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直肠侧方屏蔽可降低临床局限性前列腺癌高剂量三维适形放疗后直肠迟发性并发症:显著剂量效应的进一步证据

Lateral rectal shielding reduces late rectal morbidity following high dose three-dimensional conformal radiation therapy for clinically localized prostate cancer: further evidence for a significant dose effect.

作者信息

Lee W R, Hanks G E, Hanlon A L, Schultheiss T E, Hunt M A

机构信息

Fox Chase Cancer Center, Department of Radiation Oncology, Philadelphia, PA 19111, USA.

出版信息

Int J Radiat Oncol Biol Phys. 1996 May 1;35(2):251-7. doi: 10.1016/0360-3016(96)00064-8.

DOI:10.1016/0360-3016(96)00064-8
PMID:8635930
Abstract

PURPOSE

Using conventional treatment methods for the treatment of clinically localized prostate cancer central axis doses must be limited to 65-70 Gray (Gy) to prevent significant damage to nearby normal tissues. A fundamental hypothesis of three-dimensional conformal radiation therapy (3DCRT) is that, by defining the target organ(s) accurately in three dimensions, it is possible to deliver higher doses to the target without a significant increase in normal tissue complications. This study examines whether this hypothesis holds true and whether a simple modification of treatment technique can reduce the incidence of late rectal morbidity in patients with prostate cancer treated with 3DCRT to minimum planning target volume (PTV) doses of 71-75 Gy.

METHODS AND MATERIALS

The 257 patients with clinically localized prostate cancer who completed 3DCRT by December 31, 1993 and received a minimum PTV dose of 71-75 Gy are included in this report. The median follow-up time was 22 months (range: 4-67 months); 98% of patients had follow-up of longer than 12 months. The calculated dose at the center of the prostate was < 74 Gy in 19 patients, 74-76 Gy in 206 patients, and > 76 Gy in 32 patients. Late rectal morbidity was graded according to the Late Effects Normal Tissue (LENT) scoring system. Eighty-eight consecutive patients were treated with a rectal block added to the lateral fields. In these patients the posterior margin from the prostate to the block edge was reduced from the standard 15 to 5 mm for the final 10 Gy, which reduced the dose to portions of the anterior rectal wall by approximately 4-5 Gy. Estimates of rates for rectal morbidity were determined by Kaplan-Meier actuarial analysis. Differences in morbidity percentages were evaluated by the Pearson chi-square test.

RESULTS

Grade 2-3 rectal morbidity developed in 46 out of 257 patients (18%) and in the majority of cases consisted of rectal bleeding. No patient has developed Grade 4 or 5 rectal morbidity. The actuarial rate of Grade 2-3 morbidity is 23% at 24 months and the median time to the development of Grade 2-3 complications is 15 months. A statistically significant dose effect is evident. The incidence of Grade 2-3 rectal morbidity increased as the dose at the center of the prostate increased (p = 0.05). In patients receiving minimum PTV doses of < or = 76 Gy the use of a rectal block significantly reduced the incidence of Grade 2-3 toxicity; 6 out of 88 (7%) with a block vs. 30 out of 137 (22%) without a block, (p = 0.003).

CONCLUSION

The incidence of late rectal morbidity with 3DCRT to minimum PTV doses of 71-75 Gy is acceptable and to date no Grade 4-5 rectal morbidities have been observed. In our experience, higher doses to the center of the prostate are associated with an increased likelihood of developing Grade 2-3 rectal morbidity but treatment techniques that reduce the total dose to the anterior rectal wall have reduced the incidence of late rectal morbidity. If clinical studies indicate improved tumor control with minimum PTV doses above 71 Gy, then dose escalation above 76 Gy to the center of the prostate should be pursued cautiously with treatment techniques that limit the total dose to the anterior rectal wall.

摘要

目的

采用传统治疗方法治疗临床局限性前列腺癌时,为防止对附近正常组织造成严重损伤,中心轴剂量必须限制在65 - 70戈瑞(Gy)。三维适形放射治疗(3DCRT)的一个基本假设是,通过在三维空间中精确界定靶器官,可以在不显著增加正常组织并发症的情况下,向靶区给予更高剂量的辐射。本研究旨在检验这一假设是否成立,以及治疗技术的简单改进能否降低接受3DCRT且最小计划靶体积(PTV)剂量为71 - 75 Gy的前列腺癌患者晚期直肠并发症的发生率。

方法与材料

本报告纳入了1993年12月31日前完成3DCRT且最小PTV剂量为71 - 75 Gy的257例临床局限性前列腺癌患者。中位随访时间为22个月(范围:4 - 67个月);98%的患者随访时间超过12个月。前列腺中心计算剂量<74 Gy的有19例,74 - 76 Gy的有206例,>76 Gy的有32例。晚期直肠并发症根据正常组织晚期效应(LENT)评分系统进行分级。连续88例患者在侧野添加了直肠挡块。在这些患者中,前列腺至挡块边缘的后缘在最后10 Gy时从标准的15 mm减至5 mm,这使直肠前壁部分的剂量降低了约4 - 5 Gy。直肠并发症发生率的估计通过Kaplan - Meier精算分析确定。并发症发生率的差异通过Pearson卡方检验进行评估。

结果

257例患者中有46例(18%)发生2 - 3级直肠并发症,大多数病例为直肠出血。无患者发生4 - 5级直肠并发症。24个月时2 - 3级并发症的精算发生率为23%,发生2 - 3级并发症的中位时间为15个月。剂量效应具有统计学意义。随着前列腺中心剂量的增加,2 - 3级直肠并发症的发生率升高(p = 0.05)。在接受最小PTV剂量≤76 Gy的患者中,使用直肠挡块显著降低了2 - 3级毒性的发生率;有挡块的88例中有6例(7%)发生,无挡块的137例中有30例(22%)发生,(p = 0.003)。

结论

3DCRT至最小PTV剂量为71 - 75 Gy时晚期直肠并发症的发生率是可接受的,且迄今为止未观察到4 - 5级直肠并发症。根据我们的经验,前列腺中心较高剂量与发生2 - 3级直肠并发症的可能性增加相关,但降低直肠前壁总剂量的治疗技术已降低了晚期直肠并发症的发生率。如果临床研究表明最小PTV剂量高于71 Gy时肿瘤控制得到改善,那么在采用限制直肠前壁总剂量的治疗技术时,应谨慎地将前列腺中心剂量提高至76 Gy以上。

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