Bone metastasis as an independent prognostic factor for survival in patients with advanced melanoma treated with immune checkpoint blockade.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22045-e22045
Author(s):  
Marcos Rezende Teixeira ◽  
Milton Jos De Barros E Silva ◽  
Natasha Carvalho Pandolfi ◽  
Vinicius Fernando Calsavara ◽  
Thiago Bueno Oliveira ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bone Metastasis ◽  
Prognostic Factor ◽  
Immune Checkpoint ◽  
Cox Regression ◽  
Immune Checkpoint Blockade ◽  
Advanced Melanoma ◽  
Independent Prognostic Factor ◽  
Checkpoint Blockade ◽  
The Impact

e22045 Background: Immune checkpoint blockade (ICB) has changed the natural history advanced melanoma (AM) with response rates about 40% and overall survival in 5 years of more than 30%. Interestingly, the site of metastasis may have impact on immune response due to the quantity and quality of immune infiltrate as we have seen in patients (pts) with liver metastasis treated with ICB. We have hypothesized that bone metastasis(BM) represents an immune less responsive site of disease Methods: We conducted a retrospective observational analysis of patients with AM treated with ICB at A.C. Camargo Cancer Center (AC) in São Paulo, Brazil. We analyze the impact of BM on progression-free (PFS) and overall survival (OS) using Kaplan Meier method, log-rank test and time-dependent COX regression model. Results: We analyzed 170 pts with AM treated with anti-PD1 (79%) or anti-PD1 + anti-CTLA4 (21%) between September 2013 and December 2019. Fifty-five percent in first-line, 22.4% second-line and the remaining in third or more lines of therapy. Ninety- four were male (55.3%), median age of 60.5 years (24.8 to 88.3) and 61 (35.9%) pts had BRAF mutation. Among stage IV patients (94%), 52 (32.4%) were M1c, 36 (22.4%) M1d and 46 (27%) had elevated LDH. Forty-two (26%) pts had BM. The overall response rate was 30.9% for pts with BM compared to 57.7% for pts without BM (p:0.004). In a median follow-up of 23.6 months (95% CI: 18.0-29.1), the median PFS and OS for pts with and without BM were 3.8 x 18.8 months (p 0.005) and 19.4months x not achieved (p 0.001), respectively. The 24-month analysis shows an overall survival rate of 38% for patients with BM compared to 62% for the rest of the cohort population. In a multivariate analysis for overall survival, acral melanoma, elevated LDH, ECOG performance status of 1 or 2 and BM were independent adverse prognostic factors (bone metastasis - HR: 2.3; 95%CI: 1.18-4.1; p:0.013). Conclusions: In this analysis, the presence of bone disease seems to be a worse independent prognostic factor for survival. A hypothesis would be the unfavorable bone microenvironment for the action of the immunotherapy.

scholarly journals Immune Checkpoint Blockade for Metastatic Uveal Melanoma: Patterns of Response and Survival According to the Presence of Hepatic and Extrahepatic Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3359
Author(s):  
Elias Koch ◽  
Anne Petzold ◽  
Anja Wessely ◽  
Edgar Dippel ◽  
Anja Gesierich ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Uveal Melanoma ◽  
Hepatic Metastasis ◽  
Immune Checkpoint ◽  
Objective Response ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Response To Treatment ◽  
Extrahepatic Metastasis ◽  
The Impact

