Can systemic inflammation at diagnosis predict benefit from primary resection in metastatic colorectal cancer (mCRC)?

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 410-410 ◽  
Author(s):  
Ben Tran ◽  
Hui-Li Wong ◽  
Jayesh Desai ◽  
Jeanne Tie ◽  
Kathryn Maree Field ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Systemic Inflammation ◽  
De Novo ◽  
Primary Resection ◽  
Rank Test ◽  
Tumour Resection ◽  
Prognostic Impact ◽  
Neutrophil Lymphocyte Ratio ◽  
Significant Difference

410 Background: In CRC, the tumor associated immune response can manifest as, (1) a good prognostic anti-tumor local (intra-tumoral) inflammatory response; or (2) a poor prognostic tumor promoting systemic inflammatory response. As suggested for renal cancer, the survival advantage associated with primary resection in mCRC patients (pts) might relate to modification of the tumor associated immune response, through reduction in tumor bulk and the resulting reduction in tumor promoting cytokines. We examine if systemic inflammation at diagnosis predicts benefit from primary resection in mCRC. Methods: A prospectively collected multi-disciplinary CRC database was used to explore clinicopathological data from pts diagnosed with de novo mCRC from Jan 2009 to Jul 2012. Evidence of systemic inflammation was defined as serum albumin (SA) <35g/L or neutrophil-lymphocyte ratio (NLR) >4 at diagnosis. Pts with primary resection >42 days from diagnosis were excluded. Survival analyses utilised the Kaplan-Meier method and log-rank test. Results: Of 212 pts diagnosed with mCRC, 154 (72%) had de novo mCRC. 92 (60%) of these underwent primary resection, 62 (40%) had primary left in situ. SA was available in 141 pts, 71 (50%) had SA <35g/L. NLR was available in all pts, 93 (60%) had NLR >4. Primary resection was associated with superior overall survival (OS): median 32.5mo v 8.4mo (HR 0.29, p<0.001). Systemic inflammation was associated with inferior OS using either SA <35g/L (median 8.4mo v 19.8mo, HR 2.54, p<0.001) or NLR >4 (median 16.8 mo v 13.1 mo, HR 1.59, p=0.03). There was no difference in OS advantages associated with primary resection in pts with SA <35g/L (HR 0.25, p<0.001) compared to normal SA (HR 0.28, p<0.001) at diagnosis; a non significant difference was observed for NLR ≤4 (HR 0.15, p<0.001) compared to NLR >4 (HR 0.42, p=0.001). Data regarding resolution of systemic inflammation following primary resection will be presented. Conclusions: Our study confirms the OS benefit from primary resection in mCRC and the adverse prognostic impact of systemic inflammation. Based on our current data, any benefit from primary tumour resection cannot be explained by an impact on the tumor associated immune response.

Are the survival benefits associated with primary resection in de novo metastatic colorectal cancer (mCRC) mediated by reversal of systemic inflammation?

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 464-464
Author(s):  
Phillip V. Tran ◽  
Mathu Samanthaby ◽  
Hui-li Wong ◽  
Jayesh Desai ◽  
Jeanne Tie ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Primary Tumor ◽  
De Novo ◽  
Tumor Resection ◽  
Primary Resection ◽  
Primary Tumors ◽  
Axial Diameter ◽  
Neutrophil Lymphocyte Ratio ◽  
Metastatic Burden ◽  
Tumour Bulk

