Both age and location predict survival in childhood ependymoma: A SEER study

9545 Background: Supratentorial (SUP) ependymoma in childhood has been reported in studies with limited samples to carry improved overall survival (OS) compared to infratentorial (INF) tumors, with spinal (SPI) ependymoma having the best outcome. Moreover, radiation therapy (XRT) for INF tumors has been considered standard of care, though there have been case reports of children treated successfully without XRT. Thus, we aimed to examine how age, gender, location, XRT and race influence OS in childhood ependymoma by rigorous analysis of a large registry. Methods: We queried the Surveillance Epidemiology End Results (SEER) registry from 1973 to 2003, strictly defining ependymomas by histology (ICD-O-3: 9391–9394). ICD-0–2 site codes, when available, were used to distinguish SUP, INF, and SPI tumors. OS was compared by age, gender, race, location, and XRT, using Kaplan-Meier analysis with logrank tests in SPSS 12.0 (Chicago, IL). Cox regression incorporated all significant covariates from univariate analysis. A similar analysis was conducted to determine whether findings differed in adults. Results: 635 children <18 years at diagnosis were identified (265 females; 510 whites, 77 blacks; 106 SUP, 193 INF, 55 SPI) with 5-year OS 57.1% ± standard error 2.3%. With univariate analysis, OS did not differ by gender or race. For location, 5-year OS did not differ between SUP 59.5% ± 5.4% and INF 57.1% ± 4.1%, but was significantly better for SPI 86.7% ± 5.2%. With multivariate analysis, location and age remained significant predictors for OS, with younger children having worse outcome. A similar multivariate analysis in 1388 adults again showed age and location to be significant. Adults fared better than children (logrank p <0.0001). XRT of INF tumors was associated with significantly improved OS in children (logrank p <0.018), but did not lead to an OS difference among adults. Conclusions: Age and location directly influence OS in childhood ependymoma. SPI tumors are associated with a significantly better prognosis than other ependymomas. This study could not show a difference in OS between SUP and INF tumors, proposed recently to have different stem cell origins. SPI tumors may represent a distinct biological entity. Curiously, XRT is associated with improved OS in pediatric, but not adult, INF ependymomas. No significant financial relationships to disclose.

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Immunoscore Combining CD8, FoxP3 and CD68 Expression and Distribution Predicts the Prognosis of Head and Neck Cancer Patients

10.21203/rs.3.rs-176581/v1 ◽

2021 ◽

Author(s):

Sonia Furgiuele ◽

Géraldine Descamps ◽

Jérôme R. Lechien ◽

Didier Dequanter ◽

Fabrice Journe ◽

...

Keyword(s):

Multivariate Analysis ◽

Head And Neck Cancer ◽

Head And Neck ◽

Cancer Patients ◽

Neck Cancer ◽

Immune Cell ◽

Cox Regression ◽

Histological Grade ◽

Univariate Analysis ◽

Kaplan Meier

Abstract Purpose: The objective of this study was to assess immune cell infiltrates to develop an immunoscore for prognosis and to investigate its correlation with clinical data of patients with head and neck squamous cell carcinomaMethods: CD8, FoxP3 and CD68 were evaluated by immunohistochemistry in 258 carcinoma samples and counted in stromal and intra-tumoral compartments. Optimal cut-offs were assessed to divide population regarding to survival while the prognostic value was established by using Kaplan-Meier curves and Cox regression models for each immune marker alone and in combination.Results: We found with univariate analysis that infiltration of immune cells in both compartments was predictive for RFS and OS. Multivariate analysis revealed that CD8+ number influenced independently patient prognosis. Additionally, the combination of CD8, FoxP3 and CD68 in an immunoscore provided a significant association with OS (p=0.002, HR=9.87). Such immunoscore stayed significant (p=0.018, HR=11.17) in a multivariate analysis in comparison to tumour stage and histological grade which had lower prognostic values.Conclusion: Altogether, our analysis indicated that an immunoscore including CD8, FoxP3 and CD68 immunostaining was a strong, independent, and significant prognostic marker which could be introduced into the landscape of current tools to improve the clinical management of head and neck cancer patients.

