cfDNA TP53 mutations with treatment history and disease progression in metastatic CRPC.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 263-263
Author(s):  
Lynne Chapman ◽  
Elisa Ledet ◽  
Marcus Marie Moses ◽  
Ashkan Shahbandi ◽  
Peter Steinwald ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Targeted Therapy ◽  
Disease Progression ◽  
Prognostic Significance ◽  
Treatment Resistance ◽  
Individual Sample ◽  
Tp53 Mutations ◽  
Treatment History ◽  
Free Dna ◽  
Brca2 Mutations

263 Background: Cell free DNA (cfDNA) has made it possible to actively monitor alterations of genes during the course of therapy. Herein we evaluate cfDNA pathologic mutations in TP53 after treatment resistance to AR targeted therapy and taxanes in mCRPC. In addition to the presence or absence of pathologic mutations, the quantity of the mutations was characterized as present/absent, quantitatively as > or < 1%, or >or <10%. Methods: A retrospective study was done for 111 patients, with 226 separate cfDNA testing dates. Each cfDNA test was treated as an individual sample; of the 226 tests, 112 were positive for pathologic TP53 mutations, and 114 were negative. Treatment histories were collected and TP53 data analyzed in relation to resistance for abiraterone (abi), enzalutamide (enza), abi + enza, or abi + enza and a taxane. Treatment resistance was categorized as being present for those patients completing therapy with an agent. Results: Patients with pathologic TP53 mutations were more likely to have had progression after a novel hormone and a taxane (P = 0.005). Higher concentrations of TP53 mutational loads as measured by cfDNA concentration of >1% and >10% were more likely to be present in patients progressing after a taxane, abi, and enza. Common alterations associated with TP53 included AR amplifications and mutations, MYC amplifications, and BRCA2 mutations. Conclusions: TP53 mutations in cfDNA of mCRPC are progressively more likely to be present in patients, especially after patients receiving both taxanes and a novel hormonal agent. The predictive and prognostic significance of these changes are being further evaluated.[Table: see text]

Predictive value of clinical and MRI parameters for disease progression in multiple sclerosis – a longitudinal retrospective study

2009 ◽  
Vol 36 (S 02) ◽  
Author(s):  
A Hahn ◽  
T Schmidt-Wilcke ◽  
S Prügl ◽  
G Schuierer ◽  
U Bogdahn ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Retrospective Study ◽  
Disease Progression ◽  
Predictive Value

scholarly journals Prognostic significance of peritoneal cytology in low-risk endometrial cancer: comparison of laparoscopic surgery and laparotomy

2021 ◽  
Author(s):  
Satoe Fujiwara ◽  
Ruri Nishie ◽  
Shoko Ueda ◽  
Syunsuke Miyamoto ◽  
Shinichi Terada ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Laparoscopic Surgery ◽  
Retrospective Study ◽  
Prognostic Significance ◽  
Low Risk ◽  
Peritoneal Cytology ◽  
Chi Square ◽  
Significant Difference ◽  
Chi Square Test ◽  
Positive Peritoneal Cytology

Abstract Background There is uncertainty surrounding the prognostic value of peritoneal cytology in low-risk endometrial cancer, especially in laparoscopic surgery. The objective of this retrospective study is to determine the prognostic significance of positive peritoneal cytology among patients with low-risk endometrial cancer and to compare it between laparoscopic surgery and conventional laparotomy. Methods From August 2008 to December 2019, all cases of pathologically confirmed stage IA grade 1 or 2 endometrial cancer were reviewed at Osaka Medical College. Statistical analyses used the Chi-square test and the Kaplan–Meier log rank. Results A total of 478 patients were identified: 438 with negative peritoneal cytology (232 who underwent laparotomy and 206 who undertook laparoscopic surgery) and 40 with positive peritoneal cytology (20 who underwent laparotomy and 20 who received laparoscopic surgery). Survival was significantly worse among patients with positive peritoneal cytology compared to patients with negative peritoneal cytology. However, there was no significant difference among patients with negative or positive peritoneal cytology between laparoscopic surgery and laparotomy. Conclusion This retrospective study suggests that, while peritoneal cytology is an independent risk factor in patients with low-risk endometrial cancer, laparoscopic surgery does not influence the survival outcome when compared to laparotomy.

