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探讨氨磷汀对局部晚期直肠癌新辅助放疗同期伊立替康化疗的减毒作用：对154例病例的回顾性队列研究
Exploring the attenuating effect of amifostine on neoadjuvant radiotherapy with concurrent use of irinotecan for locally advanced rectal cancer: a retrospective cohort study of 154 cases
- 中国癌症杂志 2024年34卷第10期 页码：957-965
- 作者机构：
1. 复旦大学附属肿瘤医院闵行分院放疗科，上海 200240
2. 复旦大学附属肿瘤医院放射治疗中心，复旦大学上海医学院肿瘤学系，上海 200032
- 作者简介：
[ "第一作者：储亚娟（ORCID: 0000-0003-4183-1217），硕士，主治医师。" ]
马金利（ORCID: 0000-0001-6127-648X），博士，副主任医师。
- 基金信息：闵行区自然科学研究课题(2021MHZ094)
DOI：10.19401/j.cnki.1007-3639.2024.10.005
中图分类号： R35.3+7收稿：2024-05-20，
修回：2024-10-21，
纸质出版：2024-10-30
- 稿件说明：
移动端阅览
储亚娟, 张蕾, 李云海, 等. 探讨氨磷汀对局部晚期直肠癌新辅助放疗同期伊立替康化疗的减毒作用：对154例病例的回顾性队列研究[J]. 中国癌症杂志, 2024,34(10):957-965.
Yajuan CHU, Lei ZHANG, Yunhai LI, et al. Exploring the attenuating effect of amifostine on neoadjuvant radiotherapy with concurrent use of irinotecan for locally advanced rectal cancer: a retrospective cohort study of 154 cases[J]. China Oncology, 2024, 34(10): 957-965.
储亚娟, 张蕾, 李云海, 等. 探讨氨磷汀对局部晚期直肠癌新辅助放疗同期伊立替康化疗的减毒作用：对154例病例的回顾性队列研究[J]. 中国癌症杂志, 2024,34(10):957-965. DOI： 10.19401/j.cnki.1007-3639.2024.10.005.
Yajuan CHU, Lei ZHANG, Yunhai LI, et al. Exploring the attenuating effect of amifostine on neoadjuvant radiotherapy with concurrent use of irinotecan for locally advanced rectal cancer: a retrospective cohort study of 154 cases[J]. China Oncology, 2024, 34(10): 957-965. DOI： 10.19401/j.cnki.1007-3639.2024.10.005.
摘要
背景与目的：
直肠癌是全球范围内严重危害人群健康的恶性肿瘤之一，发病率位居第三，死亡率排名第二。随着社会经济水平发展，中国的结直肠癌发病率及死亡率呈增高趋势，成为全球结直肠癌高发的国家之一。局部晚期直肠癌推荐治疗方式为新辅助放化疗联合手术治疗，这极大地改善了患者的预后。然而，新辅助放化疗引起的腹泻等肠道不良反应增多，部分患者因严重的毒性和不良反应被迫延迟或中断治疗。氨磷汀是一种广谱正常细胞保护剂，对于多种放化疗毒性都有良好的防护效果。本研究通过回顾性资料分析接受新辅助放疗联合伊立替康同步化疗的局部晚期直肠癌患者，探讨同期使用氨磷汀是否可减轻胃肠道和血液学毒性。
方法：
本研究采用回顾性队列分析方法。回顾性收集2018年1月1日—2019年12月31日在复旦大学附属肿瘤医院接受新辅助放化疗的局部晚期直肠癌患者的临床数据。按是否同期使用氨磷汀分组。主要研究目的是分析氨磷汀是否能减轻胃肠道与血液学毒性，次要研究目的包括氨磷汀是否能改变肿瘤标志物水平、直肠系膜筋膜侵犯（mesorectal fascia invasion，MRF）阳性率、壁外血管侵犯（extramural vascular invasion，EMVI）阳性率及病理学完全缓解率（pathological complete response，pCR）。采用SAS9.4统计软件，对于连续变量，进行了正态性检验。腹泻等级不符合正态分布行Wilcoxon秩和检验；血液学毒性组内比较行方差分析，组间比较行Wilcoxon秩和检验；肿瘤标志物的变化值因为组间不均衡性，故采用广义估计方程进行前后组间差值的比较。本研究严格遵循流行病学观察性研究报告指南（STrengthening the Reporting of OBservational studies in Epidemiology，STROBE），确保研究方法的透明度和结果的可靠性。
结果：
最终纳入了154例符合条件的患者，按是否同期使用氨磷汀分组，其中氨磷汀组78例，对照组76例。氨磷汀组腹泻最高分级为1.00（1.00，1.00）低于对照组的2.00（2.00，3.00），组间差异有统计学意义（
P
<
0.01）。放疗后两组间白细胞计数（white blood cell count，WBC）、血红蛋白（hemoglobin，HB）、中性粒细胞绝对值（absolute neutrophil count，ANC）和血小板计数（platelet count，PLT）变化值差异均无统计学意义（
P
>
0.05），两组新辅助治疗期间最低血常规WBC、RBC、PLT值差异均无统计学意义（
P
>
0.05），氨磷汀似乎不能减轻血液学毒性。两组肿瘤标志物糖类抗原72-4（carbohydrate antigen 72-4，CA72-4）（
Z
= 2.22，
P
= 0.03）、糖类抗原50（carbohydrate antigen 50，CA50）（
Z
= -2.49，
P
= 0.01）、糖类抗原24-2（carbohydrate antigen 24-2，CA24-2）（
