Overall survival of patients with metastatic castrate-resistant prostate cancer (mCRPC) who have PTEN tumor suppressor gene loss of function.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 58-58
Author(s):  
Shilpa Gupta ◽  
Ibrahim M. Abbass ◽  
Christopher Craggs ◽  
Sacha Satram ◽  
Tu My To ◽  
...  

58 Background: It is estimated that more than 40% of patients with mCRPC have functional loss of phosphatase and tensin homolog (PTEN) tumor suppressor gene, which is associated with unfavorable prognosis and reduced response to androgen receptor-targeting therapy. We describe patient characteristics and survival outcomes by PTEN LOF status among patients with mCRPC in real-world clinical practice. Methods: We conducted a retrospective cohort study using data from the nationwide Flatiron Health-Foundation Medicine mCRPC Clinico-Genomic database (FH-FMI CGDB), a de-identified database linking data derived from electronic health records with genomic data derived from FMI comprehensive genomic profiling (CGP) tests. The study included patients ≥18 years old, with a primary diagnosis of mCRPC between 1/1/2013 and 6/30/2019 who underwent FMI CGP testing and who had a valid PTEN LOF status. Patients were included if their PTEN report date and mCRPC diagnosis date occurred before death or censoring. PTEN LOF status was identified via FMI’s CGP testing. Kaplan-Meier (KM) methods assessed overall survival (OS) by PTEN LOF status from the date of mCRPC diagnosis (later of metastasis and castration resistance) until death or end of study follow-up. A stratified Cox regression model was used to estimate the hazard of death. The Cox model was adjusted for age, race and sequence of metastasis/CRPC diagnoses, and was stratified by the year of mCRPC diagnosis. Adjustments to account for left-truncation and survivorship bias were made in the KM analysis and the Cox regression model. Results: Among the 458 patients who met the eligibility criteria, 174 (38%) had PTEN LOF. The majority of the study sample (76%) was diagnosed with castration-resistance after metastasis. The PTEN LOF group had a higher percentage of white patients (80% vs. 68%; p= 0.01) compared to the PTEN non-LOF group. The mean age of the study sample was 68 years, and there was no difference in mean age at diagnosis by PTEN LOF status ( p= 0.17). Based on the KM estimates adjusted for left-truncation, the median OS was 14.3 months (95% confidence interval [CI]: 11.1-19.7) in the PTEN LOF group compared to 18.3 months (95%CI: 15.5-21.5) in the PTEN non-LOF group (log-rank p= 0.049). In the multivariable Cox model, the PTEN LOF group had numerically 30% higher risk of death compared to the PTEN non-LOF group (hazard ratio = 1.30; 95% CI: 0.99-1.71; p= 0.057). Conclusions: Among real-world patients with mCRPC in the CGDB, PTEN LOF could be associated with poorer survival outcomes, potentially highlighting the unmet need among these patients. Additional studies with larger cohorts are needed to better evaluate the survival outcomes of patients with PTEN LOF. Therapeutic agents acting on the PTEN/PI3K/AKT/mTOR pathway are being tested in clinical trials, and could potentially improve outcomes in this subgroup of patients with mCRPC.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 405-405
Author(s):  
Michael W. Kattan ◽  
Cora N. Sternberg ◽  
Faisal Mehmud ◽  
Kamalnayan Bhatt ◽  
Debasis Chakrabarti ◽  
...  

