Association of gender, age, and ethnicity with survival in patients with pancreas cancer

e15587 Background: Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States. However little is still known about factors that influence its development and progression. Recent data suggest that PC is, at least in part, an estrogen- dependent disease; there is growing epidemiological evidence that aspects of reproductive history and hormonal exposure are associated with risk of this disease. It was shown that age at menarche of <13 is associated with less risk of PC. However no data are available whether gender is associated with outcome in patients with PC. The purpose of this study was to test whether age, gender or ethnicity influence the outcome in PC. Methods: The data of the 50,302 adults diagnosed with PC between 1988 and 2004 were extracted from the Surveillance Epidemiology and End Results public use database. These included 24,240 patients diagnosed with localized pancreatic cancer (LPC) and 26,062 patients with metastatic pancreatic cancer (MPC). Demographic, clinical variables and survival time were retrieved. The primary endpoint was overall survival. We constructed Cox proportional hazards models to evaluate association between patient characteristics and survival in LPC and MPC separately. Pair interactions were also tested. Results: On multivariate analysis gender, age, race, marital status, tumor size, grade, histology, type of treatment and lymph node involvement were found to be independent predictors of survival. Females had a significant longer survival, with an HR of 0.959 (95% CI: 0.932–0.987) among patients with LPC and an HR of 0.918 (95%CI: 0.894–0.942) among patients with MPC. Each age group displayed a significant longer survival than its correspondent older age group. When we combined age and gender in the analysis, females had a longer survival than males in each single age group in the MPC group. In the LPC group the longer survival of female patients was only observed in the youngest age group. Conclusions: This is the first and largest study to address gender and outcome in PC. Our data suggest that the estrogen pathway may play an important prognostic role in patient with this disease. These data also warrant further in vitro and in vivo investigations on the mechanisms of estrogen and pancreas progression. No significant financial relationships to disclose.

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Survival outcomes following cytoreductive nephrectomy (CN) in patients with metastatic renal cell sarcomas (MRCS).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e22519 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e22519-e22519

Author(s):

Midhun Malla ◽

Sarah E Johnston ◽

Yan D Zhao ◽

Vipul Pareek

Keyword(s):

Proportional Hazards ◽

Soft Tissue Sarcomas ◽

Patient Characteristics ◽

The United States ◽

Current Treatment ◽

Cox Proportional Hazards ◽

Age At Diagnosis ◽

Spindle Cell Sarcoma ◽

Kidney Tumors ◽

Level 1

e22519 Background: RCS are rare soft tissue sarcomas and account for 0.8-2.7% of malignant kidney tumors. Level 1 evidence guiding optimal patient management is lacking due to the rarity of this disease. Utilizing the NCDB, we analyzed prognostic factors, the current treatment patterns and outcomes in patients with RCS in the United States. Methods: The NCDB was queried from 2004- 2015 for patients diagnosed with MRCS. Baseline patient characteristics were summarized using descriptive statistics. Impact of baseline demographic, Clinicopathologic variables and treatment on overall survival (OS) was evaluated using univariate (UV) and multivariable (MV) cox proportional hazards analysis. Results: 454 patients diagnosed with MRCS between 2004- 2015 were included in this analysis. Median age at diagnosis was 63. Males (62%) had higher incidence of RCS compared with females. 86% (n = 389) were Caucasian, while only 9.5% (n = 43) were African American. Right and left kidneys were equally affected. Spindle cell sarcoma was the most common histology (n = 276). 37.5% (n = 170) underwent CN. 49% of patients received chemotherapy (n = 216) and 24% received radiation therapy (n = 109). Overall, 48% (n = 82) of patients who underwent nephrectomy had chemotherapy. Median OS was 4.5 months (3.8-5.2 mos.). On UV analysis age ≥ 55 years (HR: 1.92, p < 0.001), no systemic treatment (HR: 1.91, P < 0.01), and no CN (HR: 2.1, p < .001) had worse OS. On MV analysis, patients who did not undergo CN had significantly worsened OS compared to CN (7.56 vs 3.35 mos., HR-1.91, CI: 1.52- 2.41 p < 0.001). Patients who received chemotherapy after CN had a better OS (13.3 vs 3.7 mos., p < 0.001). Conclusions: MRCS is an aggressive malignancy with a median OS of less than 5 months. Age at diagnosis, CN and systemic therapy had a statistically significant impact on OS. Given the rarity of the tumor and inadequacy of guidelines, these results can be considered in making management decisions. We understand the limitations of a registry-based study and hence, prospective multi-national clinical trials are essential to further guide us on management of this rare tumor. [Table: see text]

