Study Of Clinicopathological Factors Correlated With Evaluating The Efficacy Of Neoadjuvant Therapy In Rectal Cancer

BackgroundPreoperative chemoradiotherapy is being used more and more commonly. Preoperative chemoradiotherapy (CRT) is the current standard treatment for locally advanced rectal cancer. Preoperative CRT for locally advanced rectal cancer has several potential advantages, including decrease in tumor volumes, introduction of downstaging, increase in the possibility of R0 resection, enhanced probability of anal sphincter preservation, reduction in local recurrence. However, the response of individual tumours to adjuvant therapies is not uniform. Most of patients benefit from preoperative CRT, and thus, small proportion of patient population is less likely to respond to this treatment. In order to offer patients an individual therapy, it would be of significant to identify predictive factors of cancer response to preoperative chemoradiotherapy.ObjectiveNeoadjuvant therapy of rectal cancer can reduce the tumor stage.This study was to determine pathological changes of rectal cancer between before and after preoperative chemoradiotherapy, to investigate the correlation between clinicopathological factors with TRG, to find sensitive clinicopathological factors correlated with tumor response. It can be used to predict patients who will benefit from preoperative chemoradiotherapy and guide the development of individualized treatment and avoid over-treatment to determine neoadjuvant therapy sensitivity of rectal cancer.Materials and methodsOur study design was a retrospective study. The patients were recruited from January 2002 until February 2010. This study was approved by Shandong Cancer Hospital and all patients signed an informed consent. Preoperative pelvic radiotherapy was performed with a 6MV and 15MV-X linear accelerator by using a four-pelvic- fields technique with conventional fractionation, 2.0 Gy per day, 5 fractions per week to a total dose of 45-50Gy. All 98 patients simultaneous received 5-FU-based (FolFox scheme) chemotherapy during the period of radiotherapy. Two of six 28-day cycles of preoperative chemotherapy were performed during the first and fifth week of radiotherapy. Finished the two cycles chemotherapy and radiotherapy, regardless of tumor response, surgical resection was performed 4 ~6 weeks later in 98 patients. We use the low edge of the tumor plus 2cm as a distal surgical margin. Paraffin-embedded tumor biopsies and sectioned specimens from 98 patients were collected. The slides were examined independently by two of the authors, having no information about the patients or the results of routine histologic examination. After radical surgery, all tumor specimens were examined by experienced pathologists. Tumor response was evaluated according to a modification of the tumor regression grading (TRG) as described by Dworak et a. Briefly, grade 0, no regression; grade 1, minor regression (dominant tumor mass with obvious fibrosis in 25% or less of the tumor mass); grade 2, moderate regression (dominant tumor mass with obvious fibrosis in 26% to 50% of the tumor mass); grade 3, good regression (dominant fibrosis outgrowing the tumor mass; ie, more than 50% tumor regression); and grade 4, total regression (no viable tumor cells, only fibrotic mass). Tumors with a (TRG0, TRG1 and TRG2) score were considered poor response, whereas remaining tumors (TRG3, TRG4) were classified as good response. For all statistical analysis, Statistica13.0 was used. Values of P lesser than 0.05 or 95% were considered as having a statistical significance. Chi-square or Fisher exact tests were performed to analyse the change of T stage and N stage before and after neoadjuvant therapy. All variables that were significant in the univariate analysis were entered into a multivariate model. Then, a logistic regression analysis was used to identify the significant multivariate predictors. It was used to assess correlation between factors and TRG.Results1 Compare the change of T stage and N stage from 40 patients before and after neoadjuvant therapy: 77.5%(31/40)of cases decreased T stage after preoperative radiochemotherapy, and 27.5%(11/40)of cases declined N stage simultaneously.2 The univariate analysis indicated that pretreatment CEA level≤3.4 ng/mL (P=0.002), circumferential extent of tumor≤50% (P=0.001) and Non -fixed tumor (P=0.001) were associated significantly with good response (TRG 3+4). The univariate analysis also indicated that pretreatment positive lymph-nodes was associated significantly with good response (TRG 3+4) (P=0.032).3 The multivariate logistic regression analysis showed that pretreatment CEA level was an independent factor associated significantly with good response (P=0.003). The multivariate logistic regression analysis also indicated that Non-fixed tumor and circumferential extent of tumor≤50% independently predicted good tumor response (P =0.002 and P=0.019).Conclusions1 Preoperative chemoradiotherapy in rectal cancer has been deemed to reduce tumor volume, downstage the tumor, convert an unresectable tumor into a resectable tumor, and preserve the anal sphincter.2 The pretreatment CEA level, tumor mobility and circumferential extent of tumor are associated with tumor response to preoperative chemoradiotherapy. These factors may be useful predictors of rectal tumor response to preoperative chemoradiotherapy.