405 Background: Pazopanib, an oral multikinase inhibitor, demonstrated noninferiority to sunitinib in patients with aRCC in COMPARZ (NCT00720941), a randomized, phase III trial (NEJM 2013;369:722). The purpose of this study was to develop and validate prognostic nomograms based on outcome data from COMPARZ for predicting the probability of 12-month progression-free survival (PFS) and 30-month overall survival (OS) for aRCC patients who received pazopanib. Methods: Statistical modeling was performed on a dataset consisting of 557 patients from the pazopanib arm of COMPARZ. A Cox proportional hazards regression model was fit using predictors thought to be prognostic. These predictors included neutrophil count, platelet count, LDH, and alkaline phosphatase, all relative to ULN; calcium; albumin; hemoglobin; Karnofsky score; months from diagnosis to treatment; number of metastatic sites; and presence of lung, liver, and bone metastases. Data from patients on the sunitinib arm of COMPARZ and the pazopanib arm of the VEG105192 trial (NCT00334282; J Clin Oncol 2010;28:1061) were used for validation. Missing values were imputed using chained equations. For validation with the VEG105192 dataset, bootstrap-corrected estimates of discrimination and calibration were calculated following 1000 resamples. The Cox model was plotted as a nomogram. Results: Prognostic nomograms were developed and validated for predicting the probability of 12-month PFS and 30-month OS in aRCC patients based on a Cox regression model. Calibration plots suggested reasonable correspondence between predicted probabilities and actual proportions of PFS and OS. The concordance index for 12-month PFS was 0.636 with sunitinib patients and 0.635 for pazopanib patients; the concordance index was 0.692 for 30-month OS (sunitinib patients). When examining the PFS and OS nomograms, albumin, calcium, and LDH levels appeared to be the most influential predictors of outcome. Conclusions: The nomograms predict, with reasonable accuracy, treatment outcomes in patients with aRCC receiving pazopanib, based on their baseline clinical characteristics.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16231-e16231
Author(s):  
Veronica Placencio-Hickok ◽  
Marie Lauzon ◽  
Natalie Moshayedi ◽  
Michelle Guan ◽  
Sungjin Kim ◽  
...  

e16231 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with an estimated five-year survival rate of 10%. The dense desmoplastic stroma in PDAC contributes to its aggressive nature and treatment resistance. Among the components comprising the stroma, hyaluronan (HA) has been demonstrated to play a critical role in tumor progression and survival. Previous preliminary studies have suggested differences in HA expression in primary and metastatic foci in PDAC. However, the effects of treatment and location of HA expression as well as the role of CD44, a known receptor for HA, on HA as a biomarker signature remain unknown. Thus, we investigated the potential of HA as a biomarker in primary PDAC and metastases. Methods: PDAC tissue from primary (n = 43) and metastatic (n = 66) sites were obtained from Cedars-Sinai Medical Center along with associated clinical data. Tissue slides were stained with H&E, HA using a histochemical assay, and CD44 by immunohistochemistry. HA staining was scored according to the proportion of stromal staining at an intensity greater than the background stroma. HA status was defined as ≥ 50% staining being HA high and < 50% as being HA low. CD44 staining was recorded as an H-score (percentage of tumor cells staining multiplied by intensity of staining on a scale from 0 to 3). Associations between HA levels and the requested variables were examined with t-test, Wilcoxon rank-sum test, Chi-squared test, Fisher’s exact test, or Cox regression model where appropriate. Kaplan-Meier curves were created to assess progression free survival and overall survival. Analyses were performed using SAS 9.4 with two-sided tests and a significance level of 0.05. Results: HA score was significantly higher in primary PDAC tissue compared to sites of metastases (p = 0.0148). Within the metastases, HA score was significantly higher in liver metastasis compared to other sites of metastasis (p = 0.0478). In the liver metastasis tissue, HA score trended lower in patients with previously treated tissue compared to treatment naïve tissue (p = 0.0622). In the treatment naive liver metastasis cohort, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status (p = 0.0032 and p = 0.0478, respectively). Using HA score and CD44 in a Cox regression model demonstrated that for every one unit increase in HA score, the risk for recurrence/progression increased by 4.4% at any fixed point in time, adjusting for CD44 score (p = 0.0049). Conclusions: HA score is variable between primary PDAC, PDAC metastatic to the liver, and PDAC metastatic to other sites. Within liver metastases, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status. HA levels can serve as a potential biomarker to guide pancreatic cancer treatments and trial design for agents targeting the stroma.


2021 ◽  
pp. 106689692110560
Author(s):  
Hao Cheng ◽  
Chi Yihebali ◽  
Hongtu Zhang ◽  
Lei Guo ◽  
Susheng Shi

