Pretreatment anemia and survival in nasopharyngeal carcinoma.

Due to the low incidence of pretreatment anemia in nasopharyngeal carcinoma (NPC), the true prognostic impact of pretreatment anemia may be underestimated before. We retrospectively analyzed the association of pretreatment anemia with disease-specific survival (DSS), distant-metastasis-free survival (DMFS), and locoregional-relapse-free survival (LRFS) by Cox regression in a cohort of 5830 patients, stratifying by midtreatment anemia, smoking, body mass index (BMI), etc. Pretreatment anemia was significantly associated with adverse DSS (hazard ratio (HR) = 2.15, 95 % confidence interval (CI) 1.62-2.85, P < 0.001) and DMFS (HR = 1.53, 95 % CI 1.08-2.17, P = 0.018), comparing to patients with normal hemoglobin, after adjusting for covariates. Moreover, the association with DSS remained unchanged regardless of smoking status and clinical stage, whereas it was limited in the subgroups of above 45 years, male sex, and BMI <25 kg/m(2). With restriction to midtreatment anemic patients, pretreatment anemia was still strongly correlated with inferior DSS and DMFS. This study, in the largest reported cohort, is the first to show the adverse prognostic impact of pretreatment anemia on DSS and DMFS in NPC.

The prognostic impact of preoperative blood monocyte count in pathological T3N0M0 rectal cancer without neoadjuvant chemoradiotherapy.

It remains controversial whether adjuvant therapy should be delivered to pathological T3N0M0 rectal cancer without neoadjuvant chemoradiotherapy. Thus identification of patients at high risk is of particular importance. Herein, we aimed to evaluate whether the absolute peripheral blood monocyte count can stratify the pathological T3N0M0M0 rectal cancer patients in survival. A total of 270 pathological T3N0M0 rectal cancer patients with total mesorectal excision-principle radical resection were included. The optimal cut-off value of preoperative monocyte count was determined by receiver operating characteristic curve analysis. Overall survival and disease-free survival between low- and high-monocyte were estimated by Kaplan-Meier method and Cox regression model. The optimal cut-off value for monocyte count was 595 mm(3). In univariate analysis, patients with monocyte counts higher than 595/mm(3) had significantly inferior 5-year overall survival (79.2 vs 94.2 %, P = 0.006) and disease-free survival (67.8 vs 86.0 %, P < 0.001). With adjustment for the known covariates, monocyte count remained to be associated with poor overall survival (HR = 2.55, 95 % CI 1.27-5.10; P = 0.008) and disease-free survival (HR = 2.63, 95 % CI 1.48-4.69; P = 0.001). Additionally, the significant association of monocyte count with disease-free survival was hardly influenced in the subgroup analysis, whereas this correlation was restricted to the males and patients with normal carcinoembryonic antigen (CEA) level (<5 µg/L), tumor grade II, and with adjuvant therapy. High preoperative monocyte count is independently predictive of worse survival of pathological T3N0M0 rectal cancer patients without neoadjuvant chemoradiotherapy. Postoperative adjuvant therapy might be considered for patients with high-monocyte count.

External validity of a prognostic nomogram for locoregionally advanced nasopharyngeal carcinoma based on the 8th edition of the AJCC/UICC staging system: a retrospective cohort study.

