BIOM-15. SERUM AMYLOID-β42 AS A NONINVASIVE BIOMARKER FOR PROGNOSIS AND HISTOLOGIC FEATURES OF GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi13-vi13
Author(s):  
Kihwan Hwang ◽  
Minhee Noh ◽  
Jay Park ◽  
So Young Ji ◽  
Jung Ho Han ◽  
...  
Keyword(s):  
Molecular Subtype ◽  
Statistical Significance ◽  
Progression Free Survival ◽  
Ki 67 ◽  
Who Grade ◽  
Primary Tumors ◽  
Poor Outcome ◽  
Egfr Expression ◽  
Multiple Imaging ◽  
Noninvasive Biomarker

Abstract INTRODUCTION Glioma is the most common primary tumor in central nervous system and is often refractory. Histopathologic examination is essential to establish initial diagnosis, and multiple imaging studies are conducted to assess for treatment response. However, those conventional approaches usually accompanies high risks and costs during treatment. The purpose of this study is to find a novel candidate of noninvasive biomarker for histologic prediction and prognostic assessment of glioma. METHODS Serum was prepared from blood samples collected preoperatively from 65 patients with WHO grade II–IV glioma from October 2004 to December 2017 in a single tertiary-level institution. Concentration of amyloid beta-42 (Aβ42) was measured by SMCxPRO (Merck) immunoassay. Clinical characteristics and histologic features of the patients including the molecular subtype were reviewed. Progression-free survival has been evaluated for the primary outcome. RESULTS The mean age of the patients was 53.7±12.2 years. 37 (56.9%) patients were males and 21 (32.3%) cases were primary tumors. In Kaplan-Meier survival analysis, higher serum Aβ42 (>5.7 pg/ml) group showed poor outcome with a statistical significance (p=0.014). In multivariate regression analysis, the concentration of serum Aβ42 showed a significant association with EGFR expression, or Ki-67 labeling index. The higher concentration of serum Aβ42 was associated with EGFR wild type (odds ratio 0.237, p=0.022), high cell proliferation (β=0.339, p=0.007) and poor outcome (hazard ratio 0.339, p=0.046). CONCLUSION Serum Aβ42 level is a possible good candidate of noninvasive biomarkers for prediction of histologic features and prognosis in glioma patients. Further studies with large cohorts might be mandatory for the clinical use of Aβ42.

scholarly journals Serum amyloid beta-42 as a noninvasive biomarker for the prognosis and histologic features of glioma

2021 ◽  
Author(s):  
Kihwan Hwang ◽  
Minhee Noh ◽  
Jay J. Park ◽  
Kwang-Sung Ahn ◽  
Junhyung Kim ◽  
...  
Keyword(s):  
Amyloid Beta ◽  
Molecular Subtype ◽  
Progression Free Survival ◽  
Multivariate Regression Analysis ◽  
Ki 67 ◽  
Who Grade ◽  
Primary Tumors ◽  
Egfr Expression ◽  
Multiple Imaging ◽  
Amyloid Beta 42

Abstract PURPOSE Glioma is often refractory. Histopathologic examination is essential to establish an initial diagnosis, and multiple imaging studies are conducted to assess the treatment response. However, these conventional approaches are usually accompanied by high risks and costs during treatment. The purpose of this study was to identify a novel, noninvasive, candidate biomarker for the histological prediction and prognostic assessment of glioma. METHODS Serum was prepared from blood samples collected preoperatively from 65 patients with WHO grade II–IV glioma between October 2004 and December 2017 in a single tertiary-level institution. The concentration of amyloid beta-42 (Aβ42) was measured by SMCxPRO (Merck) immunoassay. The clinical characteristics and histologic features of the patients, including the molecular subtype, were reviewed. Progression-free survival was evaluated as the primary outcome. RESULTS The mean age of the patients was 53.7 ± 12.2 years. Thirty-seven (56.9%) patients were male, and 21 (32.3%) patients had primary tumors. In Kaplan-Meier survival analysis, the group with higher serum Aβ42 (> 5.7 pg/ml) showed a poorer outcome (p = 0.014). In multivariate regression analysis, the serum Aβ42 concentration showed a significant association with EGFR expression and the Ki-67 labeling index. A higher serum Aβ42 concentration was associated with wild-type EGFR expression (odds ratio 0.237, p = 0.022), increased cell proliferation (β = 0.339, p = 0.007) and a poor outcome (hazard ratio 0.339, p = 0.046). CONCLUSION The serum Aβ42 level would be a good, noninvasive, candidate biomarker for the prediction of histological features and prognosis in glioma patients. Further studies with large cohorts might be required for its clinical use.

