Preoperative Chemoradiotherapy For Rectal Cancer Research Articles

Outcomes of preoperative chemoradiotherapy for rectal cancer with lateral pelvic lymph node metastasis

Outcomes of preoperative chemoradiotherapy for rectal cancer with lateral pelvic lymph node metastasis

Is the pathological regression level of metastatic lymph nodes associated with oncologic outcomes following preoperative chemoradiotherapy in rectal cancer?

PurposeThe oncologic impact of the lymph node (LN) regression level after preoperative chemoradiotherapy (PCRT) has not been thoroughly evaluated. Hence, this study aimed to examine whether the regression level of metastatic LNs following PCRT is associated with oncologic outcomes in rectal cancer.ResultsThe optimal number of cut points for LRG sum was determined to be three. The three LRG groups demonstrated different distributions according to the ypT and ypN stages (p < 0.001 for both). However, the distribution of the LRG groups was not associated with the TRG of the primary tumor (p = 0.527). The RFS significantly differed according to the LRG groups (p = 0.001). Moreover, the differences in RFS remained when the LRG groups were analyzed within each separate ypN stage. The LRG group was confirmed as a factor associated with RFS in the multivariate analysis (p=0.018), while the ypN stage was not (p=0.4).Patients and MethodsWe analyzed the outcomes of 142 rectal cancer patients diagnosed with ypN1 disease after PCRT followed by radical resection. The pathological responses of the primary tumor and LNs to PCRT were evaluated using the tumor regression grade (TRG) and LN regression grade (LRG), respectively. The impact of LRG on recurrence-free survival (RFS) was analyzed. The K-adaptive partitioning for survival data method was applied to determine the optimal number of cut points for the LRG-sum and the optimal number of subgroups.ConclusionThe LRG as an indicator of response to PCRT should be considered as a prognostic determinant in rectal cancer patients. Future large-scale prospective studies are needed to confirm this finding.

Biomarker-Based Scoring System for Prediction of Tumor Response After Preoperative Chemoradiotherapy in Rectal Cancer by Reverse Transcriptase Polymerase Chain Reaction Analysis.

Numerous molecular markers have been investigated to predict tumor response after preoperative chemoradiotherapy for rectal cancer. This study aimed to evaluate the predictive value of biomarkers for the prediction of tumor response after preoperative chemoradiotherapy. Tumor specimens have been collected prospectively from 80 patients with rectal cancer who underwent curative resection at 8 weeks after completing preoperative chemoradiotherapy. With the use of reverse transcriptase polymerase chain reaction analysis, mRNA expression levels of 7 candidate biomarkers (p53, p21, Ki-67, VEGF, CD133, CD24, and CD44) were evaluated from fresh tumor samples collected before preoperative chemoradiotherapy. The correlation between biomarker expression levels and the pathologic response was assessed based on histopathological staging (pTNM) and tumor regression grade. The mRNA expression levels of 4 biomarkers (p53, p21, Ki67, and CD133) significantly correlated with tumor regression grade response and pathologic complete response. Patients showing low expression of p53 and/or high expression of p21, Ki67, and CD133 exhibited a significantly greater tumor regression grade response and pathologic complete response rate. A scoring system devised so that 1 point was given for each biomarker whose expression level correlated with pathologic complete response (score range: 0-4) showed that 9 of 62 patients with scores of 0 to 2 achieved pathologic complete response, whereas 15 of 18 patients with scores of 3 to 4 achieved pathologic complete response (14.5% vs 83.3%, p < 0.001). For prediction of pathologic complete response, the scoring system showed 62.5% sensitivity, 94.6% specificity, an 83.3% positive predictive value, and an 85.5% negative predictive value. Small patient numbers have limitations related to the reproducibility and ability to provide quantitative information. In addition, this study lacks test and validation sets. The pretreatment mRNA expression levels of 4 biomarkers correlated with pathologic tumor response after intraoperative chemoradiotherapy in rectal cancer. Furthermore, the scoring system combining values of biomarker expression might have predictive power with high positive and negative predictive values.

