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Lymph node status as a prognostic factor after palliative resection of primary tumor for patients with metastatic colorectal cancer.

ABSTRACT: Lymph node (LN) status is one of the most important predictors for M0 colorectal cancer patients. However, its clinical impact on stage IV colorectal cancer remains unclear. The study aimed to explore the prognostic value of LN status after palliative resection of primary tumor for patients with metastatic colorectal cancer (mCRC). We combined analyses of mCRC patients in Surveillance, Epidemiology and End Results (SEER) database and Fudan University Shanghai Cancer Center (FUSCC).A total of 17,553 patients with mCRC were identified in SEER database. X-tile program was adopted to identify 2 and 10 as optimal cutoff values for negative lymph node (NLN) count to divide patients into 3 subgroups of high, middle and low risk of cancer related death. N stage and NLN count were verified as independent prognostic factors in multivariate analyses of patients in whole cohort and in subgroup analyses of each N stage (P<0.05). Validation of FUSCC cohort of patients demonstrated that metastatic tumor burden (P = 0.042), NLN count (P = 0.039) and sequential chemotherapy (P = 0.040) were significant predictors of poorer CSS. Specifically, the prognosis of patients at stage N0 was significantly more favorable than that of patients at stage N2 (P = 0.038). In conclusion, primary tumor LN status was a strong predictor of CSS after palliative resection of metastatic colorectal cancer. Advanced N stage and small number of NLN were correlated with high risk of cancer related death after palliative resection of primary tumor.

SUBMITTER: Li Q

PROVIDER: S-EPMC5564651 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Survival Impact of Primary Tumor Lymph Node Status and Circulating Tumor Cells in Patients with Colorectal Liver Metastases.

Project description:The aim of this study was to analyse the survival impact of primary tumor nodal status (N0/N+) in patients with resectable colorectal liver metastases (CLM), and to determine the value of circulating and disseminated tumor cells (CTCs/DTCs) in this setting.In this prospective study of patients undergoing resection of CLM from 2008 to 2011, peripheral blood was analyzed for CTCs using the CellSearch System®, and bone marrow was sampled for DTC analyses just prior to hepatic resection. The presence of one or more tumor cells was scored as CTC/DTC-positive. Following resection of the primary tumor, the lymph nodes (LNs) were examined by routine histopathological examination.A total of 140 patients were included in this study; 38 patients (27.1%) were negative at the primary colorectal LN examination (N0). CTCs were detected in 12.1% of all patients; 5.3% of patients in the N0 group and 14.7% of patients in the LN-positive (N+) group (p = 0.156), with the LN-positive group (N+) consisting of both N1 and N2 patients. There was a significant difference in recurrence-free survival (RFS) when analysing the N0 group versus the N+ group (p = 0.007) and CTC-positive versus CTC-negative patients (p = 0.029). In multivariate analysis, CTC positivity was also significantly associated with impaired overall survival (OS) [p = 0.05], whereas DTC positivity was not associated with survival.In this cohort of resectable CLM patients, 27% had primary N0 colorectal cancer. Assessment of CTC in addition to nodal status may contribute to improved classification of patients into high- and low-risk groups, which has the potential to guide and improve treatment strategies.

| S-EPMC5491630 | biostudies-literature

A reappraisal of lymph node dissection in colorectal cancer during primary surgical resection.

