Overall Survival P-value Research Articles

S1604 Prognostic Value of Systemic Inflammatory Markers in Gastric MALT Lymphoma

Introduction: Several studies have shown the role of inflammatory markers, especially the neutrophil-to-lymphocyte Ratio (NLR), as indicators of poor prognosis in various gastrointestinal malignancies. We aimed to examine the prognostic value of NLR, among other markers, and their relationship with the presence of baseline distant metastasis in patients with MALT Lymphoma. Methods: We retrospectively reviewed the charts of 139 patients with Gastric MALT Lymphoma treated at a tertiary care cancer center from 2012 to 2018. We examined the relationship between absolute eosinophilic count (AEC), absolute lymphocyte count (ALC), absolute monocytic count (AMC), absolute neutrophil count (ANC), monocyte to lymphocyte ratio (MLR), NLR, and platelet to lymphocyte ratio (PLR) with the presence distant metastases, and overall survival (OS). We used multivariable logistic regression analyses to test the association between the variables and the presence of baseline distant metastases. Results: The median age was 55 years, and males comprised 67.6% of the patients. The ROC value of 3.4 was determined as the cutoff value for NLR. High NLR (NLR > 3.4 µL) was significantly associated with the presence of distant metastasis at diagnosis (P-value, 0.02, Odds Ratio (OR): 2.4, CI: 1.14- 5.10). High ALC ( >1819) was also associated with the presence of baseline distant metastasis (P-value, 0.04, OR: 0.46, CI: 0.22- 0.98). Multivariable analysis showed that high NLR (P-value, 0.02, OR 2.4 95% CI 1.1-5.1) was an independent risk factor for distant metastasis at presentation (Figure). High ANC, NLR, and PLR, were associated with poor OS, (P-value, 0.027, 0.016, and 0.011 respectively). Conclusion: High systemic inflammatory markers are associated with poor prognosis (the presence of distant metastasis) and poor OS in patients with Gastric MALT Lymphoma. To our knowledge, this is the first study examining the association between these inflammatory markers and the presence of distant metastases in MALT Lymphoma. Whether these markers could predict the response to treatment is unknown (Table).Figure 1.: (Top)Kaplan Meier curve for overall survival of patients with ANC (Middle). Kaplan Meier curve for overall survival of patients with NLR (Bottom). Kaplan Meier curve for overall survival of patients with PLR Table 1. - The association between systemic inflammatory markers and overall survival Parameter Median OS P-value Hazard Ratio 95% Confidence Interval ANC >5100 6.4 months 0.027 1.5 1.04–2.1 ANC≤5100 10.9 months ALC >1819 7.6 months 0.19 0.80 0.55–1.1 ALC≤1819 6.7 months AMC > 603 6.3 months 0.66 1.1 0.76–1.6 AMC≤ 603 7.8 months NLR > 2.75 6.2 months 0.016 1.5 1.1–2.2 NLR ≤ 2.75 12.2 months MLR >0.32 6.3 months 0.36 1.2 0.83–1.7 MLR≤0.32 10.5 months PLR >0.16 6.2 months 0.011 1.6 1.1–2.3 PLR≤0.16 10.9 months

Abstract 5269: Imaging the tumor microenvironment in rectal cancer: Decline in tumor blood flow (BF) during neoadjuvant treatment predicts excellent outcome

