scholarly journals Expression signature, prognosis value, and immune characteristics of MUC1 identified by pan-cancer analysis

2021 ◽  
Author(s):  
Zi-Jian Zhang ◽  
YunPeng Huang ◽  
Zhong-Tao Liu ◽  
Kai Liu ◽  
Yong-Xiang Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Disease Free Survival ◽  
Spearman Correlation ◽  
Free Survival ◽  
Spearman Correlation Test ◽  
The Relationship ◽  
Pan Cancer ◽  
Disease Free

Abstract Background: Mucin 1 (MUC1) plays a major role in the occurrence and development of tumor by regulating the process of tumor cell proliferation, epithelial-mesenchymal transformation and epigenetics. However, the relationship between MUC1 expression and tumor prognosis and its role in tumor immunity is still worth exploring. Methods: MUC1 expression was analyzed via GTEx database and TCGA database. We used the Kaplan-Meier survival estimation method to evaluate the influence of MUC1 on tumor prognosis through the survival information from TGCA database. The correlations between MUC1 and immune cell infiltration, tumor microenvironment were investigated through TIMER algorithm and ESTIMATE. In addition, we used Spearman correlation test to examine the correlation between MUC1 and TMB, MSI. Spearman correlation test was also designed to predict the correlation between MUC1 and immune checkpoint genes, four methyltransferases. Further, Gene Set Enrichment Analysis was used to explore the potential mechanism of MUC1 in Adrenocortical carcinoma (ACC) and Liver hepatocellular carcinoma (LIHC). Results: Our study reported that MUC1 is highly expressed in most tumors, differing between cancer types. In most cancers, high expression of MUC1 means poor prognosis indicators, such as overall survival (OS), disease free survival (DSS), disease free survival (DFS) and progression free survival (PFS). MUC1 was positively correlated with infiltrating levels of B cells, CD4+ T cells and CD8+ T cells, dendritic cells, macrophages, neutrophils in LIHC, Prostate adenocarcinoma (PRAD) and Thyroid carcinoma (THCA). Besides, we reported that the expression of MUC1 correlated significantly with immune checkpoint gene, TMB and MSI and in most tumors. However, we found that MUC1 is negatively correlated with most immunotherapy-related indicators in BRCA and LUAD. The relationship between MUC1 and tumor neoantigens and DNA methylase is different in different tumors.In ACC and LIHC, MUC1 can promote the metabolism of many substances. MUC1 can inhibit amyotrophic lateral sclerosis, DNA replication, base excision repair, proteasome in ACC. Similarly, MUC1 inhibits axon guidance, the interaction of cytokine and cytokine receptor, focal adhesion, and endocytosis in LIHC. Conclusions: Our research demonstrates that MUC1 is correlated with prognosis and tumor-infiltrating immune cells, including those of B cells, CD8+ T cells, CD4+ T cells, dendritic cells, macrophages, neutrophils in different tumors. In addition, MUC1 is related to immune checkpoint gene, neoantigen, and some prognostic indicators of immunotherapy such as TMB and MSI, suggesting that MUC1 can also be invoked as a target and prognostic biomarker of immunotherapy. By analyzing the relationship between the expression of MUC1 and methyltransferase, we found that MUC1 regulates DNA methylation. Finally, we used GSEA to study the function of MUC1 in ACC and LIHC. Briefly, our study highlights the significance of MUC1 in the study of tumor immunity from the perspective of pan-cancer.

