scholarly journals Acquisition of IDH2 Mutations in Relapsed/Refractory AML Is Associated with Worse Patient Outcomes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-20
Author(s):  
Amy Song ◽  
Omar Altabbakh ◽  
David A. Sallman ◽  
Eric Padron ◽  
Chetasi Talati ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Rank Test ◽  
Refractory Disease ◽  
Disease Course ◽  
Mutation Status ◽  
Persistent Disease ◽  
Isocitrate Dehydrogenase 2 ◽  
Significant Difference ◽  
Idh2 Mutation

Introduction Isocitrate dehydrogenase 2 (IDH2) is mutated in ~10% of acute myeloid leukemia (AML). However, the clonal evolution of IDH2 mutations through the course of AML has not been clearly elucidated. The presence of targeted therapy, Enasidenib, for the treatment of IDH2 mutated AML underscores the importance of understanding the clonal dynamics of IDH2 mutations. Methods IRB approval was obtained. In this study, we analyzed ~6000 patients with NGS results to identify 120 AML patients with IDH2 mutations and longitudinal next generation sequencing (NGS) testing. Disease status was determined for each NGS test date by chart review. IDH2 mutation status was chronicled for each of the following disease states: diagnosis, remission, relapse, and persistent disease. Cytogenetic risk category was based on ELN 2017 guidelines. Statistical analyses were performed using SPSS. Results Of the 120 patients, there were 62 patients (51.67%) with AML-NOS and 58 patients (48.33%) with AML with myelodysplasia-related changes (AML-MRC). The most commonly co-occurring mutated genes included DNMT3A, SRSF2, RUNX1, ASXL1, NRAS, BCOR, NPM1, STAG2, FLT3, and PHF6 in order of frequency. Concurrent IDH1 and IDH2 mutations were seen in 2 patients, although IDH1/2 mutations were previously reported to be mutually exclusive. Of the total patients with IDH2 mutations, 105 patients (88%) were IDH2-positive at the initial diagnosis and 15 patients (12%) were IDH2-negative at diagnosis and acquired the mutation later in disease. Of those 15 patients, 7 patients gained the mutation during persistent disease, 6 during relapse, and 2 at remission (neither of whom relapsed). Forty-eight patients (40%) who were IDH2-positive in a prior test were found to be IDH2-positive with persistent AML, while 11 patients (9%) with IDH2-positive AML lost the IDH2 mutation despite the presence of persistent AML. Twenty-one patients (18%) who were IDH2-positive in a prior test were found to remain IDH2-positive in remission, while 49 patients (41%) cleared the IDH2 mutation. Twenty-four patients (20%) with IDH2-positive AML were found to be IDH2-positive at disease relapse, while 7 patients (6%) lost the IDH2 mutation at relapse. Kaplan-Meier survival analysis and the log-rank test were used to analyze overall survival (OS) to control for confounding factors of AML category (AML-MRC vs AML-NOS) and cytogenetic risk (Figure 1). Patients who were IDH2-positive at diagnosis had significantly better survival than patients who gained the IDH2 mutation later in disease (Figure 1A, p=0.024). Patients who were IDH2-negative at remission had significantly improved survival compared to patients who were IDH2-positive at remission (Figure 1B, p=0.002). Patients who had lost the IDH2 mutation with persistent disease had significantly greater overall survival than those who remained IDH2-positive with persistent AML (Figure 1C, p=0.035). No significant difference in OS was found based on IDH2 mutation status at relapse. Conclusion In summary, in the largest study of IDH2 clonal dynamics to date, we found that IDH2 mutations are not stable during AML disease course and frequent genetic testing of AML patients in necessary to tailor personalized therapy. Most patients (70%) cleared IDH2 in disease remission. In those with refractory disease, 18% of IDH2+ AMLs lose IDH2. In the relapse setting, 22% of IDH2+ AML show loss of IDH2. Overall, 12% of patients gained IDH2 mutation later in disease course usually in the setting of refractory/relapsed AML. These patients, along with those who remained IDH2+ in remission and during refractory disease, fared worse than their counterparts. Thus, the longitudinal IDH2 mutation testing at different disease stages may be helpful in prognostic stratification. Figure 1 Disclosures Sallman: Agios, Bristol Myers Squibb, Celyad Oncology, Incyte, Intellia Therapeutics, Kite Pharma, Novartis, Syndax: Consultancy; Celgene, Jazz Pharma: Research Funding. Padron:BMS: Research Funding; Novartis: Honoraria; Kura: Research Funding; Incyte: Research Funding. Talati:Pfizer: Honoraria; BMS: Honoraria; Astellas: Speakers Bureau; Jazz: Speakers Bureau; AbbVie: Honoraria. Hussaini:Boston Biomedical: Consultancy; Stemline: Consultancy; Adaptive: Honoraria.

