目的 评估重组人血管内皮抑制素联合螺旋断层放射治疗(TOMO)不可切除且不能耐受同步放化疗的Ⅲ期非小细胞肺癌患者的有效性和安全性。方法 收集2014-09至2020-01空军特色医学中心放射治疗科收治的38例非小细胞肺癌患者临床资料,均为不能接受手术且不能耐受同步放化疗的Ⅲ期患者。采用TOMO联合重组人血管内皮抑制素治疗,TOMO放疗剂量60～70 Gy,分15~25次完成,5次/周;重组人血管内皮抑制素于TOMO前一周采用静脉给药模式,剂量7.5 mg/(m2·d),至少4个周期(持续给药14 d,间隔7 d为一个周期)。评估患者治疗后疗效、安全性及生存时间。结果 共纳入38例,中位随访时间[M (95% CI)]为42.6(17.2,87.4)个月。在38例中,ⅢA和ⅢB期分别为25例(65.8%)和13例(34.2%)。腺癌、鳞癌和其他类型分别为18例(47.4%)、11例(29.0%)和9例(23.7%)。所有患者均按计划完成治疗,其中重组人血管内皮抑制素治疗大于6周期的16例(42.1%)。患者中位总生存期和无进展生存期[M (95% CI)]为37.3(11.3,85.2)个月和23.1(4.6,85.2)个月;3年总生存率和无进展生存率为51.4%和39.8%。多变量分析表明,患者总生存时间和无进展生存时间主要与性别、年龄、吸烟史和TNM分期有关,而体重下降仅与总生存时间相关。放疗剂量模式仅与局部无复发生存时间相关,但与区域无复发生存和远处转移无关。1～2级急性不良反应发生率为28.9%(11例),3级5.3%(2例);1～2级晚期不良反应发生率为5.3%(2例),3级2.6%(1例)。结论 TOMO联合重组人血管内皮抑制素应用于不能手术且不能耐受同步放化疗的Ⅲ期非小细胞肺癌患者的治疗疗效显著,且不良反应可以耐受。
Abstract
Objective To assess the efficacy and safety of recombinant human endostatin (Rh-endostatin) in combination with tomotherapy (TOMO) in the treatment of inoperable stage Ⅲ non-small cell lung cancer (NSCLC) patients who could not tolerate concurrent chemoradiotherapy.Methods Clinical data of 38 inoperable stage Ⅲ NSCLC patients were retrospectively reviewed, who could not tolerate concurrent chemoradiotherapy in the department of radiotherapy of Characteristics Medical Center of Chinese PLA Air Force from September 2014 to January 2020. All patients were treated with TOMO therapy combined with Rh-endostatin. The dosage of TOMO was 60-70 Gy in 15-25 fractions (5 fractions /week). Rh-endostatin was administered intravenously one week before TOMO at a dose of 7.5 mg/m2 qd for 14 consecutive days, and repeated at an interval of one week for at least 4 cycles. Clinical efficacy, safety, and survival were assessed after the treatment.Results All patients were followed-up for a median duration of 42.6 (17.2-87.4) months. There were 25 (65.8%) patients with stage ⅢA NSCLC, and 13 (34.2%) patients with stage ⅢB NSCLC. In terms of pathological types, there were 18 (47.4%) cases of adenocarcinoma, 11 (29.0%) cases of squamous cell carcinoma, and 9 cases (23.7%) of others. All patients completed TOMO and at least 4 cycles of Rh-endostatin therapy, and 16 (42%) patients received more than 6 cycles of Rh-endostatin therapy among them. The median total survival time and progression-free survival time were 37.3 months 95%CI (11.3,85.2) and 23.1 months 95% CI(4.6,85.2) respectively, and the 3-year OS and PFS rate were 51.4% and 39.8% respectively.Multivariate analysis suggested that gender, age, smoking history and TNM stage were significantly associated with progression-free survival (PFS) and overall survival (OS), while weight loss was associated only with OS. TOMO dosage was only associated with local recurrence-free survival, but not with regional recurrence-free survival or distant metastases. The incidences of acute toxicities of grade 1/2 was 28.9% (n=11), and grade 3 was 5.3% (n=2). The incidence of late toxicities of grade 1/2 was 5.3% (n=2) and that of grade 3 was 2.6% (n=1); No grade 4/5 late toxicity occurred.Conclusions Rh-endostatin combined with TOMO is effective in the treatment of stage III non-small cell lung cancer patients who are inoperable and cannot tolerate concurrent chemoradiotherapy, and the adverse reactions are tolerable.
关键词
非小细胞肺癌 /
螺旋断层放射治疗 /
重组人血管内皮抑制素 /
不良反应
Key words
non-small cell lung cancer /
tomotherapy /
Rh-endostatin /
toxicity
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Rebecca L S, Kimberly D M,Ahmedin J.Cancer statistics, 2020[J]. Cancer J Clin, 2020, 70 (1): 7-30.
