Prognostic significance of blood-based cancer detection in plasma cell-free DNA (cfDNA): Evaluating risk of overdiagnosis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1545-1545
Author(s):  
Geoffrey R. Oxnard ◽  
Xiaoji Chen ◽  
Eric T. Fung ◽  
Ting Ma ◽  
Jafi Lipson ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Diagnostic Method ◽  
Proportional Hazards ◽  
Multivariate Analyses ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Cox Proportional Hazards ◽  
Screening Tests ◽  
Screening Methods ◽  
Test Set

1545 Background: Screening tests for early cancer detection are often criticized due to risk of overdiagnosis—detection of good prognosis cancers which may not require immediate treatment. We recently reported development of cfDNA sequencing approaches for cancer detection; longitudinal follow-up (F/U) data were utilized here to evaluate prognostic significance of cancer detection using cfDNA. Methods: Plasma cfDNA samples were subjected to whole-genome bisulfite sequencing (WGBS, 30X) as part of a previously-reported Circulating Cell-free Genome Atlas (CCGA; NCT02889978) substudy. This exploratory analysis evaluated the overall survival (OS) of training and test set participants (pts) with cancer (20 cancer types, any stage I-IV). Combining train and test set pts, univariate and multivariate analyses (Cox proportional hazards) assessed OS association with WGBS result (cancer detected vs not detected, set at 98% specificity), clinical stage (IV vs I-III), diagnostic method (symptom- vs screen-detected), sex, age, and histologic grade. Results: Of 827 pts from the training set with F/U (median 12.2 mo), 334 (40.4%) had WGBS-detected cancer. Among 127 (15.4%) pts with cancer that died during F/U, cancer was detected in 104 (81.9%). Results were similar in the test set. In univariate analyses all variables were associated with prognosis, including WGBS result (HR 7.7 p<0.001). In multivariate analyses accounting for other covariates, the three variables that most significantly remained prognostic were WGBS (HR 3.0, p<0.001), clinical stage (HR 3.3, p<0.001), and diagnostic method (HR 3.0, p<0.001). Validation of these findings is ongoing in an independent cohort of ~5,000 cancer pts from CCGA using an optimized assay; updated performance results will be reported. Conclusions: Cancers detected using WGBS of cfDNA had a worse prognosis than cancers not detected. WGBS cancer detection carried comparable prognostic significance as clinical stage. By preferentially detecting higher risk cancers, cancer detection using plasma cfDNA may avoid some of the overdiagnosis that has been seen with some existing cancer screening methods. Clinical trial information: NCT02889978.

The Significance of Pretreatment Thrombocytosis and Its Association With Neutrophilia in Patients With Surgically Treated Endometrial Cancer

2017 ◽  
Vol 27 (7) ◽  
pp. 1399-1407 ◽  
Author(s):  
Ryoko Takahashi ◽  
Seiji Mabuchi ◽  
Hiromasa Kuroda ◽  
Katsumi Kozasa ◽  
Eriko Yokoi ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Proportional Hazards ◽  
Independent Predictor ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Myometrial Invasion ◽  
Cox Proportional Hazards ◽  
Peritoneal Cytology ◽  
Advanced Stage ◽  
Advanced Clinical Stage

ObjectiveThe aim of this study was to investigate the prognostic significance of a pretreatment thrombocytosis and its association with neutrophilia in patients with surgically treated endometrial cancer.MethodsThe baseline characteristics and outcome data of 508 patients with surgically treated endometrial cancer between January 2000 and December 2010 were collected and retrospectively reviewed. The patients were separated into 4 groups according to their platelet counts and the neutrophil counts, and the progression-free and overall survival rates of the 4 groups were compared. A Cox proportional hazards regression model was used to explore the independent prognostic factors.ResultsPretreatment thrombocytosis was found to be associated with advanced stage (P = 0.0186), nonendometrioid histology (P = 0.0139), a deeper myometrial invasion (P = 0.0103), lymphovascular space involvement (P = 0.0404), cervical involvement (P = 0.004), positive peritoneal cytology (P = 0.0198), lymph node metastasis (P = 0.0301), and more frequent treatment failure (P = 0.0006). Multivariate analysis demonstrated that an older age (hazard ratio [HR], 2.54; 95% confidence interval [CI], 1.46–4.51; P = 0.0009), advanced clinical stage (HR, 5.27; 95% CI, 2.94–9.86; P < 0.0001), lymphovascular space involvement (HR, 3.37; 95% CI, 1.74–7.07; P = 0.0002), and pretreatment thrombocytosis (HR, 4.99; 95% CI, 2.47–9.39; P < 0.0001) were significant predictors of survival. When examined according to clinical stage, pretreatment thrombocytosis was prognostically significant only in patients with stage III–IV disease. The neutrophil count in patients who display thrombocytosis was significantly greater than that observed in patients without thrombocytosis (median, 6702 vs 4406/μL; P < 0.0001). Moreover, patients who displayed both thrombocytosis and neutrophilia had significantly shorter survival than that in those with either thrombocytosis or neutrophilia alone.ConclusionsPresence of thrombocytosis at the time of the initial diagnosis is an independent predictor of shorter survival in patients with advanced-stage (stages III–IV) endometrial cancer. Moreover, pretreatment thrombocytosis and concurrent neutrophilia are an independent predictor of shorter survival regardless of clinical stage.