Evaluating high-grade prostatic intraepithelial neoplasia as a predictor of outcome following radical prostatectomy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4612-4612
Author(s):  
P. M. Pierorazio ◽  
S. M. Lambert ◽  
T. R. McCann ◽  
A. E. Katz ◽  
C. A. Olsson ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Perineural Invasion ◽  
Disease Free Survival ◽  
Intraepithelial Neoplasia ◽  
High Grade ◽  
Free Survival ◽  
Pathologic Stage ◽  
Significant Difference ◽  
The Relationship ◽  
Disease Free

4612 Background: The presence of high-grade prostatic intraepithelial neoplasia (HGPIN) has been associated with future development of prostate cancer. High-grade intraepithelial neoplasia in other malignancies is associated with adverse outcome. This study examines the relationship between the presence of HGPIN in prostatectomy specimens, biochemical disease free survival (bDFS) and other cancer specific outcomes following radical retropubic prostatectomy (RRP). Methods: The Columbia University Urologic Oncology Database was reviewed and 2,522 were identified who had undergone radical prostatectomy from 1988 to 2005; 2,133 patients with or without HGPIN were included. Two-sample proportion analysis of means with 95% confidence intervals and ANOVA techniques were used to evaluate the relationship between HGPIN and pathologic stage, Gleason sum, perineural invasion, multifocality, extracapsular extension (ECE), margin status, and nodal status. Kaplan-Meier analysis with log-rank test and a multivariate Cox proportional hazard model controlling for preoperative PSA, Gleason sum and pathologic stage were used to assess differences in bDFS. Results: 1,885 of 2,133 (88.4%) patients demonstrated HGPIN. There was no significant difference in the distribution of pathologic stage or Gleason sum between the patients with and without HGPIN. The HGPIN-positive group had higher rates of perineural invasion (69.9 vs. 57.5%; p = 0.003), multifocality (63.0 vs. 38.4%; p = 0.000) and ECE (56.4% vs. 48.4%; p = 0.059). There was no statistically significant difference observed in nodal status or margin status between the two groups. Patients without HGPIN had an increased bDFS demonstrated by a predicted disease free survival of 73.6% versus 67.0% at 9 years (p = 0.045) with a median follow-up of 50 months. In the multivariate Cox hazard model HGPIN, PSA, Gleason sum and pathologic stage were validated as independent predictors of failure (p < 0.001). The risk of failure was 1.9 × greater in the HGPIN-positive group than the HGPIN-negative group (p=0.006). Conclusions: The presence of HGPIN in the radical prostatectomy specimen denotes a significantly higher rate of tumor multifocality, perineural invasion, ECE, and ultimately biochemical recurrence. No significant financial relationships to disclose.

Long-Term Results of RTOG Trial 8911 (USA Intergroup 113): A Random Assignment Trial Comparison of Chemotherapy Followed by Surgery Compared With Surgery Alone for Esophageal Cancer

2007 ◽  
Vol 25 (24) ◽  
pp. 3719-3725 ◽  
Author(s):  
David P. Kelsen ◽  
Katryn A. Winter ◽  
Leonard L. Gunderson ◽  
Joanne Mortimer ◽  
Norman C. Estes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Preoperative Chemotherapy ◽  
Disease Free Survival ◽  
R0 Resection ◽  
Free Survival ◽  
R1 Resection ◽  
The Relationship ◽  
Disease Free

Purpose We update Radiation Therapy Oncology Group trial 8911 (USA Intergroup 113), a comparison of chemotherapy plus surgery versus surgery alone for patients with localized esophageal cancer. The relationship between resection type and between tumor response and outcome were also analyzed. Patients and Methods The chemotherapy group received preoperative cisplatin plus fluorouracil. Outcome based on the type of resection (R0, R1, R2, or no resection) was evaluated. The main end point was overall survival. Disease-free survival, relapse pattern, the influence of postoperative treatment, and the relationship between response to preoperative chemotherapy and outcome were also evaluated. Results Two hundred sixteen patients received preoperative chemotherapy, 227 underwent immediate surgery. Fifty-nine percent of surgery only and 63% of chemotherapy plus surgery patients underwent R0 resections (P = .5137). Patients undergoing less than an R0 resection had an ominous prognosis; 32% of patients with R0 resections were alive and free of disease at 5 years, only 5% of patients undergoing an R1 resection survived for longer than 5 years. The median survival rates for patients with R1, R2, or no resections were not significantly different. While, as initially reported, there was no difference in overall survival for patients receiving perioperative chemotherapy compared with the surgery only group, patients with objective tumor regression after preoperative chemotherapy had improved survival. Conclusion For patients with localized esophageal cancer, whether or not preoperative chemotherapy is administered, only an R0 resection results in substantial long-term survival. Even microscopically positive margins are an ominous prognostic factor. After a R1 resection, postoperative chemoradiotherapy therapy offers the possibility of long-term disease-free survival to a small percentage of patients.

