scholarly journals Colorectal Cancer-Associated Immune Exhaustion Involves T and B Lymphocytes and Conventional NK Cells and Correlates With a Shorter Overall Survival

2021 ◽  
Vol 12 ◽  
Author(s):  
Carlo Sorrentino ◽  
Luigi D’Antonio ◽  
Cristiano Fieni ◽  
Stefania Livia Ciummo ◽  
Emma Di Carlo
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
T Cell ◽  
B Cell ◽  
Nk Cells ◽  
Rank Test ◽  
Cell Markers ◽  
Immune Exhaustion ◽  
Log Rank Test ◽  
Wide Range

Colorectal cancer (CRC) is one of the most common cancer worldwide, with a growing impact on public health and clinical management. Immunotherapy has shown promise in the treatment of advanced cancers, but needs to be improved for CRC, since only a limited fraction of patients is eligible for treatment, and most of them develop resistance due to progressive immune exhaustion. Here, we identify the transcriptional, molecular, and cellular traits of the immune exhaustion associated with CRC and determine their relationships with the patient’s clinic-pathological profile. Bioinformatic analyses of RNA-sequencing data of 594 CRCs from TCGA PanCancer collection, revealed that, in the wide range of immune exhaustion genes, those coding for PD-L1, LAG3 and T-bet were associated (Cramér’s V=0.3) with MSI/dMMR tumors and with a shorter overall survival (log-rank test: p=0.0004, p=0.0014 and p=0.0043, respectively), whereas high levels of expression of EOMES, TRAF1, PD-L1, FCRL4, BTLA and SIGLEC6 were associated with a shorter overall survival (log-rank test: p=0.0003, p=0.0188, p=0.0004, p=0.0303, p=0.0052 and p=0.0033, respectively), independently from the molecular subtype of CRC. Expression levels of PD-L1, PD-1, LAG3, EOMES, T-bet, and TIGIT were significantly correlated with each other and associated with genes coding for CD4+ and CD8+CD3+ T cell markers and NKp46+CD94+EOMES+T-bet+ cell markers, (OR >1.5, p<0.05), which identify a subset of group 1 innate lymphoid cells, namely conventional (c)NK cells. Expression of TRAF1 and BTLA co-occurred with both T cell markers, CD3γ, CD3δ, CD3ε, CD4, and B cell markers, CD19, CD20 and CD79a (OR >2, p<0.05). Expression of TGFβ1 was associated only with CD4+ and CD8+CD3ε+ T cell markers (odds ratio >2, p<0.05). Expression of PD-L2 and IDO1 was associated (OR >1.5, p<0.05) only with cNK cell markers, whereas expression of FCRL4, SIGLEC2 and SIGLEC6 was associated (OR >2.5; p<0.05) with CD19+CD20+CD79a+ B cell markers. Morphometric examination of immunostained CRC tissue sections, obtained from a validation cohort of 53 CRC patients, substantiated the biostatistical findings, showing that the highest percentage of immune exhaustion gene expressing cells were found in tumors from short-term survivors and that functional exhaustion is not confined to T lymphocytes, but also involves B cells, and cNK cells. This concept was strengthened by CYBERSORTx analysis, which revealed the expression of additional immune exhaustion genes, in particular FOXP1, SIRT1, BATF, NR4A1 and TOX, by subpopulations of T, B and NK cells. This study provides novel insight into the immune exhaustion landscape of CRC and emphasizes the need for a customized multi-targeted therapeutic approach to overcome resistance to current immunotherapy.

scholarly journals EYA4 could be an indicator signifying colorectal cancer sufferers' prognoses

2020 ◽  
Author(s):  
Yang Yan ◽  
Xiaohui Du ◽  
Shaoyou Xia ◽  
Songyan Li ◽  
Da Teng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Survival Curve ◽  
Mrna Level ◽  
Clinicopathological Characteristics ◽  
Rank Test ◽  
Normal Tissues ◽  
Log Rank Test ◽  
Low Expression

Abstract Background Eyes absent 4 (EYA4) is involved in various biological processes. The aim of this study was to investigate the expression of EYA4 and its prognostic value in colorectal cancer (CRC). Methods The mRNA level of EYA4 in diseased tissues and adjacent normal tissues of CRC patients were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The association between EYA4 expression and clinicopathological characteristics was analyzed by χ2 test. Kaplan-Meier analysis with log rank test was performed to evaluate the effects of EYA4 expression on overall survival of CRC patients. Cox regression model was applied for prognosis analysis in CRC. Results The mRNA level of EYA4 was significantly decreased in CRC tissues compared with that in the adjacent normal tissue (P < 0.01). And its expression was affected by DUKE stage (P = 0.034), differentiation (P = 0.027) and vascular invasion (P = 0.037). Survival curve showed that patients with low expression of EYA4 had a significantly shorter overall survival than those with high expression (log rank test, P = 0.008). Low expression of EYA4 (HR = 1.989, 95%CI = 1.090-3.62902, P = 0.025) was an independent biomarker for poor prognosis in CRC patients. Conclusion EYA4 expression is decreased in CRC patients and negatively correlated with aggressive tumor progression. EYA4 may be a potential prognostic biomarker for CRC.

