Prognostic factors of overall (OS) and relapse-free survival (RFS) for patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy (IC): Multivariate analyses from the QUAZAR AML-001 trial of oral azacitidine (Oral-AZA).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7014-7014
Author(s):  
Gail J. Roboz ◽  
Andrew H. Wei ◽  
Farhad Ravandi ◽  
Christopher Pocock ◽  
Pau Montesinos ◽  
...  

7014 Background: Demographic and disease factors influence outcomes for patients (pts) with AML. In the phase 3 QUAZAR AML-001 trial, Oral-AZA significantly prolonged OS and RFS vs. placebo (PBO) for pts with AML in first remission after IC (Wei, NEJM, 2020). Univariate analyses showed OS and RFS benefits with Oral-AZA vs. PBO across pt subgroups defined by baseline (BL) characteristics. MV analyses were performed to identify BL characteristics independently predictive of OS/RFS in QUAZAR AML-001, and to assess Tx effects of Oral-AZA vs. PBO on survival when adjusted for BL factors. Methods: Pts were aged ≥55 yrs with AML in complete remission (CR) or CR with incomplete count recovery (CRi) after induction ± consolidation. Within 4 months of CR/CRi, pts were randomized 1:1 to receive Oral-AZA 300 mg or PBO for 14d/28d cycle. Cox proportional hazards models were used to estimate Tx effects of Oral-AZA vs. PBO on OS and RFS, adjusting for BL age, sex, ECOG PS score, cytogenetic risk at diagnosis (Dx), prior MDS, geographic region, CR/CRi after induction (per investigator) and at BL (per sponsor), MRD status, receipt of consolidation, number of consolidation cycles, platelet count, and ANC. In a stepwise procedure, randomized Tx and BL variables were selected incrementally into a Cox model if P ≤ 0.25. After each addition, the contribution of the covariate adjusted for other covariates in the model was evaluated and retained in the model if P ≤ 0.15. Results : Oral-AZA Tx remained a significant independent predictor of improved OS (HR 0.70) and RFS (HR 0.57) vs. PBO after controlling for BL characteristics (Table). MRD status, cytogenetic risk, and pt age were each also independently predictive of OS and RFS. Response after induction (CR vs. CRi) and BL ANC were predictive of OS but not RFS, whereas prior MDS, CR/CRi at BL, and number of consolidation cycles were only predictive of RFS. Conclusions: Tx with Oral-AZA reduced the risk of death by 30% and risk of relapse by 43% vs. PBO independent of BL characteristics. Cytogenetic risk at Dx, MRD status, and pt age also independently predicted survival outcomes. Clinical trial information: NCT01757535. [Table: see text]

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 560-560 ◽  
Author(s):  
D. A. Patt ◽  
Z. Duan ◽  
G. Hortobagyi ◽  
S. H. Giordano

560 Background: Adjuvant chemotherapy for breast cancer is associated with the development of secondary AML, but this risk in an older population has not been previously quantified. Methods: We queried data from the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database for women who were diagnosed with nonmetastatic breast cancer from 1992–1999. We compared the risk of AML in patients with and without adjuvant chemotherapy (C), and by differing C regimens. The primary endpoint was a claim with an inpatient or outpatient diagnosis of AML (ICD-09 codes 205–208). Risk of AML was estimated using the method of Kaplan-Meier. Cox proportional hazards models were used to determine factors independently associated with AML. Results: 36,904 patients were included in this observational study, 4,572 who had received adjuvant C and 32,332 who had not. The median patient age was 75.3 (66.0–103.3). The median follow up was 63 months (13–132). Patients who received C were significantly younger, had more advanced stage disease, and had lower comorbidity scores (p<0.001). The unadjusted risk of developing AML at 10 years after any adjuvant C for breast cancer was 1.6% versus 1.1% for women who had not received C. The adjusted HR for AML with adjuvant C was 1.72 (1.16–2.54) compared to women who did not receive C. HR for radiation was 1.21 (0.86–1.70). HR was higher with increasing age but p>0.05. An analysis was performed among women who received C. When compared to other C regimens, anthracycline-based therapy (A) conveyed a significantly higher hazard for AML HR 2.17 (1.08–4.38), while patients who received A plus taxanes (T) did not have a significant increase in risk HR1.29 (0.44–3.82) nor did patients who received T with some other C HR 1.50 (0.34–6.67). Another significant independent predictor of AML included GCSF use HR 2.21 (1.14–4.25). In addition, increasing A dose was associated with higher risk of AML (p<0.05). Conclusions: There is a small but real increase in AML after adjuvant chemotherapy for breast cancer in older women. The risk appears to be highest from A-based regimens, most of which also contained cyclophosphamide, and may be dose-dependent. T do not appear to increase risk. The role of GCSF should be further explored. No significant financial relationships to disclose.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 240-240
Author(s):  
Sina Vatandoust ◽  
Ganessan Kichenadasse ◽  
Michael E O'Callaghan ◽  
Tina Kopsaftis ◽  
Scott Walsh ◽  
...  