scholarly journals Prognostic Significance of Preoperative Neutrophil-to-Lymphocyte Ratio in Patients With Meningiomas

2020 ◽  
Vol 10 ◽  
Author(s):  
Yuki Kuranari ◽  
Ryota Tamura ◽  
Noboru Tsuda ◽  
Kenzo Kosugi ◽  
Yukina Morimoto ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Laboratory Data ◽  
Progression Free Survival ◽  
Cost Effective ◽  
Tumor Location ◽  
Neutrophil To Lymphocyte Ratio ◽  
Ki 67 ◽  
Who Grade ◽  
Lymphocyte Ratio ◽  
Subtotal Removal

BackgroundMeningiomas are the most common benign intracranial tumors. However, even WHO grade I meningiomas occasionally show local tumor recurrence. Prognostic factors for meningiomas have not been fully established. Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic factor for several solid tumors. The prognostic value of NLR in meningiomas has been analyzed in few studies.Materials and MethodsThis retrospective study included 160 patients who underwent surgery for meningiomas between October 2010 and September 2017. We analyzed the associations between patients’ clinical data (sex, age, primary/recurrent, WHO grade, extent of removal, tumor location, peritumoral brain edema, and preoperative laboratory data) and clinical outcomes, including recurrence and progression-free survival (PFS).ResultsForty-four meningiomas recurred within the follow-up period of 3.8 years. WHO grade II, III, subtotal removal, history of recurrence, Ki-67 labeling index ≥3.0, and preoperative NLR value ≥2.6 were significantly associated with shorter PFS (P < 0.001, < 0.001, 0.002, < 0.001, and 0.015, respectively). Furthermore, NLR ≥ 2.6 was also significantly associated with shorter PFS in a subgroup analysis of WHO grade I meningiomas (P = 0.003). In univariate and multivariate analyses, NLR ≥2.6 remained as a significant predictive factor for shorter PFS in patients with meningioma (P = 0.014).ConclusionsNLR may be a cost-effective and novel preoperatively usable biomarker in patients with meningiomas.

scholarly journals P14.95 Is the pathological-grade relevant in “IDH-wild type, TERT-mutant” diffuse-gliomas? An analysis in 147 patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii90-iii90
Author(s):  
A E Danyeli ◽  
C B Akyerli ◽  
A Dinçer ◽  
E Coşgun ◽  
U Abacıoğlu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
Lower Grade ◽  
Wild Type ◽  
Ki 67 ◽  
Who Grade ◽  
Free Survival ◽  
Tert Promoter ◽  
Diffuse Gliomas

Abstract BACKGROUND Although the word “glioblastoma” still denotes a grade-IV pathology, basic molecular studies have clearly indicated that a significant proportion of lower-grade gliomas harbor genetic alterations typical of glioblastomas. Based on these findings cIMPACT-NOW update 3 has defined an entity called the “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV”. A TERT-promoter mutation is one of these typical molecular markers of glioblastomas. In this study we analyzed IDH-wild type, TERT-mutant diffuse gliomas of different pathological grades to look for differences in demographic, clinical and survival characteristics. MATERIAL AND METHODS 147 adult hemispheric diffuse-gliomas with wild-type IDH1/2 and mutant TERT-promoter (C228T or C250T) were retrospectively analyzed. Primary thalamic, cerebellar brainstem or spinal cases were excluded. 126 (86%), 16(11%) and 5(3%) patients were WHO grade IV, III and II respectively. After surgical treatment or stereotactic biopsy all patients underwent chemoradiation. Median follow-up was 16mo (1–110). Tumors of different grades were compared for age, gender, multifocality, gliomatosis pattern, Ki-67 index, progression-free survival and overall-survival. RESULTS Mean age at presentation for grade II, III and IV were comparable (58.1, 58 and 58.1; ANOVA, p=0.72). There was a slight male predominance in both lower-grades and WHO-grade IV (M:F ratios 1.625 and 1.74). Mean Ki-67 index was significantly higher in higher grades (0.06, 0.14 and 0.25 for grades II, III and IV; ANOVA, p=0.001). Multifocality was comparable (chi-sq, p=1) in lower-grades (3/21; 14.3%) vs. WHO-grade IV (18/126; 14.3%). Gliomatosis pattern was comparable (chi-sq, p=0.095) in lower-grades (2/21; 9.5%) vs. (3/126; 2.3%). Median recurrence free survival (RFS) was 16 months (0–63) in lower-grades and 8months (1–50) in WHO-grade IV. PFS was significantly different between 3 WHO-grades (Log rank, p=0.007) and also between lower-grades and WHO-grade IV (Log rank, p=0.002). Median overall survival was 26 months(2–110) in lower-grades and 15mo(1–91) in WHO-grade IV. OS was significantly different between 3 WHO-grades (Log rank, p=0.014) and also between lower-grades and WHO-grade IV (Log rank, p=0.007). CONCLUSION Increasing pathological grades of hemispheric “IDH-wild type, TERT-mutant diffuse gliomas” have similar demographic and clinical characteristics but incrasing proliferation indices, decrasing progression free survival and shorter overall survival. The findings may be suggesitve of different grades of one common tumor entity.