Abstract Introduction: A watch-and-wait strategy for rectal cancer patients may possibly omit surgery after neoadjuvant treatment. To optimally stratify patients for such strategy, reliable and preferably non-invasive biomarkers that repeatedly can assess neoadjuvant therapy response are needed. Recognizing the importance of the tumor microenvironment, we investigated a less explored imaging marker assessing tumor BF for its potential to predict overall survival (OS). Methods: 24 rectal cancer patients given curative-intent neoadjuvant radiotherapy (RT) underwent a multi-echo dynamic magnetic resonance imaging (MRI) sequence with gadolinium contrast for estimation of tumor BF before either 25x2 Gy (n=18) with concomitant chemotherapy or 5x5 Gy (n=6). 4-7 weeks post-RT the MRI was repeated. Baseline blood samples were analyzed for lactate dehydrogenase (LDH) and angiopoietin-2 (ANGPT-2). Tumor volumes were measured before and after RT. After the subsequent surgery, ypT scoring assessed tumor RT response. Cox regression for OS analysis and t-test for group comparisons were performed. Results: 7 patients were non-survivors and the median follow-up for survivors was 55 months (range, 44-60). The change in tumor BF (ΔBF) during neoadjuvant RT was identified as a significant marker of OS (Table). Tumor stage and volume were not significant. All patients with more than 20% decline in BF were survivors. Separating cases in two groups based on ΔBF revealed that patients with increase or a low decrease had higher baseline levels of LDH (p = 0.032) and ANGPT-2 (p = 0.028). Discussion: MRI-assessed tumor ΔBF during neoadjuvant treatment is a significant predictor of OS in rectal cancer patients, making ΔBF a potential biomarker for treatment stratification in a watch-and-wait strategy. Blood LDH and ANGPT-2 indicate that non-responding tumors may have a hypoxic microenvironment insusceptible to RT. Parameter Hazard ratio for impaired OS p-value Tumor stage 1.08 [0.40-2.95] 0.88 ypT score of the surgical specimen 1.54 [0.76-3.12] 0.23 RT fractionation (25x2 Gy versus 5x5 Gy) 2.24 [0.50-9.90] 0.29 Baseline BF 0.96 [0.92-1.00] 0.05 Post-RT BF 1.02 [1.00-1.04] 0.11 ΔBF 1.03 [1.01-1.05] 0.01 Baseline tumor volume 1.01 [0.99-1.04] 0.43 Post-RT tumor volume 1.01 [0.98-1.05] 0.42 Δtumor volume 1.03 [0.99-1.07] 0.15 Citation Format: Kine M. Bakke, Sebastian Meltzer, Endre Grøvik, Anne Negård, Stein H. Holmedal, Lars G. Lyckander, Arne E. Færden, Atle Bjørnerud, Kjell-Inge Gjesdal, Anne H. Ree, Kathrine R. Redalen. Imaging the tumor microenvironment in rectal cancer: Decline in tumor blood flow (BF) during neoadjuvant treatment predicts excellent outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5269.

High Expression of CLEC11A Predicts Favorable Prognosis in Acute Myeloid Leukemia.

BackgroundAcute myeloid leukemia (AML) is a heterogeneous disease of the hematopoietic system, for which identification of novel molecular markers is potentially important for clinical prognosis and is an urgent need for treatment optimization.MethodsWe selected C-type lectin domain family 11, member A (CLEC11A) for study via several public databases, comparing expression among a variety of tumors and normal samples as well as different organs and tissues. To investigated the relationship between CLEC11A expression and clinical characteristics, we derived an AML cohort from The Cancer Genome Atlas (TCGA); we also investigated the Bloodspot and HemaExplorer databases. The Kaplan-Meier method and log-rank test were used to evaluate the associations between CLEC11A mRNA expression, as well as DNA methylation, and overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). DNA methylation levels of CLEC11A from our own 28 de novo AML patients were assessed and related to chemotherapeutic outcomes. Bioinformatics analysis of CLEC11A was carried out using public databases.ResultsMultiple public databases revealed that CLEC11A expression was higher in leukemia. The TCGA data revealed that high CLEC11A expression was linked with favorable prognosis (OS p-value = 2e-04; EFS p-value = 6e-04), which was validated in GSE6891 (OS p-value = 0; EFS p-value = 0; RFS p-value = 2e-03). Methylation of CLEC11A was negatively associated with CLEC11A expression, and high CLEC11A methylation level group was linked to poorer prognosis (OS p-value = 1e-02; EFS p-value = 2e-02). Meanwhile, CLEC11A hypermethylation was associated with poor induction remission rate and dismal survival. Bioinformatic analysis also showed that CLEC11A was an up-regulated gene in leukemogenesis.ConclusionCLEC11A may be used as a prognostic biomarker, and could do benefit for AML patients by providing precise treatment indications, and its unique gene pattern should aid in further understanding the heterogeneous AML mechanisms.

