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局部晚期直肠癌对含奥沙利铂短程诱导化疗的个体肿瘤体积反应——针对肿瘤的放射敏感性?

Individual tumor volume responses to short-course oxaliplatin-containing induction chemotherapy in locally advanced rectal cancer - Targeting the tumor for radiation sensitivity?

作者信息

Flatmark Kjersti, Saelen Marie G, Hole Knut H, Abrahamsen Torveig W, Fleten Karianne G, Hektoen Helga H, Redalen Kathrine R, Seierstad Therese, Dueland Svein, Ree Anne H

机构信息

Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Norway; Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway.

Department of Tumor Biology, Norwegian Radium Hospital, Oslo University Hospital, Norway; Institute of Clinical Medicine, University of Oslo, Norway.

出版信息

Radiother Oncol. 2016 Jun;119(3):505-11. doi: 10.1016/j.radonc.2016.02.020. Epub 2016 Mar 8.

Abstract

BACKGROUND

Neoadjuvant treatment of locally advanced rectal cancer (LARC) involves chemoradiotherapy (CRT), which may cause significant toxicity, and the potential role and sequential placement of neoadjuvant chemotherapy (NACT) relative to CRT is under debate.

PATIENTS AND METHODS

In a non-randomized study of 72 LARC patients, short-course oxaliplatin-containing NACT was administered prior to CRT. Tumor volumes were calculated from magnetic resonance images before and after NACT, and four weeks after CRT, and associations between tumor volume responses and outcome were analyzed. Additionally, the impact of oxaliplatin exposure on radiosensitivity was examined in colorectal carcinoma cell lines.

RESULTS

All tumors except one responded to NACT, with better responses in T3 than T4 cases, and 69/72 patients obtained additional tumor volume reduction after subsequent CRT. However, no associations were found between tumor volume reduction and long-term outcome. Of note, oxaliplatin-resistant cells were significantly more radiosensitive than the oxaliplatin-sensitive counterparts.

CONCLUSIONS

Oxaliplatin-containing NACT led to substantial tumor volume reduction with particularly good responses in T3 cases. NACT did not impede subsequent CRT response, and experimental results rather suggested enhanced radiosensitivity in oxaliplatin-exposed cells, encouraging studies to explore the administration of NACT prior to CRT. Data are still lacking to support omitting radiation in LARC management.

摘要

背景

局部晚期直肠癌(LARC)的新辅助治疗包括放化疗(CRT),这可能会导致显著的毒性,新辅助化疗(NACT)相对于CRT的潜在作用和序贯安排仍存在争议。

患者和方法

在一项对72例LARC患者的非随机研究中,在CRT之前给予含奥沙利铂的短程NACT。根据NACT前后以及CRT后四周的磁共振图像计算肿瘤体积,并分析肿瘤体积反应与预后之间的关联。此外,在结肠癌细胞系中研究了奥沙利铂暴露对放射敏感性的影响。

结果

除1例肿瘤外,所有肿瘤对NACT均有反应,T3期病例的反应优于T4期病例,72例患者中有69例在随后的CRT后肿瘤体积进一步缩小。然而,未发现肿瘤体积缩小与长期预后之间存在关联。值得注意的是,奥沙利铂耐药细胞比奥沙利铂敏感细胞对放射更敏感。

结论

含奥沙利铂的NACT导致肿瘤体积显著缩小,T3期病例反应尤其良好。NACT并未阻碍随后的CRT反应,实验结果反而表明奥沙利铂暴露细胞的放射敏感性增强,这鼓励开展研究探索在CRT之前给予NACT。在LARC治疗中仍缺乏支持省略放疗的数据。

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