The impact of sorafenib on the treatment and survival of advanced hepatocellular carcinoma (HCC): Analysis of the National Cancer Database (NCDB) from 2004 to 2014.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15682-e15682
Author(s):  
Aman Opneja ◽  
Gino Cioffi ◽  
Asrar Alahmadi ◽  
Nirav Patil ◽  
David Lawrence Bajor ◽  
...  

e15682 Background: HCC is a common cause of mortality in the U.S. among men and women (5thand 7th, respectively) with overall five-year survival of ~18%. Sorafenib was the only FDA approved therapy for advanced HCC from 2007 until 2018. This study analyzes trends in the treatment and survival of advanced HCC before and after sorafenib approval. Methods: Adult patients ( > 18 years) with diagnosis of HCC treated with only chemotherapy from 2004 – 2014 were identified in NCDB database. Comparisons were made between 3 time frames: 2004 – 2007 (pre-sorafenib), 2008 – 2011 (early sorafenib) and 2012 – 2014 (late sorafenib). Patients treated with single or multi-agent chemotherapy were analyzed. Cox proportional hazards models were used for univariate and multivariable analyses. Kaplan-Meier method was used for survival analysis. Results: The NCDB contained 33,136 patients with HCC diagnosed between 2004 – 2014 and treated with chemotherapy alone. Patients were generally men (77.4%), over the age of 50 years (92.4%), with an elevated AFP at diagnosis (64.4%), and had limited co-morbidities (76.0%, Charlson/Deyo score of 0-1). The T-stages were T1 (26.3%), T2 (20.5%), T3 (25.6%), and T4 (16.2%). The number and proportion of patients treated with single agent chemotherapy increased significantly during the study period: 2,733 (45.3%) pre-sorafenib, 9,723 (72.7%) early sorafenib, and 13,502 (86.1%) late sorafenib. The proportion of all HCC patients in the NCDB receiving only chemotherapy increased from 17.2% to 26.4% to 28.3% across the 3 time frames. The survival of patients with advanced HCC treated only with chemotherapy improved significantly in the early and late sorafenib cohorts compared to the pre-sorafenib cohort (10.3 months (95% CI: 9.8-10.6) vs. 12.3 months (12.0-12.7) vs. 15.5 months (15.1-15.9), p-value < 0.001). Age > 70 years, male sex, higher Charlson/Deyo score ( > 1), elevated AFP at diagnosis, and higher T-stage were associated with worse survival (p value < 0.001). Conclusions: The approval of sorafenib has dramatically increased the use of chemotherapy for the treatment of advanced HCC and has resulted in a significant survival advantage.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 504-504
Author(s):  
Richard T. Lee ◽  
Gino Cioffi ◽  
Aman Opneja ◽  
Asrar Alahmadi ◽  
Nirav Patil ◽  
...  

504 Background: This study analyzes the pattern of use of SACT in the treatment and survival of AHCC before and after sorafenib was FDA approved in late 2007. Methods: Adult patients diagnosed with HCC and treated with only chemotherapy (CT) from 2004 – 2014 were identified in NCDB database. Patients were analyzed during 3 time frames: 2004–2006 (pre-sorafenib (PS), 2007–2011 (early sorafenib (ES) and 2012–2014 (late sorafenib (LS)). Cox proportional hazards models and Kaplan-Meier method were used for analyses. Results: The NCDB contained 31,107 patients with HCC diagnosed from 2004–2014 and treated with CT alone. Patients were generally men (77.3%), >50 years of age (92.5%), and with a variety of T-stages - T1 (31.0%), T2 (23.9%), T3 (28.3%), and T4 (16.9%). The use of SACT was only 6.2% in the PS period, increased to 15.5% in the ES period, and to 22.3% in the LS period (p<0.0001). During this later period, the highest proportion of SACT is among academic and integrated network facilities (23.4%) as compared to community facilities (16.4%, p<0.0001). The MS of patients with AHCC treated only with CT has improved significantly over the study periods from 10 months (m) (95% CI: 9.5-10.6) to 12.5m (12.0-12.9) to 16m (15.6-16.4, p< 0.001). Significant differences in MS were found between facility types in all time frames (Table). Multivariate analysis indicates worse outcomes for patients treated at community cancer programs (HR 1.66, 1.53-1.79) as compared to academic programs as well as for no insurance (HR 1.13, 1.05-1.22) and estimated household income of <$63,000 (HR 1.09, 1.05-1.13). Conclusions: Despite an overall improvement in survival for AHCC patients treated with only CT, significant differences in the utilization of SACT and survival exist by facility type, insurance status, and income. [Table: see text]


RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e001015 ◽  
Author(s):  
Fernando Pérez Ruiz ◽  
Pascal Richette ◽  
Austin G Stack ◽  
Ravichandra Karra Gurunath ◽  
Ma Jesus García de Yébenes ◽  
...  

ObjectiveTo determine the impact of achieving serum uric acid (sUA) of <0.36 mmol/L on overall and cardiovascular (CV) mortality in patients with gout.MethodsProspective cohort of patients with gout recruited from 1992 to 2017. Exposure was defined as the average sUA recorded during the first year of follow-up, dichotomised as ≤ or >0.36 mmol/L. Bivariate and multivariate Cox proportional hazards models were used to determine mortality risks, expressed HRs and 95% CIs.ResultsOf 1193 patients, 92% were men with a mean age of 60 years, 6.8 years’ disease duration, an average of three to four flares in the previous year, a mean sUA of 9.1 mg/dL at baseline and a mean follow-up 48 months; and 158 died. Crude mortality rates were significantly higher for an sUA of ≥0.36 mmol/L, 80.9 per 1000 patient-years (95% CI 59.4 to 110.3), than for an sUA of <0.36 mmol/L, 25.7 per 1000 patient-years (95% CI 21.3 to 30.9). After adjustment for age, sex, CV risk factors, previous CV events, observation period and baseline sUA concentration, an sUA of ≥0.36 mmol/L was associated with elevated overall mortality (HR=2.33, 95% CI 1.60 to 3.41) and CV mortality (HR=2.05, 95% CI 1.21 to 3.45).ConclusionsFailure to reach a target sUA level of 0.36 mmol/L in patients with hyperuricaemia of gout is an independent predictor of overall and CV-related mortality. Targeting sUA levels of <0.36 mmol/L should be a principal goal in these high-risk patients in order to reduce CV events and to extend patient survival.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4138-4138
Author(s):  
A. B. Siegel ◽  
R. McBride ◽  
D. Hershman ◽  
R. S. Brown ◽  
J. Emond ◽  
...  

4138 Background: Multiple case series have described the use of current therapies for hepatocellular carcinoma (HCC), but recent estimates of treatment utilization in the general population and the impact of various treatments on survival are not known. Methods: We first identified 2898 adults diagnosed with HCC with known tumor size and stage in the Surveillance, Epidemiology, and End-Results Program (SEER), from 1998–2002. Treatment was categorized as transplant, resection, ablation, or none of these. We created a second data set of 1856 HCC patients who were potentially operable, as defined by SEER. We used these patients to construct Kaplan-Meier survival curves and adjusted Cox proportional hazards models. Results: The median age of the larger cohort at HCC diagnosis was 62 (range:18–96). Approximately 42% were white, 32% Asian, 16% Hispanic, and 10% African American. Overall, 10% received a transplant, 18% resection, 8% ablation, and 65% none of these. Only 5% of African Americans with HCC received a transplant, versus 12% of whites, 10% of Hispanics, and 8% of Asians. Asians were most likely to receive resection (24%) and ablation (9%), and least likely to have non-surgical treatment (60%). Using the restricted cohort, improved survival in the multivariate analysis was seen with later year of diagnosis, younger age, female sex, Asian race, smaller tumor size, lower tumor grade, and localized disease. Treatment was highly correlated with survival. This was greatest in the transplanted group (1, 3, and 5-year survivals 93%, 79%, and 71%), followed by resection (70%, 45%, and 29%), and ablation (71%, 33%, and 18%). The non-surgical group had poor survival (33%, 9%, and 0%). Conclusions: Transplantation yields excellent survival on a population scale, similar to reported series, and resection gives relatively good outcomes as well. Asians are more likely to be resected and ablated than other groups. They also had better survival than other groups, perhaps due to underlying etiology of HCC (hepatitis B) and better preserved liver function. No significant financial relationships to disclose.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 666-666
Author(s):  
Anuj K. Patel ◽  
Mei Sheng Duh ◽  
Victoria Barghout ◽  
Mihran Ara Yenikomshian ◽  
Yongling Xiao ◽  
...  

