Magnitude Of Improvement In Survival Research Articles

Patient Prognostic Score and Associations With Survival Improvement Offered by Radiotherapy After Breast-Conserving Surgery for Ductal Carcinoma In Situ: A Population-Based Longitudinal Cohort Study.

Radiotherapy (RT) after breast-conserving surgery (BCS) is a standard treatment option for the management of ductal carcinoma in situ (DCIS). We sought to determine the survival benefit of RT after BCS on the basis of risk factors for local recurrence. A retrospective longitudinal cohort study was performed to identify patients with DCIS diagnosed between 1988 and 2007 and treated with BCS by using SEER data. Patients were divided into the following two groups: BCS+RT (RT group) and BCS alone (non-RT group). We used a patient prognostic scoring model to stratify patients on the basis of risk of local recurrence. We performed a Cox proportional hazards model with propensity score weighting to evaluate breast cancer mortality between the two groups. We identified 32,144 eligible patients with DCIS, 20,329 (63%) in the RT group and 11,815 (37%) in the non-RT group. Overall, 304 breast cancer-specific deaths occurred over a median follow-up of 96 months, with a cumulative incidence of breast cancer mortality at 10 years in the weighted cohorts of 1.8% (RT group) and 2.1% (non-RT group; hazard ratio, 0.73; 95% CI, 0.62 to 0.88). Significant improvements in survival in the RT group compared with the non-RT group were only observed in patients with higher nuclear grade, younger age, and larger tumor size. The magnitude of the survival difference with RT was significantly correlated with prognostic score (P < .001). In this population-based study, the patient prognostic score for DCIS is associated with the magnitude of improvement in survival offered by RT after BCS, suggesting that decisions for RT could be tailored on the basis of patient factors, tumor biology, and the prognostic score.

Factors affecting survival in women with ductal carcinoma in situ (DCIS): Race and the delivery of adjuvant radiotherapy.

29 Background: Recent publications questioned the survival impact of adjuvant radiotherapy (A-RT) in the treatment of DCIS. These reports had in common a short follow up. We wanted to know, in a disease where long term follow up is required, the magnitude of improvement in survival and assess any correlation with race and income. Methods: Search in the Surveillance, Epidemiology and End Results database, of patients diagnosed with DCIS between 1988 and 2012, younger than 70 years old. Analyses of age, race, hormonal receptors (HR), tumor size, surgery, ART and household income. Survival analyses with Kaplan-Meier and multifactorial with Cox proportional-hazard regression. Results: 125,805 patients. Mean follow-up 7.9 years. Patients treated with A-RT resulted in a mortality by breast cancer (DBC) significantly lower (-1.10%; HR: 0.54 [IC95%:0.48-0.59]; p &lt; 0.0001). Based on the type of surgery, mastectomy resulted on a DBC significantly higher than those treated with tumorectomy and A-RT (+1.15%; HR: 2.08 [IC95%:1.84-2.36]; p &lt; 0.0001). Patients with HR+ presented a significantly lower DBC. Black race was the one with the lowest household income (43% &lt; 53900$) opposite to the Asian which was the one with the highest (47% &gt; 71520$). Black race, also presented a DBC significantly higher than the other ones. In the multifactorial analyses (see table), the only variables which presented a significantly influence in DBC were -ART (it decreases DBC) and race (black race increases DBC). Conclusions: These results show blacks, which are the ones with lowest household income, have a significantly increase in cancer mortality than the other races, and that A-RT cuts mortality rates quite drastically in women with DCIS. [Table: see text]