Prognostic Significance of Pretreatment Thrombocytosis in Cervical Cancer Patients Treated With Definitive Radiotherapy

2015 ◽  
Vol 25 (9) ◽  
pp. 1656-1662 ◽  
Author(s):  
Mahiru Kawano ◽  
Seiji Mabuchi ◽  
Yuri Matsumoto ◽  
Tomoyuki Sasano ◽  
Ryoko Takahashi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Platelet Count ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Cox Proportional Hazards ◽  
Initial Diagnosis ◽  
Advanced Clinical Stage ◽  
Definitive Radiotherapy

ObjectiveThe aim of this study was to investigate the prevalence and prognostic significance of an elevated platelet count at the time of the initial diagnosis in patients with cervical cancer who are treated with definitive radiotherapy.MethodsThe baseline characteristics and outcome data of cervical cancer patients who were treated with definitive radiotherapy between November 1993 and December 2011 were collected and retrospectively reviewed. The patients were separated into 2 groups according to their platelet counts. The clinicopathological characteristics and overall survival rates of the 2 groups were compared. A Cox proportional hazards regression model was used to investigate the prognostic significance of an elevated platelet count.ResultsAn elevated platelet count was found to be associated with younger age (P = 0.0003), an advanced clinical stage (P < 0.0001), larger tumors (P = 0.0025), lower hemoglobin levels (P < 0.0001), and more frequent treatment failure (P = 0.0015). Multivariate analysis demonstrated that an advanced clinical stage (hazards ratio [HR], 2.93; 95% confidence interval [CI], 1.47–6.70; P = 0.0015), nonsquamous cell carcinoma histology (HR, 2.67; 95% CI, 1.52–4.42; P = 0.0011), larger tumors (HR, 3.86; 95% CI, 2.18–7.03; P < 0.0001), lower hemoglobin levels (HR, 1.99; 95% CI, 1.34–2.93; P = 0.0008), and an elevated platelet count (HR, 1.65; 95% CI, 1.03–2.56; P = 0.0395) were significant predictors of survival.ConclusionsAn elevated platelet count at the time of the initial diagnosis is an independent prognostic factor in cervical cancer patients who are treated with definitive radiotherapy.

scholarly journals Comparison of Treatment Strategies for Patients With Clinical Stage T1–3/N2 Lung Cancer

2020 ◽  
Vol 18 (2) ◽  
pp. 143-150 ◽  
Author(s):  
Ya-Fu Cheng ◽  
Wei-Heng Hung ◽  
Heng-Chung Chen ◽  
Ching-Yuan Cheng ◽  
Ching-Hsiung Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Therapy ◽  
Concurrent Chemoradiotherapy ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Multivariate Analyses ◽  
Clinical Stage ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage T1