666 Background: FTD/TPI and REG both prolong survival in refractory mCRC and have similar indications with different side effect profiles. This study compares real-world treatment patterns with FTD/TPI and REG for mCRC in a large, representative US claims database. Methods: Retrospective data from 10/2014 to 7/2016 from the US Symphony Health Solutions’ Integrated Dataverse (IDV®) database were analyzed for patients receiving FTD/TPI or REG. The index date was the date of first FTD/TPI or REG prescription. Patients were included if: 1) age ≥18 years old, 2) ≥1 CRC diagnosis, 3) no diagnosis of gastric cancer or gastrointestinal stromal tumor, and 4) continuous clinical activity for ≥3 months before and after index date. The observation period spanned from index date to end of data, end of continuous clinical activity, or switch to another mCRC treatment. Adherence was assessed using medication possession ratio (MPR) ≥0.80 and proportion of days covered (PDC) ≥0.80 at 3 months. Compliance was assessed using time to discontinuation over the observation period using allowable gaps of 45, 60, or 90 days. Patients who never discontinued therapy were censored at the end of the observation period. Outcomes were compared between FTD/TPI and REG using multivariate logistic regression and Cox proportional hazards models, adjusting for demographic and clinical baseline characteristics. Results: A total of 1,630 FTD/TPI patients and 1,425 REG patients were identified. Mean ± standard deviation (SD) age of FTD/TPI patients was 61.0 ± 11.0 compared to 62.8 ± 10.9 for REG patients (p < 0.001). FTD/TPI patients were 80% more likely to have a MPR ≥0.80 compared to those on REG (Odds Ratio [OR] = 1.80, p < 0.001) and more than twice as likely to have a PDC ≥0.80 (OR = 2.66, p < 0.001) at 3 months. FTD/TPI patients were 37% less likely to discontinue their treatment compared to those on REG when using gaps of 60 days (Hazard Ratio = 0.63, p < 0.001). Similar results were found with 45 and 90 days. Conclusions: In this retrospective study of mCRC patients, patients on FTD/TPI were significantly more likely to adhere and comply with therapy compared to those on REG.


Lung ◽  
2022 ◽  
Author(s):  
Hyun J. Kim ◽  
Laurie D. Snyder ◽  
Megan L. Neely ◽  
Anne S. Hellkamp ◽  
David L. Hotchkin ◽  
...  

Abstract Purpose To assess the impact of concomitant emphysema on outcomes in patients with idiopathic pulmonary fibrosis (IPF). Methods The IPF-PRO Registry is a US registry of patients with IPF. The presence of combined pulmonary fibrosis and emphysema (CPFE) at enrollment was determined by investigators’ review of an HRCT scan. Associations between emphysema and clinical outcomes were analyzed using Cox proportional hazards models. Results Of 934 patients, 119 (12.7%) had CPFE. Compared with patients with IPF alone, patients with CPFE were older (median 72 vs 70 years); higher proportions were current/former smokers (88.2% vs 63.7%), used oxygen with activity (49.6% vs 31.9%) or at rest (30.8% vs 18.4%), had congestive heart failure (13.6% vs 4.8%) and had prior respiratory hospitalization (25.0% vs 16.7%); they had higher FVC (median 71.8 vs 69.4% predicted) and lower DLco (median 35.3 vs 43.6% predicted). In patients with CPFE and IPF alone, respectively, at 1 year, rates of death or lung transplant were 17.5% (95% CI: 11.7, 25.8) and 11.2% (9.2, 13.6) and rates of hospitalization were 21.6% (14.6, 29.6) and 20.6% (17.9, 23.5). There were no significant associations between emphysema and any outcome after adjustment for baseline variables. No baseline variable predicted outcomes better in IPF alone than in CPFE. Conclusion Approximately 13% of patients in the IPF-PRO Registry had CPFE. Physiologic characteristics and comorbidities of patients with CPFE differed from those of patients with IPF alone, but the presence of emphysema did not drive outcomes after adjustment for baseline covariates. Trial registration ClinicalTrials.gov, NCT01915511; registered August 5, 2013.