Leukotriene B4 receptors abnormal gene expression is associated with either shorter or longer survival in breast cancer patients depending on the intrinsic tumour molecular subtype

Abstract Background Leukotrienes receptor signaling is involved in tumor development and progression. Expression of leukotriene B4 receptors 1 and 2 (LTB4R and LTB4R2) promotes cell proliferation, survival, migration and metastasis. Aberrant LTB4R gene expression blocks anti-proliferative responses of TGF-β1 in breast cancer (BC) cell lines. LTB4R2 ectopic expression is associated with increased invasiveness of BC cells. Earlier, we reported LTB4R and LTB4R2 genes abnormal demethylation that is potent of initiating ectopic gene expression in a subset of triple-negative BC (TNBC) samples. Methods We acquired the TCGA BRCA level 3 RNA-seq data and clinical datasheet using TCGA data portal. LTB4R/LTB4R2 gene expression cut-off values were defined using maximally selected rank statistics. Kaplan-Meier overall survival (OS) curves were compared with Mantel-Cox (log-rank) method. Results TNBC exhibit a significantly lower survival probability in LTB4R expressing group. Vice versa, in Normal-Like and LumB subtypes absence of LTB4R and LTB4R2 expression respectively is associated with shorter OS (Table). Table: 57P . Overall survival comparison in various molecular BC subtypes. Asteriks (*) stand for p-value less then 0.05. Median OS are presented in days Expression groups/ Molecular groups No subtyping LumA LumB HER2 TNBC Normal-Like Median OS p-value Median OS p-value Median OS p-value Median OS p-value Median OS p-value Median OS p-value LTB4R = high 3945 0.42 3926 0.81 3941 0.059 6456 0.08 7455 0.0029* 4267 0.0034* LTB4R = low 3736 3873 2483 2127 NA 1688 LTB4R2 = high 3945 0.53 3873 0.51 3941 0.026* 6456 0.59 7455 0.74 4267 0.58 LTB4R2 = low 3472 2965 2573 3063 3472 1759 Conclusions Our findings suggest that LTB4R/LTB4R2 gene expression is a new potential BC prognostic biomarker, yet its use requires proper molecular subtyping of the tumors, as far as prognosis would depend upon the intrinsic tumor subtype. This also applies to the potential use of LTB4R/LTB4R2 expression as a marker predictive of tumors sensitivity to leukotriene receptor inhibitors, in case they enter clinical studies. Legal entity responsible for the study Research Centre for Medical Genetics. Funding The research was carried out within the state assignment of Ministry of Science and Higher Education of the Russian Federation. Disclosure All authors have declared no conflicts of interest.

Plasma CA 19-9 in Advanced Non-Small Cell Lung Cancer

Background: Lung cancer is the leading cause of cancer death worldwide however no serum marker is routinely recommended till now.Patients and Methods: This is a prospective case control study including two groups of adults, Group I: Includes healthy volunteers as controls. Group II: Includes patients with advanced non-small cell lung cancer (NSCLC). Plasma CA19-9 levels were measured at baseline by ELISA before first line chemotherapy. Primary end point was comparison between the levels of CA19-9 in patients and controls. Secondary endpoint was correlation between CA19-9 level and clinical response (CR), progression free survival (PFS) and overall survival (OS) in advanced NSCLC.Results: 34 healthy adults and 35 patients with advanced NSCLC were included and followed up during the period from October 2009 to February 2013 with median follow up of 10.5 months. The mean and median pre-treatment plasma CA 19-9 concentrations of NSCLC patients were 240.7 and 231U/ml respectively. There was statistically significant difference between the patient and control groups (p < 0.001). No significant correlations were found between CA19-9 levels and CR, PFS and OS p-values: 0.5, 0.3 and 0.6 respectively Conclusion: Plasma CA19-9 is a reliable marker for advanced NSCLC.

Abstract P2-13-02: Effect of aspirin (ASP) or celecoxib (CC) use on outcomes in postmenopausal breast cancer patients randomized to adjuvant exemestane or anastrozole: NCIC CTG MA.27