BACKGROUND: The tumor-node-metastasis (TNM) staging system does not perform well for guiding individualized induction or adjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We attempted to externally validate the Pan's nomogram, developed based on the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system, for patients with locoregionally advanced disease. In addition, we investigated the reliability of Pan's nomogram for selection of participants in future clinical trials. METHODS: This study included 535 patients with locoregionally advanced NPC who were treated between March 2007 and January 2012. The 5-year overall survival (OS) rates were calculated using the Kaplan-Meier method and compared with predicted outcomes. The calibration was tested using calibration plots and the Hosmer-Lemeshow test. Discrimination ability, which was assessed using the concordance index, as compared with other predictors. RESULTS: Pan's nomogram was observed to underestimate the 5-year OS of the entire cohort by 8.65% [95% confidence interval (CI) - 9.70 to - 7.60%, P < 0.001] and underestimated the 5-year OS of each risk group. The differences between the predicted and observed 5-year OS rates were smallest among low-risk patients (< 135 points calculated using Pan's nomogram; which predicted minus observed OS, - 6.41%, 95% CI - 6.75 to - 6.07%, P < 0.001) and were largest among high-risk patients (≥ 160 points) (- 13.56%, 95% CI - 15.48 to - 11.63%, P < 0.001). The Hosmer-Lemeshow test suggested that the predicted and observed 5-year OS rates had no ideal relationship (P < 0.001). Pan's nomogram had better discriminatory ability compared with the levels of Epstein-Barr virus DNA acid (EBV DNA) and the 7th or 8th AJCC/UICC staging system, although not better compared with the combination of EBV DNA and the 8th staging system. Additionally, Pan's nomogram was marginally inferior to our predictive model, which included the 8th AJCC/UICC N-classification, age, gross primary tumor volume, lactate dehydrogenase, and body mass index. CONCLUSIONS: Pan's nomogram underestimated the 5-year OS of patients with locoregionally advanced NPC at our cancer center, and may not be a precise tool for selecting participants for clinical trials.

The total number of lymph nodes harvested from pathological T3N0 rectal cancer patients: Prognostic significance and potential indication for postoperative radiotherapy.

BACKGROUND: Lymph node status is important in staging colorectal cancer. The use of combination treatment for pathological T3N0 (pT3N0) rectal cancer patients has been controversial. We aimed to explore the prognostic significance of the total number of lymph nodes harvested from pT3N0 rectal cancer patients. METHODS: Between June 2004 and November 2011, 289 pT3N0 rectal cancer patients who received total mesorectal excision (TME) with or without postoperative chemotherapy were retrospectively reviewed. The main independent variable was the total number of harvested lymph nodes, and the endpoints included local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). RESULTS: The patients had a median of 13 lymph nodes harvested. When compared with patients who had < 12 lymph nodes harvested, patients who had ≥12 lymph nodes harvested had higher 5-year LRFS (84.7% vs. 98.0%, P < 0.001), DFS (71.4% vs. 86.8%, P < 0.001), and OS (77.6% vs. 94.9%, P < 0.001) rates. Multivariate analysis demonstrated that the patients who had ≥12 lymph nodes harvested had a significantly lower risks of local relapse (hazard ratio [HR], 0.099; P < 0.001), treatment failure (HR: 0.291; P < 0.001), and death (HR: 0.231; P < 0.001) when compared with patients who had <12 lymph nodes harvested. CONCLUSIONS: The number of lymph nodes harvested was independently associated with local relapse, treatment failure, and OS rates in pT3N0 rectal cancer patients who received initial TME with or without postoperative chemotherapy. Postoperative radiotherapy should not be omitted for pT3N0 rectal cancer patients who had <12 lymph nodes harvested.

Validation and comparison of the 7th and 8th edition of AJCC staging systems for non-metastatic nasopharyngeal carcinoma, and proposed staging systems from Hong Kong, Guangzhou, and Guangxi.

OBJECTIVES: We aimed to validate and compare the 7th and 8th edition of AJCC staging systems for non-metastatic nasopharyngeal carcinoma, and proposed staging systems from Hong Kong, Guangzhou, and Guangxi. MATERIALS AND METHODS: We retrospectively included 899 patients treated between November 5, 2002 and May 27, 2010. Separation and discrimination of each staging system in overall survival were primarily compared. RESULTS: Compared with the 7th AJCC, the 8th AJCC and all proposed staging systems well separated across T-classification. T-classification from Guangzhou seemed to perform best in discrimination (C-index 0.6454), followed by the 8th AJCC (0.6451), the 7th AJCC (0.6386), Hong Kong (0.6376) and Guangxi (0.5889). For N-classification, no staging systems improved the weakness of the 7th AJCC in separating N2 and N1, except that suggestion from Guangzhou showed higher potential (P=0.096). Besides, N-classification from Guangzhou had a C-index of 0.6444, larger than that of the 8th AJCC (0.6235), the 7th AJCC (0.6179), Hong Kong (0.6175) and Guangxi (0.6175). Accordingly, stage group of staging system from Guangzhou showed higher discrimination (C-index 0.6839), compared with the 8th AJCC (0.6791), the 7th AJCC (0.6766), Hong Kong (0.6765) and Guangxi (0.6688), despite that stage I and II remained inseparable (P=0.322). CONCLUSIONS: The 8th AJCC staging system appeared to be better than the 7th AJCC. But the proposed staging system from Guangzhou was more likely to improve the separation and discrimination abilities.

