scholarly journals Triple class experience after initiation of combination antiretroviral treatment in Australia: survival and projections

Sexual Health ◽  
2011 ◽  
Vol 8 (3) ◽  
pp. 295 ◽  
Author(s):  
Sadaf Marashi Pour ◽  
Ian Woolley ◽  
Peter Canavan ◽  
John Chuah ◽  
Darren B. Russell ◽  
...  
Keyword(s):  
Antiretroviral Treatment ◽  
Proportional Hazards ◽  
Treatment Options ◽  
Cox Proportional Hazards ◽  
New Drugs ◽  
Factors Associated ◽  
Current Trends ◽  
Cox Proportional Hazards Models ◽  
Number Of Patients ◽  
Significant Difference

Background Patients who have become triple class experienced (TCE) are at a high risk of exhausting available treatment options. This study aims to investigate factors associated with becoming TCE and to explore the effect of becoming TCE on survival. We also project the prevalence of TCE in Australia to 2012. Methods: Patients were defined as TCE when they stopped a combination antiretroviral treatment (cART) that introduced the third of the three major antiretroviral classes. Cox proportional hazards models were used to investigate factors associated with TCE and the effect of TCE on survival. To project TCE prevalence, we used predicted rates of TCE by fitting a Poisson regression model, together with the estimated number of patients who started cART in each year in Australia, assuming a mortality rate of 1.5 per 100 person-years. Results: Of the 1498 eligible patients, 526 became TCE. Independent predictors of a higher risk of TCE included current CD4 counts below 200 cells μL–1 and earlier calendar periods. No significant difference in survival was observed between those who were TCE and those who were not yet TCE. An increasing number of patients are using cART in Australia and if current trends continue, the number of patients who are TCE is estimated to increase from 2800 in 2003 to 5000 in 2012. Conclusion: Our results suggest that the prevalence of TCE in Australia is estimated to plateau after 2003. However, as an increasing number of patients are becoming TCE, it is necessary to develop new drugs that come from new classes or do not have overlapping resistance.

scholarly journals Malaria is associated with Kaposi sarcoma-associated herpesvirus (KSHV) seroconversion in a cohort of western Kenyan children

2020 ◽  
Author(s):  
Katherine R Sabourin ◽  
Ibrahim Daud ◽  
Sidney Ogolla ◽  
Nazzarena Labo ◽  
Wendell Miley ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Proportional Hazards ◽  
Kaposi Sarcoma ◽  
Cox Proportional Hazards ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cox Proportional Hazards Models ◽  
Malaria Exposure ◽  
Significant Difference ◽  
Transmission Region ◽  
Multiplex Bead

Abstract Background We aimed to determine whether Plasmodium falciparum (Pf) infection affects age of Kaposi sarcoma-associated herpesvirus (KSHV) seroconversion in Kenyan children. Methods Kenyan children (n=144) enrolled at age one month, from two sites with different levels of malaria transmission (stable/high malaria vs. unstable/low malaria transmission) were followed through 24 months. Plasma was tested for KSHV antibodies using enzyme-linked immunosorbent assay (ELISA) (K8.1 and LANA) and a multiplex bead-based assay (K8.1, K10.5, ORF38, ORF50, and LANA) and whole blood tested for Pf DNA using quantitative-PCR. Cox proportional hazards models were used to assess associations between Pf DNA detection, malaria annualized rate (Pf detections/person-years), and enrollment site (malaria-high vs malaria-low) with time to KSHV seroconversion. Results KSHV seroprevalence was 63% by 2 years of age when assessed by multiplex assay. Children with Pf were at increased hazards of earlier KSHV seroconversion and among children with malaria, the hazard of becoming KSHV seropositive increased significantly with increasing malaria annualized rate. Children from the malaria-high transmission region had no significant difference in hazards of KSHV seroconversion at 12 months but were more likely to become KSHV seropositive by 24 months of age. Discussion Malaria exposure increases the risk for KSHV seroconversion early in life.

