Does chronomodulated radiotherapy improve pathological response in locally advanced rectal cancer?

<p>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 <i>p</i> < 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 (<i>p</i> < 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 (<i>p</i> = 0.035) and improved nodal downstaging. There were also more favourable responses amongst patients with longer time to surgical resection postradiotherapy (<i>p</i> < 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.</p

The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern

<p><b>Background:</b> Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis.</p> <p><b>Methods:</b> Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel–Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics.</p> <p><b>Results:</b> Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis, median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (<i>p</i> < .001) in both datasets. BRAF mutation was strongly associated with peritoneal metastases (relative risk = 1.8, <i>p</i> < .001) with lower incidence of lung (RR = 0.3, <i>p</i> = .004) and liver (RR = 0.7, <i>p</i> = .005) limited metastases. Lung-only metastases were more frequent with KRAS/RAS mutation (RR = 1.4, <i>p</i> = .007). Left colon tumors were associated with bone (RR = 1.6, <i>p</i> < .001) and lung-only metastases (RR = 2.3, <i>p</i> = .001) while peritoneal spread was less frequent compared with right colon tumors (RR = 0.6, <i>p</i> < .001). Rectal cancer was associated with brain, bone and lung metastases (RR = 1.7; <i>p</i> = .002, 1.7; <i>p</i> < .001, 2.0; <i>p</i> < .001). Liver-only metastases were less frequent in deficient MMR tumors (RR = 0.7, <i>p</i> = .01).</p> <p><b>Conclusion:</b> Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.</p