Browsing by Subject "survival"
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Item Adult Comorbidity Evaluation 27 score as a predictor of survival in endometrial cancer patients(Elsevier, 2016-12) BINDER, Pratibha S; PEIPERT, Jeffrey F; KALLOGJERI, D; BROOKS, Rebecca A; MASSAD, Leslie S; MUTCH, David G; POWELL, Matthew A; THAKER, Premal H; McCOURT, Carolyn K; Obstetrics and Gynecology, School of MedicineBACKGROUND The incidence of endometrial cancer increases with age and is associated with medical comorbidities such as obesity and diabetes. While a few cohort studies of less than 500 patients showed an association between comorbidity and survival in endometrial cancer patients, the degree of association needs to be better described. The Adult Comorbidity Evaluation 27 (ACE-27) is a validated comorbidity instrument that provides a score (0–3) based on the number and severity of medical comorbidities. OBJECTIVE This study was performed to explore the association between medical comorbidities and survival of endometrial cancer patients. STUDY DESIGN Patients diagnosed with endometrial cancer from 2000–2012 were identified from the prospectively maintained Siteman Cancer Center tumor registry. Patients undergoing primary surgical treatment for endometrioid, serous and clear cell endometrial carcinoma were included. Patients primarily treated with radiation, chemotherapy or hormone therapy were excluded. Patients with uterine sarcomas or neuroendocrine tumors were excluded. Patients with missing ACE-27 scores were also excluded from analysis. Information including patient demographics, ACE-27 score, tumor characteristics, adjuvant treatment and survival data were extracted from the database. The association of ACE-27 and overall as well as recurrence-free survival was explored in a multivariable Cox regression analysis after controlling for variables found to be significantly associated with survival in univariable analysis. RESULTS A total of 2073 patients with a median age of 61 years (range 20–94) at diagnosis were identified. ACE-27 score was 0, 1, 2 and 3 in 22%, 38%, 28% and 12% of patients, respectively. Stage distribution was I (73%), II (5%), III (15%) and IV (7%) and grade distribution was 1 (52%), 2 (23%) and 3 (25%). Most patients had endometrioid histology (87%) followed by serous (11%) and clear cell (3%). The median OS for the entire cohort was 54 months [95% confidence interval (CI) 3, 154 months] and median PFS was 50 months [95% CI 2, 154 months]., On univariable analysis, age, race, marital status, stage, grade, histology and treatment type were significantly associated with overall survival and recurrence-free survival. After adjusting for these covariates, patients with ACE-27 score of 2 had a 52% higher risk of death [95% CI 1.16, 2.00] and patients with ACE-27 score of 3 had a 2.35-fold increased risk of death [95% CI 1.73, 3.21] compared to patients with an ACE-27 score of 0. Similarly, patients with ACE-27 score of 2 had a 38% higher risk of recurrence [95% CI 1.07, 1.78] and patients with ACE-27 score of 3 had a 2.05-fold increased risk of recurrence [95% CI 1.53, 2.75] compared to patients with an ACE-27 score of 0. We found no interaction between ACE-27 score and age, stage or treatment type. CONCLUSIONS Our findings demonstrate the importance of comorbidities in estimating the prognosis of endometrial cancer patients, even after adjusting for age and known tumor-specific prognostic factors like stage, grade, histology and adjuvant treatment.Item Alkaline phosphatase in metastatic castration-resistant prostate cancer: reassessment of an older biomarker(Future Medicine, 2018-06-21) Heinrich, Daniel; Bruland, Øyvind; Guise, Theresa A; Suzuki, Hiroyoshi; Sartor, Oliver; Medicine, School of MedicineSince most patients with metastatic castration-resistant prostate cancer (mCRPC) have bone metastases, it is important to understand the potential impact of therapies on prognostic biomarkers, such as ALP. Clinical studies involving mCRPC life-prolonging agents (i.e., sipuleucel-T, abiraterone, enzalutamide, docetaxel, cabazitaxel, and radium-223) have shown that baseline ALP level is prognostic for overall survival, and may be a better prognostic marker for overall survival than prostate-specific antigen in patients with bone-dominant mCRPC. Mechanism of action differences between therapies may partly explain ALP dynamics during treatment. ALP changes can be interpreted within the context of other parameters while monitoring