Background: The therapeutic strategies for clinical stage T1–3N2 (cT1–3N2) lung cancer are controversial. For operable tumors, treatment can vary by center, region, and continent. This study aimed to identify the optimal therapeutic method and type of surgical strategy for cT1–3N2 lung cancer. Methods: This retrospective evaluation analyzed the records of 17,954 patients with cT1–3N2 lung cancer treated in 2010 through 2015 from the SEER database. The effects of different therapeutic methods and types of surgical strategies on overall survival (OS) were assessed. Univariate and multivariate analyses were performed using a Cox proportional hazards model. Results: The 5-year OS rates were 27.7% for patients with T1N2 disease, 21.8% for those with T2N2 disease, and 19.9% for T3N2 disease. Neoadjuvant therapy plus operation (OP) plus adjuvant therapy, and OP plus adjuvant therapy, provided better 5-year OS rates than OP alone or concurrent chemoradiotherapy (34.1%, 37.7%, 29.3%, and 16.1%, respectively). In the T1N2, T2N2, and T3N2 groups, lobectomy provided better 5-year OS than pneumonectomy, sublobectomy, and no surgery. Both univariate and multivariate analyses showed that young age, female sex, well-differentiated histologic grade, adenocarcinoma cell type, neoadjuvant and adjuvant therapy, lobectomy, and T1 stage were statistically associated with better 5-year OS rates. Conclusions: In cT1–3N2 lung cancer, multimodal treatments tended to provide better 5-year OS than OP alone or concurrent chemoradiotherapy. In addition, lobectomy was associated with better survival than other operative methods.

scholarly journals Expression Profile and Prognostic Values of SMC Family Members in HCC

2021 ◽  
Author(s):  
Wei Yan ◽  
Dan-dan Wang ◽  
He-da Zhang ◽  
Jinny Huang ◽  
Jun-Chen Hou ◽  
...  
Keyword(s):  
Gene Family ◽  
Expression Profile ◽  
Proportional Hazards ◽  
Wide Spectrum ◽  
Clinical Stage ◽  
Family Members ◽  
Enrichment Analysis ◽  
Cox Proportional Hazards ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas

Abstract Background: The structural maintenance of chromosome (SMC) gene family, comprising 6 members, is involved in a wide spectrum of biological functions in many types of human cancers. However, there is little research on the expression profile and prognostic values of SMC genes in hepatocellular carcinoma (HCC). Based on updated public resources and integrative bioinformatics analysis, we tried to determine the value of SMC gene expression in predicting the risk of developing HCC. Methods and materials: The expression data of SMC family members were obtained from The Cancer Genome Atlas (TCGA). The prognostic values of SMC members and clinical features were identified. A gene set enrichment analysis (GSEA) was conducted to explore the mechanism underlying the involvement of SMC members in liver cancer. The associations between tumor immune infiltrating cells (TIICs) and the SMC family members were evaluated using the Tumor Immune Estimation Resource (TIMER) database. Results: Our analysis demonstrated that mRNA downregulation of SMC genes was common alteration in HCC patients. SMC1A, SMC2, SMC3, SMC4, SMC6 were upregulated in HCC. Upregulation of SMC2, SMC3 and SMC4, along with clinical stage, were associated with a poor HCC prognosis based on the results of univariate and multivariate Cox proportional hazards regression analyses. SMC2, SMC3 and SMC4 are also related to tumor purity and immune infiltration levels of HCC. The GSEA results indicated that SMC members participate in multiple biological processes underlying tumorigenesis. Conclusion: This study comprehensively analyzed the expression of SMC gene family members in patients with HCC. This can provide insights for further investigation of the SMC family members as potential targets in HCC and suggest that the use of SMC inhibitor targeting SMC2, SMC3 and SMC4 may be an effective strategy for HCC therapy.

A Comprehensive Analysis of Treatment Management and Survival Outcomes in Nasopharyngeal Carcinoma

2020 ◽  
pp. 019459982097324
Author(s):  
Khodayar Goshtasbi ◽  
Brandon M. Lehrich ◽  
Jack L. Birkenbeuel ◽  
Arash Abiri ◽  
Jeremy P. Harris ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Sociodemographic Factors ◽  
Cox Proportional Hazards ◽  
Stage Iii ◽  
Definitive Treatment ◽  
National Cancer Database ◽  
Cox Proportional Hazards Models ◽  
Undifferentiated Histology

