Clinical significance of CTC enumeration on the Epic Sciences platform in metastatic castration-resistant prostate cancer (mCRPC) patients treated with AR signaling inhibitors (ARSi).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5571-5571
Author(s):  
Joseph Schonhoft ◽  
Audrey Gill ◽  
Ryon P Graf ◽  
Adam Jendrisak ◽  
Ethan Barnett ◽  
...  
Keyword(s):  
Intact Cell ◽  
Prognostic Significance ◽  
Circulating Tumor Cell ◽  
Continuous Variable ◽  
Castration Resistant Prostate Cancer ◽  
Risk Of Death ◽  
Signaling Inhibitors ◽  
Pre Treatment ◽  
Prostate Cancers ◽  
Line Of Therapy

5571 Background: Circulating Tumor Cell (CTC) number, enumerated using the analytically valid FDA cleared Cell Search (Menarini Silicon Biosystems) platform has been shown to be prognostic for survival pre- and post-therapy, and used as an aid to monitoring breast, colorectal and prostate cancers. The assay uses antibody-based capture and defines a CTC as an EpCAM+ and CD45- intact cell. In contrast, with the Epic sciences CTC detection platform red blood cells are first lysed and all nucleated cells deposited on pathology slides, fixed, and imaged. There is no affinity selection and CTCs for this analysis were defined in silico as any cytokeratin (CK)+, CD45- cell with an intact DAPI+ nucleus. Here we report the prognostic significance of the CK+ CTCs detected on the EPIC Sciences platform in mCRPC patients prior to treatment with an AR signaling inhibitor. Methods: A pre-treatment blood sample was collected from 181 unique patients with progressing mCRPC about to start an ARSI as 1st, 2nd or 3rd line therapy at MSKCC. CTCs were enumerated on the Epic Sciences platform and verified by a trained human technician. Results: At least 1 CTC was detected (median = 1, 0-711 CTCs/ml) in 134 (74%) of cases, with higher counts observed in patients with visceral or multiple osseous sites relative to those with lymph node only disease. Counts increased by line of therapy. The table shows the associated risk of death for CTCs modeled as a continuous variable. Conclusions: The results support the clinical validity of CTC number determined on the Epic Sciences platform as a significant baseline prognostic factor. In multivariate modeling CTC number was found to be the most significant blood-based predictor of poor OS with each doubling representing a 20% greater risk of death observed with adjustment for therapy line, LDH, PSA, and ALK. [Table: see text]

Abstract P098: Slower Gait Speed is Associated with Increased Mortality Risk in Chronic Kidney Disease.

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Baback Roshanravan ◽  
Cassiane Robinson-Cohen ◽  
Kushang V Patel ◽  
Greg Levin ◽  
Ian H de Boer ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gait Speed ◽  
Proportional Hazards ◽  
Prognostic Significance ◽  
Continuous Variable ◽  
Hazard Ratio ◽  
Risk Of Death ◽  
Social Security Death Index