scholarly journals Risk of depressive disorders after tobacco smoking cessation: a retrospective cohort study in Fukuoka, Japan

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e025124 ◽  
Author(s):  
Takako Fujita ◽  
Akira Babazono ◽  
Yumi Harano ◽  
Peng Jiang
Keyword(s):  
Smoking Cessation ◽  
Cohort Study ◽  
Survival Analysis ◽  
Retrospective Cohort ◽  
Depressive Disorders ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Proportional Hazards Models ◽  
Cox Proportional Hazards Models ◽  
Significant Difference

ObjectiveWe sought to examine the effect of smoking cessation on subsequent development of depressive disorders.DesignThis was a retrospective cohort study.MethodsWe used administrative claim and health check data from fiscal years 2010 to 2014, obtained from the largest health insurance association in Fukuoka, Japan. Study participants were between 30 and 69 years old. The end-point outcome was incidence of depressive disorders. Survival analysis and Cox proportional hazards models were conducted. The evaluated potential confounders were sex, age, standard monthly income and psychiatric medical history.ResultsThe final number of participants was 87 255, with 7841 in the smoking cessation group and 79 414 in the smoking group. The result of survival analysis showed no significant difference in depressive disorders between the two groups. The results of Cox proportional hazards models showed no significant difference by multivariate analysis between participants, including users of smoking cessation medication (HR 1.04, 95% Cl 0.89 to 1.22) and excluding medication use (HR 0.97, 95% Cl 0.82 to 1.15).ConclusionsThe present study showed that there were no significant differences with respect to having depressive disorders between smoking cessation and smoking groups. We also showed that smoking cessation was not related to incidence of depressive disorders among participants, including and excluding users of smoking cessation medication, after adjusting for potential confounders. Although the results have some limitations because of the nature of the study design, our findings will provide helpful information to smokers, health professionals and policy makers for improving smoking cessation.

Impact of multidisciplinary bladder cancer care for muscle invasive bladder cancer: A propensity score matched analysis of survival outcomes.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 455-455 ◽  
Author(s):  
Girish S. Kulkarni ◽  
Thomas Hermanns ◽  
Kathy Li ◽  
Yanliang Wei ◽  
Bimal Bhindi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Treatment Options ◽  
Cox Proportional Hazards ◽  
Survival Outcomes ◽  
Primary Therapy ◽  
Bladder Preservation ◽  
Trimodal Therapy ◽  
Significant Difference

455 Background: We started in 2008 a Multidisciplinary Bladder Cancer Clinic (MDBCC), where complex bladder cancer patients are assessed concurrently by urologic and radiation oncologists, with support from medical oncologists. Patients have the opportunity to discuss various treatment options including radical cystectomy (RC) or bladder sparing trimodal therapy (TMT; endoscopic resection, radiotherapy and chemotherapy). Although reports have shown comparable outcomes of TMT to cystectomy, no direct comparison to RC has been published and no randomized studies are available. We report our long term outcomes of multidisciplinary care, comparing TMT to surgery using propensity-matched analyses. Methods: Patients seen in our MDBCC receiving TMT for MIBC from 2008 to 2012 were identified and matched, using propensity scores, to patients operated by RC. Matching occurred on age, ECOG status, Charlson comorbidity score, cT stage, cN stage and date of treatment. Overall survival (OS) and disease-specific survival (DSS) were assessed with Cox Proportional hazards modeling and competing risk analysis, respectively. Results: Between 2008 and 2012, 248 patients were assessed in the MDBCC. Of these, 162 (65%) had MIBC. Nearly half (80) opted for radiotherapy +/- concurrent cisplatin chemotherapy and 49 underwent full bladder preservation with TMT as their primary therapy. We matched 48 TMT patients with 48 RC patients with no imbalances. Median age of the cohort was 67.5 years with 29.2% cT3/cT4. With a median follow up time of 3.62 years, there were 19 (39.6%) deaths (7 from bladder cancer) in the RC group and 15 (31.3%) deaths (6 from bladder cancer) in the TMT group. 5 year DSS was 85.2% and 84.7% with TMT and surgery, respectively (p > 0.05). There was no statistically significant difference in DSS between the two groups (HR for TMT 1.31 (0.40-4.23), p = 0.66) or in OS (HR for TMT 0.77 (0.34-1.75), p = 0.53). Conclusions: Bladder cancer patients benefit from a multidisciplinary approach.. In selected patients with MIBC, chemo-radiation yields survival outcomes similar to matched RC patients. BC patients should be offered the possibility to discuss various treatment options.

