scholarly journals Increase in Mortality and Second Neoplasms in Chronic Lymphocytic Leukemia with Pro/Pro Genotype of TP53 Codon 72

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-14
Author(s):  
Martin Cabero-Becerra ◽  
Jose Antonio Garcia Vela ◽  
Pedro Sanchez-Godoy ◽  
Angel Arias-Arias ◽  
Miguel Piris-Villaespesa ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tp53 Mutation ◽  
Conflicts Of Interest ◽  
The Other ◽  
Complex Karyotype ◽  
Codon 72 ◽  
Risk Of Death ◽  
Second Neoplasms ◽  
Number Of Patients ◽  
Increased Risk

Chronic Lymphocytic Lymphoma (CLL) is a heterogeneous disease in which many important factors for its prognosis have been identified. The normal functioning of p53 is one of the most critical barriers against cancer; therefore, if it has a deletion and/or mutation, it is a robust biomarker for the therapeutic response in CLL. The possibility was raised that some germline single - nucleotide polymorphisms of TP53 in healthy populations may also affect p53 function. One of the most studied polymorphisms of the TP53 gene is codon 72 in exon 4, a CGC to CCC transition (R72P), due to its potential effect on cancer risk. As with many types of cancer, its association with a worse prognosis in CLL is unclear. We analyzed the relationship of the genotypes of the TP53 codon 72 polymorphism in a large cohort of patients with CLL, to demonstrate the association of codon 72 with the evolution of the disease. Using the IDIPHIM patient database, 558 patients with a diagnosis of CLL were included, with clinical data, immunophenotype studies, FISH, IgHV, and karyotype, at the time of diagnosis and during follow-up. The TP53 codon 72 Arg/Arg, Arg/Pro, and Pro/Pro genotypes were analyzed using RT-PCR and Sanger sequencing techniques. After analyzing the sample of patients, 321 patients with the Arg/Arg genotype, 202 with the Arg/Pro genotype, and 35 with the Pro/Pro genotype were found. In the comparative analysis of the three groups, the patients with the Pro/Pro genotype had a higher number of patients in advanced stages B and C. The latter had a significant association with Binet staging (p = 0.002) compared to the other groups. Likewise, patients with the Pro/Pro genotype had a higher incidence of Richter transformation, whose association was significant (p = 0.013). Also, the patients who were within the Pro/Pro genotype group showed a significant association (p = 0.030) with the Time to the first treatment (TFT), also observing that the group of patients with the Arg/Pro genotype had a more considerable time until your first treatment. 19.7% (110/558) had a second neoplasm, having a significantly higher association with the homozygous groups (Arg/Arg and Pro/Pro) than with the Arg/Pro group, which on the contrary, had fewer second neoplasms (p = 0.016) (see Table 1). Regarding the type of tumors, we found 14.5% of the bladder, 14.5% of the skin, 14.5% of the colon, 13.6% of the prostate, and 12.7% of the lung. No associations were found between Codon 72 and CD38+, ZAP70+, complex karyotype, IgHV, NOTCH-1, del 11q, 12+, p53, del 13q, TP53 mutation. Still, when forming a group between the p53 deletion and TP53 mutation, if significant differences were found (p = 0.023), Pro / Pro group had the highest percentage. The overall survival was 156.32 months (139.92 - 172.72), showing that patients with the Arg/Pro genotype live 40 months more significantly than the other groups (p = 0.028) (see Figure 1). Finally, in the multivariate analysis, age, complex karyotype, 11q deletion, p53 deletion, unmutated IgHV, and Pro/Pro genotype at codon 72 were identified as independent variables associated with an increased risk of death (see Table 2). In conclusion, the Pro/Pro genotype of TP53 Codon 72 has a potential role in the progression and the higher mortality of patients with CLL. Conversely, the Arg / Pro genotype was associated with a lower incidence of second malignancies and higher overall survival. Disclosures No relevant conflicts of interest to declare.

Prognostic Impact of Comorbidities In A Cohort of 788 MDS Patients Based On A CIRS-G Derived Score. A MDS Piedmont Registry Prospective Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1729-1729
Author(s):  
Emanuela Messa ◽  
Daniela Gioia ◽  
Claudia Bertassello ◽  
Gianni Ciccone ◽  
Bernardino Allione ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Impact ◽  
Risk Of Death ◽  
Number Of Patients ◽  
Increased Risk ◽  
Risk Patients ◽  
Progression Risk ◽  
Cox Analysis ◽  
Severe Grade