scholarly journals Impact of Treatment Facility Chracteristics on Patient (Pt) Outcomes in Acute Myeloid Leukemia (AML) Using Data from the National Cancer Database (NCDB)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-22
Author(s):  
Allison Taylor ◽  
Kimberley Doucette ◽  
Bryan Chan ◽  
Xiaoyang Ma ◽  
Jaeil Ahn ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hazard Analysis ◽  
Treatment Options ◽  
Academic Research ◽  
High Volume ◽  
Rank Test ◽  
Rural Residence ◽  
Integrated Network ◽  
Kaplan Meier ◽  
Significant Difference

Introduction The literature suggests a widespread reduction in the availability and accessibility of newer treatment options among marginalized groups in AML. Studies from large national databases point to lower socio-economic status, Hispanic and African American race, Medicare or no insurance, being unmarried, treatment at non-academic centers, and rural residence as negatively impacting overall survival (OS) and rates of chemotherapy utilization in AML patients (Patel et al. 2015, Jaco et al. 2017, Bhatt et al. 2018, Master et al. 2016). We hypothesized that facility affiliation and pt volume would also have important effects on time to treatment (TTT) and OS in AML, even when these socioeconomic disparities were accounted for. Methods For this retrospective analysis, we used NCDB data that included 124,988 pts over the age of 18 with AML between the years 2004-2016. Variables analyzed included facility types described as community cancer programs (CP), comprehensive community cancer programs (CCP), academic/research center cancer programs (AC) and integrated network cancer programs (IN), and volume of facilities defined as high volume (HV) and low volume (LV). HV facilities had case volumes of ≥ 99th percentile and all other facilities were classified as LV. Multivariate analyses (MVA) included demographic and socioeconomic covariables. We used Cox proportional hazard analysis for both TTT and OS MVA. The Kaplan-Meier method was used to estimate median TTT and OS, and the log rank test used to compare TTT and OS across predictor variables. Results The median age of AML patients was 63 yrs (range 18-90) with 54% males, and 86% Caucasian. Five percent of patients were treated at CP, 30% at CCP, 44% at AC, and 10% at IN. 21% at HV facilities and 79% at LV facilities. Median TTT in days at CP facilities was 7, compared to 5 days in CCP and AC facilities versus 4 days at IN (p<0.0001). TTT was 5 days at HV facilities versus 4 days at LV facilities (p<0.0001). Kaplan-Meier curves showed that TTT was similar between HV and LV facilities(figure 1). The median OS was 3.25 months in CP compared to 4.34 months at CCP, 5.06 months at IN and 9.53 months at AC (p<0.0001). For facility volume, the median OS was 13.11 months in HV facilities compared to 6.93 months in LV facilities (p<0.0001). When sex, race, age, Hispanic Origin, education, urban/rural residence, Charlson-Deyo Comorbidity score and Great Circle Distance were adjusted for in MVA (table 1), the OS was higher in AC versus CP facilities (hazard ratio [HR] of 0.90 (0.87-0.93, p<0.0001), and there was no statistically significant difference with comparison of other facility types to CP. Similarly, there was a lower OS at LV versus HV facilities with a HR of 1.14 (1.12-1.16, p<0.0001). CCP facilities had a shorter TTT compared to CP with a HR of 1.21 (1.17-1.26, p<0.0001). AC had a shorter TTT than CP with a HR of 1.17 (1.13-1.22, p<0.0001), and IN had a shorter TTT compared to CP with a HR of 1.29 (1.24-1.34, p<0.0001). Additionally, TTT in the MVA for facility volume was shorter in LV facilities compared to HV facilities with HR of 1.05 (1.04-1.07, p<0.0001) [table 1]. Conclusion When adjusting for various socioeconomic factors, we found that TTT was longest in CP compared to CCP, AC, and IN. Treatment at a LV facility resulted in a decreased overall survival. LV facilities may be less familiar with treatment regimens for AML, less likely to use novel treatment options, and be less familiar with the disease. We showed that treatment at an AC compared to CP, CCP and IN facilities improved survival. Given poor outcomes for AML, these results show the importance of going to AC and HV facilities with more experience in treating AML for improved outcomes. Disclosures Lai: Astellas: Speakers Bureau; Jazz: Speakers Bureau; Abbvie: Consultancy; Agios: Consultancy; Macrogenics: Consultancy.