Impact of Novel Treatments on Multiple Myeloma Survival

BACKGROUNDMultiple myeloma survival has significantly improved with the introduction of new therapeutic classes in the early 2000s. The magnitude of improvement in survival with better tolerated therapy is essentially transforming the disease from an acute condition, to a potentially manageable chronic disease . The impact of further advances in multiple myeloma therapy is not yet known but can be projected based on analysis of historical data and positive outcomes that are expected for future clinical trials. METHODOLOGYAnalysis of data from the Surveillance, Epidemiology and End Results (SEER) were performed using SEERStat software. The first part of this analysis compares the median relative survival, based on cohort analysis, and five year relative survival, based on period analysis, for different time periods that coincided with the introduction of newer, better tolerated, more effective therapies for treating multiple myeloma. The second part of this analysis attempts to estimate future changes in survival, that may potentially result from additional disease modifying therapies planned to become available over the next 5-10 years. This will be accomplished through analysis of evidence-based metrics including extrapolation from early phase clinical trial data and validation with key opinion leaders. RESULTSMedian, cumulative and 5 year relative survival of multiple myeloma have improved over the last decade primarily as a result of the introduction of newer therapies such as thalidomide, lenalidomide and bortezomib. Based on analysis of SEER data, median relative survival from the 1980s to 2000 showed modest changes, averaging approximately 30 months through the two decades. Thereafter, median survival increased to nearly 50 months by 2007 (FIGURE 1). Five year relative survival improved from about 30% in 1990 to over 46% in 2010 (FIGURE 2). SUMMARYThis analysis highlights the dramatic improvements in multiple myeloma survival over the last three decades in the U.S., and demonstrates the transformative impact and value of novel therapies for multiple myeloma. The most substantial improvements were observed during the period between 2001 and 2007, when multiple myeloma median survival rates increased by 45%. This improvement has predominantly been driven by the introduction of novel classes of drugs and agents, including immunomodulatory and proteasome inhibitors. Over the next 10 years we expect to see a similar trend, where further advances in the treatment of multiple myeloma will yield additional novel therapies that could result in improvements of comparable or better magnitude. [Display omitted] [Display omitted] DisclosuresKaura:Celgene: Employment, Equity Ownership. Kiely:Celgene: Employment, Equity Ownership. Hussein:Celgene: Employment, Equity Ownership. Durie:Celgene: Advisory Board Celgene, IRC Onyx, DMC Millennium, IRC J&J Other.

Disease-specific survival for patients with multiple myeloma: significant improvements over time in all age groups

This study analyzed the survival of patients with multiple myeloma. Surveillance, Epidemiology, and End Results (SEER) and Centers for Disease Control and Prevention (CDC) databases were queried to calculate myeloma cause-specific survival curves by the Kaplan and Meier product-limit method. The Cox proportional hazards model was used to assess univariate and multivariate predictors of myeloma cause-specific survival. The outcome of interest was death due to myeloma. Results from a Cox proportional hazards model restricted to age and time period at diagnosis demonstrated that the magnitude of improvement in survival by time period varied by age at diagnosis. Among patients under 60 years at diagnosis, hazard ratios for myeloma cause-specific death decreased by more 50% from the first interval of observation to the last. Hazard ratios decreased during the study period by 39% among patients 60–69 years of age and by 27% among patients who were 70 years of age and older. Survival is improving in patients with myeloma of all ages.

Survival Among Lymphoma Patients Over the Past Three Decades: A Single Institution Based Retrospective Review From 1976 to 2006.