Background Synovial sarcoma (SS) is a rare soft tissue sarcoma. Available data regarding survival outcomes of patients with SS still remains limited. In this study, a single center retrospective analysis was performed to investigate the clinical characteristics, pathology and survival outcomes in patients with SS in China. Methods Patient data were systematically reviewed at the National Cancer Center from January 2015 to December 2020. The general information and treatment condition of patients were collected. Overall survival (OS) was evaluated using the Kaplan-Meier and Cox regression method. Results A total of 237 consecutive patients were included in this study (follow-up cut-off date: December, 2020). The median age of patients involved was 35 years (ranging from 5 to 83 years) and the mean tumor diameter was 5.3 cm (ranging from .2 to 26.0 cm). The main findings of the immunohistochemical staining analyses were EMA (111/156) (71%), keratin (32/64) (50.0%), keratin (12/20) (60%), keratin (42/70) (60%), S-100 (18/160) (11%), BCL-2 (128/134) (96%), CD99 (137/148) (93%) and TLE1 (23/26) (88%). It was found that 109 patients (66%) were presented with monophasic subtype and 55 (34%) with biphasic subtype. A total of 137 patients were tested by FISH method and 119 patients (87%) demonstrated SS18 rearrangement, whereas 18 patients (13%) did not show SS18 rearrangement. Generally, it was found that the 3-year OS rate was 86% and the 3-year DFS was 55%. Results of univariate analysis revealed that age, tumor size, tumor site, radiotherapy and targeted therapy were significantly correlated with the overall survival ( P < .05). Further, multivariate Cox regression analysis revealed that age, tumor size and radiotherapy were significantly associated with OS ( P < .05). Conclusions In conclusion, this study shows that the outcomes of patients with SS significantly decrease with age and tumor size. It was evident that radiotherapy is an independent and positive prognostic factor for patients with SS. In addition, it was shown that the prognosis of SS varies with tumor location. For instance, primary tumors in lower extremities have a higher prognosis, whereas tumors located in thorax have a lower prognosis.


2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang

Abstract Background: Lung cancer is one of the most common cancers, with high morbidity and mortality. MiRNAs are proved to play important roles in various human cancers. In our study, we aimed to explore the prognostic value of miR-181 in lung cancerMethods: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the expression level of miR-181 in lung cancer tissues and the paired non-cancerous tissues. The relationship between miR-181 expression and clinicopathologic parameters were analyzed by chi-square test. Kaplan-Meier method with log rank test was applied for overall survival analysis. Furthermore, the Cox regression analyses were performed to evaluate the prognostic value of miR-181 in lung cancer.Results: Down-regulated miR-181 expression was observed in lung cancer tissues (P<0.001), moreover, its expression was significantly correlated with TNM stage (P=0.015) and metastasis (P=0.000). In addition, lung cancer patients with lower miR-181 expression level had poorer overall survival than those with higher expression (log rank test, P=0.011). Cox regression analysis suggested that miR-181 was an independent prognostic factor for lung cancer (HR=1.961, 95%CI=1.135-3.388, P=0.016).Conclusion: MiR-181 may be a tumor suppressor gene in lung cancer, which can predict outcomes for the patients.


2020 ◽  
Vol 10 ◽  
Author(s):  
Akshitkumar M. Mistry ◽  
Nishit Mummareddy ◽  
Sanjana Salwi ◽  
Larry T. Davis ◽  
Rebecca A. Ihrie

ObjectiveTo determine the relationship between survival and glioblastoma distance from the ventricular-subventricular neural stem cell niche (VSVZ).Methods502 pre-operative gadolinium-enhanced, T1-weighted MRIs with glioblastoma retrieved from an institutional dataset (n = 252) and The Cancer Imaging Atlas (n=250) were independently reviewed. The shortest distance from the tumor contrast enhancement to the nearest lateral ventricular wall, the location of the VSVZ, was measured (GBM-VSVZDist). The relationship of GBM-VSVZDist with the proportion of glioblastomas at each distance point and overall survival was explored with a Pearson’s correlation and Cox regression model, respectively, adjusting for the well-established glioblastoma prognosticators.Results244/502 glioblastomas had VSVZ contact. The proportion of non-VSVZ-contacting glioblastomas correlated inversely with GBM-VSVZDist (partial Pearson’s correlation adjusted for tumor volume R=-0.79, p=7.11x10-7). A fit of the Cox regression model adjusted for age at diagnosis, Karnofsky performance status score, post-operative treatment with temozolomide and/or radiotherapy, IDH1/2 mutation status, MGMT promoter methylation status, tumor volume, and extent of resection demonstrated a significantly decreased overall survival only when glioblastoma contacted the VSVZ. Overall survival did not correlate with GBM-VSVZDist.ConclusionsIn the two independent cohorts analyzed, glioblastomas at diagnosis were found in close proximity or in contact with the VSVZ with a proportion that decreased linearly with GBM-VSVZDist. Patient survival was only influenced by the presence or absence of a gadolinium-enhanced glioblastoma contact with the VSVZ. These results may guide analyses to test differential effectiveness of VSVZ radiation in VSVZ-contacting and non-contacting glioblastomas and/or inform patient selection criteria in clinical trials of glioblastoma radiation.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10111-10111
Author(s):  
Santhanam Sundar ◽  
James Price ◽  
Kirsty Clarke ◽  
Thomas Wolfe ◽  
D Thurairasa ◽  
...  