Prognostic significance of K- ras and TP53 mutations in the role of adjuvant chemotherapy on survival in patients with dukes C colon cancer

2001 ◽  
Vol 44 (3) ◽  
pp. 358-363 ◽  
Author(s):  
W. A. Bleeker ◽  
V. M. Hayes ◽  
A. Karrenbeld ◽  
R. M. W. Hofstra ◽  
E. Verlind ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Significance ◽  
Tp53 Mutations ◽  
Dukes C

COMPARISON OF CLINICOPATHOLOGICAL PARAMETERS WITH HISTOLOGICAL AND MOLECULAR CLASSIFICATION OF BREAST CANCERS

2021 ◽  
pp. 144-149
Author(s):  
K. Indumathi ◽  
E. Theranirajan ◽  
G. Bhavani
Keyword(s):  
Retrospective Study ◽  
Targeted Therapy ◽  
Tertiary Care ◽  
Radical Mastectomy ◽  
Immunohistochemical Method ◽  
Proliferation Index ◽  
Clinicopathological Parameters ◽  
P Value ◽  
Luminal B ◽  
Classi Cation

BACKGROUND: This is a retrospective study of 60 cases, to detect the expression of ER, PR, HER2neu, CK5/6 and Ki67 proliferation index in breast carcinomas by immunohistochemical method and to determine the newer molecular classication. Few patients have recurrence inspite of being diagnosed under the category of low risk and few do well in the high risk group which can be attributed to the molecular level differentiation. AIM: The aim of this study is to categorize the patients under molecular classication, and to compare the clinicopathological parameters with it and to denote the signicance of targeted therapy. MATERIALS AND METHODS: A retrospective study of detecting the expression of the above said markers in modied radical mastectomy specimens received at a tertiary care centre during the period from January 2015 to June 2018. A total of 60 cases which included 30 of IDC NST and 30 cases of special variants were selected for immunohistochemical analysis. RESULTS: Out of the 60 cases studied, the most common was found to be the luminal A type comprising 37% and the least common was the luminal B and hybrid types each comprising 8%. The most common grade for HER2 was Grade III (50%). The association of histological grade with the molecular classication was statistically signicant with the p value of 0.01. Basal type (56%) had the highest incidence of N3 stage. ER, PR, HER2 neu, CK5/6 expression and proliferation index with Ki67 had a statistically signicant association with the molecular classication. High proliferation index (>14%) with Ki67 was noted in Luminal B, Basal and Hybrid types. 78% of the total 60 cases were alive and healthy. One death was reported in HER2, Hybrid and Basal types. The negative kappa value obtained while studying the agreement between the histopathological and molecular classication, indicates that the agreement is worse than chance and hence the importance of molecular classication is substantiated for the targeted therapy.

Cabozantinib versus placebo in patients with radioiodine-refractory differentiated thyroid cancer who have progressed after prior VEGFR-targeted therapy: Results from the phase 3 COSMIC-311 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6001-6001
Author(s):  
Marcia S. Brose ◽  
Bruce Robinson ◽  
Steven I. Sherman ◽  
Barbara Jarzab ◽  
Chia-Chi Lin ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Disease Progression ◽  
Differentiated Thyroid Cancer ◽  
Statistical Significance ◽  
Phase 1 ◽  
Objective Response ◽  
Standard Of Care ◽  
Clinical Activity ◽  
Phase 3