disease activity to better understand the underlying pathology. This review evaluates the current role of ALP in mCRPC.Item Childhood acute lymphoblastic leukemia treatment in an academic hospital in Kenya: Treatment outcomes and health‐care providers’ perspectives(Wiley, 2021-12) Olbara, Gilbert; van der Wijk, Thyra; Njuguna, Festus; Langat, Sandra; Mwangi, Henry; Skiles, Jodi; Vik, Terrry A.; Kaspers, Gertjan J.L.; Mostert, Saskia; Pediatrics, School of MedicineBackground Early deaths and treatment nonadherence are major reasons for low childhood acute lymphoblastic leukemia (ALL) survival in low- and middle-income countries. This study assessed treatment outcomes of children presenting with ALL and evaluated perspectives of health-care providers (HCP) on ALL treatment at a Kenyan academic hospital. Methods This was a combined retrospective medical records and cross-sectional questionnaire study. Treatment outcomes of 136 children diagnosed with ALL between 2010 and 2016 were collected. Questionnaires were completed by 245 HCP (response rate, 86%) between September and October 2016. Results Childhood ALL treatment outcomes were death (30%), progressive or relapsed disease (26%), abandonment (24%), and event-free survival (20%). Of all deaths, 80% were early deaths (prior or during induction), whereas 20% occurred in remission. Probability of event-free survival at three years was 18%. Only 57% of HCP believed childhood ALL can be cured, with more doctors (96%) than other HCP (45%) believing in curability of ALL (P < 0.001). The majority of HCP (96%) thought that experienced doctors should put more time and effort into making parents understand the diagnosis and necessity to complete treatment. According to HCP, reasons for protocol nonadherence included parental financial difficulties (94%) and use of alternative treatment (79%). Conclusions Event-free survival for ALL in Kenya is low. The primary reason for treatment failure is early death from treatment-related complications. More efforts should be directed toward improving supportive care strategies. In the opinion of HCPs, improved communication with parents and supervision of junior staff will improve ALL treatment outcomes.Item Distinct cachexia phenotypes and the importance of adipose tissue loss on survival of patients with advanced pancreatic cancer on FOLFIRINOX chemotherapy(2017-12) Kays, Joshua; Zimmers, Teresa A.; Koniaris, Leonidas G.By the traditional definition of unintended weight loss, cachexia develops in ~80% of patients with pancreatic ductal adenocarcinoma (PDAC). Here we measure the longitudinal body composition changes in patients with advanced PDAC undergoing FOLFIRINOX therapy. We performed a retrospective review of 53 patients with advanced PDAC on FOLFIRINOX as first line therapy at Indiana University Hospital from July 2010 to August 2015. Demographic, clinical, and survival data were collected. Body composition measurement, trend, univariate and multivariate analysis were performed. Three cachexia phenotypes were identified. The majority of patients, 64%, had Muscle-and-Fat Wasting (MFW), while 17% had Fat-Only Wasting (FW) and 19% had No Wasting (NW). NW had significantly improved overall median survival (OMS) of 22.6 months vs. 13.0 months for FW and 12.2 months for MFW (p=0.02). FW (HR=5.2; 95%CI=1.5-17.3) and MFW (HR=1.8; 95%CI=1.1-2.9) were associated with an increased risk of mortality compared to NW. OMS and risk of mortality did not differ between FW and MFW. Progression of disease, sarcopenic obesity at diagnosis, and primary tail tumors were also associated with decreased OMS. On multivariate analysis cachexia phenotype and chemotherapy response were independently associated with survival. Three phenotypes of cachexia were observed. Moreover, three phenotypes suggests molecular or genetic heterogeneity of host or tumor. Identifying these differences will be vital to defining optimal treatment for cachexia. Survival among FW was as poor as MFW suggesting adipose tissue plays a crucial role in cachexia. Blunting or possibly preventing cachexia may confer a significant survival advantage in patients with advanced PDAC.Item Efficacy of Post-Induction Therapy for High-risk Neuroblastoma Patients with End-Induction Residual Disease(Wiley, 2022) Desai, Ami V.; Applebaum, Mark A.; Karrison, Theodore G.; Oppong, Akosua; Yuan, Cindy; Berg, Katherine R.; MacQuarrie, Kyle; Sokol, Elizabeth; Hall, Anurekha G.; Pinto, Navin; Wolfe, Ian; Mody, Rajen; Shusterman, Suzanne; Smith, Valeria; Foster, Jennifer