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特殊情况内膜癌的放疗,2016-11-13,因内科疾病无法手术的内膜癌,高龄患者比率不断增加,65岁以上患者达18.2%尽管手术技术(阴式手术、腔镜手术等)、麻醉和围手术期管理水平不断提高约3-9%患者因内科合并症或高龄无法完成手术体外放疗近距离治疗内分泌治疗的模式可有明显获益,Medically inoperable stage I adenocarcinoma of the endometrium treated with radiotherapy lone,I期内膜癌的5年无进展生存率G1 94%G2 92%G3 78%,IJROBP 1987;13:483-8,Systemic review: Radiation therapy alone in medical non-operable endometrial carcinoma,纳入25项研究2694例单纯放疗的患者1976-2013年分期I-IV,European Journal of Cancer 65 (2016) 172-81,治疗效果,副反应,Systemic review: Radiation therapy alone in medical non-operable endometrial carcinoma,European Journal of Cancer 65 (2016) 172-81,Image-based three-dimensional conformal brachytherapy for medically inoperable endometrial carcinoma,I期内膜癌的精确放疗,共38例患者,2007-2013年MRI/CT based HDR-BTEBRTCTV包括宫体、宫颈、阴道1-2cm,Brachytherapy 13 (2014) 542-547,Image-based three-dimensional conformal brachytherapy for medically inoperable endometrial carcinoma,中位随访15个月2年局控率 90.6%2年总生存率 94.4% 未发生2级远期副反应,Brachytherapy 13 (2014) 542-547,Consensus statement for brachytherapy for the treatment of medically inoperable endometrial cancer,American Brachytherapy Society(ABS),Brachytherapy 14 (2015) 587-599,Consensus statement for brachytherapy for the treatment of medically inoperable endometrial cancer,American Brachytherapy Society(ABS),Brachytherapy 14 (2015) 587-599,Consensus statement for brachytherapy for the treatment of medically inoperable endometrial cancer,建议 I期 内膜癌:,单纯近距离放疗可用于I期无淋巴结转移且MRI未深肌层受侵的患者。无法行MRI的情况下,建议体外联合腔内放疗。CTV D90 近距离治疗48Gy 联合放疗65GyGTV 80Gy,限量,乙状结肠&直肠D2cc70-75Gy膀胱D2cc80-100Gy肠管D2cc65Gy,American Brachytherapy Society(ABS),Brachytherapy 14 (2015) 587-599,Consensus statement for brachytherapy for the treatment of medically inoperable endometrial cancer,体外联合近距离治疗EBRT45-50Gy包括全部宫体、宫颈、淋巴引流区(宫颈旁、闭孔、髂内、髂外、髂总骶前)施源器包括环或阴道卵圆体宫颈剂量勾画GTV(包括可见肿瘤、内膜线、宫颈)勾画CTV(包括全部宫体超过浆膜层、宫颈、上1-2cm阴道)CTV D90 EQD270-75GyGTV EQD2 80-90Gy,American Brachytherapy Society(ABS),Brachytherapy 14 (2015) 587-599,建议 II期 内膜癌:,Consensus statement for brachytherapy for the treatment of medically inoperable endometrial cancer,体外联合近距离治疗EBRT45-50Gy包括全部宫体、宫颈、淋巴引流区(宫颈旁、闭孔、髂内、髂外、髂总骶前)增大淋巴结可采用IMRT加量至65Gy*小肠限量V555cm3#勾画GTV(包括任何可见肿瘤、内膜线、宫颈)勾画CTV(包括全部宫体超过浆膜层、宫颈、上1-2cm阴道)CTV D90 EQD270-75GyGTV EQD2 80-90Gy,*Pract Radiat Oncol2014;4:90-98#Int J Radiat Oncol Biol Phys 2013;85:1262-1268American Brachytherapy Society(ABS),Brachytherapy 14 (2015) 587-599,建议 III期 内膜癌:,推荐的EBRT+BT剂量,Consensus statement for brachytherapy for the treatment of medically inoperable endometrial cancer,American Brachytherapy Society(ABS),Brachytherapy 14 (2015) 587-599,对于无法行手术治疗的内膜癌患者,选择放疗的局控率和副反应发生率可接受影像学MRI评估,放疗范围更明确精确放疗可能进一步提高疗效需进一步研究,复发性子宫内膜癌的放疗,早期内膜癌术后约10-15%出现盆腔复发其中3/4为单纯阴道复发PORTEC1后续分析显示阴道复发后挽救性根治放疗后5年总生存率65%,GOG99, Gynecol Oncol 2004;92:74451PORTEC-1 trial., J Clin Oncol 2011;29:1692700Gynecol