Pei Rong Ding

Elevated preoperative neutrophil to lymphocyte ratio predicts risk of recurrence following curative resection for stage IIA colon cancer

Background and ObjectivesAdjuvant chemotherapy for stage II colon cancer remains controversial but may be considered for patients with high-risk features. Recent studies have shown that elevated neutrophil to lymphocyte ratio (NLR) is a worse prognostic factor and a predictor of response to chemotherapy in patients with advanced colorectal cancer. The purpose of this study was to evaluate whether NLR predicts risk of recurrence in patients with stage IIA colon cancer undergoing curative resection without adjuvant chemotherapy.MethodsWe retrospectively reviewed 141 consecutive patients with stage IIA colon cancer treated with curative surgery alone from 2002 to 2006. NLR, as well as demographics, clinical, histopathologic, and laboratory data were analyzed. Univariate and multivariate analyses were conducted to identify prognostic factors associated with recurrent-free survival (RFS).ResultsCox’s regression analysis demonstrated that elevated NLR (>4) (hazard ratio, 4.88; P < 0.01) and less lymph node sampling (<15 lymph nodes; hazard ratio, 3.80; P < 0.05) were adverse prognostic factors for RFS. The 5-year RFS was 91.4% (95% CI, 88.6–94.2%) for patients with normal NLR and 63.8% (51.1–76.3%) for patients with elevated NLR. The 5-year RFS for patients with 0, 1, and 2 of the identified risk factors was 95.1%, 87.4%, and 33.3%, respectively (P < 0.001).ConclusionsElevated preoperative NLR is an independent predictor of worse RFS for patients with stage IIA colon cancer and a potential biomarker to identify candidates for adjuvant chemotherapy.

Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer

Background: Elevated neutrophil to lymphocyte ratio (NLR) is linked with worse survival in many malignancies, whereas its association with pancreatic cancer (PC) remains unclear. Methods: We retrospectively reviewed 95 patients with locally advanced or metastatic PC receiving gemcitabine-based chemotherapy. The prognostic value of NLR was evaluated. Results: Elevated pretreatment NLR (>5) was observed in 16 out of 89 eligible patients, which was identified as an independent prognostic factor for overall survival (OS). The median OS for patients with elevated and normal NLR were 2.4 months and 7.7 months, respectively (p <0.001). Conclusions: Elevated NLR is a predictor of shorter survival in patients with advanced PC.

Plasma Epstein-Barr virus DNA level strongly predicts survival in metastatic/recurrent nasopharyngeal carcinoma treated with palliative chemotherapy

Plasma Epstein‐Barr virus (EBV) DNA is widely used in screening, monitoring, and prediction of relapse in nonmetastatic nasopharyngeal carcinoma (NPC). However, data regarding utility of plasma EBV DNA in metastatic NPC are rare. The current study was to test the prognostic implication of plasma EBV DNA level in metastatic/recurrent NPC patients treated with palliative chemotherapy.

Elevated neutrophil to lymphocyte ratio predicts poor prognosis in nasopharyngeal carcinoma

Elevated neutrophil to lymphocyte ratio (NLR) has been reported to be associated with worse survival in many malignancies, whereas its role in nasopharyngeal carcinoma (NPC) remains unclear. We retrospectively reviewed 363 consecutively, newly diagnosed, non-disseminated, and biopsy-proven NPC patients. Disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were compared according to NLR level. Multivariate analysis was performed to assess the prognostic value of NLR. The 5-year DSS, DMFS, and LRFS rates for patients with elevated or non-elevated NLR (> or ≤3.73) were 59.6% vs. 76.6% (p = 0.03), 69.7% vs. 86.6% (p = 0.002), and 78.5% vs. 87.3% (p = 0.105), respectively. For patients with locoregionally advanced disease, NLR was not only an independent prognostic factor, but also a predictor of response to chemoradiotherapy. The 5-year DSS, DMFS, and LRFS rates for patients with elevated or non-elevated NLR were 47.2% vs. 73.7% (p < 0.001), 59.2% vs. 85.1% (p < 0.001), and 72.3% vs. 84.6% (p = 0.041), respectively. Compared with radiation alone, chemoradiotherapy significantly improved DSS and LRFS for patients with non-elevated NLR, but not for those with elevated NLR. Pre-treatment NLR is a strong prognostic factor for NPC patients. For patients with locoregionally advanced disease, NLR might also be a useful indicator for selection of treatment strategies.

