Patterns of Care and Age-Specific Impact of Extent of Resection and Adjuvant Radiotherapy in Pediatric Pineoblastoma

Neurosurgery ◽  
2020 ◽  
Vol 86 (5) ◽  
pp. E426-E435 ◽  
Author(s):  
Michael C Jin ◽  
Laura M Prolo ◽  
Adela Wu ◽  
Tej D Azad ◽  
Siyu Shi ◽  
...  
Keyword(s):  
Disease Management ◽  
Older Patients ◽  
Tumor Resection ◽  
Extent Of Resection ◽  
Patterns Of Care ◽  
Categorical Variables ◽  
Prognostic Impact ◽  
Younger Patients ◽  
Chi Squared ◽  
Poor Outcomes

Abstract BACKGROUND Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. Controversy remains regarding optimal disease management. OBJECTIVE To evaluate patterns of care and optimal clinical management of pediatric pineoblastoma. METHODS A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients diagnosed between 2004 and 2015 were queried from the National Cancer Database. Wilcoxon rank-sum statistics and chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of covariates. Propensity-score matching was used to balance baseline characteristics. RESULTS Older patients (age ≥ 4 yr) experienced improved overall survival compared to younger patients (age < 4 yr) (hazard ratio [HR] = 0.41; 95% CI 0.25-0.66). Older patients (adjusted odds ratio [aOR] = 5.21; 95% CI 2.61-10.78) and those residing in high-income regions (aOR = 3.16; 95% CI 1.21-8.61) received radiotherapy more frequently. Radiotherapy was independently associated with improved survival in older (adjusted HR [aHR] = 0.31; 95% CI 0.12-0.87) but not younger (aHR = 0.64; 95% CI 0.20-1.90) patients. The benefits of radiotherapy were more pronounced in patients receiving surgery than in those not receiving surgery (aHR [surgical patients] = 0.23; 95% CI 0.08-0.65; aHR [nonsurgical patients] = 0.46; 95% CI 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P = .041); extent of resection was not associated with survival in younger patients (P = .880). CONCLUSION Aggressive tumor resection was associated with improved survival only in older pediatric patients. Radiotherapy was more effective in patients receiving surgery. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.

scholarly journals Patterns of Care and Age Specific Impact of Resection Extent and Adjuvant Radiotherapy in Pediatric Pineoblastoma

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Michael Chuwei Jin ◽  
Laura M Prolo ◽  
Adela Wu ◽  
Tej D Azad ◽  
Siyu Shi ◽  
...  
Keyword(s):  
Disease Management ◽  
Older Patients ◽  
Extent Of Resection ◽  
Categorical Variables ◽  
Subtotal Resection ◽  
Prognostic Impact ◽  
Younger Patients ◽  
Chi Squared ◽  
Poor Outcomes ◽  
Multimodal Management

Abstract INTRODUCTION Pediatric pineoblastomas are highly aggressive tumors that portend poor outcomes despite multimodal management. While treatment often utilizes a combination of surgical resection, radiotherapy, and chemotherapy, controversy remains regarding optimal disease management. METHODS A total of 211 pediatric (age 0-17 yr) histologically confirmed pineoblastoma patients were queried from the National Cancer Database, a nationwide, hospital-based registry. Wilcoxon rank-sum statistics and Chi-squared analyses were used to compare continuous and categorical variables, respectively. Univariable and multivariable Cox regressions were used to evaluate prognostic impact of demographic, tumor, and treatment-related covariates. Propensity-score matching was used to balance baseline characteristics. RESULTS Older patients (age = 4) experienced improved overall survival compared to younger patients (age < 4) (hazard ratio [HR] = 0.41; 95% confidence interval [CI] = 0.25-0.66). Radiotherapy usage was associated with age and socioeconomic factors, with older patients (adjusted odds-ratio [aOR] = 5.21; 95% CI = 2.61-10.78) and those residing in high-income regions (aOR = 3.16; 95% CI = 1.21-8.61) receiving radiotherapy more frequently. Radiotherapy was associated with improved survival after adjusting for covariates in older (HR = 0.31; 95% CI = 0.12-0.87) but not younger (HR = 0.64; 95% CI = 0.20-1.90) patients. Patients receiving either gross total resection (GTR) or subtotal resection (STR) demonstrated greater survival benefits with addition of radiotherapy than patients receiving neither (surgery HR = 0.23; 95% CI = 0.08-0.65; no surgery HR = 0.46; 95% CI = 0.22-0.97). Older patients experienced improved outcomes associated with aggressive resection (P = .041); extent of resection was not associated with survival in younger patients (P = .880). CONCLUSION Aggressive resection of pineoblastoma was associated with improved survival only in older patients. Radiotherapy extended survival in patients receiving surgery compared to those receiving neither. Age-stratified approaches might allow for improved disease management of pediatric pineoblastoma.