Project description:PURPOSE:Controversy exists regarding the extent to which lymph node dissection (LND) should be performed for operable colorectal cancers (CRCs) during primary surgical resection. We reappraised the role of LND in CRCs. METHODS:Seventy-three CRC patients (mean age, 65.3?years; 43 males) undergoing primary surgical resection at Taipei Hospital, Ministry of Health and Welfare, Taiwan, within a 3-year period were retrospectively analyzed. Their pathological T/N/M statuses and cancer stages were defined according to the American Joint Committee on Cancer (AJCC) 8th edition staging system. The numbers of total dissected lymph nodes (TDLNs), positive dissected lymph nodes (PDLNs), and negative dissected lymph nodes (NDLNs) for each CRC patient were recorded in detail (TDLNs = PDLNs + NDLNs). Possible prognostic variables were evaluated. RESULTS:An advanced N status (N1/N2 vs. N0; HR, 5.749/17.677 vs. 1.000; p = 0.056/0.009) and M1 status (M1 vs. M0; HR, 7.517 vs. 1.000; p = 0.010) were independent variables for a poor prognosis. For all 73 CRC patients (p = 0.030), as well as T2 CRC patients (p = 0.061), those with > 15 TDLNs tended to have more PDLNs than those with ? 15 TDLNs. For 42?N(+) CRC patients (p = 0.007), as well as N2 CRC patients (p = 0.011), those with > 21 TDLNs tended to have more PDLNs than those with ? 21 TDLNs. CONCLUSION:For CRC patients undergoing primary surgical resection, the number of TDLNs influences the accuracy of nodal staging. A minimum of 15 TDLNs is necessary for positive lymph nodes to be identified in CRC patients, and 21 TDLNs is sufficient for the severity of the N(+) status to be distinguished in N(+) CRC patients.

| S-EPMC7232835 | biostudies-literature

Limited effect of lymph node status on the metastatic pattern in colorectal cancer.

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| S-EPMC5077970 | biostudies-literature

Palliative resection or radiation of primary tumor prolonged survival for metastatic esophageal cancer.

Project description:PurposeWe aimed to explore the value of palliative resection or radiation of primary tumor for metastatic esophageal cancer (EC) patients.MethodsSurveillance, Epidemiology, and End Results database was used for identifying metastatic EC patients. The patients were divided into resection and nonresection groups. And patients without resection were divided into radiation and nonradiation groups. Propensity score matching (PSM) analyses were adopted to reduce the baseline differences between the groups. Cancer specific survivals (CSSs) and overall survivals (OSs) were compared by Kaplan-Meier (K-M) curves. Multivariable analyses by COX proportion hazards model were performed to identify risk factors for CSS and OS. Predictive nomograms were conducted according to both postoperative factors and preoperative factors.ResultsA total of 7982 metastatic EC patients were selected for our analyses. After PSM, 978 patients were included in the survival analyses comparing palliative resection and nonresection. The CSS and OS for patients underwent palliative resection were significantly longer than those without resection (median CSS: 21 months vs 7 months, P < .001; median OS: 20 months vs 7 months, P < .001). In the overall population without resection, 654 patients were matched for radiation and nonradiation groups. And K-M curves showed that patients with radiation had longer CSS and OS than those without radiation (median CSS: 11 months vs 6 months, P < .001; median OS: 10 months vs 6 months, P < .001). Nomograms were generated for prediction of 1-, 2-, and 3-year CSS and OS. All C-indexes implied moderate discrimination and accuracy. And all nomograms had good calibration.ConclusionPalliative resection or radiation of primary tumor could prolong CSS and OS of metastatic EC patients.

| S-EPMC6885868 | biostudies-literature

Bevacizumab efficacy in metastatic colorectal cancer is dependent on primary tumor resection.

Project description:PurposeBevacizumab plus fluoropyrimidine-based chemotherapy is standard treatment for first-line and second-line metastatic colorectal cancer (mCRC). However, to date, there is no current biomarker predictive for the benefit of bevacizumab use for these patients. Preclinical data suggest that the presence of the primary tumor could be involved in less efficient antitumor activity of antiangiogenic agents, but no clinical data currently support this hypothesis.MethodsWe performed a retrospective analysis of factors associated with overall survival (OS) in a study cohort of 409 mCRC patients. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of primary tumor resection and bevacizumab use on OS. We evaluated associations linking bevacizumab use and OS among patients who previously underwent or did not undergo primary tumor resection. Results were externally validated in a second independent cohort of 328 mCRC patients.ResultsIn the study cohort, bevacizumab use and resection of the primary tumor were associated with improved OS. However, subgroup analyses indicate that bevacizumab did not influence survival of patients bearing a primary colorectal tumor (hazard ratio (HR) 0.98, 95 % confidence interval (CI) 0.60-1.61, log-rank test P = 0.6). By contrast, the survival benefit of bevacizumab was restricted to patients who previously underwent primary tumor resection (HR 0.71, 95 % CI 0.55-0.92, P = 0.009). Similar results were observed in the validation cohort.ConclusionsAddition of bevacizumab to chemotherapy is associated with improvement of OS only in patients with primary tumor resection. These data support the rationale to validate prospectively the influence of primary tumor resection on bevacizumab antitumor effect in synchronous mCRC.

| S-EPMC3975091 | biostudies-literature

Influence of primary tumor location and resection on survival in metastatic colorectal cancer.