Primary Plasma Cell Leukaemia and Autologous Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 731-731
Author(s):  
Mary B. Drake ◽  
Simona Iacobelli ◽  
Anja van Biezen ◽  
Jane F. Apperley ◽  
Dietger W. Niederwieser ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Plasma Cell ◽  
Autologous Transplantation ◽  
Cell Leukaemia ◽  
Rank Test ◽  
Tumour Mass ◽  
Data Set ◽  
Significant Difference ◽  
Plasma Cell Leukaemia

Abstract Introduction: Primary plasma cell leukaemia (PCL) is a rare disorder representing less than 5% of malignant plasma cell disease and is associated with a poor prognosis with median survivals in PCL reported at 8 to 12 months, significantly shorter than for Multiple Myeloma even when the comparison is adjusted to compare only with Multiple Myeloma of high tumour mass. Treatment of PCL with alkylating agent-based therapy is ineffective and while polychemotherapy may offer improved survival, results remain disappointing with a few exceptions. Autologous transplantation is now being used widely in the treatment of these patients and this report summarises the European Blood and Marrow Transplant (EBMT) experience of this disorder. Patients and Methods: A retrospective study was carried out with 20844 patients with common type multiple myeloma (58% IgG, 21% IgA and 19% light chain types only) and 272 patients with primary plasma cell leukaemia who underwent first autologous transplantation between 1980 and 2006. All patients were reported to the EBMT registry using MED-A (limited data set) or MED-B (more extensive data set) forms. All autografted patients were included in the study regardless of the availability of complete MED-A or MED-B data. The proportion of patients that could be evaluated for each parameter was noted and the number of evaluable patients included in the result. Comparisons between the two groups were made using Chi-squared test for categorical data and the Mann-Whitney test for continuous data. Overall Survival and Progression-Free Survival were calculated using the Kaplan-Meier method and comparisons were made using the Log-Rank test. Relapse/Progression and Death without relapse or progression probabilities were computed by the proper non-parametric estimator for outcomes with competing risks and compared by the Gray test. Results: There were no significant differences in age and gender of the PCL and myeloma groups. Calcium and albumin were also not significantly different, however, haemoglobin was significantly lower in the PCL group (11g/dl versus 9g/dl - P=0.000) while creatinine was significantly higher in the PCL group - 92 micro mol/l versus 122 micro mol/l - P=0.000). B2 microglobulin was significantly higher in the PCL group which tends to be diagnosed with a more advanced disease. There was no difference in the type of graft used or in the use of total body irradiation but the PCL group were transplanted within a shorter time from diagnosis (6.0 v 7.7 months - P=0.000). While there was no significant difference in engraftment, PCL patients were more likely than myeloma patients to enter CR post-autologous transplantation. Despite this, overall survival for the PCL patients was greatly inferior to the myeloma patients - 62.3 months (CI 60.4–64.3) versus 25.7 months (CI 19.5–31.9 - P=0.000). Poor survival is accounted for by an increase in relapse-related mortality and post-transplant responses of short duration. Conclusion: This is the largest study of plasma cell leukaemia patients ever reported. Our data shows an improved outcome for these patients with use of autologous transplantation but undoubtedly this transplant group represents the fittest of such patients and their outcome is still greatly inferior to comparable myeloma patients.