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Natural history definition and a suggested clinical approach to Buerger's disease: a case-control study with survival analysis

Vascular ◽

10.1258/vasc.2011.oa0323 ◽

2012 ◽

Vol 20 (4) ◽

pp. 198-202 ◽

Cited By ~ 6

Author(s):

Bahare Fazeli ◽

Hassan Ravari ◽

Reza Assadi

Keyword(s):

Multivariate Analysis ◽

Natural History ◽

Cox Regression ◽

Major Amputation ◽

Clinical Approach ◽

Buerger’S Disease ◽

Buerger's Disease ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

History Of

The aim of this study was first to describe the natural history of Buerger's disease (BD) and then to discuss a clinical approach to this disease based on multivariate analysis. One hundred eight patients who corresponded with Shionoya's criteria were selected from 2000 to 2007 for this study. Major amputation was considered the ultimate adverse event. Survival analyses were performed by Kaplan–Meier curves. Independent variables including gender, duration of smoking, number of cigarettes smoked per day, minor amputation events and type of treatments, were determined by multivariate Cox regression analysis. The recorded data demonstrated that BD may present in four forms, including relapsing-remitting (75%), secondary progressive (4.6%), primary progressive (14.2%) and benign BD (6.2%). Most of the amputations occurred due to relapses within the six years after diagnosis of BD. In multivariate analysis, duration of smoking of more than 20 years had a significant relationship with further major amputation among patients with BD. Smoking cessation programs with experienced psychotherapists are strongly recommended for those areas in which Buerger's disease is common. Patients who have smoked for more than 20 years should be encouraged to quit smoking, but should also be recommended for more advanced treatment for limb salvage.

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Prognostic Factors Associated with Outcomes in Small Bowel Neuroendocrine Tumors

The American Surgeon ◽

10.1177/000313481708301033 ◽

2017 ◽

Vol 83 (10) ◽

pp. 1174-1178 ◽

Cited By ~ 1

Author(s):

Nicholas Manguso ◽

Jeffrey Johnson ◽

Attiya Harit ◽

Nicholas Nissen ◽

James Mirocha ◽

...

Keyword(s):

Small Bowel ◽

Neuroendocrine Tumors ◽

Cox Regression ◽

Univariate Analysis ◽

Disease Free Survival ◽

Nodal Metastasis ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Open Operation ◽

Recurrence Group

Small bowel neuroendocrine tumors (SBNET) account for most gastrointestinal neuroendocrine tumors. Patients often present with late-stage disease; however, there is little information regarding factors that contribute to recurrence. Database review identified 301 patients diagnosed with SBNET between 1990 and 2013. Univariate analysis included patients who underwent complete resection. Survival was estimated by the Kaplan–Meier method. A total of 147 patients met study criteria. Average age was 60 years (range 21–91); 49 per cent were male. Thirty-seven (25.3%) patients had laparoscopic resection, and 29 (19.9%) patients had only small bowel disease, whereas 108 (72.6%) had nodal metastasis. Five-year overall and disease-free survival were 97.5 and 73.5 per cent. Forty-seven (32%) patients had recurrence. The recurrence group was more likely to have an open operation (59.6 vs 32%, P < 0.01), mesenteric invasion, or lymphatic metastasis (87.2 vs 67%, P < 0.01) compared with the no-recurrence group. Cox regression analysis showed that variables associated with recurrence included nodal disease (HR 9.06, P = 0.03), lymphovascular invasion (LVI) (3.95, P < 0.01), perineural invasion (PNI) (3.48, P < 0.01), and mesenteric involvement (3.77, P = 0.03). Patients with SBNET presenting with nodal metastasis, mesenteric involvement, LVI, or PNI have a higher risk of recurrence. Closer surveillance should be considered after operative resection.