Z
= -2.29，
P
= 0.02）差值相比均有统计学意义。两组组间MRF阳性率（
P
= 0.11）、EMVI阳性率（
P
= 0.61）、pCR率（
P
= 0.94）相比差异均无统计学意义。
结论：
接受新辅助放化疗的局部晚期直肠癌患者同期使用氨磷汀可以减轻胃肠道毒性，并且降低肿瘤标志物CA72-4、CA50和24-2水平。但在改善血液学毒性、MRF和EMVI阳性率及pCR率等方面似无明显作用。
Abstract
Background and purpose:
Rectal cancer is one of the malignant tumors that seriously harm human health in the world
ranking third in incidence and second in mortality. With the development of social and economic level
the incidence and mortality of colorectal cancer in China are increasing
and China becomes one of the countries with high incidence of colorectal cancer disease in the world. The recommended treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy combined with surgery
which greatly improves the prognosis of patients. However
intestinal adverse reactions such as diarrhea caused by neoadjuvant chemoradiotherapy are increased
and some patients are forced to delay or interrupt treatment due to serious side effects. Amifostine is a broad-spectrum normal cell protective agent
which has good protective effect against various radiochemotherapy toxicity. We conducted a retrospective analysis of patients with locally advanced rectal cancer who received neoadjuvant radiotherapy combined with irinotecan concurrent chemotherapy to investigate whether concurrent use of amifostine alleviated gastrointestinal and hematological toxicities.
Methods:
A retrospective cohort analysis was used in this study. Clinical data of patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy at the Affilia
ted Cancer Hospital of Fudan University during the period of discharge from January 1
2018 to December 31
2019 were retrospectively collected. The patients were divided into 2 groups by whether amifostine was used during the same period. The main purpose of the study was to analyze whether amifostine can reduce gastrointestinal and hematological toxicities
and secondary objectives included whether amifostine could alter tumor marker levels
mesorectal fascia invasion (MRF) positive rate
extramural vascular invasion
positive rate of EMVI and pathological complete response (pCR). Using SAS9.4 statistical software
the normality test was carried out for continuous variables. The rank sum test of Wilcoxon was performed when the diarrhea grade did not conform to normal distribution. Analysis of variance was performed for intra-group comparison
and Wilcoxon rank sum test was performed for inter-group comparison. Because of the imbalance between groups
the difference between the two groups was compared using a generalized linear model. This study strictly followed the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines to ensure the transparency of the research methodology and the reliability of the results.
