Objective: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). Background Data: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. Methods: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. Results: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm (P=0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm (P=0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P=0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P=0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. Conclusions: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.

The prognostic nutritional index (PNI) has been widely applied for predicting survival outcomes of patients with various malignant tumors. Although a low PNI predicts poor prognosis in patients with colorectal cancer after tumor resection, the prognostic value remains unknown in patients with stage III colon cancer undergoing curative tumor resection followed by adjuvant chemotherapy. This study aimed to investigate the prognostic value of PNI in patients with stage III colon cancer. Medical records of 274 consecutive patients with stage III colon cancer undergoing curative tumor resection followed by adjuvant chemotherapy with oxaliplatin and capecitabine between December 2007 and December 2013 were reviewed. The optimal PNI cutoff value was determined using receiver operating characteristic (ROC) curve analysis. The associations of PNI with systemic inflammatory response markers, including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) level, and clinicopathologic characteristics were assessed using the Chi square or Fisher’s exact test. Correlation analysis was performed using Spearman’s correlation coefficient. Disease-free survival (DFS) and overall survival (OS) stratified by PNI were analyzed using Kaplan–Meier method and log-rank test, and prognostic factors were identified by Cox regression analyses. The preoperative PNI was positively correlated with LMR (r = 0.483, P < 0.001) and negatively correlated with NLR (r = − 0.441, P < 0.001), PLR (r = − 0.607, P < 0.001), and CRP level (r = − 0.333, P < 0.001). A low PNI (≤ 49.22) was significantly associated with short OS and DFS in patients with stage IIIC colon cancer but not in patients with stage IIIA/IIIB colon cancer. In addition, patients with a low PNI achieved a longer OS and DFS after being treated with 6–8 cycles of adjuvant chemotherapy than did those with < 6 cycles. Multivariate analyses revealed that PNI was independently associated with DFS (hazard ratios 2.001; 95% confidence interval 1.157–3.462; P = 0.013). The present study identified preoperative PNI as a valuable predictor for survival outcomes in patients with stage III colon cancer receiving curative tumor resection followed by adjuvant chemotherapy.

Background: Although colorectal oligometastases to the liver can potentially be cured with aggressive local ablation, the efficacy of adjuvant chemotherapy (ACT) for such metastasis remains unclear. The present study explored the effects of ACT on patients with colorectal liver oligometastases (CLO) after curative resections and aimed to identify patients who could benefit from ACT. Methods: We retrospectively analyzed 264 eligible patients with CLO who underwent curative resection between September 1999 and June 2015. Recurrence‐free survival (RFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and log‐rank test; prognostic factors were a by Cox regression modeling. Results: Among 264 patients, 200 (75.8%) patients received ACT and 64 (24.2%) did not receive ACT. These two groups did not significantly differ in clinicopathologic characteristics, and had comparable 3‐year OS and RFS rates (RFS: 42.1% vs. 45.7%, P = 0.588; OS: 69.7% vs. 62.7%, P = 0.446) over a median follow‐up duration of 35.5 months, irrespective of preoperative chemotherapy. ACT markedly improved 3‐year OS in high‐risk patients with Memorial Sloan‐Kettering Cancer Center clinical risk scores (MSKCC‐CRS) of 3–5 (68.2% vs. 33.8%, P = 0.015), but presented no additional benefit in patients with MSKCC‐CRS of 0–2 (72.2% vs. 78.6%, P = 0.834). In multivariate analysis, ACT was independently associated with improved OS in patients with MSKCC‐CRS of 3–5. Conclusions: ACT might offer a prognostic benefit in high‐risk patients with CLOs after curative liver resection, but not in low‐risk patients. Therefore, patients’ risk status should be determined before ACT administration to optimize postoperative therapeutic strategies.

