Preoperative chemoradiotherapy with concomitant small field boost irradiation for locally advanced rectal cancer: a multi-institutional phase II study (KROG 04-01).

Center for Colorectal Cancer, Research Institute and Hospital, National Cancer Center, Goyang, South Korea.
Diseases of the Colon & Rectum (Impact Factor: 3.34). 11/2006; 49(11):1684-91. DOI:10.1007/s10350-006-0678-z
Source: PubMed

ABSTRACT This study was designed to determine the effect of concomitant small field boost irradiation given during preoperative chemoradiotherapy for patients with locally advanced rectal cancer.
The study prospectively enrolled 38 patients scheduled for preoperative chemoradiotherapy. Pelvic radiotherapy of 43.2 Gy/24 fractions was delivered and boost radiotherapy of 7.2 Gy/12 fractions was concomitantly administered during the latter half of the pelvic radiotherapy treatment period. Two cycles of a bolus 5-fluorouracil and leucovorin injection in the first and fifth weeks of radiotherapy were administered. The median time to surgery after completion of chemoradiotherapy was six weeks. Tumor responses to chemoradiotherapy were assessed by using magnetic resonance volumetry and post-chemoradiotherapy pathology tests to determine tumor downstaging and tumor regression rate.
Thirty-six of 38 patients (94.7 percent) underwent the scheduled surgery. The mean tumor volume reduction rate was 70.3 percent, and the clinical response rate was 66.7 percent. The downstaging rates were 41.7 percent for T classification, 85.2 percent for N classification, and 72.2 percent for stage. Tumor regression grades after preoperative chemoradiotherapy were Grade 1 in 5 patients (13.9 percent), Grade 2 in 24 patients (66.7 percent), Grade 3 in 3 patients (8.3 percent), and Grade 4 in 4 patients (11.1 percent). Ten patients (26.3 percent) experienced > or = Grade 3 acute toxicity.
Our data suggest that concomitant boost irradiation does not improve clinical outcomes compared with other published preoperative chemoradiotherapy regimens. In addition, the clinicians choosing to use concomitant small field boost irradiation should be cautious to minimize the risk of unplanned sphincter ablation.

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    ABSTRACT: Preoperative chemoradiotherapy has become a standard treatment modality for locally advanced rectal cancer. Favorable long-term outcomes have been reported for patients with good responses to chemoradiotherapy. Therefore, predictive factors for chemoradiotherapy responses can be useful for their applicability to risk-adaptive therapy in patients with colorectal cancer. The aim of this study was to investigate whether hydroxymethylglutaryl-coenzyme A synthase 2, a key enzyme in ketogenesis, is associated with the responses of colorectal cancer cells to chemoradiotherapy. Hydroxymethylglutaryl-coenzyme A synthase 2 was identified by a 2-dimensional gel electrophoresis -based proteome analysis. It was analyzed in 12 colorectal cancer cells for associations with radiation or 5-fluorouracil susceptibility by Western blotting, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium Bromide assay, and small interfering RNA transfection. Then, tumor tissues obtained from 45 patients with rectal cancer before chemoradiotherapy were analyzed by Western blotting for associations with chemoradiotherapy responses. Expression of hydroxymethylglutaryl-coenzyme A synthase 2 was significantly correlated with intrinsic radiation resistance of 12 cancer cells. Hydroxymethylglutaryl-coenzyme A synthase 2 expression was significantly affected by treatment with either 5-fluorouracil or radiation depending on cell types. The artificial suppression of hydroxymethylglutaryl-coenzyme A synthase 2 did not result in the change of chemoradiation susceptibility in colorectal cancer cells. Nevertheless, in multivariate analyses, hydroxymethylglutaryl-coenzyme A synthase 2 expression in rectal cancer tissues was shown to be a significant predictive factor for chemoradiotherapy responses, as evaluated in terms of tumor regression grade and downstaging. Overall findings in vitro showed that the expression level of hydroxymethylglutaryl-coenzyme A synthase 2 was highly variable depending on colon cancer cell types, and it cannot directly affect on chemoradiotherapy responses. The molecular mechanism underpinning the association between hydroxymethylglutaryl-coenzyme A synthase expression and chemoradiotherapy responses needs to be elucidated through future research. Hydroxymethylglutaryl-coenzyme A synthase 2 was associated with the effects of chemoradiotherapy on human colorectal cancer cells. Pretreatment levels of hydroxymethylglutaryl-coenzyme A synthase 2 in rectal cancer may be useful in predicting the responses to chemoradiotherapy.
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    American journal of clinical oncology 05/2011; 35(5):424-431. · 2.21 Impact Factor
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    ABSTRACT: Even in patients undergoing an optimal surgical technique (e.g., total mesorectal excision), radiotherapy provides a significant benefit in the local control of rectal cancer. Compared with postoperative treatment, chemoradiotherapy given preoperatively has been shown to decrease local recurrence rates and toxicity. Additionally, preoperative chemoradiotherapy permits the early identification of tumor responses to this cytotoxic treatment by surgical pathology. Pathological parameters reflecting the tumor response to chemoradiotherapy have been shown to be surrogate markers for long-term clinical outcomes. Post-chemoradiotherapy downstaging from cStage II-III to ypStage 0-I indicates a favorable prognosis, with no difference between ypStage 0 and ypStage I. Research is ongoing to develop useful tools (clinical, molecular, and radiological) for clinical determination of the pathologic chemoradiotherapeutic response before surgery, and possibly even before preoperative treatment. In the future, risk-adapted strategies, including intensification of preoperative therapy, conservative surgery, or the selective administration of postoperative chemotherapy, will be realized for locally-advanced rectal cancer patients based on their response to preoperative chemoradiotherapy.
    Journal of the Korean Society of Coloproctology 08/2012; 28(4):179-87.

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