Distribution and Impact of Comorbidities on Survival and Leukemic Transformation in Myeloproliferative Neoplasm (MPN)-Associated Myelofibrosis (MF)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4264-4264
Author(s):  
Justyna Bartoszko ◽  
Tony Panzarella ◽  
Caroline Jane McNamara ◽  
Anthea Lau ◽  
Aaron D. Schimmer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Primary Outcome ◽  
Secondary Analysis ◽  
Rank Test ◽  
Leukemic Transformation ◽  
Advisory Committees ◽  
Log Rank Test ◽  
Comorbidity Scores ◽  
The Impact

Abstract Introduction. Myelofibrosis is a disease characterized by aberrant bone marrow function with eventual fibrosis. Current widely-used disease prognostic indices, such as the Dynamic International Prognostic Scoring System (DIPSS) do not take into account comorbidities, which may have significant effects on patient survival as well as disease course. We sought to describe the comorbidity distribution in this patient population and assess the impact of comorbidities as scored by two different widely used scales in clinical practice, the Adult Comorbidity Evaluation 27 (ACE-27) and the Hematopoietic Cell Transplant Comorbidity Index (HCT-CI), on overall survival and leukemic transformation in myelofibrosis. A score of 3 on ACE-27 or ≥3 on HCT-CI generally indicates a high burden (severe) comorbidities. Methods. We conducted a retrospective study of 309 patients seen at the MPN program at the Princess Margaret Cancer Centre, with a confirmed diagnosis of myelofibrosis [primary myelofibrosis (PMF), post-essential thrombocytopenia (PET-MF) or post-polycythemia vera (PPV-MF)]. Patients were seen from 1999-2014 with a median follow-up time of 2 years. Time to death and leukemic transformation was examined from the date of first presentation to our centre. Our primary aim was to examine the impact of comorbidity scores, as assessed by ACE-27 and the HCT-CI, on overall survival. In a secondary analysis we examined the impact of comorbidity scores on leukemic transformation. Multivariable Cox proportional hazards models were constructed for the primary and secondary outcomes. A series of descriptive analyses were carried out examining the distribution of various comorbidities as captured by the two scales. Results. The most common comorbidities captured by ACE-27 were hypertension (n=92, 22.3%), diabetes mellitus (n=43, 10.4%), venous disease (n=26, 6.3%), solid tumour including melanoma (n=26, 6.3%), and angina/coronary artery disease (n=23, 5.6%). The most common comorbidities captured by HCT-CI were cardiac (n=49, 17.3%), diabetes (n=43, 15.2%), mild hepatic (n=28, 9.9%), cerebrovascular disease (n=25, 8.8%), prior solid tumour (n=24, 8.5%). The distribution of comorbidity scores as compared between scales is shown in Table 1. A total of 78 patients (25.2%) experienced the primary outcome of interest, which was all-cause death. For the primary outcome of overall survival, there were differences across groups of patients with different comorbidity scores using ACE-27 or HCT-CI, with the highest severity groups having worse outcomes (Figure 1). Progressively increasing DIPSS categories (Low, Intermediate-1, Intermediate-2, and High risk) were also associated with worse overall survival. On multivariable survival analysis, an ACE-27 score of 3 when compared to a lower score of 0-1 was associated with an almost two-fold increase in the risk of all-cause death [HR 1.95 (95% CI 1.06-3.58), p=0.03]. On multivariable analysis, an HCT-CI score of 3+ when compared with 0-1 was marginally significantly associated with an increased risk of all-cause death [HR 1.60 (95% CI 0.96-2.68), p=0.07]. Interaction terms were tested between the scores and age at presentation and no effect of age on survival across varying severities of comorbidities was found. In our secondary analysis, there was no impact of the ACE-27 or HCT-CI on leukemic transformation. Conclusions. ACE-27 picked up severe co-morbidities in 13% of patients in our cohort while HCT-CI picked up severe comorbidities in 23%. Although the incidence of severe co-morbidities was lower when assessed by ACE-27, the overall impact on survival of severe comorbidities as assessed by both scores is likely to be similar. The presence of severe comorbidities at the time of diagnosis conferred a significant survival disadvantage in patients with myelofibrosis, but had no impact on progression to leukemic transformation. Table Overall survival by ACE-27 comorbidity category, showing differences between categories of comorbidity severity (p=0.047, log rank test). Table. Overall survival by ACE-27 comorbidity category, showing differences between categories of comorbidity severity (p=0.047, log rank test). Figure Figure. Disclosures Panzarella: Cellgene: Consultancy. Schimmer:Novartis: Honoraria. Schuh:Amgen: Membership on an entity's Board of Directors or advisory committees. Yee:Novartis Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding. Gupta:Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Research Funding.

