The Significance of Inflammatory Markers in the Prognosis of Newly Diagnosed Multiple Myeloma Patients

Objective: To explore the significance of the ratio of neutrophils to lymphocytes (NLR), monocytes to lymphocytes (MLR), and platelets to lymphocytes (PLR) in the prognosis of patients with newly diagnosed multiple myeloma. Methods: A total of 60 patients with MM who were diagnosed in Jiangning Hospital Affiliated to Nanjing Medical University and Zhongda Hospital Affiliated to Southeast University from August 2011 to March 2020 were retrospectively analysed. According to NLR, MLR, PLR, the patients were divided into the low NLR group (NLR < 3.61) or high NLR group (NLR ≥ 3.61), low MLR group (MLR < 0.33) or high MLR group (MLR ≥ 0.33), low PLR group (PLR < 129.78) and high PLR group (PLR ≥ 129.78). Overall survival (OS) was used as the prognostic evaluation criteria, and Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate analysis on clinical and laboratory parameters. Results: Among the 60 patients, 33 were male and 27 were female, the median age of the patients was 65 years old, 19 were in the high NLR group, 41 were in the low NLR group, 24 were in the high MLR group, 36 were in the low MLR group, 26 were in the high PLR group, and 34 were in the low PLR group. The univariate analysis showed the prognosis was influenced by factors including NLR, PLR, age, ISS stages, hemoglobin (HGB), albumin (ALT). MLR, type of immunoglobulin, white globulin ratio (A/G), gender, β2-microglobulin(β2-MG), lactate dehydrogenase (LDH) and creatinine were not correlated with the total survival time of patients. The multivariate analysis showed that ISS III stages, PLR ≥ 129.78, HGB < 100g/L were independent risk factors influencing the prognosis of MM patients. Conclusion: ISS III stages, PLR ≥ 129.78, HGB < 100g/L are independent prognostic risk factors in newly diagnosed multiple myeloma patients, which can be used as an economical and effective method for early evaluation of patient prognosis.

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The Significance of Inflammatory Markers in the Prognosis of Newly Diagnosed Multiple Myeloma Patients

Blood ◽

10.1182/blood-2020-136326 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 15-15

Author(s):

Lin Gui ◽

Fei Wang ◽

Jinning Shi ◽

Baoan Chen

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Overall Survival ◽

Multivariate Analysis ◽

Survival Time ◽

Cox Regression ◽

Conflicts Of Interest ◽

Univariate Analysis ◽

Rank Test ◽

Newly Diagnosed

Objective: To explore the significance of the ratio of neutrophils to lymphocytes (NLR), monocytes to lymphocytes (MLR), and platelets to lymphocytes (PLR) in the prognosis of patients with newly diagnosed multiple myeloma. Methods: We retrospectively reviewed the data for 60 multiple myeloma patients who were diagnosed in Jiangning Hospital Affiliated to Nanjing Medical University from August 2011 to March 2020. According to NLR、MLR、PLR, the patients were divided into the low NLR group (NLR<3.61) or high NLR group (NLR≥3.61), low MLR group (MLR<0.33) or high MLR group (MLR ≥0.33), low PLR group (PLR< 129.78) and high PLR group (PLR ≥129.78). Overall survival time (OS) was used as the prognostic evaluation criteria, and Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate analysis on clinical and laboratory parameters. Results: Among the 60 patients, 33 were male and 27 were female, the median age of onset was 65 years old, 19 were in the high NLR group, 41 were in the low NLR group, 24 were in the high MLR group, 36 were in the low MLR group, 26 were in the high PLR group, and 34 were in the low PLR group. The univariate analysis showed the prognosis was influenced by factors including NLR, PLR, age, ISS stages, hemoglobin (HGB), albumin (ALT). MLR, type of immunoglobulin, white globulin ratio (A/G), gender, β2-microglobulin, lactate dehydrogenase (LDH) and creatinine were not correlated with the total survival time of patients. The multivariate analysis showed that ISS III stages, PLR≥129.78、HGB<100g/L were independent risk factors influencing the prognosis of MM patients. Conclusion: ISS III stages, PLR≥129.78、HGB<100g/L are independent prognostic risk factors in newly diagnosed multiple myeloma patients, which can be used as an economical and effective method for early evaluation of patient prognosis. Key Wordsmultiple myeloma; overall survival; NLR; PLR; MLR Disclosures No relevant conflicts of interest to declare.

