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摘要:
目的 分析胰腺癌的精确放疗疗效及预后因素。 方法 2003年1月至2012年6月间接受精确放疗的胰腺癌患者102例, 其中根治性放疗54例, 辅助性放疗48例; 三维适形放疗平均16例, 调强放疗86例; 中位放疗剂量50 Gy, 1.8~2.2 Gy/次。13例同步卡培他滨化疗。 结果 所有患者总生存时间(overall survival, OS)为(14±1.2)个月, 无进展生存时间(progress-free survival, PFS)为(9±1.1)个月。1、2、5年生存率分别为63.3%、22.6%、10%。毒性反应包括3级消化道毒性5例, 未发生3、4级血液学和4级消化道毒性反应。单因素分析结果表明, 治疗前体重下降 > 5 kg(P < 0.0001)、T分期(P=0.011)、TNM分期(P=0.007)、是否行肿瘤切除术(P=0.001)是影响OS的预后因素, 同时也是PFS的预后因素。多因素分析结果表明, 肿瘤切除术是OS的预后因素(χ2=5.416, P=0.020)。 结论 在胰腺癌的根治性放疗和辅助性放疗中, 三维适形放疗和调强放疗都可以较好地耐受, 3、4级毒性反应较少, 为放化疗同步及肿瘤放疗剂量的提升提供了可行性; 手术切除提高了OS。 Abstract:Objective To analyze the effectiveness and prognostic factors of precise radiotherapy for pancreatic cancer. Methods Totally 102 patients with pancreatic cancer received precise radiotherapy in our hospital between January 2003 and June 2012, among whom 54 received radical radiotherapy and 48 underwent adjuvant radiotherapy. Three-dimensional conformal radiotherapy (3D-CRT) was performed in 16 cases and intensity-modulated radiotherapy (IMRT) in 86 cases, with a median radiotherapy dose of 50 Gy (1.8~2.2 Gy/fraction). Concurrent capecitabine chemotherapy was carried out in 13 cases. Results The average overall survival time (OS) and the average time to progress-free survival (PFS) was (14±1.2) months and (9±1.1) months, respectively. The 1-, 2-, and 5-year survival rates were 63.3%, 22.6%, and 10%, respectively. Grade 3 gastrointestinal toxicity occurred in 5 cases. No grade 3 or 4 hematologic toxicity and grade 4 gastrointestinal toxicity was observed. Univariate analysis showed that weight loss of > 5 kg before treatment (P < 0.0001), T stage (P=0.011), TNM stage (P=0.007), and surgical excision (P=0.001) were significantly associated with OS and PFS. Multivariate analysis showed that surgical excision was a prognostic factor for OS (χ2=5.416, P=0.020). Conclusions The precise radiotherapy including 3D-CRT and IMRT can be tolerated with fewer grade 3 and 4 toxicities in pancreatic cancer patients after radical radiotherapy and adjuvant radiotherapy, thus make it feasible for the concurrent chemotherapy and the increase of radiotherapy dose. Surgical excision can improve the OS of pancreatic cancer patients. -
表 1 胰腺癌放疗患者基本临床资料
临床资料 例(%) 性别 男 60(58.8%) 女 42(41.2%) 年龄(岁) ≤60 42(41.2%) >60 60(58.8%) 腹痛 有 69(67.6%) 无 33(32.4%) 黄疸 有 23(22.5%) 无 79(77.5%) 体重减轻(kg) ≤5 59(57.8%) >5 43(42.2%) 肿瘤部位 胰头 50(49.0%) 胰体 52(51.0%) T分期 T1 1(1.0%) T2 4(3.9%) T3 46(45.1%) T4 51(50.0%) N分期 N0 69(67.6%) N1 33(32.4%) TNM分期 ⅠB 4(3.9%) ⅡA 27(26.5%) ⅡB 27(26.5%) Ⅲ 44(43.1%) 手术 有 48(47.1%) 无 54(52.9%) 化疗 有 52(51.0%) 无 50(49.0%) 放疗剂量(Gy) ≤45 13(12.7%) 45~55 48(47.1%) >55 41(40.2%) 表 2 影响总生存时间及无进展生存时间的单因素分析
因素 总生存时间 无进展生存时间 月(x±s) χ2值 P值 月(x±s) χ2值 P值 性别 男 14±1.6 0.696 0.404 9±1.7 0.245 0.621 女 15±2.2 9±1.5 年龄(岁) ≤61 15±1.2 1.445 0.229 10±1.9 1.342 0.247 >61 14±1.8 9±1.2 体重下降(kg) ≤5 18±3.9 14.500 <0.0001 11±1.9 14.606 <0.0001 >5 11±2.2 6±0.8 肿瘤部位 胰头 16±0.9 0.333 0.564 10±1.4 0.310 0.577 胰体 12±1.7 7±1.2 T分期 T1 6 11.180 0.011 3 15.717 0.001 T2 17±0.8 5±0.0 T3 17±2.0 11±1.7 T4 11±1.0 7±0.7 N分期 N0 15±1.3 3.334 0.068 10±1.1 2.807 0.094 N1 12±2.5 7±0.9 TNM分期 ⅠB 17±0.0 12.073 0.007 5±0.0 12.989 0.005 ⅡA 23±8.8 19±7.9 ⅡB 11±3.8 7±1.3 Ⅲ 12±1.1 7±0.8 手术 有 22±3.2 11.885 0.001 11±2.1 10.250 0.001 无 11±1.3 7±0.6 放疗剂量(Gy) ≤45 13±3.9 0.133 0.936 7±0.8 0.158 0.924 45~55 14±1.6 10±2.3 >55 15±1.9 8±1.2 CA19-9(kU/L) ≤200 16±2.2 2.779 0.096 10±0.8 1.288 0.256 >200 13±1.7 7±0.8 表 3 影响总生存时间及无进展生存时间的多因素分析
因素 总生存时间 无进展生存时间 Wald值 P值 Wald值 P值 性别(男,女) 0.215 0.643 0.047 0.829 年龄(≤61岁,>61岁) 0.062 0.804 0.177 0.674 体重下降(≤5 kg,>5 kg) 1.839 0.175 3.541 0.060 肿瘤部位(胰头,胰体) 0.784 0.376 0.811 0.368 T分期(1,2,3,4) 0.457 0.499 1.359 0.244 N分期(0,1) 3.675 0.055 0.833 0.361 TNM分期(ⅠB, ⅡA, ⅡB, Ⅲ) 1.435 0.231 2.599 0.107 手术(有,无) 5.416 0.020 2.799 0.094 放疗剂量(45 Gy,45~55 Gy,
55 Gy)1.010 0.315 0.536 0.464 CA19-9(≤200 kU/L,>200 kU/L) 0.730 0.393 1.348 0.246 -
