Impact of FISH and Cytogenetics On Overall and Event Free Survival in Myeloma: An IMWG Analysis of 9,897 Patients.

Abstract Abstract 743 Background There has been considerable recent focus upon the molecular classification of myeloma. However, the prognostic impact of molecular changes has mostly been assessed from small and/or incomplete studies from single institutions or groups. There has been no large scale analysis of molecular features linked to ISS stage. Methods In order to clarify the overall impact of molecular changes we undertook a collective analysis of 9,897 patients through the International Myeloma Working Group (IMWG). Within this population 2,295 patients had presence of cytogenetic abnormalities (Any CA); 1,713 hypodiploidy; 1,673 hyperdiploidy; 2,309 cytogenetic deletion 13; 3,226 deletion 13 by FISH; 1,573 FISH t(4;14); 1,486 FISH del p17; 1, 683 FISH t(11:14); and 366 FISH t(4;16). Enrolled patients had complete clinical and treatment details available including baseline standard prognostic factors, ISS stage, as well as both progression free survival (PFS) and overall survival (OS) information. Data came from 14 sites: 3 from the US and the remainder from Europe, Asia, and Latin America as for the ISS staging system analyses. Univariate and multivariate analyses were performed. Results Each of the known adverse molecular features had a negative impact upon both PFS and OS (p=002 - <0.0001). Among the deleterious FISH abnormalities the t(4;14) abnormality was the most highly correlated with poorer outcomes by PFS: 4 year estimate: 32% vs. 60% (p<0.0001). The t(4;14) abnormality combined with ISS Stage also significantly enhanced predictive capability: ISS Stage I without t(4;14) OS 81% @ 4 years; ISS Stage III with t(4;14) OS 22% @ 4 years (P<0.0001) [Figure 1]. The best outcomes were for ISS Stage I in the presence of t(11;14): OS 89% @ 4 years. Absence of any one adverse feature correlated with 80-81% OS @ 4 years for Stage I. Presence of any one adverse feature had a more variable impact and correlated with 22%-40% OS at 4 years for Stage III. In univariate correlations the most predictive correlations with OS were presence of Any CA, t(4;14), 17p-, hypodiploidy, cytogenetic 13q- with R2 values of 6.9%, 4.5%, 4.1% and 3.8% respectively. In multivariate analyses, ISS stage provided the best predictions: R2 values = 13.3%. The added contributions from molecular features were: t(4;14) 3.8%; cytogenetic 13q- 2.9%; Any CA 2.3%; and 17p- 1.0%. The maximum total R2 for OS was 22%. Conclusions This large multicenter analysis confirms the correlations between abnormal molecular findings and outcomes. Combinations with ISS Stage provide the best predictive capability. Presence of Any CA, t(4;14), 17p-, hypodiploidy and cytogenetic 13q- contribute to poorer outcomes by ISS stage. The presence of hyperdiploidy and/or t(11;14) contribute to better outcomes. There is thus validation of prior molecular studies related to prognosis utilizing this large IMWG database. Disclosures: No relevant conflicts of interest to declare.

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Hypopharyngeal cancer treatment based on definitive radiotherapy: who is suitable for laryngeal preservation?

The Journal of Laryngology & Otology ◽

10.1017/s0022215107000692 ◽

2007 ◽

Vol 122 (5) ◽

pp. 506-512 ◽

Cited By ~ 10

Author(s):

S-W Chen ◽

M-H Tsai ◽

S-N Yang ◽

J-A Liang ◽

A-C Shiau ◽

...

Keyword(s):

Prognostic Factors ◽

Proportional Hazards Model ◽

Multivariate Analyses ◽

Local Relapse ◽

Hypopharyngeal Cancer ◽

Stage I ◽

Stage Iii ◽

Relapse Free Survival ◽

Free Survival ◽

Laryngeal Preservation

AbstractAims:To investigate prognostic factors for survival and locoregional control in patients with stage I–IVA hypopharyngeal cancer treated with laryngeal preservation radiotherapy.Methods:This study was a retrospective analysis of 108 patients with stage I–IVA squamous cell carcinoma of the hypopharynx, treated with laryngeal preservation radiotherapy. Actuarial survival, disease-specific survival and local relapse-free survival were calculated, and multivariate analyses were performed using Cox's proportional hazards model.Results:After a median follow-up duration of 39 months, the five-year local relapse-free survival rate was 35 per cent for all patients, 66 per cent for those with stage I–II disease, 46 per cent for those with stage III disease and 20 per cent for those with stage IVA disease (p = 0.004). Multivariate analyses showed that tumour and node stages were independent prognostic factors.Conclusions:Patients with stage I–II disease were suitable for laryngeal preservation radiotherapy. For most patients with stage III–IVA disease, other than those who were T1 N1 or T2 N1, the treatment results were poor.

