摘要 目的:探讨125碘粒永久植入及氯化锶[89Sr]静脉注射治疗雄激素非依赖型伴骨转移前列腺癌的疗效。方法:在直肠B超引导下,经会阴穿刺将125I粒子植入到前列腺组织中进行组织间放疗,静脉注射89SrCl2 111~148MBq/次,治疗前列腺癌伴骨转移患者11例。结果:随访3-12个月,8例前列腺体积缩小,3例PSA降至正常,5例PSA较术前呈不同程度下降,2例PSA术前术后无变化,1例PSA上升;骨痛完全缓解3例,部分缓解5例,2-6个月后X光片及骨扫描显示病灶部分消失、变淡5例;治疗一周后4例出现白细胞及血小板计数下降,但4-5周后渐恢复治疗前水平;术后未出现严重放射并发症。结论:125碘粒永久植入及氯化锶[89Sr]静脉注射治疗雄激素非依赖型伴骨转移前列腺癌是比较有效而且安全。
125I Brachytherapy Combined with 89SrCl2 radiotherapy for osseous metastases in hormone non-independent prostate cancer
Liu Guanzhao1, Chen Ping2, Zeng Guohua1, Yuan Jian1
( 1Department of Urology, Minimal Invasive Surgical Center, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, 510230
2Department of Nuclear Medicine, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, 510120 )
[Abstract] Purpose: To study the efficiencyof125I Brachytherapy combined with 89SrCl2 radiotherapy forosseous metastases in hormone non-independent prostate cancer. Materials And Methods: 11 hormone non-independent prostate cancer patients with osseous metastases were performed with 125I Brachytherapy by transperineal under transrectal ultrasound guidance ,combined with 89SrCl2 radiotherapy by intravenous. Results: Following up for 3-12 months after treatment, prostate volume decreased in 8 cases. PSA recovered to normal in 3 cases, PSA decreased in 5 compared with preoperation, PSA had no changes in 2, PSA increased in 1. 3 patients experienced bone-pain disappearance ,5 relieved. The X ray and bone radionuclide scan showed that 5 cases achieved complete or partial focus disappearance at 2-6 months after therapy. Leukocytes and platelets decreased in 4 cases at 1 week after therapy, and selfrecovered after 4-5 weeks. No serious radiotherapy complications were noted. Conclusions: 125I Brachytherapy combined with 89SrCl2 radiotherapy for osseous metastases in hormone non-independent prostate cancer was relatively effective and safe.
[Key words] Prostate cancer, Bone neoplasms, 125I seed, 89SrCl2
讨论