scholarly journals Prognostic Impact of Hypoxia-InduciblemiRNA-210in Patients with Lung Adenocarcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jun Osugi ◽  
Yuka Kimura ◽  
Yuki Owada ◽  
Takuya Inoue ◽  
Yuzuru Watanabe ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Disease Free Survival ◽  
Inverse Correlation ◽  
Prognostic Impact ◽  
Free Survival ◽  
Cox Analysis ◽  
Medical University ◽  
Disease Stages ◽  
The Relationship ◽  
Disease Free

Objective. The aim of this study was to investigate the prognostic value ofMicroRNA-210(miR-210) expression in patients with non-small-cell lung cancer (NSCLC).Methods. We examined themiR-210expression of samples of 80 patients, who underwent surgical resection at Fukushima Medical University from 2004 to 2007, by using quantitative RT-PCR. The relationship betweenmiR-210expression and clinicopathological factors as well as histological subtype was statistically analyzed.Results.miR-210expression showed an inverse correlation with disease-free and overall survival in patients with NSCLC. Significant correlations were found betweenmiR-210expression and lymph node metastasis, late disease stages, and poor prognosis in patients with adenocarcinoma. Multivariate Cox analysis indicated thatmiR-210expression was an independent prognostic factor for disease-free survival in patients with adenocarcinoma.Conclusions. We showed thatmiR-210may be a prognostic biomarker for patients with NSCLC, especially for those with lung adenocarcinoma.

scholarly journals Therapy of 4s Chimeric Antigen Receptor T Cells Achieves Long-Term Disease-Free Survival with No Severe CRS or Cres in Patients with Relapsed and Refractory Acute Lymphoblastic Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2696-2696 ◽  
Author(s):  
Sanfang Tu ◽  
Rui Huang ◽  
Lan Deng ◽  
Xuan Zhou ◽  
Yanjie He ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Lymphoblastic Leukemia ◽  
Objective Response ◽  
Disease Free Survival ◽  
Tumor Burden ◽  
Fourth Generation ◽  
Free Survival ◽  
Car T ◽  
Disease Free