2020 ◽  
pp. bjophthalmol-2020-316617
Author(s):  
Samuel Berchuck ◽  
Alessandro Jammal ◽  
Sayan Mukherjee ◽  
Tamara Somers ◽  
Felipe A Medeiros

AimsTo assess the impact of anxiety and depression in the risk of converting to glaucoma in a cohort of glaucoma suspects followed over time.MethodsThe study included a retrospective cohort of subjects with diagnosis of glaucoma suspect at baseline, extracted from the Duke Glaucoma Registry. The presence of anxiety and depression was defined based on electronic health records billing codes, medical history and problem list. Univariable and multivariable Cox proportional hazards models were used to obtain HRs for the risk of converting to glaucoma over time. Multivariable models were adjusted for age, gender, race, intraocular pressure measurements over time and disease severity at baseline.ResultsA total of 3259 glaucoma suspects followed for an average of 3.60 (2.05) years were included in our cohort, of which 911 (28%) were diagnosed with glaucoma during follow-up. Prevalence of anxiety and depression were 32% and 33%, respectively. Diagnoses of anxiety, or concomitant anxiety and depression were significantly associated with risk of converting to glaucoma over time, with adjusted HRs (95% CI) of 1.16 (1.01, 1.33) and 1.27 (1.07, 1.50), respectively.ConclusionA history of anxiety or both anxiety and depression in glaucoma suspects was associated with developing glaucoma during follow-up.


SLEEP ◽  
2020 ◽  
Author(s):  
Hedström Anna Karin ◽  
Ola Hössjer ◽  
Rino Bellocco ◽  
Weimin Ye ◽  
Lagerros Ylva Trolle ◽  
...  

Abstract Study Objectives The relationship between insomnia and suicide risk is not completely understood. We aimed to investigate the influence of insomnia on suicide risk, taking both sleep duration and depression into consideration. Methods The present study is based on a Swedish prospective cohort study of 38,786 participants with a mean follow-up time of 19.2 years. Cox proportional hazards models with attained age as time-scale were used to estimate hazard ratios (HRs) of death by suicide with 95% confidence intervals (CI) for participants categorized by frequency of insomnia symptoms. Causal mediation analysis was performed to assess to what extent the relationship between insomnia and suicide risk is mediated by depression. Results Insomnia was only associated with suicide risk among short sleepers, whereas no significant association was observed among those who slept 7 h/night or more. The total effect of insomnia in the context of short sleep on suicide risk, expressed on the HR scale, was 2.85 (95% CI 1.42–5.74). The direct effect was 2.25 (95% CI 1.12–4.54) and the indirect effect, mediated by depression, was 1.27 (95% CI 1.05–1.53). Of the total effect, 32% was mediated by depression. The association between insomnia and suicide risk became more pronounced with decreasing depressive symptoms (p value for trend &lt;0.05). Conclusions Insomnia in the context of short sleep increases suicide risk, both directly and indirectly by affecting the risk of depression. Abnormalities of sleep duration and insomnia symptoms should be evaluated when assessing suicide risk.


Author(s):  
Zhiqiang Wang

Confounding is a major issue in observational epidemiological studies. This paper describes two postestimation commands for assessing confounding effects. One command (confall) displays and plots all possible effect estimates against one of p-value, Akaike information criterion, or Bayesian information criterion. This computing-intensive procedure allows researchers to inspect the variability of the effect estimates from various possible models. Another command (chest) uses a stepwise approach to identify variables that have substantially changed the effect estimate. Both commands can be used after most common estimation commands in epidemiological studies, such as logistic regression, conditional logistic regression, Poisson regression, linear regression, and Cox proportional hazards models.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14016-e14016
Author(s):  
Brian S. Seal ◽  
Benjamin Chastek ◽  
Mahesh Kulakodlu ◽  
Satish Valluri