scholarly journals Mitotic and Proliferative Indices in WHO Grade III Meningioma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3351
Author(s):  
Andrea Daniela Maier ◽  
Christian Beltoft Brøchner ◽  
Jiri Bartek Jr. ◽  
Frank Eriksson ◽  
Heidi Ugleholdt ◽  
...  
Keyword(s):  
Mitotic Index ◽  
Hot Spot ◽  
Progression Free Survival ◽  
Ki 67 ◽  
Who Grade ◽  
Free Survival ◽  
Phosphohistone H3 ◽  
Proliferative Indices ◽  
Who Grade Iii ◽  
Grade Iii

Meningiomas with inherently high mitotic indices and poor prognosis, such as WHO grade III meningiomas, have not been investigated separately to establish interchangeability between conventional mitotic index counted on H&E stained slides (MI) and mitotic index counted on phosphohistone-H3 stained slides (PHH3 MI). This study investigates the agreement of MI and PHH3 MI and to analyze the association of progression-free survival (PFS) and MI, PHH3 MI, and the proliferative index (PI, Ki-67) in WHO grade III meningioma. Tumor specimens from 24 consecutive patients were analyzed for expression of Ki-67, PHH3 MI, and MI. Quantification was performed independently by two observers who made replicate counts in hot spots and overall tumor staining. Repeatability in replicate counts from MI and PHH3 MI was low in both observers. Consequently, we could not report the agreement. MI, PHH3 MI and hot spot counts of Ki-67 were associated with PFS (MI hot spot HR = 1.61, 95% CI 1.12–2.31, p = 0.010; PHH3 MI hot spot HR = 1.59, 95% CI 1.15–2.21, p = 0.006; Ki-67 hot spot HR = 1.06, 95% CI 1.02–1.11. p = 0.004). We found markedly low repeatability of manually counted MI and PHH3 MI in WHO grade III meningioma, and we could not conclude that the two methods agreed. Subsequently, quantification with better repeatability should be sought. All three biomarkers were associated with PFS.

Effect of temozolomide chronotherapy in patients with high-grade glioma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14525-e14525 ◽  
Author(s):  
Himachandana Atluri ◽  
Jian Li Campian ◽  
Grayson Talcott ◽  
Melissa Meyer ◽  
Emily Slat ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Biological Rhythms ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Well Being ◽  
Current Therapy ◽  
High Grade ◽  
Who Grade ◽  
Significant Difference ◽  
Morning Administration