464 Background: Despite reported survival benefits for primary tumor resection in de novo mCRC, its use remains controversial, particularly as the biological explanation remains unclear. We explored whether reversal of systemic inflammation, a marker of a tumor-promoting immune response and poor prognosis, is associated with improved survival in pts undergoing primary resection. Methods: We identified pts who underwent primary resection for de novo mCRC from a prospective CRC database, excluding pts who had metastatectomy. Neutrophil-lymphocyte ratio (NLR) was used to represent systemic inflammation. Survival differences associated with reversal of systemic inflammation, as defined by NLR falling from an elevated level (> 5) at diagnosis to ≤ 5 postoperatively, were examined. Associations between falling NLR and primary tumor bulk (maximal length assessed by pathologist) as well as metastatic burden (maximal axial diameter of largest metastasis assessed by radiologist) were explored. Results: Baseline and postoperative NLR were examined in 156 pts with median age 69y and median overall survival (OS) 18.3 mo. Baseline NLR was elevated in 66 (42%) pts; primary resection resulted in falling NLR in 37 of these pts (56%). Compared to pts with persistent NLR >5, a falling NLR was significantly associated with improved OS (HR 0.53, p = 0.012). Falling NLR was also associated with larger primary tumors, although this was not significant (median length 55mm vs. 45mm, p = 0.059). In a preliminary analysis of 26 pts with retrievable radiology, falling NLR was associated with lower metastatic burden compared to an unchanged NLR (median diameter 29mm vs. 41mm, p = 0.046). Conclusions: Our data demonstrates improved OS in pts who have reversal of systemic inflammation following primary resection in de novo mCRC. The possible associations between reversed systemic inflammation with larger primary tumors or a lower metastatic burden suggest an immune mediated response to reduced tumour bulk as an explanation for the reported survival advantage associated with primary resection. If confirmed, this might define a subgroup of pts who might benefit most from primary resection.

scholarly journals The influence of sepsis as a complication after trauma on immune response to injury

2011 ◽  
Vol 139 (3-4) ◽  
pp. 179-184
Author(s):  
Maja Surbatovic ◽  
Darko Mirkovic ◽  
Sonja Radakovic ◽  
Miodrag Jevtic ◽  
Nikola Filipovic
Keyword(s):  
Immune Response ◽  
Mortality Rate ◽  
Inflammatory Response ◽  
Proinflammatory Cytokine ◽  
Inflammatory Cytokine ◽  
Elisa Test ◽  
Sepsis Group ◽  
Blood Samples ◽  
Significant Difference ◽  
Anti Inflammatory Cytokine

Introduction. Mortality rate in trauma complicated with sepsis is exceeding 50%. Outcome is not determined only by infection or trauma, but also by the intensity of immuno-inflammatory response. Objective. The aim of this study was to determine the influence of sepsis on the immuno-inflammatory response, in the group of 35 traumatized men, of which in 25 cases trauma was complicated with sepsis. Methods. Cytokines were measured by ELISA test in plasma. Blood samples were drown on the first, third and fifth day after ICU admission. Results. Proinflammatory cytokine IL-8 was 230-fold higher in trauma + sepsis group (1148.48 vs. 5.05 pg/ml; p<0.01), and anti- inflammatory cytokine IL-1ra was 4-fold higher (1138.3 vs. 310.05 pg/ml; p<0.01), whereas IL-12 and IL-4 showed no significant difference between the groups. Conclusion. We concluded that sepsis, as a complication after trauma, drastically enhances immuno-inflammatory response to insult, as indicated by IL-8 and IL-1ra, but not IL-12 and IL-4.

scholarly journals 2,2’4,4’-Tetrabromodiphenyl Ether (PBDE-47) Modulates the Intracellular miRNA Profile, sEV Biogenesis and Their miRNA Cargo Exacerbating the LPS-Induced Pro-Inflammatory Response in THP-1 Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Valeria Longo ◽  
Alessandra Longo ◽  
Giorgia Adamo ◽  
Antonino Fiannaca ◽  
Sabrina Picciotto ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Innate Immune Response ◽  
De Novo ◽  
In Silico Analysis ◽  
Innate Immune ◽  
Macrophage Cell ◽  
Intracellular Expression ◽  
Different Levels ◽  
Silico Analysis