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Renal Remission Status and Longterm Renal Survival in Patients with Lupus Nephritis: A Retrospective Cohort Analysis

The Journal of Rheumatology ◽

10.3899/jrheum.161554 ◽

2018 ◽

Vol 45 (5) ◽

pp. 671-677 ◽

Cited By ~ 16

Author(s):

Julie E. Davidson ◽

Qinggong Fu ◽

Beulah Ji ◽

Sapna Rao ◽

David Roth ◽

...

Keyword(s):

Lupus Nephritis ◽

Cox Regression ◽

Cohort Analysis ◽

Standard Of Care ◽

Renal Survival ◽

Endstage Renal Disease ◽

American College Of Rheumatology ◽

Remission Status ◽

Kaplan Meier ◽

Remission Criteria

Objective.This observational study was a retrospective analysis of prospectively collected Hopkins Lupus Cohort data to compare longterm renal survival in patients with lupus nephritis (LN) who achieved complete (CR), partial (PR), or no remission following standard-of-care LN induction therapy.Methods.Eligible patients with biopsy-proven LN (revised American College of Rheumatology or Systemic Lupus Collaborating Clinics criteria) were identified and categorized into ordinal (CR, PR, or no remission) or binary (response or no response) renal remission categories at 24 months post-diagnosis [modified Aspreva Lupus Management Study (mALMS) and modified Belimumab International Lupus Nephritis Study (mBLISS-LN) criteria]. The primary endpoint was longterm renal survival [without endstage renal disease (ESRD) or death].Results.In total, 176 patients met the inclusion criteria. At Month 24 postbiopsy, more patients met mALMS remission criteria (CR = 59.1%, PR = 30.1%) than mBLISS-LN criteria (CR = 40.9%, PR = 16.5%). During subsequent followup, 18 patients developed ESRD or died. Kaplan–Meier plots suggested patients with no remission at Month 24 were more likely than those with PR or CR to develop the outcome using either mALMS (p = 0.0038) and mBLISS-LN (p = 0.0097) criteria for remission. Based on Cox regression models adjusted for key confounders, those in CR according to the mBLISS-LN (HR 0.254, 95% CI 0.082–0.787; p = 0.0176) and mALMS criteria (HR 0.228, 95% CI 0.063–0.828; p = 0.0246) were significantly less likely to experience ESRD/mortality than those not in remission.Conclusion.Renal remission status at 24 months following LN diagnosis is a significant predictor of longterm renal survival, and a clinically relevant endpoint.

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A New Cytokine-Based Stratification Is Highly Predictive of Survivals in AML Patients

Blood ◽

10.1182/blood-2019-125774 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1412-1412

Author(s):

Pierre Peterlin ◽

Joelle Gaschet ◽

Thierry Guillaume ◽

Alice Garnier ◽

Marion Eveillard ◽

...

Keyword(s):