e14525 Background: High grade gliomas (HGG) (the most common being glioblastoma) are the most common primary CNS malignancy in adults. Mainstay of therapy is surgical resection followed by concurrent radiation and temozolomide (TMZ) followed by adjuvant TMZ. Unfortunately, prognosis remains poor and optimization of current therapy is critical. Chronotherapy is defined as improvement in treatment outcomes by maximizing treatment efficacy and minimizing toxicity by administering medications in accordance with biological rhythms of the patient. In a mouse model, there was greater anti-tumor efficacy during morning administration of TMZ. This trial was designed to determine the feasibility and potential clinical impact of chrono-therapeutically administering TMZ in patients with HGG. Methods: Adult patients ( > 18 years) with HGG (WHO Grade III/IV) were eligible. Patients were screened and consented prior to initiation of monthly TMZ therapy. Eligible patients were randomized to TMZ in the morning (AM) before 10AM or in the evening (PM) after 8PM. Pill diaries were recorded for drug administration time and compliance. Fact-Br Quality of Life (QoL) surveys were administered to patients at the time of enrollment in the trial and at the end of treatment to measure differences in QoL in both groups. Circadian rhythm was recorded by Actiwatch. Adverse events (AE), overall survival (OS) and progression free survival (PFS) were measured for each group. Results: At the time of submission, a total of 28 patients were evaluated. 15 patients were in AM group and 13 in PM group. It is feasible for participants to take TMZ per study assignment. There was no significant difference in the QoL based on the Fact-Br dataset in the four main categories of physical well-being, social/family well-being, functional well-being and emotional well-being. The Friedman’s two-way nonparametric ANOVA tests were used to analyze the differences across time points. Cytopenias are a known adverse effect of TMZ. There was a trend towards worsening lymphocyte counts in the AM group compared to PM group, although not statistically significant. There was no statistical significance in PFS or OS in patients with newly diagnosed glioblastoma. Conclusions: Chronotherapy with TMZ is feasible. A trend of worsening lymphocyte counts is noted in AM treatment group compared to PM group but was not statistically significant. No difference in OS or PFS was noted, although sample size was too small to effectively assess this. A larger study will need to be conducted to effectively assess the effect of chronotherapy on survival. Clinical trial information: NCT02781792.

Safety and efficacy of anti-EGFR monoclonal antibody (SCT200) as second-line therapy in advanced esophageal squamous cell cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16046-e16046
Author(s):  
Ming Bai ◽  
Ting Deng ◽  
Yi Ba
Keyword(s):  
Monoclonal Antibody ◽  
Squamous Cell ◽  
Tp53 Mutation ◽  
Statistical Significance ◽  
Cell Cancer ◽  
Objective Response ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Open Label ◽  
Egfr Expression

e16046 Background: The mainstay treatment of esophageal squamous cell carcinoma (ESCC) involves chemotherapy and immunotherapy. However, alternative therapies are required for patients refractory or intolerant to the existing therapies. Methods: In this single-arm, multicenter, open-label phase Ib study, 30 patients received an intravenous infusion of SCT200, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, 6.0 mg/kg once a week for six weeks, followed by 8.0 mg/kg once every two weeks until disease progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: Thirty patients were enrolled between July 2018 and May 2019. The ORR was 16.7% (95%CI: 5.6%–34.7%). The median PFS and OS was 3.1 months (95%CI: 1.5–4.3) and 6.8 months (95%CI: 4.7–10.1) respectively. Numerical difference without a statistical significance in ORR was observed in patients with different EGFR expression (≥50%: 25.0% vs. < 50%: 0%, P = 0.140) or TP53 mutation abundance ( < 10%: 23.8% vs. ≥10%: 0%, P = 0.286). Improved median PFS (3.4 vs. 1.4 months, P = 0.006) and OS (8.0 vs. 4.2 months, P = 0.027) were associated with TP53 mutation abundance of < 10%. The most common treatment-related adverse events of grade 3 or 4 (occurring in ≥2 patients) were hypomagnesemia (7 [23.3%]) and rash (2 [6.7%]). No treatment-related death occurred. Conclusions: SCT200 monotherapy as second- or further-line for advanced ESCC showed favorable efficacy, with an acceptable safety profile. TP53 mutation abundance might serve as potential predictive biomarkers. Clinical trial information: NCT03817567. [Table: see text]

Spinal ependymoma in adults: a multicenter investigation of surgical outcome and progression-free survival

2018 ◽  
Vol 28 (6) ◽  
pp. 654-662 ◽  
Author(s):  
Maria Wostrack ◽  
Florian Ringel ◽  
Sven O. Eicker ◽  
Max Jägersberg ◽  
Karl Schaller ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Progression Free Survival ◽  
Adult Patients ◽  
Gross Total Resection ◽  
Adjuvant Radiation ◽  
Total Resection ◽  
Ki 67 ◽  
Who Grade ◽  
Free Survival ◽  
Spinal Ependymoma