Statistical analysis of episensitization using transition probability functions and PFS2 for “ROCKET”, a two stage phase II study of RRx-001, a multi-epigenetic agent, investigating resensitization to irinotecan in colorectal cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS775-TPS775
Author(s):  
Nacer Abrouk ◽  
Tony R. Reid ◽  
George A. Fisher ◽  
Corey Allan Carter ◽  
Paul M. Thambi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Transition Probability ◽  
Rank Test ◽  
Two Stage ◽  
Probability Functions ◽  
Risk Of Death ◽  
Log Rank Test ◽  
The Impact ◽  
To Receive

TPS775 Background: The development of resistance to chemotherapies in cancer leads to disease progression resulting in impaired survival. RRx-001, a ROS-mediated DNMT and HDAC inhibitor, may resensitize patients to previously effective, now refractory therapies, improving survival. A randomized two-stage Phase 2 trial of RRx-001 vs regorafenib (ROCKET) is underway to assess the impact of resensitization to irinotecan on overall survival in irinotecan refractory tumors. Transition Probability Functions (TPF) using Markov Chains have previously been used in clinical trials and provide a powerful tool for resensitization analysis. Methods: Patients with metastatic colorectal cancer who previously responded, then progressed on irinotecan-based therapies, with or without bevacizumab, cetuximab or panitumumab and an ECOG PS 0-1 are randomized to receive RRx-001 1x/week or regorafenib until progression or unacceptable toxicity in Stage 1. Patients then advance to Stage 2 to receive irinotecan-based therapies. This trial is designed to detect an increase in median OS of 3 mo., corresponding to a 33% reduction in risk of death. The primary endpoint, overall survival (OS), employs a two-sided log-rank test to compare treatment groups. The hazard ratio and its 95% CI are derived from the Cox proportional hazards model. Kaplan-Meier survival curve estimates are graphically depicted by treatment group. Secondary endpoints include PFS, PFS2 and Transition Probability Functions to address the resensitization hypothesis, KRAS or p53 status dependence. The analysis of PFS2, defined as time to progression (or death) from randomization to progression in Stage 2 (post Irinotecan therapy) is a key secondary endpoint and its analysis uses the standard two-sided log-rank test. TPF estimates will be derived from the Markov Chain transition probability matrix. The study should provide compelling evidence in support of the ability to return to previously beneficial chemotherapy treatment. Recruitment is ongoing. Clinical trial information: NCT02096354.

Prognostic value of piR-39980 in patients with colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16087-e16087
Author(s):  
Wei Peng ◽  
Jingfeng Mei ◽  
Jianwei Lu ◽  
Jun Bao ◽  
Guoren Zhou
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Value ◽  
Cox Regression ◽  
Survival Curve ◽  
Prognostic Significance ◽  
Rank Test ◽  
Chi Square ◽  
Log Rank Test ◽  
Independent Indicator

e16087 Background: Colorectal cancer (CRC) accounts for a common gastrointestinal malignancy all over world. Piwi-interacting RNAs (piRNAs) show a substantial role in the oncogenesis of a variety of tumors. The objective of this work was to uncover the expression profile of piR-39980 and its prognostic value in CRC. Methods: The levels of piR-39980 expression in CRC tissues and paired normal tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Association of piR-39980 with CRC clinical feathers was assessed by Chi-square test. Overall survival curve was built via log-rank test by Kaplan–Meier analysis. The prognostic significance of piR-39980 in CRC was measured by Cox regression model. Results: piR-39980 was upregulated in CRC specimens than the paired normal specimens ( P < 0.001). Importantly, upregulation of piR-39980 was related to tumor size and T stage (all P < 0.05). Survival evaluation suggested that CRC folks with high expression of piR-39980 went through poorer overall survival than folks with low piR-39980 expression (log rank test, P = 0.0429). piR-39980 could be an independent indicator for CRC patients’ prognosis (HR = 3.308, 95% CI = 1.762-6.594, P = 0.043). Conclusions: piR-39980 plays oncogenic roles in CRC tumorigenesis and may be an independent indicator for CRC prognosis.