Pre-operative chemoradiotherapy using capecitabine and cetuximab followed by definitive surgery in patients with operable rectal cancer

BackgroundAchieving a high rate of complete pathological response with pre-operative chemoradiotherapy in rectal cancer is an unmet need. We evaluated the efficacy and toxicity of the combination of cetuximab, capecitabine and radiation therapy in the pre-operative setting of localized rectal cancer. Patients and methodsPatients with clinically staged T3, T4 or nodepositive rectal cancer were treated with concurrent capecitabine and radiotherapy with weekly cetuximab starting one week before the start of radiation. This was followed by total mesorectal excision within 6-8 weeks. All patients achieving R0 resection received adjuvant capecitabine for 6 cycles. ResultsFifteen patients were treated and all underwent surgery. Sphincter preservation was achieved in 11 patients (73.3%) and pathological complete response in two. With a median follow up of 48 months (range 8.4-57.5), 12 patients were relapse-free and 14 were alive with 4-year relapse free survival of 80%. Overall survival was 93%. Significant grade 3 and 4 toxicity was mainly cetuximab-induced skin reactions (33%), radiation-induced skin toxicity (13%) and diarrhea (20%). ConclusionsAdding cetuximab to pre-operative concurrent capecitabine and radiotherapy provides modest efficacy with manageable toxicity.

Clinical Significance of the Endoscopic Finding in Predicting Complete Tumor Response to Preoperative Chemoradiation Therapy in Rectal Cancer.

There are reports that suggest conservative treatment when a tumor shows clinically complete response (CR) after preoperative chemoradiotherapy in rectal cancer. The aim of this study is to investigate the association between endoscopic complete response (E-CR) and pathologic CR (pCR) and to determine the sensitivity and specificity of E-CR and its clinical utility after preoperative chemoradiotherapy in rectal cancer. We analyzed prospectively collected data of patients with middle and lower rectal cancers who underwent preoperative chemoradiotherapy, between January 2010 and January 2015. Nineteen patients (17.9%) showed E-CR, and 87 patients showed E-non CR. Twenty-three patients (21.7%) were confirmed to have pCR. E-CR was closely associated with pCR (p<0.001). E-CR reflected pCR with an accuracy of 88.7%, sensitivity of 65.2%, specificity of 95.2%, PPV of 78.9%, NPV of 90.8%, and a p value of <0.001. E-CR after preoperative chemoradiotherapy in rectal cancer is significantly associated with pCR. However, a wait and see policy should be performed carefully with current endoscopic prediction for pCR to avoid inadequate treatment in patients who show E-CR after preoperative chemoradiotherapy.

Use of sequential endorectal US to predict the tumor response of preoperative chemoradiotherapy in rectal cancer

Accurate prediction of the response to preoperative chemoradiotherapy (CRT) potentially assists in the individualized selection of treatment. Endorectal US (ERUS) is widely used for the pretreatment staging of rectal cancer, but its use for preoperatively predicting the effects of CRT is not well evaluated because of the inflammation, necrosis, and fibrosis induced by CRT. This study assessed the value of sequential ERUS in predicting the efficacy of preoperative CRT for locally advanced rectal cancer. Forty-one patients with clinical stage II/III rectal adenocarcinoma were enrolled prospectively. Radiotherapy was delivered to the pelvis with concurrent chemotherapy of capecitabine and oxaliplatin. Total mesorectal excision was performed 6 to 8 weeks later. EUS measurements of primary tumor maximum diameter were performed before (ERUS1), during (ERUS2), and 6 to 8 weeks after (ERUS3) CRT, and the ratios of these were calculated. Correlations between ERUS values, tumor regression grade (TRG), T down-staging rate, and pathologic complete response (pCR) rate were assessed, and survival was analyzed. There was no significant correlation between ERUS2/ERUS1 and TRG. The value of ERUS3/ERUS1 correlated with pCR rate and TRG but not T down-staging rate. An ERUS3 value of 6.3mm and ERUS3/ERUS1 of 52% were used as the cut-off for predicting pCR, and patients were divided into good and poor prognosis groups. Although not statistically significant, 3-year recurrence and survival rates of the good prognosis group were better than those of the poor prognosis group. Sequential ERUS may predict therapeutic efficacy of preoperative CRT for locally advanced rectal cancer. (Clinical trial registration number: NCT01582750.).

Preoperative Chemoradiotherapy for Rectal Cancer in Patients Aged 75 Years and Older: Acute Toxicity, Compliance with Treatment, and Early Results.