Incidence and Prognostic Impact of Gene Mutations in Older Patients with AML Treated in the ALFA-9801 Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1525-1525
Author(s):  
Aline Renneville ◽  
Sylvie Castaigne ◽  
Sylvie Chevret ◽  
Laura Llopis ◽  
Nathalie Philippe ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Older Patients ◽  
Gene Mutations ◽  
Significant Prognostic Factor ◽  
Prognostic Impact ◽  
Npm1 Mutation ◽  
Younger Patients ◽  
Mutational Status ◽  
Cebpa Mutations ◽  
The Impact

Abstract Introduction: The impact of gene mutations, i.e. poor-prognosis FLT3 internal tandem duplications (ITDs) and good-prognosis NPM1 or CEBPA mutations, has been welldocumented in several recent reports dealing with younger patients with acute myeloid leukemia (AML). As these mutations were associated with cytogenetically normal (CN) AML, most of these reports focused on CN-AML patients. Both FLT3-ITD and NPM1 mutations were also associated with higher WBC. The objective of the present study was to evaluate the incidence, correlations, and prognostic value of these mutations in older patients with the disease. Methods: The French ALFA group has screened a total of 583 patients, including 333 younger patients (15–50 years) treated in the ALFA-9802 trial and 250 older patients (50–70 years) treated in the ALFA-9801 trial. The older ALFA-9801 trial included 468 patients with previously untreated de novo AML and studied the role of idarubicin (IDA) as compared to high-dose daunorubicin (DNR) as well as interleukine-2 as a maintenance therapy (C. Pautas et al. ASH 2007, abstract #162). Comparison between the 250 patients tested for mutations in that trial and the 218 patients not tested showed no differences in age, sex ratio, FAB classification, bone marrow blasts percentage, randomization arm, and performance status at entry in the study. There was, however, a higher rate of patients with intermediate cytogenetics (p=.01) or increased WBC (p=.01) in the former subgroup. Results: Median age of the 250 patients tested was 60 years. Cytogenetics was studied in 232 patients (12 favorable, 174 intermediate, 46 unfavorable). One hundred twenty-two patients (49%) had CN-AML. CR rate was 67.5% and estimated 4-year OS was 26% (95% CI, 20–33). Incidences of FLT3-ITD, NPM1, and CEBPA mutations were 37/250 (15%), 64/249 (26%), and 20/249 (8%), respectively. These incidences were very similar than in the younger ALFA-9802 population [50/329 (15%), 76/321 (24%), and 24/316 (8%), respectively]. In these older AML patients, the correlation between increased WBC and FLT3-ITD (p&lt;.001) or NPM1 mutation (p&lt;.001) was still observed. Conversely, NPM1 mutations only (p&lt;.001), but not FLT3-ITDs (p=.10) or CEBPA mutations (p=.99), were significantly associated with CN-AML. In the whole group of 249 patients with either normal or abnormal karyotype tested for all mutations, 46 were NPM1+/FLT3-ITDwt, 19 FLT3-ITD+/NPM1wt, 18 FLT3-ITD+/NPM1+, and 166 NPM1wt/FLT3-ITDwt. CR rate was 87%, 84%, 56%, and 75% and median OS was 20.5, 18.6, 6.0, and 14.6 months, respectively. In the 20 CEBPA+ patients, CR rate was 80% and median OS was 22.8 months. In the group of 122 CN-AML patients tested for all mutations, 36 were NPM1+/FLT3-ITDwt, 8 FLT3-ITD+/NPM1wt, 15 FLT3-ITD+/NPM1+, and 63 NPM1wt/FLT3- ITDwt. CR rate was 92%, 87.5%, 60%, and 78% and median OS was 20.5, 16.9, 7.0, and 16.8 months, respectively. In the 10 CEBPA+ patients, CR rate was 80% and median OS was not reached. In multivariate analysis including age, WBC, cytogenetics (favorable versus others), and gene mutational status (NPM1+ or CEBPA+ if FLT3-ITDwt versus others), a pejorative effect of age (p=.02) and WBC (p&lt;.001), but a protective effect of mutational status (HR= 0.66, p=.05) and favorable cytogenetics (HR=0.43, p=.06) was observed in the whole patient population. Nevertheless, estimated 4-year OS was only 37% (95% CI, 23–50) in patients with a favorable mutational status. In those with CNAML and a favorable mutational status, estimated 4-year OS reached only 40% (95% CI, 23–56). In this subgroup of patients with CN-AML, WBC was the only significant prognostic factor identified in multivariate analysis (p&lt;.001). Conclusion: This study conducted in a large cohort of patients aged 50 to 70 years and prospectively treated in the same trial showed that gene mutational status still affect the outcome of older patients with AML. Mutation incidences are in the same range than in younger patients. Nevertheless, their impact on OS appeared to be less marked than in younger patients, probably due to the worse general outcome observed in these older patients.