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Persistence With Human Immunodeficiency Virus Pre-exposure Prophylaxis in the United States, 2012–2017

Clinical Infectious Diseases ◽

10.1093/cid/ciaa037 ◽

2020 ◽

Cited By ~ 1

Author(s):

Ya-Lin A Huang ◽

Guoyu Tao ◽

Dawn K Smith ◽

Karen W Hoover

Keyword(s):

Human Immunodeficiency Virus ◽

Proportional Hazards ◽

Patient Characteristics ◽

The United States ◽

Cox Proportional Hazards ◽

Research Database ◽

Female Sex ◽

Younger Age ◽

Immunodeficiency Virus ◽

Exposure Prophylaxis

Abstract Background Daily oral pre-exposure prophylaxis (PrEP) is highly effective in preventing human immunodeficiency virus (HIV) infection if used adherently throughout periods of HIV risk. We estimated PrEP persistence among cohorts of persons with commercial or Medicaid insurance. Methods We analyzed data from the IBM MarketScan Research Database to identify persons aged 18–64 years who initiated PrEP between 2012 and 2017. We assessed PrEP persistence by calculating the time period that each person continued filling PrEP prescriptions until there was a gap in prescription fills > 30 days. We used Kaplan-Meier time-to-event methods to estimate the proportion of PrEP users who persisted with PrEP at 3, 6, and 12 months after initiation, and constructed Cox proportional hazards models to determine patient characteristics associated with nonpersistence. Results We studied 11 807 commercially insured and 647 Medicaid insured persons with PrEP prescriptions. Commercially insured patients persisted for a median time of 13.7 months (95% confidence interval [CI], 13.3–14.1), compared to 6.8 months (95% CI, 6.1–7.6) among Medicaid patients. Additionally, female sex, younger age, residence in rural location, and black race were associated with shorter persistence. After adjusting for covariates, we found that female sex (hazard ratio [HR], 1.81 [95% CI, 1.56–2.11]) and younger age (18–24 years: HR, 2.38 [95% CI, 2.11–2.69]) predicted nonpersistence. Conclusions More than half of commercially insured persons who initiated PrEP persisted with it for 12 months, compared to a third of those with Medicaid. A better understanding of reasons for nonpersistence is important to support persistent PrEP use and to develop interventions designed for the diverse needs of at-risk populations.

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Garlic Consumption and All-Cause Mortality among Chinese Oldest-Old Individuals: A Population-Based Cohort Study

Nutrients ◽

10.3390/nu11071504 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1504 ◽

Cited By ~ 1

Author(s):

Shi ◽

Lv ◽

Mao ◽

Yuan ◽

Yin ◽

...

Keyword(s):