Treatment of locally advanced rectal cancer (T3-T4 or N+) is based on short-course radiotherapy (RT) or chemoradiotherapy (CRT) followed by surgery. It is estimated that 30-40% of rectal cancer occurs in patients aged 75years or more. Data on adherence to neoadjuvant CRT and its safety remain poor owing to the under-representation of older patients in randomized clinical trials and the discordance in the results from retrospective studies. The aim of this study was to assess adherence with preoperative CRT and tolerability in older patients with a stage II/III unresectable rectal cancer. Patients aged 75years or more with stage II/III rectal cancer treated with preoperative CRT at the University Hospital of Besancon from 1993 to 2011 were included. Feasibility, toxicities, overall survival, and local recurrence rates were studied. Fifty-six patients with a Charlson score from 2 to 6 were included. The mean age was 78years. The compliance rates for RT and chemotherapy were 91 and 41.1%, respectively. Two patients stopped CRT; one for hemostatic surgery, and one for severe sepsis. For CRT, the rate of grade ≥3 toxicity was 14.29%, mainly the digestive type. Fifty-two patients underwent tumor resection, including 76.79% total mesorectal excision resection with 84.6% complete resection, and a rate of postoperative complications of 39.6%. At 2years, the overall survival and local recurrences rates were 87.3 and 7.8%, respectively. In older patients, selected preoperative CRT, with an adapted chemotherapy dose, is well tolerated. The main toxicity was gastrointestinal. Adherence to RT is comparable to that of younger patients.

Timely tumor response analysis after preoperative chemoradiotherapy and curative surgery in locally advanced rectal cancer: A multi-institutional study for optimal surgical timing in rectal cancer

Background and purposeThe definite surgical timing in rectal cancer after preoperative chemoradiotherapy (CRT) has not yet been fully examined. We assess the tumor response and identify the optimal operation timing after preoperative CRT in rectal cancer. Methods and materialsThe study included data of 1786 patients with locally advanced rectal cancer (cT3-4N0-2M0). They received preoperative CRT followed by total mesorectal excision. Total radiation dose was 50.4Gy in 28 fractions. Interval time between preoperative CRT and surgery ranged from 2 to 26weeks, with a median interval of 7.2weeks. Primary endpoint was to evaluate the period of highest downstaging and pathological complete response (ypCR) rates to determine the optimal timing for curative surgery after CRT. ResultsDownstaging rates peaked between 6 and 7weeks after CRT and declined afterward. ypCR rates increased from 5 to 6weeks after CRT and decreased after 9 to 10weeks. Downstaging rates were similar between the two arms showing 36.9% in the early arm (⩽7weeks) and 37.0% in the delayed arm (>7weeks). ypCR rates were significantly higher in the delayed arm, as compared to the early arm (12.3% vs. 8.6%, p=0.011). The delayed arm had higher sphincter preservation rates than the early arm with a marginal significance (92.4% vs. 89.9%, p=0.078). There was no statistically significant difference regarding relapse-free survival and overall survival between the two arms. ConclusionsypCR rates increased after 5weeks and decreased after 10weeks and the delayed (>7weeks after CRT) group showed significantly increased ypCR rates than the early arm (⩽7weeks after CR). The optimal timing for curative surgery in rectal cancer when tumor response is maximal is after 7weeks and before 10weeks following preoperative CRT.

Clinical significance of enlarged lateral pelvic lymph nodes before and after preoperative chemoradiotherapy for rectal cancer.

Preoperative chemoradiotherapy (CRT) with total mesorectal excision (TME) is the widely accepted treatment for rectal cancer (RC) in Western countries. However, there remains controversy as to whether preoperative CRT is useful in tumors that extend beyond the mesorectum, including metastasis to the lateral pelvic lymph nodes (LPLN). The aim of this study was to assess the prognostic significance of LPLN enlargement in patients with RC who receive preoperative CRT followed by TME without LPLN dissection. We evaluated the prognostic effect of radiographic LPLN enlargement before and after CRT, as well as the patients' clinicopathological and genetic profiles. Of the 104 patients investigated, pretreatment imaging identified 19 (18%) as LPLN-positive (>7 mm in diameter). Of these 19 patients, 7 (37%) exhibited LPLN downsizing to <7 mm following CRT. The median follow-up period was 52 months. The 5-year cancer-specific survival (CSS) or relapse-free survival (RFS) did not differ significantly between patients who did and those who did not have positive LPLN on pretreatment imaging. However, LPLN that remained positive after CRT were significantly associated with poorer 5-year CSS (73 vs. 84%, respectively; P=0.0052) and RFS (32 vs. 78%, respectively; P=0.0264). None of the patients whose LPLN were downsized to <7 mm following CRT developed recurrence; however, those with positive LPLN after CRT had a 55% higher recurrence rate, characterized by delayed local recurrence, a pattern that may be affected by certain chemokines. In conclusion, changes in initially positive LPLN (>7 mm) may predict the prognosis of patients with RC who receive preoperative CRT-TME. LPLN positivity after CRT was associated with shorter CSS and RFS. Strategies to improve patient survival may include selective LPLN dissection or more aggressive multimodality therapy.