Objective: Skeletal muscle dysfunction (sarcopenia) is an under-recognized complication of chronic kidney disease (CKD) that may have important clinical consequences. Gait speed is associated with sarcopenia and comorbid disease burden among older adults; however, little is known about the prognostic significance of gait speed in CKD. We determined the association of gait speed with all-cause mortality in a prospective cohort of non-dialysis CKD patients. Methods: We measured usual gait speed over 4-meters in 309 participants from a prospective study of non-dialysis CKD. Included subjects had an estimated glomerular filtration rate (eGFR ckdepi ) <90mL/min/1.73m 2 , were stroke-free and did not require a wheelchair for ambulation. Study coordinators assessed mortality during follow-up by phone contacts, medical record review, and the social security death index. We evaluated gait speed continuously, and using a cut point of 0.8 m/s, consistent with previous studies. We used Cox's proportional hazards to estimate the association of gait speed with mortality after adjustment for age, sex, race, smoking, diabetes, pre-existing CAD, BMI, eGFR and hemoglobin. Results: Median follow-up time was 2.7 years; range 27 days to 4.8 years. The mean age was 58.9 ± 13 years and mean eGFR by cystatin C (eGFR cysc ) was 48.5 ± 23mL/min/1.73m 2 . There were a total of 31 deaths (10.4%) during follow-up. Unadjusted mortality rates were 23 and 80 deaths per 1,000 person-years among participants who had a gait speed of >0.8m/s versus ≤0.8m/s, respectively. After full adjustment, gait speed ≤0.8m/s was associated with a 2.8-fold greater risk of death compared to a gait speed >0.8 m/s. Gait speed was also strongly associated with mortality when analyzed as a continuous variable ( Table ) and a stronger predictor of death than age, history of CAD, or diabetes. No. Deaths (%) Model 1 + Model 2 # Hazard Ratio 95% CI Hazard Ratio 95% CI Gait speed * 32(10) 0.74 (0.64-0.86) 0.75 (0.64-0.87) >0.8m/s 13 (6) Reference Reference ≤0.8m/s 19(19) 3.49 (1.54-7.95) 2.84 (1.25-6.48) * Gait speed analyzed continuously per 10cm/s increase in speed. +Model 1: Adjusted for age, sex, race, study site #Model 2: adds smoking, BMI, eGFR cysc , diabetes, prevalent coronary disease. Conclusion: Gait speed is strongly associated with death in a cohort of middle-aged CKD patients.

Clinical significance of AR mRNA quantification from circulating tumor cells (CTCs) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone (Abi) or enzalutamide (Enza).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 132-132 ◽  
Author(s):  
John Silberstein ◽  
Brandon Luber ◽  
Hao Wang ◽  
Changxue Lu ◽  
Yan Chen ◽  
...  
Keyword(s):  
Cox Regression ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Continuous Variable ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Mrna Quantification ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Psa Progression

132 Background: AR-targeting agents remain the backbone of mCRPC therapy. We previously reported an association between AR-V7 mRNA detection in CTCs and resistance to Abi/Enza (NEJM 2014). Here, we report the prognostic significance of full-length androgen receptor (AR-FL) mRNA quantification from CTCs in pts starting Abi or Enza. Methods: We prospectively enrolled mCRPC pts starting Abi or Enza, and examined the prognostic value of AR-FL detection using a CTC-based mRNA assay (modified AdnaTest, Qiagen). We examined PSA50 responses, PSA progression free survival (PSA-PFS), clinical/radiologic PFS (PFS), and overall survival (OS). We constructed multivariable (MVA) Cox regression models adjusting for AR-V7 status, PSA level, Gleason sum, number of prior therapies, prior Abi/Enza use, prior taxane use, presence of visceral disease, and ECOG score. Results: We enrolled 202 pts (median f/u 12.9 mo). AR-FL status was negative in 97/202 pts (48%), < median in 52/202 (26%) and > median in 53/202 (26%). Higher AR-FL levels correlated with positive AR-V7 detection (35.5 copies [range: 2.5–1209] in AR-V7+ vs 1.4 copies [range: 0–172.5] in AR-V7–, P< .001), as well as lower PSA50 responses (55.4 copies in nonresponders vs 6.7 copies in responders, P< .001). In Kaplan-Meier analysis, PSA-PFS, PFS and OS differed significantly between AR-FL negative, AR-FL < median, and AR-FL > median (Table). In MVA models, AR-FL level (as a continuous variable) was prognostic for PSA-PFS (HR 1.06, 95%CI 1.00–1.12, P= .04) and trended with prognosis for PFS (HR 1.04, 95%CI 0.99–1.11, P= .13) and OS (HR 1.07, 95%CI 1.00–1.15, P= .06). AR-V7 status was also independently prognostic for all outcomes in MVA analyses. Conclusions: This study demonstrates CTC-derived AR-FL copy number is prognostic for clinical outcomes in Abi/Enza-treated mCRPC pts. In addition to AR-V7 status, AR-FL quantification could serve as another molecular biomarker of Abi/Enza sensitivity after analytical validation/standardization. [Table: see text]

