Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression in Patients Receiving Racotumomab Immunotherapy

Expression of N-glycolyl GM3 (NeuGcGM3) ganglioside was detected in the tumor specimens of patients who were on Racotumomab anti-idiotype vaccine maintenance treatment, and prognostic significance as a biomarker was investigated. No statistically significant association was observed in the multivariate analysis between overall survival and tissue NeuGcGM3 IHC levels. Although numerically there was a difference favoring less intense IHC for better prognosis, this did not reach statistical power. However, there was a strong correlation between Racotumomab doses and overall survival (OS). Mean OS of the patient with more than 10 Racotumomab application was significantly longer than the patient who had less than 10 injections (70.7 months vs. 31.1 months, p<0.001). We propose that, regardless of staining intensity, the presence of NeuGcGM3 in patient tissues might be an indicator of benefit in Racotumomab treatment.

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Clinicopathological Characteristics and Prognostic Factors in Axial Chondroblastomas: A Retrospective Analysis of 61 Cases and Comparison with Extra-Axial Chondroblastomas

10.21203/rs.3.rs-1242480/v1 ◽

2022 ◽

Author(s):

Bo-Wen Zheng ◽

Bo-Yv Zheng ◽

Hua-Qing Niu ◽

Xiao-Bin Wang ◽

Guo-Hua Lv ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Univariate Analysis ◽

Prognostic Significance ◽

Clinicopathological Characteristics ◽

Motor Dysfunction ◽

Surrounding Tissue ◽

Wide Resection ◽

Tissue Specimens

Abstract Background The clinical characteristics and prognostic factors of axial chondroblastoma (ACB) are still poorly understood. Purpose To characterize clinicopathological characteristics in a large ACB cohort and investigate their correlation with survival. We also sought to compare these results with extra-axial CB (EACB). Methods Our institution's local database was retrospectively reviewed and included a total of 132 CB patients, including 61 ACB patients and 71 EACB patients. Immunohistochemistry was used to assess the expression levels of Vimentin (Vim), S100, and cytokeratin (CK) on tumor cells in 132 tissue specimens. Results Overall, ACB and EACB had similar characteristics, except for older age and tumor size, as well as higher Vim expression, incidence of surrounding tissue invasion and postoperative sensory or motor dysfunction. Whereas wide resection and absence of invasion of surrounding tissues were consistently associated with favorable survival in the ACB and EACB cohorts in univariate analysis, most parameters showed differential prognostic significance between the 2 groups. Significant prognostic factors for local recurrence-free survival in multivariate analysis included the type of resection and chicken-wire calcification in the ACB cohort. Multivariate analysis of overall survival demonstrated that the type of resection was a significant predictor in the ACB cohort, whereas the type of resection and postoperative sensory or motor dysfunction were predictive of overall survival in the EACB group. Conclusion These data suggest that there may be distinct biological behaviors between ACB and EACB and may provide useful information to better understand the prognostic characteristics of patients with ACB and to improve outcome prediction in patients with ACB.

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The Clinical and Prognostic Significance of Protein Arginine Deiminases 2 and 4 in Colorectal Cancer

Pathobiology ◽

10.1159/000518414 ◽

2021 ◽

pp. 1-11

Author(s):