H.; Nassin, Michele; LaBelle, James L.; Bagatell, Rochelle; Cohn, Susan L.; Radiology and Imaging Sciences, School of MedicineBackground: High-risk neuroblastoma patients with end-induction residual disease commonly receive post-induction therapy in an effort to increase survival by improving response prior to autologous stem cell transplant (ASCT). We conducted a multi-center, retrospective study to investigate the efficacy of this approach. Methods: Patients diagnosed between 2008 and 2018 without progressive disease (PD) with ≤ partial response (PR) at end-induction were stratified according to post-induction treatment: i) no additional therapy prior to ASCT (Cohort 1); ii) post-induction “bridge” therapy prior to ASCT (Cohort 2); and iii) post-induction therapy without ASCT (Cohort 3). Chi-square tests were used to compare patient characteristics. Three-year event-free survival (EFS) and overall survival (OS) were estimated by the Kaplan-Meier method and survival curves were compared by log-rank test. Results: The study cohort consisted of 201 patients; Cohort 1 (n=123); Cohort 2 (n=51); and Cohort 3 (n=27). Although end-induction response was better for Cohort 1 than Cohorts 2 and 3, outcome for Cohort 1 and 2 was not significantly different (EFS; p=0.77 and OS; p=0.85). Inferior outcome was observed for Cohort 3 (EFS; p<0.001 and OS; p=0.06). Among patients with end-induction stable metastatic disease, 3-year EFS was significantly improved for Cohort 2 compared to Cohort 1 (p=0.04). Cohort 3 patients with complete response (CR) in metastatic sites following post-induction therapy had significantly better 3-year EFS compared to those with residual metastatic disease (p=0.01). Conclusions: Prospective studies to confirm the benefits of bridge treatment and the prognostic significance of metastatic response observed in this study are warranted.Item A new survival model based on ferroptosis-related genes for prognostic prediction in clear cell renal cell carcinoma(Impact Journals, 2020-07-20) Wu, Guangzhen; Wang, Qifei; Xu, Yingkun; Li, Quanlin; Cheng, Liang; Pathology and Laboratory Medicine, School of MedicineIn this study, we analyzed the clinical significance of ferroptosis-related genes (FRGs) in 32 cancer types in the GSCA database. We detected a 2-82% mutation rate among 36 FRGs. In clear cell renal cell carcinoma (ccRCC; n=539) tissues from the The Cancer Genome Atlas database, 30 of 36 FRGs were differentially expressed (up- or down-regulated) compared to normal kidney tissues (n=72). Consensus clustering analysis identified two clusters of FRGs based on similar co-expression in ccRCC tissues. We then used LASSO regression analysis to build a new survival model based on five risk-related FRGs (CARS, NCOA4, FANCD2, HMGCR, and SLC7A11). Receiver operating characteristic curve analysis confirmed good prognostic performance of the new survival model with an area under the curve of 0.73. High FANCD2, CARS, and SLC7A11 expression and low HMGCR and NCOA4 expression were associated with high-risk ccRCC patients. Multivariate analysis showed that risk score, age, stage, and grade were independent risk factors associated with prognosis in ccRCC. These findings demonstrate that this five risk-related FRG-based survival model accurately predicts prognosis in ccRCC patients, and suggest FRGs are potential prognostic biomarkers and therapeutic targets in several cancer types.Item Plasma 25-Hydroxyvitamin D Levels and Survival in Patients with Advanced or Metastatic Colorectal Cancer: Findings from CALGB/SWOG 80405 (Alliance)(American Association for Cancer Research, 2019-12-15) Yuan, Chen; Sato, Kaori; Hollis, Bruce W.; Zhang, Sui; Niedzwiecki, Donna; Ou, Fang-Shu; Chang, I.-Wen; O'Neil, Bert H.; Innocenti, Federico; Lenz, Heinz-Josef; Blanke, Charles D.; Goldberg, Richard M.; Venook, Alan P.; Mayer, Robert J.; Fuchs, Charles S.; MeyerhardtMeyerhardt, Jeffrey A.; Ng, Kimmie; Medicine, School of MedicinePurpose: Previous studies have suggested that higher circulating 25-hydroxyvitamin D [25(OH)D] levels are associated with decreased colorectal cancer (CRC) risk and improved survival. However, the influence of vitamin D status on disease progression and patient survival remains largely unknown for patients with advanced or metastatic CRC. Experimental design: We prospectively collected blood samples in 1,041 patients with previously untreated advanced or metastatic CRC participating in a randomized phase III clinical trial of