scholarly journals IL15RA and SMAD3 Genetic Variants Predict Overall Survival in Metastatic Colorectal Cancer Patients Treated with FOLFIRI Therapy: A New Paradigm

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1705
Author(s):  
Elena De Mattia ◽  
Jerry Polesel ◽  
Rossana Roncato ◽  
Adrien Labriet ◽  
Alessia Bignucolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Prognostic Score ◽  
Chemotherapeutic Agents ◽  
Rank Test ◽  
P Value ◽  
Genetic Determinants ◽  
New Paradigm

A new paradigm in cancer chemotherapy derives from the interaction between chemotherapeutics, including irinotecan and 5-fluorouracil (5-FU), and the immune system. The patient’s immune response can modulate chemotherapy effectiveness, and, on the other hand, chemotherapeutic agents can foster tumor cell immunogenicity. On these grounds, the analysis of the cancer patients’ immunogenetic characteristics and their effect on survival after chemotherapy represent a new frontier. This study aims to identify genetic determinants in the immuno-related pathways predictive of overall survival (OS) after FOLFIRI (irinotecan, 5-FU, leucovorin) therapy. Two independent cohorts comprising a total of 335 patients with metastatic colorectal cancer (mCRC) homogeneously treated with first-line FOLFIRI were included in the study. The prognostic effect of 192 tagging genetic polymorphisms in 34 immune-related genes was evaluated using the bead array technology. The IL15RA rs7910212-C allele was associated with worse OS in both discovery (HR: 1.57, p = 0.0327, Bootstrap p-value = 0.0280) and replication (HR:1.71, p = 0.0411) cohorts. Conversely, SMAD3 rs7179840-C allele was associated with better OS in both discovery (HR:0.65, p = 0.0202, Bootstrap p-value = 0.0203) and replication (HR:0.61, p = 0.0216) cohorts. A genetic prognostic score was generated integrating IL15RA-rs7910212 and SMAD3-rs7179840 markers with inflammation-related prognostic polymorphisms we previously identified in the same study population (i.e., PXR [NR1I2]-rs1054190, VDR-rs7299460). The calculated genetic score successfully discriminated patients with different survival probabilities (p < 0.0001 log-rank test). These findings provide new insight on the prognostic value of genetic determinants, such as IL15RA and SMAD3 markers, and could offer a new decision tool to improve the clinical management of patients with mCRC receiving FOLFIRI.

Outcomes of Surgical and Nonsurgical Treatment for Colorectal Cancer in Nonagenarian Patients

2021 ◽  
pp. 000313482199506
Author(s):  
Youngbae Jeon ◽  
Kyoung-Won Han ◽  
Won-Suk Lee ◽  
Jeong-Heum Baek
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Surgical Treatment ◽  
Postoperative Complications ◽  
Postoperative Mortality ◽  
Nonsurgical Treatment ◽  
Perioperative Outcomes ◽  
Rank Test ◽  
Kaplan Meier ◽  
Number Of Patients

Purpose This study is aimed to evaluate the clinical outcomes of surgical treatment for nonagenarian patients with colorectal cancer. Methods This retrospective single-center study included patients diagnosed with colorectal cancer at the age of ≥90 years between 2004 and 2018. Patient demographics were compared between the operation and nonoperation groups (NOG). Perioperative outcomes, histopathological outcomes, and postoperative complications were evaluated. Overall survival was analyzed using Kaplan-Meier methods and log-rank test. Results A total of 31 patients were included (16 men and 15 women), and the median age was 91 (range: 90‐96) years. The number of patients who underwent surgery and who received nonoperative management was 20 and 11, respectively. No statistical differences in baseline demographics were observed between both groups. None of these patients were treated with perioperative chemotherapy or radiotherapy. Surgery comprised 18 (90.0%) colectomies and 2 (10.0%) transanal excisions. Short-term (≤30 days) and long-term (31‐90 days) postoperative complications occurred in 7 (35.0%) and 4 (20.0%) patients, respectively. No complications needed reoperation, such as anastomosis leakage or bleeding. No postoperative mortality occurred within 30 days: 90-day postoperative mortality occurred in two patients (10.0%), respectively. The median overall survival of the operation group was 31.6 (95% confidence interval: 26.7‐36.5) and that of NOG was 12.5 months (95% CI: 2.4‐22.6) ( P = 0.012). Conclusion Surgical treatment can be considered in carefully selected nonagenarian patients with colorectal cancer in terms of acceptable postoperative morbidity, with better overall survival than the nonsurgical treatment.