Validation of published nomograms and accordingly individualized induction chemotherapy in nasopharyngeal carcinoma.

OBJECTIVES: We have attempted to validate two published nomograms in nasopharyngeal carcinoma (NPC) and individualize induction chemotherapy (IC) accordingly. MATERIALS AND METHODS: From 2007 to 2011, 920 patients were included in the study. The validity of the nomograms was assessed by Harrell's concordance index (C-index), areas under the curve (AUC), and calibration curves. Disease-free survival (DFS) and overall survival (OS) by IC were evaluated in and out of risk stratified patients with and without propensity score matching analysis. RESULTS: Compared with the 7th edition of the Union for International Cancer Control (UICC) staging system, Tang's nomogram better discriminated DFS (C-index 0.629 versus 0.569, P=0.002; AUC 0.635 versus 0.576, P=0.018), whereas Yang's nomogram had no advantage in predicting OS (C-index 0.648 versus 0.606, P=0.184; AUC 0.643 versus 0.604, P=0.157). Calibration curves indicated good agreement between predicted and observed DFS or OS probability. Without risk stratification, patients achieved no benefit from IC in DFS (P⩾0.101) or OS (P⩾0.370). However, among 580 high-risk patients stratified by Tang's nomogram, IC improved five-year DFS from 68.8 to 74.8% (P=0.072), and OS from 82.6 to 87.9% (P=0.065), and the improvement of DFS and OS increased to 9.3% (P=0.019) and 7.3% (P=0.036), respectively, in 426 propensity-matched patients. CONCLUSIONS: Tang's nomogram helps to stratify stage III-IVa-b NPC, and IC is beneficial to high-risk patients in clinical practice.

Evaluation of Body Mass Index and Survival of Nasopharyngeal Carcinoma by Propensity-Matched Analysis: An Observational Case-Control Study.

The effect of pretreatment body mass index on survival of nasopharyngeal carcinoma remains contradictory.All patients (N = 1778) underwent intensity-modulated radiotherapy with or without chemotherapy. Body mass index was categorized as underweight (<18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (22.9-27.5 kg/m2), and obesity (≥27.5 kg/m2). Propensity score matching method was used to identify patients with balanced characteristics and treatment regimen. Disease-specific survival (DSS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival were estimated by Kaplan-Meier method and Cox regression.Following propensity matching, 115 (underweight vs normal), 399 (overweight vs normal), and 93 (obese vs normal) pairs of patients were selected, respectively. In univariate analysis, underweight patients had inferior DSS/OS (P = 0.042) and DMFS (P = 0.025) while both overweight and obese patients showed similar survival across all the endpoints (P ≥ 0.098) to those with normal weight. In multivariate analysis, underweight remained predictive of poor DSS/OS (P = 0.044) and DMFS (P = 0.040), whereas overweight (P ≥ 0.124) or obesity (P ≥ 0.179) was not associated with any type of survival.Underweight increased the risk of death and distant metastasis, whereas overweight or obese did not affect the survival of nasopharyngeal carcinoma. This provides support for early nutritional intervention during the long waiting time before treatment.

Outcomes of Induction Chemotherapy Plus Intensity-Modulated Radiotherapy (IMRT) Versus IMRT Plus Concurrent Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma: A Propensity Matched Study.