Validation of nuclear-localized AR-V7 on circulating tumor cells (CTC) as a treatment-selection biomarker for managing metastatic castration-resistant prostate cancer (mCRPC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 273-273 ◽  
Author(s):  
Howard I. Scher ◽  
Ryon P Graf ◽  
Nicole A. Schreiber ◽  
Eric Winquist ◽  
Brigit McLaughlin ◽  
...  
Keyword(s):  
Decision Making ◽  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Castration Resistant Prostate Cancer ◽  
Cross Sectional ◽  
Risk Of Death ◽  
Physician Decision Making ◽  
Line Of Therapy ◽  
Taxane Chemotherapy

273 Background: A previous analysis of 161 patients (pts) tested for nuclear-localized AR-V7(+) CTCs showed a therapy interaction between AR-V7 positivity and improved overall survival (OS) on taxane chemotherapy vs. androgen receptor signaling inhibitors (ARSI). To validate the use of the biomarker result for physician decision making, we prospectively analyzed an independent, multicenter, blinded, cross-sectional cohort (n = 225) to confirm a therapy interaction with AR-V7. We corrected for possible pt selection bias by the treating physician by analyzing the association of therapy to OS in low and high risk groups defined by the test cohort. Methods: Two analyses were performed: (1) the validation of a therapy interaction between AR-V7 positivity and superior OS benefit for pts treated with taxanes in the context of use for 2nd+ line pts; and (2) as the choice between ARSI or taxanes was at the discretion of the attending physician, pt risk was incorporated into the predictive biomarker assessment. A pt-specific risk score was developed from line of therapy and other covariates to stratify pts as low and high risk, and the association of AR-V7 status and OS was performed within each risk group to correct for physician decision making and address possible confounding with treatment assignment. Results: (1) A therapy interaction between AR-V7(+) pts and lower risk of death on taxanes vs. ARSI (HR: 0.23, p = 0.003, 95% CI: 0.09 – 0.61) was validated. (2) In the validation cohort, high risk AR-V7(+) pts had an OS benefit when treated with taxanes (p = 0.02) and the AR-V7(-) pts had an improved OS with ARSI therapy (p = 0.02). AR-V7 incidence was low in the low risk pts, precluding the analysis for this sub-cohort. Conclusions: The results validate that the nuclear-localized AR-V7(+) biomarker has an interaction with therapy and improved survival on taxanes. Further, when adjusting for pt risk, the biomarker is predictive of OS in the high risk group. Nuclear-localized AR-V7 protein in CTCs can aid in the decision between ARSI and taxane chemotherapy in the 2nd or greater line of therapy for mCRPC.

Evaluating the prognostic significance of significant weight loss in patients with stage III non-small cell lung cancer (NSCLC) undergoing definitive chemoradiation (CRT) after FDG-PET staging.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20045-e20045
Author(s):  
Clare Senko ◽  
Julie Moore ◽  
Karen Hay ◽  
Zarnie Lwin ◽  
Gary Pratt ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Fdg Pet ◽  
Prognostic Significance ◽  
Stage Iii ◽  
Risk Of Death ◽  
Retrospective Audit ◽  
Increased Risk ◽  
Stage Iii Nsclc ◽  
Pre Treatment