e14016 Background: Improvements in survival for advanced-stage CRC patients who receive chemotherapy have been reported. We compared survival rates for patients with 3+ vs. <3 lines of therapy. Methods: Adult patients with a diagnosis of CRC between 01/01/05 and 05/31/10 were identified from the Impact Intelligence Oncology Management (IIOM) registry. Patients with either stage 4 CRC at original diagnosis or development of metastasis were included. Registry data included original stage and date of diagnosis. Linked healthcare claims from the Life Sciences Research Database, a large US health insurance database affiliated with OptumInsight, were used to identify lines of therapy after metastases and patient characteristics. Death data were obtained from the Social Security Administration’s master death file. Patients were categorized by number of lines of therapy received (0, 1, 2, 3+) and original stage at diagnosis (0-2, 3, 4, unknown). Survival following metastases was evaluated using Cox proportional hazards models controlling for lines of therapy received, stage, and other patient characteristics. Results: 598 patients, followed for a mean of 653 days after becoming metastatic, were included. Mean unadjusted length of follow-up was lowest among patients who received no chemotherapy (516 days) or only 1 line (511 days), and increased to 627 days for those with 2 lines and 930 days for those with 3+ lines. However, multivariate analysis indicated that patients with 3+ lines had comparable survival vs. those with 0 (HR=0.79), 1 (HR=1.59), or 2 (HR=1.15) lines of therapy (p>0.05 for all comparisons). Compared to patients who presented with stage 4 CRC, those who progressed from stage 0-2 (HR=1.22), stage 3 (HR=0.83), or unknown stage (HR=1.18) had similar survival after metastases (p>0.05 for all comparisons). After excluding 94 patients who didn’t receive chemotherapy, patients treated with an oxaliplatin-based regimen (HR=1.28; p=0.24) in first line had similar survival compared to patients treated with an irinotecan-based or anti-EGFR regimen in first line. Conclusions: Lines of therapy received and initial stage were not associated with survival after development of metastases.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 311-311
Author(s):  
Renata D'Alpino Peixoto ◽  
Daniel John Renouf ◽  
Sharlene Gill ◽  
Winson Y. Cheung ◽  
Hagen F. Kennecke ◽  
...  

311 Background: Although both the SHARP and the Asian-Pacific trials showed improved OS for sorafenib when compared to placebo, the magnitude of benefit was substantially less for Asian pts, who have a higher prevalence of hepatitis B (HBV) infection. Whether the worse prognosis is related to ethnicity or to the etiology of HCC remains unclear. BC has a sizeable Asian population that can provide a good comparison to Caucasian pts with HCC. The aim of this study was to identify prognostic factors among pts with HCC who received sorafenib. Methods: 257 consecutive pts with advanced HCC who initiated sorafenib from January 2008 to February 2013 were identified using our pharmacy database. Clinicopathological variables and outcomes were retrospectively collected. Prognostic factors were assessed by univariate (Kaplan-Meier curves and log-rank tests) and multivariate analyses (Cox proportional hazards models). Results: Median age was 62 years (range 22-93), 80.5% were men, and 37.7% were Asian. Among them, 34.2% had HBV and 29.6% had hepatitis C (HCV). In addition, 68.4% had cirrhosis and 46.3% had liver-limited disease. Median progression-free survival (PFS) was 3.7 months (95% CI 3.2-4.1). Median OS from initiation of sorafenib to death was 7.4 months (95% CI 5.7-9.1). On univariate analysis, good ECOG PS, AFP < 250 and history of HCV were associated with better OS (p < 0.001, 0.002 and 0.025, respectively). Ethnicity, age, gender, HBV, cirrhosis and extra-hepatic metastases were not significantly associated with OS. On multivariate analysis, good ECOG PS, AFP < 250 and HCV positivity correlated with better OS (p < 0.001, 0.001 and 0.006, respectively), while ethnicity did not. Conclusions: When treated with sorafenib at the same institution, Asians and Caucasians with advanced HCC had similar OS. ECOG PS, AFP and HCV were the only significant prognostic factors. A higher proportion of HCVpositivity might explain why the SHARP trial achieved better OS when compared to the Asian-Pacific trial.


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