近年来前列腺癌的检出率有所提高,临床上发现的仍多为中晚期患者,相当部分确诊时已有骨转移,失去了前列腺癌根治手术的时机,一直对去雄激素治疗敏感的患者在治疗过程中出现雄激素非依赖性癌细胞,激素治疗失去作用,或者当癌细胞最初由正常细胞转变时,已有一部分细胞变成不需要雄激素而可生存,后期不需要雄激素的细胞成为主要的成分。肿瘤表现为雄激素非依赖性生长,使病情进展、恶化,给病人带来痛苦及致病人死亡。
本组11例曾服用缓退瘤或康士得治疗,在术前2~5月发现PSA连续升高,出现不同程度骨痛或在原有基础上加剧,行X光及骨扫描检查发现全身多处骨转移灶或较前加剧。放射治疗对前列腺癌细胞具有破坏杀伤作用,适用于不宜采用根治手术切除、对去雄激素治疗不敏感、需要缩小肿瘤体积、缓解症状的晚期前列腺癌患者。
自Pasteau和Degrais1911年开始应用镭针插植放疗治疗前列腺癌,此技术经历了不断演变。125碘粒永久植入近距离放疗治疗前列腺癌近年来在欧美等国广泛应用(1),Bice 等(2)1998年报道125碘粒间质植入近距离放疗治疗前列腺癌集中多中心的治疗后分析,认为此法可行、合适。近年来国内学者也对该治疗作相关报道(3),从治疗概况、操作方法、核素选择、疗效评价等进行阐述。125碘粒半衰期为59.6天,能量为27.4~31.5KevX射线及30.5Kev达玛射线,种植在组织间放疗,具有靶心准的特点,既能达到靶内高剂量,又能避免对周围正常组织及全身损伤,病人全身反应少,疗效好。
125碘粒永久植入近距离放疗治疗的近期并发症主要表视为尿路阻塞和刺激症状,文献报道约4~8%的患者可能需要术后导尿,与局部炎症水肿有关,本组有不同程度的尿路刺激症状,偶有尿道灼热感,随访1~3月均能自行缓解,部分排尿情况较术前有所改善,与IPSS评分下降,前列腺经直肠B超发现有不同程度缩小有关。有学者报道有TURP史患者病人患尿道坏死、尿失禁的比例可达50%,无TURP者发生比例仅1%(4,5)。但也有报道认为TURP后至少等待2~3个月再进行近距离治疗,这样缺陷的组织可以再生,只要放射性粒子离开尿道一定距离则可避免并发症,Wallner等(6)报道19例有TURP史患者中仅1例发生尿失禁。本组11例中有4例2~3年前曾行TURP,治疗前B超发现再次增生,与本组无尿失禁发生有关。
Beyer等(7)报道治疗前PSA<10ng/ml预后较好,Gleason评分≤6同样是重要的影响预后的因素。对临床分期T2b~T3a,Gleason≥7或PSA原始水平较高、有骨转移的患者,有学者认为如侵犯包膜外,应加外照射治疗。我们单用植入近距离放疗的方法亦取得良好的效果,比加外照射损伤小。另外,术后PSA的测定是了解放射治疗效果的简易有效方法,一般治疗6个月后PSA下降或降至正常,如果增高表明肿瘤继续存在,但Morita等(8)报道近40%患者治疗后短期内有PSA反弹增高的现象。本组随访复查PSA,2例PSA术前后变化不大,1例PSA反弹上升,3例6个月后PSA降至<2ng/ml,5例均呈下降趋势,表明治疗效果明显。
对有骨转移的前列腺癌患者,常伴有难以忍受的骨性疼痛症状,而放射性核素氯化锶[89Sr]静脉注射治疗可以缓解疼痛症状。89Sr是唯一FDA批准的治疗转移性前列腺癌的同位素,89Sr具有亲骨性,注入体内70%以上聚集于骨,在骨转移瘤的聚集可高达正常骨的3倍以上,其产生的β射线可对病灶集中照射,使瘤体缩小、破坏,减少瘤体致痛物的产生,达到缓解疼痛的目的(9)。随访X光片及骨扫描显示病灶部分消失、变淡5例,有效率45.4%,无变化4例,病灶增多或增大2例,碱性磷酸酶总体水平呈下降。Porter等(10)报道Trans Canadian研究结果,89Sr控制疼痛完全有效率可达20%,并能延长疼痛缓解期。钟甘平等(11)报道27例应用89Sr治疗前列腺癌有骨转移患者,完全缓解9例达33%,部分缓解14例达51%,总有效率85%。本组11例中骨痛完全缓解3例,部分缓解5例,总有效率72.7%,疗效良好。
应用89Sr治疗的主要副作用为白细胞及血小板减少,一般在治疗后4~8周出现,停药后可逐渐回复术前水平。文献报道89Sr治疗后患者可能出现暂时性骨痛加重(反弹现象)(12),一般几天到几周内出现,可能是暂时性炎症反应、病损部位内压力发生改变的结果,给予激素治疗可缓解症状。
我们采用125碘粒永久植入及氯化锶[89Sr]静脉注射的方法,治疗雄激素非依赖型伴骨转移前列腺癌患者,随访3-12个月,11例均无出现膀胱、尿道、直肠的放射损伤,无血尿、血便、尿失禁等症状,达到缩小肿瘤体积、缓解症状的目的,疗效满意。
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