Project description:BackgroundPatients with right sided colorectal cancer are known to have a poorer prognosis than patients with left sided colorectal cancer, whatever the cancer stage. To this day, primary tumor resection (PTR) is still controversial in a metastatic, non resectable setting.AimTo explore the survival impact of PTR in patients with metastatic colorectal cancer (mCRC) depending on PTL.MethodsWe retrospectively collected data from all consecutive patients treated for mCRC at the Centre Georges Francois Leclerc Hospital. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of PTR on survival. We then evaluated the association between PTL and overall survival among patients who previously underwent or did not undergo PTR. A propensity score was performed to match cohorts.ResultsFour hundred and sixty-six patients were included. A total of 153 (32.8%) patients had unresected synchronous mCRC and 313 (67.2%) patients had resected synchronous mCRC. The number of patients with right colic cancer, left colic cancer and rectal cancer was respectively 174 (37.3%), 203 (43.6%) and 89 (19.1%). In the multivariate analysis only PTL, PTR, resection of hepatic and or pulmonary metastases and the use of oxaliplatin, EGFR inhibitors or bevacizumab throughout treatment were associated to higher overall survival rates. Survival evaluation depending on PTR and PTL found that PTR improved the prognosis of both left and right sided mCRC. Results were confirmed by using a weighted propensity score.ConclusionIn mCRC, PTR seems to confer a higher survival rate to patients whatever the PTL.

| S-EPMC7667454 | biostudies-literature

Mesenteric Lymph Node Recurrence of a Primary Colorectal Leiomyosarcoma.

Project description:Primary colorectal leiomyosarcoma is an excessively rare entity. It is associated with an aggressive behavior and typically favor hematogenous spread. The current standard of care is surgical resection. A 49-year-old patient presented with a 2-month history of fever. A PET-scan revealed a hypermetabolic mass in the transverse colon, and colonoscopy confirmed a tumor. A right hemicolectomy was performed. Histopathological diagnosis was of a leiomyosarcoma. Fourteen months after the surgery, a follow-up abdominal scan revealed a 2?cm mesenteric lymph node that was hypermetabolic on PET-scan. The mesenteric lymph node was resected and histopathology confirmed a leiomyosarcoma metastasis. This case opens the controversy on the management of rare lymph node recurrences in colorectal leiomyosarcoma.

| S-EPMC7125469 | biostudies-literature

Primary tumor location as a prognostic factor in metastatic colorectal cancer.

Project description:We sought to clarify the prognostic impact of primary tumor location in metastatic colorectal cancer (mCRC). We evaluated the association between tumor location and survival parameters in patients with previously untreated mCRC receiving first-line chemotherapy ± bevacizumab in three independent cohorts: a prospective pharmacogenetic study (PROVETTA) and two randomized phase III trials, AVF2107g and NO16966. Cancers proximal or distal of the splenic flexure were classified as right-sided or left-sided, respectively. The primary end point was overall survival (OS). Data were analyzed with Cox proportional hazards and logistic regression models. All statistical tests were two-sided. Among evaluable patients in the PROVETTA (n = 200), AVF2107g (n = 559), and NO16966 (n = 1268) studies, 72.0%, 63.1%, and 73.7% had left-sided tumors, respectively. In PROVETTA, patients with left-sided tumors had superior OS (left-sided vs right-sided: hazard ratio [HR] = .44, 95% confidence interval [CI] = .28 to .70, P < .001) and progression-free survival (HR = .52, 95% CI = .36 to .75, P < .001) outcomes. Multivariable analyses confirmed right-sided location as a negative prognostic variable, independent of mucinous histology and BRAF mutational status. Data from the AVF2107g (HR for OS = .55, 95% CI = .43 to .70) and NO16966 trials (HR for OS = .71, 95% CI = .62 to .82 both P < .001) also showed favorable outcomes in patients with left-sided tumors. In both randomized studies, the efficacy of bevacizumab was independent of tumor location. These data demonstrate that primary tumor location is an important prognostic factor in previously untreated mCRC. Given the consistency across an exploratory set and two confirmatory phase III studies, side of tumor origin should be considered for stratification in randomized trials.