10111 Background: Single fraction radiotherapy (RT) is standard of care for palliation of pain from bone metastases (ASTRO IJROBP 2011 79:965). But costly, complex, multi-fraction RT is quite often used for palliation of symptoms from various organs. Health care costs are burgeoning (ASCO JCO 2012 30: 1715). Costs can be constrained by judiciously reducing use of unnecessary multi-fraction RT in pts with limited life expectancy. But radiation oncologists’ ability to predict survival is inaccurate. (Chow IJROBP 2005 61:870). Hence we assessed clinical utility of Neutrophil Lymphocyte ratio (NLR) - a routinely available biomarker. Methods: 233 patients (pts) undergoing palliative RT over a 3 month at Nottingham University Hospital. Predominant Tumour SITES: Lung 28% Breast 13% Prostate 13% Colorectal 9% Gastro-Oesophageal 5% Myeloma 5% Bladder 5%. Predominant HISTOLOGY: Adenocarcinoma 61% Squamous Cell 14%. NLR available for 158 pts. Results: A NLR of 4.5 was highly predictive of 90-day mortality & overall survival in an unselected real world population. (Table). No survival benefit seen for multi-fraction RT over single fraction RT across all tumour sites. On survival analysis by Cox regression, increased NLR was significant with a hazard ratio of 2.2 (95% CI 1.3 to 3.7) whereas total radiation dose, use of multiple fractions , age, serum haemoglobin, serum albumin & histology were not significant. Conclusions: In palliative care of advanced cancer, for pts with high NLR (>4.5), Single fraction RT should be the standard of care for palliation of symptoms. [Table: see text]


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 242-242 ◽  
Author(s):  
Gustavo Jankilevich ◽  
Luciana Gennari ◽  
Matias Salazar ◽  
Claudio Graziano ◽  
Eduardo Saravia ◽  
...  

242 Background: Tumor stage, Gleason score, PSA, Performance Status have been identified as important predictors of survival in prostate cancer. The Charlson Comorbidity Index (CCI) is a validated score used to stratify patients according to comorbidities. To evaluate the prognostic role of CCI in patients with CPRC. Methods: A retrospective study based on an analysis of medical records of 212 patients with CRPC treated at Durand Hospital between 2010-2015. The CCI was calculated for each patient and a correlation with overall survival was performed. Statistical analysis included univariate analysis and multivariate analysis (Cox regression). Patients were stratified according CCI ≤ 7.6 or ≥ 7.6. Survival analysis was performed using the Kaplan-Meier curve. Results: We analyzed records of 212 patients with prostate cancer, of which 59 were resistant to castration. Median age 69 years, the PFS with androgen blockade was 32.4 months. Patients with CPRC 54% perform chemotherapy as first-line treatment of castration resistance and 46% performed treatment of hormonal manipulation (Enzalutamide or Abiraterone Acetate). Median overall survival of patients with CCI < 7.6 was 75 months versus 62 months for those with CCI > 7.6 HR: 1.19 (1.03 to 1.36) p: 0.01. In multivariate analysis the ICC was an independent predictor of mortality in these patients HR: 1.23 (1.03 to 1.48) p: 0.02. (Table 1) CCI ≤ 7,6 was predictor to subsequent lines in CPRC setting. Gleason score, PS were independent predictors of survival. Conclusions: Based on our results we can consider the CCI as an independent predictor of survival in CPRC patients. CCI could be an useful tool useful to select patients in clinical trial and community settings. [Table: see text]


2021 ◽  
Vol 12 ◽  
Author(s):  
Susu Zheng ◽  
Xiaoying Xie ◽  
Xinkun Guo ◽  
Yanfang Wu ◽  
Guobin Chen ◽  
...  