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Risk Factors for Hepatocellular Carcinoma After Splenectomy in Liver Cirrhotic Patients

The American Surgeon ◽

10.1177/00031348211041562 ◽

2021 ◽

pp. 000313482110415

Author(s):

Naruhiko Honmyo ◽

Tsuyoshi Kobayashi ◽

Shintaro Kuroda ◽

Kentaro Ide ◽

Masahiro Ohira ◽

...

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Portal Hypertension ◽

Cox Regression ◽

Univariate Analysis ◽

Hemoglobin Level ◽

Rank Test ◽

Predictive Index ◽

Preoperative Hemoglobin ◽

Preoperative Hemoglobin Level

Background Splenectomy is sometimes indicated for portal hypertension caused by cirrhosis, which is a risk for hepatic carcinogenesis. This study aimed to identify risk factors for hepatocellular carcinoma (HCC) development after splenectomy. Methods This retrospective study included 65 patients who underwent splenectomy for portal hypertension between 2009 and 2017. Cox regression analyses were performed to identify factors related to HCC development after splenectomy. The predictive index for HCC development was constructed from the results of multivariate analysis, and 3 risk-dependent groups were defined. Discrimination among the groups was estimated using Kaplan-Meier curves and the log-rank test. Results Post-splenectomy, 36.9% of patients developed HCC. In the univariate analysis, the etiology of cirrhosis (hepatitis C virus antibody, P = .005, and hepatitis B surface antigen, P = .008, referring to non-B and non-C patients, respectively), presence of HCC history ( P < .001), and preoperative hemoglobin level ( P = .007) were related to HCC development, and the presence of HCC history ( P = .002) and preoperative hemoglobin level ( P = .022) were independent risk factors. The predictive index classified three groups at risk; the hazards in each group were significantly different (low vs middle risk, P = .035, and middle vs high risk, P = .011). Discussion The etiology of cirrhosis, presence of HCC history, and hemoglobin level were associated with HCC development after splenectomy. The predictive model may aid in HCC surveillance after splenectomy for patients with portal hypertension.

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Different factors underlie recurrent and de novo organ involvement in immunoglobulin G4–related disease

Rheumatology ◽

10.1093/rheumatology/kez321 ◽

2019 ◽

Author(s):

Ichiro Mizushima ◽

Syunsuke Tsuge ◽

Yuhei Fujisawa ◽

Satoshi Hara ◽

Fae Suzuki ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Cox Regression ◽

De Novo ◽

Univariate Analysis ◽

Organ Involvement ◽

Blood Eosinophil ◽

Immunoglobulin G4 ◽

Related Disease ◽

Igg4 Related Disease

Abstract Objectives In IgG4-related disease (IgG4-RD), relapse including recurrent organ involvement (ROI) and de novo organ involvement (DNOI) occurs frequently during the clinical course. This study aimed to clarify the differences between the risk factors underlying ROI and DNOI in IgG4-RD. Methods We retrospectively investigated factors related to ROI and DNOI in 86 IgG4-RD patients. For assessment of factors related to ROI and DNOI, we performed uni- and multivariate Cox regression analyses. On stepwise multivariate analysis, we applied the variables with P < 0.1 in the univariate analysis and the predictors of relapse suggested in past reports. Results During the mean follow-up period of 63.1 months, ROI was detected at 1.0–120 months after diagnosis in 20 patients, 4 of whom were not receiving glucocorticoid (GC) at the time of ROI. In contrast, DNOI was detected at 5.0–120 months after diagnosis in 15 patients, 8 of whom were not receiving GC at the time of DNOI. In the multivariate analysis, blood eosinophil counts at diagnosis [per 100/μl; hazard ratio (HR) 1.072 (95% CI 1.018, 1.129)] and continuation of GC [vs discontinuation or observation without GC; HR 0.245 (95% CI 0.076, 0.793)] had a significant impact on the time to DNOI, whereas age [HR 0.942 (95% CI 0.899, 0.986)] and ANA positivity [vs negativity; HR 6.632 (95% CI 1.892, 23.255)] had a significant impact on the time to ROI. Conclusion The present study suggests that the risk factors of ROI and DNOI are different in IgG4-RD, highlighting the need for different preventative strategies.

