久精品国产一区二区成人| 少妇熟女aⅴ在线视频| 观看美女的网站| 欧美高清成人免费视频www| 亚洲精品粉嫩美女一区| 人人妻人人看人人澡| 女生性感内裤真人,穿戴方法视频| 中文字幕久久专区| 成年女人永久免费观看视频| 久久久久久久久中文| 欧美日韩中文字幕国产精品一区二区三区| 日韩欧美在线乱码| 一级毛片久久久久久久久女| 少妇熟女aⅴ在线视频| 嫩草影院新地址| 内射极品少妇av片p| 观看美女的网站| 国产免费男女视频| 99国产精品一区二区蜜桃av| 婷婷精品国产亚洲av| 男女视频在线观看网站免费| 国产老妇女一区| 99riav亚洲国产免费| 亚洲专区国产一区二区| 日本一二三区视频观看| 国产女主播在线喷水免费视频网站 | 成人av一区二区三区在线看| 国产麻豆成人av免费视频| 成人av一区二区三区在线看| 少妇人妻精品综合一区二区 | 中国美白少妇内射xxxbb| 欧美色欧美亚洲另类二区| 午夜福利高清视频| 久久精品国产亚洲网站| 少妇人妻一区二区三区视频| 精品99又大又爽又粗少妇毛片 | 免费观看精品视频网站| 成人特级av手机在线观看| 国产伦精品一区二区三区四那| 琪琪午夜伦伦电影理论片6080| 国产欧美日韩精品一区二区| 亚洲无线在线观看| 久久久久免费精品人妻一区二区| 国产伦人伦偷精品视频| 婷婷亚洲欧美| a在线观看视频网站| 国产熟女欧美一区二区| 国产欧美日韩一区二区精品| 男人舔奶头视频| 麻豆精品久久久久久蜜桃| 国产男靠女视频免费网站| 久久99热6这里只有精品| 无遮挡黄片免费观看| 极品教师在线视频| 亚洲美女视频黄频| 亚洲人成网站高清观看| 亚洲国产欧美人成| 欧美高清成人免费视频www| av在线天堂中文字幕| 欧美激情国产日韩精品一区| 久久久久精品国产欧美久久久| 日本欧美国产在线视频| 老司机福利观看| 日本在线视频免费播放| 亚洲五月天丁香| 99热6这里只有精品| 综合色av麻豆| 亚洲av熟女| 别揉我奶头~嗯~啊~动态视频| 精品午夜福利视频在线观看一区| 乱码一卡2卡4卡精品| 亚洲性久久影院| 99视频精品全部免费 在线| 91午夜精品亚洲一区二区三区 | 日韩欧美精品免费久久| 国产美女午夜福利| 中文字幕人妻熟人妻熟丝袜美| 91在线观看av| 国产一级毛片七仙女欲春2| 久久欧美精品欧美久久欧美| 国内揄拍国产精品人妻在线| 色综合站精品国产| www.www免费av| 亚洲国产欧美人成| 18禁黄网站禁片午夜丰满| 日日摸夜夜添夜夜添小说| 99久久九九国产精品国产免费| 欧美三级亚洲精品| 少妇丰满av| 99九九线精品视频在线观看视频| 久久九九热精品免费| 国产单亲对白刺激| 韩国av一区二区三区四区| 国产午夜福利久久久久久| eeuss影院久久| 日本a在线网址| 精品无人区乱码1区二区| 最近最新中文字幕大全电影3| 欧美不卡视频在线免费观看| 国产三级在线视频| 国产精品三级大全| 午夜免费激情av| 亚洲国产精品久久男人天堂| 中文资源天堂在线| 国产一级毛片七仙女欲春2| 久久久成人免费电影| 亚洲av第一区精品v没综合| 国产成人av教育| 老师上课跳d突然被开到最大视频| 特级一级黄色大片| 男人舔奶头视频| 国产精品久久久久久精品电影| а√天堂www在线а√下载| 中文字幕精品亚洲无线码一区| 蜜桃久久精品国产亚洲av| 日韩在线高清观看一区二区三区 | 麻豆久久精品国产亚洲av| 黄色女人牲交| 免费人成视频x8x8入口观看| 国产精品久久电影中文字幕| 大又大粗又爽又黄少妇毛片口| 亚洲图色成人| 欧美区成人在线视频| 久久中文看片网| 中亚洲国语对白在线视频| 色精品久久人妻99蜜桃| av女优亚洲男人天堂| 美女 人体艺术 gogo| 成人亚洲精品av一区二区| 日日摸夜夜添夜夜添av毛片 | 亚洲性夜色夜夜综合| 久99久视频精品免费| 国产精品一区二区免费欧美| 日韩中文字幕欧美一区二区| 国产主播在线观看一区二区| 91久久精品国产一区二区成人| 亚洲在线自拍视频| 97人妻精品一区二区三区麻豆| 