6001 Background: Cabozantinib (C), an inhibitor of VEGFR2, MET, AXL, and RET, showed clinical activity in patients (pts) with radioiodine (RAI)-refractory differentiated thyroid cancer (DTC) in phase 1/2 studies (Cabanillas 2017; Brose 2018). This phase 3 study (NCT03690388) evaluated the efficacy and safety of C vs placebo (P) in pts with RAI-refractory DTC who had progressed during/after prior VEGFR-targeted therapy for whom there is no standard of care. Methods: In this double-blind, phase 3 trial, pts were randomized 2:1 to receive C (60 mg QD) or P, stratified by prior lenvatinib treatment (L; yes, no) and age (≤65, > 65 yr). Pts with RAI-refractory DTC must have received L or sorafenib for DTC and progressed during or following treatment with ≤ 2 prior VEGFR inhibitors. Pts randomized to P could cross over to open-label C upon disease progression per blinded independent radiology committee (BIRC). The primary endpoints were objective response rate (ORR) in the first 100 randomized pts and progression-free survival (PFS) in all randomized pts. PFS and ORR were assessed by BIRC per RECIST v1.1. The study was designed to detect an ORR for C vs P (2-sided α = 0.01) and a hazard ratio (HR) for PFS of 0.61 (90% power, 2-sided α = 0.04). A prespecified interim PFS analysis was planned for the ITT population at the time of the primary ORR analysis. Results: As of 19 Aug 2020,125 vs 62 pts had been randomized to the C and P arms, respectively; median age was 66 yr, 55% were female and 63% received prior L. Median (m) follow-up was 6.2 months (mo). At the planned interim analysis, the trial met the primary endpoint of PFS with C demonstrating significant improvement over P (HR 0.22, 96% CI 0.13–0.36; p < 0.0001). mPFS was not reached for C vs 1.9 mo for P; PFS benefit was observed in all prespecified subgroups including prior L (yes, HR 0.26; no, HR 0.11) and age (≤65 yr, HR 0.16; > 65 yr, HR 0.31). ORR was 15% for C vs 0% for P (p = 0.0281) but did not meet the prespecified criteria for statistical significance (p < 0.01). A favorable OS trend was observed for C vs P (HR 0.54, 95% CI 0.27–1.11). Treatment-emergent adverse events (AEs) of any grade with higher occurrences in the C vs P arm included diarrhea (51% vs 3%), hand-foot skin reaction (46% vs 0%), hypertension (28% vs 5%), fatigue (27% vs 8%), and nausea (24% vs 2%); grade 3/4 AEs were experienced by 57% of pts with C vs 26% with P. Dose reductions due to any grade AEs occurred in 57% of pts with C vs 5% with P. Treatment discontinuations due to AEs not related to disease progression occurred in 5% of pts with C vs 0% with P. No treatment-related deaths occurred in either arm. Conclusions: C showed a clinically and statistically significant improvement in PFS over P in pts with RAI-refractory DTC after prior VEGFR-targeted therapy with no unexpected toxicities. C may represent a new standard of care in pts with previously treated DTC. Clinical trial information: NCT03690388.

Prognostic significance of blood-based multi-cancer detection in plasma cell-free DNA

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Oscar D. Pons-Belda ◽  
Amaia Fernandez-Uriarte ◽  
Annie Ren ◽  
Eleftherios P. Diamandis
Keyword(s):  
Plasma Cell ◽  
Cancer Detection ◽  
Prognostic Significance ◽  
Cell Free Dna ◽  
Free Dna

Abstract P550: High Uric Acid Levels Correlate With Treatment- Resistant Hypertension

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Badhma Valaiyapathi ◽  
Mohammed Siddiqui ◽  
Suzanne Oparil ◽  
David A Calhoun ◽  
Tanja Dudenbostel
Keyword(s):  
Uric Acid ◽  
Retrospective Study ◽  
Resistant Hypertension ◽  
Missing Values ◽  
Antihypertensive Agents ◽  
Treatment Resistance ◽  
Patient Characteristics ◽  
Control Group ◽  
Increased Risk ◽  
The University

Background: Serum uric acid (sUA) levels have been found to be positively associated with increased risk of hypertension (HTN), independent of other cardiovascular risk factors. The role of sUA elevation in patients with resistant hypertension (RHTN) is unknown. We hypothesized that sUA levels are higher in RHTN patients compared to patients with controlled HTN. Methods: This retrospective study included, 140 patients from the University of Alabama at Birmingham Hypertension Clinic. Patient characteristics including body mass index (BMI), office blood pressure (BP) and sUA levels were analyzed. RHTN was defined as office BP > 140/90 mmHg on ≥ 3 or more different antihypertensive agents including a diuretic. Patients with RHTN were compared with a control group with controlled hypertension. Patients with sUA levels <3 mg/dl, who were on treatment with allopurinol, and those with missing values were excluded from the study. Results: Patient characteristics of 91 included patients were: 53.4% female, 40.7% African American, mean age 58.8 ± 12.4 years, mean BMI 33.1 ± 7.5 kg/m 2 , mean sUA 6.6 ± 1.9 mg/dL. Mean sUA was higher among RHTN patients compared to the control group (p = 0.0031). Treatment resistance was found to be strongly correlated with sUA levels of ≥ 6 mg/dl (p = 0.0065). Conclusion: In this retrospective study, sUA levels were found to be significantly higher among resistant HTN patients compared to controlled HTN patients, indicating that high sUA levels (≥ 6 mg/dl) may play a role in treatment resistance among hypertensive patients.

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