Mohamed Gijon ◽

Rachael L. Metheringham ◽

Michael S. Toss ◽

Samantha J. Paston ◽

Lindy G. Durrant

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Survival Time ◽

Patient Survival ◽

Prognostic Significance ◽

High Expression ◽

Related Protein ◽

Post Translational Modification

Introduction: Protein arginine deiminases (PADIs) are a family of enzymes that catalyse the post-translational modification of proteins. Association between PADI expression and clinicopathology, protein expression, and outcome was determined. Methods: PADI2 and PADI4 expression was assessed immunohistochemically in a cohort of colorectal cancer (CRC) patients. Results: CRC tissues expressed variable levels of PADI2 which was mainly localised in the cytoplasm and correlated with patient survival (p = 0.005); high expression increased survival time from 43.5 to 67.6 months. Expression of cytoplasmic PADI2 correlated with the expression of nuclear β catenin, PADI4, and alpha-enolase. In contrast, expression of nuclear PADI2 correlated with a decrease in survival (p = 0.010), with high expression decreasing survival from 76.4 to 42.9 months. CRC tissues expressed variable levels of PADI4 in both the nucleus and cytoplasm. Expression of cytoplasmic PADI4 correlated with survival (p = 0.001) with high expression increasing survival time from 48.1 to 71.8 months. Expression of cytoplasmic PADI4 correlated with expression of nuclear β catenin, alpha-enolase (p ≤ 0.0001, p = 0.002), and the apoptotic related protein, Bcl-2. Expression of nuclear PADI4 also correlated with survival (p = 0.011), with high expression of nuclear PADI4 increasing survival time from 55.4 to 74 months. Expression of nuclear PADI4 correlated with p53, alpha-enolase, and Bcl-2. Multivariate analysis showed that TNM stage, cytoplasmic PADI2, and PADI4 remained independent prognostic factors in CRC. Both PADI2 and PADI4 are good prognostic factors in CRC. Conclusion: High expression of cytoplasmic PADI2, PADI4, and nuclear PADI4 were associated with an increase in overall survival.

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Prognostic factors in duodenal adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15797 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15797-e15797

Author(s):

Brandon M Huffman ◽

Zhaohui Jin ◽

Cristobal T. Sanhueza ◽

Mindy L. Hartgers ◽

Benny Johnson ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Lymph Node ◽

Tumor Invasion ◽

Univariate Analysis ◽

Prognostic Significance ◽

Clinical Staging ◽

Lymph Node Status ◽

Duodenal Adenocarcinoma

e15797 Background: Duodenal adenocarcinoma is a rare tumor representing approximately 0.3% of all gastrointestinal tract cancers. Prognostic factors in relation to survival outcomes for these patients are sporadically reported in the medical literature. We aimed to evaluate outcomes of patients with duodenal adenocarcinoma who underwent pancreaticojejunostomy treated at Mayo Clinic Rochester from January 1, 2006 to December 31, 2016. Methods: Clinicopathological data of 52 duodenal cancer patients were collected. JMP software was used for statistical analysis. Kaplan-Meier method and log-rank tests were used for survival analysis, and multivariate cox proportional hazards model was used to evaluate the prognostic effect of pertinent clinical variables. All tests were two sided and a P value of < 0.05 was considered significant. Results: The median age at diagnosis was 65.9 years (range 39-81). The median overall survival was 51 months (95% CI 31.3-105.4) and the median progression free survival was 30.4 months with median follow up of 73.4 months. There were 3, 9, 21, and 19 patients with stage I, II, III, and IV disease, respectively. Depth of tumor invasion (p = 0.0156) and lymph node metastasis (p = 0.0441) were associated with overall survival on multivariate analysis. Advanced clinical staging influenced overall survival in univariate analysis, but lost prognostic significance in multivariate analysis. Age, gender, surgical technique, presence of metastases, tumor size, number of lymph nodes removed, location of duodenal segment involvement, and adjuvant treatment had no significant impact on overall survival. Laparoscopic approach did not influence survival but was associated with less hospital days (p = 0.0437). Conclusions: Depth of tumor invasion and lymph node status were associated with improved overall survival in patients with duodenal adenocarcinoma. Laparoscopic procedure decreased the hospital stay without affecting outcomes.