Proportional Hazards ◽

Oldest Old ◽

Experimental Studies ◽

Population Based ◽

Cox Proportional Hazards ◽

Sensitivity Analyses ◽

Protective Effects ◽

All Cause Mortality

In vitro and in vivo experimental studies have shown garlic has protective effects on the aging process; however, there is no evidence that garlic consumption is associated with all-cause mortality among oldest-old individuals (≥80 years). From 1998 to 2011, 27,437 oldest-old participants (mean age: 92.9 years) were recruited from 23 provinces in China. The frequencies of garlic consumption at baseline and at age 60 were collected. Cox proportional hazards models adjusted for potential covariates were constructed to estimate hazard ratios (HRs) relating garlic consumption to all-cause mortality. Among 92,505 person-years of follow-up from baseline to September 1, 2014, 22,321 participants died. Participants who often (≥5 times/week) or occasionally (1–4 times/week) consumed garlic survived longer than those who rarely (less than once/week) consumed it (p < 0.001). Participants who consumed garlic occasionally or often had a lower risk for mortality than those who rarely consumed garlic at baseline; the adjusted HRs for mortality were 0.92(0.89–0.94) and 0.89(0.85–0.92), respectively. The inverse associations between garlic consumption and all-cause mortality were robust in sensitivity analyses and subgroup analyses. In this study, habitual consumption of garlic was associated with a lower all-cause mortality risk; this advocates further investigation into garlic consumption for promoting longevity.

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Combination of 177lutetium-Satetraxetan-Lilotomab and Rituximab Results in Improved Therapeutic Effect in Preclinical Models of Non-Hodgkin Lymphoma

Blood ◽

10.1182/blood.v128.22.4189.4189 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4189-4189

Author(s):

Ada H.V. Repetto-Llamazares ◽

Roy Hartvig Larsen ◽

Adam O'Shea ◽

Jostein Dahle

Keyword(s):

Therapeutic Effect ◽

Combination Treatment ◽

Tumor Volume ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Employment Equity ◽

Non Hodgkin Lymphoma ◽

Equity Ownership

Abstract Aim: To investigate the therapeutic effect of combined treatment with the anti-CD37 antibody radionuclide conjugate (ARC) 177Lu-satetraxetan-lilotomab (177Lu-p-SCN-Bn-DOTA-HH1, tradename Betalutin®, short name 177Lu-lilotomab) and the anti-CD20 immunotherapy with rituximab in a subcutaneous (s.c.) preclinical model of non-Hodgkin lymphoma (NHL). These studies build on previously presented data that showed that treatment with 177Lu-lilotomab increased binding of rituximab in NHL cells in-vitro and in-vivo. Materials and Methods:The therapeutic effect of the combination of 177Lu-lilotomab and rituximab was studied in nude mice with s.c. Burkitt's lymphoma (Daudi) xenografts using 250 MBq/kg 177Lu-lilotomab, 1 dose of 40 mg/kg rituximab, 4 doses of 10 mg/kg rituximab orNaCl. Treatmentswere given every 3 to 4 days (Table 1). Nine to 10 mice bearinga total of 16 to 18 tumors per group were used in the study. Tumor volume was measured every 2-3 days and weekly after study day 100. The therapeutic effect of the combination treatmentswas compared with the therapeutic effect of each of the treatments alone using Log-Rank and clustered cox-proportional hazards tests. Results:The effect of the combination treatment in mice with s.c. xenografts was better than that of each treatment alone (Figure 1 & 2). The median survival of mice given the combination treatment was longer (>157 days) than each of the treatments alone (31-60 days) and of the sum of both treatments alone (91-100 days), but the difference was not statistically significant (Table 2). The study is currently on-going and none of the mice given the combination treatment have any palpable tumors, so it is expected that the median survival of those mice eventually will double the sum of both treatments alone. Median time to quadruplicate tumor volume was 2 times longer for the combination treatments (>157 days) than in any of the treatments alone (25-49 days) and longer than the sum of both treatments alone (74-82 days) (Table 2). When using time to quadruplicate tumor volume as end-point, the 177Lu-lilotomab + 4 x rituximab combination was significantly different from either treatment alone (p < 0.01, clustered cox-proportional hazards model). Moreover, the median time to complete remission of tumors in mice given the combination treatment was 5 times shorter (13 days) than each of the treatments alone (>66 days) (p<0.05). Three mice in the combination treatment of 177Lu-lilotomab + 4 x rituximab and one mouse in the combination treatment of 177Lu-lilotomab + 1 x rituximab doses were sacrificed due to body weight loss 14, 110, 118 and 157 days after injection of 177Lu-lilotomab respectively. It is not known if this was normal age-related symptoms or random occurrences or due to treatment toxicity. Histopathology examination will be included in the next mice tobe sacrificed to study this in more detail and evaluate if there is any late toxicity due to the combination treatment. Conclusion:Treatment of NHL in-vitro and in-vivo with 177Lu-lilotomab results in an increased binding, tumor uptake and tumor suppression of anti-CD20 immunotherapy. If the same effect is confirmed in clinical studies, it could change the way ARC and CD20 immunotherapy would be used in the future. Disclosures Repetto-Llamazares: Nordic Nanovector ASA: Employment, Equity Ownership. Larsen:Nordic Nanovector ASA: Equity Ownership. O'Shea:Nordic Nanovector ASA: Employment, Equity Ownership. Dahle:Nordic Nanovector ASA: Employment, Equity Ownership.