Objectives To comprehensively investigate nasopharyngeal carcinoma (NPC) treatment, overall survival (OS), and the influence of clinical/sociodemographic factors on outcome. Study Design Retrospective database study. Setting National Cancer Database. Methods The 2004-2015 National Cancer Database was queried for all patients with NPC receiving definitive treatment. Log-rank tests and Cox proportional hazards models were used for statistical analyses. Results A total of 8260 patients with NPC were included (71.4% male; 42.5% with keratinizing histology; mean ± SD age, 52.1 ± 15.1 years), with a 5-year OS of 63.4%. Multivariate predictors of mortality included age ≥65 years (hazard ratio [HR], 1.81; P < .001), Charlson/Deyo score ≥1 (HR, 1.27; P = .001), American Joint Committee on Cancer clinical stage III to IV (HR, 1.85; P < .001), and government insurance or no insurance (HR, 1.53; P < .001). Predictors of survival included female sex (HR, 0.82; P = .002), Asian/Pacific Islander race (HR, 0.74; P < .001), nonkeratinizing/undifferentiated histology (HR, 0.79; P = .004), and receiving treatment at academic centers (HR, 0.87; P = .02). Chemoradiotherapy (CRT) demonstrated improved OS as compared with radiotherapy (RT) only for stage II ( P = .006) and stage III ( P = .005) and with RT or chemotherapy only in stage IVA NPC ( P < .001). When compared with CRT alone, surgery plus CRT provided OS benefits in keratinizing ( P = .013) or stage IVA ( P = .030) NPC. When compared with RT, CRT provided OS benefits in keratinizing ( P = .005) but not nonkeratinizing ( P = .240) or undifferentiated ( P = .390) NPC. Substandard radiation dosing of <60 Gy and <30 fractions were associated with inferior OS (both P < .001). Conclusions NPC survival is dependent on a variety of clinical/sociodemographic factors. Stage-specific treatments with optimal OS include CRT or RT for stages I to II and CRT for stage III to IV. The large representation of nonendemic histology is valuable, as these cases are not well characterized.

Histopathologic Features that Predict Transplant Glomerulopathy Progression in a Chinese Cohort

2019 ◽  
Vol 49 (6) ◽  
pp. 425-434 ◽  
Author(s):  
Xue Li ◽  
Jinsong Chen ◽  
Dongrui Cheng ◽  
Wei Wang ◽  
Kenan Xie ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Proportional Hazards ◽  
Linear Regression Analysis ◽  
Prognostic Significance ◽  
Immunoglobulin A ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Chinese Cohort ◽  
Transplant Glomerulopathy ◽  
Histopathologic Features

Background: Transplant glomerulopathy (TG) represents a major cause of long-term allograft failure and is the leading cause of overall post-transplant proteinuria. The extent to which histopathologic features predicts prognostication is uncertain. Methods: A single-center retrospective cohort with biopsy-proven TG was investigated. Renal biopsies were scored according to Banff 2017. The primary outcome was death-censored graft failure defined as return to dialysis or estimated glomerular filtration rate (eGFR) decreased to <15 mL/min/1.73 m2. The prognostic significance of clinical and histopathologic parameters was determined using Cox proportional hazards models. Results: Data from 180 cases were available for analysis with a median follow-up of 5.0 (2.6–8.2) years. In multivariable models, ci + ct score (HR 3.1; 95% CI 2.0–4.9), cg score (HR 1.7; 95% CI 1.1–2.8), eGFR (HR 2.1; 95% CI 1.4–3.2) and proteinuria (HR 2.4; 95% CI 1.6–3.7) were independent predictors of the primary outcome. Mesangial Immunoglobulin A deposition did not significantly affect allograft survival. The only significant pathologic factors for the severity of proteinuria were cg and g + ptc (adjusted R2 = 0.46) as determined by multivariable stepwise linear regression analysis. Conclusions: Severe ci + ct and cg at biopsy were predictors of unfavorable allograft prognosis in TG patients even after taking into consideration clinical characteristics. Histologic severity of cg and g + ptc was significantly associated with clinical proteinuria.

Tailored surgical staging and radiation therapy in clinical stage I endometrioid endometrial adenocarcinoma (EEA)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16511-e16511
Author(s):  
K. M. Bermudez Wagner ◽  
M. B. Thomas ◽  
C. Miyamoto ◽  
B. Micaily ◽  
E. Hernandez
Keyword(s):  
Adjuvant Therapy ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Endometrial Adenocarcinoma ◽  
Myometrial Invasion ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Outcome Analysis

