Squire Tim, Buchanan Grant, Rangiah David, Davis Ian, Yip Desmond, Chua Yu Jo, Rich Tyvin, Elsaleh Hany
a The Canberra Hospital , Department of Radiation Oncology , Garran , Australian Capital Territory , Australia.
d University of Notre Dame Australia, School of Medicine , Darlinghurst , New South Wales , Australia.
Chronobiol Int. 2017;34(4):492-503. doi: 10.1080/07420528.2017.1301462. Epub 2017 Mar 29.
The predominant mode of radiation-induced cell death for solid tumours is mitotic catastrophe, which is in part dependent on sublethal damage repair being complete at around 6 h. Circadian variation appears to play a role in normal cellular division, and this could influence tumour response of radiation treatment depending on the time of treatment delivery. We tested the hypothesis that radiation treatment later in the day may improve tumour response and nodal downstaging in rectal cancer patients treated neoadjuvantly with radiation therapy. Recruitment was by retrospective review of 267 rectal cancer patients treated neoadjuvantly in the Department of Radiation Oncology at the Canberra Hospital between January 2010 and November 2015. One hundred and fifty-five patients met the inclusion criteria for which demographic, pathological and imaging data were collected, as well as the time of day patients received treatment with each fraction of radiotherapy. Data analysis was performed using the Statistical Package R with nonparametric methods of significance for all tests set at p < 0.05. Of the 45 female and 110 male patients, the median age was 64. Seventy-three percent had cT3 disease and there was a mean tumour distance from the anal verge of 7 cm. Time to surgical resection following radiotherapy ranged from 4 to 162 days with a median of 50 days, with a complete pathological response seen in 21% of patients. Patients exhibiting a favourable pathological response had smaller median pre- and postradiotherapy tumour size and had a greater change in tumour size following treatment (p < 0.01). Patients who received the majority of their radiotherapy fractions after 12:00 pm were more likely to show a complete or moderate pathological response (p = 0.035) and improved nodal downstaging. There were also more favourable responses amongst patients with longer time to surgical resection postradiotherapy (p < 0.004), although no relationship was seen between response and tumour distance from the anal verge. Females were less likely to exhibit several of the above responses. Neoadjuvant radiotherapy for locally advanced rectal cancer performed later in the day coupled with a longer time period to surgical resection may improve pathological tumour response rates and nodal downstaging. A prospective study in chronomodulated radiotherapy in this disease is warranted.
实体瘤中辐射诱导细胞死亡的主要方式是有丝分裂灾难，这部分取决于亚致死性损伤修复在大约6小时时是否完成。昼夜节律变化似乎在正常细胞分裂中起作用，这可能会根据放疗的时间影响肿瘤对放疗的反应。我们检验了这样一个假设：对于接受新辅助放疗的直肠癌患者，在一天中较晚时间进行放疗可能会改善肿瘤反应和淋巴结降期。通过回顾性分析2010年1月至2015年11月期间在堪培拉医院放射肿瘤学系接受新辅助治疗的267例直肠癌患者进行招募。155例患者符合纳入标准，收集了其人口统计学、病理和影像学数据，以及患者每次放疗的时间。使用统计软件R进行数据分析，所有检验的非参数显著性方法设定为p<0.05。在45例女性和110例男性患者中，中位年龄为64岁。73%的患者患有cT3疾病，肿瘤距肛缘的平均距离为7厘米。放疗后至手术切除的时间为4至162天，中位时间为50天，21%的患者出现完全病理缓解。表现出良好病理反应的患者放疗前后肿瘤大小的中位数较小，治疗后肿瘤大小的变化更大（p<0.01）。在下午12:00之后接受大部分放疗分次的患者更有可能表现出完全或中度病理反应（p=0.035）并改善淋巴结降期。放疗后至手术切除时间较长的患者也有更良好的反应（p<0.004），尽管未观察到反应与肿瘤距肛缘距离之间的关系。女性出现上述几种反应的可能性较小。一天中较晚时间进行局部晚期直肠癌的新辅助放疗并延长至手术切除的时间间隔可能会提高肿瘤病理反应率和淋巴结降期。有必要对这种疾病进行时辰调制放疗的前瞻性研究。