Association of thymidylate synthase polymorphisms with the tumor response to preoperative chemoradiotherapy in rectal cancer: a systematic review and meta-analysis.

Preoperative chemoradiotherapy (pCRT) followed by surgery is currently the standard therapy for patients with locally advanced rectal cancer. It is very important to develop biomarkers to prior identify the patients who have a higher likelihood of responding to pCRT. Recently, a series of studies have been conducted to investigate the association of thymidylate synthase (TYMS) polymorphisms with the tumor response to pCRT in rectal cancer, but the results were not consistent and conclusive. In the present study, we performed a systematic literature search for relevant studies up to 30 March 2015 and conducted a meta-analysis to summarize and clarify the association between the TYMS polymorphisms and the tumor response to pCRT in rectal cancer. Finally, 7 studies containing 892 cases for TYMS 2R/3R polymorphism, 7 studies involving 715 cases for TYMS 1494del6 polymorphism and 6 studies containing 616 cases for TYMS 5' untranslated region (UTR) expression allele polymorphism were analyzed in the meta-analysis. The results suggested that TYMS 2R/3R was associated with the response and the patients with 2R/2R or 2R/3R genotype with rectal cancer might benefit more from pCRT than others. On the contrary, neither 1494del6 nor 5'UTR expression allele polymorphisms was associated with the response to pCRT.

An 80-gene set to predict response to preoperative chemoradiotherapy for rectal cancer by principle component analysis.

Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer not only improves the postoperative local control rate, but also induces downstaging. However, it has not been established how to individually select patients who receive effective preoperative CRT. The aim of this study was to identify a predictor of response to preoperative CRT for locally advanced rectal cancer. This study is additional to our multicenter phase II study evaluating the safety and efficacy of preoperative CRT using oral fluorouracil (UMIN ID: 03396). From April, 2009 to August, 2011, 26 biopsy specimens obtained prior to CRT were analyzed by cyclopedic microarray analysis. Response to CRT was evaluated according to a histological grading system using surgically resected specimens. To decide on the number of genes for dividing into responder and non-responder groups, we statistically analyzed the data using a dimension reduction method, a principle component analysis. Of the 26 cases, 11 were responders and 15 non-responders. No significant difference was found in clinical background data between the two groups. We determined that the optimal number of genes for the prediction of response was 80 of 40,000 and the functions of these genes were analyzed. When comparing non-responders with responders, genes expressed at a high level functioned in alternative splicing, whereas those expressed at a low level functioned in the septin complex. Thus, an 80-gene expression set that predicts response to preoperative CRT for locally advanced rectal cancer was identified using a novel statistical method.

Pathologic prognostic factors on residual disease after preoperative chemoradiotherapy for rectal cancer

Pathologic prognostic factors on residual disease after preoperative chemoradiotherapy for rectal cancer

Clinical influence of cancer stem cells on residual disease after preoperative chemoradiotherapy for rectal cancer.