Abstract Abstract 1729 Background: Management of neoplastic patients is strongly influenced by comorbidities, especially in more advanced ages. Due to that, comorbidities evaluation is a critical issue in the global assessment of patients (pts) affected by myelodysplastic syndromes (MDS). Until now, there is no agreement on which comorbidity index (CI) is more suitable in this setting and different CI has been proposed. Recently a new MDS-specific score (MDS-CI) has been published by Della Porta et al., while the majority of CI in use has been developed in geriatric oncology setting. One of the most useful is Cumulative Illness Rating Scale of Geriatrics (CIRS-G). Aim of our study: Aim of our study was to test the usefulness of the conventional and easy to apply CIRS-G score among a cohort of MDS pts enrolled in the MDS Piedmont Registry from 1999 to 2010 in predicting OS and leukemic progression. Materials and methods: 788 patients from the MDS Piedmont Registry with CIRS-G evaluation at diagnosis were included in our statistical analysis. 78% of the patients were low and Int-1 IPSS risk, the remaining 22% were Int-2-high risk. The majority of patients (69%) carried an histological diagnosis of non RAEB MDS according to WHO classification, the remaining 31% were RAEB I-II. Age stratification was as follows: 10% up to 60, 23% from 61 to 70, 43% from 71 to 80, 24% over 80 years. Comorbidities with score up to 2 were considered mild while the ones with values higher than 2 were considered severe. We evaluated the global impairment of each patient creating two comorbidity scores based on the number of mild comorbidities (mild comorbidities score, MCS) and severe comorbidities (severe comorbidities score, SCS). Results: The majority of our patients showed only mild comorbidities and the comorbidities with the greater number of patients carrying severe grade of impairment are the cardiac (25%), hypertensive (30%) and endocrinological (20%) ones. COX analysis did not show an impact of comorbidities on leukemic progression risk while there is a statistically significant impact on overall survival of respiratory, renal, urological and osteo-muscular comorbidities (HR respectively of 1,18; 1,3; 1,3; 1,16). There is a trend of increased risk of non MDS related death in patients with severe grade of each comorbidity. Then we set up a Fine and Gray regression model in order to evaluate the global impact of comorbidities on leukemic progression and overall survival according to SCS and MCS. Neither SCS nor MCS showed an impact on the leukemic progression risk. Considering overall survival (OS), MCS showed a HR of 1,12 (p= 0,009) and moreover SCS has a strong impact on the risk of death (HR 1,59; p= 0,000). MCS remains statistically significant in low IPSS risk patients (p<0,001) while there is no influence of MCS on OS considering high IPSS risk patients (p=0,244). COX analysis stratifying pts for performance status (PS) and age classes confirmed the results obtained in the whole population. We performed a multivariate analysis and confirmed that SCS score (p=0,0006), age and IPSS (all p<0,0001) but not PS (p=0,22) are independent prognostic factors in OS prediction. Conclusions: Our data based on a prospective evaluation of 788 MDS patients enrolled in the MDS Piedmont Registry showed that CIRS-G evaluation is a suitable and easy to apply method useful in patients evaluation at diagnosis and during disease management. In our multivariate analysis IPSS is the most useful tool for leukemic progression evaluation, while SCS score (derived from CIRS-G evaluation) and age are the most important variables able to predict overall survival while PS at diagnosis does not add any useful information for this evaluation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The effect of adjuvant radiotherapy on overall survival in adults with intracranial ependymoma

2019 ◽  
Vol 7 (4) ◽  
pp. 391-399
Author(s):  
Roshan S Prabhu ◽  
Christopher D Corso ◽  
Matthew C Ward ◽  
John H Heinzerling ◽  
Reshika Dhakal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Propensity Score ◽  
Adjuvant Radiotherapy ◽  
Subtotal Resection ◽  
National Cancer Database ◽  
Risk Of Death ◽  
Increased Risk ◽  
Intracranial Ependymoma ◽  
Male Sex ◽  
Grade 3

Abstract Background Adult intracranial ependymoma is rare, and the role for adjuvant radiotherapy (RT) is not well defined. Methods We used the National Cancer Database (NCDB) to select adults (age ≥ 22 years) with grade 2 to 3 intracranial ependymoma status postresection between 2004 and 2015 and treated with adjuvant RT vs observation. Four cohorts were generated: (1) all patients, (2) grade 2 only, (3) grade 2 status post–subtotal resection only, (4) and grade 3 only. The association between adjuvant RT use and overall survival (OS) was assessed using multivariate Cox and propensity score matched analyses. Results A total of 1787 patients were included in cohort 1, of which 856 patients (48%) received adjuvant RT and 931 (52%) were observed. Approximately two-thirds of tumors were supratentorial and 80% were grade 2. Cohorts 2, 3, and 4 included 1471, 345, and 316 patients, respectively. There was no significant association between adjuvant RT use and OS in multivariate or propensity score matched analysis in any of the cohorts. Older age, male sex, urban location, higher comorbidity score, earlier year of diagnosis, and grade 3 were associated with increased risk of death. Conclusions This large NCDB study did not demonstrate a significant association between adjuvant RT use and OS for adults with intracranial ependymoma, including for patients with grade 2 ependymoma status post–subtotal resection. The conflicting results regarding the efficacy of adjuvant RT in this patient population highlight the need for high-quality studies to guide therapy recommendations in adult ependymoma.