Abstract Background: CD19 targeting chimeric antigen receptor T cells(CART19) therapy have shown great therapeutic potential in relapsed and refractory B cell acute lymphoblastic leukemia (ALL), but associated with risk of life-threatening adverse effects as severe cytokine release syndrome (sCRS) and CAR-T-cell-related encephalopathy syndrome (CRES).It's been reported that high leukemia burden before CART therapy, and high does infused CART cells are associated with severity of CRS and CRES. To decrease the risk of severe adverse effect, we applied integrated therapeutic strategy of using fourth generation CART cells , reducing leukemia blasts burden in bone marrow, and decreasing the dose of infused CART cells (www.clinicaltrials.gov; #NCT03407859 and #NCT03125577 ). Methods: Between May 23, 2016 and July 2, 2018,the trial enrolled 20 patients (pts) who were exhausted with all available treatment options, life expectancy >2 months,CD19-positive and diagnosis of B lineage ALL.T cells were apheresis collected and transduced with an apoptosis-inducible, safety-engineered lentivector CAR with the following intracellular signaling domains: CD28/CD27/CD3ζ-iCasp9 (4SCAR). In vitro amplication of CART was not performed. In pts with bone marrow blasts exceeding 50.0%, VDCP or similar chemotherapy was given to reduce the tumor burden, and then received FC conditioning regimen (FLU 30mg/m2, d1-3; CTX 300mg/m2, d1-3), while FC regimen was directly carried out in pts with bone marrow blasts less than 50.0%.In this trial, Pts received single CD19-targeted CARTs or multi-CARTs targeting CD19 and an additional antigen of CD22 or CD123.The level of CAR-T cells and cytokines in peripheral blood, as well as tumor burden was measured after infusion. Results: 20 pts were enrolled and infused with CAR-T cells. The median age is 37.5 (16-67) years old. Of these pts, 5 had prior HSCT and 14 had adverse genetic abnormalities, including 4 pts (20%) who were Philadelphia chromosome-positive(Ph+). All pts were previously treated with 2-22 courses of cytotoxic chemotherapy regimens. The overall objective response rate was 85%(17/20), and the complete response(CR) rate was 80%(16/20). The complete remission rate of 12 pts receiving single CD19-targeted CART therapy was 83 %(10/12), while 33%(4/12) of them had disease relapse at 6 months after infusion. Of the 7 people who received multi-CARTs infusion, 71%(5/7) achieved complete remission, with relapse rate of 29%(2/7) at 6 months after infusion. 3 pts who relapsed post transplantation received combination therapy of anti-CD19 CART and anti-CD123 CART, and all achieved minimal residual disease-negative CR within 1 month after CART infusion, 2 of whom maintained disease-free survival for 7 months and 11 months to date, respectively. Among the 7 people who underwent HSCT after achieving CR, 6 of them maintained disease-free survival for 3 months to 9 months. At a median follow-up of 115.5 days (ranging from14 to 384), the median overall survival was 269 days and the median event-free survival was 232 days. During treatment and follow-up, the most common adverse events were grade 1-2 cytokine release syndrome (CRS), with an incidence of 55%.No grade 3 or higher CRS was observed.12 pts were infused with a dose equal to or exceeding 5*10^5/kg, 10 of whom had CRS response. While only 2 of the 8 pts who received the infusion dose of less than 5*10^5/kg had CRS reaction and both of them were grade 1 CRS, suggesting low CAR-T cell doses decrease the risk of CRS (P=0.009). Interestingly, the objective response rate did not differ significantly between the low dose and high dose group. Conclusions: Based on fourth generation CART system, a therapeutic strategy of low tumor burden and low CART infusion dose shows a safer profiling while remaining potent efficacy against leukemia. Disclosures No relevant conflicts of interest to declare.

Association of mucin production and survival in colon cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
John Hogan ◽  
Georges Samaha ◽  
John Burke ◽  
David Waldron ◽  
Eoin Condon ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Mucin Production ◽  
Kaplan Meier ◽  
The Relationship ◽  
Disease Free

512 Background: Debate persists regarding the relationship between mucin production and cancer-related outcome following curative resection for colon cancer. Lack of consensus is due to (amongst other factors) discrepancies in definition, small cohort studies and the integration of both colon and rectal cancers. This study characterizes the relationship between mucin production and cancer-related outcome in an homogenous single-institute based cohort. Methods: A database spanning demographics, clinico-pathologic characteristics and prognostic factors was generated for all patients undergoing curative-intent colonic resection in the interval 2000 to 2010. Patients were categorized simply as mucin producing (i.e. MC) or non-mucin producing adenocarcinoma (NMC). Primary outcomes included overall survival (time to death from any cause) and disease free survival (time to loco-regional and systemic recurrence). Trends were established for MC and NMC using Kaplan-Meier estimates, plotted and compared using log-rank analysis. Findings significant on univariate analysis were incorporated into multivariate analysis. Cox proportional hazards model was employed to determine the associated hazard of both death and disease recurrence in each group. Statistical analysis was performed using R version 2.15. P < 0.05 was considered significant. Results: 77 mucinous carcinomas (MC) and 358 non mucinous carcinomas (NMC) were included. On univariate analysis, MC was associated with improved overall survival (OS) (P=0.007). Both N1 (HR 1.625, P=0.011) and N2 (HR 2.7, P<0.001) status were associated with adverse OS. On multivariate analysis, MC approached but did not reach statistical significance for improved OS (HR 0.543, P=0.061). A comparison of Kaplan-Meier estimates for overall survival in MC and NMC groups indicated that OS was significantly improved in the MC cohort (P=0.011). There was no difference in disease free survival (P=0.224). Systemic recurrence was greater in the NMC group (P=0.042). Conclusions: Mucin production in colonic adenocarcinoma appears associated with improved overall but not disease-free survival. In addition, the absence of mucin was associated with adverse systemic but not local recurrence.

Randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III colon cancer and deficient mismatch repair (ATOMIC, Alliance A021502).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15169-e15169 ◽  
Author(s):  
Frank A. Sinicrope ◽  
Fang-Shu Ou ◽  
Tyler Zemla ◽  
Andrew B. Nixon ◽  
Kabir Mody ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cells ◽  
Randomized Trial ◽  
Mismatch Repair ◽  
Total Duration ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Free Survival ◽  
Disease Free

e15169 Background: In metastatic colorectal cancer with deficient DNA mismatch repair (dMMR), anti-PD-1 antibody monotherapy produced high tumor response rates and extended progression-free survival compared to lack of benefit for cancers with proficient MMR. In an ongoing phase III randomized trial, we will determine if the addition of the anti-PD-L1 antibody, atezolizumab (Genentech), to adjuvant FOLFOX can improve patient disease-free survival (DFS) vs FOLFOX alone in patients with stage III colon cancers with dMMR. By blocking the PD-1/PD-L1 interaction, atezolizumab may activate T cells, thereby, restoring their ability to detect and attack tumor cells. Limited data suggest that FOLFOX may increase intratumoral cytotoxic CD8+ T cells that could serve as ‘immune priming'. Methods: Patients with curatively resected stage III colon carcinomas with evidence of dMMR are randomized to modified FOLFOX6 for 6 months (12 cycles) alone (control arm) or combined with atezolizumab (840 mg IV q2 wk) with continuation of the antibody as monotherapy for an additional 6 months (total duration of 12 months) [experimental arm]. Patients will be stratified by T, N stage and tumor sidedness. Local testing for MMR proteins is allowed. Atezolizumab must begin by/with cycle 2. One cycle of FOLFOX is allowed pre-registration. The targeted accrual goal of 700 patients and 165 disease-free survival (DFS) events will provide 90% power to detect an effect size expressed as hazard ratio of 0.6 for the primary endpoint of DFS at two-sided alpha of 0.05. Interim analyses are planned at 50% and 75% of events. Secondary endpoints include overall survival, treatment tolerability, and quality of life. Results: This study is being conducted by the Alliance for Clinical Trials in Oncology, was approved by NCI CTEP and activated in 09/2017. The study is actively accruing and, as of 02/11/2019, 152 patients are enrolled. We are actively exploring an international collaboration. Conclusions: This is a current clinical trial in progress. Clinical trial information: NCT02912559.

EORTC 1707 VESTIGE: Adjuvant immunotherapy in patients with resected gastric cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): An open-label randomized controlled phase II study.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS467-TPS467 ◽  
Author(s):  
Elizabeth Catherine Smyth ◽  
Maren Kristina Knoedler ◽  
Magnus Nilsson ◽  
Anna Dorothea Wagner ◽  
Markus H. Moehler ◽  
...  
Keyword(s):  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Immune Checkpoint ◽  
Phase Ii Study ◽  
Disease Free Survival ◽  
Immune Checkpoint Blockade ◽  
Open Label ◽  
Free Survival ◽  
Gastroesophageal Adenocarcinoma ◽  
Disease Free