We evaluated the clinical influence of cancer stem cells (CSCs) on residual disease after preoperative chemoradiotherapy (CRT) in patients with rectal cancer. The surgical specimens of 145 patients with residual rectal cancer after preoperative CRT were assessed. To identify CSCs, immunohistochemistry was performed using their surrogate makers (CD44 and aldehyde dehydrogenase 1 [ALDH1]) in full section tissues. Of the 145 cases, ALDH1 and CD44 positivity was found in 80.0% (n = 116) and 47.6% (n = 69), respectively; ALDH1 positivity showed weakly positive correlation with CD44 (r s = 0.269, P = 0.002). ALDH1 and CD44 positivity was related to lower tumor regression grade (TRG) (P = 0.009 and 0.003, respectively). Additionally, ALDH1 positivity was associated with positive circumferential resection margin (P = 0.019). However, ALDH1 and CD44 positivity showed no relationship with KRAS or BRAF mutation. In univariate analysis, ALDH1 positivity was associated with short recurrence-free survival (RFS) (P = 0.005) and rectal cancer-specific survival (RCSS) (P = 0.043), but not CD44 positivity (RFS, P = 0.725; RCSS, P = 0.280). In multivariate analysis, ALDH1 positivity was an independent prognostic factor for poor RFS (P = 0.039; hazard ratio = 2.997; 95% confidence interval = 1.059-8.478), but not RCSS (P = 0.571). The expression of ALDH1 assessment independently predicts RFS in patients with residual disease after CRT. These results suggest that targeting CSCs could be an effective therapeutic approach to rectal cancer patients receiving preoperative CRT.

Surrogacy of progression-free survival (PFS) for overall survival (OS) in rectal cancer trials with preoperative therapy: Literature-based meta-analysis.

734 Background: Disease-free survival (DFS) after adjuvant chemotherapy in colon cancer has been validated as a surrogate endpoint for OS. An analysis of individual patient data from two randomized controlled trials evaluating preoperative chemoradiotherapy for rectal cancer has already shown that PFS might be a surrogate endpoint for OS (Eur J Cancer, 2012). However, since the report was derived from only two trials, the further evaluation of surrogacy with a larger number of trials is desirable. This study was conducted to explore the trial level correlations between PFS and OS in resectable rectal cancer with preoperative therapy. Methods: A systematic literature search of randomized trials of preoperative chemoradiotherapy, radiotherapy or chemotherapy for rectal cancer reported from January 1990 to September 2014 was conducted using PubMed and the Cochrane library. Weighted linear regression using sample size of each trial as a weight was used to estimate coefficient of determination (R2) within PFS and OS. 95% confidence interval of R2 was estimated by bootstrap method. The primary analysis included trials in which the HR of PFS and OS were reported. A sensitivity analysis included the trials in which either HR or 5 years point estimates of PFS and OS was reported. In the sensitivity analysis, HR was estimated from the point estimates of PFS and OS assuming exponential distribution. Results: Of 1,048 articles, 14 trials (7,233 patients) were selected for the primary analysis and 18 (8,020) for the sensitivity analysis. Median numbers of enrolled patients were 332 (range 113-1,805) in primary analysis, and 296 (113-1,805) in sensitivity analysis. The primary analysis did not show the correlation between treatment effects on PFS and OS(R2 0.408; 95% CI [0.133-0.845]). The sensitivity analysis showed modest correlation between PFS and OS (R2 0.603; 95% CI [0.296-0.871]). Conclusions: The primary analysis showed that PFS was not suitable as a surrogate endpoint, which is contradictory to the previous report. Based on our results, OS is still preferable as the primary endpoint in the trials of preoperative therapy for resectable rectal cancer.

Impression of prognosis regarding pathologic stage after preoperative chemoradiotherapy in rectal cancer.

To ascertain pathologic stage as a prognostic indicator for rectal cancer patients receiving preoperative chemoradiotherapy (PCRT). Patients with mid- and low rectal carcinoma (magnetic resonance imaging - based clinical stage II or III) between 2000 and 2009 and treated with curative radical resection were identified. Patients were divided into two groups: PCRT and No-PCRT. Recurrence-free survival (RFS) was examined according to pathologic stage and addition of adjuvant treatment. Overall, 894 patients were identified. Of these, 500 patients received PCRT. Adjuvant chemotherapy was delivered to 81.5% of the No-PCRT and 94.8% of the PCRT patients. Adjuvant radiotherapy was given to 29.4% of the patients in the No PCRT group. The 5-year RFS for the No-PCRT group was 92.6% for Stage I, 83.3% for Stage II, and 72.9% for Stage III. The 5-year RFS for the PCRT group was 95.2% for yp Stage 0, 91.7% for yp Stage I, 73.9% for yp Stage II, and 50.7% for yp Stage III. Pathologic stage can predict prognosis in PCRT patients. 5-year RFS is significantly lower among PCRT patients than No-PCRT patients in pathologic stage II and III. These results should be taken into account when considering adjuvant treatment for patients treated with PCRT.