scholarly journals Prognostic Impact of NOTCH1 Hotspot Mutation in TP53-Mutated Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3283-3283
Author(s):  
Barbara Kantorova ◽  
Jitka Malcikova ◽  
Veronika Navrkalova ◽  
Jana Smardova ◽  
Kamila Brazdilova ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Tp53 Mutation ◽  
Direct Sequencing ◽  
Lymphocytic Leukemia ◽  
The Other ◽  
Wild Type ◽  
Tp53 Mutations ◽  
Time To First Treatment ◽  
Hotspot Mutation

Abstract Introduction A presence of activating mutations in NOTCH1 gene has been recently associated with reduced survival and chemo-immunotherapy resistance in chronic lymphocytic leukemia (CLL). However, a prognostic significance of the NOTCH1 mutations with respect to TP53mutation status has not been fully explained yet. Methods An examined cohort included 409 patients with CLL enriched for high risk cases; in 121 patients consecutive samples were investigated. To determine the TP53 mutation status, a functional analysis of separated alleles in yeast (FASAY, exons 4-10) combined with direct sequencing was performed; the ambiguous cases were retested using an ultra-deep next generation sequencing (MiSeq platform; Illumina). The presence of NOTCH1 hotspot mutation (c.7544_7545delCT) was analyzed using direct sequencing complemented by allele-specific PCR in the selected samples. In several patients harboring concurrent NOTCH1 and TP53 mutations, single separated cancer cells were examined using multiplex PCR followed by direct sequencing. A correlation between mutation presence and patient overall survival, time to first treatment and other molecular and cytogenetic prognostic markers was assessed using Log-rank (Mantel-cox) test and Fisher's exact test, respectively. Results The NOTCH1 and TP53 mutations were detected in 16% (65/409) and 27% (110/409) of the examined patients, respectively; a coexistence of these mutations in the same blood samples was observed in 11% (19/175) of the mutated patients. The detected increased mutation frequency attributes to more unfavorable profile of the analyzed cohort; in the TP53-mutated patients missense substitutions predominated (75% of TP53 mutations). As expected, a significantly reduced overall survival in comparison to the wild-type cases (147 months) was observed in the NOTCH1-mutated (115 months; P = 0.0018), TP53-mutated (79 months; P < 0.0001) and NOTCH1-TP53-mutated patients (101 months; P = 0.0282). Since both NOTCH1 and TP53 mutations were strongly associated with an unmutated IGHV gene status (P < 0.0001 and P = 0.0007), we reanalyzed the IGHV-unmutated patients only and interestingly, the impact of simultaneous NOTCH1 and TP53 mutation presence on patient survival was missed in this case (P = 0.1478). On the other hand, in the NOTCH1 and/or TP53-mutated patients significantly reduced time to first treatment was identified as compared to the wild-type cases (41 months vs. 25 months in NOTCH1-mutated, P = 0.0075; 17 months in TP53-mutated, P < 0.0001; and 18 months in NOTCH1-TP53-mutated patients, P = 0.0003). The similar results were observed also in the subgroup of the IGHV-unmutated patients, with the exception of patients carrying sole NOTCH1 mutation (P = 0.2969). Moreover, in the NOTCH1-TP53-mutated patients an increased frequency of del(17p)(13.1) was found in comparison to the TP53-mutated patients only (72% vs. 56%); this cytogenetic defect was not detected in the patients with sole NOTCH1 mutation. Our results might indicate, that NOTCH1 mutation could preferentially co-selected with particular, less prognostic negative type of TP53 defects. Notably, in our cohort the NOTCH1 mutation predominated in the patients harboring truncating TP53 mutations localized in a C-terminal part of the TP53 gene behind the DNA-binding domain (P = 0.0128). Moreover, in one of the NOTCH1-TP53-mutated patients the analysis of separated cancer cells revealed a simultaneous presence of NOTCH1 mutation and TP53 in-frame deletion in the same CLL cell. In contrast, in the other examined NOTCH1-TP53-mutated patient the concurrent NOTCH1 mutation and TP53 missense substitution (with presumed negative impact on patient prognosis) were found in different CLL cells. Conclusions The parallel presence of NOTCH1 hotspot mutation might be detected in a significant proportion of TP53-mutated patients and it seems to be associated with less prognostic unfavorable TP53 mutations. Nevertheless, these preliminary data should be further confirmed in a large cohort of patients. This study was supported by projects VaVPI MSMT CR CZ.1.05/1.1.00/02.0068 of CEITEC, IGA MZ CR NT13493-4/2012, NT13519-4/2012 and CZ.1.07/2.3.00/30.0009. Disclosures Brychtova: Roche: Travel grants Other. Doubek:Roche: Travel grants Other.