Background: Since there is no standardized and effective treatment for advanced uveal melanoma (UM), the prognosis is dismal once metastases develop. Due to the availability of immune checkpoint blockade (ICB) in the real-world setting, the prognosis of metastatic UM has improved. However, it is unclear how the presence of hepatic and extrahepatic metastasis impacts the response and survival after ICB. Methods: A total of 178 patients with metastatic UM treated with ICB were included in this analysis. Patients were recruited from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of hepatic metastasis, two cohorts were compared: patients with liver metastasis only (cohort A, n = 55) versus those with both liver and extra-hepatic metastasis (cohort B, n = 123). Data were analyzed in both cohorts for response to treatment, progression-free survival (PFS), and overall survival (OS). The survival and progression probabilities were calculated with the Kaplan–Meier method. Log-rank tests, χ2 tests, and t-tests were performed to detect significant differences between both cohorts. Results: The median OS of the overall population was 16 months (95% CI 13.4–23.7) and the median PFS, 2.8 months (95% CI 2.5–3.0). The median OS was longer in cohort B than in cohort A (18.2 vs. 6.1 months; p = 0.071). The best objective response rate to dual ICB was 13.8% and to anti-PD-1 monotherapy 8.9% in the entire population. Patients with liver metastases only had a lower response to dual ICB, yet without significance (cohort A 8.7% vs. cohort B 16.7%; p = 0.45). Adverse events (AE) occurred in 41.6%. Severe AE were observed in 26.3% and evenly distributed between both cohorts. Conclusion: The survival of this large cohort of patients with advanced UM was more favorable than reported in previous benchmark studies. Patients with both hepatic and extrahepatic metastasis showed more favorable survival and higher response to dual ICB than those with hepatic metastasis only.

Obesity Is Poor Prognostic Factor in Lower Risk Myelodysplastic Syndrome

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5018-5018
Author(s):  
Asmita Mishra ◽  
Dana E Rollison ◽  
Najla H Al Ali ◽  
Maria Corrales-Yepez ◽  
Pearlie K Epling-Burnette ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Myelodysplastic Syndrome ◽  
Lower Risk ◽  
Cox Regression ◽  
Cancer Center ◽  
Kaplan Meier ◽  
Baseline Characteristics ◽  
Md Anderson ◽  
The Impact

Abstract Abstract 5018 Background: Obesity was associated with a more than 2-fold greater risk of myelodysplastic syndrome (MDS) in a recent epidemiological study (Ma et al, Am J Epidemiol. 2009 June 15; 169(12): 1492–1499). The impact of obesity on outcome of disease in patients with an established diagnosis of MDS has not been studied. We examined the prognostic value of obesity in a large cohort of lower risk MDS patients treated at the Moffitt Cancer Center (MCC). Methods: Data were collected retrospectively from the Moffitt Cancer Center (MCC) MDS database and individual charts reviewed. The primary objective was to evaluate the impact of obesity on overall survival (OS) in lower risk patients with MDS. Patients with low or intermediate-1 (int-1) risk disease by International Prognostic Scoring System (IPSS) were included. Obesity was defined as a body mass index (BMI) ≥ 30 (Standard definition) measured at time of referral to MDS program at MCC. Patients were divided into two groups according to BMI ≥ 30 or BMI < 30. All analyses were conducted using SPSS version 19.0. Chi square and independent t-test were used to compare baseline characteristics between the 2 groups for categorical and continuous variables, respectively. The Kaplan–Meier method was used to estimate median overall survival. Log rank test was used to compare Kaplan–Meier survival estimates between two groups. Cox regression was used for multivariable analysis. Results: Between January 2001 and December 2009, 479 low/int-1 IPSS risk MDS patients were included. Among those, 132 (27.6%) had BMI ≥ 30 and 325 (67.8%) had BMI <30; BMI was missing in 22 patients (4.6%). The baseline characteristics between the two groups were comparable. No difference was noted in mean age, WHO subtype, karyotype, MD Anderson risk model group, red blood cell transfusion dependency (RBC-TD), or serum ferritin (Table-1). The median OS was 59 mo (95%CI 48–70) in patients with BMI <30 compared to 44 (95%CI 38–50) in patients with BMI ≥ 30. (p=0.03). There was no difference in rate of AML transformation according to BMI, 12.9% and 15.7% respectively for BMI ≥ 30 and BMI <30. (P=0.3). In Cox regression analysis obesity predicted inferior OS (Hazard ratio (HR) 1.7 (95%CI 1.15–2.4) (P=0.007) after adjustment for age, MD Anderson risk group, serum ferritin, RBC-TD, use of hypomethylating agents and tobacco use. Conclusion: Our data suggest that obesity is an independent adverse prognostic factor for OS in patients with lower risk MDS. Obesity may be associated with other comorbidities and metabolic dearrangements that contribute to the pathogenesis of the underlying disease. Disclosures: No relevant conflicts of interest to declare.