Oncologic impact of pathologic response on clinical outcome after preoperative chemoradiotherapy in locally advanced rectal cancer.

PurposeDownstaging after chemoradiotherapy (CRT) for rectal cancer usually occurs. The present study aimed to evaluate pathologic y-stage (yp-stage) and its influence on local recurrence and systemic recurrence in rectal cancer patients treated with CRT followed by surgical resection.MethodsWe retrospectively analyzed 261 patients underwent preoperative CRT and radical resection for rectal cancer between August 2004 and December 2010. Patients received preoperative CRT consisting of 5-fluorouracil and leucovorin delivered with concurrent pelvic radiation of 45.0-50.4 Gy, followed by radical surgery at 6-8 weeks after CRT.ResultsOf the 261 patients, 24 (9.2%) had yp-stage 0, 83 (31.8%) had yp-stage I, 86 (32.9%) had yp-stage II, and 68 (26.1%) had yp-stage III. Patients with yp-stage III had a greater prevalence of preoperative CEA, poorly differentiated tumor, lymphovascular invasion (LVI) and perineural invasion (PNI) than patients with lower yp-stages. We found that yp-stage, preoperative CEA, LVI, PNI and tumor regression grade were significant prognostic factors for both local and systemic recurrence. In multivariate analysis, yp-stage, LVI and PNI were significant factors for local and systemic recurrence. During the median follow-up of 37.5 months, the five-year local recurrence-free survival rate was 100.0%, 95.0%, 89.3%, and 80.6% of yp-stage 0-III, respectively. The five-year systemic recurrence-free survival was 95.8%, 75.3%, 71.4%, and 48.8% of yp-stages 0-III, respectively.ConclusionThe yp-stage after preoperative CRT for rectal cancer is closely correlated with local and systemic recurrence-free survival. Therefore, yp-stage should be considered as a prognostic factor for rectal cancer patients having a course of preoperative CRT.

Evaluation of current imaging in restaging rectal cancer after neoadjuvant therapy

The combination of preoperative chemoradi-otherapy and surgery has become the standard treatment for locally advanced rectal cancer. Up to 30% of patients received pathologic complete response(pCR) after neoadjuvant therapy, for whom low rates of local recurrence and improved outcome after surgery were achieved. Given that, some authors have recommended local resection for clinical extensive response or non operative "wait and see" policy for clinical complete response(cCR) respectively, in which radical surgery-associated complication and dysfunction can be avoided. Current imaging can provide excellent accuracy in primary staging of rectal cancer, however, when used for restaging, the ability is less satisfactory, especially for pCR prediction, as a result of modification on tumor and surrounding tissue induced by neoadjuvant therapy. The question on how to identify patients with pCR before surgery has received more attention recently. On the basis of pathological findings after surgery, in this article, we review the reliability and predictive ability of current imaging for restaging and pCR after preoperative chemoradiotherapy in rectal cancer.

Prediction of pathologic staging with magnetic resonance imaging after preoperative chemoradiotherapy in rectal cancer: Pooled analysis of KROG 10-01 and 11-02

Background and purposeThe reported overall accuracy of MRI in predicting the pathologic stage of nonirradiated rectal cancer is high. However, the role of MRI in restaging rectal tumors after neoadjuvant CRT is contentious. Thus, we evaluate the accuracy of restaging magnetic resonance imaging (MRI) for rectal cancer patients who receive preoperative chemoradiotherapy (CRT). Methods and materialsWe analyzed 150 patients with locally advanced rectal cancer (T3–4N0–2) who had received preoperative CRT. Pre-CRT MRI was performed for local tumor and nodal staging. All patients underwent restaging MRI followed by total mesorectal excision after the end of radiotherapy. The primary endpoint of the present study was to estimate the accuracy of post-CRT MRI as compared with pathologic staging. ResultsPathologic T classification matched the post-CRT MRI findings in 97 (64.7%) of 150 patients. 36 (24.0%) of 150 patients were overstaged in T classification, and the concordance degree was moderate (k=0.33, p<0.01). Pathologic N classification matched the post-CRI MRI findings in 85 (56.6%) of 150 patients. 54 (36.0%) of 150 patients were overstaged in N classification. 26 patients achieved downstaging (ycT0–2N0) on restaging MRI after CRT. 23 (88.5%) of 26 patients who had been downstaged on MRI after CRT were confirmed on the pathological staging, and the concordance degree was good (k=0.72, p<0.01). ConclusionsRestaging MRI has low accuracy for the prediction of the pathologic T and N classifications in rectal cancer patients who received preoperative CRT. The diagnostic accuracy of restaging MRI is relatively high in rectal cancer patients who achieved clinical downstaging after CRT.

