Jun Zhong Lin

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.

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.

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.

Cutoff value of carcinoembryonic antigen and carbohydrate antigen 19-9 elevation levels for monitoring recurrence in patients with resectable gastric adenocarcinoma.

BACKGROUND The aim of this longitudinal study was to try and improve the specificity of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in monitoring tumor recurrence in patients with resectable gastric adenocarcinoma by setting suitable elevation levels. METHODS One hundred eighty-one patients with resectable gastric adenocarcinoma were considered. Serum samples were obtained preoperatively and every 3 months postoperatively. RESULTS Preoperative CEA and CA19-9 positivity rates were 19.9% and 18.2%. The specificity and sensitivity of CEA elevation to monitor recurrence were 92.9% and 23.4% versus 76.5% and 78.9% in CEA-negative versus CEA-positive patients, respectively. For CA19-9 the specificity and sensitivity were 95.0% and 18.8% versus 60.0% and 83.3% in CA19-9-negative versus CA19-9-positive patients, respectively. When we set the elevation level of CEA at 5 ng/mL, the specificity of CEA elevation to monitor recurrence increased to 94.1% for CEA-positive patients. The specificity increased to 93.3% for CA19-9-positive patients when the CA19-9 elevation level was set at 100 U/mL. CONCLUSIONS For CEA- or CA19-9-positive patients with resectable gastric adenocarcinoma we can increase the specificity of CEA and CA19-9 by setting the elevation level of CEA at 5 ng/mL and CA19-9 at 100 U/mL.

Phase II study of pre-operative radiotherapy with capecitabine and oxaliplatin for rectal cancer and carcinoembryonic antigen as a predictor of pathological tumour response

This study investigated the efficacy and tolerability of pre-operative radiotherapy with concurrent capecitabine and oxaliplatin in patients with rectal cancer. Forty-seven patients with rectal adenocarcinoma (stages T3 – T4; node-positive) were enrolled and received radiotherapy (46 Gy in 23 fractions) in combination with capecitabine (1000 mg/m2 twice daily on days 1–14 and 22–35) and oxaliplatin (130 mg/m2 on days 1 and 22) (XELOX regimen). The main endpoints were safety and efficacy, as assessed by pathological complete response (pCR). All patients received pre-operative chemoradiotherapy (CRT) as planned. The most common severe toxicity was diarrhoea (12.8%); post-operative complications were rare (9.8%). The pCR rate was 20.9% in all patients and 34.8% in patients with normal pre-CRT serum carcinoembryonic antigen (CEA < 5 ng/ml) level, compared with 5.0% in the patients with elevated CEA (> 5 ng/ml). In conclusion, pre-operative radiotherapy with concurrent XELOX regimen in rectal cancer patients is feasible and effective. Serum CEA may be a suitable predictor of pCR.

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.

Patterns of recurrence in patients achieving pathologic complete response after neoadjuvant chemoradiotherapy for rectal cancer

PurposeThe aim of this study was to characterize the patterns of recurrence in patients achieving pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer.MethodsPatients with locally advanced rectal cancer treated with neoadjuvant CRT and who achieved pCR from January 2004 to December 2012 were collected. The primary outcome measurement was the patterns of recurrence.ResultsAmong 195 patients who achieved pCR, 18 developed recurrence. Furthermore, local recurrence occurred in 1.5% of patients (3/195), while distant metastases occurred in 7.7% of patients (15/195), which included 7 lung metastases, 1 liver metastasis, and 8 metastases in other locations.ConclusionsOur study indicated that patients achieving pCR following neoadjuvant CRT have a favorable prognosis, with distant metastases predominating in all recurrences. Among patients with distant metastases, non-liver metastases were the predominant pattern.

Is early surveillance with CT scan necessary in patients with stage II/III colorectal cancer: a retrospective study.

This analysis aims to evaluate the value of early surveillance within 6 months after resection for stage II/III colorectal cancer (CRC).

Comparison of survival between right-sided and left-sided colon cancer in different situations

Mountain of studies has showed that right‐sided colon cancer (RSCC) and left‐sided colon cancer (LSCC) have different clinical presentation and biologic features and should be considered as two distinct disease entities. The survival difference between RSCC and LSCC remains controversial. Using Surveillance, Epidemiology, and End Results (SEER) database, we identified colon adenocarcinoma patients from 2004 to 2013. The 5‐year cause‐specific survival (CSS) was our primary endpoint. All statistical analyses were performed using the Intercooled Stata 13.0. All statistical tests were two‐sided. The study included 95,847 (58.72%) RSCC and 67,385 (41.28%) LSCC patients. RSCC patients were older, more often females, more Caucasian, more unmarried, more advanced T and N stage, larger tumor sizes, and more poorly differentiated tumor, while LSCC patients had more stage IV diseases. Location was an independent prognostic factor in the multivariable analysis. Compared with RSCC patients, the hazard ratio for LSCC was 0.87, 95% CI: 0.85–0.89 P < 0.001. There was no survival difference between RSCC and LSCC in the following situations: older than 68 years old, T3–4, N0, poorly differentiated, and undifferentiated diseases. We firstly reported that RSCC patients had a better prognosis than LSCC in mucinous adenocarcinoma/signet ring cell carcinoma patients. RSCC patients also had a better prognosis than LSCC in stage II disease. There is a need for further subdivisions when analyzing the survival difference between RSCC and LSCC patients. RSCC had lower mortality rate than LSCC in stage II disease and mucinous adenocarcinoma/signet ring cell carcinoma patients.