Concomitant Cisplatin Significantly Improves Locoregional Control in Advanced Head and Neck Cancers Treated With Hyperfractionated Radiotherapy

2004 ◽  
Vol 22 (23) ◽  
pp. 4665-4673 ◽  
Author(s):  
Pia Huguenin ◽  
Karl T. Beer ◽  
Abdelkarim Allal ◽  
Kaspar Rufibach ◽  
Corinne Friedli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Failure ◽  
Head And Neck ◽  
Combined Treatment ◽  
Late Toxicity ◽  
Locoregional Control ◽  
Rank Test ◽  
Hyperfractionated Radiotherapy ◽  
Log Rank Test ◽  
Metastatic Relapse

Purpose To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. Patients and Methods From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. Results There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease–free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. Conclusion The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.

Bioinformatics Analysis of The Expression of ATP Binding Cassette Transporters and The Screening of Regulatory Genes in PTEN/PI3K/Akt/mTOR Signaling Pathway in The Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Tingdan Zheng ◽  
Wuqi Song ◽  
Aiying Yang
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Bioinformatics Analysis ◽  
Wilcoxon Test ◽  
Rank Test ◽  
Short Term ◽  
Term Survival ◽  
Log Rank Test ◽  
Short Term Survival

Abstract Objective Here we performed the Bioinformatics analysis on the data from The Cancer Genome Atlas (TCGA), in order to find the correlation between the expression of ATP Binding Cassette (ABC) Transporters’ genes and hepatocellular carcinoma (HCC) prognosis; Methods Transcriptome profiles and clinical data of HCC were obtained from TCGA database. Package edgeR was used to analyze differential gene expression. Patients were divided into low-ABC expression and high-ABC expression groups based on the median expression level of ABC genes in cancer. The overall survival and short-term survival (n= 341) of the two groups was analyzed using the log-rank test and Wilcoxon test; Results We found that ABC gene expression was correlated with the expression of PIK3C2B (p<0.001, ABCC1: r=0.27; ABCC10: r=0.57; ABCC4: r=0.20; ABCC5: r=0.28; ABCB9: r=0.17; ABCD1: r=0.21). All patients with low-ABC expression showed significantly increased overall survival. Significantly decreased overall survival (Log-rank test: p<0.05, Wilcoxon test: p<0.05) was found in patients with high expression of ABCC1 (HR=1.58), ABCD1 (HR=1.45), ABCC4 (HR=1.56), and ABCC5 (HR=1.64), while decreased short-term survival (Log-rank test: p>0.05, Wilcoxon test: p<0.05) was correlated with the increased expression of ABCC10 (HR=1.29), PIK3C2B (HR=1.29) and ABCB9 (HR=1.23); Conclusions Our findings indicate that the specific ABC gene expression correlates with the prognosis of HCC. Therefore, ABC expression profile could be a potential indicator for HCC patients.

scholarly journals Phenotype of recovering lymphoid cell populations after marrow transplantation.

1985 ◽  
Vol 161 (6) ◽  
pp. 1483-1502 ◽  
Author(s):  
K A Ault ◽  
J H Antin ◽  
D Ginsburg ◽  
S H Orkin ◽  
J M Rappeport ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Nk Cells ◽  
Cell Types ◽  
Lymphoid Cells ◽  
The Other ◽  
Hla Dr ◽  
T Cell Antigens ◽  
Leu 7

Four patients who received bone marrow transplants were studied sequentially during the posttransplant period to define the pattern of recovering lymphoid cell types. Three patients received T cell-depleted, HLA-matched marrow, and one received untreated marrow from an identical twin. Blood lymphoid cells were labeled with 25 different pairs of monoclonal antibodies. In each sample, one antibody was conjugated to fluorescein and one to phycoerythrin, thus allowing simultaneous assessment of the expression of the two markers using the fluorescence activated cell sorter. A total of 14 antibodies were used, routinely including HLE, Leu-M3, Leu-4, Leu-1, Leu-5, Leu-9, Leu-6, Leu-2, Leu-3, HLA-DR, Leu-7, Leu-11, Leu-15, and Leu-12. Other antibodies were used to further define some populations. This study has allowed us to define six distinct cell types that have appeared in all four patients by day 90 posttransplantation, and which account for 90-100% of all circulating lymphoid cells. These cell types are (a) T helper cells expressing Leu-1, Leu-4, Leu-9, Leu-5, Leu-3, and variable amounts of HLA-DR; (b) T suppressor cells expressing Leu-1, Leu-4, Leu-9, Leu-5, Leu-2, and variable amounts of HLA-DR; (c) B cells expressing Leu-12, B1, HLA-DR, IgD, and IgM, but none of the T cell antigens; (d) an unusual B cell phenotype (Leu-1 B) expressing all of the B cell markers, and also having low amounts of Leu-1, but none of the other T cell antigens; (e) natural killer (NK) cells expressing Leu-11, Leu-15, Leu-5 but none of the other T cell or B cell markers; (f) NK cells expressing Leu-11, Leu-15, Leu-5, and low levels of Leu-2. Both NK types also express Leu-7 on some, but not all cells. The relative frequencies of these cell types varied among the patients and with time, but the striking findings were the presence of relatively few mature T cells, large numbers of NK cells, and the preponderance of the unusual Leu-1 B cell over conventional B cells in all three patients who developed B cells. Sorting experiments confirmed the NK activity of the major NK cell phenotypes, and DNA analysis confirmed that all of the cells studied were of donor origin. In addition, analysis of Ig genes in one patient showed that the Leu-1 B cells were not clonally rearranged.(ABSTRACT TRUNCATED AT 400 WORDS)