Short term results of neoadjuvant chemoradiotherapy with fluoropyrimidine alone or in combination with oxaliplatin in locally advanced rectal cancer: A meta analysis

BACKGROUND Oxaliplatin (OX), in combination with fluoropyrimidine (5-fluorouracil or Capecitabine, FU)-based regimens and radiation, has been expected to both enhance primary tumour shrinkage and reduce micrometastases at distant sites in the neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). However, results in terms of pathologic complete response (pCR) and toxicities were inconsistent. The aim of this meta analysis was to evaluate the short term efficacy and toxicities of adding OX to FU in CRT for LARC. METHODS We searched PubMed, EMBASE, ISI databases, Chinese Biomedical Literature Database and the Cochrane library before December, 2011. Additionally, abstracts presented at American Society of Clinical Oncology conferences held between January, 2000, and July, 2011, were searched to identify relevant clinical trials. Only randomised studies with an analysis by an intention-to-treat principle were included, and searches were restricted to those databases citing articles in English. Summary incidence rates and 95% confidence intervals (CIs) were calculated using a fixed-effects or random-effects model, depending on the heterogeneity of the included studies. Four randomised clinical trials comparing OX/FU versus FU alone regimens in CRT for LARC met our search criteria and were assessed. A total of 3863 patients (FU, n=1937; OX/FU, n=1926) were included in the analysis. FINDINGS The addition of OX to FU significantly improved pathologic complete response (pCR), and reduced peri-operative metastases (including intra-abdominal metastases) with an odd ratios (OR) for OX/FU compared with FU of 1.20 (95% CI, 1.01-1.42; P=0.04) and 0.51 (95% CI, 0.34-0.77; P=0.001), respectively. The grade 3/4 toxicity rate was significantly higher for OX/FU versus FU alone with an OR of 2.29 (95% CI, 1.31-4.00; P=0.004). There was no difference in the rates of positive circumferential resection margin, permanent stoma, surgical complication and death within 60 d between the OX/FU and FU alone patients. The OR for the proportion of patients completing full-dose radiotherapy and completing full-dose chemotherapy were 0.32 (95% CI, 0.15-0.69; P=0.004), and 0.71 (95% CI, 0.35-1.42; P=0.33), respectively. INTERPRETATION Adding weekly OX to FU in neoadjuvant CRT of LARC appeared to modestly increase the pCR rate and reduced the rate of intra-abdominal or peri-operative metastases in this meta analysis. Although OX/FU significantly increased grade 3/4 toxicity, it did not result in more surgical complications or postoperative deaths within 60 d. The concept of combination of OX and FU in the pre-operative setting for LARC still seems promising, either with a modified schedule, or as induction therapy prior to CRT or after CRT, prior to surgery.

A Low Lymphocyte-to-Monocyte Ratio Predicts Unfavorable Prognosis in Pathological T3N0 Rectal Cancer Patients Following Total Mesorectal Excision.

Neoadjuvant radio-chemotherapy followed by total mesorectal excision (TME) is the standard treatment option for stage II and III rectal cancer. However, for pT3N0 rectal cancer patients who receive upfront TME, the lack of an efficient method to predict their prognosis hampers postoperative treatment. A low lymphocyte-to-monocyte ratio (LMR) is associated with an unfavorable prognosis for certain malignancies; however, this association has not been investigated in rectal cancer. The purpose of this study was to evaluate whether LMR can predict the prognosis of pT3N0 rectal cancer patients following TME. Rectal cancer patients who received radical TME without preoperative treatment between June 2004 and Nov. 2011 at the Sun Yat-sen University Cancer Center were retrospectively reviewed. Counts for pre-surgery peripheral absolute lymphocytes and monocytes were obtained and used to calculate the LMR. A retrospective cohort of 280 pT3N0 rectal cancer patients who received TME was recruited. Significantly worse disease-free survival can be observed in patients with lower LMR levels (<3.78) using univariate and multivariate analyses (P=0.01 and P=0.015, respectively). Subgroup analysis in patients with elevated carcinoembryonic antigen (CEA) and LMR <3.78 exhibited an accumulated 5-year disease failure rate of approximately 40%, whereas patients with normal CEA regardless of LMR and patients with LMR ≥3.78 exhibited accumulated 5-year disease failure rates of only approximately 15%. Low pre-surgery peripheral LMR was significantly unfavorable for pT3N0 rectal cancer patient prognosis, especially in patients with elevated CEA. This easily obtained variable might serve as a valuable marker to predict the outcomes of pT3N0 rectal cancer and indicate appropriate postoperative management.