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Inhibition of glioblastoma and enhancement of survival via the use of mibefradil in conjunction with radiosurgery

Journal of Neurosurgery ◽

10.3171/2012.11.jns121087 ◽

2013 ◽

Vol 118 (4) ◽

pp. 830-837 ◽

Cited By ~ 14

Author(s):

Jason P. Sheehan ◽

Zhiyuan Xu ◽

Britney Popp ◽

Leigh Kowalski ◽

David Schlesinger

Keyword(s):

Tumor Volume ◽

Proportional Hazards ◽

Chemotherapeutic Agents ◽

Cox Proportional Hazards ◽

In Vitro Assays ◽

Rank Test ◽

Group 4 ◽

Group 2

Object The survival of patients with high-grade gliomas remains unfavorable. Mibefradil, a T-type calcium channel inhibitor capable of synchronizing dividing cells at the G1 phase, has demonstrated potential benefit in conjunction with chemotherapeutic agents for gliomas in in vitro studies. In vivo study of mibefradil and radiosurgery is lacking. The authors used an intracranial C6 glioma model in rats to study tumor response to mibefradil and radiosurgery. Methods Two weeks after implantation of C6 cells into the animals, each rat underwent MRI every 2 weeks thereafter for 8 weeks. After tumor was confirmed on MRI, the rats were randomly assigned to one of the experimental groups. Tumor volumes were measured on MR images. Experimental Group 1 received 30 mg/kg of mibefradil intraperitoneally 3 times a day for 1 week starting on postoperative day (POD) 15; Group 2 received 8 Gy of cranial radiation via radiosurgery delivered on POD 15; Group 3 underwent radiosurgery on POD 15, followed by 1 week of mibefradil; and Group 4 received mibefradil on POD 15 for 1 week, followed by radiosurgery sometime from POD 15 to POD 22. Twenty-seven glioma-bearing rats were analyzed. Survival was compared between groups using Kaplan-Meier methodology. Results Median survival in Groups 1, 2, 3, and 4 was 35, 31, 43, and 52 days, respectively (p = 0.036, log-rank test). Two animals in Group 4 survived to POD 60, which is twice the expected survival of untreated animals in this model. Analysis of variance and a post hoc test indicated no tumor volume differences on PODs 15 and 29. However, significant volume differences were found on POD 43; mean tumor volumes for Groups 1, 2, 3, and 4 were 250, 266, 167, and 34 mm3, respectively (p = 0.046, ANOVA). A Cox proportional hazards regression test showed survival was associated with tumor volume on POD 29 (p = 0.001) rather than on POD 15 (p = 0.162). In vitro assays demonstrated an appreciable and dose-dependent increase in apoptosis between 2- and 7-μM concentrations of mibefradil. Conclusions Mibefradil response is schedule dependent and enhances survival and reduces glioblastoma when combined with ionizing radiation.

