Huiming Lin

A nomogram predicting pathological complete response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer: implications for organ preservation strategies

PURPOSE To determine predictors of pathological complete response (pCR) in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), and develop a predictive nomogram. METHODS A total of 522 locally advanced rectal cancer patients undergoing nCRT and curative resection between 2008 and 2014 were included. Uni- and multivariate analysis was performed to identify predictors of pCR. A nomogram was developed and validated by internal (n=425) and external validation (n=97). RESULTS With a median follow-up of 55 months, pCR was associated with better 5-year overall and disease-free survival, distant control, but similar local control. Logistic regression showed that post-CRT distance from the anal verge (OR =0.840, P = 0.022), post-CRT tumor size (OR = 0.565, P = 0.003), post-CRT circumferential extent of tumor (OR = 0.021, P < 0.001), pre-CRT CEA level (OR = 2.004, P = 0.033), and post-CRT CEA level (OR = 3.767, P = 0.038) were independently associated with pCR. A nomogram was developed with a C-index of 0.81 and 0.75 on internal and external validation, respectively. CONCLUSION pCR was associated with better long-term outcome. A nomogram was successfully developed to predict pCR. It could support decision-making in organ preservation strategies.Purpose To determine predictors of pathological complete response (pCR) in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), and develop a predictive nomogram. Methods A total of 522 locally advanced rectal cancer patients undergoing nCRT and curative resection between 2008 and 2014 were included. Uni- and multivariate analysis was performed to identify predictors of pCR. A nomogram was developed and validated by internal (n=425) and external validation (n=97). Results With a median follow-up of 55 months, pCR was associated with better 5-year overall and disease-free survival, distant control, but similar local control. Logistic regression showed that post-CRT distance from the anal verge (OR =0.840, P = 0.022), post-CRT tumor size (OR = 0.565, P = 0.003), post-CRT circumferential extent of tumor (OR = 0.021, P < 0.001), pre-CRT CEA level (OR = 2.004, P = 0.033), and post-CRT CEA level (OR = 3.767, P = 0.038) were independently associated with pCR. A nomogram was developed with a C-index of 0.81 and 0.75 on internal and external validation, respectively. Conclusion pCR was associated with better long-term outcome. A nomogram was successfully developed to predict pCR. It could support decision-making in organ preservation strategies.

Effect of Interval between Neoadjuvant Chemoradiotherapy and Surgery on Oncological Outcome for Rectal Cancer: A Systematic Review and Meta-Analysis

Aim. To evaluate the influence of interval between neoadjuvant chemoradiotherapy (NCRT) and surgery on oncological outcome. Methods. A systematic search was conducted in PubMed, the Cochrane Library, and Embase databases for publications reporting oncological outcomes of patients following rectal cancer surgery performed at different NCRT-surgery intervals. Relative risk (RR) of pathological complete response (pCR) among different intervals was pooled. Results. Fifteen retrospective cohort studies representing 4431 patients met the inclusion criteria. There was a significantly increased rate of pCR in patients treated with surgery followed 7 or 8 weeks later (RR, 1.45; 95% CI, 1.18–1.78; and P < 0.01 and RR, 1.49; 95% CI, 1.15–1.92; and P = 0.002, resp.). There is no consistent evidence of improved local control or overall survival with longer or shorter intervals. Conclusion. Performing surgery 7-8 weeks after the end of NCRT results in the highest chance of achieving pCR. For candidates of abdominoperineal resection before NCRT, these data support implementation of prolonging the interval after NCRT to optimize the chances of pCR and perhaps add to the possibility of ultimate organ preservation.