first-line chemotherapy plus biologic therapy. We examined the association of baseline plasma 25(OH)D levels with overall survival (OS) and progression-free survival (PFS). Cox proportional hazards models were used to calculate hazard ratios (HRs) and confidence intervals (CIs), adjusted for prognostic factors and confounders. Results: At study entry, 63% of patients were vitamin D deficient (<20 ng/mL) and 31% were vitamin D insufficient (20 to <30 ng/mL). Higher 25(OH)D levels were associated with an improvement in OS and PFS (Ptrend=0.0009 and 0.03, respectively). Compared to patients in the bottom quintile of 25(OH)D (≤10.8 ng/mL), those in the top quintile (≥24.1 ng/mL) had a multivariable-adjusted HR of 0.66 (95% CI, 0.53 to 0.83) for OS and 0.81 (95% CI, 0.66 to 1.00) for PFS. The improved survival associated with higher 25(OH)D levels was consistent across patient subgroups of prognostic patient and tumor characteristics. Conclusions: In this large cohort of patients with advanced or metastatic CRC, higher plasma 25(OH)D levels were associated with improved OS and PFS. Clinical trials assessing the benefit of vitamin D supplementation in CRC patients are warranted.Item Platelet count correlates with stage and predicts survival in melanoma(Taylor & Francis, 2019) Rachidi, Saleh; Kaur, Maneet; Lautenschlaeger, Tim; Li, Zihai; Radiation Oncology, School of MedicineCancer is a chronic inflammatory state which is often associated with increased platelet counts. Cancer cells induce thrombopoiesis and activate platelets, which in turn facilitate cancer invasion and metastasis. In this study, we investigate the correlation between platelet counts with each of stage and overall survival in melanoma. This is a retrospective cohort study of 642 melanoma patients diagnosed or treated at a tertiary medical center between 2000 and 2016. Multivariable analysis adjusted for age, sex, stage, and treatment modality. Using multivariable analysis, patients with thrombocytosis around time of diagnosis were more likely to present with distant metastasis (Prevalence Ratio 3.5, 95% CI 2.35–5.22). In patients with metastatic disease and in all stages combined, thrombocytosis predicted decreased 5-year overall survival in univariate and multivariable analysis, and this was most pronounced during the first year after diagnosis. Finally, we show that mice with thrombocytopenia due to the lack of heat shock protein gp96 in their megakaryocytes are protected from melanoma dissemination to the lungs. These findings are concordant with preclinical studies showing a role for platelets in cancer metastasis and suppression of antitumor immunity, further supporting targeting platelets as an adjuvant to immunotherapy in melanoma.Item Salvage therapy for relapsed testicular cancer(Impact Journals, 2017-09-14) Adra, Nabil; Einhorn, Lawrence H.; Medicine, School of MedicineItem The survival advantage of pancreas after kidney transplant(Wiley, 2019) Fridell, Jonathan A.; Niederhaus, Silke; Curry, Michael; Fox, Abigail; Odorico, Jon; Surgery, School of MedicinePatient survival after pancreas after kidney transplant (PAK) has been reported to be inferior to patient survival after simultaneous pancreas–kidney transplant (SPK). The authors examine national data to further explore allograft (kidney and pancreas) and patient survival after PAK. Kaplan–Meier and Cox proportional hazard models were used to analyze Organ Procurement and Transplantation Network data from 1995 to 2010. The analysis compared PAK and SPK candidates and recipients. Kaplan–Meier analysis results showed that PAK after either a living or a deceased donor kidney transplant is associated with increased kidney graft survival compared with recipients with type 1 diabetes who received only a kidney. The best kidney allograft survival was for patients who received a living donor kidney followed by PAK. Receiving a living donor kidney was associated with increased pancreas allograft survival compared with receiving a deceased donor kidney. PAK transplant recipients who receive both organs have a survival advantage compared with uremic candidates who receive neither (SPK waitlist). Compared with uremic diabetic waitlist patients, SPK and PAK recipients showed similar overall patient survival. Successful PAK offers a survival advantage compared with receiving neither a kidney nor a pancreas transplant. These data also suggest that receiving a pancreas (after kidney) transplant may have a protective effect on the kidney allograft.