| S-EPMC4565528 | biostudies-literature

Synchronous Resectable Metastatic Colorectal Cancer: Lymph Node Involvement Predicts Poor Outcome.

Project description:To evaluate the value of lymph node status of primary tumors in predicting the prognosis of synchronous resectable metastatic colorectal cancer (mCRC).The characteristics of resectable mCRC are substantially different from other cancers, and the prognostic factors of resectable mCRC are still controversial.The data of 2007 patients with mCRC who received resection of the primary tumors and metastatic lesions synchronously were reviewed from the Surveillance, Epidemiology and End-Result database. The Kaplan-Meier method was used to evaluate the capacity of different prognostic factors. Univariate and multivariate logistic regression models were used to evaluate the relationship between the lymph node status and other factors. The mRNA profiles of primary resectable mCRC tumors were obtained by microarray at our center.The median survival times were 50, 36, 32, 27, and 19 months in the N0-stage, N1a-stage, N1b-stage, N2a-stage, and N2b-stage subgroups according to the 7th American Joint Committee on Cancer (AJCC) Tumor Lymph Node Metastasis (TNM) N-classification (P = 0.000), and 40, 29, 22, and 15 months in patients with metastatic lymph node ratio (LNR) <0.25, 0.25-0.49, 0.5-0.74, and ?0.75 subgroups (P = 0.000). In the COX model, the 7th AJCC TNM N-stage and LNR were independent prognostic factors. The mRNA profile was not associated with lymph node involvement.Both the N-stage according to the 7th AJCC TNM staging system and LNR had the capacity to subclassify synchronous resectable mCRC with different prognoses. The lymph node might be integrated into the AJCC staging system as a diagnose-delay prognostic factor for stage IV disease.

| S-EPMC4554134 | biostudies-literature

Lymph Node Tumor Burden Correlates With Tumor Budding and Poorly Differentiated Clusters: A New Prognostic Factor in Colorectal Carcinoma?

Project description:IntroductionMolecular lymph node (LN) staging in early colorectal cancer (CRC) has demonstrated to be more precise than conventional histopathology pN staging. Tumor budding (TB) and poorly differentiated clusters (PDCs) are associated with LN metastases, recurrences, and lower survival in CRC. We evaluated the correlation between the total tumor load (TTL) in LNs from CRC surgical specimens with patient outcome, TB, and PDC.MethodsIn this retrospective multicentre study, 5,931 LNs from 342 stage I-III CRC were analyzed by both hematoxylin and eosin and molecular detection of tumor cytokeratin 19 mRNA by one-step nucleic acid amplification. TB and PDC were evaluated by hematoxylin and eosin and cytokeratin 19 immunohistochemistry.ResultsOne-step nucleic acid was positive in 38.3% patients (n = 131). Tumor Budding was low in 45% cases, intermediate in 25%, and high in 30%. Poorly Differentiated Clusters were low-grade G1 in 53%, G2 in 32%, and G3 in 15%. TB and PDC correlated with TTL, high-grade, lymphovascular and perineural invasion, pT, pN and stage (P < 0.001). TB, PDC, and TTL ≥ 6,000 copies/µL were associated with worse overall survival (P = 0.002, P = 0.013, and P = 0.046) and disease-free survival (P < 0.001).DiscussionThe implementation of more sensitive molecular methods to assess LN status is a promising alternative approach to pN staging, which could be integrated to other factors to help risk stratification and management of patients with early-stage CRC. This study demonstrates the correlation of the amount of LN tumor burden with TB and PDCs. TTL is related to the outcome and could be used as a new prognostic factor in CRC (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A512).

| S-EPMC7909319 | biostudies-literature

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