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Treatment utilization trends and outcomes in renal liposarcoma (RLS): A National Cancer Database (NCDB) analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.559 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 559-559

Author(s):

Midhun Malla ◽

Abhishek Tripathi ◽

Ying Zhang ◽

Sanjay Patel ◽

Vipul Pareek

Keyword(s):

Rare Disease ◽

Proportional Hazards ◽

Case Reports ◽

Patient Characteristics ◽

The United States ◽

Current Treatment ◽

Cox Proportional Hazards ◽

Age At Diagnosis ◽

Adjuvant Radiation ◽

Poor Outcomes

559 Background: RLS is an extremely rare neoplasm with only few case reports documented in the literature. Due to the rarity of this disease, level 1 evidence guiding optimal patient management is lacking. Utilizing the NCDB, we analyzed the current treatment patterns and outcomes in patients with RLS in the United States. Methods: The NCDB was queried from 2004- 2015 for patients diagnosed with T1-4N0-1M0 RLS. Baseline patient characteristics were summarized using descriptive statistics. Impact of baseline demographic, clinicopathologic variables and treatment on overall survival (OS) was evaluated using univariate (UV) and multivariable (MV) cox proportional hazards analysis. Results: 136 patients diagnosed with non-metastatic RLS between 2004- 2015 were included in this analysis. Median age at diagnosis was 64.7 years. Males and females had equal preponderance (50% each). 89% (n = 121) were Caucasian, while only 6% were African American. T staging was based on AJCC 8th edition. 20% of patients had T1 disease, 17% had T2, while T3 and T4 stage was present in 26% and 37% of cases respectively. Only 7% (n = 10) had lymph node (LN) involvement. Dedifferentiated RLS was the most common histology (44%). 59% (n = 80) had radical nephrectomy, 12% (n = 17) had partial nephrectomy, and 17% had nephrectomy NOS. Adjuvant radiation and chemotherapy were used in 15% (n = 20) and 3.6% (n = 5) of patients respectively. Median OS was 41 months (20-76 mos). On UV analysis age ≤ 70 years and sex had a statistically significant effect on OS (HR: 0.387 and 0.549, p < 0.001 and 0.04 respectively). On MV analysis adjusting for age and sex, female patients had a significantly improved OS compared to males (47 vs 36.7mos, HR-0.45, CI: 0.250-0.804 p < 0.05). Conclusions: RLS is a rare and aggressive malignancy with poor outcomes even at localized stage. Age at diagnosis and sex had a statistically significant impact on OS. Given the lack of prospective data, our study provides insights into the prognosis of this rare disease. Additional studies are needed to better guide the optimal management of this rare disease.

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Life Expectancy after Liver Transplantation for Non-Cirrhotic Hepatocellular Carcinoma

Progress in Transplantation ◽

10.1177/15269248211002793 ◽

2021 ◽

pp. 152692482110027

Author(s):

Robert M. Shavelle ◽

Ji Hun Kwak ◽

Rachel Saur ◽

Jordan C. Brooks ◽

Philip Rosenthal

Keyword(s):

Liver Transplantation ◽

Life Expectancy ◽

Proportional Hazards ◽

The United States ◽

Lymph Node Involvement ◽

Cox Proportional Hazards ◽

Related Factors ◽

Term Survival ◽

Transplant Patients ◽

Node Involvement

Background: Hepatocelluar carcinoma typically occurs with underlying cirrhosis. However roughly 20% of cases arise in a non-cirrhotic liver. There is limited literature that addresses the long-term survival of the narrow subgroup who received transplantation. For such patients we sought to calculate life expectancies both at time of transplant and several years later, stratified by key risk factors, and to determine if survival has improved in recent years. Such information can be helpful in making treatment decisions. Methods: Data on 4,373 non-cirrhotic HCC patients who underwent liver transplantation in the MELD era (2002-2018) from the United States OPTN database were analyzed using the Cox proportional hazards regression model and life table methods. Results: Demographic and past medical history factors related to survival were patient age, donor age over 20, and the presence of ascites or severe hepatic encephalopathy. Survival did not vary by race or sex. HCC-specific factors significantly related to survival were the total number of tumors, extrahepatic spread, lymph node involvement, satellite lesions, micro- or macrovascular invasion, tumor differentiation (grade), and pre-transplant treatment. Survival improved over the study period, at 4% per calendar year during the first 5 years post transplant and 1% per year thereafter. Conclusions: Life expectancy in non-cirrhotic HCC transplant patients is much reduced from normal, and varies according to age and tumor-related factors. Survival improved modestly over the study period.