Abstract 4527 BackgroundThe incidence of lymphoma has doubled in the past 3 decades in the US and most western countries. Since the advent of multi-drug chemotherapy, studies have shown improvement in survival in specific diagnostic groups such as diffuse large B-cell lymphomas. However, there have been few studies showing the impact of evolving therapies on survival for the total burden of lymphoma patients. We assessed survival for an aggregate population of all patients presenting with lymphoma to a regional tertiary university hospital over the past 3 decades. GoalTo assess the magnitude of improvement in survival for patients with lymphoma over the past 3 decades. MethodsWe analyzed data from the Penn State Hershey Medical Center Cancer Registry, selecting all cases diagnosed with lymphoma by ICD-0-3 codes from Jan 1st 1976 to Dec 31st 2006. Five and ten year (yr) absolute survival rates during five time periods [group (gp) 1: 1976-1980, gp 2: 1981-1985, gp 3: 1986-1990, gp 4: 1996-2000, gp 5: 2001-2006] were obtained by using conventional period analysis (PA). In addition, a period Cox Proportional Model (CPH) was fit to the data, allowing for survival risk estimates of 5 yr survival, statistical testing of time periods, and adjustments for age at diagnosis. SAS v 9.1 was used to obtain estimates, with Brenner's PERIOD macro used for PA and PHREG used for CPH. ResultsOf 2843 patients, Hodgkin's lymphoma accounted for 17%, high grade lymphoma 4%, intermediate grade lymphoma 29%, low grade lymphoma 17%, cutaneous T-cell lymphoma 6%, chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) 13%, malignant lymphoma not otherwise specified (NOS) 14%. Median age was 56 yr and mean was 52 yr with a standard deviation (SD) of 20.9 yr. Median follow up was 4 yr and mean was 6 yr with SD 6.5 yr. Approximately 25% (N=700) survived beyond 10 yr. CPH adjusted for age demonstrated a 5 yr improvement among all lymphomas of 8%, Hazard Ratio (HR)=1.31, 95%, p=0.0192, between gp 5 and gp 1. Consistent improvements in 5 yr survival were detected for intermediate grade lymphoma (15%, HR=1.5, p=0.0219), high grade lymphoma (40%, HR=12.83, p<0.0001), and malignant lymphoma NOS (19%, HR=1.8, p=0.069) comparing gp 5 to gp 1. Changes in survival rates for Hodgkin's lymphoma, low grade lymphoma, CLL/SLL, and cutaneous T-cell lymphoma were not significant. Results for conventional PA were similar. There was a 7% improvement in 5 yr survival between gp 5 and gp 1 for all patients with lymphoma. However, improvement in 10 yr survival between available time intervals was minimal. For the PA, significant improvement in 5 yr survival was seen for intermediate grade lymphoma (24%), high grade lymphoma (28%), malignant lymphoma NOS (19%) comparing gp 5 to gp 1. Interestingly, cutaneous T-cell lymphoma showed a descriptive decline in both 5 yr and 10 yr survival of 29% and 14% respectively. ConclusionThere has been a significant improvement of 8% in overall 5 yr survival in lymphoma patients over the past 3 decades after adjusting for age. There was an improvement in survival in both intermediate and high grade groups. There was a trend towards declining survival in cutaneous T cell lymphoma. This could be attributed to diagnostic drift with changing classification and to the fewer number of cases diagnosed in the earlier years as compared to later years. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Survival Among Leukemia Patients Over the Past Three Decades: A Single Institution Based Retrospective Review From 1976 to 2006.

Abstract 1394Poster Board I-416 Background:Leukemia is the fifth most common cause of cancer death in men and seventh most common cause in women in the US. Since the advent of multi-drug chemotherapy, studies have shown improvement in survival for specific age groups. However, there have been few studies showing the impact of evolving therapies on survival for the total burden of leukemia patients. We assessed survival for an aggregate population of all patients presenting with leukemia to a regional tertiary university hospital over the past 3 decades. Goal:To assess the magnitude of improvement in survival for patients with leukemia over the past 3 decades. Methods:We analyzed data from the Penn State Hershey Medical Center Cancer Registry, selecting all cases diagnosed with leukemia by ICD-0-3 codes, excluding chronic lymphocytic leukemia, from Jan 1st 1976 to Dec 31st 2006. Five and ten year (yr) absolute survival rates during five time periods [group (gp) 1: 1976-1980, gp 2: 1981-1985, gp 3: 1986-1990, gp 4: 1996-2000, gp 5: 2001-2006] were obtained using conventional period analysis (PA). In addition, a period Cox Proportional Model (CPH) was fit to the data, allowing for survival risk estimates of 5 yr survival, statistical testing of time periods, and adjustments for age at diagnosis. SAS v 9.1 was used to obtain estimates, with Brenner's PERIOD macro used for PA and PHREG used for CPH. Results:Of 1892 patients, chronic myeloid leukemia (CML) accounted for 11%, acute myeloid leukemia (AML) 52% and acute lymphoblastic leukemia (ALL) 37%. Median age was 44 yr and mean was 40 yr with a standard deviation (SD) of 27.2 yr. Median follow up was 1.6 yr and mean was 3.9 yr with SD 5.1 yr. Approximately 13% (N=249) survived beyond 10 yr. CPH adjusted for age demonstrated an improvement in 5 yr survival among all patients with leukemia of 16%, Hazard Ratio (HR)=1.57, p=0.0002, and 16% in 10 yr survival, HR=1.6, p= 0.0001, between gp 5 and gp 1. Consistent improvements in age adjusted 5 yr survival were detected for CML (24%, HR=2.06, p=0.124), AML (17%, HR=1.53, p<0.0015) and ALL (21%, HR=1.8, p=0.01) comparing gp 5 to gp 1. Results for conventional PA were similar. There was a 19% improvement in 5 yr survival between gp 5 and gp1 for all patients with leukemia. There was greater variability by PA in the subgroups, CML(58% 5 yr), AML (7% 5 yr) and ALL (24% 5 yr). Conclusion:Our analysis shows that there is a significant improvement of 16% in overall five and ten year survival rates in all leukemia patients over the last 30 years after adjusting for age at diagnosis. Subgroup analysis shows comparable improvements among the three diagnostic groups. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Heart Failure in Women: Epidemiology, Biology and Treatment