scholarly journals Association of Mid- to Late-Life Blood Pressure Patterns With Risk of Subsequent Coronary Heart Disease and Death

2021 ◽  
Vol 8 ◽  
Author(s):  
Menghui Liu ◽  
Shaozhao Zhang ◽  
Xiaohong Chen ◽  
Xiangbin Zhong ◽  
Zhenyu Xiong ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Proportional Hazards ◽  
Late Life ◽  
Cox Proportional Hazards ◽  
Atherosclerosis Risk In Communities ◽  
Cox Proportional Hazards Models ◽  
Significant Difference ◽  
All Cause Mortality

Background: The elevated blood pressure (BP) at midlife or late-life is associated with cardiovascular disease and death. However, there is limited research on the association between the BP patterns from middle to old age and incident coronary heart disease (CHD) and death.Methods: A cohort of the Atherosclerosis Risk in Communities (ARIC) Study enrolled 9,829 participants who attended five in-person visits from 1987 to 2013. We determined the association of mid- to late-life BP patterns with incident CHD and all-cause mortality using multivariable-adjusted Cox proportional hazards models.Results: During a median of 16.7 years of follow-up, 3,134 deaths and 1,060 CHD events occurred. Compared with participants with midlife normotension, the adjusted hazard ratio for all-cause mortality and CHD was 1.14 (95% CI, 1.04–1.25) and 1.28 (95% CI, 1.10–1.50) in those with midlife hypertension, respectively. In further analyses, compared with a pattern of sustained normotension from mid- to late-life, there was no significant difference for the risk of incident death (HR, 1.15; 95% CI, 0.96–1.37) and CHD (HR, 1.33; 95% CI, 0.99–1.80) in participants with a pattern of midlife normotension and late-life hypertension with effective BP control. A higher risks of death and CHD were found in those with pattern of mid- to late-life hypertension with effective BP control (all-cause mortality: HR, 1.24; 95% CI, 1.08–1.43; CHD: HR, 1.65; 95% CI 1.30–2.09), pattern of midlife normotension and late-life hypertension with poor BP control (all-cause mortality: HR, 1.27; 95% CI, 1.12–1.44; CHD: HR, 1.53; 95% CI, 1.23–1.92), and pattern of mid- to late-life hypertension with poor BP control (all-cause mortality: HR, 1.49; 95% CI, 1.30–1.71; CHD: HR, 1.87; 95% CI, 1.48–2.37).Conclusions: The current findings underscore that the management of elderly hypertensive patients should not merely focus on the current BP status, but the middle-aged BP status. To achieve optimal reductions in the risk of CHD and death, it may be necessary to prevent, diagnose, and manage of hypertension throughout middle age.

scholarly journals Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study

2020 ◽  
Vol 5 ◽  
pp. 46
Author(s):  
Faith W. Kamau ◽  
Agnes Gwela ◽  
Andrew K. Nyerere ◽  
Victor Riitho ◽  
James M. Njunge ◽  
...  
Keyword(s):  
Antiretroviral Treatment ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Inverse Sampling ◽  
Art Initiation ◽  
Inflammatory Conditions ◽  
Cox Proportional Hazards Models ◽  
Infection And Inflammation ◽  
Adults And Children ◽  
Sources Of Infection