The 2,2’4,4’-tetrabromodiphenyl ether (PBDE-47) is one of the most prominent PBDE congeners detected in the environment and in animal and human tissues. Animal model experiments suggested the occurrence of PBDE-induced immunotoxicity leading to different outcomes and recently we demonstrated that this substance can impair macrophage and basophil activities. In this manuscript, we decided to further examine the effects induced by PBDE-47 treatment on innate immune response by looking at the intracellular expression profile of miRNAs as well as the biogenesis, cargo content and activity of human M(LPS) macrophage cell-derived small extracellular vesicles (sEVs). Microarray and in silico analysis demonstrated that PBDE-47 can induce some epigenetic effects in M(LPS) THP-1 cells modulating the expression of a set of intracellular miRNAs involved in biological pathways regulating the expression of estrogen-mediated signaling and immune responses with particular reference to M1/M2 differentiation. In addition to the cell-intrinsic modulation of intracellular miRNAs, we demonstrated that PBDE-47 could also interfere with the biogenesis of sEVs increasing their number and selecting a de novo population of sEVs. Moreover, PBDE-47 induced the overload of specific immune related miRNAs in PBDE-47 derived sEVs. Finally, culture experiments with naïve M(LPS) macrophages demonstrated that purified PBDE-47 derived sEVs can modulate macrophage immune response exacerbating the LPS-induced pro-inflammatory response inducing the overexpression of the IL-6 and the MMP9 genes. Data from this study demonstrated that PBDE-47 can perturb the innate immune response at different levels modulating the intracellular expression of miRNAs but also interfering with the biogenesis, cargo content and functional activity of M(LPS) macrophage cell-derived sEVs.

The IC50 Assay Is Predictive of Molecular Response, and Indicative of Optimal Dose in De-Novo CML Patients.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1109-1109
Author(s):  
Deborah L White ◽  
Verity A Saunders ◽  
Thea Kalebic ◽  
Timothy P Hughes
Keyword(s):  
De Novo ◽  
Statistical Significance ◽  
Continuous Variable ◽  
Rank Test ◽  
P Value ◽  
Molecular Response ◽  
Optimization Strategy ◽  
Log Reduction ◽  
Significant Difference ◽  
The Impact

Abstract We have previously demonstrated significant interpatient variability in the IC50imatinib, a measure of the intrinsic sensitivity of a patient to imatinib induced kinase inhibition. Furthermore, this measure is predictive of the achievement of major molecular response (MMR &gt; 3 log reduction in BCR-ABL) in de-novo CML patients treated with imatinib (n=60)1. In an expanded patient pool (n=116) we now perform an evaluation of the IC50 as a predictor of response, and address the IC50imatinib as a guide to dose selection. Samples were obtained with informed consent from de novo CML patients enrolled to either the TIDEL (600mg imatinib) or TOPS (randomised 400mg vs 800mg imatinib) trials. Blood was collected pre therapy, and the IC50 was performed as previously1. Outcome data was assessed using Kaplan Meier Analysis and the log rank test was used to assess statistical significance. In our previous analysis the IC50imatinib was divided about the median value for the cohort (0.6μM) into low and high IC50, with a significantly greater proportion of patients with low IC50imatinib achieving MMR by 12 months. In this expanded patient pool, we confirm this finding (&lt;median of 0.7μM for this patient group) (low IC50 65% of patients achieve MMR by 12 mo vs high IC50 39% of patients p=0.014) Dividing the IC50’s into quartiles we now demonstrate that the IC50imatinib is a continuous variable with a greater proportion of patients in the lower quartile achieving MMR than those in the higher (Table 1 Total). Addressing the issue of dose we demonstrate that no patients with IC50&gt;0.95uM achieve MMR on 400mg, and that this is statistically significantly when compared to all other groups. At 600mg while there is no overall significant difference there is a statistically relevant difference between groups 1, 2 and 4 as indicated. In contrast, at 800 mg the effect of IC50imatinib is overcome. MMR by 12 months Total 400mg 600mg 800mg p value Group1 &lt;0.5μM 67% (27) 83% (12)* 50% (8)* 86% (7) 0.470 Group 2 &gt;0.5&lt;0.7μM 63% (30) 67% (6)* 53% (17)* 71% (7) 0.337 Group 3 &gt;0.7&lt;0.95μM 45% (31) 40%(5)* 30% (10) 56% (16) 0.139 Group 4&gt;0.95μM 32% (28) 0% (7)* 22% (9)* 58% (12) 0.016 P value 0.042 0.018 0.108 0.778 Table 1: Dividing the patients into quartile based on the IC50 imatinib and assessing the Impact of dose on the achievement of MMR by 12 month. *p value &lt;0.05 between groups (n). The failure to achieve a Complete Cytogenetic Response by 12 months is considered a suboptimal response. Assessing the molecular equivalent (≥2 log reduction in BCR-ABL) we demonstrate that a significantly greater proportion of patients with IC50imatinib&gt;0.7μM fail to achieve a 2 log reduction when treated with 400mg (IC50 &lt;0.7μM 11%: &gt;0.7μM 33% p=0.034), and 600mg (IC50 &lt;0.7μM 12%: &gt;0.7μM 22% p=0.036). However, there is no significant difference in the 800mg patient cohort (IC50 &lt;0.7μM 7%: &gt;0.7μM 14% p=0.79). This analysis confirms that the IC50imatinib, is predictive of imatinib response. Patients with an IC50imatinib &lt;0.7μM are likely to respond well to doses of 400mg imatinib, as suggested by evaluation of statistically relevant outcome benefit. In contrast patients with higher IC50imatinib (&gt;0.7μM) may benefit from higher dosing regimens (p=0.012). Thus, the accurate assessment of IC50imatinib could support dose optimization strategy for patients with a suboptimal response.