e20045 Background: In the pre-PET era, weight loss is a harbinger of occult metastatic disease in patients with stage III NSCLC. Identifying the relationship between weight loss and pattern of relapse (POR), may enable stratification of patients into prognostic groups associated with increased risk of relapse. We sought to identify if weight loss remains a negative independent prognostic factor after FDG-PET staging. Methods: A retrospective audit (using web-based and electronic databases) was conducted in all patients with stage III NSCLC treated with definitive CRT between 01/07/2013 and 30/06/2018 at the Royal Brisbane and Women’s Hospital and The Prince Charles Hospital, Queensland, Australia. A descriptive analysis was applied to describe the primary end-point of PFS and secondary end-points of OS and POR, in relation to the percentage of pre-treatment weight loss (0-10% vs > 10-20% vs > 20%). A subset analysis looked at other prognostic factors identified in NSCLC to account for potential confounders. Results: Of the 127 patients (mean age 65 years, mean weight 76kg, 57% male, 42% current smokers) who commenced treatment during the study period, 24% lost > 10% and 3% lost > 20% weight. Median TTP for the entire cohort was 9 months. Based on multivariable modelling, risk of PD or death was 45% higher with > 10% loss of body weight (p = 0.004), and risk of death was 36% higher with > 10% of body weight (p = 0.05). Of the 54% that died during follow-up, 31 had distant PD, 18 had locoregional PD, 6 had local PD, and 10 had no PD. Males were at increased risk of PD. Conclusions: A prognostic link continues to be identified between significant (> 10%) weight loss and risk of progressive disease or death in stage III NSCLC treated with definitive CRT despite pre-treatment FDG-PET. These findings identify a sub-group of patients where weight loss could still be a surrogate for micro-metastases not detected on PET, or other adverse prognostic markers. Other treatment strategies or improved diagnostic strategies are warranted.

Development and validation of circulating tumor cell (Epic Sciences) enumeration as a prognostic biomarker in men with metastatic castration-resistant prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 157-157
Author(s):  
Howard I. Scher ◽  
Andrew J. Armstrong ◽  
Joseph D. Schonhoft ◽  
Audrey Gill ◽  
Jimmy Zhao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cell ◽  
Validation Cohort ◽  
Prognostic Significance ◽  
Circulating Tumor Cell ◽  
Cancer Center ◽  
Significant Prognostic Factor ◽  
Castration Resistant Prostate Cancer ◽  
Discovery Cohort ◽  
Castration Resistant

157 Background: We evaluated the prognostic significance of circulating tumor cell (CTC) number as determined on the Epic Sciences platform in men with metastatic castration resistant prostate cancer (mCRPC) treated with an androgen receptor signaling inhibitor (ARSI). Methods: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a 1st, 2nd or 3rd line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N=175) or as a 1st and 2nd line therapy as part of the multi-center PROPHECY trial (NCT02269982) (Validation cohort, N=107). Enumeration was performed on the Epic Sciences platform and associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. Matched blood samples from the Validation cohort were to CTC counts measured on the CellSearch Circulating Tumor Cell kit. Results: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (< 3 CTCs/mL versus ≥ 3 CTCs/mL; HR = 1.8, (1.3-3.0, 95% CI)) and as a continuous variable when adjusting for line of therapy, presence of visceral metastases, PSA, lactate-dehydrogenase, and alkaline-phosphatase. The findings were validated in an independent dataset (PROPHECY trial) - (HR (95% CI) = 1.8, (1.1-3.0) for OS and 1.7 (1.1-2.9), for PFS). A strong correlation was observed between CTC counts determined in matched samples on the CellSearch and Epic platforms (r = 0.84). Conclusions: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.

Association of plasma tumor DNA (ptDNA) with increased risk of venous thromboembolism (VTE) in metastatic castration resistant prostate cancer patients (mCRPC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5048-5048
Author(s):  
Vincenza Conteduca ◽  
Emanuela Scarpi ◽  
Daniel Wetterskog ◽  
Fabio Ferroni ◽  
Alice Rossi ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Serum Lactate ◽  
Serum Lactate Dehydrogenase ◽  
Castration Resistant Prostate Cancer ◽  
Targeted Next Generation Sequencing ◽  
Castration Resistant ◽  
Increased Risk ◽  
Significant Difference ◽  
Signaling Inhibitors ◽  
Pre Treatment