Background: Neoadjuvant chemoradiotherapy followed by surgery is recommended as the standard of care for locally advanced rectal cancer, reducing local recurrence but not distant metastasis. Intensified systemic therapy is warranted to reduce the risk of distant metastasis. The present study aimed to evaluate the safety and efficacy of neoadjuvant oxaliplatin and capecitabine (XELOX) combined with bevacizumab plus radiotherapy for locally advanced rectal cancer. Methods: Patients with stages II to III rectal cancer received one cycle of induction chemotherapy and concurrent chemoradiotherapy with XELOX plus bevacizumab. Surgery was performed 6–8 weeks after completion of radiotherapy, and postoperative chemotherapy with three cycles of XELOX and two cycles of capecitabine were given. The primary endpoints were pathologic complete response (pCR) rate and safety, and the secondary endpoints were 3‐year overall survival and progression‐free survival. Results: Forty‐five patients were enrolled between February 2013 and April 2015. All completed the neoadjuvant therapy. Seven patients (15.6%) refused subsequent surgical therapy for personal reasons, and the other 38 patients received radical resection, with a sphincter preservation rate of 84.2% and a pCR rate of 39.5%. Toxicity was acceptable, with grades 3–4 hematological toxicity and diarrhea observed in six and two patients, respectively. Incidence of anastomotic leak that required surgical intervention was 13.3%. After a median follow‐up period of 37 months, five patients developed disease progression and two died of cancer. The 3‐year overall survival rate and 3‐year progression‐free survival rate were 95.3% and 88.6%, respectively. Conclusions: The addition of bevacizumab to neoadjuvant chemoradiotherapy resulted in a satisfying pCR rate and 3‐year survival, but also may increase the risk of anastomotic leak, thus this regimen is not suitable to be considered for regular recommendation for locally advanced rectal cancer. Trial registration Clinicaltrials.gov identifierNCT01818973

A scoring system based on artificial neural network for predicting 10-year survival in stage II A colon cancer patients after radical surgery

Voltage-gated sodium channel 1.5 (Nav1.5) potentially promotes the migratory and invasive behaviors of colon cancer cells. Hitherto, the prognostic significance of Nav1.5 expression remains undetermined. The present study aimed to explore the associations of Nav1.5 expression with clinical outcomes and estrogen receptor-β (ER-β) expression in non-metastatic colon cancer patients receiving radical resection. A total of 269 consecutive patients with pathologically confirmed stages I–III colon cancer who underwent radical resection were selected. Nav1.5 and ER-β expression was detected by using immunohistochemistry (IHC) on tissue microarray constructed from paraffin-embedded specimens. IHC score was determined according to the percentage and intensity of positively stained cells. Statistical analysis was performed with the X-tile method, k coefficient, Chi square test or Fisher’s exact test, logistic regression, log-rank test, and Cox proportional hazards models. We found that Nav1.5 was commonly expressed in tumor tissues with higher mean IHC score as compared with matched tumor-adjacent normal tissues (5.1 ± 3.5 vs. 3.5 ± 2.7, P < 0.001). The high expression of Nav1.5 in colon cancer tissues was associated with high preoperative carcinoembryonic antigen level [odds ratio (OR) = 2.980; 95% confidential interval (CI) 1.163–7.632; P = 0.023] and high ER-β expression (OR = 2.808; 95% CI 1.243–6.343; P = 0.013). Log-rank test results showed that high Nav1.5 expression contributed to a low 5-year disease-free survival (DFS) rate in colon cancer patients (77.2% vs. 92.1%, P = 0.048), especially in patients with high ER-β expression tumor (76.2% vs. 91.3%, P = 0.032). Analysis with Cox proportional hazards model demonstrated that high Nav1.5 expression [hazard ratio (HR) = 2.738; 95% CI 1.100–6.819; P = 0.030] and lymph node metastasis (HR = 2.633; 95% CI 1.632–4.248; P < 0.001) were prognostic factors for unfavorable DFS in colon cancer patients. High expression of Nav1.5 was associated with high expression of ER-β and indicated unfavorable oncologic prognosis in patients with non-metastatic colon cancer.