Observational cohort study of 1st line bevacizumab combined with chemotherapy in metastatic colorectal cancer (HGCSG0802): Sub-group analysis by the GERCOR index.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 743-743
Author(s):  
Osamu Muto ◽  
Satoshi Yuki ◽  
Tetsuhito Muranaka ◽  
Takashi Kato ◽  
Takashi Meguro ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
High Risk ◽  
Performance Status ◽  
Group Analysis ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Prognostic Impact ◽  
First Line ◽  
Significant Difference ◽  
Line Chemotherapy

743 Background: The GERCOR index based on performance status and serum LDH was reported to be useful to predict survival for patients with previously untreated mCRC. However, the validity of the GERCOR index has not been reported in patients treated with bevacizumab (Bev)-based first line chemotherapy. Methods: 115 patients with mCRC treated with Bev contained first line chemotherapy were registered from 15 centers in Japan. Univariate and multivariate analysis for overall survival (OS) were performed using patient characteristics. Survival analyses were performed with the Kaplan-Meier method, log-rank test and the Cox proportional hazards model. The analysis was also designed to determine whether the GERCOR index could be extended to progression-free survival (PFS). Results: All data were available for prognostic categorization in 108 patients. Patients with the GERCOR index of low, intermediate and high risk were 45, 57, and 6, respectively. The pts characteristics between low risk (L) and intermediate/high risk (I/H) were generally balanced except for prior colorectomy (75.6% in L, 54.0% in I/H; p = 0.027), based cytotoxic agent (oxaliplatin) (80.0% in L, 93.7% in I/H; p = 0.039), liver metastasis (53.3% in L, 79.4% in I/H; p = 0.006) and median number of metastatic organ (1 in L, 2 in I/H; p = 0.024). The distribution and median OS / PFS for the GERCOR index were as follows: L (n = 45; 29.9/10.0 months), I/H (n = 63; 17.0/8.5 months). For OS, there was significant difference between L and I/H (p = 0.003). For PFS, there was not significant difference between L and I/H (p = 0.522). In the Cox multivariate analysis, GI did not show an independent prognostic impact (L vs I/H ; HR 1.499, p = 0.120) and predictive impact (L vs I/H ; HR 0.922, p = 0.733). Conclusions: In this analysis, the GERCOR index might be neither the predictive nor prognostic factor in the bevacizumab combined first line chemotherapy for patients with mCRC.

Prognostic impact of primary tumor location in patients with metastatic colorectal cancer (mCRC) at the salvage lines.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 741-741 ◽  
Author(s):  
Tomoyuki Nagaoka ◽  
Takeru Wakatsuki ◽  
Eiji Shinozaki ◽  
Izuma Nakayama ◽  
Mitsukuni Suenaga ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Tumor Location ◽  
Clinical Impact ◽  
Rank Test ◽  
Test Time ◽  
Prognostic Impact ◽  
Front Line ◽  
Primary Tumor Location ◽  
Significant Difference ◽  
Line Chemotherapy