Although women account for a significant proportion of the growing heart failure epidemic, they have been poorly represented in clinical trials. As emerging epidemiologic data reveal a growing prevalence and burden of disease among women, it is increasingly important that treating physicians and researchers recognize sex-based differences. Despite the overall incidence of heart failure being lower in women compared with men, the magnitude of improvement in survival over the last several decades has been less apparent in women. Women with heart failure are more likely to be older, have preserved systolic function and nonischemic cardiomyopathy. While clinical trials have demonstrated improved outcomes among heart failure patients, they have predominantly included men, yielding results that are sometimes inadequately powered to detect a benefit for women. Without adequate representation of women in clinical trials, one cannot assume that the same level of therapeutic evidence also applies to women. Nonetheless, it appears that beta-blockers and angiotensin-converting enzyme inhibitors provide the same survival benefits in women with systolic dysfunction as in men. In addition, some studies suggest that angiotensin-receptor blockers may lead to a better survival in women when compared with angiotensin-converting enzyme inhibitors. Focused research is needed to understand and guide the management of women with heart failure.

Locally advanced non-small cell lung cancer: Do we know the questions?: A survey of randomized trials from 1966–1993

Background. Substantial lack of consensus exists regarding the appropriate management of patients with locally advanced non-small cell lung cancer (NSCLC). The purpose of the present study was to investigate why published clinical trials have not resolved this uncertainty, and to examine the potential of current randomized studies to resolve the major controversies regarding the treatment of locally advanced NSCLC. Methods. A literature search identified papers addressing the therapy of locally advanced NSCLC published in the English language from January 1966 through March 1993. The treatment modalities studied in these trials were recorded. The CD-ROM Physician Data Query database was used to identify ongoing studies in NSCLC. For phase III trials in stage III NSCLC, the treatment modalities, eligibility criteria, outcome measures, and statistical considerations were recorded. Results. A total of 164 reports of phase III trials were identified, representing 11% of the 1516 publications meeting search criteria. A wide range of comparisons have been reported; the number of study arms, the number of different modalities employed as control arms, and the number of modalities employed as investigational arms increased over time. Eighteen active phase III protocols open to patients with stage HI NSCLC were identified. In trials which enrolled patients with stage IIIB disease, therapy in control arms employed six different strategies of surgery, radiation, or chemotherapy, alone or in combination, and investigational arms were equally heterogeneous. Variation was also present in the spectrum of disease stages studied, in patient eligibility criteria, and in the clinical outcome measures investigated. The magnitude of improvement in survival sought was varied in its absolute magnitude, in the selection of survival probability for the control arm, and in the time point of its evaluation. Implications. We demonstrated diversity in research practice reflected in five major types of variation: (i) selection of control arms, (ii) selection of study investigational arms, (iii) choice of eligibility criteria, (iv) outcome measures selected for study, and (v) type and magnitude of benefit sought in the primary outcome measure. This variation has important implications regarding the inability of these studies to address some fundamental management controversies, and the ability to generalize the results of these trials to the general population of NSCLC patients. This diversity reflects a poorly defined process for setting the goals of clinical research. The generation of future trials may be improved by strategies that identify the most important controversies, identify important outcome measures, improve consensus among physicians, and provide the opportunity to incorporate patients' preferences in this clinical situation.