Background: In advanced HIV, significant mortality occurs soon after starting antiretroviral treatment (ART) in low- and middle-incomes countries. Calprotectin is a biomarker of innate response to infection and inflammatory conditions. We examined the association between plasma calprotectin at initiation of ART and mortality among individuals with advanced HIV. Methods: We conducted a pilot case-cohort study among HIV infected adults and children over 5 years old with CD4+ <100/mm3 at ART initiation at two Kenyan sites. Participants received three factorial randomised interventions in addition to ART within the REALITY trial (ISRCTN43622374). Calprotectin was measured by ELISA in archived plasma of those who died within 24 weeks (cases) and randomly selected participants who survived for 48 weeks (non-cases) for whom samples were available. Factors associated with baseline plasma calprotectin were investigated using linear regression. To test association with mortality, Cox proportional hazards models with inverse sampling probability weights and adjusted for age, sex, site, BMI, viral load, randomised treatments, and clustered by CD4 count were fitted. Results: Baseline median (IQR) plasma calprotectin was 6.82 (2.65–12.5) µg/ml in cases (n=39) and 5.01 (1.92–11.5) µg/ml in non-cases (n=58). Baseline calprotectin was associated with age, neutrophil count and the presence of cough, but not other measured indicators of infection. In adjusted multivariable models, baseline calprotectin was associated with subsequent mortality: HR 1.64 (95% CI 1.11 - 2.42) and HR 2.77 (95% CI 1.58 - 4.88) for deaths during the first twenty-four and four weeks respectively. Calprotectin levels fell between baseline and 4 weeks among both cases and non-cases irrespective of randomised interventions. Conclusion: Among individuals with advanced HIV starting ART in Kenya, plasma calprotectin may have potential as a biomarker of early mortality. Validation in larger studies, comparison with other biomarkers and investigation of the sources of infection and inflammation are warranted.

Treatment patterns and survival among patients with extensive disease small cell lung cancer (ED-SCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20026-e20026 ◽  
Author(s):  
Mark D. Danese ◽  
Michelle L. Gleeson ◽  
Deborah P. Lubeck ◽  
Beata Korytowsky ◽  
Sarah Bobiak
Keyword(s):  
Proportional Hazards ◽  
Treatment Options ◽  
Cox Proportional Hazards ◽  
Second Primary ◽  
Mobility Limitations ◽  
High Poverty ◽  
Poor Overall Survival ◽  
Factors Associated ◽  
Poverty Area ◽  
Outpatient Chemotherapy

e20026 Background: There has been little change to the ED-SCLC treatment landscape in the past 30 years. Patients with ED-SCLC have limited treatment options after recurrence and poor overall survival (OS). Prior work has described OS in patients with ED-SCLC but did not report OS beyond first-line (1L) therapy. Methods: This study used linked data from the Surveillance, Epidemiology, and End Results program and Medicare claims. Patients aged ≥66 years with a first primary, pathologically confirmed ED-SCLC diagnosis between 01/01/2007 and 12/31/2011 and who had Medicare Parts A and B coverage were included. Patients were followed from diagnosis until death, end of follow-up, second primary cancer diagnosis, or switch to managed care coverage. OS from ED-SCLC diagnosis and from initiation of 1L and second-line (2L) outpatient chemotherapy were estimated. Cox proportional hazards models were used to identify factors associated with OS from diagnosis. Results: Of 5498 patients with ED-SCLC (mean age: 75 years [range: 66, 98]) included in this study, 49% were male, 86% were white, 40% had ≥1 indicator of mobility limitations, and 23% lived in an area with high poverty (≥20%). Median OS for all patients was 4.7 months (untreated [n = 2484]: 1.3 months; treated with outpatient chemotherapy within 90 days of diagnosis [n = 3014]: 8.3 months). Among all patients, factors associated with shorter OS included older age, male sex, ≥1 indicator of mobility limitations, and residence in a high poverty area. In the 3014 patients who received 1L outpatient chemotherapy (86% platinum/etoposide; 4% platinum/irinotecan; 10% other), median OS from initiation of 1L therapy was 7.9 months overall (platinum/etoposide: 8.0 months; platinum/irinotecan: 7.8 months; other: 6.4 months). A total of 1162 patients received 2L chemotherapy (38% topotecan monotherapy; 28% platinum regimens; 34% other). Median OS from initiation of 2L therapy was 4.4 months overall (topotecan: 4.0 months; platinum regimens: 6.4 months; other: 3.7 months). Conclusions: OS was poor in this cohort of real-world patients with ED-SCLC especially in those not treated with outpatient chemotherapy. These findings underscore the need for new treatments for this population.