TPS467 Background: Gastroesophageal adenocarcinoma patients with metastatic lymph nodes (ypN+) or a microscopically incomplete surgical resection (R1) following neoadjuvant chemotherapy are at high risk of disease recurrence. Current practice is to continue with the same perioperative chemotherapy used prior to surgery, despite these suboptimal outcomes. Immune checkpoint blockade with nivolumab and ipilimumab has demonstrated activity in advanced gastroesophageal adenocarcinoma. We hypothesise that high risk (ypN+ and/or R1) post resection gastroesophageal adenocarcinoma patients who are treated with nivolumab and ipilimumab will have better disease free survival than patients who continue with standard post-operative chemotherapy. Methods: VESTIGE is an ongoing, international, open label randomized phase II study designed to evaluate the efficacy of adjuvant nivolumab plus ipilimumab versus standard post-operative chemotherapy in high risk (ypN+ and/or R1) post resection gastroesophageal adenocarcinoma patients. Eligible patients (n=240) will be randomised 1:1 to receive post-operative adjuvant chemotherapy (identical regimen as pre-operatively) or nivolumab 3mg/kg IV q2w plus ipilimumab 1mg/kg IV q6w x 1 year. Key inclusion criteria include ypN+ and/or R1 status following neoadjuvant chemotherapy plus surgery and an adequate pre-specified surgical resection. The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety, toxicity and quality of life. The trial will recruit 240 patients at 24 number of sites in the Czech Republic, France, Germany, Israel, Italy, Norway, Poland, Portugal, Spain, and United Kingdom. Recruitment commenced July 2019 and is anticipated to take 30 months. The VESTIGE translational research programme includes collection of pre-treatment biopsies, post-chemotherapy resection specimens and serial liquid biopsy on treatment to explore biomarkers predictive of immune checkpoint blockade efficacy. Clinical trial information: NCT03443856.

Immune System Profiling Following Autologous Stem Cell Transplant for High-Risk Neuroblastoma Predicts Disease-Free Survival

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2251-2251
Author(s):  
Michele L Nassin ◽  
Elitsa V Nicolaou ◽  
Hillary M Hecktman ◽  
Caitlin W Cohen ◽  
Susan L Cohn ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Disease Free Survival ◽  
Chimeric Antibody ◽  
Cd4 Cells ◽  
Cell Recovery ◽  
Free Survival ◽  
Disease Free