Multivariate Analysis ◽

Risk Stratification ◽

Univariate Analysis ◽

Standard Of Care ◽

Healthy Controls ◽

First Line ◽

Serum Samples ◽

Gm Csf ◽

Significant Difference ◽

The Impact

Introduction: Recently, a significant impact of the kinetics of Fms-like tyrosine kinase 3 ligand concentration (FLc) during induction (day[D]1 to D22) has been reported on survivals in first-line acute myeloid leukemia (AML) patients (pts) (Peterlin et al, 2019). Three different FLc profiles were disclosed i) sustained increase of FLc (FLI group, good-risk), ii) increase from D1 to D15, then decrease at D22 (FLD group, intermediate-risk) and iii) stagnation of low levels (<1000 pg/mL, FLL group, high-risk). An update of this prospective monocentric study (www.ClinicalTrials.gov NCT02693899) is presented here evaluating also retrospectively the impact on outcomes of 6 other cytokine level profiles during induction. Methods: Between 05/2016 and 01/2018, 62 AML pts at diagnosis (median age 59 yo [29-71], <60 yo n=33) eligible for first intensive induction were included and provided informed consent. They received standard of care first-line chemotherapy. Serum samples collected on D1, 8, 15 & 22 of induction were frozen-stored until performing ELISA for FL, TNFa, SCF, IL-1b, IL-6, IL-10, GM-CSF. Normal values were assessed in 5 healthy controls. Pts outcomes considered were relapse/leukemia-free (LFS) and overall (OS) survivals. Results: FLI, FLD and FLL profiles were observed for 26, 22 and 14 pts respectively. A total of 372 samples were assayed for the 6 other cytokines. Median concentrations at D1, D8, D15, D22 for these 6 cytokines were as follows, considering the whole cohort (and healthy donors): TNFa: 0.53, 0, 0, 0 (0); SCF: 5.91, 0, 0, 0 (3); IL-1b : 0, 0, 0, 0 (0); IL-6: 4.85, 16.28, 10.11, 7.1 (0), IL-10: 0, 0, 0, 0 (0) and GM-CSF:1.63, 1.8, 0.67, 1.34 (9.98). Median IL-6 and GM-CSF levels, compared to healthy controls, were respectively higher and lower during induction. No significant difference was observed in terms of median cytokine concentrations at any time when comparing the three FL sub-groups or FLI vs FLD pts. With a median follow-up of 28 months (range: 17-37), FLI and FLD pts show now similar 2-y LFS (62.9% vs 59%, p=0.63) and OS (69.2% vs 63.6%, p=0.70). FLL pts have a significantly higher rate of relapse (85,7% vs FLI 19,2% vs FLD 32%, p=0,0001). Comparing FLL vs FLI+FLD pts disclosed significantly different LFS (7.1% vs 61.1%, p<0.001) but not OS (36.7% vs 66.6%, p=0.11). In univariate analysis, 2y LFS and OS were not affected by the concentration (< or > median) of the 7 cytokines studied except for LFS and GM-CSFc at D8 (p=0,04) and D15 (p=0,08), for LFS and FLc at D1 (p=0.06), D8 (p=0,03), D15 (p=0,04) and D22 (p=0,03) and for OS and GM-CSF at D15 (p=0.08). A significant association between LFS was observed with ELN 2017 risk stratification (2-y LFS: favorable: 68,1% vs intermediate: 48,1% vs unfavorable: 30,7%, p=0.03) but not OS (2 y: 77% vs 55,5% vs 46,1%, p=0.09). Multivariate analysis showed that no factor was independently associated with OS while LFS remained significantly associated with the FLc profile (FLL vs others, HR: 5.79. 95%CI: 2.48-13.53, p<0.0001) and GM-CSF at D15 (HR: 0.45; 95%CI: 0.20-0.98, p=0.04) but not with ELN 2017 risk stratification (p=0.06). Cytokine levels were then assessed to try to better discriminate FLI and FLD pts. A significant higher IL-6 level at D22 was found in relapsed or deceased FLI/FLD pts (median:15,34 vs 5,42 pg/mL, p=0,04). FLI/FLD pts with low IL-6 at D22 (< median, 15.5 pg/mL, n=35 vs n=14 with high level) had significant better 2y LFS and OS (74,2% vs 38,4%, p=0,005 and 77,1% vs 38,4%, p=0,009, respectively). A new prognostic risk-stratification could thus be proposed, i.e. FLI/FLD with IL-6 <15.5 pg/mL (favorable), FLI/FLD with IL-6 >15.5 pg/mL (intermediate) and FLL (unfavorable). This new classification was considered for a second multivariate analysis, showing that it is the strongest factor associated with OS (p=0.006, ELN p=0.03, FL profile p=0.04) and LFS (p<0.0001, ELN p=0.005, GM-CSFc D15 p=0.03) (figure 1). Conclusion: This study confirms stagnation of low FLc during AML induction as a strong poor prognosis factor. Moreover, IL-6 levels at D22 further discriminate FLI/FLD pts. Thus, a new cytokine-based risk-stratification integrating FL kinetics and IL-6 levels during induction may help to better predict outcomes in first-line AML patients. These results need to be validated on a larger cohort of AML patients while anti-IL-6 therapy should be tested in combination with standard 3+7 chemotherapy. Figure 1 Disclosures Peterlin: AbbVie Inc: Consultancy; Jazz Pharma: Consultancy; Daiichi-Sankyo: Consultancy; Astellas: Consultancy. Moreau:Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Chevallier:Jazz Pharmaceuticals: Honoraria; Incyte: Consultancy, Honoraria; Daiichi Sankyo: Honoraria.