ΝFΚΒΙΕ Deletions: A Novel Marker of Clinical Aggressiveness in Primary Mediastinal B-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 609-609
Author(s):  
Daniel Noerenberg* ◽  
Larry Mansouri* ◽  
Emma Young ◽  
Frick Mareike ◽  
Maysaa Abdulla ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
High Frequency ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Gene Mutations ◽  
B Cell Lymphoma ◽  
Mutation Status ◽  
Lymphoid Malignancies ◽  
Ann Arbor

Abstract Deregulated NF-κB signaling is a hallmark of most, if not all, lymphoid malignancies, and recurrent gene mutations in both the canonical and non-canonical NF-κB pathway are known to lead to NF-κB activation. However, the full compendium of NF-κB gene mutations in lymphoid malignancies remains to be elucidated. Recently, we reported a 4-bp truncating mutation in the NFKBIE gene, which encodes IκBε, a negative regulator of NF-κB, in patients with chronic lymphocytic leukemia (CLL). The NFKBIE deletion was enriched in clinically aggressive CLL patients (7-8%) and associated with a worse clinical outcome. At the functional level, NFKBIE-deleted CLL showed reduced IκBε levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65, compared to wildtype patients. Preliminary data has indicated an increased frequency of NFKBIE aberrations in other lymphoid malignancies as well. To explore this further, we screened for NFKBIE deletions in a large cohort of patients diagnosed with a range of different lymphoid neoplasms. Overall, NFKBIE deletions were identified in 76 of 1414 patients (5.4%). While NFKBIE deletions were relatively infrequent in patients diagnosed with follicular lymphoma (3/225, 1.3%), splenic marginal zone lymphoma (3/175, 1.7%), and T-cell acute lymphoblastic leukemia (1/94, 1.1%), moderate frequencies were observed among diffuse large B-cell lymphoma (18/521, 3.5%), mantle cell lymphoma (8/189, 4.2%), and primary CNS lymphoma (1/34, 2.9%) patients. In contrast, a remarkably high frequency of NFKBIE deletions (41/176 cases, 23%) was observed among primary mediastinal B-cell lymphoma (PMBL) patients. Noteworthy, the prevalence of NFKBIE-deleted PMBL cases was similar in the different contributing centers. All PMBL patients in the present series received a CHOP based treatment regime; in ~75% of cases rituximab was added and ~25% were treated with dose intensified schemes. For the latter, the vast majority of patients received CHOEP, while individual cases were treated with MegaCHOEP, DA-EPOCH or ACVBP. Regarding clinicobiological associations, there were no significant differences between NFKBIE-deleted and wildtype PMBL patients with respect to age, sex, Ann Arbor stage, IPI risk-groups, extranodal or bone marrow involvement, bulky disease, and LDH elevation. However, NFKBIE-deleted patients were more likely to be refractory to primary chemotherapy (31% vs. 3%, P=.001) and had a shorter overall survival compared to wildtype patients (5-year overall survival: 63% vs 84%, P=.013). In multivariate analysis (including age, gender, Ann Arbor stage, IPI, and NFKBIE mutation status), NFKBIE mutation status (95% CI: 1.23-10.61; HR: 3.61; P=0.020) remained an independent factor for poor prognosis. In summary, we document NFKBIE deletions as a common genetic event across B-cell malignancies, albeit at varying frequencies. The high frequency of NFKBIE deletions in PMBL alludes to the critical role of this aberration in the pathophysiology of the disease. NFKBIE deletions were associated witha worse clinical outcome, hence potentially representing a novel poor-prognostic marker in PMBL. *Contributed equally as first authors. **Contributed equally as senior authors. Disclosures Stamatopoulos: Gilead: Consultancy, Honoraria, Research Funding; Abbvie: Honoraria, Other: Travel expenses; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Other: Travel expenses, Research Funding.