Survival Outcome and Insurance Status Among Hodgkin's Lymphoma (HL) Patients: Data from SEER 2007-2014

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 915-915
Author(s):  
Qian Wang ◽  
Changchuan Jiang ◽  
Yaning Zhang ◽  
Stuthi Perimbeti ◽  
Prateeth Pati ◽  
...  
Keyword(s):  
Cox Regression ◽  
Conflicts Of Interest ◽  
Age Groups ◽  
Survival Outcome ◽  
Disease Stage ◽  
Insurance Status ◽  
Risk Of Death ◽  
Increased Risk ◽  
The Us ◽  
Insured Patients

Abstract Introduction: Previous studies have shown that uninsured and Medicaid patients had higher morbidity and mortality due to limited access to healthcare. Disparities in cancer-related treatment and survival outcome by different insurance have been well established (Celie et al. J Surg Oncol.,2017). There are approximately 8,260 newly diagnosed HL cases in the US yearly (Master et al. Anticancer Res.2017). Therefore, we aim to investigate the variation of survival outcome and insurance status among HL patients. Methods: We extracted data from the US National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) 18 program. HL patients who were diagnosed from 2007-2014 were included. Demographic information including age, sex, race, annual household income, education and insurance were also collected. Insurance includes uninsured, insured and any Medicaid. Race/ethnicity includes white, black and other (including American Indian/AK native, Asian/Pacific Islander). HL is categorized by using International Classification of Disease for Oncology (ICD-O-3) into classical HL NOS (CHL NOS), nodular lymphocyte predominant HL (NLP), lymphocyte rich (LR), mixed cellularity (MC), lymphocyte depleted (LD), and nodular sclerosis (NS). Treatment modality included RT alone, CT alone, RT and CT combined, and no RT or CT. Survival time was estimated by using the date of diagnosis and one of the following dates: date of death, date last known to be alive or date of the study cutoff (December 31, 2014). Chi-square test and multivariate Cox regression were performed by using SAS 9.4 (SAS Institute Inc., Cary, NC, USA). Exclusion criteria include: 1) patients with unknown or unspecified race; 2) patients who survived less than 6 months because time of radiotherapy/chemotherapy was not known to the time of diagnosis; 3) patients with any other type of cancer prior to the diagnosis of HL; 4) patients with second or later primaries, and who were not actively followed. Results: A total of 14.286 HL patients were included in the analysis. Table 1 indicates the insurance status and demographic and tumor characteristics among HL patients diagnosed between 2007 and 2014. Patients with black race, male sex, and B symptoms were more likely to be uninsured and on any Medicaid compared to other races, female sex and without B symptoms (p&lt;0.01). As stage of disease increased, the percentage of insured patients decreased from 82.0% to 71.7%, (p&lt;0.01). As with year of diagnosis advanced, the percentage of uninsured did not appear to be changed however the proportion of both those with insurance and any Medicaid decreased slightly by 2.4% (p&lt;0.01). Those who received RT only were most likely to have insurance (89.6%) followed by combination modality (80.1%). As expected, uninsured status was associated with lower income and education level (p&lt;0.01). Table 2 shows the insurance and hazard ratio among HL patients by year of diagnosis adjusting for race, sex, histology type, income, education, and year of diagnosis. Any Medicaid patients had the highest HR of death from 2007-2010 compared to insured patients. Without insurance was also associated with increased risk of death but only significant in 2008, HR=2.26, 95% CI (1.35, 3.80). The survival outcomes comparing different insurance status by age groups (&lt;=29 and 30-64) were demonstrated in Kaplan-Meier Curve. In the age 29 or less group, insured patient showed has the best survival outcome followed by any Medicaid and then the uninsured. In the age 30-64 group, Medicaid patients had the worst survival outcome compared to those with or without insurance. Conclusion: Insurance status is one of the most important contributors of health disparity, especially in malignancy given the significant financial toxicity of therapies. We found that the proportion of the uninsured was trending up before the Affordable Care Act (ACA). Regarding the HL outcome, insured patients had the best survival across all age groups even though not significantly while Medicaid patients had the worst outcomes in almost all age groups, even worse than the uninsured after adjusting for the disease stage at diagnosis and sociodemographic factors. It would be of interest to explore the reason behind Medicaid patients' relatively poor outcomes. Future studies may also investigate how ACA, Medicaid expansion, and the possible upcoming republican healthcare reform influence HL outcome. Disclosures No relevant conflicts of interest to declare.