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Complete Remissions (CRs) with Azacitidine Regimens Compared to Crs with 7+3 Induction Chemotherapy and the Effect on Overall Survival

Blood ◽

10.1182/blood.v128.22.1613.1613 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1613-1613 ◽

Cited By ~ 2

Author(s):

Megan Othus ◽

Mikkael A Sekeres ◽

Sucha Nand ◽

Guillermo Garcia-Manero ◽

Frederick R. Appelbaum ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Research Funding ◽

Cox Regression ◽

Intensive Therapy ◽

Univariate Analysis ◽

Multivariable Analysis ◽

Curative Intent ◽

Kaplan Meier ◽

The Impact

Abstract Background: CR and CR with incomplete count recovery (CRi) are associated with prolonged overall survival (OS) for acute myeloid leukemia (AML) patients (pts) treated with curative-intent, induction therapy. For AML pts treated with azacitidine (AZA), response (CR, partial response, marrow CR, or hematologic improvement) is also associated with prolonged OS. We evaluate whether patients given AZA for myelodysplastic syndromes (MDS) or AML had longer OS if they achieved CR. We also compare the effect size of CR on OS between AZA regimens and 7+3. Patients and Methods: We analyzed four SWOG studies: S1117 (n=277) was a randomized Phase II study comparing AZA to AZA+lenalidomide or AZA+vorinostat for higher-risk MDS and CMML pts (median age 70 years, range 28-93); S0703 (n=133) treated AML pts not eligible for curative-intent therapy with AZA+mylotarg (median age 73 years, range 60-88). We analyzed the 7+3 arms of S0106 (n=301 were randomized to 7+3, median age 48 years, range 18-60) and S1203 (n=261 were randomized to 7+3, median age 48 years, range 19-60). CR was defined per 2003 International Working Group criteria. In S1117 CR was assessed every 16 weeks and patients remained on therapy until disease progression. In S0703, S0106, and S1203 CR was assessed following 1-2 induction cycles; patients not achieving CR (S0106) or CRi (S0703 and S1203) were removed from protocol treatment. OS was measured from date of study registration. To avoid survival by response bias, we performed landmark analyses of OS. We present results based on the study-specific landmark date that 75% of pts who eventually achieved a CR had done so (S1117 144 days, S0703 42 days, S0106 44 days, S1203 34 days). Pts who did not achieve CR by this date were analyzed with pts who never achieved CR. Pts who died or were lost to follow-up before this date were excluded from analyses. As a sensitivity analysis we also analyzed based on the 90% date; results were not materially different. Log-rank tests were used to compare survival curves and Cox regression models were used for multivariable modeling including baseline prognostic factors age, sex, performance status, white blood cell count, platelet count, marrow blast percentage, de novo disease (versus antecedent MDS or therapy-related disease), study arm (for S1117 only), and cytogenetic risk (IPSS criteria for S1117, SWOG criteria for S0703, S0106, and S1203). The following analysis considers morphologic CR only. S0106 treated CR with incomplete count recover (CRi) pts as treatment failures (S0703 and S1203 did not) and CRi was not defined for S1117. Hematologic improvement was only defined for S1117 patients. Results: In univariate analysis, CR was significantly associated with prolonged survival among MDS pts treated with azactidine on S1117 (HR=0.55, p=0.017), confirming the results seen in AML pts treated with azacitidine (and mylotarg, S0703, HR=0.60, p=0.054) and 7+3 (S0106 HR=0.44, p<0.001; S1203 HR=0.32, p<0.0001) (Figure 1). For each study this relationship remained significant in multivariable analysis controlling for baseline prognostic factors (S1117 HR=0.25, p<0.001; S0703 HR=0.64, p=0.049; S0106 HR=0.45, p<0.001; S1203 HR=0.41, p<0.001). There was no evidence that the impact of CR varied across the four cohorts (interaction p-value = 0.76). In the full cohort, the effect of CR was associated with a HR of 0.45 (Table 1). Conclusion: Adjusting for pt characteristics, achievement of morphologic CR was associated with a 60% improvement in OS, on average, compared to that seen in pts who don't achieve a CR, regardless of whether pts were treated with 7+3 or AZA containing regimens, and suggesting that value CR is similar of whether pts receive more or less "intensive" therapy for these high grade neoplasms. Support: NIH/NCI grants CA180888 and CA180819 Acknowledgment: The authors wish to gratefully acknowledge the important contributions of the late Dr. Stephen H. Petersdorf to SWOG and to study S0106. Figure 1 Kaplan-Meier plots of landmark survival by response. Figure 1. Kaplan-Meier plots of landmark survival by response. Table 1 Multivariable analysis, N=878 Table 1. Multivariable analysis, N=878 Disclosures Othus: Glycomimetics: Consultancy; Celgene: Consultancy. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees. Erba:Millennium Pharmaceuticals, Inc.: Research Funding; Amgen: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Agios: Research Funding; Gylcomimetics: Other: DSMB; Juno: Research Funding; Daiichi Sankyo: Consultancy; Sunesis: Consultancy; Pfizer: Consultancy; Ariad: Consultancy; Jannsen: Consultancy, Research Funding; Incyte: Consultancy, DSMB, Speakers Bureau; Celator: Research Funding; Astellas: Research Funding; Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau.