e16511 Background: Pelvic lymph node dissection (LND) requirement to adequately stage endometrial cancer has been subject of debate. We conducted an outcome analysis of clinical stage I endometrioid endometrial adenocarcinoma (EEA) patients who underwent surgery with tailored LND and adjuvant therapy (radiation (RT) or chemotherapy) between 1997 and 2008. Methods: Retrospective chart review was performed at our institution. All patients underwent exploratory laparotomy, cytology, total abdominal hysterectomy and bilateral salpingoophorectomy. Pelvic and para-aortic LND was perforned in high-risk patients when technically possible. Cox proportional hazards and the Kaplan Meier method were used for data analysis. Results: 119 patients (stage I 92, II 11, III 15, and IV 1) were identified. Median BMI was 34 and 81% had significant co-morbidities. 50% underwent para-aortic LND (median 4 nodes) and 25% underwent pelvic LND (median 15 nodes), of whom 8% and 10% were positive, respectively. Postoperative complications occurred in 22%. 26% received RT. With a mean follow-up of 20 months, 5-year progression-free survival (PFS) and overall survival (OS) was 71% and 84%. The OS for stage I and IIIC was 88% and 83%, respectively. OS for patients with or without LND was not statistically different ( 73% vs.82%). 12 (10%) recurrences were noted, 8 of which were hematological (HF) with a 5-year HF probability of 21%. On multivariate analysis only myometrial invasion > 50% was independent risk factor for HF. Patients receiving RT showed a trend toward decreased in local recurrences ( 0% vs.30% p = 0.1) but no improvement in OS. Conclusions: In patients with EEA, a tailored approach to LND and adjuvant therapy results in good outcome, but many still have therapy-associated adverse events. Although no difference was found in OS between patients who underwent LND and those who did not, similar survival for patients with stages I and IIIC suggests that therapy directed by the knowledge of nodal status may have an impact on survival. No significant financial relationships to disclose.

Pre-treatment neutrophil to lymphocyte ratio (NLR) association with curative intent metastasectomy (MSX) in metastatic renal cell carcinoma (RCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16051-e16051
Author(s):  
Aline Fusco Fares ◽  
Daniel Vilarim Araujo ◽  
Eliza Dalsasso Ricardo ◽  
Marcelo Corassa ◽  
Maria Nirvana Cruz Formiga ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Regression Tree ◽  
Positive Association ◽  
Cox Proportional Hazards ◽  
Curative Intent ◽  
Risk Of Death ◽  
Metastatic Rcc

e16051 Background: NLR is a marker of inflammation and when elevated is associated with poor outcome in many tumors, including RCC. Hereby we evaluate the association of NLR with the likelihood of curative intent MSX. Methods: We retrospectively studied 846 patients diagnosed with metastatic RCC between 2007 and 2016. 116 patients fulfilled inclusion criteria: previous nephrectomy, no sarcomatoid features and available tumor specimens from metastatic site. Regression tree for censored data method was used to find the best NLR cut-off value. NLR was examined baseline – prior to MSX or targeted therapy. Chi-square test was used to evaluate associations between variables. We estimated overall survival (OS) using Kaplan-Meier curves. Cox proportional hazards regression models were fitted to evaluate the prognostic significance of NLR in univariable and multivariable analysis. Results: The median OS for the whole cohort was 45 months (95% CI, 27.6 to 62.4 months), and the median follow-up was 78.2 months. The best cut-off NLR value was 4.07. Higher NLR was associated with shorter OS when compared to the lower NLR cohort (11.5 months vs 68.3 months HR = 0.26, 95% CI: 0.15 – 0.97, p ≤ 0.0001, respectively). Univariate analysis revealed that bone metastasis and poor IMDC criteria were associated with worse OS and that MSX and lower NLR were associated with better OS. On multivariate analysis MSX, lower NLR and favourable/intermediate group on IMDC criteria were associated with a decreased risk of death (HR = 0.41, 95% CI 0.19-0.85, p = 0.018 and HR = 0.45, 95% CI 0.22-0.90, p = 0.025, HR = 0.35, 95% CI 0.16-0.79, p = 0.012, respectively). We found a positive association of lower NLR and curative intent MSX (p = 0.002). Conclusions: NLR is a prognostic marker in metastatic RCC and a ratio ≤ 4,07 is associated with a higher likelihood of curative intent MSX.

Prognostic relevance of neutrophil to lymphocyte ratio (NLR) before anti-PD1 therapy in metastatic melanoma patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21045-e21045
Author(s):  
Daniel Vilarim Araujo ◽  
Rafael Vanin de Moraes ◽  
Victor Aurelio Ramos Sousa ◽  
Mauro Daniel Spina Donadio ◽  
Aline Fusco Fares ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Metastatic Melanoma ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Melanoma Patients