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Distant metastasis in head and neck cancer: Baseline factors.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e16021 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e16021-e16021

Author(s):

Rahul Krishnatry ◽

Tejpal Gupta ◽

Vedang Murthy ◽

Sudhir Vasudevan Nair ◽

Deepa Nair ◽

...

Keyword(s):

Multivariate Analysis ◽

Distant Metastasis ◽

Cox Regression ◽

Univariate Analysis ◽

Cell Cancer ◽

Locally Advanced ◽

Disease Free Survival ◽

Stage Iv ◽

Rank Test ◽

Advanced Tumor

e16021 Background: Loco-regional relapse is predominant pattern of failure in locally advanced head & neck squamous cell cancer (HNSCC). Distant metastasis (DM) is increasingly detected on follow-up. this study attempts to identify baseline patient, tumor & treatment characteristics which determine poor survival in radically treated HNSCC patients developing DM. Methods: Clinical outcome audit of HNSCC receiving radical treatment from 1990-2010 in a single HNCC radiotherapy (RT) clinic who developed DM, using electronic search of a prospectively maintained database. The Disease free survival (DFS) & overall survival (OS) were calculated using Kaplan Meier method. The Log rank test & Cox regression (p< 0.05 significant) were used for univariate & multivariate analysis respectively. Results: 104 HNC patients developed DM, baseline characteristics are shown in table 1. DM was detected at a median of 7(IQR 3-14) months from treatment completion & median survival after diagnosis of DM was 2.6 (0-6) months. The median DFS & OS were 19(13-26), 21.5(16-29) months respectively. On univariate analysis, factors affecting DFS & OS were advanced tumor and nodal stage, perinodal extension & treatment factors (surgery & RT gap >30 days). On multivariate analysis stage and PNE remained significant for DFS while only stage showed significance for OS. Conclusions: Locally advanced stage of presentation (stage IV, T4, N2+) is the most important baseline factor determining poor outcome in HNC patients developing DM. Trials for aggressive primary systemic treatment (chemotherapy, targeted agents) are needed. [Table: see text]

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The Role of Delayed Radiotherapy Initiation in Patients with Newly Diagnosed Glioblastoma with Residual Tumor Mass

Journal of Neurological Surgery Part A Central European Neurosurgery ◽

10.1055/s-0041-1730965 ◽

2021 ◽

Author(s):

Johannes Kasper ◽

Clara Frydrychowicz ◽

Katja Jähne ◽

Tim Wende ◽

Florian Wilhelmy ◽

...

Keyword(s):

Dna Methyltransferase ◽

Tumor Volume ◽

Cox Regression ◽

Statistical Significance ◽

Univariate Analysis ◽

Residual Tumor ◽

Rank Test ◽

Survival Prediction ◽

Newly Diagnosed ◽

Entire Cohort

Abstract Objective Treatment for newly diagnosed isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) includes maximum safe resection, followed by adjuvant radio(chemo)therapy (RCx) with temozolomide. There is evidence that it is safe for GBM patients to prolong time to irradiation over 4 weeks after surgery. This study aimed at evaluating whether this applies to GBM patients with different levels of residual tumor volume (RV). Methods Medical records of all patients with newly diagnosed GBM at our department between 2014 and 2018 were reviewed. Patients who received adjuvant radio (chemo) therapy, aged older than 18 years, and with adequate perioperative imaging were included. Initial and residual tumor volumes were determined. Time to irradiation was dichotomized into two groups (≤28 and >28 days). Univariate analysis with Kaplan–Meier estimate and log-rank test was performed. Survival prediction and multivariate analysis were performed employing Cox proportional hazard regression. Results One hundred and twelve patients were included. Adjuvant treatment regimen, extent of resection, residual tumor volume, and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation were statistically significant factors for overall survival (OS). Time to irradiation had no impact on progression-free survival (p = 0.946) or OS (p = 0.757). When stratified for different thresholds of residual tumor volume, survival predication via Cox regression favored time to irradiation below 28 days for patients with residual tumor volume above 2 mL, but statistical significance was not reached. Conclusion Time to irradiation had no significant influence on OS of the entire cohort. Nevertheless, a statistically nonsignificant survival prolongation could be observed in patients with residual tumor volume > 2 mL when admitted to radiotherapy within 28 days after surgery.