Overall survival trends in pediatric osteosarcoma patients over the past three decades

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10041-10041
Author(s):  
R. van Schie ◽  
M. Hagleitner ◽  
P. Hoogerbrugge ◽  
U. Flucke ◽  
H. Schreuder ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Rank Test ◽  
Histological Response ◽  
Treatment Protocols ◽  
Treatment Regimens ◽  
The Past ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Pediatric Osteosarcoma

10041 Background: In the late seventies, the combination of chemotherapy and surgery, significantly improved survival of osteosarcoma patients. However, the chemotherapeutic drugs used for treatment of osteosarcoma patients has not significantly changed since then although surgery clearly improved further and adjuvant chemotherapy have been added. In this study, we retrospectively evaluated, whether after the introduction of neoadjuvant chemotherapy in the late seventies, further improvement in outcome of pediatric osteosarcoma patients was achieved. Methods: Since 1978 and 2008, 54 previously untreated pediatric patients with osteosarcoma were enrolled in six consecutive regimens of different agents and intensity. The main difference between the treatment protocols is the addition of either methothrexate or ifosfamide. Overall survival (OS) and event free survival (EFS) in relationship to the different treatment regimens was calculated using the Kaplan-Meier method. Significance of difference in outcome were calculated using the log rank test. Results: The 5-year EFS and OS of the whole group was 54.7% and 61.1%, respectively. There was no significant difference in outcome in patients treated between 1978 and 1993 (n = 18), as compared to patients treated after 1993 (n = 36, OS 47.1% vs 69.4%, p = 0.34). Of all treatment regimens used, OS was the highest in patients treated with cisplatin, doxorubicin, and methotrexate (OS after 5 year 70%). Multivariate analysis showed that EFS and OS significantly correlated with the histological response but not with one of the treatment regimens used. Conclusions: No significant improvement in overall survival has been accomplished in pediatric osteosarcoma patients during the past thirty years. Histological response after neoadjuvant chemotherapy was the most important prognostic factor. No significant financial relationships to disclose.

Prognosis and comorbidities in stage III and IV endometrial cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16553-e16553
Author(s):  
K. Wright ◽  
E. Munro ◽  
M. del Carmen ◽  
A. K. Goodman
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Stage Iv ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Rank Test ◽  
Laboratory Values ◽  
Significant Difference ◽  
Baseline Creatinine

e16553 Background: While endometrial cancer may be associated with many comorbid conditions, none have been characterized as changing overall prognosis. The aim of this study was to identify medical conditions or laboratory values, that may serve as prognostic factors in stage III and IV endometrial cancer. Methods: A retrospective chart review identified 112 women with stage III or IV endometrial cancer between years 1993–1998. Information about medical comorbidities and presenting lab values were collected using electronic medical records. Progression free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier survival method and the log rank test. Results: The average age was 64.9 yrs. 79 women (70.5%) had stage III disease and 33 women (29.5%) had stage IV disease. For those with a baseline creatinine <1.2 (n = 91), the PFS and OS were not significantly different from those with a baseline creatinine ≥1.2 (n = 17; p = 0.554 and p = 0.487, respectively). There was a non-significant trend toward worse PFS for the 41 patients with hypertension (HTN) compared to the 62 without (48.0 and 61.2 months, p = 0.191). The overall survival was significantly worse for those with HTN (38.7 months vs. 56.0 months p = 0.046). For those with known coronary artery disease, no significant difference in PFS or OS was found (p = 0.792 and p = 0.312 respectively). Those with diabetes (n = 15) did not have a significantly different PFS compared to those who did not (n = 88; p = 0.728). The OS was worse at 20.1 months for those with diabetes compared to 54.3 months for those without (p = 0.001). Baseline albumin had a significant effect on both PFS and OS. Those with an albumin <3.5 (n = 54) had a PFS of 46.2 months compared to 94.0 months for those with an albumin ≥3.5 (n = 23; p = 0.007), and the OS for those with low albumin was 44.8 months compared to 83.4 months for those with the higher albumin (p = 0.005). Conclusions: These results suggest that past medical history and some baseline laboratory values may be important in considering prognosis. In particular, patients with a history of HTN or diabetes have a worse overall survival. Those with a baseline albumin of <3.5 have a worse PFS and OS. No significant financial relationships to disclose.