587P - Carbohydrate Antigen 19-9 Levels Associated with Pathological Responses to Preoperative Chemoradiotherapy in Rectal Cancer

ABSTRACT Aim: To investigate whether pretreatment serum carbohydrate antigen 19-9 (CA 19-9) levels are associated with pathological responses to preoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: In total, 260 patients with locally advanced rectal cancer (cT3 4NanyM0) who underwent preoperative CRT and radical surgery were analyzed retrospectively. CRT consisted of 50.4 Gy pelvic radiotherapy and concurrent chemotherapy. Radical surgery was performed at median 7 weeks after CRT completion. Pathological CRT response criteria included downstaging (ypStage 0-I) and ypT0-1. A discrimination threshold of CA 19-9 level was determined using a receiver operating characteristics analysis. A multivariate logistic regression model was constructed to identify factors independently associated with pathological CRT responses. Results: The median CA 19-9 level was 8.0 (1.0-648.0) U/mL. Downstaging occurred in 94 (36.2%) patients and ypT0-1 in 50 (19.2%). The calculated optimal threshold of CA 19-9 level was 10.2 U/mL for downstaging and 9.0 U/mL for ypT0-1. On univariate analysis, tumor size, cT classification, carcinoembryonic antigen (CEA), and CA 19-9 showed significant associations with downstaging. Tumor size, cN classification, histological grade, CEA, and CA 19-9 were significantly associated with ypT0-1. A CA 19-9 level of ≤ 10.0 U/mL or ≤ 9.0 U/mL was a positive predictor of downstaging and ypT0-1. On multivariate analysis, CA 19-9 (≤ 9.0 U/mL) was significantly associated with downstaging (odds ratio, 2.089; 95% confidence interval, 1.189-3.669; P = 0.010) or ypT0-1 (OR, 2.207; 95% CI, 1.079-4.512; P = 0.030), independent of clinical stage or CEA. Conclusions: This study firstly showed a significant association of pretreatment serum CA 19-9 levels with pathological CRT responses of rectal cancer. Disclosure: All authors have declared no conflicts of interest.

Clinical significance of thrombocytosis before preoperative chemoradiotherapy in rectal cancer: predicting pathologic tumor response and oncologic outcome.

Thrombocytosis is considered an adverse prognostic factor in various malignancies. However, the clinical significance of thrombocytosis in rectal cancer patients is unknown. We investigated the predictive value of thrombocytosis for pathologic tumor response to preoperative chemoradiotherapy (CRT) and oncologic outcomes in patients with rectal cancer. A total of 314 patients who underwent preoperative CRT and subsequent rectal resection for rectal cancer were retrospectively evaluated at two tertiary institutions. Univariate and multivariate analyses of the clinical parameters were performed to identify markers predictive of a pathologic complete response (pCR). The Kaplan-Meier method was used to estimate 3-year disease-free and overall survival rates. Sixty-nine patients (22%) had thrombocytosis before CRT, which significantly correlated with a large tumor size and advanced tumor depth. Thirty-nine patients (12.4%) achieved a pCR. In the multivariate analyses, a platelet count of <370,000/μl (odds ratio 5.483; 95% confidence interval, 1.271-23.653; P=0.023) and a carcinoembryonic antigen (CEA) level of<5ng/dl (odds ratio, 3.084; 95% confidence interval, 1.291-7.368; P=0.011) were identified as independent predictive factors for a pCR. Patients with pretreatment thrombocytosis had lower 3-year disease-free (P=0.037) and overall survival (P=0.001) rates than patients with normal pretreatment platelet counts. Thrombocytosis is a negative predictive factor for a pCR and has an adverse impact on survival in rectal cancer. The predictive value of this easily available clinical factor should not be underestimated, and better therapeutic strategies for these tumors are required.