OBJECTIVESpinal ependymomas are rare glial neoplasms. Because their incidence is low, only a few larger studies have investigated this condition. There are no clear data concerning prognosis and therapy. The aim of the study was to describe the natural history, perioperative clinical course, and local tumor control of adult patients with spinal ependymomas who were surgically treated under modern treatment standards.METHODSThe authors performed a multicenter retrospective study. They identified 158 adult patients with spinal ependymomas who had received surgical treatment between January 2006 and June 2013. The authors analyzed the clinical and histological aspects of these cases to identify the predictive factors for postoperative morbidity, tumor resectability, and recurrence.RESULTSGross-total resection (GTR) was achieved in 80% of cases. At discharge, 37% of the patients showed a neurological decline. During follow-up the majority recovered, whereas 76% showed at least preoperative status. Permanent functional deterioration remained in 2% of the patients. Transient deficits were more frequent in patients with cervically located ependymomas (p = 0.004) and in older patients (p = 0.002). Permanent deficits were independently predicted only by older age (p = 0.026). Tumor progression was observed in 15 cases. The 5-year progression-free survival (PFS) rate was 80%, and GTR (p = 0.037), WHO grade II (p = 0.009), and low Ki-67 index (p = 0.005) were independent prognostic factors for PFS. Adjuvant radiation therapy was performed in 15 cases. No statistically relevant effects of radiation therapy were observed among patients with incompletely resected ependymomas (p = 0.079).CONCLUSIONSDue to its beneficial value for PFS, GTR is important in the treatment of spinal ependymoma. Gross-total resection is feasible in the majority of cases, with acceptable rates of permanent deficits. Also, Ki-67 appears to be an important prognostic factor and should be included in a grading scheme for spinal ependymomas.

scholarly journals Clinicopathological and Prognostic Significance of CD47 Expression in Lung Neuroendocrine Tumors

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mario Orozco-Morales ◽  
Alejandro Avilés-Salas ◽  
Norma Hernández-Pedro ◽  
Rodrigo Catalán ◽  
Graciela Cruz-Rico ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Neuroendocrine Tumors ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Large Cell ◽  
Ki 67 ◽  
Typical Carcinoid ◽  
Free Survival ◽  
Wide Range

Background. Lung neuroendocrine tumors account for approximately 15% of all lung cancer cases. LNET are subdivided into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small-cell lung cancer (SCLC). The Ki-67 index has been used for decades to evaluate mitotic counts however, the role of Ki-67 as a biomarker for assessing prognosis and guiding therapy in metastatic LNET still lacks feasible clinical validation. Recent clinical trials have indicated that inhibition of CD47 with anti-CD47 antibodies exerts a promising antitumor effect against several human malignancies, including NSCLC, melanoma, and hematologic malignancies. However, the clinical relevance of CD47 expression in LNET has remained unclear. Methods. We performed a retrospective study in which we analyzed tumor biopsies from 51 patients with a confirmed diagnosis of LNET that received treatment at our hospital. Then, we analyzed if there was any correlation between CD47 expression with any clinical or pathological characteristic. We also analyzed the prognostic significance of CD47, assessed as progression-free survival and overall survival. Results. A total of 51 patients with LNET were enrolled in our study. The mean age at diagnosis was 57.6 (±11.6) years; 30 patients were women (59%). 27.5% of patients were positive for CD47 expression, and 72.5% of patients showed a CD47 expression of less than 1% and were considered as negatives. In patients with high-grade tumors (this time defined as Ki ‐ 67 > 40 % ), the positive expression of CD47 was strongly associated with an increased PFS. Albeit, these differences did not reach statistical significance when analyzing OS. Conclusion. Contrary to what happens in a wide range of hematologic and solid tumors, a higher expression of CD47 in patients with LNET is associated with a better progression-free survival, especially in patients with a Ki ‐ 67 ≥ 40 % . This “paradox” remains to be confirmed and explained by larger studies.