Myelodysplastic Syndromes in Adolescent Young Adults (AYA)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2898-2898
Author(s):  
Joanna (Asia) Grabska ◽  
Bijal D. Shah ◽  
Najla H. Al Ali ◽  
Eric Padron ◽  
Hanadi Ramadan ◽  
...  
Keyword(s):  
Lower Risk ◽  
Older Patients ◽  
Research Funding ◽  
Advisory Board ◽  
Categorical Variables ◽  
Younger Patients ◽  
Poor Risk ◽  
Disease Biology ◽  
Grant Support ◽  
Baseline Characteristics

Abstract Introduction: There has been little improvement in cancer survival of adolescent and young adult (AYA) patients, ages 18-39, possibly reflecting different disease biology in this subgroup. Myelodysplastic syndrome (MDS) is mainly a disease of the elderly. The characteristics, outcomes and response to treatment are not well described among AYA population. Patients and Methods: Retrospective review of patients from the Moffitt Cancer Center MDS database. We compared baseline characteristics and outcomes of AYA population to older patients. Descriptive statistics were used for baseline characteristics. Chi-square test was used for categorical variables, and t-test for continuous variables comparison. Kaplan-Meier estimates were used for overall survival (OS), and cox regression method for multivariable analysis. Results: We identified 51 AYA and 1,897 older MDS patients. Table-1 summarizes baseline characteristics. More females and Hispanics were noted in AYA group. The AYA patients had higher risk disease, more circulating myeloblasts and more hypoplastic MDS. Autoimmune disorders were more prevalent in older patients. The median OS was 47 months (mo) in the AYA group versus 40 mo in the older group (p 0.26). The median OS was 47 mo versus 56 months in lower risk (low and intermediate-1(int-1)) IPSS MDS AYA group and older group respectively (p 0.46). In the higher risk IPSS group (int-2 and high), median OS was 82 mo in AYA group compared to 17 mo in older group (p 0.001). Thirty individuals were transplanted in the AYA versus 241 in the older group. The median OS for transplanted patients was 55 mo in the AYA group and 46 mo in the older (p 0.4). Whereas, in the non-transplanted patients median survival was 31 months for AYA and 39 months for the older group (p 0.9). The rate of AML transformation was 37% versus 28% in AYA and older group respectively (p 0.17). No difference in use or response to hypomethylating agents was observed. Lenalidomide therapy was seldom used in younger patients. In AYAs, poor karyotype was the only variable strongly associated with worse outcome. Fifteen patients had poor risk karyotype. The median OS was 47 months, not reached and 29 months among patients with good, intermediate and poor risk cytogenetics, respectively (p 0.035) Conclusion: MDS is rare and tends to be more aggressive in the AYA population. The karyotype was the most important prognostic factor. The differences in underlying disease biology should be further explored. Allogeneic stem cell transplant offered younger patients best outcomes. Table 1. Baseline characteristics of AYA and Older Patient Characteristic AYA (18-39) (N= 51) Older Patients (> 39 years old) (N=1,897) P value Gender Female 25 (49%) 655 (34.5%) 0.025 Race White Black Hispanic Other 34 (66.7%) 2 (3.9%) 13 (25.5%) 2 (3.9%) 1,736 (91.5%) 47 (2.5%) 57 (3%) 41 (2.2%) 0.000 t-MDS Yes 10 (19.6%) 359 (18.9%) 0.902 WHO Subtype RA RARS RCMD Deletion 5q RAEB-1 RAEB-2 AML CML MDS-U MDS/MPN 3 (5.9%) 1 (2%) 22 (43.1%) 0 (0%) 11 (21.6%) 10 (19.6%) 0 (0%) 0 (0%) 1 (2%) 2 (3.9%) 196 (10.4%) 151 (8%) 583 (30.8%) 51 (2.7%) 372 (19.7%) 336 (17.7%) 1 (0.1%) 60 (3.2%) 44 (2.3%) 94 (5%) 0.188 IPSS Lower risk Higher risk 28 (59.6%) 19 (40.4%) 1,264 (68.2%) 590 (31.8%) IPSS-R Very low/low Intermediate High/very high 13 (30.1%) 14 (32.6%) 16 (37.3%) 826 (45.3%) 394 (21.6%) 602 (33%) Hypoplastic BM Yes 11 (23.4%) 178 (9.8%) 0.009 LGL clone Yes 0 (0%) 159 (8.4%) 0.033 Autoimmune disease Yes 8 (15.7%) 500 (26.4%) 0.055 Karyotype Good Intermediate Poor 24 (50%) 9 (18.8%) 15 (31.3%) 1120 (60.4%) 300 (16.2%) 434 (23.4%) 0.324 Peripheral Blasts Yes 14 (29.8%) 246 (13.2%) 0.003 RBC Transfusion Dependent 36 (70.6%) 1274 (67.3%) 0.372 Disclosures Shah: Seattle Genetics: Research Funding; Rosetta Genomics: Other: Grant support; Acetylon: Other: Advisory board; Plexus Communications: Honoraria; Pharmacyclics: Speakers Bureau; Spectrum: Other: Advisory board, Speakers Bureau; Bayer: Honoraria; Celgene: Other: Advisory board, Speakers Bureau; DeBartolo Institute for personalized medicine: Other: Grant support. Lancet:Pfizer: Consultancy; Kalo-Bios: Consultancy; Boehringer-Ingelheim: Consultancy; Amgen: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy, Research Funding. List:Celgene Corporation: Honoraria, Research Funding. Komrokji:Celgene: Consultancy, Research Funding; Incite: Consultancy; Novartis: Speakers Bureau; GSK: Research Funding.