Results:
Finally
154 eligible patients were included
of whom 78 were in the amifostine group and 76 were in the control group. The highest grade of diarrhea in amifostine group was 1.00(1.00
1.00)
lower than that in control group (2.00
3.00)
and the difference between groups was statistically significant (
P
<
0.01). After radiotherapy
white blood cell count (WBC)
hemoglobin (HB) and absolute neutrophil count (ANC) from the two groups were obtained. ANC and platelet count (PLT) showed no statistically significant difference (
P
>
0.05)
and the lowest values of WBC
RBC and PLT did not have statistically significant difference between the two groups during neoadjuvant period (
P
>
0.05). Amifostine may
not alleviate hematological toxicity. Carbohydrate antigen 72-4 (CA72-4) (
Z
=2.22
P
=0.03)
carbohydrate antigen 50 (CA50) (
Z
=-2.49
P
=0.01) and carbohydrate antigen 24-2 (CA24-2) had statistically significant difference (
Z
=-2.29
P
=0.02). There were no significant differences in MRF positive rate (
P
=0.11)
EMVI positive rate (
P
=0.61) and pCR rate (
P
=0.94) between the two groups.
Conclusion:
Concurrent administration of amifostine in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy can reduce gastrointestinal toxicity and reduce the levels of tumor markers CA72-4
CA50 and CA24-2. However
it may have no significant effect on improving hematological toxicity
MRF and EMVI positive rate and pCR rate.
关键词
Keywords
references
SUNG H , FERLAY J , SIEGEL R L , et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2021 , 71 ( 3 ): 209 - 249 .
郑荣寿 , 陈茹 , 韩冰峰 , 等 . 2022年中国恶性肿瘤流行情况分析 [J ] . 中华肿瘤杂志 , 2024 , 46 ( 3 ): 221 - 231 .
ZHENG R S , CHEN R , HAN B F , et al. Cancer incidence and mortality in China, 2022 [J ] . Chin J Oncol , 2024 , 46 ( 3 ): 221 - 231 .
LI Y , WANG J , MA X W , et al. A review of neoadjuvant chemoradiotherapy for locally advanced rectal cancer [J ] . Int J Biol Sci , 2016 , 12 ( 8 ): 1022 - 1031 . DOI: 10.7150/ijbs.15438 http://doi.org/10.7150/ijbs.15438
刘思潮 , 陈小娇 , 杨怡萍 . 新辅助放疗在直肠癌中的应用及研究进展 [J ] . 临床医学进展 , 2023 , 13 ( 7 ): 10854 - 10862 .
LIU S C , CHEN X J , YANG Y P . Application and advances of neoadjuvant radiotherapy in rectal cancer [J ] . Adv Clin Med , 2023 , 13 ( 7 ): 10854 - 10862 .
KOUVARIS J R , KOULOULIAS V E , VLAHOS L J . Amifostine: the first selective-target and broad-spectrum radioprotector [J ] . Oncologist , 2007 , 12 ( 6 ): 738 - 747 . DOI: 10.1634/theoncologist.12-6-738 http://doi.org/10.1634/theoncologist.12-6-738
冯国双 . 重复测量数据的常用统计分析方法 [J ] . 中华预防医学杂志 , 2020 , 54 ( 7 ): 804 - 812 .
FENG G S . Statistical methods for repeated measurement data in scientific research [J ] . Chin J Prev Med , 2020 , 54 ( 7 ): 804 - 812 .
SMITH H G , NILSSON P J , SHOGAN B D , et al. Neoadjuvant treatment of colorectal cancer: comprehensive review [J ] . BJS Open , 2024 , 8 ( 3 ): zrae038.
XU Y Y , ZOU H Z , SHAO Z Y , et al. Efficacy and safety of different radiotherapy doses in neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: a retrospective study [J ] . Front Oncol , 2023 , 13 : 1119323 .