240 Background: In 15-30% of pts with metastatic PCa who progress on Maximal Androgen Blockade (MAB), withdrawal of the antiandrogen agent (AAWD) and continuing the LHRH agonist alone, leads to PSA decreases of ≥50% and prolonged progression free survival. Here we describe patient and disease characteristics, treatment history and outcomes of pts who have been managed with AAWD. Methods: Data were obtained from SA-PCCOC (a longitudinal, observational registry of biopsy-proven PCa cases, throughout the Australian state of South Australia since 1998). Proportions were compared using a Chi squared test. A multivariable model used competing risks (Fine and Gray) and Cox proportional Hazards models to assess overall survival and Prostate cancer specific mortality (PCSM). Survival was calculated from the date of rising PSA for patients on LHRH and AA. Results: 140 pts were found to have MAB. Of these, 31(22.1%) had AAWD. In the AAWD group, median age was 81y (51-95). Age at diagnosis, Gleason score at biopsy and diagnostic PSA were not significantly different amongst the two groups. Treatment PSA was significantly lower in the AAWD group (20.55 (range 0.6-9,995) vs 50.50 (range 0.95-4378) p= 0.02). There was a significant association of AAWD with PCSM (sHR 0.35, 95% CI 0.16-0.76; p = 0.008). Also significant in the model was prior time on hormones (sHR [per month increase] 0.96 95% CI 0.95-0.98, p<0.001). There was also a significant association of AAWD with overall survival (HR 0.22, 95% CI 0.10-0.46; p <0.001). Again, prior time on hormones was also significant (HR [per month increase] 0.96 95% CI 0.95-0.98, p<0.001). Multivariate analysis was performed on data from 80 pts (60 pts omitted due to missing data). Conclusions: Pts in whom AAWD was used were older and had lower treatment PSA. In this small cohort, AAWD was associated with both reduced PCSM and overall risk of death. The time spent on MAB also appeared to be significant. This retrospective observational study may be subject to confounding, however the observation warrants further investigation in larger cohorts and in a prospective setting.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16659-e16659
Author(s):  
Sunyoung S. Lee ◽  
Yehia I. Mohamed ◽  
Aliya Qayyum ◽  
Manal Hassan ◽  
Lianchun Xiao ◽  
...  

e16659 Background: Child-Turcotte-Pugh (CTP) score is widely used in the assessment of prognosis of HCC and CTP-A is the standard criterion for active therapy and clinical trials entry. Recently, ALBI and insulin-like growth factor-1 (IGF)-CTP scores have been reported to improve survival prediction over CTP score. However, comparative studies to compare both scores and to integrate IGF into Albi score are lacking. Methods: After institutional board approval, data and samples were prospectively collected. 299 HCC patients who had data to generate both IGF-CPG and Albi index were used. The ALBI index, and IGF score were calculated, Cox proportional hazards models were fitted to evaluation the association between overall survival (OS) and CTP, IGF-CTP, Albi and IGF, albumin, bilirubin. Harrell’s Concordance index (C-index) was calculated to evaluate the ability of the three score system to predict overall survival. And the U-statistics was used to compare the performance of prediction of OS between the score system. Results: OS association with CTP, IGF-CTP and Albi was performed (Table). IGF-CTP B was associated with a higher risk of death than A (HR = 1.6087, 95% CI: 1.2039, 2.1497, p = 0.0013), ALBI grade 2 was also associated with a higher risk of death than 1 (HR = 2.2817, 95% CI: 1.7255, 3.0172, p < 0.0001). IGF-1(analyzed as categorical variable) was independently associated with OS after adjusting for the effects of ALBI grade. Which showed IGF-1 ≤26 was significantly associated with poor OS, P = 0.001. Conclusions: Although ALBI grade and IGF-CTP score in this analysis had similar prognostic values in most cases, their benefits might be heterogenous in some specific conditions. We looked into corporation of IGF-1 into ALBI grade, IGF score with cutoff ≤26 which clearly refined OS prediction and better OS stratification of ALBI-grade.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19114-e19114
Author(s):  
Jennifer Kay Plichta ◽  
Christel N. Rushing ◽  
Holly C. Lewis ◽  
Dan G. Blazer ◽  
Terry Hyslop ◽  
...  