5048 Background: Cancer is a risk factor for VTE. In mCRPC, ptDNA is an independent predictor of outcome ( Romanel, Sci Transl Med 2015; Conteduca, Br J Cancer 2020). We firstly aimed to investigate the association between ptDNA and VTE in mCRPC men treated with androgen receptor signaling inhibitors (ARSI) Methods: This prospective biomarker study included mCRPC patients treated with abiraterone and enzalutamide from April 2013 to December 2018. We excluded patients with a previous VTE history and/or ongoing anticoagulation. Targeted next-generation sequencing was performed to determine ptDNA fraction from pre-treatment plasma samples. Assessment of VTE risk based on survival analysis was performed using cumulative incidence function and estimating sub-distributional hazard ratio (SHR) Results: Median age of 180 enrolled patients was 74 years (range 42-90). Of these, 60 (33.3%) were chemotherapy-naive. At a median follow-up of 58 months (range 0.5-111.0), 21 patients experienced VTE (venous thrombosis and/or pulmonary embolism) with a cumulative incidence of VTE at 12 months of 17.1% (95% CI 10.3-23.9). Before starting ARSI, ptDNA fraction above median value of 0.175, presence of visceral metastasis (mets), prior chemotherapy and serum lactate dehydrogenase (LDH) were significantly associated with higher incidence of VTE compared with patients with no thrombosis (12-month estimate, 18.6 vs 3.5%, P=0.0003; 44.4 vs 14.8%, P=0.015; 24.7 vs 4.5%, P=0.006; and 30.0 vs 13.5%, P=0.050, respectively). In the multivariate analysis (Table) including baseline ptDNA level, visceral, liver and lung mets, number of lesions, LDH, high ptDNA fraction was the only independent factor associated with the risk of thrombosis (HR 5.78, 95% confidence interval [CI] 1.63-20.44, P=0.006). All these patients received anticoagulant therapy for VTE. No ARSI discontinuation and VTE-related death were reported, and no significant difference in progression-free/overall survival was observed in mCRPC patients with and without VTE. Conclusions: These results suggest that baseline ptDNA fraction in mCRPC patients treated with ARSI is associated with increased risk of VTE. These patients may be followed up more closely for the risk of VTE and the need for a primary thromboprophylaxis should be taken into account in mCRPC with elevated ptDNA concentration. Validation of these findings in larger multicenter trials is warranted.[Table: see text]

Pilot study of anti-prostate-specific membrane antigen (PSMA) antibody J591 for men with metastatic castration-resistant prostate cancer (mCRPC) and unfavorable circulating tumor cell (CTC) count.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 120-120
Author(s):  
Justin M Lebenthal ◽  
Michael Sun ◽  
Jones T. Nauseef ◽  
Muhammad Junaid Niaz ◽  
Dunya Imad ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Single Agent ◽  
Circulating Tumor Cell ◽  
Post Treatment ◽  
Risk Category ◽  
Castration Resistant Prostate Cancer ◽  
Psma Pet ◽  
Pre Treatment ◽  
Ecog Ps ◽  
A Prospective Study

120 Background: Elevated CTC counts are associated with a poor prognosis in men with mCRPC. PSMA targeted radionuclide therapy has been associated with decline in CTC count, but it remains unclear whether this effect results from radionuclide-induced cytotoxicity. J591 was engineered to have antibody-dependent cytotoxicity. A subset of patients was observed to have CTC count decline following imaging with 111In-J591, so a prospective study was launched to test the hypothesis that “naked” J591 leads to CTC count decline. Methods: In a Simon 2-stage dose de-escalation study, men with progressive mCRPC and unfavorable CTC count (CellSearch > 4) received a single dose of J591. Initial dose cohort 300 mg with de-escalation to 20 mg. CTC count was re-assessed 4, 8, and 12 weeks following therapy along with PSA and standard imaging. An optional PSMA PET was included prior to treatment. The primary endpoint was proportion of subjects with conversion to favorable CTC count ( < 5 CTCs/7.5 mL blood) and/or > 30% decline from baseline within 12 weeks post-treatment. Results: 10 men were enrolled, 9 of whom were evaluable (1 died of progressive mCRPC prior to post-treatment CTC count). Median age was 71.5 years (range 60-81), 78% had prior chemo, ECOG PS 1 in 45% and 2 in 55%. 7 of 9 (78%) evaluable subjects were Halabi CALGB prognostic poor risk category and 2 (22%) intermediate. 6 of 9 had pre-treatment PSMA PET/CT (three 89Zr-J591 and three 68Ga-PSMA11). Though not required, all scans showed > 1 lesion with SUVmax > liver SUV (range 9.12-70.15). 2 of 6 in the 300 mg cohort had CTC count decline; 1 of 6 converted to favorable count (9 to 0 with decrease of 35 to 12 in other). 3 were treated with 20 mg; 1 had CTC count decline of 316 to 112, but 0 converted to favorable count. Across both cohorts, 3 of 9 had a CTC count decline at any point in time, ranging from 65-100% decline. With the pre-specified 2-stage design, enrollment was halted for futility based upon the primary endpoint of 12-week CTC count. PSA values post-treatment increased in 8 (89%) patients and remained unchanged in 1 (11%) patient. Conclusions: Single-agent anti-PSMA antibody J591 may lead to decline in CTC count, though the study did not meet its primary endpoint. A combination or maintenance approach might be preferable and is worthy of exploration.