scholarly journals Age is associated with unfavorable neuropathological and radiological features and poor outcome in patients with WHO grade 2 and 3 gliomas

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aleksandrs Krigers ◽  
Matthias Demetz ◽  
Claudius Thomé ◽  
Christian F. Freyschlag
Keyword(s):  
Older Patients ◽  
Group Analysis ◽  
Tumor Resection ◽  
Extent Of Resection ◽  
Lower Grade ◽  
Wild Type ◽  
Who Grade ◽  
Radiological Features ◽  
Age Related ◽  
Type Population

AbstractWith the rising life expectancy and availability of neuroimaging, increased number of older patients will present with diffuse and anaplastic gliomas. The aim of our study was therefore to investigate age-related prognostic clinical, neuropathological and radiological features of lower-grade gliomas. All consecutive patients with diffuse or anaplastic glioma WHO grade 2 and 3 who underwent first tumor resection between 2010 and 2018, were selected from the institutional neuro-oncological database and evaluated. The mean age of 55 males and 44 females was 46 years (SD ± 16). Wild-type IDH1 (p = 0.012), persistent nuclear ATRX expression (p = 0.012) and anaplasia (p < 0.001) were significantly associated with higher age. The CE volume before resection was found to be increased in older patients (r = 0.42, p < 0.0001), and CE rate was higher in the IDH wild-type population only (p = 0.02). The extent of resection did not differ with age. Overall, one year of life resulted in a PFS reduction of 9 days (p = 0.047); in IDH sub-group analysis, this dependency was confirmed only in wild-type tumors (p = 0.05). OS was significantly reduced in older patients (p = 0.033). In conclusion, behavior and prognosis of WHO grade 2 and 3 glioma were unfavorable in correlation to patient’s age, even if the extent of resection was comparable. Older age imparted a poorer PFS and higher CE rate only in the IDH wild-type population.

scholarly journals Primary Tumor Location is Associated with Prognosis for Women with Breast Cancer

2021 ◽  
Author(s):  
Zhuowei Tang ◽  
Yuzhu Ji ◽  
Xiaohong Zhang ◽  
Weiyun Xu ◽  
Lijuan Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Tumor ◽  
Tumor Location ◽  
Categorical Variables ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Cancer Specific Survival ◽  
Primary Tumor Location ◽  
Chi Squared ◽  
Cox Analysis