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Preoperative uracil/tegafur and concomitant radiotherapy in locally advanced rectal (LAR) cancer: Updated results with a median follow-up of 5 years and analysis of prognostic factors (PF)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.3573 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 3573-3573 ◽

Cited By ~ 1

Author(s):

C. Fernandez-Martos ◽

I. Romero ◽

J. Aparicio ◽

C. Bosch ◽

R. Girones ◽

...

Keyword(s):

Multivariate Analysis ◽

Residual Disease ◽

Statistical Significance ◽

Univariate Analysis ◽

Locally Advanced ◽

Standard Of Care ◽

Complete Information ◽

Risk Groups ◽

Attractive Alternative

3573 Background: Preop chemoradiotherapy (CRT) with CI 5-FU is a standard of care for LAR cancer. Oral fluoropyrimidines, an attractive alternative to intravenous 5-FU, are perceived by patients as more convenient. Methods: We performed a phase II study in patients with potentially resectable tumors, localized in middle or distal rectum, ultrasonographically staged as T3 or T4 or N+ who were treated with UFT (400 mg/m2/d, 5 days a week for 5 weeks) and concomitant RT to the pelvis (45 Gy; 1.8 Gy/d over 5 weeks). Pts underwent surgery 5 to 6 weeks later followed by four cycles of 5-FU/LV (Mayo Clinic Scheme). Early end points of efficacy (pCR, downstaging, sphincter preserving surgery) and toxicity have already been reported (JCO 2004;22:3016). We now present data on secondary objectives (RFS, DFS and OS) and univariate and multivariate analysis of clinical and pathological PF. Results: 94 patients were included and complete information on 88 (94%) is availablewith a median follow-up of 5 years (60.4 months). Actuarial Kaplan-Meier DFS, RFS and OS are 61%, 66%, and 70 %. Patterns of failure are 7% pelvic and 25% distant. Univariate analysis results are shown in the table . Survival rate was also higher among patients with no or few residual disease after CRT but did not reach statistical significance. In Cox multivariate analysis both ypT and ypN are independent PF for DFS and RFS but only ypT is an independent PF for OS. Conclusions: This approach with preop UFT/RT reproduces the results that have been accomplished with 5-FU. ypT and ypN could be helpful to identify different risk groups and to select adjuvant treatments. [Table: see text] No significant financial relationships to disclose.

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The prognostic value of serum IL-6 and YKL-40 in colorectal cancer patients before liver resection.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15078 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15078-e15078

Author(s):

Mathias Holsey Gramkow ◽

Reetta Peltonen ◽

Christian Dehlendorff ◽

Pia J. Osterlund ◽

Julia S. Johansen ◽

...