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Novel Mechanistic Insight into the Anticancer Activity of Cucurbitacin D against Pancreatic Cancer (Cuc D Attenuates Pancreatic Cancer)

Cells ◽

10.3390/cells9010103 ◽

2019 ◽

Vol 9 (1) ◽

pp. 103 ◽

Cited By ~ 2

Author(s):

Mohammed Sikander ◽

Shabnam Malik ◽

Sheema Khan ◽

Sonam Kumari ◽

Neeraj Chauhan ◽

...

Keyword(s):

Pancreatic Cancer ◽

The United States ◽

Cancer Therapies ◽

Dependent Manner ◽

Current Standard ◽

Invasion And Migration ◽

Anticancer Properties ◽

Cucurbitacin D

Pancreatic cancer (PanCa) is one of the leading causes of death from cancer in the United States. The current standard treatment for pancreatic cancer is gemcitabine, but its success is poor due to the emergence of drug resistance. Natural products have been widely investigated as potential candidates in cancer therapies, and cucurbitacin D (Cuc D) has shown excellent anticancer properties in various models. However, there is no report on the therapeutic effect of Cuc D in PanCa. In the present study, we investigated the effects of the Cuc D on PanCa cells in vitro and in vivo. Cuc D inhibited the viability of PanCa cells in a dose and time dependent manner, as evident by MTS assays. Furthermore, Cuc D treatment suppressed the colony formation, arrest cell cycle, and decreased the invasion and migration of PanCa cells. Notably, our findings suggest that mucin 13 (MUC13) is down-regulated upon Cuc D treatment, as demonstrated by Western blot and qPCR analyses. Furthermore, we report that the treatment with Cuc D restores miR-145 expression in PanCa cells/tissues. Cuc D treatment suppresses the proliferation of gemcitabine resistant PanCa cells and inhibits RRM1/2 expression. Treatment with Cuc D effectively inhibited the growth of xenograft tumors. Taken together, Cuc D could be utilized as a novel therapeutic agents for the treatment/sensitization of PanCa.

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Repurposing N,N-Dimethylacetamide (DMA), a Pharmaceutical Excipient, as a Prototype Novel Anti-inflammatory Agent for the Prevention and/or Treatment of Preterm Birth

Current Pharmaceutical Design ◽

10.2174/1381612824666180130121706 ◽

2018 ◽

Vol 24 (9) ◽

pp. 989-992 ◽

Cited By ~ 4

Author(s):

Samir Gorasiya ◽

Juliet Mushi ◽

Ryan Pekson ◽

Sabesan Yoganathan ◽

Sandra E. Reznik

Keyword(s):

Preterm Birth ◽

Ex Vivo ◽

The United States ◽

Occurrence Rate ◽

Pharmaceutical Excipient ◽

Ongoing Work ◽

Exciting Line ◽

Pregnant Mice

Background: Preterm birth (PTB), or birth that occurs before 37 weeks of gestation, accounts for the majority of perinatal morbidity and mortality. As of 2016, PTB has an occurrence rate of 9.6% in the United States and accounts for up to 18 percent of births worldwide. Inflammation has been identified as the most common cause of PTB, but effective pharmacotherapy has yet to be developed to prevent inflammation driven PTB. Our group has discovered that N,N-dimethylacetamide (DMA), a readily available solvent commonly used as a pharmaceutical excipient, rescues lipopolysaccharide (LPS)-induced timed pregnant mice from PTB. Methods: We have used in vivo, ex vivo and in vitro approaches to investigate this compound further. Results: Interestingly, we found that DMA suppresses cytokine secretion by inhibiting nuclear factor-kappa B (NF-κB). In ongoing work in this exciting line of investigation, we are currently investigating structural analogs of DMA, some of them novel, to optimize this approach focused on the inflammation associated with PTB. Conclusion: Successful development of pharmacotherapy for the prevention of PTB rests upon the pursuit of multiple strategies to solve this important clinical challenge.

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