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Impact of the Number of Dissected Lymph Nodes on Survival for Gastric Cancer after Distal Subtotal Gastrectomy

Gastroenterology Research and Practice ◽

10.1155/2011/476014 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Chang-Ming Huang ◽

Jian-Xian Lin ◽

Chao-Hui Zheng ◽

Ping Li ◽

Jian-Wei Xie ◽

...

Keyword(s):

Gastric Cancer ◽

Survival Rate ◽

Lymph Nodes ◽

Distal Gastrectomy ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Prognostic Impact ◽

Term Survival

Objectives. To investigate the prognostic impact of the number of dissected lymph nodes (LNs) in gastric cancer after curative distal gastrectomy.Methods. The survival of 634 patients who underwent curative distal gastrectomy from 1995 to 2004 was retrieved. Long-term surgical outcomes and associations between the number of dissected LNs and the 5-year survival rate were investigated.Results. The number of dissected LNs was one of the most important prognostic indicators. Among patients with comparable T category, the larger the number of dissected LNs was, the better the survival would be (). The linear regression showed that a significant survival improvement based on increasing retrieved LNs for stage II, III and IV (). A cut-point analysis yields the greatest variance of survival rate difference at the levels of 15 LNs (stage I), 25 LNs (stage II) and 30 LNs (stage III).Conclusion. The number of dissected LNs is an independent prognostic factor for gastric cancer. To improve the long-term survival of patients with gastric cancer, removing at least 15 LNs for stage I, 25 LNs for stage II, and 30 LNs for stage III patients during curative distal gastrectomy is recommended.

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Staging Breast Cancer - Screening for Occult Metastases

Tumori Journal ◽

10.1177/030089168507100404 ◽

1985 ◽

Vol 71 (4) ◽

pp. 339-344 ◽

Cited By ~ 12

Author(s):

Stefano Ciatto ◽

Paolo Pacini ◽

Patrizia Bravetti ◽

Luigi Cataliotti ◽

Gaetano Cardona ◽

...

Keyword(s):

Breast Cancer ◽

Early Detection ◽

Detection Rate ◽

Clinical Stage ◽

Preoperative Staging ◽

Stage I ◽

Stage Iii ◽

Prognostic Impact ◽

Detection Rates ◽

Occult Metastases

The authors report on 1,017 consecutive breast cancer cases without symptomatic metastases staged by means of chest X-ray (CXR), skeletal survey (BXR) and bone scintigraphy (BS). Occult metastases (DM) detection rate was 0.88 %: 0.29 % for lung and 0.59 % for bone DM. The detection rate was correlated with clinical stage: 0.36 % for stage I, 0.20 % for stage II, 0.26 % for stages I and II, and 2.77 % for stage III cases. The sensitivity based on DM cases prevalent or surfacing within 6 months of follow-up was 0.30 for CXR, 0.22 for BXR and 0.55 for BS; specificity was 0.99, 0.98 and 0.90, respectively. The study confirms the possibility of early detection of DM with preoperative staging, but the extremely low detection rates in stage I and II cancers do not advise such a routine procedure. The higher detection rate of DM may suggest adoption of the routine staging procedure in stage III cancers. In these cases, although no evidence is available of a favorable prognostic impact of early detection and treatment of DM, an unnecessary mastectomy could be avoided in about 3 % of cases in the presence of DM detected by the staging procedure.