PURPOSE: It deserves investigation whether induction chemotherapy (IC) followed by intensity-modulated radiotherapy (IMRT) is inferior to the current standard of IMRT plus concurrent chemotherapy (CC) in locoregionally advanced nasopharyngeal carcinoma. METHODS: Patients who received IC (94 patients) or CC (302 patients) plus IMRT at our center between March 2003 and November 2012 were retrospectively analyzed. Propensity-score matching method was used to match patients in both arms at equal ratio. Failure-free survival (FFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: In the original cohort of 396 patients, IC plus IMRT resulted in similar FFS (P = .565), OS (P = .334), DMFS (P = .854), and LRFS (P = .999) to IMRT plus CC. In the propensity-matched cohort of 188 patients, no significant survival differences were observed between the two treatment approaches (3-year FFS 80.3% vs 81.0%, P = .590; OS 93.4% vs 92.1%, P = .808; DMFS 85.9% vs 87.7%, P = .275; and LRFS 93.1% vs 92.0%, P = .763). Adjusting for the known prognostic factors in multivariate analysis, IC plus IMRT did not cause higher risk of treatment failure, death, distant metastasis, or locoregional relapse. CONCLUSIONS: IC plus IMRT appeared to achieve comparable survival to IMRT plus CC in locoregionally advanced nasopharyngeal carcinoma. Further investigations were warranted.

Effect of intensity-modulated radiotherapy versus two-dimensional conventional radiotherapy alone in nasopharyngeal carcinoma.

BACKGROUND: Albeit intensity-modulated radiotherapy (IMRT) is currently the recommended radiation technique in treating nasopharyngeal carcinoma, the effect of IMRT versus two-dimensional conventional radiotherapy (2DCRT) alone is still contradictory. RESULTS: In the original unmatched cohort of 1198 patients, IMRT obtained comparable 5-year overall survival (OS) (91.3% vs 87.1%, P = 0.120), locoregional relapse-free survival (LRFS) (92.3% vs 90.4%, P = 0.221) and distant metastasis-free survival (DMFS) (92.9% vs 92.1%, P = 0.901) to 2DCRT. In the propensity-matched cohort of 604 patients, no significant survival differences were observed between the two arms (5-year OS 90.9% vs 90.5%, P = 0.655; LRFS 92.5% vs 92.4%, P = 0.866; DMFS 92.5% vs 92.9%, P = 0.384). In multivariate analysis, IMRT did not significantly lower the risk of death, locoregional relapse or distant metastasis, irrespective of tumor stage. METHODS: Overall, 1198 patients who underwent IMRT (316 patients) or 2DCRT (882 patients) without any chemotherapy was retrospectively analyzed. Patients in both arms were matched at equal ratio using propensity-score matching method. OS, LRFS and DMFS were assessed with Kaplan-Meier method, log-rank test and Cox regression. CONCLUSIONS: In this propensity-matched study, IMRT showed no survival advantage over 2DCRT alone in nasopharyngeal carcinoma.

Pathological Assessment of the AJCC Tumor Regression Grading System After Preoperative Chemoradiotherapy for Chinese Locally Advanced Rectal Cancer.

We used American Joint Committee on Cancer (AJCC) Staging Manual system to assess the prognostic significance of tumor regression grading (TRG) for locally advanced rectal cancer (LARC) (T3/4 or N+) patients who were treated with preoperative chemoradiotherapy (CRT).The 4 AJCC-TRG classifications were evaluated on surgical specimens from 295 LARC patients receiving CRT. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated using Kaplan-Meier method and Cox regression model.Classifications of TRG 0, 1, 2, and 3 were found in 27.5%, 19.3%, 45.7%, and 7.5% of the resected specimens, respectively. Three-year OS was 95.5% for TRG0, 91.5% for TRG1, 84.8% for TRG2, and 85.7% for TRG3 (P = 0.035). Three-year DFS was 89.0% for TRG0, 74.4% for TRG1, 70.9% for TRG2, and 62% for TRG3 (P = 0.018). By multivariate analysis, AJCC-TRG (P = 0.033), residual lymph node metastasis (ypN+) (P < 0.001) and pretreatment CA19-9 level (P = 0.035) were significant predictors of OS. Pathological T category (P = 0.006) and nodal status (P < 0.001) after CRT were the most important independent prognostic factors for DFS.AJCC-TRG is a prognostic factor for LARC patients receiving CRT, independent of pathological staging.

Tumor deposits: markers of poor prognosis in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy.