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Outcomes for Myeloma in the Era of Lenalidomide Maintenance Are Not Different Among Ethnic Groups Following Autologous Transplant

Blood ◽

10.1182/blood.v124.21.3973.3973 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3973-3973

Author(s):

Chandra Pooja ◽

Ajay K. Nooka ◽

Monica S. Chatwal ◽

Sungjin Kim ◽

Zhengjia Chen ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Maintenance Therapy ◽

Ethnic Groups ◽

Research Funding ◽

Maintenance Treatment ◽

Post Transplant ◽

Factors Associated ◽

Lytic Lesions ◽

White Patients

Abstract Background: Multiple myeloma (MM) is the most common hematological malignancy among African Americans (AA). The introduction of postransplant maintenance has had a significant improvement in progression free and overall survival for myeloma patients as demonstrated in large phase III clinical trials. However, the impact of race on the outcome of patients receiving maintenance treatment remains unknown. Methodology: We conducted a retrospective analysis of 299 consecutive patients transplanted for MM from 2005 to 2013 at the Winship Cancer Institute of Emory University. Survival analyses were estimated by Kaplan-Meier methods and univariate and multivariate analysis were performed using a cox proportional hazard model. Results: Baseline characteristics such as stage (International Staging System, ISS), presence of lytic lesions or plasmocytomas, immunoglobulin subtype, and cytogenetic risk category at presentation, were comparable between AA and white patients. Among AA, 57.1% received triple therapy with an immune modulator and a proteasome inhibitor (IMID+PI, lenalidomide (R) or thalidomide (T) and bortezomib (V) and dexamethasone), 49% received doublets (RD, TD or VD) and 29% received other bortezomib based regimens. In white patients 50.3% were treated with IMID+PI, 37% with doublets, 13.6% with received other bortezomib based regimens. Both populations had comparable ORR and >VGPR at day 100 (AA: ORR:90.74% and >VGPR:74.07% vs White ORR:90.65% and >VGPR: 77.57%, p>0.1). Of the 299 patients, 128 patients underwent maintenance treatment with lenalidomide (AA: 61 and White:67 patients) while 171 did not receive lenalidmode as they transplanted prior approval of lenalidomide maintenance. Maintenance treatments improved progression free survival in both ethnic cohorts. AA patients receiving maintenance therapy have not yet reached their median PFS with a median follow up of 8 years (60%), while median PFS was 4.8 years among those who did not receive maintenance (p=0.4). Similarly, in white patients, the PFS improved from 2.8 years without maintenance to 5.4 years with maintenance (p=0.01). Furthermore race did not affect PFS in both maintenance treated cohorts. Within the cohort of patients that did not receive maintenance therapy, we observed a trend of improvement in overall survival in AA patients ( p=0.06), which could suggest difference in the risk of the disease. However, no differences in staging or cytogenetics were identified between both ethnic groups at diagnosis that could explain this difference. Factors associated with longer PFS in univariate and multivariate analysis included AA race and immunoglobulin subtype (IgG and kappa light chain MM). In AA multivariate analysis identified the presence of lytic lesions as a factors associated with shorter PFS. In white patients, factors such as plasma cell leukemia at diagnosis were associated with worst PFS. In conclusion, race did not impact the improvement in PFS associated with post-transplant maintenance therapy. To our knowledge this preliminary analysis provides the first assessment of the influence of race in MM outcomes post-transplant during the lenalidomide maintenance era Disclosures Lonial: Millennium: The Takeda Oncology Company: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding.

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Prognostic Significance of microRNA-7 and its Roles in the Regulation of Cisplatin Resistance in Lung Adenocarcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000477884 ◽

2017 ◽

Vol 42 (2) ◽

pp. 660-672 ◽

Cited By ~ 13

Author(s):

Mao-Wei Cheng ◽

Ze-Tian Shen ◽

Gu-Yu Hu ◽

Li-Guo Luo

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Lung Adenocarcinoma ◽

Survival Data ◽

Proportional Hazards Model ◽

Prognostic Significance ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Expression Level ◽