e19114 Background: National cancer registries are valuable tools used to analyze patterns of care and clinical oncology outcomes; yet, patients with missing data may impact the accuracy and generalizability of these data. We sought to evaluate the association between missing data and overall survival (OS). Methods: Using the NCDB and SEER, we compared data missingness among patients diagnosed with invasive breast cancer from 2010-2014. Key variables included: demographic variables (age, race, ethnicity, insurance, education, income), tumor variables (grade, ER, PR, HER2, TNM stage), and treatment variables (surgery in both databases; chemotherapy and radiation in NCDB). OS was compared between those with and without missing data via Cox proportional hazards models. Results: Overall, 775,996 patients in the NCDB and 263,016 in SEER were identified; missingness of at least 1 key variable was 29% and 13%, respectively. Of those, the majority were missing a tumor variable (NCDB 80%; SEER 88%), while demographic and treatment variables were missing less often. When compared to patients with complete data, missingness was associated with a greater risk of death; NCDB 17% vs. 14% (HR 1.23, 99% CI 1.21-1.25) and SEER 27% vs 14% (HR 2.11, 99% CI 2.05-2.18). Rate of death was similar whether the patient was missing 1 or ≥2 variables. When stratified by the type of missing variable, differences in OS between those with and without missing data in the NCDB were small. In SEER, reductions in OS were largest for those missing tumor variables (HR 2.26, 99% CI 2.19-2.33) or surgery data (HR 3.84, 99% CI 3.32-4.45). Among the tumor variables specifically, few clinically meaningful differences in OS were noted in the NCDB, while the most significant differences in SEER were noted in T and N stage (table). Conclusions: Missingness of select variables is associated with a worse OS and is not uncommon within large national cancer registries. Therefore, researchers must use caution when choosing inclusion/exclusion criteria for outcomes studies. Future research is needed to elucidate which patients are most often missing data and why OS differences are observed. [Table: see text]


2021 ◽  
Author(s):  
◽  
Christiana Kartsonaki

Background: Policymakers need robust data to respond to the COVID-19 pandemic. We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, the world's largest international, standardised cohort of hospitalised patients. Methods: The dataset analysed includes COVID-19 patients hospitalised between January 2020 and May 2021. We investigated how symptoms on admission, comorbidities, risk factors, and treatments varied by age, sex, and other characteristics. We used Cox proportional hazards models to investigate associations between demographics, symptoms, comorbidities, and other factors with risk of death, admission to intensive care unit (ICU), and invasive mechanical ventilation (IMV). Findings: 439,922 patients with laboratory-confirmed (91.7%) or clinically-diagnosed (8.3%) SARS-CoV-2 infection from 49 countries were enrolled. Age (adjusted hazard ratio [HR] per 10 years 1.49 [95% CI 1.49-1.50]) and male sex (1.26 [1.24-1.28]) were associated with a higher risk of death. Rates of admission to ICU and use of IMV increased with age up to age 60, then dropped. Symptoms, comorbidities, and treatments varied by age and had varied associations with clinical outcomes. Tuberculosis was associated with an 86% higher risk of death, and HIV with an 87% higher risk of death. Case fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients. Interpretation: The size of our international database and the standardized data collection method makes this study a reliable and comprehensive international description of COVID-19 clinical features. This is a viable model to be applied to future epidemics.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6122-6122
Author(s):  
B. E. Lally ◽  
F. C. Detterbeck ◽  
C. R. Thomas ◽  
M. Machtay ◽  
A. A. Miller ◽  
...  