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Multivariate Analysis of Risk Factors for Clinically Overt Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v106.11.5295.5295 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5295-5295

Author(s):

Kanger Zhu ◽

Chunhui Ma ◽

Tao Zhang ◽

Juan Zhong

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Cox Regression ◽

Hemorrhagic Cystitis ◽

Univariate Analysis ◽

Male Gender ◽

Gvhd Prophylaxis ◽

Increased Risk ◽

Grade Ii ◽

Grade Iii

Abstract Objective: To analyze the risk factors of clinically overt hemorrhagic cystitis (HC) (grade ≥II) in 114 patients undergoing allo-HSCT to predict the occurrence of HC. Methods: We retrospectively analyzed 29 cases of clinically overt HC from a series of 114 patients given allo-HSCT from April 1997 to December 2004. The time of follow-up began from the day of initiating conditioning to day 180 post-transplant. The 11 clinical parameters were selected for univariate analysis using a Cox regression: age, sex, underlying disease, conditioning regimen, disease status at transplant, aGVHD, donor type, use of ATG, GVHD prophylaxis, platelet and neutrophil engraftment. Factors that were significant at the 0.1 level on univariate analysis were evaluated by multivariate analysis using a Cox regression. The cumulative incidence of grade ≥ II HC within the day 180 after transplantation was calculated by the method of Kaplan and Meier. Results: 29 out of 114 patients (26%) developed HC with grade II in 12/29 cases (41.4%), grade III in 11/29 cases (37.9%) and grade IV in 6/29 cases (20.7%). The following factors were associated with an increased risk of HC by univariate analysis: male gender (RR=2.885, P=0.021),younger than 26 years (RR=3.265, P=0.007),grade III~IV aGVHD (RR=4.039, P=0.002),unrelated doner (RR=4.347, P=0),intense GVHD prophylaxis (RR=2.218, P=0.045),advanced disease (RR=2.668, P=0.009). These risk factors were entered into a multivariate model. Only male gender (RR=2.993, 95% CI 1.218–7.358; P=0.017) and unrelated donor (RR=4.478, 95% CI 2.049–9.786; P=0.000) were identified as being significantly associated with the occurrence of hemorrhagic cystitis. Conclusion: We found that in multivariate analysis, patients were at increased risk of HC if they were male or had received graft from unrelated donors.

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ML-09 The REAL-WORLD of Elderly PCNSL Therapy in Tohoku and Niigata Area According to Retrospective Analysis: A Collaborative Investigation of the Tohoku Brain Tumor Study Group

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa143.072 ◽

2020 ◽

Vol 2 (Supplement_3) ◽

pp. ii17-ii17

Author(s):

Kenichiro Asano ◽

Yoji Yamashita ◽

Takahiro Ono ◽

Manabu Natsumeda ◽

Takaaki Beppu ◽

...

Keyword(s):

Risk Factors ◽

Central Nervous System ◽

Nervous System ◽

Real World ◽

Cox Regression ◽

Univariate Analysis ◽

Central Nervous System Lymphoma ◽

Rank Test ◽

Cox Regression Analysis ◽

The Real

Abstract Introduction: Recently, the number of cases of primary central nervous system lymphoma in elderly patients(EL-PCNSL) has been increasing. However, the treatment may be insufficient because of poor performance status and pre- and posttreatment complications. Therefore, we analyzed the risk factors for EL-PCNSL in the Tohoku and Niigata areas of Japan and clarified the REAL-WORLD of EL-PCNSL therapy. Materials & Methods: We investigated surgical and nonsurgical cases of patients aged 71 years or older from eight facilities during the last 8 years. We analyzed patient information, radiotherapy/chemotherapy or not, PFS, OS, RRs, second-line therapy, pre- and posttreatment complications, outcomes, and risk factors for poor prognosis. The log-rank test was used for univariate analysis, and Cox regression analysis was used for a multivariate analysis of risk factors. Results: Of the 142 cases registered, five differed from PCNSL pathologically, three receiving BSC were excluded, 31 were treated without biopsy, three were treated based on CSF-findings, and 100 were treated with biopsy. Total 134 cases were followed. The median age was 76 years, pretreatment KPS was 50%, and 118 cases(88%) had 217 pretreatment complications. The treatment contents consisted of various combinations depending on the attending physician. The retrospective overall PFS was 16 months and OS was 24 months. In the early treatment phase, out of 16 cases with dropout, four tumor and four complication deaths occurred. There were 77 deaths(58%), 39 internal tumor deaths(51%), and 33 complication deaths(43%). Poor prognostic risk factors were <60% posttreatment KPS, complications involving pretreatment cardiovascular and central nervous system disease, posttreatment pneumonia or severe infection, and absence of radiation or chemotherapy. Conclusions: Pretreatment KPS did not affect poor outcomes, but posttreatment KPS <60% and pre- and posttreatment complications did. Radiotherapy and chemotherapy are reportedly effective, but additional research to clarify the details of these modalities is needed.