Oncol 2003;89:2019,NCCN指南对复发肿瘤放疗的建议,Definitive salvage for vaginal recurrence of endometrial cancer: The impact of modern intensity-modulated-radiotherapy with image-based HDR brachytherapy and the interplay of the PORTEC 1 risk stratification,理论上, 精确放疗科提高肿瘤控制率并降低副反应发生率2004-2013年,共41例,中位年龄71岁80%单纯阴道复发,20%阴道+淋巴结复发阴道复发肿瘤大小2.6 (07.5)cm90%采用IMRT行45Gy/25f98%体外+腔内放疗2%单纯腔内放疗,Radiotherapy and Oncology 113 (2014) 126131,Definitive salvage for vaginal recurrence of endometrial cancer: The impact of modern intensity-modulated-radiotherapy with image-based HDR brachytherapy and the interplay of the PORTEC 1risk stratification,中位随访时间18个月3级急性副反应0%3级远期副反应8%,Radiotherapy and Oncology 113 (2014) 126131,Definitive salvage for vaginal recurrence of endometrial cancer: The impact of modern intensity-modulated-radiotherapy with image-based HDR brachytherapy and the interplay of the PORTEC 1risk stratification,远处转移和总生存的影响因素:肌层浸润深度、FIGO分期、FIGO分级,Radiotherapy and Oncology 113 (2014) 126131,GOG0238 (NCT00492778) II期研究:阴道/盆腔复发,未接受过放疗,45Gy/25f EBRT+近距离放疗/体外加量+同步顺铂化疗对于阴道/盆腔淋巴结复发患者,存在高危复发风险的患者可考虑放疗联合化疗,ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer,Dec,2014, Milan, Italy,放疗后复发,体外放疗后复发多位于盆腔外对于放射野内复发的患者,再程放疗多不可行再程放疗/再程姑息放疗可能导致严重的副反应,包括出血或疼痛-ABS guideline根据ER/PR选择激素治疗或考虑化疗/靶向药物,肿瘤性质对放疗选择的影响,ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer,Dec,2014, Milan, Italy,Substantial LVSI is a significant risk factor for recurrence in endometrial cancer,大量脉管瘤栓是强烈预后影响因素盆腔局部复发 (HR 6.2 CI 2.416)远处转移(HR 3.6 CI 1.96.8) 总生存(HR 2.0 CI 1.33.1).,European Journal of Cancer(2015) 51, 17421750,EBRT降低盆腔局部复发率(HR 0.3 CI 0.10.8),Substantial LVSI is a significant risk factor for recurrence in endometrial cancer,European Journal of Cancer(2015) 51, 17421750,Substantial LVSI is a significant risk factor for recurrence in endometrial cancer,治疗决定应基于“大量”脉管瘤栓存在。,European Journal of Cancer(2015) 51, 17421750,A prospective phase II study of chemoradiation followed by adjuvant chemotherapy for FIGO stage I-IIIa (1988) uterine papillary serous carcinoma of the endometrium,Gynecol Oncol. 2013 May ; 129(2): 304309,前瞻性II期研究,FIGO1988-I-IIIa期子宫内膜浆乳癌32例,2001-2009完整手术分期术后同步紫杉醇周疗(50 mg/m2)、盆腔放疗45Gy阴道残端加量4周期辅助紫杉醇化疗,A prospective phase II study of chemoradiation followed by adjuvant chemotherapy for FIGO stage I-IIIa (1988) uterine papillary serous carcinoma of the endometrium,Gynecol Oncol. 2013 May ; 129(2): 304309,同步化疗完成率:60%完成5周期33%完成4周期2%完成3周期紫杉醇辅助化疗完成率:77%完成4周期,10%完成3周期,7%完成2周期,2%例未行辅助放疗。,放疗完成率100%完成放疗,90%完成全部放疗,2例接受43.2Gy,1例接受39.6Gy。,A prospective phase II study of chemoradiation followed by adjuvant chemotherapy for FIGO stage I-IIIa (1988) uterine papillary serous carcinoma of the endometrium,子宫内膜浆乳癌术后同步放化疗+化疗的II期临床研究,与历史对照相比,Gynecol Oncol. 2013 May ; 129(2): 304309,J Gynecol Oncol Vol. 26, No. 1:25-31,

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