741 Background: Recently it has been suggested that primary tumor location may have a clinical impact on the front line chemotherapies; namely, right-sided tumor benefit less from cytotoxic and targeted agents compared with left-sided tumor. Regorafenib and TAS 102 have recently emerged and the prognostic impacts of tumor location on these agents are unknown. Methods: Clinical information of patients who were administrated Regorafenib and/or TAS 102 was retrospectively collected. Patients’ demographics by tumor location were compared using Fisher’s exact test. Time to treatment failure (TTF), and overall survival (OS) by tumor location were calculated using Kaplan-Meyer Methods and compared using Log-rank test. In addition, subgroup analyses were performed to see the interactions between tumor location and covariates in each agent. All tests were performed at the two-sided .05 significance level. Results: The median TTF (mTTF) and OS (mOS) were 2.0 and 8.0 months in the regorafenib group (n = 98) and were 2.4 and 7.9 months in the TAS102 group (n = 95), respectively. In the regorafenib group, 71 patients had a left-sided tumor and 27 patients had a right-sided tumor. In the TAS102 group, 64 patients had a left-sided and 31 patients had a right-sided tumor. There was no significant difference between right and left sides in both groups with the exception that a greater number of older patients was seen in right-sided in the TAS102 group. No significant difference of TTF and OS by primary site were observed in regorafenib (HR 0.92, 95% CI 0.68-1.70, P = 0.71 for TTF, HR 1.09, 95% CI 0.68-1.81, P = 0.74 for OS) and in TAS 102 (HR 0.84, 95%CI 0.53-1.36, P = 0.48 for TTF, HR 1.26, 95% CI 0.72-2.33 P = 0.43 for OS). Significant interactions were shown between presence of liver metastasis and tumor location both in TTF and OS in regorafenib (p < 0.05). On the other hand, in TAS102, significant interactions were shown between period from 1st line chemotherapy and tumor location in TTF and between time to metastasis and tumor location in OS (p < 0.05). Conclusions: In contrast to front line chemotherapy, no clinical impact of tumor location was demonstrated at the salvage lines in mCRC.

scholarly journals The Effect of Remote Ischaemic Preconditioning on the Immune Response

2021 ◽  
Author(s):  
◽  
Jennifer Mae Williams-Spence
Keyword(s):  
Immune Response ◽  
Cardiac Surgery ◽  
Immune System ◽  
Inflammatory Response ◽  
Direct Effect ◽  
Peripheral Blood ◽  
Serum Levels ◽  
Ischaemic Preconditioning ◽  
Significant Difference ◽  
Remote Ischaemic Preconditioning

<p>Remote ischaemic preconditioning (RIPC) describes the phenomenon where brief intermittent periods of limb ischaemia are used to protect the heart and other organs from subsequent prolonged ischaemic insults. RIPC has been identified as a promising intervention for use during cardiac surgery and has consistently shown a beneficial effect in animal models; however, the results of early clinical trials have not been as successful. The exact mechanisms involved in mediating RIPC have not yet been characterised and a better understanding of the pathways through which RIPC exerts its protective effects will be essential in order to progress the translation of this intervention into the clinical setting. There is increasing evidence that RIPC modifies the inflammatory response, therefore the central aim of the research presented in this thesis was to investigate how RIPC affects the human immune system.  We performed a double-blind randomised controlled trial of RIPC in 96 high-risk cardiac surgery patients and found no evidence that the intervention reduced myocardial injury or altered peri-operative expression levels of the key inflammatory cytokines, interleukin (IL)-6, IL-8, and IL-10, during simple or more complex procedures. There was a trend towards higher levels of IL-6 and IL-8 in the preconditioned patients; however, confounding variables in the trial design and the heterogeneous patient population limited our ability to interpret the results.  We next conducted a paired-analysis trial with 10 healthy male volunteers to assess the direct effect of preconditioning on the early immune response, away from any form of ischaemic injury or comorbidities. We found that RIPC directly and significantly decreased serum levels of the chemokines MIP-1α and MIP-1β, but did not increase the serum concentrations of a range of key cytokines or alter the cytokine producing potential of peripheral blood leukocytes. These findings strongly suggest that a cytokine is not likely to be the humoral mediator associated with transmitting the RIPC protective signal.  RIPC did not alter the immunophenotype or extravasation of peripheral leukocyte populations, or the proliferative and cytokine responses of peripheral blood mononuclear cells (PBMC) to pharmacological, physiological, and antigen-specific stimuli. However, preconditioning did appear to reduce the ability of monocytes and neutrophils to respond to activation signals, as indicated by lower levels of CD11b expression in stimulated cultures, and a significant increase in the basal production of IL-22 was also detected in PBMC cultured for 6 days following preconditioning. These alterations may reduce neutrophil and monocyte tissue infiltration and limit the inflammatory response during the early window of RIPC-induced protection and enhance tissue and wound repair several days later. A multivariate analysis confirmed that there was a significant difference in the response between the control and RIPC treatments and the main contributing factors were identified as changes in neutrophil and T cell activation, serum levels of MIP-1α and β, and production of IL-10 and IL-22 from PBMC cultured for 6 days.  Overall, our results suggest that RIPC has a subtle but direct effect on the systemic innate immune response during the early window of protection in healthy volunteers, whereas the effects on the adaptive immune system seem to be considerably delayed. The changes detected following RIPC are likely to contribute to protection against ischaemia-reperfusion injury but not solely account for the extent of the beneficial effects of RIPC detected in animals. Our findings reinforce the safety profile of this intervention and have defined a number of immune parameters that are altered by preconditioning for focusing future research.</p>

