Hyper engorged cancer associated macrophage-like cells in circulation predict for multi-organ metastatic disease in solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3039-3039
Author(s):  
Daniel J Gironda ◽  
Raymond C. Bergan ◽  
Steven H. Lin ◽  
R. Katherine Alpaugh ◽  
Massimo Cristofanilli ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Metastatic Disease ◽  
Metastatic Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Strong Relationship ◽  
Tumor Burden ◽  
Multiple Organ ◽  
Organ Metastasis ◽  
Single Organ

3039 Background: Patients with multiple organ metastases have poorer prognoses than those with a single organ metastasis, are frequently associated with drug resistance, and have higher tumor burden. Engorged (≥50um) Cancer Associated Macrophage-Like Cells (CAMLs) are a circulating stromal cell subtype detected in the blood of patients with solid tumors at high risk for recurrence or progression. While numerous studies have shown that ≥50um CAMLs predict poor clinical outcomes, meta-analysis of these studies have also suggested that hyper engorged CAMLs ≥100um (heCAMLs) may be associated with multifocal metastatic disease and even worse outcomes. In this prospective study, we evaluated the presence of heCAMLs in patients with metastatic disease and demonstrated a strong relationship with multi organ spread, which also correlated with shorter Progression Free Survival (PFS) and Overall Survival (OS). Methods: We prospectively recruited 151 patients with metastatic (m) mbreast (n = 58), mlung (n = 34), mprostate (n = 39), and mrenal (n = 20) cancers. Peripheral blood was collected prior to the induction of new treatment for metastatic cancer. Cells were isolated following standard CellSieve techniques, then imaged and measured in ZenBlue. Multi organ metastasis was defined as spread to ≥2 distant organ sites, or any spread to the brain. Single factor ANOVA was conducted to compare heCAML presence in multi organ metastatic patients versus patients with single organ site metastasis. Univariate and multivariate analysis was run to evaluate for PFS and OS against heCAMLs, and all known clinical parameters. Results: 150 viable samples (excluding 1 failed sample) were obtained. Multi organ metastases were present in 55% (n = 83/150) of patients. heCAMLs were found in 59% (n = 49/83) of the multi organ metastatic population, but only in 16% (n = 11/67) of the single site metastatic cohort (p < 0.001). heCAML presence appeared to differentiate multi organ vs single organ metastases in mbreast (85% vs. 52%, p = 0.006), mlung (71% vs. 26%, p = 0.025), mprostate (75% vs. 37%, p = 0.029), and mRCC (88% vs. 36%, p = 0.025). Further, in all n = 150 patients, heCAML presence predicted a significantly shorter median PFS of 4.5 versus 7.2 months, 24 month PFS (HR = 1.67, 95%CI = 1.13-2.45, p = 0.013), and significantly shorter median OS of 13.1 versus 20.4 months, 24 month OS (HR = 2.05, 95%CI = 1.24-3.39, p = 0.008). Conclusions: We examined a non-invasive prognostic blood based assay to determine its relationship to multi organ metastatic spread as well as its prognostic value in several solid cancers. These results showed patients with heCAMLs had higher rates of multi organ metastases, and appear to predict for shorter PFS and OS. Studies of larger cohorts are needed for prospective validation of these initial findings.

scholarly journals Systematic Review and Meta-Analysis of Correlation of Progression-Free Survival-2 and Overall Survival in Solid Tumors

2020 ◽  
Vol 10 ◽  
Author(s):  
Simon Chowdhury ◽  
Paul Mainwaring ◽  
Liangcai Zhang ◽  
Suneel Mundle ◽  
Eneida Pollozi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Solid Tumors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Free Survival

Efficacy, safety, tolerability and price of newly approved drugs in solid tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18336-e18336
Author(s):  
Tristan Alexandra Barnes ◽  
Eitan Amir ◽  
Arnoud J. Templeton ◽  
Susana Gomez Garcia ◽  
Beatriz Navarro ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Meta Analysis ◽  
Market Price ◽  
Progression Free Survival ◽  
Tolerability Profile ◽  
Cancer Therapies ◽  
Control Groups ◽  
Group 4 ◽  
Significant Difference ◽  
Lower Magnitude