Evaluation of clinical phenotype, survival, and circulating tumor cell (CTC) enumeration in men with metastatic castration-resistant prostate cancer (mCRPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5031-5031 ◽  
Author(s):  
Rhonda Lynn Bitting ◽  
Patrick Healy ◽  
Susan Halabi ◽  
Daniel J. George ◽  
Jung Hyun Ko ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Specific Antigen ◽  
Circulating Tumor Cell ◽  
Tumor Burden ◽  
Castration Resistant Prostate Cancer ◽  
Bone Microenvironment ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Androgen Receptor Activity ◽  
The Relationship

5031 Background: The presence of ≥ 5 CTCs is prognostic for shorter survival in mCRPC men. However, many men have low CTCs despite widespread metastatic disease, suggesting heterogeneity in CTC phenotype or detection. We evaluated the association of baseline CTC enumeration with clinical characteristics and survival in mCRPC men at our institution. Methods: CTCs were enumerated with the standard CellSearch method in mCRPC men in a prospective correlative clinical study. The association between baseline CTC count and prostate-specific antigen (PSA), alkaline phosphatase (AP), lactate dehydrogenase (LDH) was explored using the Spearman correlation (r), and the relationship with Gleason sum, sites of metastasis (mets), and prior docetaxel exposure was explored using summary statistics. The overall survival probability (OS) was estimated by the Kaplan-Meier method. Results: In our cohort, 59/82 men had prior docetaxel exposure, and the median CTC count was 16.5. There were 25 men with visceral mets, 55 with bone-predominant mets, and 2 with lymph node only mets. We found a weak relationship between CTCs and PSA (r=0.20), but a more moderate and significant association with AP (r=0.48) and LDH (r= 0.50). We found no relationship between CTCs and Gleason sum, site of mets, or prior docetaxel. 66 men died, and the median OS was 11.2 months (95% CI: 9.2, 12.7). OS was improved in patients with <5 CTCs at baseline compared to ≥ 5 (8.9 vs. 16.6 months, HR=0.47 (95% CI: 0.27, 0.80)). CTC enumeration may further stratify outcomes in men with mCRPC and either visceral or bone metastasis as shown in the table below. Conclusions: The prognostic significance of CTCs is distinct from other established biomarkers and may reflect a unique biology of metastasis, dissociated in part from androgen receptor activity (as reflected by PSA values) but related in part to bone microenvironment, hypoxia, and tumor burden (as reflected by AP and LDH values). These associations need to be validated in larger trials. [Table: see text]

scholarly journals Prognostic Significance of Pre-treatment Serum Inflammatory Biomarkers on Survival in Patients with Carcinoma Cervix Treated by Radical Radiotherapy or Chemo-radiation