scholarly journals P54 Pneumocystis jirovecii prophylaxis in patients on rituximab

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_4) ◽  
Author(s):  
Kishore Warrier1 ◽  
Catherine Salvesani ◽  
Samundeeswari Deepak
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Pneumocystis Jirovecii ◽  
Current Evidence ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Number Of Patients ◽  
Increased Risk

Abstract Background Rituximab is a chimeric monoclonal antibody that depletes the B cell population by targeting cells bearing the CD20 surface marker and is used widely in the management of paediatric rheumatological conditions like juvenile systemic lupus erythematosus (JSLE), juvenile dermatomyositis (JDM), mixed connective tissue disease (MCTD) and juvenile idiopathic arthritis (JIA). Pneumocystis jirovecii pneumonia (PCP) is a potentially fatal opportunistic infection associated with congenital and acquired defects in T cell–mediated immunity. Our guideline did not recommend prophylaxis against PCP for patients on rituximab, unlike patients on cyclophosphamide, who are on cotrimoxazole until three months after cessation of the treatment. Cyclophosphamide is an alkylating agent which affects both B and T lymphocytes. Following the death of 16 year-old girl with JSLE due to PCP, the team reviewed the possible contributing factors, undertook a review of literature and discussed this at multi-disciplinary meetings involving the microbiology and immunology teams. This patient was found to have other risk factors for PCP – low CD4 T cells, concomitant use of corticosteroids and hypogammaglobulinaemia (IgG 3.0g/L). Although there is limited evidence that rituximab on its own increases the risk of PCP, there is emerging data that B cells may have a role in the protection against pneumocystis. Following the review, it was concluded that children on rituximab and an additional immunosuppressant (including corticosteroids) should receive prophylactic cotrimoxazole to cover PCP. Methods Retrospective audit carried out by the team to look at adherence to the new guideline regarding the use of cotrimoxazole for PCP prophylaxis in patients who have had rituximab between August 2017 and May 2019. Results P54 Table 1 Total number of patients who had rituximab 10 Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months) 7 Number of patients on rituximab monotherapy 2 Number of patients who are 6 months post-treatment 1 Number of patients with other risk factors for PCP 1 (hypogammaglobulinaemia) Number of patients who are eligible for prophylaxis, as per the guideline 8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia) Number of patients on cotrimoxazole 7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole We achieved 87.5% compliance in prescribing cotrimoxazole for PCP prophylaxis to all rheumatology patients receiving rituximab alongside another immunosuppressant agent; the one patient who this was not adhered to was due to potential adverse drug pharmacodynamic interaction between cotrimoxazole and methotrexate. Conclusion Although the current evidence points to increased risk of PCP in patients with inherited and iatrogenic defect of T cell function, there is emerging evidence that B cells may have a role too. Hence more work is required to determine the risk of PCP in patients on B cell targeted therapy (BCTT) and the need for prophylaxis. Conflicts of Interest The authors declare no conflicts of interest.

PS02.235: POOR ORAL HEALTH INCREASES RISK OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA: THE FOLLOW-UP STUDY OF THE LINXIAN NUTRITION INTERVENTION TRIAL

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 188-189
Author(s):  
Pei Yu ◽  
Su Zhang ◽  
Ming Wang ◽  
He Liang ◽  
Hu Fan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Health ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Risk Of Death ◽  
Increased Risk ◽  
Cumulative Rate

Abstract Background Several studies have suggested an association between poor oral health and esophageal squamous cell carcinoma (ESCC). We conduct this study to further examine the association between oral hygiene and ESCC risk in Linxian, the high risk area of China. Methods We recruit 29,553 healthy and 3318 esophageal squamous dysplasia participants aged between 40 and 69 in 1985 and then followed up until April, 2015. Basic characteristics were collected and oral related diseases were examined by trained doctors. Cox regression models were used to calculate hazard rations (HRs) and 95% confidence intervals (CIs). Results In general group, 2577 participants’ dead for ESCC and the cumulative rate of ESCC death was 12.9%. Teeth loss more than 20, before age of 40, bleeding of teeth, chapped lips, oral leukoplakia were significantly associated with risk of death from ESCC, and with 1.28 (95% CI: 1.18–1.38), 1.12 (95% CI: 1.03–1.23), 1.28 (95% CI: 1.13–1.45), 1.14 (95% CI: 1.04–1.25), 1.23 (95% CI: 1.12–1.35) fold increased risk of death from ESCC respectively in models adjusted for potential confounders. In dysplasia group, 540 participants’ dead for ESCC and the cumulative rate was 24.7%. Those who loss teeth more than 20, before age of 40, bleeding of teeth, have 1.24 (95% CI: 1.02–1.51), 1.25 (95%CI: 1.02–1.52), 1.35(95%CI: 1.06–1.70) fold increased risk after adjustment. Association between chapped lips and ESCC death was not found. Conclusion Severe teeth loss, early age teeth loss and teeth bleeding were associated with ESCC death and excess risk increased as dysplasia occurred. Chapped lips loss association with ESCC death in dysplasia group, it may reveals that it react before dysplasia change. Further studies are warranted to find the mechanism association and improvements of protecting oral health should be done. Disclosure All authors have declared no conflicts of interest.

