International Journal of Radiation Oncology*Biology*Physics
Clinical investigationRectumAssociation of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer
Introduction
Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, or statins, are cholesterol-lowering medications in widespread use to reduce the risk of heart disease and all-cause mortality (1, 2). There has been growing interest in the potential anticancer activity of these medications (3, 4), including experimental evidence in colorectal cancer (5, 6, 7, 8). Furthermore, a recently reported case-control study suggests that statin use might reduce the risk of colorectal cancer in healthy subjects by as much as 46% (9). Limited clinical data suggest that statins might have some benefit in other solid malignancies (10, 11), but the potential impact of statin use on standard therapy for rectal cancer is unknown.
Adjuvant chemoradiation for rectal cancer is an established treatment that improves clinical outcomes compared with surgical resection alone in patients with transmural or node-positive disease (12, 13, 14). Neoadjuvant chemoradiation has been increasingly used for sphincter preservation with equivalent outcomes (15), and pathologic response to neoadjuvant therapy might have prognostic significance (16, 17, 18, 19). We hypothesized that statin use might improve the efficacy of neoadjuvant chemoradiation in rectal cancer. Therefore, we retrospectively investigated the possible association of HMG CoA reductase inhibitor use with a higher pathologic complete response (pCR) rate.
Section snippets
Methods and materials
A total of 423 patients in the prospective colorectal surgery database underwent surgery at Memorial Sloan-Kettering Cancer Center (MSKCC) between January 1996 and June 2001 after neoadjuvant chemoradiation for rectal cancer. We excluded 65 patients who either had clinical evidence of metastatic disease at presentation or required intraoperative radiation therapy, leaving a cohort of 358 subjects who all received external beam radiation therapy with concurrent chemotherapy before surgery at
Perioperative findings and pathologic complete response rate
At the time of surgery, 23 patients (7%) were found to have evidence of metastatic disease on either radiologic or intraoperative restaging; all were non-statin users. The results of the findings at the time of surgery are presented in Table 3. Of the 349 patients, a total of 65 (18.7%) achieved a pCR. On univariate analysis, only lower T-stage according to DRE or ultrasound had a statistically significant difference in the likelihood of a pCR (Table 4). There was a trend toward a higher pCR
Discussion
In this retrospective study, we found a possible association of statin use with an improved pCR rate after neoadjuvant chemoradiation. Although there has been increasing preclinical evidence to suggest that statins might have anticancer activity, and recently presented data suggests a possible role for statins in colon cancer chemoprevention (3, 4, 9), there are few published data on humans demonstrating that these drugs have any therapeutic effect in patients with established cancers. To our
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Is preoperative chemoradiation in rectal cancer patients modulated by ACE inhibitors? Results from the Dutch Cancer Registry
2019, Radiotherapy and OncologyCitation Excerpt :A schematic overview of the literature on possible (chemo)radiation sensitizers is provided in Supplementary Table II. Retrospective studies have suggested that patients receiving statins during rectal cancer treatment can have a 1.5 to 4-fold increase in pCR rates [34–36]. However, no prospective data are available and other studies showed no benefit of statin use in rectal cancer patients [19,37,38].
Survival benefit of statins in older patients with rectal cancer: A Swedish population-based cohort study
2019, Journal of Geriatric OncologyCitation Excerpt :Statins, also known as 3- hydroxy-3-methylglutaryl-Coenzyme A reductase inhibitors, are a group of drugs traditionally prescribed for treating hyperlipidemia and to prevent cardiovascular disease [1]. Interestingly, in recent years it has been suggested that statins may even have antitumor effects in a variety of human malignancies [2–10] by inhibiting cell proliferation and inducing apoptosis [11,12]. Regarding colorectal cancer, the potential benefit of statin use has been investigated in previous studies, but with different results.
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B.M. receives research support and honoraria and serves as a consultant and on the speaker’s bureau for Pfizer. L.B.S. is an advisor for Pfizer and receives research funding from Pfizer and Bristol Myers Squibb.