Abstract Background: The prognostic impact of tumor location on breast cancer patients is not consistent and still controversial. We aimed to investigate the prognostic role of primary tumor location on the survival of patients with breast cancer. Methods: Using the Surveillance, Epidemiology, and End Results database, we identified 53,905 patients diagnosed with tumors in the lower quadrants (n=11,065), upper quadrants (n=38,974), or central and nipple (n=3,866). Chi-squared test was used to compare categorical variables across the groups. Cox proportional hazard models were applied to estimate the factors associated with prognosis.Results: Compared with the other quadrants, patients with central and nipple lesions showed generally more unfavorable clinicopathologic features and worse breast cancer-specific survival (BCSS) and overall survival (OS). Multivariate Cox analysis showed a higher hazard ratio (HR) for tumor location of central and nipple (BCSS: HR, 1.145, p = 0.036, 95% confidence interval [CI], 1.009-1.299; OS: HR, 1.118, p = 0.024, 95% CI: 1.015-1.232), while lower HR were observed for upper quadrants (BCSS: HR, 0.888, p = 0.004, 95% CI: 0.818-0.964; OS: HR, 0.930, p = 0.023, 95% CI: 0.873-0.990). Multivariate logistic regression indicated that tumors located in central and nipple were more likely to be inoperable disease (HR, 1.460, 95% CI: 1.300-1.640, p < 0.001), while tumors located in upper quadrants tend to be operable disease (HR, 0.895, p = 0.005, 95% CI, 0.829-0.967).Conclusion: Tumors located in central and nipple had negative contact with BCSS and OS, while tumor located in upper quadrants had favorable contact with survival.

scholarly journals Molecular Genetics and Prognosis in Younger Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3025-3025
Author(s):  
Daniel Helbig ◽  
Ghaith Abu Zeinah ◽  
Erica B Bhavsar ◽  
Richard R. Furman ◽  
John N. Allan
Keyword(s):  
Prognostic Factors ◽  
Board Of Directors ◽  
Molecular Genetics ◽  
Older Patients ◽  
Categorical Variables ◽  
Genetic Mutations ◽  
Advisory Committees ◽  
Younger Patients ◽  
Tp53 Mutations ◽  
The Difference

Background: While CLL is commonly diagnosed in older patients, there are ~15% of patients diagnosed at ages younger than 50. Several past studies have investigated differences in clinical parameters and treatment outcomes in younger patients with CLL, including a shorter time to first treatment (TTFT) among younger patients (Parikh et al. 2014). However, few studies have reported on the genetic mutational differences between younger and older cohorts. To bridge this gap, we investigated the mutational landscape between younger and older patients and evaluated the clinical outcome TTFT, hypothesizing that our younger cohort of patients would associate with higher risk lesions and behave more aggressively. Methods: We conducted a single center retrospective database review of 557 patients diagnosed with CLL from 1980 to 2019 who underwent whole exome profiling between 2015 to 2019 with a lymphoid specific 75-gene next generation sequencing (NGS) panel (Genoptix Inc). A Pearson's chi-square test was used to compare categorical variables between groups and a Wilcoxon rank sum test was used to compare medians. The TTFT was estimated using Kaplan-Meier methods, and the difference between groups was compared using the log-rank test. Multivariate regression using a Cox proportional hazards model was used to compare TTFT between groups independent of well-accepted clinical risk factors for treatment initiation. Results: Of the 557 patients who underwent NGS testing, 92 (16.5%) were younger than 50 years old with a median age of 44.9 years old compared to a median age of 62.7 years old in the 465 (83.5%) patients older than 50 years old. There was no difference between the two groups with regards to previous treatment prior to NGS testing with 29.2% in the older patients and 26.1% in the younger patients having previously been treated (p=0.63). The median time from CLL diagnosis to initial NGS testing was 5.2 years in the younger cohort vs. 3.2 years in the older cohort (p=0.04). There were no differences in baseline prognostic factors between younger and older patients, including Rai stage, IGVH status, CD38 positivity, ZAP70 expression, and cytogenetic abnormalities. We found a lower frequency of TP53 mutations in younger compared to older patients (6.5% vs 15.7%, p=0.03) but otherwise found no differences in any other genetic mutations between the two groups, including NOTCH1, FAT1, ATM, and SF3B1 (Table 1). There was a longer TTFT in younger patients with a median TTFT of 7.61 years compared to 4.42 years in older patients (p=<0.001) (Figure 1). The difference in TTFT was independent of TP53 mutation status in a multivariate analysis. Conclusions: We found no enrichment of specific genetic mutations in younger versus older patients except a lower prevalence of TP53 mutations in our younger patient population. We found younger patients have a longer TTFT, which is contrary to previous studies that have identified younger age as a negative prognostic marker. Future research is needed to determine why younger patients in our cohort appear to have a more indolent disease course in terms of TTFT despite similar baseline prognostic factors and molecular genetics to older patients. Disclosures Furman: Acerta Pharma: Consultancy; Genentech: Consultancy; Incyte: Consultancy; AstraZeneca: Consultancy; Abbvie: Consultancy; Beigene: Consultancy; TG Therapeutics: Consultancy; Sunesis: Consultancy; Oncotracker: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy; Verastem: Consultancy. Allan:AbbVie, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta Pharma: Consultancy; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics LLC, an AbbVie company: Consultancy; Bayer: Consultancy; Sunesis Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria; Verastem Oncology, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Patterns of Care and Predictors of Survival in Adolescents and Young Adults with Hodgkin Lymphoma: A Population-Based Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2191-2191
Author(s):  
Justine M. Kahn ◽  
Fran Maguire ◽  
Qian Li ◽  
Elysia Alvarez ◽  
Theresa H.M. Keegan
Keyword(s):  
Hodgkin Lymphoma ◽  
Older Patients ◽  
De Novo ◽  
Initial Therapy ◽  
Population Based ◽  
Patterns Of Care ◽  
Younger Patients ◽  
Treatment Regimens ◽  
Risk Of Death ◽  
Race Ethnicity