BACKGROUND: Tumor deposits (TDs) were reported to be poor prognoses in colorectal carcinoma, but the significance in locally advanced rectal cancer (LARC) (T3-4/N+) following neoadjuvant chemoradiotherapy (neo-CRT) and surgery is unclear. Since adjuvant chemotherapy showed no benefit for LARC following neo-CRT, it is of great value to investigate whether TDs can identify the subgroup of patients who may benefit from adjuvant chemotherapy. METHODS: Between 2004 and 2012, 310 LARC patients following neo-CRT and surgery were retrospectively reviewed. Overall survival (OS), disease-free survival (DFS), distant metastasis free survival (DMFS) and local recurrence free survival (LRFS) were evaluated by Kaplan-Meier method, log-rank test and Cox models. RESULTS: TDs-positive patients showed adverse OS, DFS and DMFS (all P ≤ 0.001), but not LRFS (P = 0.273). In multivariate analysis, TDs continued to be associated with poor OS (HR = 2.44, 95% CI 1.32-4.4, P = 0.004) and DFS (HR = 1.99, 95% CI 1.21-3.27, P = 0.007), but not DMFS (HR = 1.77, 95% CI 0.97-3.20, P = 0.061) or LRFS (HR = 1.85, 95% CI 0.58-5.85, P = 0.298). Among TDs-positive patients, adjuvant chemotherapy significantly improved OS (P = 0.045) and DMFS (P = 0.026), but not DFS (P = 0.127) or LRFS (P = 0.862). CONCLUSIONS: TDs are predictive of poor survival in LARC after neo-CRT. Fortunately, TDs-positive patients appear to benefit from adjuvant chemotherapy.

Propensity score matching analysis of cisplatin-based concurrent chemotherapy in low risk nasopharyngeal carcinoma in the intensity-modulated radiotherapy era.

BACKGROUND: Patients with stage II nasopharyngeal carcinoma were reported to benefit from adding cisplatin-based concurrent chemotherapy to two-dimensional conventional radiotherapy. But this benefit becomes uncertain in the intensity-modulated radiotherapy (IMRT) era, owing to its significant advantage. METHODS: We enrolled 661 low risk (T1N1M0, T2N0-1M0 or T3N0M0, the 2010 UICC/AJCC staging system) patients who underwent IMRT with or without concurrent chemotherapy. Particularly, patients with IMRT alone or IMRT plus cisplatin-based concurrent chemotherapy were equally matched using propensity-score matching method. Overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression. RESULTS: Among 661 patients, IMRT alone achieved parallel OS (P = 0.379), DMFS (P = 0.169) and LRFS (P = 0.849) to IMRT plus concurrent chemotherapy. In the propensity-matched cohort of 482 patients, similar survival were observed between both arms (4-years OS 97.4% vs 96.1%, P = 0.134; DMFS 96.5% vs 95.1%, P = 0.763; LRFS 93.8% vs 91.5%, P = 0.715). In multivariate analysis, cisplatin-based concurrent chemotherapy did not lower the risk of death, distant metastasis or locoregional relapse. And this association remained unchanged in subgroups by age, sex, histology and stage. CONCLUSIONS: In this study, low risk nasopharyngeal carcinoma patients who underwent IMRT could not benefit from cisplatin-based concurrent chemotherapy.

Effect of taxanes-based induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A large scale propensity-matched study.

OBJECTIVES: The effect of taxanes-based induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) was quite contradictory in two phase II randomized controlled trials with small sample size. We aimed to investigate it in this large scale propensity-matched study. MATERIALS AND METHODS: Totally, 779 LA-NPC patients who underwent intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy with or without taxanes-based IC were included. Patients in both treatment arms were matched using propensity score matching method at the ratio of 1:1. Failure-free survival (FFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression analysis. RESULTS: After matching, 534 patients were identified for analysis. In univariate analysis, both treatment arms resulted in parallel survival (4-years FFS 78.0% vs 74.1%, P = 0.304; OS 87.5% vs 87.3%, P = 0.595; DMFS 88.2% vs 84.4%, P = 0.154; and LRFS 91.2% vs 90.1%, P = 0.960). In multivariate analysis, taxanes-based IC did not improve any survival (P ⩾ 0.139). And this association remained unchanged in subgroup analysis by age, sex and histology, and among patients with stage III and T4N0M0. But among patients with T4N1-2M0 and stage IVb, taxanes-based IC significantly prolonged the 4-year DMFS by 11.2% (86.1% vs 74.9%, P = 0.034), and marginally improved FFS (P = 0.133) and OS (P = 0.215) in both univariate and multivariate analysis. CONCLUSIONS: In this large scale propensity-matched study, LA-NPC patients could not benefit from taxanes-based IC on the whole. But the risk of distant metastasis significantly decreased by above 10% for patients with T4N1-2M0 and stage IVb.