2021 ◽  
Vol 6 (4) ◽  
pp. 417-423
Author(s):  
Lekha Madhavan Nair ◽  
Aneesha Babu ◽  
Jagathnath Krishna K M ◽  
Aswin Kumar ◽  
Susan Mathews ◽  
...  
Keyword(s):  
Serum Albumin ◽  
Prognostic Significance ◽  
Significant Risk ◽  
Inflammatory Biomarkers ◽  
Carcinoma Cervix ◽  
Albumin Ratio ◽  
Lymphocyte Ratio ◽  
Risk Of Death ◽  
Pre Treatment ◽  
Risk Of Relapse

Background: Inflammation has an important role in the initiation and progression of carcinoma cervix. The measurement of inflammatory biomarkers is a cost-effective method of identifying patients at high risk of recurrence after treatment. This study was done to identify the influence of pre-treatment inflammatory biomarkers on survival in patients treated with radical chemo-radiation or radiation. Methods: Patients with biopsy proven carcinoma cervix treated with Radiotherapy or Chemo-radiation from January 1st, 2016 to September 30th, 2017 were included. Pre-treatment complete blood counts, differential counts, serum albumin and C-reactive protein (CRP) were obtained. Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and CRP Albumin ratio (CAR) were calculated. The best cut off values for NLR, PLR, serum albumin, CRP and CAR were found out from receiver operating characteristic (ROC) curves. OS (Overall Survival) and DFS (Disease Free Survival) were estimated using Kaplan -Meier method. The prognostic value of inflammatory biomarkers on survival was assessed by cox regression model. Results: Sixty-three patients were included. The median follow up was 42.5 months. The best cut off values for NLR, PLR, albumin, CRP and CAR from the ROC curve were 2.36, 122.725, 3.95, 0.65 and 0.8 respectively. The three-year OS and DFS probability were 68.3% and 63.5% respectively. Patients with CAR >0.8 had 5.7 times more risk of death and 6.01 times risk of relapse or progression compared to patients with CAR ≤0.8. Conclusion: Patients with a CRP-Albumin ratio of more than 0.8 are at significant risk of relapse and death after chemoradiation or radiation.

scholarly journals Value of Early Circulating Tumor Cells Dynamics to Estimate Docetaxel Benefit in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2334
Author(s):  
Rebeca Lozano ◽  
David Lorente ◽  
Isabel M. Aragon ◽  
Nuria Romero-Laorden ◽  
Paz Nombela ◽  
...  
Keyword(s):  
Cox Regression ◽  
Progression Free Survival ◽  
Circulating Tumor Cell ◽  
Pooled Analysis ◽  
Post Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Improved Outcomes ◽  
Signaling Inhibitors ◽  
Psa Response ◽  
Psa Progression

Circulating tumor cell (CTC) enumeration and changes following treatment have been demonstrated to be superior to PSA response in determining mCRPC outcome in patients receiving AR signaling inhibitors but not taxanes. We carried out a pooled analysis of two prospective studies in mCRPC patients treated with docetaxel. CTCs were measured at baseline and 3–6 weeks post treatment initiation. Cox regression models were constructed to compare 6-month radiographical progression-free survival (rPFS), CTCs and PSA changes predicting outcome. Among the subjects, 80 and 52 patients had evaluable baseline and post-treatment CTC counts, respectively. A significant association of higher baseline CTC count with worse overall survival (OS), PFS and time to PSA progression (TTPP) was observed. While CTC response at 3–6 weeks (CTC conversion (from ≥5 to <5 CTCs), CTC30 (≥30% decline in CTC) or CTC0 (decline to 0 CTC)) and 6-month rPFS were significantly associated with OS (all p < 0.005), the association was not significant for PSA30 or PSA50 response. CTC and PSA response were discordant in over 50% of cases, with outcome driven by CTC response in these patients. The c-index values for OS were superior for early CTC changes compared to PSA response endpoints, and similar to 6-month rPFS. Early CTC declines were good predictors of improved outcomes in mCRPC patients treated with docetaxel in this small study, offering a superior and/or earlier estimation of docetaxel benefit in comparison to PSA or rPFS that merits further confirmation in larger studies.

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