Introduction: Hodgkin lymphoma (HL) is one of the most treatable cancers affecting adolescent and young adult (AYA) patients (15 - 39 years), however optimal therapy for de novo disease in this population remains a subject of debate. Population-based studies in HL consistently report a survival disadvantage for AYAs when compared with younger patients. Though the etiology of these disparities is unclear, analyses of clinical trials data suggest that observed survival differences may relate to treatment, rather than to age. Because registry analyses are often limited by lack of information about clinical characteristics and therapeutic exposures, the independent effect of age on HL-outcome outside of the cooperative group setting is unknown. To address this gap in the literature, we: (1) examined initial treatment regimen and patterns of care in a population-based cohort of AYAs compared to children with de novo HL, and (2) examined the impact of sociodemographic and clinical variables on overall survival (OS) and disease-specific survival (DSS) by age, after adjusting for therapy. Methods: Data for 4,426 patients aged 0 - 39 years diagnosed with classical HL between 2007 and 2016 were obtained from the California Cancer Registry (CCR). Detailed treatment information for each patient was extracted from unstructured free-text fields in the CCR database. Chemotherapy regimens were classified based on standard treatment approaches for adult and pediatric HL (Table). Multivariable cox proportional hazards regression models were used to examine the influence of sociodemographic and clinical variables on OS and DSS, overall and by age group, and are presented as adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Models were adjusted for race/ethnicity, sex, insurance, neighborhood socioeconomic status, histology, stage, B symptoms, treatment location at a NCI (National Cancer Institute)-designated cancer center, and radiation therapy (RT). Results: Of the 4,426 patients in this cohort, 33% were <21 years (y) (N= 1,479) and 67% were 22 - 39y (N= 2,947). At median follow-up of 4.4 years, 3-year OS in the full cohort was 95%. Front-line therapy for patients with HL differed significantly across age groups (Table). Approximately 42% of patients <21y received ABVD vs. 69% of older patients. Compared with older patients, a higher proportion of younger patients received ABVE-PC (younger: 8.8% vs. <1%) and modified treatment regimens (younger: 24% vs. 9.6%). Regimens were considered modified if they omitted one drug from a standard protocol but were otherwise administered according to expected dosing schedules; the most common were ABV (18%) and AVD (15%). A higher proportion of patients with private (vs. public/no) insurance received STANFORD V chemotherapy. In total, 40% of patients aged <21y received RT as part of initial therapy vs. 27% of patients 22 - 39y. In survival models, increasing age was associated with a higher risk of death. Compared with patients <14y, the hazard of death from HL was over three-fold higher in patients 22 - 29y (aHR=3.1, CI: 1.1, 9.1) and 30 - 39y (aHR=3.8, CI: 1.3, 11.2). In multivariable models stratified by age, race/ethnicity, insurance, B-symptoms and stage were each significantly associated with survival. In patients <21y, NHBs (aHR: 7.1, CI: 2.4, 20.6) and Hispanics (aHR: 2.5, CI: 1.0, 6.4) experienced worse DSS than NHWs. Having public or no insurance also conferred worse OS (aHR: 1.9, CI: 1.1, 3.5), but initial therapy did not significantly impact OS or DSS. Among those aged 22 - 39y, NHB patients had worse OS (aHR: 1.7, CI: 1.0, 2.8) as did patients with public or no insurance (aHR: 1.7, CI: 1.2, 2.3). Stage IV disease was associated with inferior OS (aHR: 2.9, CI: 1.3, 6.8) and DSS (aHR: 3.3, CI: 1.1, 9.6). Finally, modified treatment regimens (vs. ABVD) were associated with worse OS (aHR: 1.6, CI: 1.0, 2.5), but did not significantly impact DSS in AYAs. Conclusion: In this large, population-based cohort of children and AYAs with HL, we observed that initial therapy varies, but that the majority of AYAs receive ABVD. Variation in therapy was largely insufficient to explain observed survival disparities, as older age, NHB and Hispanic race/ethnicity, and public or no insurance each conferred increased risk of death, even after adjustment for chemotherapy regimen. Further analyses examining comorbidities, treatment-related toxicities, and cause of death are ongoing. Disclosures No relevant conflicts of interest to declare.