Correlation of MTAP Immunohistochemistry With CDKN2A Status Assessed by Fluorescence In Situ Hybridization and Clinicopathological Features in CNS WHO Grade 2 and 3 Meningiomas: A Single Center Cohort Study

2021 ◽  
Author(s):  
Shoh Sasaki ◽  
Maiko Takeda ◽  
Takanori Hirose ◽  
Tomomi Fujii ◽  
Hiroe Itami ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Surrogate Marker ◽  
Progression Free Survival ◽  
Mitotic Rate ◽  
Genetic Alterations ◽  
Homozygous Deletion ◽  
Clinicopathological Features ◽  
Ki 67 ◽  
Who Grade ◽  
Grade 3

Abstract CDKN2A homozygous deletion has occasionally been reported in atypical and anaplastic meningiomas and is considered as one of the genetic alterations commonly involved in their recurrence and malignant progression. Methylthioadenosine phosphorylase (MTAP) immunohistochemistry is a promising surrogate marker for CDKN2A homozygous deletion in different cancers but has not been examined in meningiomas. We performed CDKN2A FISH and MTAP immunohistochemistry on specimens from 30 patients with CNS WHO grade 2 (n = 27) and 3 (n = 3) meningiomas, including specimens from primary and recurrent tumors and then determined whether MTAP immunohistochemistry correlated with CDKN2A homozygous deletion and clinicopathological features. CDKN2A homozygous deletion was detected in 12% (3/26) of CNS WHO grade 2 and 67% (2/3) of CNS WHO grade 3 meningiomas; 3 cases exhibited temporal and/or spatial heterogeneity. MTAP loss was in excellent concordance with CDKN2A homozygous deletion (sensitivity; 100%, specificity; 100%). MTAP loss/CDKN2A homozygous deletion correlated with cellular proliferation (mitotic rate; p = 0.001, Ki-67 labeling index; p = 0.03) and poor prognosis (overall survival; p = 0.01, progression free survival; p &lt; 0.001). Thus, MTAP immunostaining can be a surrogate marker for CDKN2A homozygous deletion in meningiomas, and MTAP loss/CDKN2A homozygous deletion may be an important prognostic factor for meningiomas.

mRNA expression profiles in circulating tumor cells (CTCs) of patients with metastatic breast cancer (MBC) treated with aromatase inhibitors (AI).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11045-11045
Author(s):  
Esther Anneke Reijm ◽  
Anieta M. Sieuwerts ◽  
Joan Bolt-de Vries ◽  
Bianca Mostert ◽  
Wendy Onstenk ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Mrna Expression ◽  
Expression Profiles ◽  
Statistical Significance ◽  
Metastatic Breast ◽  
First Line ◽  
Primary Tumors ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Poor Outcome

11045 Background: Enumeration of CTCs can be used to assess prognosis in MBC and to evaluate treatment response. Besides enumeration, molecular CTC characterization is a promising tool to develop a more personalized treatment approach. Here, we evaluated the association between mRNA expression of currently known CTC-specific genes and response to first-line AI in MBC patients with estrogen receptor (ER)+ primary tumors. Methods: CTCs were isolated and enumerated from blood of 25 MBC patients before first-line therapy with an AI. Fourteen patients received a non-steroidal AI (8 letrozole, 6 anastrozole) and 11 patients were treated with exemestane. mRNA expression levels of 96 genes were measured by quantitative RT-PCR as previously described (Sieuwerts et al. Clin Cancer Res. 17:3600-3618, 2011). Expression levels of these genes were studied for their association with time to progression (TTP) after start first-line AI. Results: Median TTP was 338 (range 14–1,239) days. Median baseline CTC count for the 25 patients was 14 (range 0–753). In this relatively small cohort, the clinically relevant cut-off level of ≥5 CTCs in association with TTP did not reach statistical significance (Hazard Ratio [HR] 4.76, 95% Confidence Interval [CI]: 0.59–38.22, P=0.14). For type of AI, when comparing steroidal with non-steroidal AI, the measures in Cox univariate regression analysis were HR 2.54 (95% CI: 0.67–9.64), P=0.17. A 10-gene CTC profile was constructed based on the Wald statistics of the contribution of the individual genes in univariate Cox regression analysis of TTP. To identify patients with good and poor outcome, the Wald corrected sum of the 10 genes was used to dichotomize the continuous 10-gene predictor (HR 12.87 [95% CI: 1.60–103.56], P=0.016). In multivariate analysis, corrected for the clinically relevant variables type of AI and CTC count, only the 10-gene CTC profile was an independent factor associated with TTP (HR 12.46 [95% CI: 1.29-120.08], P=0.029). Conclusions: A 10-gene CTC predictor was constructed which distinguishes good and poor outcome to first-line AI in MBC patients. This profile is currently being validated in an independent group of patients.

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