6122 Background: Since radiation treatment planning and delivery techniques have evolved over time, we investigated if the risk of CD and PD after PORT for NSCLC has decreased. Methods: We selected postoperative patients with non-metastatic NSCLC diagnosed in 1980–1995 from the SEER data. To account for peri-operative mortality, patients with survival less than 6 months were excluded. Variables analyzed included age, gender, laterality, disease stage, SEER geographic region, ethnicity/race, and histology. CD and PD were calculated at 10 years and compared for patients diagnosed during 1980–83, 1984–88, 1989–91, and 1992–95. Cox proportional hazards models (CPHM) were used to calculate the hazard of CD and PD. Results: This analysis included 29,093 patients treated with observation (OB) and 8334 patients who received PORT. For the patients treated with OB, the 10 yr mortality rates for CD/PD were 17%/2%, 15%/3%, 15%/3%, and 14%/<0.1% for years of diagnosis of 1980–83, 1984–88, 1989–91, and 1992–95, respectively. For the patients who were treated with PORT, the 10 yr mortality rates for CD/PD were 21%/3%, 21%/4%, 15%/4%, and 14%/<0.1% for years of diagnosis of 1980–83, 1984–88, 1989–91, and 1992–95, respectively. CPHM showed the hazard of CD for patients treated with OB to be significantly decreasing; 1980–83 (HR=1.412; CI=1.257–1.585; p<0.0001), 1984–88 (HR=1.260; CI=1.124–1.413; p<0.0001), 1989–91 (HR=1.180; CI=1.054–1.321; p=0.0042), and 1992–95 (HR=1.00; Ref.). CPHM showed the hazard of CD for patients who received PORT to be significantly decreasing; 1980–83 (HR=1.568; CI=1.222–2.011; p=0.0004), 1984–88 (HR=1.435; CI=1.125–1.830; p=0.0036), 1989–91 (HR=0.992; CI=0.767–1.282; p=0.9504), and 1992–95 (HR=1.00; Ref.). Although PD showed a similar decreasing trend relative to year of diagnosis, CPHM did not demonstrate this to be statistically significant. Conclusions: There was a greater reduction in the CD rate in the PORT group compared to the OB group. While there appeared to be a trend in the reduction of PD, the results were not significant which may be secondary to too few events occurring. No significant financial relationships to disclose.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9625-9625
Author(s):  
J. A. Berlin ◽  
P. J. Bowers ◽  
S. Rao ◽  
S. Sun ◽  
K. Liu ◽  
...  

9625 Background: When cancer patients (pts) with chemotherapy-induced anemia (CIA) respond to erythropoietic-stimulating agents (ESA), hemoglobin (Hb) typically increases within 4–8 weeks. This exploratory analysis examined whether mortality differs depending on Hb response after 4 or 8 weeks of epoetin alfa (EPO) treatment or depending on transfusion. Methods: Pt-level data were analyzed from 31 randomized studies (7,215 pts) of epoetin alfa vs non-EPO (15 studies) or placebo (16 studies) in pts with CIA. A landmark analysis was used; Hb change was set at a specific time (4 and 8 weeks) and subsequent survival was examined separately for EPO and placebo. Pts were categorized as “Hb increased” (>0.5 g/dL), “Hb decreased” (>0.5 g/dL), or “Hb stable” (within ±0.5 g/dL) compared to baseline. Hb stable was compared to other Hb change categories with Cox proportional hazards models, stratified by study and adjusted for potential confounders. Results: The hazard ratio (HR) for Hb decreased versus Hb stable at 4 weeks was 1.44 for EPO (95% CI: 1.04, 1.99), indicating worse survival for pts with a decline in Hb. This association was weaker for placebo (HR: 1.12; 95% CI: 0.74, 1.67). Increased risk with declining Hb in EPO-treated pts was most pronounced in studies that maintained Hb ≥12 g/dL or treated pts for >12–16 weeks (1,876 pts). Patterns were similar using the 8-week landmark. In both EPO-treated and placebo pts, transfusion increased the rate of on-study death ∼3.5 fold (treating transfusion as a time-dependent variable). Conclusions: These exploratory findings suggest that both decreased Hb after 4 or 8 weeks of EPO treatment and transfusion are associated with increased risk of death. In spite of adjustment for other prognostic factors, it is likely that this association reflects poorer underlying prognosis of pts whose Hb fails to respond. ESAs should be discontinued in the absence of a Hb response. [Table: see text]


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 119-119
Author(s):  
Christopher Leigh Hallemeier ◽  
Jennifer Moughan ◽  
Michael G. Haddock ◽  
Arnold M. Herskovic ◽  
Bruce D. Minsky ◽  
...  