scholarly journals Prognostic Impact of Postoperative Systemic Inflammatory Response in Patients with Stage II/III Gastric Cancer

2021 ◽  
Author(s):  
Kenji Kuroda ◽  
Takahiro Toyokawa ◽  
Yuichiro Miki ◽  
Mami Yoshii ◽  
Tatsuro Tamura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Inflammatory Response ◽  
Systemic Inflammation ◽  
Early Phase ◽  
Prognostic Significance ◽  
Infectious Complications ◽  
Systemic Inflammatory Response ◽  
Stage Ii ◽  
Prognostic Impact ◽  
Maximum Serum

Abstract Background: Several studies have shown that postoperative infectious complications correlate with poor prognosis in various malignancies, but the prognostic significance of the postoperative inflammatory response in patients with gastric cancer remains unclear. This study examined whether the systemic inflammatory response present in the early phase of the postoperative state correlates with long-term outcomes and to identify markers in patients with stage II/III gastric cancer.Methods: This study retrospectively reviewed 444 consecutive patients who underwent radical gastrectomy for stage II/III gastric cancer. We evaluated maximum serum C-reactive protein (CRPmax) and white blood cell count (WBCmax), defined as the maximum serum CRP level and maximum WBC count during the interval from surgery until discharge, as systemic inflammation markers.Results: In univariate analyses, CRPmax, WBCmax and infectious complications were significantly associated with both overall survival (OS) (p<0.001, p<0.001 and p=0.011, respectively) and relapse-free survival (RFS) (p<0.001, p=0.001 and p<0.001, respectively). Multivariate analysis revealed that high-CRPmax (>9.2 mg/dL) was an independent prognostic factor for OS (hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.18–2.42, p=0.004) and RFS (HR 1.42, 95%CI 1.02–1.98, p=0.038), while WBCmax and infectious complications were not. Conclusion: CRPmax, which reflects the magnitude of systemic inflammation induced by surgical stress and postoperative complications in the early phase after surgery, may be a promising prognostic indicator in patients with stage II/III gastric cancer who undergo curative resection.

Outcomes in AML patients age ≥70: A very large single institution experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7031-7031
Author(s):  
Jeffrey E. Lancet ◽  
Jongphil Kim ◽  
Najla Al Ali ◽  
Marina Sehovic ◽  
Tea Reljic ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Propensity Score ◽  
De Novo ◽  
Older Age ◽  
Rank Test ◽  
Term Survival ◽  
Poor Risk ◽  
Log Rank Test ◽  
Significant Difference ◽  
Ecog Ps