scholarly journals Adjuvant Radiation in Older Patients With Glioblastoma: A Retrospective Single Institution Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jessica W. Lee ◽  
John P. Kirkpatrick ◽  
Frances McSherry ◽  
James E. Herndon ◽  
Eric S. Lipp ◽  
...  
Keyword(s):  
Older Patients ◽  
Proportional Hazards ◽  
Hospice Care ◽  
Cox Proportional Hazards ◽  
Trend Test ◽  
Adjuvant Radiation ◽  
Factors Associated ◽  
Cox Proportional Hazards Models ◽  
Short Course ◽  
Selection Of

ObjectivesStandard 6-week and hypofractionated 3-week courses of adjuvant radiation therapy (RT) are both options for older patients with glioblastoma (GBM), but deciding the optimal regimen can be challenging. This analysis explores clinical factors associated with selection of RT course, completion of RT, and outcomes following RT.Materials and MethodsThis IRB-approved retrospective analysis identified patients ≥70 years old with GBM who initiated adjuvant RT at our institution between 2004 and 2016. We identified factors associated with standard or hypofractionated RT using the Cochran-Armitage trend test, estimated time-to-event endpoints using the Kaplan-Meier method, and found predictors of overall survival (OS) using Cox proportional hazards models.ResultsSixty-two patients with a median age of 74 (range 70–90) initiated adjuvant RT, with 43 (69%) receiving standard RT and 19 (31%) receiving hypofractionated RT. Selection of short-course RT was associated with older age (p = 0.04) and poor KPS (p = 0.03). Eight (13%) patients did not complete RT, primarily for hospice care due to worsening symptoms. After a median follow-up of 37 months, median OS was 12.3 months (95% CI 9.0–15.1). Increased age (p &lt; 0.05), poor KPS (p &lt; 0.0001), lack of MGMT methylation (p &lt; 0.05), and lack of RT completion (p &lt; 0.0001) were associated with worse OS on multivariate analysis. In this small cohort, GTV size and receipt of standard or hypofractionated RT were not associated with OS.ConclusionsIn this cohort of older patients with GBM, age and KPS was associated with selection of short-course or standard RT. These regimens had similar OS, though a subset of patients experienced worsening symptoms during RT and discontinued treatment. Further investigation into predictors of RT completion and survival may help guide adjuvant therapies and supportive care for older patients.

Impact of proximity to NCI- and NCCN-designated cancer centers on outcomes for patients with prostate cancer undergoing radical prostatectomy.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 14-14 ◽  
Author(s):  
Cameron Ghaffary ◽  
Tamer Dafashy ◽  
Christopher David Kosarek ◽  
Zhigang Duan ◽  
Brian F. Chapin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Radical Prostatectomy ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Cox Proportional Hazards ◽  
Survival Outcomes ◽  
Cancer Centers ◽  
Cox Proportional Hazards Models ◽  
Significant Difference