scholarly journals Outcomes after Mastectomy and Lumpectomy in Octogenarians and Nonagenarians with Early-Stage Breast Cancer

2017 ◽  
Vol 83 (8) ◽  
pp. 887-894 ◽  
Author(s):  
Ameliay Merrill ◽  
Doris R. Brown ◽  
Heidi D. Klepin ◽  
Edward A. Levine ◽  
Marissa Howard-Mcnatt
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
Clinical Stage ◽  
Univariate Analysis ◽  
Local Treatment ◽  
Breast Conservation ◽  
Early Stage Breast Cancer ◽  
Risk Of Death ◽  
Increased Risk

Prospective studies have shown equal outcomes after mastectomy or breast conservation in patients with invasive breast cancer; however, many of these studies excluded elderly patients. We identified patients in their eighties and nineties with clinical stage 0 to II breast cancer undergoing mastectomy or lumpectomy with or without radiation from the prospective sentinel lymph node database at Wake Forest Baptist Health and analyzed their treatment and survival. Of 92 patients, 24 (26.1%) underwent mastectomy, 22 (23.9%) lumpectomy with radiation, and 46 (50.0%) lumpectomy alone. Significant differences were noted in tumor size (P = 0.018), nodal status (P = 0.013), and stage (P = 0.011) between the groups. Only 7.6 per cent of patients had chemotherapy, whereas 51.1 per cent took antiestrogen therapy. Recurrence occurred in 11 patients. In univariate analysis, overall survival did not differ by surgery. Age was the only factor that increased risk of death (HR = 1.19, P = 0.028). In this age group, neither tumor factors nor the type of local treatment significantly influenced overall survival. Octogenarians and nonagenarians with early-stage breast cancer undergoing breast-conserving surgery with or without radiation have equivalent survival to patients having a mastectomy.

Chromosomal Abnormalities in MDS Are Linked to Dysregulation of CDC20 and CEP55 Genes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 36-37
Author(s):  
Mayara Magna de Lima Melo ◽  
Daniela de Paula Borges ◽  
Antônio Wesley Araújo Dos Santos ◽  
Gabrielle Melo Cavalcante ◽  
Leticia Rodrigues Sampaio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chromosomal Instability ◽  
Spindle Assembly Checkpoint ◽  
Chromosomal Abnormalities ◽  
Bone Marrow Cells ◽  
Conflicts Of Interest ◽  
Normal Karyotype ◽  
Mitotic Arrest ◽  
Complex Karyotype ◽  
Increased Risk