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Thymidine phosphorylase expression in metastatic kidney cancer as a potential predictor of outcome in patients treated with sunitinib.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15091 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15091-e15091

Author(s):

Manuela Miscoria ◽

Carla Di Loreto ◽

Fabio Puglisi ◽

Paul Gerard Murray ◽

Laura Deroma ◽

...

Keyword(s):

Multivariate Analysis ◽

Thymidine Phosphorylase ◽

Cox Regression ◽

Univariate Analysis ◽

Objective Response ◽

Nucleotide Metabolism ◽

Rank Test ◽

Pyrimidine Nucleotide ◽

Thymidine Phosphorylase Expression

e15091 Background: Aberrant tumour angiogenesis is a hallmark of Renal Cell Carcinoma (RCC). Sunitinib is a small molecule targeting angiogenesis licensed for advanced RCC (aRCC) treatment. Thymidine Phosphorylase (TP) is an enzyme involved in pyrimidine nucleotide metabolism with a role in angiogenesis upregulation in cancer. In RCC, TP expression is associated with poor prognosis. We studied TP immunohistochemical expression in RCC samples and its association with the outcomes in a cohort of aRCC patients treated with sunitinib. Methods: We identified 59 consecutive patients with aRCC treated with sunitinib at our Institution. Nuclear (N) and cytoplasm (C) scoring for TP, using the validated Tsuda scoring, was performed. TP expression and clinico-pathological variables were studied to assess their association with the outcome of S therapy. The log rank test has been used for the univariate analysis and the Cox regression for the multivariate analysis. Results: Thirty-four patients received sunitinib as first line treatment. Fifty patients (84%) had clear cell RCC, 7 (12%) showed sarcomatoid features. Forty-five patients (76%) achieved either an objective response or stable disease. At the time of the analysis 32 patients had died, 46 had progressed and 41 had stopped the treatment. After an average follow up of 21 months, median OS and PFS were 21.2, 12.8 months respectively. N TP staining was positive in 19 patients (32%) and C staining in 36 (61%) patients. A significant association was observed between the N and C expression (p=0.004). The univariate analysis identified an association between N TP expression and longer OS (29.8 vs 17.8 months; p=0.0463) even if the association was not significant in the multivariate analysis (HR=0.56; CI 0.19-1.6). No associations were noted with PFS. Conclusions: In our study TP was overexpressed in a significant percentage of kidney cancers. In patients treated with sunitinib, N TP expression was associated with better OS. The results of the multivariate analysis were probably affected by the limited sample size. Larger and prospective studies are necessary to define the role of TP in RCC.

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A large multicenter study evaluating prognosis and chemosensitivity of metastatic colorectal cancers with microsatellite instability.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.3536 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 3536-3536 ◽

Cited By ~ 4

Author(s):

David Tougeron ◽

Benjamin Sueur ◽

David Sefrioui ◽

Lucie Gentilhomme ◽

Thierry Lecomte ◽

...

Keyword(s):