e21045 Background: Biomarkers to select the patients most likely to benefit from checkpoint inhibitors are urged. NLR is a simple way of measuring systemic inflammation and is an independent predictor of survival before Anti-CTLA4 therapy. We hypothesized if NLR is also a predictor of survival before Anti-PD1 therapy. Methods: We performed a retrospective review of the medical records of all consecutive metastatic melanoma patients who received Nivolumab treatment from January/2014 – February/2017, including 53 patients prospectively collected from an Expanded Access Program. Of 86 patients, 83 patients were included for demographic and efficacy analysis, and 74 had information about baseline pre-treatment NLR. We analyzed NLR as a continuous variable and categorised ≥ 5 vs. < 5. Kaplan-Meier method was used for survival analysis. Long-rank test compared categories and Cox proportional hazards regression model was used to assess the prognostic significance of baseline NLR in univariate and multivariable analysis. Results: Median PFS for the entire population was 6,407 months (3,28 – 9,52) and median OS was not reached (NR) with a median FU of 10,74 months. The median NLR ratio was 3,11 (0,87 – 19). 18 patients (24,3%) had a ≥ 5 NLR vs. 56 (75,7%) < 5. Median PFS for NLR ≥ 5 was: 2,3 (1,75 – 2,84) vs. 12,02 (5,11 – 18,93) for < 5 (HR = 3,11; IC95% 1,52 – 6,27; p = 0,001). Median OS ≥ 5: 3,05 (2,06 – 4,04) vs. NR for < 5 (HR = 5,88; IC95% 2,60 – 13,29; p = 0,001). NLR categorised remained statistically significant in multivariate analysis for PFS and NLR as a continuous variable remained statistically significant for both PFS and OS in multivariate analysis (Table 1). Conclusions: Baseline NLR is a rapid, simple, and cost-free predictor of survival before Anti-PD1 therapy. These results should be validated in a larger cohort of patients. [Table: see text]

Molecular biomarker analysis and survival in patients (pts) with advanced urothelial cancer (UC) previously treated with chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4529-4529
Author(s):  
Bernadett Szabados ◽  
Marlon Rebelatto ◽  
Craig Barker ◽  
Alvin Milner ◽  
Arthur Lewis ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Bootstrap Method ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Process ◽  
Cox Proportional Hazards ◽  
Multivariate Model ◽  
Significant Variable ◽  
Platinum Based Chemotherapy ◽  
Biomarker Analysis

4529 Background: The biomarkers PD-L1, FOXP3, and CD8 have been explored in pts with advanced UC who progressed after platinum-based chemotherapy (CTx). However, their relevance earlier in the disease process is less well understood. Methods: The Phase 2/3 LaMB study (NCT00949455) compared maintenance lapatinib vs placebo after first-line (1L) platinum-based CTx in pts with HER1/HER2-overexpressing stage IV advanced UC. Pre-CTx archival samples from this study were retrospectively analyzed and included both randomized and screen failure pts. PD-L1 expression was assessed (VENTANA SP263 Assay) and categorized as high (≥25% of tumor cells [TC] and/or immune cells [IC]) or low/negative ( < 25% TC and IC). Overall survival (OS) and progression-free survival (PFS) were estimated via Kaplan-Meier method; results were stratified by PD-L1 expression. The exploratory biomarkers CD8 and FOXP3 were also analyzed. The prognostic significance of the biomarkers was explored by multivariable Cox proportional hazards models and a bootstrap method for model selection. Results: Of 446 pts (232 randomized; 214 screened), 243 (54.5%) were assessed for PD-L1 expression, with 61 (25.1%) PD-L1 high and 158 (65.0%) PD-L1 low/negative. In PD-L1 high and low/negative pts, respectively, median OS (95% CI) was 12.0 (9.4–19.7) vs 12.5 months (10.4–15.5); median PFS (95% CI) was 6.5 (3.5–8.8) vs 5.0 months (4.3–6.3). PD-L1 expression was not associated with OS or PFS in univariate analysis or in a multivariate model for OS (hazard ratio [HR] for PD-L1 high vs low/negative 1.4 [95% CI, 0.8–2.3]). In a multivariate model for PFS, PD-L1 expression improved accuracy of the model by 23% and was a significant variable (HR, 2.1 [95% CI, 1.2–3.5]). Results of analyses of CD8 and FOXP3 will also be reported. Conclusions: Overall, these data suggest a lack of association between PD-L1 expression and survival in pts receiving 1L platinum-based CTx. Mechanisms underlying the potential association of PD-L1 expression with PFS remain unclear. CD8 and FoxP3 exploratory analyses may help to elucidate these results. Clinical trial information: NCT00949455.

Sign in / Sign up

Export Citation Format

Share Document