e18336 Background: New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price. Methods: Drugs approved for the treatment of solid tumors between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes or dysregulated pathways (group 1), anti-angiogenic drugs (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the reports of randomized trials supporting registration and pooled in a meta-analysis. Odds ratios (ORs) for rates of toxic death, treatment discontinuation and grade 3-4 toxicity were compared relative to control groups. The Micromedex Red Book was used to calculate the monthly price of each agent. Results: Analysis included 74 studies comprising 48,527 patients. Progression-free survival (PFS) was improved to a lesser degree with groups 3 and 4 than with groups 1 and 2, (pooled HR:0.54, 0.56, 0.63, and 0.76 for groups 1–4 respectively, p for difference < 0.001). Compared to PFS, there was a lower magnitude of improvement overall survival in all groups and the degree of benefit was less for group 4 than for other groups (pooled HR:0.77, 0.78, 0.68, and 0.83 for groups 1–4 respectively, p for difference = 0.007). Compared to control groups in individual trials, immunotherapy was associated with better safety and tolerability than other groups. Drug prices have increased over time with no statistically significant difference between groups. There was limited to no correlation between drug pricing and efficacy. Conclusions: Compared to control groups, chemotherapy improves efficacy to a lesser degree than the other groups. Immunotherapy appears to have better safety and tolerability profile compared to other cancer therapies. Market price of drugs is not related to efficacy.

Immunotherapy with checkpoint inhibitors in mismatch repair deficient (dMMR) cancers: Looking for a needle in a haystack— But, joy on finding one.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14073-e14073
Author(s):  
Amit Rauthan ◽  
Poonam Patil ◽  
Tanvi Sood ◽  
Shriniwas Subhash Kulkarni ◽  
Nitin Yashas ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Solid Tumors ◽  
Checkpoint Inhibitors ◽  
Metastatic Cancer ◽  
Objective Response ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Cost Effective ◽  
Limited Data ◽  
Deficient Mismatch Repair

e14073 Background: Pembrolizumab is approved for deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) metastatic solid tumors with objective response rate (ORR) of 39.6% and response lasting for more than 6 months in 78% patients. Nivolumab is also approved in dMMR metastatic colorectal cancers (mCRC) with ORR of 28% and response lasting greater than 6 months in 67% patients. But finding these patients is difficult as only about 5% of metastatic cancers have dMMR. There is limited data from India in this population. We report our experience with testing and treatment in these patients. Methods: This is a single centre, retrospective study of metastatic solid tumors which had progressed on standard treatment. 137 patients were tested between May 2017 and Dec 2018. MMR testing was done by immunohistochemistry (IHC). The aim was to identify patients with dMMR; and to see their ORR, progression free survival (PFS) at 1 year, and adverse events on treatment with Nivolumab. Results: 137 metastatic cancer patients were tested. 75 had colorectal cancer (mCRC), 30 gastric, 10 hepatobiliary, 10 pancreatic, 8 endometrial, 2 small bowel cancer and 2 had breast cancer. 15 (11%) patients had dMMR. 3 (37%) of endometrium, 5 (16.6%) of stomach, 6 (8%) of mCRC and 1(10%) of hepatobiliary tree cancer had dMMR. 5 of the 15 dMMR patients received immunotherapy with Nivolumab - 2 in mCRC, 2 in stomach and 1 in endometrium. ORR was 60% with 3 partial responses, stable disease was seen in 1 (20%) and progression in 1 (20%). PFS at 1 year was 80%. Treatment was well tolerated.1 patient had hypothyroidism and 1 patient had grade 1 skin toxicity. Conclusions: Testing for dMMR is important in metastatic solid tumors as these patients are ideal for treatment with immunotherapy. But finding dMMR is difficult due to its infrequent presentation, and has been seen in 11% of our unselected patients. We recommend testing for dMMR by IHC in our Indian patients, as this is fast and cost effective. Finding dMMR cancers, and then treating with immunotherapy is rewarding irrespective of the site of origin. High ORR of 60% and 1 year PFS of 80% is very heartening to see in this relapsed metastatic patient group. Treating more dMMR patients and longer followup, will further elucidate the benefit of immunotherapy in our patients.

scholarly journals Prognostic role of pretreatment blood lymphocyte count in patients with solid tumors: a systematic review and meta-analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiawen Zhao ◽  
Weijia Huang ◽  
Yongxian Wu ◽  
Yihuan Luo ◽  
Bo Wu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Solid Tumors ◽  
Clinical Outcomes ◽  
Lymphocyte Count ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Cancer Type ◽  
Hazard Ratios