Survival Outcomes for Induction vs Adjuvant Chemotherapy in Squamous Cell Carcinoma of the Maxillary Sinus

2018 ◽  
Vol 160 (4) ◽  
pp. 658-663 ◽  
Author(s):  
Phoebe Kuo ◽  
Sina J. Torabi ◽  
Dennis Kraus ◽  
Benjamin L. Judson
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Maxillary Sinus ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Cox Regression ◽  
Rank Test ◽  
Controlled Clinical Trial ◽  
Log Rank Test ◽  
Kaplan Meier

Objective In advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus. Study Design Secondary database analysis. Setting National Cancer Database (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by log-rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison. Results Twenty-three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log-rank test comparing induction to adjuvant chemotherapy was not significant ( P = .076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.

Baseline neutrophil-to-lymphocyte ratio and absolute lymphocyte count in patients with HER2-negative breast cancer treated with eribulin may predict overall survival.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13005-e13005
Author(s):  
Shigeto Maeda ◽  
Keisei Anan ◽  
Kenichiro Koga ◽  
Sayaka Kuba ◽  
Hiroshi Yano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Lymphocyte Count ◽  
Group Performance ◽  
Absolute Lymphocyte Count ◽  
Neutrophil To Lymphocyte Ratio ◽  
Rank Test ◽  
Lymphocyte Ratio ◽  
Log Rank Test

e13005 Background: In Japan, eribulin has been approved for inoperative or recurrent breast cancer, following treatment with an anthracyclines and a taxanes. We reported the efficacy and safety of eribulin as a first-line to third-line treatment in patients with advanced/metastatic breast cancer (MBC) previously treated with anthracylinsanthracyclines and taxanes (Breast 2017). Briefly, the main inclusion criteria were as follows: no history of eribulin administration; an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2,; human epidermal growth factor receptor 2 (HER2)-negative,; 20–75 years; ≥4 weeks from the last dose of chemotherapy, or ≥2 weeks from the last dosing of endocrine or radiation therapy; measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1; sufficient organ function; life expectancy of ≥3 months; and no significant abnormalities on electrocardiogram. Patients in this clinical trial were enrolled between December 1, 2011, and November 30, 2013. Eribulin was administered intravenously at a dose of 1.4 mg/m2 during a 2-5 min infusion on days 1 and 8 every 3 weeks. In contrast, baseline neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) were reported to predict progression-free survival (PFS) or overall survival (OS). However, these reports were mainly retrospective analysis. Therefore, retrospective evaluation of NLR/ALC in a prospective clinical trial is important to understand the association between NLR/ALC and OS/PFS. Methods: Of 47 prospectively enrolled patients in a previous trial, 45 patients were retrospectively evaluated for baseline NLR/ACL and at the time of 3 cycles of eribulin. The association between NLR/ALC and OS/PFS was also were analyzed for association with OS/PFS. The Kaplan-Meier method was used to estimate the OS/PFS distribution. The cut-off values for baseline NLR and ALC were set at 3 and 1500 /ul, respectively. Results: The median OS of patients with a baseline NLR < 3 was significantly longer than that of patients with a baseline NLR ≥ ≧3 (769 days vs. 409 days; log-rank test p = 0.0333). The median OS of patients with a baseline ALC ≥ ≧1500 was also significantly longer than that of patients with a baseline ALC < 1500 (964 days vs.vs 427 days; log-rank test p = 0.0425). Association between baseline NLR/ALC and PFS were not seen, and also association between at the time of 3 cycles of NLR/ALC and OS/PFS were not seen neither. Conclusions: Baseline NLR and ALC in the patients with HER2- negative breast cancer who plan to treat eribulin may predict overall survival. Clinical trial information: UMIN000007121.

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