Elevated CA19-9 as the Most Significant Prognostic Factor in Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy.

It remains controversial regarding the prognostic significance of carbohydrate antigen 19-9 (CA19-9) for locally advanced rectal cancer (LARC) (T3-4/N+) patients with neoadjuvant chemoradiotherapy (neo-CRT). And it is unknown whether CA19-9 can identify patients who may benefit from adjuvant chemotherapy.Overall, 303 LARC patients with neo-CRT between 2004 and 2010 were recruited. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival across pretreatment CA19-9 were estimated by Kaplan-Meier method and Cox regression model.In univariate analysis, elevated CA19-9 (>35 U/mL) was significantly correlated with poor OS (P = 0.003), DFS (P = 0.001), and DMFS (P = 0.039). Adjusting for the known covariates, CA19-9 was significantly associated with OS (HR = 1.86, 95% CI 1.03-3.34, P = 0.039) and DFS (HR = 1.74, 95% CI 1.08-2.80, P = 0.024). In the elevated CA19-9 subgroup, patients with adjuvant chemotherapy got much better OS (P < 0.001) and DFS (P = 0.016) than those without. In consideration of both CA19-9 and carcinoembryonic antigen (CEA), we found that patients with both elevated CA19-9 and CEA (>5 ng/mL) got the worst OS (P = 0.021) and DFS (P = 0.006), and significantly benefited from adjuvant chemotherapy in OS (P < 0.001) and DFS (P = 0.026).Pretreatment CA19-9 level is a significant prognostic indicator in patients with LARC following neo-CRT. The addition of CA19-9 to CEA is valuable to discriminate the appropriate patients for adjuvant chemotherapy.

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.

Tailored selection of the interval between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer: analysis based on the pathologic stage or chemoradiation response.

BACKGROUND: The optimal interval between neoadjuvant chemoradiotherapy (CRT) and surgery has yet to be established. Additionally, it is unknown whether patients with different pathologic stages or chemoradiation responses should undergo different intervals between CRT and surgery. Therefore, the purpose of this study was to evaluate whether this interval has a differential effect on the oncologic outcome of patients with different chemoradiation responses or pathologic stages. METHODS: We performed a retrospective study of 291 rectal cancer patients who were treated with preoperative chemoradiation and surgery between March 2004 and November 2012. All patients were separated into two groups according to a 7-week treatment interval. Overall survival (OS) and disease-free survival (DFS) were compared between patients undergoing intervals that were shorter and longer than 7 weeks in the entire group and in subgroups of ypT0-2N0, ypT3-4N0 and ypT0-4N+. The recurrence patterns were also analysed in all of the subgroups. Multivariate analysis was performed to explore the clinical factors that were significantly associated with DFS, local recurrence-free survival (LRFS) and distant metastasis-free survival among patients exhibiting ypT3-4N0 and ypT0-4N+. RESULTS: For the ypT0-2N0 patients, the 5-year OS and DFS and the rates of local and distant recurrence were similar between the short and long interval groups. For the patients exhibiting ypT3-4N0, although no significant difference was found in OS or DFS between the short and long interval groups, the rate of local recurrence was higher in the long interval group, which was further confirmed by multivariate analysis. In the patients exhibiting ypT0-4N+, both OS and DFS were lower in the long interval group than in the short interval group. Furthermore, multivariate analysis indicated that the interval was significantly associated with DFS, especially LRFS. CONCLUSIONS: The interval between CRT and surgery may exert a differential effect on the prognosis of patients exhibiting different pathologic stages or chemoradiation responses. Therefore, we strongly suggest tailoring the interval between CRT and surgery in locally advanced rectal cancer.