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Prognostic impact of WT1 mutations in cytogenetically normal acute myeloid leukemia: a study of the German-Austrian AML Study Group

Blood ◽

10.1182/blood-2008-10-183392 ◽

2009 ◽

Vol 113 (19) ◽

pp. 4505-4511 ◽

Cited By ~ 116

Author(s):

Verena Ingeborg Gaidzik ◽

Richard Friedrich Schlenk ◽

Simone Moschny ◽

Annegret Becker ◽

Lars Bullinger ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Negative Impact ◽

Serum Lactate Dehydrogenase ◽

Study Group ◽

Prognostic Impact ◽

Relapse Free Survival ◽

Free Survival ◽

Acute Myeloid

AbstractTo evaluate the incidence and clinical impact of WT1 gene mutations in younger adult patients with cytogenetically normal acute myeloid leukemia (CN-AML), sequencing of the complete coding region was performed in diagnostic samples from 617 patients who were treated on 3 German-Austrian AML Study Group protocols. WT1 mutations were identified in 78 (12.6%) of the 617 patients; mutations clustered in exon 7 (54 of 78) and exon 9 (13 of 78), but also occurred in exons 1, 2, 3, and 8. WT1 mutations were significantly associated with younger age, higher serum lactate dehydrogenase levels, higher blood blast counts, and the additional presence of FLT3-ITD (P < .001) and CEBPA mutations (P = .004). There was no difference in relapse-free survival and overall survival between patients with (WT1mut) or without WT1 mutations. Subset analysis showed that patients with the genotype WT1mut/FLT3-ITDpos had a lower complete remission rate (P = .003) and an inferior relapse-free survival (P = .006) and overall survival (P < .001) compared with those with the genotype WT1mut/FLT3-ITDneg. In conclusion, in our large cohort of younger adults with CN-AML, WT1 mutation as a single molecular marker did not impact on outcome. However, our data suggest a negative impact of the genotype WT1mut/FLT3-ITDpos.

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Prognostic Impact of Clinical and Molecular Markers in Normal Karyotype AML-Results from the AMLCG 2000 Trial.

Blood ◽

10.1182/blood.v110.11.3482.3482 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3482-3482

Author(s):

Friederike Schneider ◽

Eva Hoster ◽

Marietta Rottenkolber ◽

Stephanie Schneider ◽

Annika Dufour ◽

...

Keyword(s):

Molecular Markers ◽

Risk Stratification ◽

Multivariate Analyses ◽

Normal Karyotype ◽

Molecular Techniques ◽

Prognostic Impact ◽

Clinical Parameters ◽

Single Mutation ◽

Free Survival ◽

Molecular Alterations

Abstract Background: Prognosis of AML is influenced by different clinical and molecular alterations. We performed a multivariate analysis including five molecular markers NPM1, FLT-ITD, CEBPA, FLT-TKD and MLL-PTD combined with clinical parameters at initial diagnosis to refine risk stratification. Patients and methods: Prognostic impact of clinical and molecular parameters in respect to OS, EFS, RFS and CR was assessed in 803 patients with normal karyotype included in the AMLCG (German AML Cooperative Group) 2000 trial until 01/2006. Patients were randomly assigned to treatment with TAD (thioguanine, conventional-dose AraC, daunorubicin) followed by HAM (high-dose AraC, mitoxantrone) or with the double-induction regimen consisting of two courses of HAM (quotation Buechner JCO 2006). Patient age ranged from 17 to 85 years (median: 60 yrs). 51% of patients were male, 49% female. 81% of patients had de novo AML. Performance status was normal or slightly impaired in the majority of patients (71% ECOG 0/1). Median blood counts at diagnosis were: Hb: 9.2 g/dl (4.2–16.4 g/dl); WBC: 16.0 G/l (0.1–798.2 G/l); platelets: 58 G/l (0.02–643 G/l), LDH: 410 U/l (8–14332 U/l) and bone marrow (BM) blasts: 80% (6–100%). Molecular markers’ mutation status and all mentioned clinical parameters were included in univariate analyses. In multivariate analyses only univariate significant parameters were used. Results: In 560 patients with all five molecular markers analyzed by routine molecular techniques at diagnosis the frequency of mutations were the following: 52.7% NPM1+, 29.3% FLT3-ITD+, 6.1% FLT3-TKD+, 7.5% MLL-PTD+ and 7.5% CEBPA+. The majority of analyzed patients (44.1%) showed one single mutation only. About one quarter of patients displayed either none (27.5%) or two (26.2%) mutations. A minority of 2.1% had 3 mutations, whereas the combination of four or all five molecular alterations was not found. The most frequent single mutation was NPM1 (28.4%), followed by FLT3-ITD (5.4%), CEBPA (4.8%), MLL-PTD (4.6%) and FLT3-TKD (0.9%). The combination of FLT3-ITD and NPM1 was detected in 18.8% of patients. Complete remission (CR) rate was 65.1%. Median overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) were 19.3, 7.7 and 17.2 months. Multivariate analyses identified the following parameters to have significant impact on prognosis. OS: NPM1, FLT3-ITD, WBC, age (p<0.0001 each) and CEBPA (p=0.003); EFS/RFS: NPM1, FLT3-ITD and age (p<0.0001 each / p<0.0001 each) and LDH (p=0.020 / p=0.040); CR: NPM1 and age (p=0.001 each). Conclusions: Our data show in a large cohort of 560 patients that at least one molecular marker can be identified in 72.5% of patients with NK-AML. The NPM1 mutation and age are the only parameters with an independent impact on all outcome parameters (OS, EFS, RFS, CR). These data provide the basis for a prognostic model in NK-AML that can be used for risk stratification and selection of patients that will benefit from allogeneic stem cell transplantation.