Abstract Background To evaluate the prognostic value of pretreatment lymphocyte counts with respect to clinical outcomes in patients with solid tumors. Methods Systematic literature search of electronic databases (Pubmed, Embase and Web of Science) up to May 1, 2018 was carried out by two independent reviewers. We included Eligible studies assessed the prognostic impact of pretreatment lymphocytes and had reported hazard ratios (HR) with 95% confidence intervals (CIs) for endpoints including overall survival (OS) and progression-free survival (PFS). Only English publications were included. Results A total of 42 studies comprising 13,272 patients were included in this systematic review and meta-analysis. Low pretreatment lymphocyte count was associated with poor OS (HR = 1.27, 95% CI 1.16–1.39, P < 0.001, I2 = 58.5%) and PFS (HR = 1.27, 95% CI 1.15–1.40, P < 0.001, I2 = 25.7%). Subgroup analysis disaggregated by cancer type indicated that low pretreatment lymphocytes were most closely associated with poor OS in colorectal cancer followed by breast cancer and renal cancer. Conclusions Low pretreatment lymphocyte count may represent an unfavorable prognostic factor for clinical outcomes in patients with solid tumors.

scholarly journals Prognostic Role of Pretreatment Plasma D-Dimer in Patients with Solid Tumors: a Systematic Review and Meta-Analysis

2018 ◽  
Vol 45 (4) ◽  
pp. 1663-1676 ◽  
Author(s):  
Wenhan Li ◽  
Yao Tang ◽  
Yongchun Song ◽  
Szu Hao Chen ◽  
Navard Sisliyan ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Prognostic Indicator ◽  
High Plasma ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Comprehensive Search ◽  
D Dimer

Background/Aims: Elevated pretreatment plasma D-dimer level has been reported as an unfavorable prognostic indicator in several malignancies. The aim of this meta-analysis was to evaluate the prognostic value of elevated D-dimer level in solid tumors. Methods: A comprehensive search of electronic databases up to June 10, 2017 was carried out by two independent reviewers. We included studies exploring the association between pretreatment plasma D-dimer level and patients’ survival outcomes in solid tumors. Overall survival (OS) was regarded as primary outcome and progression-free survival (PFS), disease-free survival (DFS) as well as cancer-specific survival (CSS) were chosen as secondary outcomes. Hazard ratio and 95% confidence interval (CI) were extracted directly or indirectly from included studies. Results: 49 studies with 13001 patients were included in our meta-analysis. Elevated D-dimer was markedly associated with poor OS (pooled HR = 1.90, 95% CI = 1.63 - 2.20, P < 0.001). The effect was observed in all different tumor sites, disease stages, cut-off values and ethnicities. Meanwhile, patients with a high plasma D-dimer had a shorter PFS (HR = 1.46, 95% CI = 1.22–1.76; P < 0.001), DFS (HR = 2.02, 95% CI = 1.56–2.62) and CSS (HR = 2.04, 95% CI= 1.58 – 2.64). Conclusions: Analysis of the pretreatment plasma D-dimer might provide useful information to predict prognosis in patients with solid tumors.

Prognostic value of programmed death-ligand 1 in solid tumors: A meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19121-e19121
Author(s):  
Jordan L Scott ◽  
Michelle Nadler ◽  
Alexandra Desnoyers ◽  
Fahad Almugbel ◽  
Rouhi Fazelzad ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Solid Tumors ◽  
Early Stage ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Significant Heterogeneity ◽  
Prognostic Impact ◽  
Stage Of Disease ◽  
Programmed Cell Death 1

e19121 Background: The programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway plays a crucial role in cancer immuno-surveillance and is the target of approved immunotherapeutic drugs. Available data suggest a variable prognostic impact of PD-L1 expression in solid tumors. Methods: A systematic literature search of electronic databases identified publications exploring the effect of PD-L1 on overall survival (OS) and/or progression-free survival (PFS). Hazard ratios (HR) were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on disease site, stage of disease, and method of PD-L1 quantification using the Deeks method. Results: One hundred eighty-eight studies comprised of 212,748 patients met the inclusion criteria. PD-L1 expression was associated with worse OS (HR 1.32, 95% confidence interval (CI) 1.25 - 1.38; P < 0.001). There was significant heterogeneity between disease sites (subgroup P = 0.002) with pancreatic, hepatocellular and genitourinary cancers being associated with the highest magnitude of adverse outcome (Table). PD-L1 was also associated with worse overall PFS (HR 1.19, 95% CI 1.09 - 1.30; P < 0.001). Stage of disease did not significantly affect the results (subgroup P = 0.52), nor did the method of quantification (immunohistochemistry or mRNA) (subgroup P = 0.70). Conclusions: High expression of PD-L1 is associated with worse cancer outcomes albeit with significant heterogeneity between disease sites. The effect seems consistent in early stage and metastatic disease and is not sensitive to method of PD-L1 quantification. [Table: see text]

