Department of Radiation Oncology, Konyang University College of Medicine, 158 Gwanjeodong-ro, Daejeon, 35365, Republic of Korea.
Department of Radiation Oncology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu, 42415, Republic of Korea.
Int J Clin Oncol. 2018 Apr;23(2):287-297. doi: 10.1007/s10147-017-1213-z. Epub 2017 Nov 13.
This study investigated the role of hyperthermia combined with preoperative concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer (LARC) according to hypoxic marker expression.
One hundred and nine LARC patients with tissue blocks available for immunohistochemical assessment of carbonic anhydrase 9 (CA9) expression were reviewed. CA9 expression was considered positive when the staining percentage of tumor cells was >25% (n = 31). Pelvic radiotherapy with a total dose of 39.6-45 Gy was delivered concurrently with fluorouracil-based chemotherapy. Hyperthermia was administered to 52 patients twice a week during CCRT. Treatment response and outcomes were compared between hyperthermochemoradiotherapy (HCRT) and CCRT groups.
In patients with positive CA9 expression, the rates of downstaging (p = 0.060) and pathologic complete response (p = 0.064) tended to be higher in the HCRT group than in the CCRT group. Distant metastasis-free survival (p = 0.029) and cancer-specific survival (p = 0.020) were significantly worse in tumors with both positive CA9 expression and poor tumor response. Negative CA9 expression, presence of major tumor response, and the use of hyperthermia were significant favorable prognostic factors for cancer-specific survival after the first recurrence in multivariate analysis.
Hyperthermia might selectively enhance the preoperative treatment response in LARC with positive CA9 expression and offset the negative effect of hypoxia on prognosis. Pretreatment evaluation of hypoxia could aid in the selection of patients who might benefit from hyperthermia.
本研究根据乏氧标志物表达，探讨了高温联合术前同期放化疗（CCRT）在局部进展期直肠癌（LARC）中的作用。
回顾了 109 例 LARC 患者的组织块，这些患者的组织块可用于碳酸酐酶 9（CA9）表达的免疫组织化学评估。当肿瘤细胞的染色百分比>25%（n=31）时，CA9 表达被认为是阳性。盆腔放疗总剂量为 39.6-45Gy，并与基于氟尿嘧啶的化疗同时进行。在 CCRT 期间，52 例患者每周接受两次高温治疗。比较高温化疗组（HCRT）和 CCRT 组之间的治疗反应和结果。
在 CA9 表达阳性的患者中，HCRT 组的降期率（p=0.060）和病理完全缓解率（p=0.064）均高于 CCRT 组。远处无复发生存率（p=0.029）和癌症特异性生存率（p=0.020）在 CA9 表达阳性且肿瘤反应不良的肿瘤中明显更差。在多因素分析中，CA9 表达阴性、主要肿瘤反应和使用高温是癌症特异性生存的显著有利预后因素。
高温可能会选择性地增强 CA9 表达阳性的 LARC 患者的术前治疗反应，并抵消缺氧对预后的负面影响。术前缺氧评估可以帮助选择可能受益于高温治疗的患者。