Pyroptosis is a novel kind of cellular necrosis and shown to be involved in cancer progression. However, the diverse expression, prognosis and associations with immune status of pyroptosis-related genes in Hepatocellular carcinoma (HCC) have yet to be analyzed. Herein, the expression profiles and corresponding clinical characteristics of HCC samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then a pyroptosis-related gene signature was built by applying the least absolute shrinkage and selection operator (LASSO) Cox regression model from the TCGA cohort, while the GEO datasets were applied for verification. Twenty-four pyroptosis-related genes were found to be differentially expressed between HCC and normal samples. A five pyroptosis-related gene signature (GSDME, CASP8, SCAF11, NOD2, CASP6) was constructed according to LASSO Cox regression model. Patients in the low-risk group had better survival rates than those in the high-risk group. The risk score was proved to be an independent prognostic factor for overall survival (OS). The risk score correlated with immune infiltrations and immunotherapy responses. GSEA indicated that endocytosis, ubiquitin mediated proteolysis and regulation of autophagy were enriched in the high-risk group, while drug metabolism cytochrome P450 and tryptophan metabolism were enriched in the low-risk group. In conclusion, our pyroptosis-related gene signature can be used for survival prediction and may also predict the response of immunotherapy.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shuaiqun Wang ◽  
Dalu Yang ◽  
Wei Kong

The autophagy cell, which can inhibit the formation of tumor in the early stage and can promote the development of tumor in the late stage, plays an important role in the development of tumor. Therefore, it has potential significance to explore the influence of autophagy-related genes (AAGs) on the prognosis of hepatocellular carcinoma (HCC). The differentially expressed AAGs are selected from HCC gene expression profile data and clinical data downloaded from the TCGA database, and human autophagy database (HADB). The role of AAGs in HCC is elucidated by GO functional annotation and KEGG pathway enrichment analysis. Combining with clinical data, we selected age, gender, grade, stage, T state, M state, and N state as Cox model indexes to construct the multivariate Cox model and survival curve of Kaplan Meier (KM) was drawn to estimate patients’ survival between high- and low-risk groups. Through an ROC curve drawn by univariate and multivariate Cox regression analysis, we found that seven genes with high expression levels, including HSP90AB1, SQSTM1, RHEB, HDAC1, ATIC, HSPB8, and BIRC5 were associated with poor prognosis of HCC patients. Then the ICGC database is used to verify the reliability and robustness of the model. Therefore, the prognosis model of HCC constructed by autophagy genes might effectively predict the overall survival rate and help to find the best personalized targeted therapy of patients with HCC, which can provide better prognosis for patients.


2020 ◽  
Author(s):  
Xiao-Yan Meng ◽  
Xiu-Ping Zhang ◽  
Hong-Qian Wang ◽  
Weifeng Yu

Abstract Background Whether anesthesia type is associate with the surgical outcome of Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains to be determined. This study aims to investigate the impact of volatile inhalational anesthesia (INHA) versus total IV anesthesia (TIVA) on the survival outcomes in HCC patients with PVTT. Methods A cohort of in-patients whom were diagnosed of HCC with PVTT in Eastern Hepatobiliary Surgery Hospital, Shanghai, China, from January 1, 2008 to December 24, 2012 were identified. Surgical patients receiving the INHA and TIVA were screened out. The overall survival (OS), recurrence-free survival (RFS) and several postoperative adverse events were compared according to anesthesia types. Results A total of 1513 patients were included in this study. After exclusions are applied, 263 patients remain in the INHA group and 208 in the TIVA group. Patients receiving INHA have a lower 5-year overall survival rate than that of patients receiving TIVA [12.6% (95% CI, 9.0 to 17.3) vs. 17.7% (95% CI, 11.3 to 20.8), P=0.024]. Results of multivariable Cox-regression analysis also identify that INHA anesthesia is significantly associated with mortality and cancer recurrence after surgery compare to TIVA, with HR (95%CI) of 1.303 (1.065, 1.595) and 1.265 (1.040, 1.539), respectively. Subgroup analysis suggested that in more severe cancer patients, the worse outcome related to INHA might be more significant. Conclusion This retrospective analysis identifies that TIVA has better survival outcomes compare to INHA in HCC patients with PVTT. Future prospective researches are urgent to verify this difference and figure out underlying causes of it.


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