scholarly journals The Efficacy and Safety of PD-1/PD-L1 Inhibitors in Combination with Conventional Therapies for Advanced Solid Tumors: A Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Run-Cong Nie ◽  
Chong-Bang Zhao ◽  
Xiao-Wei Xia ◽  
Ying-Shan Luo ◽  
Ting Wu ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Sensitivity Analyses ◽  
Cochrane Library ◽  
High Grade ◽  
Advanced Solid Tumors ◽  
Free Survival ◽  
Hazard Ratios ◽  
Programmed Cell Death 1

Objectives. To evaluate the efficacy of immuno-oncology combinational therapy (IOCT) versus monotherapy with programmed cell death 1 (PD-1) or PD-ligand 1 (PD-L1) inhibitors or conventional therapies, i.e., non-IOCT, in patients with advanced solid tumors. Methods. We systematically searched the PubMed, Embase, and Cochrane Library databases from January 2015 to October 2018 for eligible studies. We included randomized trials of IOCT with available hazard ratios (HR) for death. The random effects model was used to calculate pooled HR for death; heterogeneity was assessed using I2 statistics. The main outcome measure was overall survival (OS). Results. After screening 483 relevant articles, we identified twelve trials comprising 5388 patients for quantitative analysis. IOCT-treated patients had significantly higher tumor response rate (relative risk (RR): 2.51, 95% confidence interval (CI): 1.82-3.47), prolonged progression-free survival (HR 0.62, 95% CI: 0.53-0.74), and OS (HR 0.69, 95% CI: 0.61-0.78), compared with non-IOCT–treated patients. Sensitivity analyses also demonstrated the OS advantage of IOCT across different combination modalities, intervention agents, malignancy types, and PD-L1 expression (all P<0.05). Notably, there were higher odds of high-grade (grade≥3) adverse events with IOCT (RR: 1.81, 95% CI: 1.13-2.90), but the risk of treatment-related death (RR: 1.16, 95% CI: 0.84–1.60) was not increased compared with non-IOCT. Conclusions. IOCT is a preferable treatment option over PD-1/PD-L1 inhibitor monotherapy and conventional therapy for patients with advanced solid tumors. However, we should note the increased incidence rate of high-grade AEs in IOCT.

scholarly journals Clinical Outcomes and Efficacy of Stereotactic Body Radiation Therapy in Children, Adolescents, and Young Adults with Metastatic Solid Tumors

2021 ◽  
Author(s):  
Sujith Baliga ◽  
Jennifer Matsui ◽  
Brett Klamer ◽  
Ashley Cetnar ◽  
Ashlee Ewing ◽  
...  
Keyword(s):  
Overall Survival ◽  
Solid Tumors ◽  
Metastatic Disease ◽  
Cumulative Incidence ◽  
Pediatric Patients ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Local Failure ◽  
Poor Overall Survival ◽  
Metastatic Sites

Purpose Pediatric patients with metastatic solid tumors historically have a poor overall survival. Some pediatric patients may still be potentially curable with aggressive local therapy to metastatic disease. The purpose of this study is to report results of the use of SBRT in the treatment of pediatric metastatic disease. Materials and Methods Pediatric patients who received SBRT between the years 2000-2020. Study endpoints included local control (LC), progression free survival (PFS), overall survival (OS), cumulative incidence (CI) of death or local failure and toxicity. The endpoints with respect to survival and LC were calculated using the Kaplan-Meier estimate. The cumulative incidence of local failure was calculated using death as a competing risk. Results 16 patients with 36 lesions irradiated met inclusion criteria. The median OS and PFS was 17 months and 15.7 months, respectively. The 1-year OS was 75%. The 6- and 12-month LC was 85% and 78%, respectively. There were no local failures in lesions receving a BED10≥100 Gy. Patients who had ≤5 metastatic lesions at first recurrence had a superior 1-year OS of 100% versus 50% with >5 lesions. One patient (6.3%) experienced a grade 3 CNS toxicity. Conclusions LC was excellent with SBRT delivered to metastatic disease, particularly for lesions receiving a BED10≥100 Gy. High-grade toxicity was rare in our patient population. Patients with ≤5 metastatic sites have a significantly better OS compared to >5 sites. Future prospective trials with multi-institutional collaboration will be necessary to evaluate appropriate patient selection and the optimal radiation dose regimen.