Establishment of a Predictive Genetic Model for Estimating Chemotherapy Sensitivity of Colorectal Cancer with Synchronous Liver Metastasis

OBJECTIVE We examined the whole genome expression profile in advanced colorectal cancer (ACC) patients who had received FOLFOX4 chemotherapy to establish a genetic biomarker model predicting chemotherapy sensitivity. METHODS Eligible ACC patients were divided into two groups, based on postchemotherapy evaluation results: specifically, the sensitive group (experimental group) and the resistant group (control group). The genome expression profiles of colorectal cancer tissues were examined using DNA microarray analysis, and differential gene expression was identified using a significance analysis of the microarray. The probe signal log ratios were used to produce the area-under-the-curve, sensitivity, and specificity for candidate genes. Genes exhibiting differential expression and significant predictive power were used to simulate a genetic model for estimating chemotherapy sensitivity. RESULTS Totally, 30 ACC patients were eligible for the study, 13 assigned to the experimental group and 17 to the control group. In total, 30 genes showing significant differential expression were identified. Seven candidate genes (NKX2-3, FXYD6, TGFB1I1, ACTG2, ANPEP, HOXB8, and KLK11), which exhibited positive or negative correlations, were incorporated into a genetic model, with an overall accurate predication rate of 93.3%. CONCLUSIONS The predictive model involving the seven genes listed had high accuracy in estimating chemotherapy sensitivity to the FOLFOX4 regimen.

A nomogram to predict distant metastasis after neoadjuvant chemoradiotherapy and radical surgery in patients with locally advanced rectal cancer

To compare distant metastasis (DM) in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and surgery alone, and to develop a predictive nomogram for DM following nCRT.

Prognostic significance of neoadjuvant rectal score in locally advanced rectal cancer after neoadjuvant chemoradiotherapy and construction of a prediction model.

To evaluate the prognostic significance of neoadjuvant rectal (NAR) score after neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC), and to develop a nomogram predicting disease‐free survival (DFS).

Risk Factors for Early Postoperative Small Bowel Obstruction after Elective Colon Cancer Surgery: An Observational Study of 1,244 Consecutive Patients

Background: Early postoperative small bowel obstruction (EPSBO) is a common complication following colon cancer surgery. EPSBO is associated with increased hospital stays, mortality rates, and healthcare costs. The purpose of this study was to identify risk factors for EPSBO following elective colon cancer surgery. Study Design: We retrospectively reviewed the clinicopathological variables of 1,244 patients with colon cancer who underwent partial colectomy from January 2000 to December 2014. A multivariable logistic regression model was used to identify risk factors for EPSBO. Results: The EPSBO rate was 3.5%. In multivariate analysis, preoperative bowel obstruction (OR 2.378; 95% CI 0.986-5.735, p = 0.054), weight loss >10% of body weight (OR 3.029; 95% CI 1.000-9.178, p = 0.05), albumin level (in g/L; OR 0.966; 95% CI 0.937-0.996, p = 0.024), and surgical duration (in min; OR 1.008; 95% CI 1.003-1.012, p = 0.003) were significant predictors of EPSBO. Conclusion: EPSBO is more likely to develop in the presence of poor systemic conditions (e.g., weight loss >10% of body weight, hypoalbuminemia, and preoperative bowel obstruction) and following operations of longer duration. These predictors may facilitate the stratification of patients at risk for EPSBO following surgery for elective colon cancer.

A scoring system basing pathological parameters to predict regional lymph node metastasis after preoperative chemoradiotherapy for locally advanced rectal cancer: implication for local excision.

Local excision is an alternative to radical surgery that is indicated in patients with locally advanced rectal cancer (LARC) who have a good response to chemoradiotherapy (CRT). Regional lymph node status is a major uncertainty during local excision of LARC following CRT. We retrospectively reviewed clinicopathologic variables for 244 patients with LARC who were treated at our institute between December 2000 and December 2013 in order to identify independent predictors of regional lymph node metastasis. Multivariate analysis of the training sample demonstrated that histopathologic type, tumor size, and the presence of lymphovascular invasion were significant predictors of regional nodal metastasis. These variables were then incorporated into a scoring system in which the total scores were calculated based on the points assigned for each parameter. The area under the curve in the receiver operating characteristic analysis was 0.750, and the cutoff value for the total score to predict regional nodal metastasis was 7.5. The sensitivity of our system was 73.2% and the specificity was 69.4%. The sensitivity was 77.8% and the specificity was 51.2% when the scoring system was applied to the testing sample. Using this system, we could accurately predict regional nodal metastases in LARC patients following CRT, which may be useful for stratifying patients in clinical trials and selecting potential candidates for organ-sparing surgery following CRT for LARC

Selecting stage ypT0-1N0 for locally advanced rectal cancer following preoperative chemoradiotherapy: implications for potential candidates of organ-sparing management.