精品欧美国产一区二区三| 老熟妇乱子伦视频在线观看| 精品久久国产蜜桃| 内地一区二区视频在线| 一区二区三区高清视频在线| 最近最新免费中文字幕在线| 午夜免费男女啪啪视频观看 | 国内揄拍国产精品人妻在线| 国产麻豆成人av免费视频| 老熟妇乱子伦视频在线观看| 亚洲av日韩精品久久久久久密| av黄色大香蕉| 日韩欧美精品v在线| 成年人黄色毛片网站| 国产探花极品一区二区| 有码 亚洲区| 国产在视频线在精品| 午夜影院日韩av| 禁无遮挡网站| 熟妇人妻久久中文字幕3abv| 免费高清视频大片| 别揉我奶头 嗯啊视频| 国产精品福利在线免费观看| 国产亚洲精品久久久com| 成人国产综合亚洲| 精品久久国产蜜桃| 国产又黄又爽又无遮挡在线| 亚洲国产精品sss在线观看| 成人av在线播放网站| av天堂中文字幕网| 嫩草影院新地址| 精品久久久久久久人妻蜜臀av| 国产蜜桃级精品一区二区三区| 麻豆av噜噜一区二区三区| 亚洲成人久久性| 午夜福利在线观看吧| 欧美+日韩+精品| 琪琪午夜伦伦电影理论片6080| 一本精品99久久精品77| eeuss影院久久| xxxwww97欧美| 亚洲国产高清在线一区二区三| 99国产精品一区二区蜜桃av| 欧美日本视频| 少妇的逼好多水| 国产 一区 欧美 日韩| 男人舔女人下体高潮全视频| 久久久久性生活片| 精品一区二区三区视频在线观看免费| 天美传媒精品一区二区| 亚洲中文日韩欧美视频| 五月玫瑰六月丁香| 尤物成人国产欧美一区二区三区| 亚洲精品日韩av片在线观看| 国产日本99.免费观看| 国产精品综合久久久久久久免费| 一边摸一边抽搐一进一小说| 又黄又爽又免费观看的视频| av在线天堂中文字幕| 国产伦精品一区二区三区四那| 免费电影在线观看免费观看| 精品久久久久久成人av| 亚洲美女黄片视频| 一级黄片播放器| 国内少妇人妻偷人精品xxx网站| 男人的好看免费观看在线视频| 国产白丝娇喘喷水9色精品| 国产伦人伦偷精品视频| 亚洲中文日韩欧美视频| 成人特级av手机在线观看| 日日摸夜夜添夜夜添av毛片 | av在线老鸭窝| 亚洲成人中文字幕在线播放| 很黄的视频免费| 日韩精品青青久久久久久| 午夜精品久久久久久毛片777| 日本黄色视频三级网站网址| 亚洲精品影视一区二区三区av| 黄色配什么色好看| 在线观看美女被高潮喷水网站| 欧美潮喷喷水| 国产av不卡久久| 国产成人a区在线观看| 国产蜜桃级精品一区二区三区| 欧美极品一区二区三区四区| www日本黄色视频网| 美女高潮的动态| 99国产极品粉嫩在线观看| 国产精品美女特级片免费视频播放器| 九九在线视频观看精品| 一个人观看的视频www高清免费观看| 亚洲va日本ⅴa欧美va伊人久久| 国产精品自产拍在线观看55亚洲| 国产精品野战在线观看| 精品午夜福利在线看| 在线播放国产精品三级| 成人国产麻豆网| 亚洲av电影不卡..在线观看| 亚洲欧美日韩无卡精品| 欧美丝袜亚洲另类 | 欧美在线一区亚洲| 免费看光身美女| 一区二区三区四区激情视频 | 春色校园在线视频观看| 国产老妇女一区| 日韩欧美精品免费久久| 亚洲中文字幕日韩| 免费观看的影片在线观看| 亚洲电影在线观看av| a在线观看视频网站| 欧美区成人在线视频| 午夜福利在线观看吧| 三级男女做爰猛烈吃奶摸视频| 中亚洲国语对白在线视频| 欧美区成人在线视频| 99riav亚洲国产免费| 亚洲精品一卡2卡三卡4卡5卡| 色播亚洲综合网| 国产毛片a区久久久久| 夜夜爽天天搞| 精品不卡国产一区二区三区| 97热精品久久久久久| 国产精品久久久久久久电影| 在线观看午夜福利视频| 全区人妻精品视频| 中亚洲国语对白在线视频| 日韩中文字幕欧美一区二区| 亚洲欧美日韩高清专用| ponron亚洲| 韩国av在线不卡| 亚洲自拍偷在线| 成年女人毛片免费观看观看9| 一a级毛片在线观看| 国产精品久久电影中文字幕| 一进一出好大好爽视频| 99热这里只有是精品50| 亚洲熟妇中文字幕五十中出| 啦啦啦韩国在线观看视频|