Adherence to the BCLC guidelines and impact on overall survival.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 345-345 ◽  
Author(s):  
Jesna Mathew ◽  
Sasha Slipak ◽  
Anil Kotru ◽  
Joseph Blansfield ◽  
Nicole Woll ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Benefit ◽  
Cox Regression ◽  
Early Stage ◽  
Univariate Analysis ◽  
Tertiary Care ◽  
Treatment Recommendations ◽  
Rank Test ◽  
P Value ◽  
Significant Difference

345 Background: Multiple studies exist that validate the prognostic value of the Barcelona Clinic Liver Cancer (BCLC) staging. However, none have established a survival benefit to the treatment recommendations. The aim of this study was to evaluate the adherence to the BCLC guidelines at a rural tertiary care center, and to determine the effect of following the treatment recommendations on overall survival. Methods: A retrospective chart review was conducted for 97 patients newly diagnosed with hepatocellular carcinoma (HCC) from 2000 to 2012. The treatment choice was compared with the BCLC guidelines and percentage adherence calculated. Overall survival was estimated using the Kaplan-Meier method and the log rank test was used to test the difference between the two groups. Cox regression tests were used to determine independent effects of stage, treatment aggressiveness, and guideline adherence on survival. A p-value <0.05 was considered statistically significant. Results: Of 97 patients, 75% (n=73) were male. Median overall survival was 12.9 months. In 59.8% (n=58) of the patients, treatment was adherent to stage specific guidelines proposed by the BCLC classification. There was no significant difference in overall survival between the adherent and non-adherent groups (11.2 vs 14.1 months, p<0.98). However on stage specific survival analysis, we noted a significant survival benefit for adherence to the guidelines for early stage HCC (27.9 vs 14.1 months, p<0.05), but a decrease in survival for adherence in the end stage (20 days vs 9.3 months, p<0.01). On univariate analysis, more aggressive treatment was associated with increased survival (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.22 to 0.87; p = 0.018). Multivariate analysis revealed that adherence did not independently affect survival when stage and aggressiveness of treatment were included in the model (HR, 1.3; 95% CI, 0.76 to 2.2, p = 0.34). Conclusions: Although the BCLC guidelines serve as a practical guide to the management of patients with HCC, they are not universally practiced. These results indicate that survival of patients with hepatocellular cancer is determined by stage and aggressiveness of treatment, not adherence to BCLC guidelines.

Use of radiofrequency ablation and stereotactic body radiotherapy for the treatment of hepatocellular carcinoma: An analysis of the SEER-Medicare database.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 463-463 ◽  
Author(s):  
Mary Uan-Sian Feng ◽  
Vincent D. Marshall ◽  
Neehar Parikh
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Radiofrequency Ablation ◽  
Stereotactic Body Radiotherapy ◽  
Early Stage ◽  
Rank Test ◽  
The West ◽  
Liver Decompensation ◽  
Significant Difference ◽  
The Us

463 Background: Hepatocellular carcinoma (HCC) is an increasingly common and highly morbid malignancy worldwide, including the US. For early stage patients ablative strategies are important potentially curative treatment options. Stereotactic body radiotherapy (SBRT) has emerged as a promising non-surgical ablative therapy, although it is technically demanding and its comparison with radiofrequency ablation (RFA) remains confined to a single institution retrospective review. We queried the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to assess RFA and SBRT use in the US. Methods: We identified patients greater than 65 years old who were diagnosed from 2004-11 with stage I or II HCC and treated with RFA or SBRT. Survival analysis was conducted using Kaplan-Meier curves and log rank test. Factors associated with overall survival (OS) and early ( ≤ 90 day) hospital admission post-treatment were identified using propensity score (PS) adjusted multivariate analysis. Results: 825 patients were identified, 747 treated with RFA and 78 SBRT. 22 pts received both treatments and were excluded from this analysis. The mean Charlson comorbidity index was 1.0±1.1. Median age was 74, range 66-90. Patients who received RFA were more likely to live in the West and have liver decompensation. Patients who received SBRT were more likely to be white and treated in the Midwest. After using PS matching there were 78 in each cohort. In these patients, mean overall survival (OS) was 2.25 and 2.04 yrs for RFA and SBRT, p = 0.06. Younger age, lack of liver decompensation, treatment in the West, and liver transplantation were associated with longer OS, HR 0.96, p = 0.05; HR 0.37, p = 0.002; HR 0.57, p = 0.04; HR 0.18, p = 0.008, respectively. 90 day hospitalization rates did not differ between treatments; only liver decompensation was predictive of hospitalization, OR 3.33, p = 0.032. Conclusions: In a national cohort of early stage HCC patients, treatment with RFA vs SBRT resulted in no significant difference in OS. SBRT appears to be a comparable ablative strategy to RFA in this population. This highlights the need for a randomized trial comparing these two modalities.