Hyperglycemia and survival in solid tumors: A systematic review and meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18158-e18158
Author(s):  
Reeta Barua ◽  
Arnoud J. Templeton ◽  
Bostjan Seruga ◽  
Alberto Ocana ◽  
Eitan Amir ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Solid Tumors ◽  
Statistical Tests ◽  
Meta Analysis ◽  
Fasting Blood Glucose ◽  
Progression Free Survival ◽  
Tumor Stage ◽  
P Value ◽  
Diabetes Status ◽  
Meta Regression

e18158 Background: Diabetes is associated with adverse cancer outcomes. However, the effect of hyperglycemia independent of diabetes is unclear. Here we report on a meta-analysis exploring the effect of hyperglycemia on outcomes of solid tumors, and the influence of clinical factors on this association. Methods: A systematic search of electronic databases identified publications exploring the effect of hyperglycemia on overall (OS), disease-free (DFS) or progression-free survival (PFS). Definitions of hyperglycemia (fasting blood glucose, random blood glucose or HbA1c) and cut-offs varied between studies. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) or a p -value were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on method of hyperglycemia measurement (HbA1c, other) and tumor stage (early, advanced, mixed). Meta-regression was performed to evaluate the influence of clinical characteristics including baseline diabetes status on the HR for OS. All statistical tests were two-sided. Results: Eight studies comprising a total of 4342 patients were included. All studies reported HRs for OS. Two studies reported DFS outcomes, and two reported PFS. Hyperglycemia was associated with worse OS (HR 2.07, 95% CI = 1.70 - 2.52; P < 0.001) and DFS (HR 1.61, 95% CI = 1.04 - 2.49; P < 0.001), but did not decrease PFS (HR 1.08, 95% CI = 0.72 - 1.62; P = 0.71). The association with worse OS maintained in subgroups based on method of hyperglycemia measurement (subgroup difference P = 0.65) and tumor stage ( P= 0.47). Meta-regression analyses did not identify any factors significantly altering the magnitude of association between hyperglycemia and OS (see Table). Conclusions: Hyperglycemia is associated with adverse OS and DFS in patients with cancer, and the therapeutic role of optimal glycemic control warrants further investigation. [Table: see text]

scholarly journals Prognostic Role of TIGIT Expression in Patients with Solid Tumors: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Kunmin Xiao ◽  
Kunlin Xiao ◽  
Kexin Li ◽  
Peng Xue ◽  
Shijie Zhu
Keyword(s):  
Solid Tumors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cancer Type ◽  
Free Survival ◽  
Analysis Methods ◽  
Newcastle Ottawa Scale ◽  
Ottawa Scale

Background. T cell immunoglobulin and ITIM domain (TIGIT) is a recently identified immunosuppressive receptor. The expression levels of TIGIT affect the prognosis of patients with solid tumors. To fully comprehend the role of TIGIT on the prognosis of patients with solid tumors, we conducted a meta-analysis. Methods. We performed an online search of PubMed, Embase, Web of Science (WOS), and MEDLINE databases for literature published till March 31, 2021. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the literature, and Stata 16.0 and Engauge Digitizer 4.1 software were used for data analysis. Results. Our literature search identified eight papers comprising 1426 patients with solid tumors. Increased expression of TIGIT was associated with poor prognosis. High expression of TIGIT was a risk factor for overall survival (OS) { hazard   ratio   HR = 1.66 , 95% confidence interval (CI) [1.26, 2.20], P < 0.001 } and progression-free survival (PFS) ( HR = 1.44 , 95% CI [1.15, 1.81], P = 0.01 ). We performed subgroup analysis to explore the source of heterogeneity, colorectal cancer ( HR = 2.07 , 95% CI [0.23, 18.82], P = 0.518 ), lung cancer ( HR = 1.29 , 95% CI [0.96, 1.72], P = 0.094 ), esophageal cancer ( HR = 1.70 , 95% CI [1.20, 2.40], P = 0.003 ), and other cancers ( HR = 1.83 , 95% CI [1.25, 2.68], P = 0.002 ). In addition to cancer type, expression location, sample size, and different statistical analysis methods are also considered the possible causes of heterogeneity between studies. Funnel plots suggested no publication bias for OS ( P = 0.902 ), and Egger’s test supported this conclusion ( P = 0.537 ). Conclusion. TIGIT expression was associated with OS and PFS in patients with solid tumors. Patients with elevated TIGIT expression have a shorter OS and PFS, and TIGIT expression could be a novel biomarker for prognosis prediction and a valuable therapeutic target for solid tumors.

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