Hospital-Based Colorectal Cancer Survival Trend of Different Tumor Locations from 1960s to 2000s

Background Our aim is to explore the trend of association between the survival rates of colorectal cancer (CRC) and the different clinical characteristics in patients registered from 1960s to 2000s. We hypothesized that the survival rate of CRC increases over time and varies according to anatomic subsites. Methods Information from a total of 4558 stage T(1-4)N(1-2)M0 CRC patients registered from 1960s to 2008 were analyzed. The association of CRC overall survival with age, gender, tumor locations, time, histopathology types, pathology grades, no. of examined lymph nodes, the T stage, and the N stage was analyzed. The assessment of the influence of prognostic factors on patient survival was performed using Cox’s proportional hazard regression models. Results From 1960 to 2008, the studied CRC patients included 2625 (57.6%) and 1933 (42.4%) males and females, respectively. These included 1896 (41.6%) colon cancers, and 2662 (58.4%) rectum cancers. The 5-year survival rate was 49%, 58%, 58%, 70%, and 77% for the time duration of 1960s, 1970s, 1980s, 1990s and 2000s, respectively. An increased 5-year survival rate was observed in the colon cancer and rectum cancer patients. Patients older than 60 years of age were more likely to develop colonic cancer (sigmoid) than rectum cancer (49.2% vs. 39.9%). The Cox regression model showed that only rectum cancer survival was related to time duration. Conclusion The overall survival and 5-year survival rates showed an increase from the 1960s to 2000s. There is a trend of rightward shift of tumor location in CRC patients.

Neoadjuvant Sandwich Treatment With Oxaliplatin and Capecitabine Administered Prior to, Concurrently With, and Following Radiation Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial

PURPOSE Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase 2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications. METHODS AND MATERIALS Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consisting of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded. RESULTS All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively. CONCLUSIONS Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen as induction, concomitant, and consolidation chemotherapy to the conventional radiation is well tolerated. The strategy is highly effective in terms of pCR and major regression, which warrants further investigation.

Depth of Tumor Invasion Independently Predicts Lymph Node Metastasis in T2 Rectal Cancer

ObjectiveThe aim of this study was to identify risk factors of lymph node metastasis (LNM) for T2 rectal cancer.MethodsFrom a prospectively maintained single-institution database, we identified 346 consecutive pT2 rectal cancers treated with total mesorectal excision from 1998 to 2009. Univariate and multivariate analyses were performed to identify risk factors associated with overall and intermediate/apical LNM. The incidence of overall and intermediate/apical LNM was analyzed by tree analysis.ResultsAge, tumor location, pathological features, and depth of invasion were independent predictors for overall LNM. Tumor location, pathological features, and depth of invasion were independent predictors for intermediate/apical LNM. Tree analysis showed that the incidence of LNM was 7.7% for upper rectal cancer with favorable pathological features, and 3.4% for mid/lower rectal cancer without other identified risk factors. The incidence of intermediate/apical LNM was 5.7% for superficial T2 rectal cancer with favorable pathological features, and 3.1% for deep T2 rectal cancer locating in upper rectum with favorable pathological features.ConclusionsDepth of invasion is an independent predictor for LNM in T2 rectal cancer. Using tree analysis, we identified a subset of patients with low risk of LNM who may be candidates of local excision.

Evaluation of capecitabine and oxaliplatin administered prior to and then concomitant to radiotherapy in high risk locally advanced rectal cancer

Systemic failure remains a predominant issue in locally advanced rectal cancer (LARC). A new strategy using capecitabine and oxaliplatin (XELOX regimen) administered prior to and then concomitant to radiotherapy for high risk LARC is developed in our practice. The aim of the present study was to evaluate the short‐term efficacy and toxicities of this strategy.