Poor Prognostic Factor

Background: Previously, microRNA (miR)-7 has been reported to function as a tumor suppressor in human cancers, but the correlations of miR-7 expression with prognosis and cisplatin (CDDP) resistance in lung adenocarcinoma (LA) are unclear. Here, our aim is to determine the prognostic significance of miR-7 and its roles in the regulation of CDDP resistance in LA. Methods: Quantitative real-time PCR (qRT-PCR) assay was performed to determine miR-7 expression in 108 paired of LA tissues and analyze its correlations with clinicopathological factors of patients. The patient survival data were collected retrospectively by Kaplan-Meier analyses, and multivariate analysis was performed using the Cox proportional hazards model to determine the prognostic significance of miR-7 expression. The effects of miR-7 expression on the chemosensitivity of LA cells to CDDP and its possible mechanisms were evaluated by MTT, flow cytometry, Western blot and luciferase assays. Results: It was observed that the relative expression level of miR-7 in LA tissues was significantly lower than that in the adjacent normal tissues and low miR-7 expression level was closely associated with poorer tumor differentiation, advanced pathological T-factor, higher incidence of lymph node metastasis and advanced p-TNM stage. Also, patients with low miR-7 expression showed a shorter overall survival than those with high miR-7 expression, and multivariate analysis indicated that status of miR-7 expression was an independent molecular biomarker for predicting the overall survival (OS) of LA patients. In addition, upregulation of miR-7 increases the sensitivity of LA cells to CDDP via induction of apoptosis by targeting Bcl-2. Conclusions: Our finding for the first time demonstrates that low miR-7 expression may be an independent poor prognostic factor and targeting miR-7 may be a potential strategy for the reversal of CDDP resistance in LA.

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Magnetic resonance imaging volumetric assessment of the extent of contrast enhancement and resection in oligodendroglial tumors

Journal of Neurosurgery ◽

10.3171/2012.2.jns102032 ◽

2012 ◽

Vol 116 (6) ◽

pp. 1172-1181 ◽

Cited By ~ 20

Author(s):

Tejas Sankar ◽

Nina Z. Moore ◽

Joshua Johnson ◽

Lynn S. Ashby ◽

Adrienne C. Scheck ◽

...

Keyword(s):

Multivariate Analysis ◽

Contrast Enhancement ◽

Tumor Tissue ◽

Histological Grade ◽

Univariate Analysis ◽

Prognostic Significance ◽

Oligodendroglial Tumors ◽

Blinded Observer ◽

Volumetric Assessment ◽

Time To Relapse

Object Oligodendrogliomas that enhance on MR images are associated with poor prognosis. However, the importance of the volume of enhancing tumor tissue, and the extent of its resection, is uncertain. The authors examined the prognostic significance of preoperative and residual postoperative enhancing tissue volumes in a large single-center series of patients with oligodendroglioma. They also examined the relationship between enhancement and characteristic genetic signatures in oligodendroglial tumors, specifically deletion of 1p and 19q (del 1p/19q). Methods The authors retrospectively analyzed 100 consecutive cases of oligodendroglioma involving patients who had undergone T1-weighted gadolinium-enhanced MRI at diagnosis and immediately after initial surgical intervention. The presence of preoperative enhancement was determined by consensus. Preoperative and residual postoperative volumes were measured using a quantitative, semiautomated method by a single blinded observer. Intrarater reliability for preoperative volumes was confirmed by remeasurement in a subset of patients 3 months later. Intrarater and interrater reliability for residual postoperative volumes was confirmed by remeasurement of these volumes by both the original and a second blinded observer. Multivariate analysis was used to assess the influence of contrast enhancement at diagnosis and the volume of pre- and postoperative contrast-enhancing tumor tissue on time to relapse (TTR) and overall survival (OS), while controlling for confounding clinical, pathological, and genetic factors. Results Sixty-three of 100 patients had enhancing tumors at initial presentation. Presence of contrast enhancement at diagnosis was related to reduced TTR and OS on univariate analysis but was not significantly related on multivariate analysis. In enhancing tumors, however, greater initial volume of enhancing tissue correlated with shortened TTR (p = 0.00070). Reduced postoperative residual enhancing volume and a relatively greater resection of enhancing tissue correlated with longer OS (p = 0.0012 and 0.0041, respectively). Interestingly, patients in whom 100% of enhancing tumor was resected had significantly longer TTR (174 vs 64 weeks) and OS (392 vs 135 weeks) than those with any residual enhancing tumor postoperatively. This prognostic benefit was not consistently maintained with greater than 90% or even greater than 95% resection of enhancing tissue. There was no relationship between presence or volume of enhancement and del 1p/19q. Conclusions In enhancing oligodendrogliomas, completely resecting enhancing tissue independently improves outcome, irrespective of histological grade or genetic status. This finding supports aggressive resection and may impact treatment planning for patients with these tumors.