Keyword(s):

Colorectal Cancer ◽

Multivariate Analysis ◽

Liver Resection ◽

Cox Regression ◽

Univariate Analysis ◽

Elevated Serum ◽

Disease Free Survival ◽

Markers Of Inflammation ◽

Preoperative Serum ◽

Serum Cea

e15078 Background: IL-6 and YKL-40, markers of inflammation and cancer growth, are high in serum in patients with colorectal cancer (CRC) and associated with shorter overall survival (OS). We hypothesized that preoperative serum IL-6, YKL-40 and CEA are associated with disease free survival (DFS) and OS in patients with metastatic (mCRC) treated with liver resection. Methods: 457 patients (male/female: 267 (58%)/190 (42%), median age 65 [IQR: 58-71]) diagnosed with mCRC who underwent liver resection were included between March 1998 and February 2013. Preoperative serum samples were collected and stored at -80°C until analysis. Serum IL-6 (R&D Systems, UK) and YKL-40 (Quidel, USA) were determined by ELISA. For DFS and OS we estimated crude and adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CIs) with Cox regression for each biomarker separately. The biomarkers were included as log2-transformed continuous variables and adjustment included mutual adjustment between the biomarkers in addition to adjusting for sex and age. Results: The median (IQR) preoperative biomarker levels were: IL-6 (3.5 pg/ml, 2.1-6.1), YKL-40 (75 ng/ml, 48-127) and CEA (5.2 kU/L, 2.6-18.8). Univariate analysis showed that high serum IL-6 and YKL-40 were associated with shorter DFS (IL-6: HR = 1.18, 1.06-1.31, p < 0.01; YKL-40: HR = 1.19, 1.08-1.32, p < 0.01). Serum CEA was not (p = 0.80). Multivariate analysis (all biomarkers) showed that high IL-6 was associated with shorter DFS (HR = 1.15, 1.02-1.29, p = 0.02), whereas YKL-40 (p = 0.08) and CEA (p = 0.51) were not. Univariate analysis showed that high preoperative serum IL-6 and YKL-40 were associated with shorter OS (IL-6: HR = 1.16, 1.03-1.29, p = 0.01; YKL-40: HR = 1.27, 1.14-1.42, p < 0.01). Serum CEA was not associated with OS (p = 0.16). Multivariate analysis (all biomarkers) showed that high YKL-40 was associated with shorter OS (HR = 1.19, 1.05-1.34, p = 0.01), whereas IL-6 (p = 0.25) and CEA (p = 0.26) were not. Patients with elevated serum levels of all 3 biomarkers had the shortest OS (HR = 2.12; 1.29-3.50, p < 0.01). Conclusions: Serum IL-6 and YKL-40 determined before liver resection may be valuable prognostic biomarkers in patients with metastatic CRC.

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Associations between regorafenib-induced adverse events (AEs) and efficacy in metastatic colorectal cancer (mCRC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.556 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 556-556 ◽

Cited By ~ 1

Author(s):

Takeru Wakatsuki ◽

Eiji Shinozaki ◽

Mitsukuni Suenaga ◽

Izuma Nakayama ◽

Tomohiro Matsushima ◽

...

Keyword(s):