Abstract Background: ASP is hypothesized to decrease the risk of breast cancer (BRCA) and BRCA recurrences. Thus we performed an exploratory analysis of ASP and CC use within the NCIC CTG MA.27 adjuvant trial comparing exemestane (E;N=3789) to anastrozole (A; N=3787) with a factorial second randomization to CC or placebo (P). Neither A or E was superior in breast cancer outcomes. Baseline low-dose ASP use is an accepted surrogate of cardiovascular risk factors and was used as a stratification factor across all 4 arms. Randomization to CC-P was discontinued after 18 months (n = 1622) due to concerns of cardiac toxicity. Methods: Patients taking &amp;gt;81mg of ASP daily at baseline were ineligible for randomization and use of &amp;gt;81mg of ASP daily was not allowed. Women enrolled during CC randomization were included in the comparison of E and A, stratified by whether they had been randomized to CC [yes, no;N=1622] and concomitant low-dose ASP [≤81 mg/day (yes, no); N=2209]. Other stratification factors included: lymph-nodes (negative, positive, or unknown); prior adjuvant chemotherapy (yes, no). The primary endpoint, event-free-survival (EFS), was defined as time from randomization to time of locoregional or distant disease recurrence, new primary breast cancer, or death from any cause. Secondary endpoints included overall survival (OS) defined as time from randomization to time of death from any cause and distant disease-free-survival (DDFS), defined as time from randomization to time of distant disease recurrence. Univariate (uni) assessment of CC and ASP use was assessed with stratified log-rank test, adjusting for lymph-node status and adjuvant chemotherapy and applied by intention-to-treat. Exploratory multivariate (multi) analyses (N = 1622) had forced inclusion of treatment and used step-wise forward stratified Cox modeling to examine the effects of CC, ASP use and baseline patient characteristics on outcomes; a factor was added with Wald test statistic p ≤ 0.05. Results: At median follow-up of 4.1 years, 186/1622 (11%) patients had an EFS event; 125 (8%) had died from any cause, and 80 (5%) had distant BRCA relapse. CC did not have significant uni association with outcomes: EFS p-value=0.92; OS p-value p = 0.56; DDFS p-value=0.55. ASP use was associated with worse EFS [p = 0.006, HR 1.48 (95% CI 1.12–1.96)], worse OS [p = 0.0002, HR 1.87 (95% CI (1.35–2.61)], and non-significant difference in DDFS (p = 0.72). CC had no multi association with EFS, OS or DDFS. ASP use had no multi association with EFS and DDFS (p &amp;gt; 0.05). However, ASP use had multi prognostic association with worse OS [p = 0.01; HR 1.67 (95% CI 1.13–2.49)]. Conclusions: Users of either CC or low dose ASP had similar DDFS to non-users in MA.27. As expected, low-dose ASP users (with presumptive cardiovascular risk factors) had worse OS than non-users. Inadequate numbers of patients randomized to CC and lack of randomization to aspirin leaves inadequate evidence from MA.27 to determine whether anti-inflammatories influence breast cancer outcomes. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-02.

Abstract LB-444: Transforming growth factor beta polymorphisms and breast cancer survival among Chinese women

Abstract Aberrant transforming growth factor-beta (TGFB) signaling contributes to tumor progression. To clarify the role of TGFB pathway variants and breast cancer survival, we conducted a two stage study among 4,535 breast cancer patients recruited in two studies conducted in Shanghai, China. In Stage I, 111 variants in TGFB, TGFBR1, and TGFBR2 were evaluated for associations with disease-free (DFS) and overall survival (OS) among 2,923 participants with a median of 5.5 years of follow-up time after their cancer diagnosis. Nominally significant associations with either DFS or OS were found for 31 variants, which after considering linkage disequilibrium, were found to represent 13 independent loci. Stage II genotyping was conducted among 1,612 additional participants with a median follow-up time of 5.1 years; data was available for 11 loci. Genetic variants in 6 loci were not associated with breast cancer outcomes in Stage II. Variants in 4 loci showed associations in Stage II that were generally consistent, but did not reach statistical significance. One variant was significantly associated with overall breast cancer survival in both study stages, and overall and disease free survival in analyses of the two study stage samples combined. Specifically, women with two copies of the rare variant of TGFBR1 rs3773651 (GG) had increased hazards of recurrence or breast cancer specific mortality (HR: 2.05, 95% CI: 1.28–3.27) and overall mortality (HR: 2.44, 95% CI: 1.50–3.95) compared to women with one or more common alleles (AG, AA) in age adjusted analyses. Additional adjustment for disease stage, ER, PR, or treatment including surgery, chemotherapy, radiotherapy, and tamoxifen did not attenuate these effects. Further, the statistical significance of these associations was retained after consideration was made for multiple comparisons (DFS p-value 0.0027; OS p-value 0.0003). rs3773651 is located in intron six of TGFBR2, a TGFB ligand specific receptor critical for transduction of TGFB signaling. Our data support a role for individual variation in TGFBR2 in breast cancer survival outcomes; additional investigation is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-444. doi:10.1158/1538-7445.AM2011-LB-444