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The influence of body mass index (BMI) on outcome in patients with advanced germ cell tumors (GCT)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.14594 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 14594-14594

Author(s):

D. J. Vaughn ◽

M. Powell ◽

P. J. Catalano ◽

P. Loehrer ◽

C. Nichols ◽

...

Keyword(s):

Overall Survival ◽

Statistical Power ◽

Proportional Hazards ◽

Performance Status ◽

Prognostic Significance ◽

Germ Cell Tumors ◽

Response Probability ◽

Phase Iii ◽

Primary Analysis ◽

Post Surgery

14594 Background: Obesity is associated with increased mortality in a variety of cancers. Using data from ECOG 3887, a phase III study comparing cisplatin, etoposide, and bleomycin or ifosfamide in advanced GCT, we explored the prognostic significance of BMI. Methods: From 10/87 to 4/92, 286 assessable patients (pts) were enrolled in the original study. 1 pt was ineligible, 3 pts were missing weight/height; 282 pts are included in this analysis. BMI was computed by dividing weight by square of height (kg/m2), and was categorized as underweight (< 18.5), normal (18.5–24.9), overweight (25–29.9) and obese (>30). A favorable response was defined as CR, NED post-surgery, or PR for ≥ 2 years. Fisher’s Exact Test was used to examine associations between BMI and favorable response. The Kaplan-Meier method was used to estimate overall survival by BMI. Proportional hazards models were used to examine the effect of BMI on survival after adjusting for International Stage (IS) and performance status (PS). As BMI was distributed similarly between the two treatment arms and no treatment differences were observed in the primary analysis, data from both arms were pooled to maximize power with regard to BMI. Results: Fifteen pts (5%) were underweight, 171 (61%) normal, 75 (27%) overweight, and 21 (7%) obese at study entry. The favorable response proportion was 53%, 67%, 51%, and 65%, respectively, for underweight, normal, overweight and obese pts. There was no association between BMI category and favorable response probability (chi square p = 0.08). 5-year survival for underweight, normal, overweight, and obese pts was 60%, 73%, 62%, and 67%, respectively. There was no difference in overall survival associated with BMI category (logrank p = 0.28), although statistical power is limited since there were few underweight/obese pts. After adjusting for IS and PS, there remained no association between overall survival and BMI category (hazard ratio per unit BMI 1.01, 95% CI 0.97–1.06). Conclusions: We observed no association between BMI and outcome, but statistical power is limited due to the small number of underweight and obese pts. No significant financial relationships to disclose.

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Improved survival with radiation therapy in early pancreatic adenocarcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15036 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15036-15036

Author(s):