Multivariate Analysis ◽

Adverse Events ◽

Univariate Analysis ◽

Rank Test ◽

Multikinase Inhibitor ◽

Log Rank Test ◽

Kaplan Meier ◽

Almost All ◽

Therapy Target

556 Background: It is occasionally recognized that, in molecular targeted therapy, target-specific AEs can surrogate its efficacy, such as skin toxicities and anti-EGFR antibodies. Because of multikinase inhibitor, regorafenib is involved in various kinds of adverse events; however, the clinical associations between AEs and efficacy remain unclear. The aim of this study is to reveal what AEs could surrogate efficacy of regorafenib. Methods: AEs were graded according to CTCAE ver. 4.0. We defined as “CRP increased”, if CRP increased more than 5 mg/dl during treatment compared with the baseline level. Time to treatment failure (TTF) and overall survival (OS) were estimated using Kaplan-Meier methods and compared by the log-rank test. Covariates which were significant in univariate analysis were included in multivariate analysis. Results: One-hundred and two patients were enrolled in this study. Almost all patients were PS 0-1 and received 160mg of regorafenib as an initial dose. The median TTF and the median OS were 2.0 and 8.0 months, respectively. Major AEs were Hand-foot skin reaction (HFSR) in 82.4% (≥Gr3:38.2%), Hypertension (HT) in 39.2% (16.7%), Rash in 23.5% (8.8%), Blood bilirubin increased (BBI) in 58.8% (2.9%), Thrombocytopenia in 48.0% (3.9%), Neutropenia in 20.5% (0%), and CRP increased in 46.1%. Regarding TTF, in univariate analysis, BBI, AST increased Gr0-1, neutropenia, absence of CRP increased, Diarrhea, HFSR, and Rash Gr0-2 were associated with longer TTF. In multivariate analysis, HFSR (HR 0.34 95%CI 0.19-0.63, p = 0.001) and Rash ≥Gr3 (HR 2.43 95%CI 1.13-5.21, p = 0.023) retained to be significant. With respect to OS, in univariate analysis, AST increased Gr0-1, ALT increased Gr0-1, neutropenia, absence of CRP increased, HFSR, and Rash Gr0-2 were associated with longer OS. In multivariate analysis, HFSR (HR 0.47 95%CI 0.24-0.91, p = 0.026), neutropenia (HR 0.54 95%CI 0.30-0.95, p = 0.032) and AST ≥Gr2 (HR 5.72 95%CI 2.11-15.63, p = 0.023) retained to be significant. Conclusions: HFSR and neutropenia might surrogate regorafenib efficacy in mCRC. Elucidation of the mechanisms of these AEs may help to understand which the pathway is the key role of regorafenib treatment in mCRC.

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Charlson Score as prognostic factor in patients with castration-resistant prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.242 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 242-242 ◽

Cited By ~ 1

Author(s):

Gustavo Jankilevich ◽

Luciana Gennari ◽

Matias Salazar ◽

Claudio Graziano ◽

Eduardo Saravia ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Multivariate Analysis ◽

Gleason Score ◽

Cox Regression ◽

Independent Predictor ◽

Performance Status ◽

Univariate Analysis ◽

Castration Resistant Prostate Cancer ◽

Castration Resistance

242 Background: Tumor stage, Gleason score, PSA, Performance Status have been identified as important predictors of survival in prostate cancer. The Charlson Comorbidity Index (CCI) is a validated score used to stratify patients according to comorbidities. To evaluate the prognostic role of CCI in patients with CPRC. Methods: A retrospective study based on an analysis of medical records of 212 patients with CRPC treated at Durand Hospital between 2010-2015. The CCI was calculated for each patient and a correlation with overall survival was performed. Statistical analysis included univariate analysis and multivariate analysis (Cox regression). Patients were stratified according CCI ≤ 7.6 or ≥ 7.6. Survival analysis was performed using the Kaplan-Meier curve. Results: We analyzed records of 212 patients with prostate cancer, of which 59 were resistant to castration. Median age 69 years, the PFS with androgen blockade was 32.4 months. Patients with CPRC 54% perform chemotherapy as first-line treatment of castration resistance and 46% performed treatment of hormonal manipulation (Enzalutamide or Abiraterone Acetate). Median overall survival of patients with CCI < 7.6 was 75 months versus 62 months for those with CCI > 7.6 HR: 1.19 (1.03 to 1.36) p: 0.01. In multivariate analysis the ICC was an independent predictor of mortality in these patients HR: 1.23 (1.03 to 1.48) p: 0.02. (Table 1) CCI ≤ 7,6 was predictor to subsequent lines in CPRC setting. Gleason score, PS were independent predictors of survival. Conclusions: Based on our results we can consider the CCI as an independent predictor of survival in CPRC patients. CCI could be an useful tool useful to select patients in clinical trial and community settings. [Table: see text]

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