119 Background: Radiotherapy (RT) interruptions have a negative impact on outcomes in many epithelial malignancies treated with definitive RT. The purpose of this study was to analyze the impact of RT duration on outcomes in patients (pts) with esophageal cancer treated with definitive chemoradiotherapy (CRT). Methods: Pts treated with definitive CRT on RTOG trials 8501 and 9405 were included. Separate analyses were performed in pts receiving standard dose (SD-CRT; 50 Gy + 5FU + cisplatin) and high dose (HD-CRT; 64.8 Gy + 5FU + cisplatin) CRT. Local (LF) and regional (RF) failure were estimated by the cumulative incidence method. Disease-free (DFS) and overall (OS) survival were estimated by the Kaplan-Meier method. Univariate (UVA) and multivariate (MVA) Cox proportional hazards models were utilized to examine for correlation between RT duration (< vs. ≥ median) with LF, RF, DFS and OS. Results: In the SD-CRT cohort (n=235), 96 pts (41%) had ≥ 1 RT interruption for a median of 3 (IQR 1-6) days. The median RT duration was 39 (IQR 37-43) days. In UVA and MVA, RT duration was not associated with LF, RF, DFS, or OS. Estimated outcome rates are in the table. In the HD-CRT cohort (n=107), 64 pts (60%) had ≥ 1 RT interruption for a median of 3.5 (IQR 2-7.5) days. The median RT duration was 52 (IQR 50-57) days. In UVA, RT duration ≥ 52 days was associated with a 33% reduction in risk of DFS failure (HR=0.66, 95% CI [0.44-0.98], p=0.039) and a 29% reduction in risk of death (HR=0.71, 95% CI [0.48-1.06], p=0.09). When excluding the 25 pts with RT dose < 64.8 Gy, RT duration was not associated with DFS or OS. Conclusions: In pts with esophageal cancer receiving definitive SD-CRT, an association between RT duration and outcomes was not observed. In pts receiving HD-CRT, longer RT duration was associated with improved DFS, which may have been due to a significant number of deaths at RT dose < 64.8 Gy. Supported by NCI U10 grants CA21661, CA180868, CA180822, CA37422. Clinical trial information: NCT00002631. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8046-8046
Author(s):  
Eric M Maiese ◽  
Kristin Evans ◽  
Bong-Chul Chu ◽  
Debra E. Irwin

8046 Background: Survival among multiple myeloma (MM) patients has improved over time, but little is known about concurrent changes in healthcare costs. This study examined trends in both survival and healthcare costs over the same time periods in US MM patients. Methods: The MarketScan Commercial and Medicare claims dataset was used to identify 5199 adult patients diagnosed with MM from Jan. 2006 to Dec. 2014. Patients had no prior evidence of cancer, were continuously enrolled for >12 months prior to MM diagnosis, and were followed through the earliest event (death, end of enrollment, or end of the study period (9/30/2015)). Multivariate GLM and Cox proportional hazards models estimated healthcare costs and survival probabilities, respectively, for two time periods during which patients were diagnosed with MM (2006-2010 vs 2011-2014) while controlling for demographic and clinical characteristics. The recycled prediction method was used to calculate the incremental cost estimates between the time periods. Results: Patients diagnosed in 2011-2014 had a 35% lower risk of death compared to those diagnosed in 2006-2010 (HR [95% CI] = 0.65 [0.57-0.74]. Patients diagnosed in 2011-2014 had 18% (95% CI: 6-31%) higher all cause and 26% (95% CI: 6-50%) higher MM-related per patient per month costs compared to those diagnosed in 2006-2010 (Table). Conclusions: Among MM patients, survival has improved at a greater rate than the increase in healthcare costs. In addition to improvements in MM treatment, changes in overall disease management may have contributed to both the increased expenditures and survival improvements observed in this study. [Table: see text]


2017 ◽  
Vol 35 (8_suppl) ◽  
pp. 12-12 ◽  
Author(s):  
Eric Maiese ◽  
Kristin Evans ◽  
Bong-Chul Chu ◽  
Debra E. Irwin

12 Background: Survival among patients with multiple myeloma (MM)has improved over time, but little is known about concurrent changes in health care costs. This study examined trends in both survival and health care costs over the same time periods in U.S. patients with MM. Methods: The MarketScan Commercial and Medicare claims dataset was used to identify 5199 adult patients diagnosed with MM from Jan. 2006 to Dec. 2014. Patients had no prior evidence of cancer, were continuously enrolled for ≥ 12 months prior to MM diagnosis, and were followed through the earliest event (death, end of enrollment, or end of the study period (9/30/2015)). Multivariate GLM and Cox proportional hazards models estimated health care costs and survival probabilities, respectively, for two time periods during which patients were diagnosed with MM (2006-2010 vs. 2011-2014) while controlling for demographic and clinical characteristics. The recycled prediction method was used to calculate the incremental cost estimates between the time periods. Results: Patients diagnosed in 2011-2014 had a 35% lower risk of death compared to those diagnosed in 2006-2010 (HR [95% CI] = 0.65 [0.57-0.74]). Patients diagnosed in 2011-2014 had 18% (95% CI: 6-31%) higher all cause and 26% (95% CI: 6-50%) higher MM-related per patient per month costs compared to those diagnosed in 2006-2010 (see table). Conclusions: Among patients with MM, survival has improved at a greater rate than the increase in health care costs. In addition to improvements in MM treatment, changes in overall disease management may have contributed to both the increased expenditures and survival improvements observed in this study.[Table: see text]


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