A. Artinyan ◽

M. Hellan ◽

P. Mojica-Manosa ◽

J. Ellenhorn ◽

J. Kim

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Multivariate Analysis ◽

Radiation Therapy ◽

Pancreatic Adenocarcinoma ◽

Radiation Treatment ◽

Prognostic Significance ◽

Adjuvant Radiation ◽

Cox Regression Analysis ◽

Adjuvant Radiation Therapy

15036 Background: Although chemoradiation is often used following pancreatic cancer resection, recent studies have questioned the role of radiation therapy in this setting. The objective of this study was to determine the effect of adjuvant radiation therapy following pancreatectomy in patients with node-negative (N0) pancreatic cancer. Methods: The Surveillance, Epidemiology, and End Results (SEER) registry was used to identify patients with N0 pancreatic adenocarcinoma who had undergone curative-intent resection between 1988–2003. Kaplan-Meier survival curves were constructed to compare overall survival between patients ± adjuvant radiation therapy. Multivariate Cox regression analysis was performed to determine the prognostic significance of radiation therapy when additional clinicopathologic factors were assessed. The analysis also examined the potential treatment selection bias of patients with survival <3 months. Results: Query of the SEER database identified 2342 surgical patients with N0 disease. The median survival for these patients was 18 months. 889 (60.1%) patients were treated with radiation. There was no difference in gender or grade between radiation and non-radiation groups; however, radiation patients were younger (63 vs. 67 years, p<0.001) and had a greater proportion of T3 lesions (p=0.002). Radiation patients had significantly improved survival compared to non-radiation patients (20.0 vs. 15.0 months, p<0.001). On multivariate analysis, radiation therapy (HR 0.72, p<0.001), age, grade, T-stage, and tumor location were independent predictors of survival. When patients with survival <3 months were excluded from analysis, no difference in survival between radiation and non- radiation was noted (20.0 vs. 19.0 months, p=0.096). However, on subset analysis, patients with T3 tumors demonstrated improved survival with the addition of radiation (24.0 vs 16.0 months, p=0.002) and on multivariate analysis radiation therapy was an independent predictor of improved overall survival (HR 0.87, p=0.027). Conclusions: Radiation treatment is associated with improved survival in operable N0 pancreatic cancer and its use should be considered in patients with early stage N0 disease. The greatest impact of radiation therapy use appears to occur with T3 tumors. No significant financial relationships to disclose.

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Serum protein acidic and rich in cysteine (SPARC) as a prognostic marker in soft tissue sarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.10581 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 10581-10581

Author(s):

Sherif S. Morgan ◽

Raymond B. Nagle ◽

Lee D. Cranmer

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Median Survival ◽

Prognostic Significance ◽

Significant Proportion ◽

Soft Tissue Sarcomas ◽

Staining Intensity ◽

Cellular Adhesion ◽

Elevated Expression ◽

Sparc Expression

10581 Background: SPARC is a matricellular secreted glycoprotein that performs several functions, including modulating cellular adhesion and proliferation. It has been implicated in tumorigenesis and identified as an adverse prognostic factor in a number of cancers. The specific mechanisms involved have yet to be identified. Agents targeting SPARC-expressing tumors, such as nanoparticle albumin-bound-paclitaxel (NAB-P), have been developed. Soft tissue sarcomas (STS) represent a heterogeneous group of tumors with inadequate systemic therapies. Our objective was to explore the pattern of SPARC expression and its prognostic significance in STS. Methods: Formalin-fixed paraffin-embedded tissue sections were stained by immunohistochemistry using a mouse monoclonal antibody for SPARC (Abnova). Staining intensity was scored blindly. Patient survival was determined from patients’ medical records. Kaplan-Meier and log-rank analyses were used to compare survival by SPARC expression level. Results: 27 tissue specimens of various STS subtypes were investigated (Table). Elevated SPARC expression was observed in 56% of specimens, but did not correlate with underlying histology. Overall survival segregated into 2 groups based on SPARC levels. Patients who expressed low-to-moderate levels of SPARC exhibited median survival of 22.1 months, while the median survival of patients with moderate-to-high expression levels was 4.4 months (log rank; p=0.0016). Conclusions: A significant proportion of STS specimens exhibit elevated SPARC expression. Elevated SPARC does not correlate with underlying histology, although analysis of a greater number of specimens might reveal subtypes with more frequently elevated expression. Overall survival segregates strongly by degree of SPARC expression, with elevated expression being adverse. Our results suggest that analysis in STS of agents targeting SPARC, such as NAB-P, should be stratified by extent of SPARC expression. [Table: see text]

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The Prognostic Significance of ASXL1/EZH2 Co-Mutation in Comparison with ASXL1 or EZH2 Mutation Alone in Myelodysplastic Syndromes

Blood ◽

10.1182/blood-2019-132070 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5428-5428

Author(s):

Pukhraz Basra ◽

David Gajzer ◽

Mohammad O Hussaini ◽

Hailing Zhang ◽

Lynn C. Moscinski ◽

...