14 Background: National Cancer Institute (NCI) and National Comprehensive Cancer Network (NCCN)-designated cancer centers (CCs) offer patients state-of-the-art treatment. We sought to identify whether proximity to NCI/NCCN CCs was associated with survival outcomes for prostate cancer patients who undergo radical prostatectomy (RP). Methods: A total of 12,478 total patients diagnosed with clinical stage T1 or T2 prostate cancer between 2004–2011 using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data were included. Multivariable regression analyses were used to quantify overall survival and use of secondary therapies for RP patients according to proximity to NCI/NCCN CCs. Cox proportional hazards models were used to quantify the association between survival outcomes and access to NCI/NCCN CCs. Results: Patients with proximity to ≥ 2 NCI centers and those diagnosed in 2011 enjoyed a statistically significant overall survival advantage when compared to no access to an NCI center (Hazard Ratio (HR) 0.72; 95% confidence interval (CI) 0.57–0.92, p < 0.01). Proximity to an NCCN CC, when compared with men who did not have access, was associated with improved overall survival (HR 0.76; 95% CI 0.61–0.95, p = 0.015). There was no significant difference in use of secondary therapies according to NCI or NCCN access. Conclusions: Patients who undergo RP with access to an NCI/NCCN CCs experienced improved overall survival with no significant difference in utilization of secondary therapies. Given the need for improved health quality measures in cancer care, these findings may support health policy implementation and regionalization of care to these centers.

Association of BRCA alteration (alt) type with real-world (RW) outcomes to PARP inhibitors (PARPi) in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5527-5527 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Russell Madison ◽  
Jeremy Snider ◽  
Tamara Snow ◽  
Ethan Sokol ◽  
...  
Keyword(s):  
Protein Function ◽  
Proportional Hazards ◽  
Acquired Resistance ◽  
Parp Inhibitors ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Significant Difference ◽  
Castrate Resistant ◽  
Hormonal Therapies ◽  
Line Setting

5527 Background: Inactivating alts in BRCA1/2 result in homologous recombination deficiency and are predictive of PARPi response in mCRPC. BRCA reversion mutations, which restore the protein function, are frequently observed in acquired resistance to PARPi. In tumors harboring homozygous gene deletions ( BRCAdel) reversions cannot develop; thus, we hypothesize that BRCAdel pts may have prolonged benefit from PARPi compared to pts harboring other BRCA alterations. Methods: Pts were included from the Flatiron Health (FH)-Foundation Medicine (FMI) de-identified clinico-genomic database (CGDB). Inclusion criteria were diagnosis of mCRPC, treatment in the FH network and an FMI comprehensive genomic profiling result between 1/1/2011 - 9/30/2019. Time to therapy discontinuation (TTD) and overall survival (OS) from start of PARPi were estimated with Kaplan-Meier analysis and unadjusted/adjusted (age at PARPi initiation, line number, practice type) hazard ratios (HR/aHR) from Cox proportional hazards models adjusted for survival bias. Results: Out of 829 mCRPC cases, BRCA1/2 alts were detected in 15 (1.8%) and 71 (8.6%) respectively, with 2 cases included in both groups. 26% of BRCAalts were BRCAdel, 67% were coding mutations, and 7% were genomic rearrangements. 25 (28%) BRCAalt pts were treated with PARPi, 11/25 in the 1st or 2nd line setting including 43% of BRCAdel and 44% of other BRCAalt cohorts. Median age at PARPi initiation was 70 yrs and 88% were treated in community practices. TTD was significantly longer in the BRCAdel (n = 7) cohort vs. other BRCAalt cohort (n = 18) (22.7 vs. 9.2 months; HR: 0.16 [0.03-0.74]; aHR: 0.13 [0.02 – 0.92]) while a statistically nonsignificant difference in median OS was observed (31.5 vs. 11.9 months; HR: 0.20 [0.02-1.58]; aHR: 0.24 [0.02-3.15]). In comparison, no statistically significant difference in TTD was observed for BRCAdel (n= 7) vs. other BRCAalts (n=19) pts treated with 1st line hormonal therapies (abiraterone or enzalutamide) (3.4 vs. 5.7 months; HR: 1.16 [0.45-2.98]; aHR: 0.72 [0.25-2.10]). Follow up analysis with more pts and somatic/germline status and zygosity of BRCAalts will be presented. Conclusions: These data suggest a differential benefit from PARPi therapy across BRCAalt subgroups. This observation may in part be explained by the inability to develop reversion mutations to restore BRCA function in tumors with BRCAdel. Further studies are warranted to fully assess the association of BRCAalt type with outcomes to PARPi-based treatments.