Subset of patients with unfavorable T1N2-3M0 gastric cancer for whom surgery alone is the standard treatment.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 105-105
Author(s):  
Yukio Maezawa ◽  
Tsutomu Sato ◽  
Toru Aoyama ◽  
Kazuki Kano ◽  
Kenki Segami ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Standard Treatment ◽  
Stage Ii ◽  
Rank Test ◽  
Cancer Center ◽  
Tumor Diameter ◽  
Significant Difference ◽  
Macroscopic Tumor

105 Background: ACTS-GC trial demonstrated that S-1 is effective as adjuvant chemotherapy for Japanese patients who have undergone curative D2 gastrectomy for gastric cancer and were diagnosed with pathological stage II disease. However, stages T1N2M0 and T1N3M0, which are classified as part of Stage II, were excluded from the ACTS-GC trial. The aim of the present study was to identify the unfavorable subset of patients with T1N2M0 and T1N3M0 gastric cancer for whom surgery alone is the standard treatment. Methods: The present study examined 59 patients who were diagnosed with T1N2M0 or T1N3M0 gastric cancer at Kanagawa Cancer Center and Yokohama City University Hospital between January 2000 and June 2010. Univariate and multivariate analyses were performed to identify risk factors for overall survival using a Cox proportional hazards model. Results: When overall survival was compared by the log-rank test, a significant difference was observed with regard to macroscopic tumor diameter. A macroscopic tumor diameter greater than 30mm was regarded as a critical point of classification considering the survival. Mulitivariate Cox’s proportional hazard analyses demonstrated that macroscopic tumor diameter was the only significant independent prognosticator. The five-year survival was 60.0% in patients with a macroscopic tumor diameter < 30mm, and 84.6% in those with a macroscopic tumor diameter > 30mm (P = 0.027). Conclusions: Among T1N2M0 and T1N3M0 gastric cancer patients for whom surgery alone is the standard treatment, having a small T1N2-3 tumor of less than 30 mm in diameter was the sole risk factor for gastric cancer survival. These tumors might be another target for adjuvant chemotherapy.

Calcium channel blockers use and overall survival in pancreatic cancer patients receiving gemcitabine.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15756-e15756 ◽  
Author(s):  
Leszek Kraj ◽  
Andrzej Śliwczyński ◽  
Joanna Krawczyk-Lipiec ◽  
Krzysztof Woźniak ◽  
Anna Waszczuk-Gajda ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Rank Test ◽  
Channel Blockers ◽  
Test Results ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Significant Difference

e15756 Background: Preclinical studies have shown that calcium channel blockers (CCB) may potentiate anticancer effect of chemotherapy via intra-cellular drug accumulation. Gemcitabine-based chemotherapy is commonly used in pancreatic cancer (PC) patients. The aim of this study was to determine whether CCB may affect overall survival (OS) in PC patients receiving gemcitabine-based chemotherapy. Methods: The retrospective cohort of PC patients treated with gemcitabine between 2007 and 2016 was identified in the Polish National Health Fund databases. Electronic records of prescriptions were searched to identify in this cohort patients receiving CCB (amlodipine, nitrendipine, felodipine, lacidipine). The primary endpoint was OS and it was determined by Kaplan-Meier methods and compared by the log-rank test. Results: In total 4628 PC patients treated with gemcitabine (median OS 7.7 months; 95% CI: 7.4-7.9) were identified. Among these 380 patients were prescribed any CCB. There was a significant difference (p < 0.001) in median OS between patients prescribed CCB (n = 380; OS 9.3 months; 95% CI: 7.8-11.0) and those who did not (n = 4214; OS 7.6 months; 95% CI: 7.3-7.8) with hazard ratio for death 0.70 (95% CI: 0.62-0.79). Notably, the survival curves tended to flatten in CCB group, with 24% of patients alive at 2 years (95% CI: 20-29%) and 15% alive at 5 years (95% CI: 11-19%), compared with 11% (95% CI: 10-12%) and 4% (95% CI: 4-5%) in controls respectively. Conclusions: The use of CCB in PC patients receiving gemcitabine-based chemotherapy was associated with improved OS. Further validation is needed to evaluate effectiveness of CCB-gemcitabine combinations in the management of PC.

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