Prevalence of metabolic syndrome in older (50 years and older) vs younger (less than 50 years) patients with colorectal cancer diagnosed in a safety net hospital system.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 512-512
Author(s):  
Ashish Sharma ◽  
Johanna Chan ◽  
Tony Trang ◽  
Milena Gould Suarez
Keyword(s):  
Colorectal Cancer ◽  
Metabolic Syndrome ◽  
Waist Circumference ◽  
Older Patients ◽  
Safety Net ◽  
Categorical Variables ◽  
Hospital System ◽  
Younger Patients ◽  
Hospital District ◽  
Safety Net Hospital

512 Background: Colorectal cancer (CRC) incidence has declined overall with screening, though incidence in patients younger than 50 years has increased. Younger patients present with more aggressive and advanced stage CRC. Potential mechanisms are sporadic, genetics, and environmental (alcohol, smoking, metabolic syndrome). Metabolic syndrome (MetS) is an established risk factor for CRC. We examined the prevalence of MetS in younger patients ( < 50 yrs) compared with older patients ( ≥ 50 yrs) with CRC in a safety net hospital population. Methods: IRB-approved retrospective chart review of all patients diagnosed with CRC in the Harris County Hospital District cancer registry from Jan 2008 to Dec 2013. Data was collected for patient characteristics and metabolic syndrome to compare 2 patient groups: < 50 yr (younger) and ≥ 50 yr (older). MetS was defined using 2005 AHA/NHLBI criteria as ≥ 3 of the following components: abdominal obesity (waist circumference > 102 cm in men, > 88 cm in women), serum triglycerides (TG) ( > 150 mg/dL), serum HDL ( < 40 mg/dL in men and < 50 mg/dL in women), BP > 130/85 mmHg, fasting glucose/diabetes ( ≥ 100 mg/dL). Per WHO criteria, BMI > 30 was used as surrogate for waist circumference. Descriptive statistics were performed using t-test for continuous variables and Chi-square / Fisher’s exact test for categorical variables. Results: 625 cases of CRC diagnosed showed median age of 56.5 years and 54.7% female patients. The majority (77.76%) of cases occurred in the older group. Overall, 208/625 patients (33.28%) had MetS. Average BMI overall was 27.33. Prevalence of MetS was 38.27% vs 23% (older vs younger; p = 0.0001). In older compared with younger patients, average BMI 26.13 vs 25.05 (p = 0.02), obesity 25.92% vs 35.87% (p = 0.05), BP > 130/85 mmHg 56.3% vs 31.6% (p = 0.001), low HDL 41.7% vs 31.9% (p = 0.02), TG > 150 34.7 % vs 22.3 % (p = 0.02) and diabetes 36.2% vs 11.5% (p = 0.001). Conclusions: Overall prevalence of MetS in our patient cohort was similar to that of general population (which approximates 34%). Prevalence of MetS was higher in older patients with CRC than in younger patients, though this may reflect the natural history of MetS.

scholarly journals The prognostic impact of FLT3-ITD and NPM1 mutation in adult AML is age-dependent in the population-based setting