Myelodysplastic syndrome (MDS) is a clonal hematopoietic disorder characterized by cytopenias and an increased risk of progression to acute myeloid leukemia (AML). Its pathogenesis is strictly linked to chromosomal instability, which in turn provides a valuable prognostic marker. Malignant cells develop alternative routes to escape mitosis checkpoints, overcoming the mitotic arrest imposed by Spindle Assembly Checkpoint (SAC), a process dependent on CDC20 inactivation. Abnormal levels of CDC20 can inhibit mitotic arrest, promoting premature exit from mitosis. Overexpression of CEP55 also facilitates the mitotic exit, resulting in polyploidy (an event called Mitotic Slippage). Since chromosomal abnormalities are one of the most important prognostic factors for patients with MDS, this study aimed to analyze the possible link between chromosomal abnormalities and CDC20 and CEP55 mRNA expression in MDS. We evaluated the bone marrow cells from 45 patients diagnosed as MDS according to 2016 WHO-classification (1 MDS-SLD, 15 MDS-RS-MLD, 5 MDS-MLD, 1 t-MDS, and 23 MDS-EB) and 5 bone marrow of healthy controls. Conventional Karyotyping was performed by G-banding of 20 metaphases whenever possible. TaqMan expression assays for CDC20 (Hs00426680_mH) and CEP55 (Hs01070181_m1) were performed in duplicate and the expression ratios were calculated using the 2−ΔCq method. Normality was evaluated by Shapiro-Wilk test. Outliers were removed. The Student's t-test or one-way ANOVA with Tukey/Games Howell post-hoc test was used to analyze the influence of relative expression regarding variables. Patients with MDS showed increased expression of CDC20 and CEP55 compared to healthy individuals (p&lt;0.0001 and p&lt;0.0001). Regarding karyotype, there was the overexpression of CDC20 and CEP55 in patients with altered karyotype and aneuploid karyotype when compared to patients with normal karyotype (p &lt;0.0001 and p =0.001; p = 0.013 and p = 0.022, respectively) (Figure 1A-D). CDC20 and CEP55 have fundamental functions in controlling the progression of metaphase to anaphase and both, when upregulated, induce chromosomal instability. Additionally, patients with del(7q) and complex karyotype showed hyperexpression of CEP55 when compared with patients with normal karyotype (p = 0.005 and p = 0.019) (Figure 1E-F), while patients with deletion (5q) had an increased expression of CDC20 when compared with patients with normal karyotype (p &lt;0.0001). Our group previously demonstrate that high CDC20 protein expression is associated with complex karyotype in MDS patients. Thus, we hypothesized that the deregulation of CDC20 and CEP55 expression induces chromosomal changes, each one in its way. Both can cause disturbances in crucial phases of mitosis (anaphase and cytokinesis, respectively). Finally, we detected a strong correlation between CDC20 and CEP55 (r = 0.646; p &lt;0.0001), suggesting both genes may play a synergistic role during chromosomal abnormalities in MDS, creating possible new targets to be evaluated in MDS. Our data suggest CDC20 and CEP55 as possible new therapeutic targets in MDS. There is a need for further studies, validations and urgent in-depth investigations in cell lines/primary samples or murine models. Disclosures No relevant conflicts of interest to declare.

Myeloablative Second Transplants Are Associated with High Non-Relapse Mortality and Poorer Survival Than Non-Myeloablative Second Transplants.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3323-3323
Author(s):  
Brian T. Hill ◽  
Brian J. Bolwell ◽  
Lisa Rybicki ◽  
Robert Dean ◽  
Matt Kalaycio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Conflicts Of Interest ◽  
Recursive Partitioning ◽  
Multivariable Analysis ◽  
Cleveland Clinic ◽  
Disease Status ◽  
High Rate ◽  
Hematopoietic Stem ◽  
Risk Of Death ◽  
Thick Line

Abstract Abstract 3323 Poster Board III-211 Allogeneic hematopoietic stem cell transplantation (SCT) for patients who have previously undergone allogeneic or autologous SCT is potentially curative, but dangerous. In order to identify patient, disease and treatment characteristics associated with outcome, we analyzed prognostic factors in 101 consecutive patients who underwent second transplants using allogeneic donors at the Cleveland Clinic between May 1987 and October 2008. Inclusion criteria included age ≥ 18, first SCT either autologous or allogeneic, and second SCT allogeneic. The second transplant was myeloablative (MA) in 65.3% of patients and non-myeloablative (NMA) in 34.7%. Relative to NMA second transplants, patients who underwent MA second transplants were younger (median 34 vs. 45 years, P<0.001), were more likely to have undergone autologous first transplant (34.8% vs. 71.4%, P<0.001), and were more likely to have undergone their second transplant for a diagnosis of acute leukemia (56.1% vs. 17.1%, P<0.001). Patients whose second transplant was MA had higher rates of non-relapse mortality (NRM) (63.5% vs. 28.6%, P=0.008) and shorter survival than patients whose second transplant was NMA (median 3.2 vs. 20.5 months, P<.001; figure). Using recursive partitioning analysis, we found that 17 patients transplanted within 3 months of first transplant had higher NRM (hazard ratio [HR] 4.28, P<0.001) and worse survival (HR 3.03, P<0.001) than those transplanted >3 months after first transplant. 16 of these 17 patients underwent MA second transplant. Among all 17 patients transplanted within 3 months of first transplant, 1 year mortality was 91.4% and median survival was 2.3 months. Death was almost exclusively due to non-relapse causes. In multivariable analysis, we found that relative to undergoing second transplant more than 3 months after first transplant, transplant within 3 months of first transplant carried a higher rate of death and NRM (HR 2.97, P=0.001 and HR 4.58, P<0.001, respectively). Relative to NMA second transplant, MA second transplant carried higher risk of death and NRM (HR 3.69, P<0.001 and HR 4.81, P<0.001, respectively). This difference was also significant for patients transplanted more than 3 months after first transplant (HR 2.68, P<0.001 for death, and HR 3.24, P = 0.002 for NRM). Relative to autologous first transplant, having undergone myeloablative allogeneic first transplant was also prognostic for both death and NRM in multivariable analysis (HR 1.95, P = 0.024 and HR, 2.48, P = 0.018, respectively). Age, gender, diagnosis, disease status, and donor relationship were not prognostic for survival or NRM. Figure: Overall Survival of Second Transplant by Type Figure:. Overall Survival of Second Transplant by Type Kaplan-Meier estimates of overall survival for patients after MA allogeneic second transplant (thick line) or NMA allogeneic second transplant (thin line). We conclude that MA transplantation within 3 months of prior SCT carries an unacceptably high rate of NRM and should not be performed. Despite a lower incidence of relapse, MA second transplants were associated with substantially more NRM and significantly worse survival than NMA second transplants. Disclosures No relevant conflicts of interest to declare.