Abstract Objective: Neuroblastoma (NB) is the most common extra cranial solid tumor in childhood. It accounts for approximately 7% of pediatric cancer diagnoses each year in the United States yet is responsible for 15% of pediatric cancer deaths annually. Occurring overwhelmingly in patients with high-risk (HR) disease. Measurable immune surveillance correlates with improved overall disease-free survival in patients with a myriad of cancer subtypes, including NB. Current therapeutic strategies in HR-NB incorporate manipulation of the host immune response, including autologous stem cell transplantation (autoSCT), cis-retinoic acid, and chimeric antibody targeting the tumor-associated antigen disialoganglioside (GD2). Understanding how such therapies affect the immune system and its relation to clinical response is of critical importance. We speculate that patients with higher proportions of regulatory T cells (Tregs) and slower recovery of other lymphocyte subsets will have higher rates of progressive disease and/or relapse. Methods: We reviewed the records of all University of Chicago patients between 2009 and 2015 who received autoSCT as part of upfront therapy for HR neuroblastoma. Data included complete blood count and peripheral blood lymphocyte flow cytometric (FACS) subset monitoring. Our analysis aimed to determine the association between lymphocyte subset kinetics following autoSCT with pre-transplant treatment, transplant conditioning, and disease-free/overall survival. Patients who had a follow-up of greater than one-year post-transplantation were included in the analysis. Results: Thirty-four patients (59% male, median age 5.6 years) received autoSCT between 2009 and 2015 for HR neuroblastoma. Seventy-six percent (n = 26) received either carboplatin, etoposide, melphalan (CEM) or busulfan/melphalan (BuMel) for conditioning. Among those patients, twenty-seven percent received MIBG prior to their autoSCT. The other patients received BSO/melphalan or tandem transplantations. Sixty-eight percent of these patients went on to receive chimeric antibody after their autoSCT irrespective of their conditioning regimen. Antibody therapy with IL-2 or GM-CSF was initiated at a median of 101 days (mean 98.9) post-autoSCT. All patients had normal neutrophil counts at 100 days post transplant, while the total absolute lymphocyte count (ALC), CD8+ T cells, NK cells and CD19+ B cells, were below normal levels in the majority of patients, (100%, 89%, 79% and 94% of patients respectively). Patients who received MIBG prior to autoSCT had a higher proportion of CD3+CD4+CD25+ T cells, the subset containing Tregs, among their total CD3+ population at 100 days post-transplant, (79.8% versus 32.8% p-value = 0.02). Following single autoSCT, patients with higher ALC and CD4+ cells had increased disease free survival in evaluations after six months post transplant. (Figure 1) CD8+ cells, NK cells and CD19+ cell counts were not significant in this analysis. Conclusions: Patients with HR NB have differential immune cell recovery following autoSCT that is dependent on the type of therapy received prior to autoSCT. Specifically, patients who received MIBG had markedly higher proportion of CD3+CD4+CD25+ T cell recovery compared to patients not receiving pre-autoSCT MIBG. This is the subset containing Tregs, which may indicate suppression of an anti-NB immune response long-term. Immune reconstitution is globally poor in all patients at the time of chimeric antibody immunotherapy that is initiated around day 100-post autoSCT. There are features of immune reconstitution that appear to correlate with improved outcomes, including elevated ALC, CD8+ and CD4+ cell counts when evaluated at least six months post transplantation. Additional characterization of T cell subsets is currently being performed to quantify the number of Treg cells in the CD3+CD4+CD25+ T cell subset population. Prospective evaluation of both immune cell recovery and functional evaluation of cells is required to confirm these findings, which may have a profound impact on how immune modulatory therapy is scheduled for those patients with high-risk neuroblastoma. Figure 1 (Panel A) Patients with higher ALC (panel A) and CD4+ cells (panel B) checked at least 6 months after stem cell transplantation had increased disease-free survival (DFS) compared to those patients with diminished ALC and CD4+ cells recovery. Figure 1. (Panel A) Patients with higher ALC (panel A) and CD4+ cells (panel B) checked at least 6 months after stem cell transplantation had increased disease-free survival (DFS) compared to those patients with diminished ALC and CD4+ cells recovery. Disclosures No relevant conflicts of interest to declare.

scholarly journals Usefulness of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a predictor of disease-free survival in breast cancer: A cross-sectional study

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 306
Author(s):  
Yaala S. Al-Bairmany ◽  
Adil S. Aqabi ◽  
Farah H. Al-Hasnawi ◽  
Alaa S. Al-Aawad
Keyword(s):  
Disease Free Survival ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Free Survival ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
The Relationship ◽  
Disease Free

Background: The relationship between neutrophil-lymphocyte ratio (NLR) with outcome is a complex issue. A high NLR reflects systemic inflammation. This study aimed to estimate the relationship between NLR, and platelet-lymphocyte ratio (PLR) in disease-free survival (DFS). Methods: This was a cross-sectional study in which we reviewed the patient files of 102 patients with breast cancer treated at the Babylon Oncology Center from January 2009 to September 2014, who had follow-up for at least 36 months. The following data were collected from patient files: age, diagnosis date, date of recurrence and/or metastasis, follow-up, histological tumor type, tumor size, node metastasis stage, histological differentiation degree, estrogen and/or progesterone receptor expression, HER2 neu status, and metastasis site. Results: The mean age of patients was 50.4 ± 11.7 years and lowest period of follow up was 40 months. Longest DFS was 62 months, with 5 years DFS in 52.5% of patients. Stage N0 was associated with a significantly higher DFS compared to stage N1. Isolated local recurrence was seen in 15% of patients and combined local recurrences with distant metastasis was observed 37%. NLR had the highest discrimination ability to predict recurrence and distant metastasis. Conclusion: An increase in NLR was associated with poor DFS, and it can therefore be a predictive and prognostic factor. NLR’s established prediction model warrants further investigation.

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