[2] Xia C, Dong X, Li H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants[J]. Chin Med J (Engl),2022, 135(5):584-590.
[3] Zhang Y, Naci H, Wagner A K, et al. Overall survival benefits of cancer drugs approved in China from 2005 to 2020[J].JAMA Netw Open, 2022, 5(8):e2225973.
[4] Zare-Sakhvidi M J, Yang J, Mehrparvar A H, et al. Exposure to greenspace and cancer incidence, prevalence, and mortality: a systematic review and meta-analyses[J]. Sci Total Environ, 2022, 838(Pt 2):156180.
[5] David S E, Dara L A, Douglas E W, et al. NCCN guidelines insights: non-small cell lung cancer, Version 5.2018[J]. Natl Compr Canc Netw, 2018, 16(7):807-821.
[6] Fournel P. RTOG 94-10: keenly awaited results validating the best therapeutic strategy for locally advanced non-small cell lung cancer[J]. J Natl Cancer Inst, 2011, 103(19):1425-1427.
[7] Mitchell M, Rebecca P, Jennifer M, et al. Defining local-regional control and its importance in locally advanced non-small cell lung carcinoma[J]. J Thorac Oncol, 2012, 7(4):716-722.
[8] Higgins K A, Puri S, Gray J E. Systemic and radiation therapy approaches for locally advanced non-small-cell lung cancer[J]. J Clin Oncol, 2022, 40(6):576-585.
[9] Bryan A C, Brett G M H. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future[J]. Transl Lung Cancer Res, 2015, 4(1):36-54.
[10] Mitchell M, Kyounghwa B, Benjamin M, et al. Higher biologically effective dose of radiotherapy is associated with improved outcomes for locally advanced non-small cell lung carcinoma treated with chemoradiation: an analysis of the radiation therapy oncology group[J]. Int J Radiat Oncol Biol Phys, 2012, 82(1):425-434.
[11] Xia T Y, Li H Q, Sun Q X, et al. Promising clinical outcome of stereotactic body radiation therapy for patients with inoperable stage I/II non-small-cell lung cancer[J]. Int J Radiat Oncol Biol Phys, 2006, 66(1):117-125.
[12] Chang J Y, Mehran R J, Feng L, et al. STARS Lung Cancer Trials Group. Stereotactic ablative radiotherapy for operable stage I non-small-cell lung cancer (revised STARS): long-term results of a single-arm, prospective trial with prespecified comparison to surgery[J]. Lancet Oncol, 2021, 22(10):1448-1457.
[13] Li H Q,Li J, Wang X, et al. Promising clinical outcome with long term follow-up after body gamma knife stereotactic radiosurgery for patients with early stage non-small cell lung cancer[J]. Front Oncol, 2018, 21(8):618.
[14] 李宏奇, 夏廷毅. 体部 γ 刀治疗非小细胞肺癌的经验探讨[J]. 中华放射医学与防护杂志,2016, 36(10): 728-731.
[15] 许子宜, 李峻岭. 晚期非小细胞肺癌抗血管生成药物的联合治疗模式[J]. 中国肺癌杂志,2021,24(5): 357-364.
[16] 邢力刚,马晓林.2021版《中华医学会肿瘤学分会肺癌临床诊疗指南》非小细胞肺癌诊疗更新专家解读[J].疑难病杂志,2022,21(6):557-560.
[17] Mistry H B. Simulating RTOG 0617 using genomic adjusted radiation dose: comparing apples with oranges[J]. J Thorac Oncol, 2021, 16(5):e27.
[18] Yoshito K Michiko T, Yuji F, et al. A multicenter retrospective survey on a suicide trend using hydrogen sulfide in Japan[J]. Clin Toxicol (Phila), 2013, 51(5):425-428.
[19] 戈 伟,明平坡,陈文卫, 等. 恩度联合放疗对肿瘤组织血流灌注和血管生成的影响[J]. 中华实验外科杂志,2014,31(5): 1051-1053.
[20] 郑 伟,康静波,温居一, 等. 恩度联合放化疗对老年Ⅲ期非小细胞肺癌的疗效和毒副反应[J]. 中国医师杂志,2016,18(9): 3.
[21] 王 毅,栾念旭,魏 东. 恩度冲击量输注联合化疗对小细胞肺癌患者血清VEGF、循环内皮细胞、内皮抑素水平的影响[J]. 中国医师杂志,2018,20 (10): 1565-1567.
[22] 马红莲,彭 芳,翟医蕊, 等. 不可手术局部晚期 NSCLC 隔周恩度联合同步放化疗多中心五年生存分析[J]. 中华放射肿瘤学杂志,2021,30(1): 23-28.
基金
空军特色医学中心临床研究项目(2021LC009);空军特色医学中心2021年度青年博士助推计划课题(21ZT01);空军特色医学中心拔尖人才计划项目(22BJQN002)
PDF(1352 KB)