TAMI-03. PROGNOSTIC SIGNIFICANCE OF NEUTROPHIL-TO-LYMPHOCYTE RATIO (NLR) IN PATIENTS WITH BRAIN METASTASES FROM DIFFERENT TUMOR ORIGINS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi198-vi198
Author(s):  
Guanhua Deng ◽  
Lei Wen ◽  
zhaoming Zhou ◽  
Changguo Shan ◽  
Mingyao Lai ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Brain Metastases ◽  
Median Overall Survival ◽  
Cox Regression ◽  
Independent Prognostic Factor ◽  
Neutrophil To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Risk Of Death ◽  
Metastatic Sites

Abstract PURPOSE Brain metastases (BMs) represent the most common adult intracranial malignancy. The prognosis of BMs is subject to many factors, i.e., the number, size and locations of the metastatic sites, tumor origins, pathologic types, gene mutation status, metastatic sites, and KPS etc. This study aimed to evaluate the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in brain metastases. METHODS A total of 480 patients diagnosed with brain metastases from a wide range of tumor origins, i.e., NSCLC, SCLC, breast cancer, melanoma, prostate, kidney, gastrointestinal cancer, cervical carcinoma, ovarian cancer, choriocarcinoma of uterus were retrospectively analyzed. Pre-radiotherapy NLR, PLR, and LMR were calculated as total neutrophil/lymphocyte, platelet/Lymphocyte, lymphocyte/monocyte, respectively. Survival rates were estimated using the Kaplan-Meier survival analysis. Cox regression models were used to identify independent prognostic factors. RESULTS The median overall survival (OS) was 14.4 months [95%CI: 13.4-15.5]. The median overall survival after radiotherapy was significantly different between patients with NLR&lt; 4 and those with NLR≥4 (OS 16.3 mo. vs. 12.2 mo., P&lt; 0.0001). No significant difference was observed between PLR vs. OS, and LMR vs. OS (PLR&lt; 180: HR=1.221, P=0.240; LMR&lt; 4: HR=0.753, P=0.141). The Cox regression model for the continuous metric values revealed that the NLR increased every 1.0 was associated with additional 5.9% of fatal risk (HR: 1.059; 95%CI = 1.033–1.087, P&lt; 0.0001). NLR was validated as an independent prognostic factor for risk of death after adjusting for sex, age, and KPS. CONCLUSIONS We revealed pre-treatment NLR is an independent prognostic factor in patients with brain metastases for poor OS, independent of different tumor origins. The NLR warrants further studies using sub-group analysis and validation in external cohorts. Future studies in this parameter have a potential to facilitate more precise risk-stratifications to guide personalized treatment for BM.

scholarly journals Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients

2018 ◽  
Vol 10 ◽  
pp. 175883401774974 ◽  
Author(s):  
Niki Karachaliou ◽  
Maria Gonzalez-Cao ◽  
Guillermo Crespo ◽  
Ana Drozdowskyj ◽  
Erika Aldeguer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Checkpoint ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Free Survival ◽  
Melanoma Patients ◽  
Ifn Γ ◽  
Nsclc Patients ◽  
Important Marker

Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated via interferon gamma (IFN-γ). We have explored whether the expression of IFNG, the gene encoding IFN-γ, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined. Methods: Total RNA from 17 NSCLC and 21 melanoma patients was analyzed by quantitative reverse transcription PCR. STAT3 and Rantes, YAP1 and CXCL5, DNMT1, RIG1 and TET1, EOMES, IFNG, PD-L1 and CTLA4, IKBKE and NFATC1 mRNA were examined. PD-L1 protein expression in tumor and immune cells and stromal infiltration of CD8+ T-cells were also evaluated. Progression-free survival and overall survival were estimated. Results: A total of 17 NSCLC patients received nivolumab and 21 melanoma patients received pembrolizumab. Progression-free survival with nivolumab was significantly longer in NSCLC patients with high versus low IFNG expression (5.1 months versus 2 months, p = 0.0124). Progression-free survival with pembrolizumab was significantly longer in melanoma patients with high versus low IFNG expression (5.0 months versus 1.9 months, p = 0.0099). Significantly longer overall survival was observed for melanoma patients with high versus low IFNG expression (not reached versus 10.2 months p = 0.0183). There was a trend for longer overall survival for NSCLC patients with high versus low IFNG expression. Conclusions: IFN-γ is an important marker for prediction of response to immune checkpoint blockade. Further research is warranted in order to validate whether IFNG is more accurate than PD-L1.

scholarly journals Combination Therapies for the Treatment of Advanced Melanoma: A Review of Current Evidence

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mark Voskoboynik ◽  
Hendrik-Tobias Arkenau
Keyword(s):  
Overall Survival ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Advanced Melanoma ◽  
Current Evidence ◽  
Combination Therapies ◽  
Improved Outcomes ◽  
History Of ◽  
Dual Blockade

The treatment of advanced melanoma has been revolutionised in recent years with the advent of a range of new therapies. BRAF inhibitors, such as vemurafenib, have demonstrated improvements in the overall survival of patients with advanced melanoma that harbour a BRAF V600 mutation. Alongside these targeted therapies, novel immune-checkpoint inhibitors, such as ipilimumab, have also been developed and have produced similarly improved outcomes for patients. For the first time in the history of melanoma, monotherapy with each of these drugs has produced improvements in the overall survival of patients with advanced disease. Building on this initial success, there has been intense interest in developing combination therapies predominantly with either dual blockade of the MAPK oncogenic pathway or dual immune-checkpoint blockade. The current evidence for the use of these combination therapies will be presented here.

scholarly journals Objective Response by mRECIST is an Independent Prognostic Factor for overall Survival in Hepatocellular Carcinoma in SILIUS Trial

2019 ◽  
Author(s):  
Masatoshi Kudo ◽  
Kazuomi Ueshima ◽  
Yasutaka Chiba ◽  
Sadahisa Ogasawara ◽  
Shuntaro Obi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Objective Response ◽  
Independent Prognostic Factor ◽  
Combination Group ◽  
Advanced Hepatocellular Carcinoma ◽  
Sorafenib Group ◽  
Landmark Analyses

Background In SILIUS (NCT01214343), combination of sorafenib and hepatic arterial infusion chemotherapy did not significantly improve overall survival in patients with advanced hepatocellular carcinoma (HCC) compared with sorafenib alone. In this study, we explored the relationship between objective response by mRECIST and overall survival (OS) in the sorafenib group, in the combination group and in all patients in the SILIUS trial. Methods Association between objective response and OS in patients treated with sorafenib (n=103), combination (n=102) and all patients (n=205) were analyzed. The median OS of responders was compared with that of non-responders. Landmark analyses were performed according to objective response at several fixed time points, as sensitivity analyses, and the effect on OS was evaluated by Cox regression analysis with objective response as a time-dependent covariate, with other prognostic factors was performed. Results In the sorafenib group, OS of responders (n = 18) was significantly better than that of non-responders (n = 78) (p &lt; 0.0001), where median OS was 27.2 (95% CI, 16.0&ndash;not reached) months for responders and 8.9 (95% CI, 6.5&ndash;12.6) months for non-responders. HRs from landmark analyses at 4, 6, and 8 months were 0.45 (p=0.0330), 0.37 (p=0.0053), and 0.36 (p=0.0083), respectively. Objective response was an independent predictor of OS based on unstratified Cox regression analyses. In the all patients and the combination group, similar results were obtained. Conclusion In the SILIUS trial, objective response was an independent prognostic factor for OS in patients with HCC.