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Increased Expression of Macrophage Migration Inhibitory Factor (MIF) Receptor CD74 Is Associated with Inferior Outcome in Younger Patients (Pts) with Cytogenetically Normal Acute Myeloid Leukemia (CN-AML): a Cancer and Leukemia Group B (CALGB) Study.

Blood ◽

10.1182/blood.v114.22.1616.1616 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1616-1616 ◽

Cited By ~ 1

Author(s):

Eyal C. Attar ◽

Kati Maharry ◽

Krzysztof Mrózek ◽

Michael D. Radmacher ◽

Susan P. Whitman ◽

...

Keyword(s):

Overall Survival ◽

Cellular Proliferation ◽

Conflicts Of Interest ◽

Advanced Pancreatic Cancer ◽

Disease Free Survival ◽

Prognostic Impact ◽

Free Survival ◽

Expression Levels ◽

The Impact ◽

Disease Free

Abstract Abstract 1616 Poster Board I-642 CD74 is a type II integral membrane protein receptor that binds its ligand MIF to induce phosphorylation of the extracellular signal-regulated kinase-1/2 (ERK-1/2) and drive cellular proliferation via nuclear factor-kappa B (NF-kB) activation. CD74 expression has been identified in human solid tumors, and its expression is associated with adverse prognosis in advanced pancreatic cancer. As CD74 is expressed and NF-kB constitutively activated in myeloblasts, we hypothesized that CD74 expression might also be associated with adverse outcome in AML. To investigate the prognostic impact of CD74 expression in the context of other predictive molecular markers in CN-AML, we assessed CD74 expression levels by Affymetrix HG-U133 Plus 2.0 microarray in 102 younger [<60 years (y)] adults with primary CN-AML, treated on the front-line CALGB 19808 trial with an induction regimen containing daunorubicin, cytarabine, etoposide and, in some cases, the inhibitor of multidrug resistance valspodar, and consolidation with autologous stem cell transplantation. Microarray data were analyzed using the Robust Multichip Average method, making use of a GeneAnnot chip definition file, which resulted in a single probe-set measurement for CD74. At diagnosis, CD74 expression, when assessed as a continuous variable, was significantly associated only with extramedullary disease involvement (P=.006) among clinical features, and with none of the molecular prognostic variables tested, including NPM1, WT1, CEBPA, FLT3 (FLT3-ITD and FLT3-TKD) mutations, MLL partial tandem duplication, or differential BAALC and ERG expression levels. Although CD74 expression levels were not associated with achievement of complete remission (CR; 83% vs 81%), higher levels of CD74 were associated with shorter disease-free survival [DFS; P=.046, hazard ratio (HR) 1.85, 95% confidence interval (CI) 1.12-3.08] and with shorter overall survival (OS; P=.02, HR 1.32, CI 1.04-1.67). In multivariable analyses, higher CD74 expression was independently associated with shorter DFS (P=.045, HR 1.98, CI 1.16-3.40), after adjusting for WT1 mutations (P<.001) and FLT3-TKD (P=.04), and shorter OS (P=.01, HR 1.58, CI 1.11-2.25) after adjusting for FLT3-TKD (P=.02), WT1 mutations (P=.007), BAALC expression levels (P=.02), white blood counts (P=.007), and extramedullary involvement (P=.04). As quartiles 2-4 had similar expression levels distinct from the lowest quartile, to display the impact of CD74 expression levels on clinical outcome only, pts were dichotomized into low (the lowest quartile) and high (the top three quartiles) CD74 expressers. The Kaplan-Meier curves for DFS and OS (Figures 1 and 2) are shown below. In conclusion, our study identifies elevated CD74 expression as associated with adverse prognosis in younger CN-AML pts. Since we previously reported that higher CD74 expression was favorably associated with achievement of CR in AML patients receiving chemotherapy plus bortezomib, an inhibitor of the proteasome and NF-kB (Attar et al., Clin Cancer Res, 2008;14:1446-54), it is possible that in future studies elevated CD74 levels can be used not only for prognostication, but also to stratify CN-AML pts to study of bortezomib-containing chemotherapy regimens. Figure 1 Disease free survival Figure 1. Disease free survival Figure 2 Overall survival Figure 2. Overall survival Disclosures No relevant conflicts of interest to declare.

