寡转移CRPC原发灶与转移灶全覆盖放疗的疗效和毒性反应分析

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目的:探讨原发灶和所有转移灶同时全覆盖放疗治疗寡转移性去势抵抗性前列腺癌(CRPC)的疗效和毒性反应。方法:回顾性分析北京大学第一医院2011年10月至2017年6月收治的44例寡转移(≤4处转移灶)CRPC患者的临床资料。平均年龄72(57~86)岁,初诊时PSA中位值38.545(6.640~1 066.000)ng/ml,初始雄激素剥夺治疗(ADT)后PSA最低值中位值0.259(0.011~18.762)ng/ml,初始ADT至诊断转移性去势抵抗性前列腺癌(mCRPC)中位时间间隔12(4~96)个月,放疗前PSA中位值3.765(2.040~187.000)ng/ml。Gleason评分9~10分23例(52.3%),8分15例(34.0%)。初诊时,41例(93.2%)肿瘤分期为Tn 3~Tn 4期,23例(52.3%)伴淋巴结转移,29例(63.9%)伴远处转移。放疗前转移灶数量为1个22例(50.0%),2个12例(27.3%),3个6例(13.6%),4个4例(9.1%)。转移灶部位分别为盆腔淋巴结转移3例(6.8%),腹膜后淋巴结转移9例(20.5%),骨转移21例(47.7%),骨转移+淋巴结转移11例(25%),均无内脏转移。采用影像引导旋转调强放疗技术(IGRT-VMAT)对原发灶和所有转移灶全覆盖放疗。放射剂量:前列腺和精囊予常规分割76 Gy/38次,生物等效剂量(BEDn 3)为126.67 Gy;对有盆腔淋巴结转移者,盆腔淋巴结引流区46 Gy/23次。根据病灶周围不同的正常组织耐受量,转移灶局部放疗剂量BEDn 3中位值为112.26(91.14~140.77)Gy。记录本组患者的疗效和毒性反应情况。采用Kaplan-Meier法分析本组患者的总生存率和无新发转移生存率。n 结果:本组44例中,1例放疗期间出现尿路梗阻(NCI-CTCAE 3级),留置尿管2周后顺利拔管;余43例的急性和晚期毒性反应为0~2级。中位随访34.5(9~96)个月,放疗后PSA最低值0.088(0.003~132.000)ng/ml,40例(90.9%)PSA值较放疗前下降,中位降幅为87.5%(29.4%~99.9%),其中34例(77.3%)降幅>80%。本组44例治疗后1、3、5年总生存率分别为90.9%、54.5%、36.8%,无新发转移生存率分别为47.7%、25.0%和12.9%。结论:原发灶+转移灶全覆盖放疗治疗寡转移CRPC的PSA反应率高,生存状况满意,毒性反应可耐受。“,”Objectives:To investigate the efficacy and toxicity of the full coverage radiation to primary and all metastatic lesions in patients with oligometastatic castration-resistant prostate cancer (CRPC).Methods:Forty-four patients with oligometastatic CRPC was retrospective analyzed from Oct. 2011 to Jun. 2017 at Peking University 1n st Hospital. Before radiotherapy, average age was 72(57-86), the median value of initial PSA was 38.545 (6.640-1 066.000)ng/ml, the median value of PSA nadir after initial androgen deprivation therapy(ADT) was 0.259(0.011-18.762)ng/ml, the time interval between initial ADT to diagnosis of metastatic castration resistant prostate cancer(mCRPC) was 12(4-96) months, and the median PSA value pre-radiotherapy was 3.765(2.040-187.000) ng/ml. There were 23(52.3%)patients with Gleason score 9-10 and 15(34.0%) patients with Gleason score 8. At the time of initial diagnosis, there was 41(93.2%) cases with stage Tn 3-Tn 4, 23(52.3%)cases with lymph node metastasis, and 29 (63.9%) case with distant metastasis. The number of metastatic foci before radiotherapy was 1 in 22(50.0%)cases, 2 in 12(27.3%)cases, 3 in 6(13.6%)cases and 4 in 4(9.1%)cases. There were 3 cases of pelvic lymph node metastasis (6.8%), 9 cases of retroperitoneal lymph node metastasis(20.5%), 21 cases of bone metastasis(47.7%), 11 cases of bone metastasis+ lymph node metastasis(25.0%), and no visceral metastasis. Image-guided volumetric modulated arc therapy(IGRT-VMAT) was used to fully cover primary and metastatic foci. The prostate and seminal vesicle were routinely underwent 76Gy/38 fractions, and the bioequivalent dose(BEDn 3) was 126.67 Gy. For those with pelvic lymph node metastasis, the drainage area of pelvic lymph node was 46Gy/23 fractions. According to the tolerance of different normal tissues around the lesions, the median BEDn 3 of local radiotherapy dose in the metastatic foci was 112.26(91.14-140.77)Gy. The efficacy and side effects of all these patients were recorded. Kaplan-meier method was used to analyze the overall survival and the new metastasis-free survival.n Results:Only 1 patient had grade 3 urinary tract obstruction and underwent indwelling catheter. All the other patients had grade 1-2 toxic and side effects. After a median follow-up of 34.5(9-96) months, the PSA-nadir after radiotherapy was 0.088(0.003-132.000)ng/ml. Forty(90.9%) patients showed a decrease in PSA after radiotherapy, and 34(77.3%) cases. showed a decrease of >80%. The 1, 3, and 5-year overall survival rates were 90.9%, 54.5%, 36.8%, the 1, 3, and 5-year new metastasis free survival rates were 47.7%, 25.0%, 12.9%, respectively.Conclusion:The full coverage radiotherapy to primary and metastatic lesions showed high PSA response rate, the satisfactory survival and tolerable toxicity in oligometastatic CRPC patients.
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