Expression of Phosphorylated Signal Transducer and Activator of Transcription 5 (pSTAT5) Is Associated with An Increased Risk of Death In Acute Myeloid Leukemia.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1675-1675
Author(s):  
Anna Brady ◽  
Sarah Gibson ◽  
Lisa Rybicki ◽  
Eric Hsi ◽  
Edward Copelan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Myeloid Leukemia ◽  
Signal Transducer ◽  
Newly Diagnosed ◽  
Risk Of Death ◽  
Increased Risk ◽  
History Of ◽  
Acute Myeloid

Abstract Abstract 1675 Background: Acute myeloid leukemia (AML) is characterized by rapid growth, resistance to therapy, and poor overall survival. Clinical and biologic prognostic markers can help define pathogenesis, guide treatment, and identify novel therapies. Phosphorylated signal transducer and activator of transcription 5 (pSTAT5) is one such potential marker. The transcription factor STAT5 regulates many aspects of cell growth, survival, and differentiation. Constitutive activation of STAT5 (by phosphorylation) has been identified in a number of malignancies, including AML. We investigated whether the level of pSTAT5 expression correlates with complete remission (CR) rates, progression-free survival (PFS), and overall survival (OS) in patients (pts) with newly diagnosed AML. Methods: From 1999 to 2005, all adult pts with newly diagnosed AML (WHO criteria) receiving induction chemotherapy and with an available diagnostic bone marrow biopsy performed at our institution were evaluated. B5-fixed bone marrow core biopsies were reviewed for areas with the highest concentration of blasts. A tissue microarray was constructed using 1 mm cores. The cores were arrayed in duplicate in the majority of samples. Immunohistochemistry was performed for pSTAT5 with anti-pSTAT5 a/b Y695/99 mouse monoclonal antibody (AX1; Advantex Bioreagents) using automated stainers and heat-induced epitope retrieval. In each case, five hundred blasts were counted. The percentage of cells staining positive for pSTAT5 expression was determined by a pathologist blinded to clinical results. Standard metaphase karyotypes were classified into cytogenetic (CG) risk groups by CALGB criteria. Cox proportional hazards analysis was used to identify univariate and multivariate prognostic factors for CR, PFS, and OS, including age at diagnosis, history of an antecedent hematologic disorder (AHD), WBC at diagnosis, pSTAT5 expression, and CG risk group. Results: Adequate tissue and clinical data were available in 112 pts. The median age was 57 years, and median WBC at diagnosis 12.0 K/ μL. Twenty six percent of pts had favorable CG, 41% intermediate risk, 27% high risk, and 6% other (unknown or could not be classified). Nineteen percent of pts had an AHD. pSTAT5 expression was absent in 58% of pts. The remainder of the pts had: 1–5% pSTAT5 (25% of pts), 10% pSTAT5 (11% of pts), 20% pSTAT5 (4% of pts), 30% pSTAT5 (1% of pts), and 50% pSTAT5 (2% of pts). Seventy percent of all pts achieved a CR following induction chemotherapy. Sixty-four percent of pts received post-remission chemotherapy, 3.6% an autologous transplant, and 13.6% an allogeneic transplant in first CR. Median PFS and OS were 9.6 months and 16.0 months, respectively. On univariate analysis, age, history of AHD, WBC at diagnosis, CG risk, and any pSTAT5 expression were prognostic factors for PFS and OS. In multivariable analyses controlling for the above prognostic factors, pSTAT5 expression > 0 was also significantly associated with an increased risk of death (HR 1.96, 95% CI 1.19–3.23, p=0.008), progression or death (HR 1.64, 95% CI 1.01–2.66, p=0.046), and relapse after achieving CR (HR 2.31, 95% CI 1.16–4.63, p=0.018). pSTAT5 expression was not a predictor of achievement of CR. Conclusions: pSTAT5 expression in newly diagnosed adults with AML is associated with a decreased PFS, decreased OS, and increased risk of relapse. Validation of its prognostic value requires additional study. Agents targeting this signaling pathway might improve the outcome of pts with AML. Disclosures: No relevant conflicts of interest to declare.

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