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DNMT3A mutations Predict for Inferior Outcome in NPM1-Wildtype and Molecular Unfavorable Cytogenetically-Normal Acute Myeloid Leukemia: A Study of the German-Austrian AMLSG

Blood ◽

10.1182/blood.v118.21.415.415 ◽

2011 ◽

Vol 118 (21) ◽

pp. 415-415 ◽

Cited By ~ 1

Author(s):

Verena I. Gaidzik ◽

Richard F. Schlenk ◽

Peter Paschka ◽

Anja Stölzle ◽

Andrea Corbacioglu ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Negative Impact ◽

Epigenetic Modification ◽

Methylation Status ◽

Prognostic Impact ◽

Sequencing Analysis ◽

Mutational Status ◽

Acute Myeloid

Abstract Abstract 415 Background: Alteration of DNA methylation, a hallmark of epigenetic modification, is currently discussed as one important pathomechanism in leukemogenesis. Using a next-generation sequencing approach, a frameshift mutation of the gene encoding the DNA methyltransferase (DNMT3A) in an acute myeloid leukemia (AML) case was identified. DNMT3A catalyses the addition of a methyl group to the cytosine residue of CpG dinucleotides, thereby affecting promoter methylation status and gene expression. Subsequent sequencing analysis in an independent cohort of 288 AML patients (pts) revealed DNMT3A mutations (DNMT3Amut) in 22% of the pts; mutations were associated with intermediate-risk cytogenetics and poor outcome. Aims: To evaluate frequency and clinical impact of DNMT3Amut in pts with AML aged 18 to 61 years who were treated within AMLSG treatment trials AML HD98A (Schlenk et al., J Clin Oncol 2010;28:4642–8) and AMLSG 07–04 (NCT00151242). Methods: DNMT3A mutation analysis was performed in 1218 AML (HD98A, n=685; AMLSG 07–04, n=533; de novo AML, n=1102; s-AML, n=45; t-AML, n=69) using a DNA-based PCR assay for all coding exons (1 to 23) followed by direct sequencing. The median follow-up was 5.06 years. Results: DNMT3A mut were found with an overall frequency of 19.6% (239/1218); 189 mutations were located in the MTase domain clustering at amino acid R882 (79%). All but one mutation were heterozygous; only 4 cases had two mutations. DNMT3A sequence alterations included 17 frameshift, 4 nonsense, and 222 missense mutations. DNMT3A mut pts were significantly older (P=.01), more frequently females (P=.001), had higher white blood cell and platelet counts (both P<.0001), and higher bone marrow blasts percentage (P=.001). DNMT3Amut were associated with cytogenetically-normal AML (CN-AML, P<.0001), while DNMT3Amut were rare in favorable and adverse-risk karyotypes (P<.0001). Correlations with other molecular markers (NPM1, CEBPA, FLT3, IDH1/2, TET2, ASXL1) revealed a significant association with NPM1 (P<.0001), FLT3-ITD (P<.0001), and IDH1/2 (IDH1R132, P<.0001; IDH2R140, P=.0003; IDH2R172, P=.03) mutations, while co-occurrence of CEBPA (P=.02) and ASXL1 (P=.02) mutations was less frequent. DNMT3A mutational status did not impact complete remission (CR) rate, event-free (EFS) and relapse-free survival (RFS), neither in the whole cohort (P=.09, P=.98, P=.11; respectively) nor in the subgroup of CN-AML (P=.39, P=.79, P=.19, respectively). DNMT3Amut had a negative impact on overall survival (OS) in trend in the whole cohort (P=.07) and significantly in CN-AML (P=.02). In multivariable analyses, DNMT3Amut were in trend associated with a negative prognostic impact on OS (hazard ratio, 1.24; P=.06). In addition, we performed subgroup analyses according to (1) the NPM1 mutational status, and (2) the molecular risk groups of CN-AML (as defined by the European LeukemiaNet classification). DNMT3Amut did not impact OS in NPM1-mutated patients in the whole cohort as well as in CN-AML (P=.34; P=.22; respectively), while in NPM1-wildtype patients DNMT3Amut were associated with inferior OS in both, the whole cohort and in CN-AML (P=.001; P=.005; respectively). In molecular unfavorable CN-AML (NPM1-wildtype with or without FLT3-ITD, NPM1-mutated with FLT3-ITD, CEBPA-wildtype), DNMT3Amut were significantly associated with worse OS (P=.002) compared with DNMT3A-wildtype pts, even outweighing FLT3-ITD as an unfavorable prognostic marker. There was no effect of DNMT3Amut in molecular favorable-risk CN-AML. Conclusions: DNMT3A mutations are confirmed as frequent genetic aberrations in AML, associated with normal karyotype, NPM1, FLT3-ITD, and IDH1/2 mutations. DNMT3Amut predicts for inferior outcome in molecularly-defined subsets of AML, that is, NPM1-wildtype AML and molecular unfavorable CN-AML. As a single marker, DNMT3Amut only had a moderate effect on outcome. Disclosures: No relevant conflicts of interest to declare.