scholarly journals 2542

2017 ◽  
Vol 1 (S1) ◽  
pp. 83-83
Author(s):  
Arnav Srivastava ◽  
Hiten Patel ◽  
Max Kates ◽  
Zeyad Schwen ◽  
Gregory Joice ◽  
...  
Keyword(s):  
Tumor Size ◽  
Proportional Hazards ◽  
Preoperative Staging ◽  
Cox Proportional Hazards ◽  
Cancer Specific Survival ◽  
Cox Proportional Hazards Models ◽  
Number Of Patients ◽  
Patients At Risk ◽  
Study Population ◽  
Similar Survival

OBJECTIVES/SPECIFIC AIMS: Due to increased experience and favorable outcomes, the use of partial nephrectomy (PN) to treat renal cell carcinoma has grown in the past decade, with expansion to larger tumors. Performing PN for larger tumors could potentially increase the number of patients up-staged to pT3a after surgery, who may have instead been treated with radical nephrectomy (RN), if known preoperatively. We aimed to estimate the proportion of patients up-staged to T3a disease after PN stratified by size. We also compared size-stratified survival outcomes of up-staged patients to those with T1a, T1b, or T2 kidney cancer. METHODS/STUDY POPULATION: From 1998 to 2013, patients undergoing PN or RN were identified from Surveillance Epidemiology and End Results registries. The proportion of patients receiving PN found to have pT3a disease was quantified by size. Cox proportional hazards models compared cancer-specific (CSS) and overall survival (OS) for PN patients with pT1a, pT1b, and pT2 disease with appropriately size-stratified pT3a patients. Also, PN patients with pT3a disease were compared to size-stratified RN patients with pT3a disease. Comparisons by size were performed within pT3a patients receiving PN. RESULTS/ANTICIPATED RESULTS: From a total of 28,854 patients undergoing PN, the estimated proportion up-staged to pT3a increased along with increasing tumor size: 4.2% for T1a, 9.5% for T1b, and 19.5% for T2. Among patients receiving PN, adjusted survival analysis demonstrated worse CSS for up-staged pT3a patients Versus appropriately stratified pT1a (CSS: HR=1.87, p=0.02), pT1b (CSS: HR=1.91, p=0.01), and pT2 (CSS: HR=2.33, p=0.01) patients. However, when assessing OS, only the size-stratified comparison of up-staged pT3a Versus pT1a disease demonstrated worse OS for the up-staged cohort (OS: HR=1.25, p=0.04). Comparing PN and RN for pT3a disease, size-adjusted analysis revealed no statistical difference in CSS or OS. Lastly, among patients undergoing PN with pT3a disease, patients with larger tumors, measuring 4–7 cm (CSS: HR=2.83, p<0.01; OS: HR=1.44, p=0.04) or 7–16 cm (CSS: HR=8.22, p<0.01; OS: HR=2.64, p<0.01), experienced worse survival than those with smaller pT3a tumors, <4 cm. DISCUSSION/SIGNIFICANCE OF IMPACT: A greater proportion of patients appear to experience T3a up-staging after PN with increasing initial T stage. Up-staged pT3a patients have worse cancer specific survival after PN compared to those with similarly sized localized tumors. Furthermore, the up-staged pT3a patients after PN appear to experience similar survival to pT3a patients undergoing RN. However, pT3a patients undergoing PN had worse survival with increasing tumor size, reinforcing the need for improvements in preoperative staging and identifying patients at risk of up-staging.

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