Multivariate Analysis ◽

Cox Regression ◽

Univariate Analysis ◽

Objective Response ◽

Prospective Trial ◽

Prognostic Index ◽

Rank Test ◽

Colorectal Cancers ◽

First Line ◽

Peritoneal Carcinosis

3536 Background: Deficient Mismatch Repair (dMMR) in colorectal cancers (CRC) represent 12% of all tumors. In non-metastatic CRC setting, dMMR are associated with good prognosis but also with resistance to adjuvant 5-FU chemotherapy. In metastatic CRC (mCRC) setting, dMMR is found in less than 5% and its influence on prognosis and treatment response is little known. Methods: This multicenter retrospective study included all consecutive patients with dMMR mCRC treated between 2005 and 2015 in 17 centers. The Kaplan-Meier method was used to calculate overall survival (OS) and progression-free survival (PFS). Prognostic variables were evaluated in univariate analysis using the Log rank test and in multivariate analysis using the Cox regression model. Results: A total of 198 patients with dMMR mCRC were included (median age 64.6 years). dMMR mCRC were mostly diagnosed with synchronous metastases (59%) and frequent peritoneal carcinosis (43%). Lynch syndrome was found in 34% of cases and 36% of tumors had a BRAFV600E mutation. Median OS was 20.6 months. A low risk Kohne's prognostic index (HR = 0.40 [0.22-0.72], p = 0.02) and absence of peritoneal carcinosis (HR = 0.51 [0.29-0.90], p = 0.02) were associated with better OS in multivariate analysis. Main first-line regimens were 5FU-based (n = 20), oxaliplatin-based (n = 75) or irinotecan-based (n = 46) chemotherapy. Median PFS on first-line treatment was 5.9 months. The objective response rate (ORR) was 0%, 19% and 36% for 5FU-based, oxaliplatin-based and irinotecan-based chemotherapies, respectively (p = 0.02). A trend for a longer PFS (3.3, 5.5 and 10.2 months, respectively, p = 0.06) and OS (17.7, 21.1 and 34.2 months, respectively, p = 0.05) was also observed for irinotecan-based chemotherapy. The addition of bevacizumab to chemotherapy was associated with a significant increase of ORR (p = 0.01) and PFS (p = 0.04) as compared to the addition of an anti-EGFR therapy. Conclusions: This study suggests that dMMR mCRC are associated with poor prognosis and chemoresistance, especially to 5FU-based chemotherapy. Efficacy of irinotecan and bevacizumab should be evaluated in a prospective trial in combination with immune checkpoint inhibitors.

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Genetic profile of polyps and risk of advanced metachronous lesions.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.555 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 555-555

Author(s):

Oscar Murcia ◽

Miriam Juárez ◽

Maria Rodriguez-Soler ◽

Eva Hernández-Illán ◽

Cecilia Egoavil ◽

...

Keyword(s):

Logistic Regression ◽

Multivariate Analysis ◽

Cox Regression ◽

Univariate Analysis ◽

Colonic Polyps ◽

Rank Test ◽

Genetic Profile ◽

Braf Mutations ◽

Allelic Discrimination ◽

Kras Mutations

555 Background: The role of genetic profile of polyps to predict advanced metachronous lesions (AML) remains unknown. The aim is to study the relation between genetic profile of polyps and both risk of AMLs and time to develop them in surveillance. Methods: 308 patients with colonic polyps were consecutively enrolled between 2007 and 2009 for this cohort study, and followed up to 2014 (median 26 months, range 63). Variables as age, sex, smoking, weight, number of colonoscopies and number and characteristics of polyps were collected. 995 polyps were analyzed for somatic mutations on BRAF and KRAS genes using allelic discrimination by real-time PCR and direct DNA sequenciation, respectively. High level of methylation on CpG islands (CIMP-H) was also tested using MS-MLPA. AML was defined by a size higher than 9mm, high grade dysplasia or villous component. Risk of developing AML for individual genetic markers was studied using Chi-square tests and logistic regression. Log-rank test with Kaplan Meier survival curves and Cox-regression model were also performed. Multivariate analysis were adjusted by sex, age, familial colorectal cancer, smoking and features of AML in first colonoscopy. Results: 21% of polyps in first colonoscopy were CIMP-H. KRAS and BRAF mutations accounted for 25% and 17% of polyps, respectively. In univariate analysis, KRAS-mutated polyps were related to higher risk of AML in surveillance (52% KRAS-mutated polyps vs 31% non-mutated; p = 0.01). Similar results were obtained regarding CIMP-H (77% CIMP-H polyps vs 38% non-CIMP; p = 0.005). Logistic regression showed CIMP-H as the unique genetic marker of risk for AML (OR 11.41, 95% CI 2.04-63.70; p = 0.006). Regarding time to develop AML, shorter intervals were found related to CIMP-H (median of 31 vs 48 months in non-CIMP-H; p = 0.002) and KRAS-mutations (median of 36 vs 49 months in non-mutated; p = 0.029) in univariate analysis. Multivariate analysis highlighted CIMP-H as the unique independent marker associated to shorter time to develop AML (HR 4.01, 95% CI 1.36-10.46; p = 0.01). Conclusions: Presence of CIMP-H in polyps associates higher risk of subsequent AML and shorter interval to their development. Genetic profile of polyps emerges as useful tool for colonoscopy surveillance.

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