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Prognostic impact of PD-L1 expression in correlation with HLA class I expression status in stage I adenocarcinoma of the lung.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.8548 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 8548-8548

Author(s):

Kazue Yoneda ◽

Ayako Hirai ◽

Shohei Shimajiri ◽

Takeshi Hanagiri ◽

Fumihiro Tanaka

Keyword(s):

Lung Adenocarcinoma ◽

Early Stage ◽

Human Leukocyte ◽

Hla Class I ◽

Stage I ◽

Class I ◽

Prognostic Impact ◽

Leukocyte Antigen ◽

Molecular Features ◽

Poorly Differentiated

8548 Background: Programmed death-ligand 1 (PD-L1) and human leukocyte antigen (HLA) class-I, expressed on tumor cells (TCs), are important regulators in cancer immunity. The current study was conducted to assess prognostic impact of PD-L1 status in correlation with HLA class-I status in lung adenocarcinoma. Methods: A total of 94 patients with completely resected pathologic stage I lung adenocarcinoma were retrospectively reviewed. PD-L1 expression on TCs was evaluated with immunohistochemistry, in correlation with several clinicopathological and molecular features including HLA class-I expression on tumor TCs. Results: Seventeen patients (18.1%) had tumor with positive PD-L1 expression (percentage of TCs expressing PD-L1, ≥ 5%), and the incidence was higher in smokers with higher smoking index and in poorly differentiated tumor. There was no significant correlation between HLA class-I expression and PD-L1 expression. PD-L1-positivity was a significant factor to predict a poor survival (5-year survival rate, 66.7% versus 85.9%; P = 0.048), which was enhanced in tumor with normal HLA class-I expression (p = 0.029) but disappeared in tumor with reduced HLA class-I expression. Conclusions: The prognostic impact of PD-L1 expression on TCs in early-stage resectable lung adenocarcinoma was distinct according to HLA class-I expression on TCs.