[1] Jacobs NL, Que FG, Miller RC, et al. Cumulative morbidity and late mortality in long-term survivors of exocrine pancreas cancer[J]. J Gastroinstestinal Cancer, 2009, 40:46-50. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=5b094a306eeba7a69aa7f8659d58f644 [2] Spinelli GP, Zullo A, Romiti A, et al. Long-term survival in metastatic pancreatic cancer. A case report and review of the literature[J]. JOP, 2006, 7:486-491. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=Open J-Gate000001418186 [3] Keleg S, Büchler P, Ludwig R, et al. Invasion and metastasis in pancreatic cancer[J]. Mol Can, 2003, 2:14. http://europepmc.org/articles/PMC149416/ [4] Garcea G, Dennison AR, Pattenden CJ, et al. Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature[J]. JOP, 2008, 9:99-132. http://europepmc.org/abstract/MED/18326920 [5] Royal RE, Wolff RA, Crane CH. Cancer of the pancreas[M]//De Vita VTJ, Lawrence TS, Rosenberg SA, eds. Principles and practice of oncology. 8th ed. Philadelphia: Lippincott Williams & Wilkins, 2008: 1086-1123. [6] Abbott DE, Baker MS, Talamonti MS. Neoadjuvanttherapy for pancreatic cancer:acurrent review[J]. J Surg Oncol, 2010, 101:315-320. doi: 10.1002/jso.21469 [7] Abelson JA, Murphy JD, MinnAY, et al. Intensity-modulated radiotherapy for pancreatic adenocarcinoma[J]. IJROBP, 2012, 82:e595-e601. http://www.sciencedirect.com/science/article/pii/S0360301611032524 [8] Smeenk HG, van Eijick CHJ, Hop WC, et al. Long-term survival and metastatic pattern of pancreatic and periampullary cancer after adjuvant chemoradiation or observation:long-term results of EORTC trial 40891[J].Ann Surg, 2007, 246:734-740. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=WK_LWW201705250171867 [9] Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer[J]. N Engl J Med, 2004, 350:1200-1210. http://fg.bmj.com/external-ref?access_num=10.1056/NEJMoa032295&link_type=DOI [10] Stessin AM, Meyer JE, Sherr DL, et al. Neoadjuvant radiation is associated with improved survival in patients with resectable pancreatic cancer:an analysis of data from the surveillance, epidemiology, and end results (SEER) registry[J]. IJROBP, 2008, 72:1128-1133. http://www.ncbi.nlm.nih.gov/pubmed/18538501 [11] McDade TP, Hill JS, Simons JP, et al. A national propensity-adjusted analysis of adjuvant radiotherapy in the treatment of resected pancreatic adenocarcinoma[J]. Cancer, 2010, 116:3257-3266. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=de383c6596b7c068d5907451fd70a02f [12] Regine WF, Winter KA, Abrams R.Fluorouracil based chemoradiation with either gemcitabine or fluorouracil chemotherapy following resection of pancreatic adenocarcinoma:5-year analysis of the US Intergroup/RTOG 9704 phase Ⅲ trial[J]. Ann Surg Oncol, 2011, 18:1319-1326. http://www.zhangqiaokeyan.com/academic-journal-foreign-pmc_detail_thesis/040005885381.html [13] Moertel CG, Frytak S, Hang RG, et al. Therapy of locally unresectable pancreatic carcinoma:A randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads+5-fluorouracil) and high dose radiation +5-fluorouracil[J]. Cancer, 1981, 48:1705-1710. http://www.ncbi.nlm.nih.gov/pubmed/7284971 [14] Loehrer P, Powell ME, Cardenes HR, et al. A randomized phase Ⅲ study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer:E4201[J]. JOP, 2008, 9:391-397. [15] Mukherjee S, Hurt CN, Bridgewater J, et al. Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP):a multicentre, randomised, phase 2 trial[J]. Lancet Oncol, 2013, 14:317-326. http://search.ebscohost.com/login.aspx?direct=true&db=aph&AN=89067021&site=ehost-live [16] Barhoumi M, Mornex F, Bonnetain F, et al. Locally advanced unresectable pancreatic cancer:induction chemoradiotherapy followed by maintenance gemcitabine versus gemcitabine alone:definitive results of the 2000-2001 FFCD/SFRO phase Ⅲtrial[J].Cancer Radiother, 2011, 15:182-191. [17] Ben-Josef E, Griffith K, Francis IR, et al. Phase Ⅰ radiation dose-escalation trial of intensity-modulated radiotherapy (IMRT) with concurrent fixed dose-rate gemcitabine (FDR-G) for unresectable pancreatic cancer[J]. J ClinOncol, 2009, 27(15S):4602.