2020 ◽  
Vol 4 (6) ◽  
pp. 1094-1101 ◽  
Author(s):  
Gunnar Juliusson ◽  
Martin Jädersten ◽  
Stefan Deneberg ◽  
Sören Lehmann ◽  
Lars Möllgård ◽  
...  
Keyword(s):  
Clinical Relevance ◽  
Older Patients ◽  
Strong Dependence ◽  
Population Based ◽  
Prognostic Impact ◽  
Prognostic Information ◽  
Npm1 Mutation ◽  
Younger Patients ◽  
Prognostic Effect ◽  
Choice Of Treatment

Abstract In acute myeloid leukemia (AML) FLT3 internal tandem duplication (ITD) and nucleophosmin 1 (NPM1) mutations provide prognostic information with clinical relevance through choice of treatment, but the effect of age and sex on these molecular markers has not been evaluated. The Swedish AML Registry contains data on FLT3-ITD and NPM1 mutations dating to 2007, and 1570 adult patients younger than 75 years, excluding acute promyelocytic leukemia, had molecular results reported. Females more often had FLT3ITD and/or NPM1mut (FLT3ITD: female, 29%; male, 22% [P = .0015]; NPM1mut: female, 36%; male, 27% [P = .0001]), and more males were double negative (female, 53%; male, 64%; P &lt; .0001). Patients with FLT3ITD were younger than those without (59 vs 62 years; P = .023), in contrast to patients with NPM1mut (62 vs 60 years; P = .059). Interestingly, their prognostic effect had a strong dependence on age: FLT3ITD indicated poor survival in younger patients (&lt;60 years; P = .00003), but had no effect in older patients (60-74 years; P = .5), whereas NPM1mut indicated better survival in older patients (P = .00002), but not in younger patients (P = .95). In FLT3ITD/NPM1mut patients, the survival was less dependent on age than in the other molecular subsets. These findings are likely to have clinical relevance for risk grouping, study design, and choice of therapy.

scholarly journals Age-Related Prognostic Impact of Different Types of DNMT3A Mutations in Adults With Primary Cytogenetically Normal Acute Myeloid Leukemia

2012 ◽  
Vol 30 (7) ◽  
pp. 742-750 ◽  
Author(s):  
Guido Marcucci ◽  
Klaus H. Metzeler ◽  
Sebastian Schwind ◽  
Heiko Becker ◽  
Kati Maharry ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Expression Profiles ◽  
Disease Free Survival ◽  
Microrna Expression ◽  
Molecular Characteristics ◽  
Prognostic Impact ◽  
Younger Patients ◽  
Acute Myeloid

Purpose To determine the frequency of DNMT3A mutations, their associations with clinical and molecular characteristics and outcome, and the associated gene- and microRNA-expression signatures in primary cytogenetically normal acute myeloid leukemia (CN-AML). Patients and Methods Four hundred fifteen previously untreated adults were analyzed for DNMT3A mutations and established prognostic gene mutations and expression markers. Gene- and microRNA-expression profiles were derived using microarrays. Results Younger (< 60 years; n = 181) and older (≥ 60 years; n = 234) patients had similar frequencies of DNMT3A mutations (35.3% v 33.3%). Missense mutations affecting arginine codon 882 (R882-DNMT3A) were more common (n = 92; 62%) than those affecting other codons (non–R882-DNMT3A). DNMT3A-mutated patients did not differ regarding complete remission rate, but had shorter disease-free survival (DFS; P = .03) and, by trend, overall survival (OS; P = .07) than DNMT3A–wild-type patients. In multivariable analyses, DNMT3A mutations remained associated with shorter DFS (P = .01), but not with shorter OS. When analyzed separately, the two DNMT3A mutation types had different significance by age group. Younger patients with non–R882-DNMT3A mutations had shorter DFS (P = .002) and OS (P = .02), whereas older patients with R882-DNMT3A mutations had shorter DFS (P = .005) and OS (P = .002) after adjustment for other clinical and molecular prognosticators. Gene- and microRNA-expression signatures did not accurately predict DNMT3A mutational status. Conclusion DNMT3A mutations are frequent in CN-AML, and their clinical significance seems to be age dependent. DNMT3A-R882 mutations are associated with adverse prognosis in older patients, and non–R882-DNMT3A mutations are associated with adverse prognosis in younger patients. Low accuracy of gene- and microRNA-expression signatures in predicting DNMT3A mutation status suggested that the role of these mutations in AML remains to be elucidated.

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