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大剂量全腹盆腔照射治疗卵巢癌:长期毒性及疗效

High-dose whole abdominal and pelvic irradiation for treatment of ovarian carcinoma: long-term toxicity and outcomes.

作者信息

Firat Selim, Murray Kevin, Erickson Beth

机构信息

Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

出版信息

Int J Radiat Oncol Biol Phys. 2003 Sep 1;57(1):201-7. doi: 10.1016/s0360-3016(03)00510-8.

Abstract

PURPOSE

To evaluate the role of high-dose whole abdominal and pelvic irradiation (WART) in the treatment of epithelial ovarian carcinoma.

METHODS AND MATERIALS

A retrospective review was performed on 71 patients with Stage I-III ovarian carcinoma who were treated with WART using an open field technique after total abdominal hysterectomy and bilateral oophorectomy with or without omentectomy. Whole abdominal doses greater than typically recommended were used in a series of patients to enhance local control and to decrease abdominal recurrence. None of the patients had received chemotherapy before RT. Thirty-one patients received Alkeran or cyclophosphamide and two received cisplatin-based chemotherapy after WART. The median whole abdominal dose was 36 Gy (range 9-45.5), delivered in a median of 30 fractions (range 8-46). A pelvic boost was delivered using AP-PA fields during whole abdominal RT to a total midline pelvic dose of 200 cGy/d. The median pelvic dose was 51 Gy (range 16-59). The right lobe and a portion of the left lobe of the liver were shielded with custom blocks at a median dose of 25 Gy (range 9-41). The kidneys were shielded either AP-PA or PA from the first day of RT. The median dose to the kidneys was 19 Gy (range 4-30).

RESULTS

The 5-year overall survival rate was 93%, 48%, and 29% for Stage I, II, and III patients, respectively. On multivariate analysis, stage and the extent of residual disease were independent prognostic factors. The 5- and 10-year overall survival rate for the 46 patients in the intermediate-risk group was 61% and 54%, respectively. For this group, a total abdominal dose of > or /=36 Gy was associated with a longer overall survival independent of stage, grade, and the amount of residual disease. This was most likely due to a significant reduction in the incidence of abdominal recurrence in patients receiving >36 Gy to the whole abdomen (18% vs. 49%, p = 0.006). Multivariate analysis revealed that grade (p = 0.023) and abdominal dose (p = 0.018) were independent factors influencing the rate of abdominal recurrence. Pelvic recurrence was rare as a first site of failure (6%). Twenty-one percent (n = 15) of the patients developed Grade 3 or 4 (Radiation Therapy Oncology Group [RTOG] criteria) chronic small or large bowel toxicity. Eleven percent of all patients had a small bowel obstruction requiring surgery. A whole abdominal dose >30 Gy and a pelvic dose >50 Gy were associated with a significant increase in small bowel obstruction (p = 0.01) independent of other factors. Chronic Grade 3 or 4 (Common Toxicity Criteria) anemia, thrombocytopenia, and leukopenia were seen in 7%, 1%, and 4% of the patients, respectively. Transient liver enzyme elevation was common (62%). Two patients had Grade 3 (RTOG) hepatic toxicity. Grade 3 or 4 renal toxicity (RTOG) was observed in 4%, and 2 patients (3%) were diagnosed with pelvic insufficiency fractures that were managed conservatively.

CONCLUSION

Survival after RT for ovarian carcinoma rivals that achieved with systemic chemotherapy. The results of this study suggest a possible dose-control relationship between the whole abdominal dose and the risk of abdominal recurrence; however, a higher rate of small bowel obstruction was observed when greater abdominal doses and greater pelvic doses were combined. Careful attention to balancing toxicity and efficacy is imperative if RT is to have a future role in the treatment of this disease.

摘要

目的

评估大剂量全腹盆腔照射(WART)在治疗上皮性卵巢癌中的作用。

方法和材料

对71例I - III期卵巢癌患者进行回顾性研究,这些患者在全腹子宫切除术和双侧卵巢切除术(有或无大网膜切除术)后采用开放野技术接受WART治疗。在一系列患者中使用了高于通常推荐剂量的全腹照射,以增强局部控制并降低腹部复发率。所有患者在放疗前均未接受过化疗。31例患者在WART后接受了美法仑或环磷酰胺治疗,2例接受了基于顺铂的化疗。全腹中位剂量为36 Gy(范围9 - 45.5),中位分30次给予(范围8 - 46)。在全腹放疗期间使用前后位 - 后前位野给予盆腔追加剂量,使盆腔中线总剂量达到200 cGy/天。盆腔中位剂量为51 Gy(范围16 - 59)。肝脏右叶和左叶的一部分用定制铅块屏蔽,中位剂量为25 Gy(范围9 - 41)。从放疗第一天起,肾脏采用前后位 - 后前位或后前位屏蔽。肾脏的中位剂量为19 Gy(范围4 - 30)。

结果

I期、II期和III期患者的5年总生存率分别为93%、48%和29%。多因素分析显示,分期和残留疾病范围是独立的预后因素。中危组46例患者的5年和10年总生存率分别为61%和54%。对于该组患者,全腹剂量≥36 Gy与更长的总生存期相关,且与分期、分级和残留疾病量无关。这很可能是由于全腹接受>36 Gy照射的患者腹部复发率显著降低(18%对49%,p = 0.006)。多因素分析显示,分级(p = 0.023)和腹部剂量(p = 0.018)是影响腹部复发率的独立因素。盆腔复发作为首次失败部位很少见(6%)。21%(n = 15)的患者出现3级或4级(放射治疗肿瘤学组[RTOG]标准)慢性小肠或大肠毒性。所有患者中有11%发生小肠梗阻需要手术治疗。全腹剂量>30 Gy和盆腔剂量>50 Gy与小肠梗阻显著增加相关(p = 0.01),且与其他因素无关。分别有7%、1%和4%的患者出现3级或4级(常见毒性标准)慢性贫血、血小板减少和白细胞减少。短暂性肝酶升高很常见(62%)。2例患者出现3级(RTOG)肝毒性。4%的患者观察到3级或4级(RTOG)肾毒性,2例患者(3%)被诊断为盆腔不全骨折,采用保守治疗。

结论

卵巢癌放疗后的生存率与全身化疗相当。本研究结果提示全腹剂量与腹部复发风险之间可能存在剂量 - 控制关系;然而,当全腹剂量和盆腔剂量都较高时,小肠梗阻发生率较高。如果放疗要在这种疾病的治疗中发挥未来作用,必须谨慎注意平衡毒性和疗效。

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