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Prognostic impact of preoperative albumin to globulin ratio in curative colon cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.647 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 647-647

Author(s):

Yuji Toiyama ◽

Hiroyuki Fujikawa ◽

Yasuhiro Inoue ◽

Hiroki Imaoka ◽

Masato Okigami ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Poor Prognosis ◽

Early Recurrence ◽

Stage I ◽

Stage Iii ◽

Prognostic Impact ◽

Stage Iii Colon Cancer ◽

Albumin To Globulin Ratio

647 Background: Albumin to globulin ratio (AGR) has been reported to predict long term mortality in patients with several cancers. However, prognostic impact of preoperative AGR in colon cancer patients with curative intent has not yet been fully addressed. Therefore, we, for the first time, investigated the association between AGR and clinico-pathological findings including overall survival (OS) and disease free survival (DFS) in stage I-III colon cancer patients. Methods: Clinicopathological findings including preoperative laboratory data (carcinoembryonic antigen [CEA] and AGR) from 251 curative colon cancer patients were assessed as indicators of early recurrence and poor prognosis in this retrospective study. AGR was calculated as [AGR = albumin/ (total protein - albumin)]. The cut-off value of AGR was 1.32 in current study. Results: Several clinicopathological categories related with tumor progression such as lymph node metastasis, T4 tumor, large tumor size, undifferentiated tumor, venous and lymphatic invasion, and high CEA were significantly associated with low AGR level. The patients with low AGR were significantly poorer OS (P = 0.001) and DFS (P = 0.003) than those with high AGR, respectively. In addition, multivariate analyses demonstrated that low AGR was independently associated with early recurrence (HR = 2.87, P = 0.007) and poor prognosis (HR = 2.56, P = 0.008), respectively. On the other hand, sub analysis of survival curves revealed that stage III colon cancer patients with low AGR were significantly poorer OS (P = 0.007) and DFS (P = 0.02) than those with high AGR, respectively. Furthermore, significantly poorer OS and DFS were also shown in stage I-II colon cancer patients with low AGR, respectively (OS: P = 0.02, DFS: P = 0.01). Conclusions: Preoperative AGR was an independent predictor of early recurrence and poor prognosis in curative colon cancer patients. AGR may represent a simple, potentially useful predictive biomarker for selecting stage I-II colon cancer patients who might need adjuvant chemotherapy. Furthermore, AGR may select candidates who are better to introduce more intensive adjuvant chemotherapy after curative operation in stage III colon cancer patients.

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Survival after Curative Resection for Stage I Colorectal Mucinous Adenocarcinoma

10.21203/rs.3.rs-21102/v1 ◽

2020 ◽

Author(s):

Liang Huang ◽

Shuangling Luo ◽

Sicong Lai ◽

Yonghua Cai ◽

Zhanzhen Liu ◽

...

Keyword(s):

Multivariate Analysis ◽

Mucinous Adenocarcinoma ◽

Disease Free Survival ◽

Stage I ◽

Prognostic Impact ◽

Clinicopathologic Characteristics ◽

Term Outcome ◽

Long Term Outcome ◽

Free Survival ◽

Disease Free

Abstract Background : The prognostic value of the mucinous adenocarcinoma histotype on the early stages especially for stage I colorectal cancer (CRC) is still unclear. This study determined the clinicopathologic characteristics and long-term outcome of stage I colorectal mucinous adenocarcinomas (MAC).Methods : Among the total of 503 patients with stage I CRC (56 having MAC and 447 having non-MAC) who underwent radical resection, the correlation between clinicopathological factors and MAC was analyzed. Multivariate analysis was performed to determine whether mucinous histotype itself was an independent prognostic impact in stage I patients.Results : MACs were observed more frequently located in the colon than rectum ( p =0.046), more frequently displayed the microsatellite instability (MSI) phenotype ( p =0.023) and had a greater frequency of T2 stage ( p =0.001). The rate of recurrence was 13.5% and the cancer-specific mortality was 4.3% among all stage I CRC patients. There was no difference in disease-free survival and overall survival between MACs and non-MACs. On multivariate analysis, older age ( p =0.030), rectal cancer ( p =0.025), lymphovascular invasion (LVI) ( p <0.001), and microsatellite stability (MSS) phenotypes ( p =0.023) were independently associated to poor survival of stage I CRC. A high carcinoembryonic antigen (CEA) level ( p =0.031), LVI ( p =0.002) and MSS phenotypes ( p =0.012) were independently related to short disease-free survival of stage I CRC.Conclusions : Compared with non-MAC, MAC patients had more T2 patients and more MSI phenotypes in stage I CRC at presentation, but the mucinous histology is not a significant predictor of recurrence and prognosis in stage I CRC.

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