Local excision or a wait‐and‐see policy may offer the possibility of organ preservation for locally advanced rectal cancer (LARC) after preoperative chemoradiotherapy (CRT). Identifying associated factors of good responders (GR) with stage ypT0–1N0 would probably influence the selection of potential candidates who were theoretically eligible for organ‐sparing management. This study was to establish a scoring system to select stage ypT0–1N0 for LARC following preoperative CRT.

Comparative Outcomes of Preoperative Chemoradiotherapy and Selective Postoperative Chemoradiotherapy in Clinical Stage T3N0 Low and Mid Rectal Cancer

Abstract Purpose/aim: Preoperative chemoradiotherapy (pre-CRT) and total mesorectal excision (TME) have become the standard of care for patients with locally advanced rectal cancer (LARC). Nevertheless, it is a controversial issue whether pre-CRT in cT3N0M0 patients would result in potential overtreatment. Materials and methods: In total, 183 clinical stage IIA rectal cancer patients treated with and without pre-CRT between 2011 and 2014 were retrospectively analyzed. Capecitabine/FOLFOX/CAPOX chemotherapy was co-administered with preoperative radiotherapy. Surgical resection with laparoscopic or open TME was conducted 8–12 weeks after completion of the pre-CRT. Postoperative radiotherapy was routinely given to patients with pT4 lesion or circumferential margin (CRM) and/or distal resection margin (DRM) involvement. Results: In total, 108 (59%) patients received pre-CRT and 75 (41%) underwent surgery first. The pre-CRT patients presented with less-advanced pathological T stage tumors compared with the surgery-first patients (p < 0.001). However, the pathological N stage was not significantly different between the two groups (p = 0.065). The 3-year overall survival (OS), disease-free survival (DFS), and 2-year local recurrence (LR) rate were similar in the pre-CRT and surgery-first patients (88.4 versus 88.7%, p = 0.552; 79.6 versus 83.3%, p = 0.797; 2.8 versus 2.7%, p = 0.960, respectively). Cox regression analysis showed that pN stage and CRM/DRM involvement were independently correlated with an unfavorable DFS. Conclusions: In this study, the omission of pre-CRT in cT3N0M0 patients did not translate into a worse oncological outcome. Postoperative radiotherapy should remain a standard option for patients with CRM/DRM involvement and pathological T4 tumors. A generalized indication for pre-CRT in cT3N0 patients is likely to result in overtreatment.

Effect of Neoadjuvant Chemoradiotherapy on Locally Advanced Rectal Mucinous Adenocarcinoma: A Propensity Score-Matched Study

Aims. To compare the surgical and oncological outcomes of rectal mucinous adenocarcinomas treated with neoadjuvant chemoradiotherapy versus surgery alone. Methods. A total of 167 locally advanced rectal mucinous adenocarcinoma patients treated with neoadjuvant chemoradiotherapy and surgery alone between 2008 and 2014 were matched using propensity score; the surgical and oncological outcomes were compared. Results. Ninety-six patients were matched. Postoperative morbidity was similar between groups. Sphincter preservation rate was higher in patients receiving neoadjuvant chemoradiotherapy (79.2% versus 60.4%, P = 0.045), especially for tumors ≥ 3 cm but ≤5 cm from the anal verge (75.0% versus 44.0%, P = 0.036). With a median follow-up of 54.8 months, the 5-year overall survival rate (neoadjuvant chemoradiotherapy versus surgery alone: 79.6% versus 67.1%; P = 0.599) and disease-free survival rate (75.6% versus 64.2%; P = 0.888) were similar. The 5-year local recurrence rate was lower in patients receiving neoadjuvant chemoradiotherapy (7.7% versus 26.0%, P = 0.036), while no difference was observed in distant metastasis. A poor response to chemoradiation was associated with higher local recurrence (P = 0.037). Conclusions. Compared with surgery alone, neoadjuvant chemoradiotherapy was found to increase the sphincter preservation rate and reduce local recurrence, thus being beneficial for locally advanced rectal mucinous adenocarcinoma patients.