scholarly journals High PON1 Expression Predicts Poor Prognosis In Kidney Renal Clear Cell Carcinoma

2021 ◽  
Author(s):  
Chenxia Jiang ◽  
Xinyu Zhang ◽  
Xiaoyan Li ◽  
Jia Li ◽  
Hua Huang
Keyword(s):  
Overall Survival ◽  
Regression Analysis ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Independent Prognostic Factor ◽  
Cox Regression Analysis

Abstract Background: Relevant study had demonstrated that Paraoxonase-1 (PON1) had relationship with occurrence and development of tumors which suggested that PON1 was a key gene in promoting tumor progression. However, the relationship between PON1 and Kidney renal clear cell carcinoma (KIRC) is still unclear so far. Methods: We downloaded relevant data about KIRC from TCGA dataset and compared it with normal renal tissues. Immunohistochemistry (IHC) was applied to analyze the expression of PON1. Univariate cox regression analysis and multivariate cox regression analysis were also utilized to analyze independent factors associated with prognosis. Gene set enrichment analysis was conducted to find the signaling pathways of PON1 in KIRC. Finally, we also investigated whether PON1 had relationship with immunity. Results: As shown in results, PON1 expression was decreased in KIRC compared with adjacent paracancer tissues. Immunohistochemistry (IHC) was utilized to find the expression of PON1. After survival analysis, the high expression of PON1 was significantly related to overall survival (P<0.001). Univariate/Multivariate cox regression analysis both revealed that PON1 could serve as an independent prognostic factor. To analyze overall survival (OS) of patients with KIRC, nomogram was developed. GSEA revealed that PON1 was correlated with homologous recombination. Besides, PON1 had few relationships with immunity. Conclusions: Our results revealed that PON1 could serve as an independent prognostic factor for KIRC, providing a novel target for KIRC future treatments.

LAG-3 expression on peripheral blood cells identifies patients with poorer outcomes after immune checkpoint blockade

2021 ◽  
Vol 13 (608) ◽  
pp. eabf5107
Author(s):  
Ronglai Shen ◽  
Michael A. Postow ◽  
Matthew Adamow ◽  
Arshi Arora ◽  
Margaret Hannum ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Peripheral Blood ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Clinical Activity ◽  
Multiparametric Flow Cytometry ◽  
Mutation Burden ◽  
Blocking Antibodies

Immune checkpoint blocking antibodies are a cornerstone in cancer treatment; however, they benefit only a subset of patients and biomarkers to guide immune checkpoint blockade (ICB) treatment choices are lacking. We designed this study to identify blood-based correlates of clinical outcome in ICB-treated patients. We performed immune profiling of 188 ICB-treated patients with melanoma using multiparametric flow cytometry to characterize immune cells in pretreatment peripheral blood. A supervised statistical learning approach was applied to a discovery cohort to classify phenotypes and determine their association with survival and treatment response. We identified three distinct immune phenotypes (immunotypes), defined in part by the presence of a LAG-3+CD8+ T cell population. Patients with melanoma with a LAG+ immunotype had poorer outcomes after ICB with a median survival of 22.2 months compared to 75.8 months for those with the LAG− immunotype (P = 0.031). An independent cohort of 94 ICB-treated patients with urothelial carcinoma was used for validation where LAG+ immunotype was significantly associated with response (P = 0.007), survival (P < 0.001), and progression-free survival (P = 0.004). Multivariate Cox regression and stratified analyses further showed that the LAG+ immunotype was an independent marker of outcome when compared to known clinical prognostic markers and previously described markers for the clinical activity of ICB, PD-L1, and tumor mutation burden. The pretreatment peripheral blood LAG+ immunotype detects patients who are less likely to benefit from ICB and suggests a strategy for identifying actionable immune targets for further investigation.

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