Keyword(s):

Overall Survival ◽

Myelodysplastic Syndromes ◽

Research Funding ◽

Statistical Power ◽

Molecular Mechanisms ◽

Tp53 Mutation ◽

Survival Curve ◽

Statistical Significance ◽

Prognostic Significance ◽

Driver Mutations

Introduction: Advanced molecular profiling with next generation sequencing (NGS) has greatly improved the diagnostic and prognostic stratification of hematological disorders. Several driver mutations including TP53, RUNX1, ASXL1, and EZH2 mutations are independent predictors of overall survival (OS) in myelodysplastic syndromes (MDS). Frequent co-mutations of ASXL1, EZH2,RUNX1 and/or TET2 have also been described in the entity. However, studies exploring the clinical significance of co-mutations in these adverse genes are limited. Our study assesses mutation profiles and compares clinical outcomes among MDS patients with EZH2 mutation alone, ASXL1 mutation alone, ASXL1/EZH2 co-mutation, and co-mutated ASXL1/EZH2 with additional mutations. Materials and Methods: The retrospective study was approved by the institutional review board. We searched our institutional database (>4000 patients) for patients who were diagnosed with MDS and harbored only ASXL1 or EZH2 mutations, only ASXL1/EZH2 co-mutations, and co-mutated ASXL1/EZH2 plus other genes identified by targeted NGS using a myeloid gene panel (up to 54 genes). Patient demographics, diagnosis, cytogenetic abnormalities, and overall survival times were analyzed. Mann-Whitney U Test was used for statistical analysis of OS and a Kaplan Meier survival curve was generated. Results: Total 140 patients were retrieved: 71 patients with only ASXL1 mutation, 12 patients with only EZH2 mutation, 8 patients with only ASXL1/EZH2 co-mutation and 49 patients with multiple mutations. As shown in Figure 1, patients with ASXL1/EZH2 co-mutation or multiple mutations show worse OS when compared with patients with EZH2 mutation alone or ASXL1 mutation alone. However, only the differences between either the survival of patients with ASXL1 or EZH2 mutations alone vs multiple mutations are approaching statistical significance (p values = 0.0669 and 0.0927 respectively). Interestingly the patients with ASXL1 mutation alone or multiple mutations appeared more likely to harbor good cytogenetics (70.42% and 65.3%) rather than poor cytogenetics (7% and 2%, respectively). Finally, TP53 mutation appears to be mutually exclusive with ASXL1 or EZH2 mutations, occurring only in 1 patient with multiple mutations. Conclusion: In our study, MDS patients with ASXL1/EZH2 co-mutations or combined with other mutations appear to show worse prognosis than patients harboring ASXL1 mutation alone or EZH2 mutation alone, though statistical significance was not reached. This could be due to the fact that both ASXL1 and EZH2 confer such an unfavorable prognosis to the patients that additional mutation(s) will not produce any significant clinical impacts. This could also be due to the limited sample size in our study, thus the limited statistical power. A larger cohort study is needed to further explore the prognostic values of co-mutations in this setting. Similar to other reports, TP53 mutation also appears to be mutually exclusive with ASXL1 and/or EZH2; that is of value to further explore the molecular mechanisms. Figure 1 Disclosures Sallman: Abbvie: Speakers Bureau; Novartis: Speakers Bureau; Jazz: Research Funding; Incyte: Speakers Bureau; Celyad: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding, Speakers Bureau. Komrokji:celgene: Consultancy; pfizer: Consultancy; DSI: Consultancy; Novartis: Speakers Bureau; JAZZ: Speakers Bureau; Incyte: Consultancy; Agios: Consultancy; JAZZ: Consultancy.

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