JI L H , CUI P F , ZHOU S W , et al. Advances of amifostine in radiation protection: administration and delivery [J ] . Mol Pharm , 2023 , 20 ( 11 ): 5383 - 5395 .
SUN L W H , ASANA MARICAN H T , BEH L K , et al. Imaging the radioprotective effect of amifostine in the developing brain using an apoptosis-reporting transgenic zebrafish [J ] . Int J Radiat Biol , 2024 , 100 ( 3 ): 433 - 444 .
AGHAJANSHAKERI S , SALMANMAHINY A , AGHAJANSHAKERI S , et al. Modulatory effect of amifostine (WR-1065) against genotoxicity and oxidative stress induced by methotrexate in human umbilical vein endothelial cells (HUVECs) [J ] . Toxicol Mech Methods , 2023 , 33 ( 9 ): 755 - 765 .
KATSANOS K H , BRIASOULIS E , TSEKERIS P , et al. Randomized phase Ⅱ exploratory study of prophylactic amifostine in cancer patients who receive radical radiotherapy to the pelvis [J ] . J Exp Clin Cancer Res , 2010 , 29 ( 1 ): 68.
VAN REES J M , HARTMAN W , NUYTTENS J J M E , et al. Relation between body composition and severe diarrhea in patients treated with preoperative chemoradiation with capecitabine for rectal cancer: a single-centre cohort study [J ] . BMC Gastroenterol , 2021 , 21 ( 1 ): 313.
MALEK E , GUPTA V , CREGER R , et al. Amifostine reduces gastro-intestinal toxicity after autologous transplantation for multiple myeloma [J ] . Leuk Lymphoma , 2018 , 59 ( 8 ): 1905 - 1912 .
KOUKOURAKIS M I , KYRGIAS G , PANTELIADOU M , et al. Dose escalation of amifostine for radioprotection during pelvic accelerated radiotherapy [J ] . Am J Clin Oncol , 2013 , 36 ( 4 ): 338 - 343 .
CHEN Y F , YANG Y W , TANG H K , et al. ROS-responsive and pH-sensitive aminothiols dual-prodrug for radiation enteritis [J ] . Antioxidants , 2022 , 11 ( 11 ): 2145 .
GUO F , XU F , LI S J , et al. Amifostine ameliorates bleomycin-induced murine pulmonary fibrosis via NAD+/SIRT1/AMPK pathway-mediated effects on mitochondrial function and cellular metabolism [J ] . Eur J Med Res , 2024 , 29 ( 1 ): 68.
DE VOS F Y , BOS A M , SCHAAPVELD M , et al. A randomized phase Ⅱ study of paclitaxel with carboplatin +/- amifostine as first line treatment in advanced ovarian carcinoma [J ] . Gynecol Oncol , 2005 , 97 ( 1 ): 60 - 67 .
GU J D , ZHU S W , LI X B , et al. Effect of amifostine in head and neck cancer patients treated with radiotherapy: a systematic review and meta-analysis based on randomized controlled trials [J ] . PLoS One , 2014 , 9 ( 5 ): e95968.
LAWRENCE Y R , PAULUS R , LANGER C , et al. The addition of amifostine to carboplatin and paclitaxel based chemoradiation in locally advanced non-small cell lung cancer: long-term follow-up of Radiation Therapy Oncology Group (RTOG) randomized trial 9801 [J ] . Lung Cancer , 2013 , 80 ( 3 ): 298 - 305 . DOI: 10.1016/j.lungcan.2013.02.008 http://doi.org/10.1016/j.lungcan.2013.02.008
BOURHIS J , BLANCHARD P , MAILLARD E , et al. Effect of amifostine on survival among patients treated with radiotherapy: a meta-analysis of individual patient data [J ] . J Clin Oncol , 2011 , 29 ( 18 ): 2590 - 2597 . DOI: 10.1200/JCO.2010.33.1454 http://doi.org/10.1200/JCO.2010.33.1454
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