7031 Background: AML in older adults is associated with poor outcomes. The Moffitt Cancer Center AML Database was used to evaluate a very large cohort of patients (pts) age ≥ 70 with untreated AML to identify key prognostic variables affecting outcome. Methods: Overall survival (OS): Kaplan-Meier method and was compared across groups using the log-rank test. Association between OS and predictors: Cox regression model. Impact of participation of initial clinical trial on OS: Propensity score with stratified log-rank test. A predictive model for 12 month OS was developed using multiple logistic regression with backward elimination method. Results: Nine hundred eighty (980) pts were identified. M/F(%): 66/34. Median age at diagnosis: 75.7 years (range 70 – 95.7 years). De novo/secondary (%): 43/57. Fifty two % of pts had prior hematologic disease (AHD). Baseline karyotype at AML diagnosis: adverse in 31% and non-adverse in 58%. Baseline ECOG PS: 0-1 in 79%; ≥2 in 19%. Median OS was 7.1 months (95% CI 6.4 – 7.9) for the entire cohort. In the univariable model, factors associated with inferior survival included: secondary AML (sAML) status, poor-risk karyotype, ECOG ≥2, non HMA therapy (including clinical trials), Charlson Comorbidity Index ≥3, older age, increased WBC, decreased platelets (plts), and decreased hemoglobin (hgb). Independent negative predictors for OS in the multivariate model included sAML, poor-risk karyotype, ECOG ≥2, non-HMA initial therapy, older age, increased WBC, decreased plts, and decreased hgb. Propensity score matching revealed no significant difference in OS amongst pts receiving initial treatment on a clinical trial (median 7.8 months, 95% CI 6.4 – 10.4) vs not (median 7.0 months, 95% CI 6 –7.9). A model to predict OS at 12 month was developed in a subset of 446 pts. Independent predictive variables included karyotype, ECOG PS, AML type (de novo vs sAML), age, and WBC, with AUC of 0.78, indicating strong discriminatory capacity. Conclusions: In this largest reported cohort of AML pts age ≥ 70, prognostic modeling identifies differences in longer-term survival with conventional therapies, discriminating the highest risk subsets. Decision modeling to further assist choice of optimal therapies for these pts is in progress.

Hyperprogressive disease in advanced triple-negative breast cancer (aTNBC) treated with immunotherapy (IO).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1086-1086
Author(s):  
Tira Jing Ying Tan ◽  
David W. Cescon ◽  
Lisa Wang ◽  
Eitan Amir ◽  
Daniella Vieira ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Metastatic Disease ◽  
De Novo ◽  
Performance Status ◽  
Prognostic Index ◽  
Rank Test ◽  
Tumor Growth Rate ◽  
Recist 1.1 ◽  
Co Morbidity ◽  
Significant Difference

1086 Background: Hyperprogression of disease (HPD), a rapid acceleration of tumor growth rate (TGR) has been reported with IO in other tumor types. Here, we explore HPD in aTNBC. Methods: A retrospective chart review identified aTNBC patients who consented for IO clinical trials at Princess Margaret Cancer Centre between June 2013 and June 2018. Demographic data, medical history, details of trial enrolment and RECIST 1.1 response to study treatment were recorded. Patients with RECIST 1.1 measurable disease on CT scans or physical examination before trial entry, at trial baseline and at protocol-defined interval following IO start were evaluable for TGR as defined by Champiat et al. Clin Cancer Res 2017. HPD defined as a ≥2-fold increase in TGR between baseline and on-trial restaging assessment. Univariable logistic regression used to identify variables [age, co-morbidity index, prognostic index, performance status, distant disease free interval (dDFI), lactate dehydrogenase, no. of metastatic sites, visceral disease and no. of prior treatment lines] associated with HPD. Overall survival (OS) curves were estimated with the Kaplan-Meier method and compared by the log-rank test. Results: 99 patients with aTNBC consented for 15 IO clinical trials, 60% IO monotherapy, 22% chemotherapy+/-IO and 18% IO combinations. Median age 52 (range 25-78), median no. of lines of prior systemic therapy for advanced disease 1 (range 0-8). 15% had de-novo metastatic disease, 58% recurred after a dDFI of < 3 years and 25% after a dDFI of > 3 years. 61% had < 3 metastatic disease sites, and 71% had metastases involving the viscera. 66 received IO treatment, 40 patients (20 monotherapy, 7 IO combination, 13 chemotherapy+/-IO) were evaluable for TGR. Median TGR pre-IO was 74.3 (range -17 – 1680) and post-IO was 2.5 (-71.4 – 223). 4 patients (10%) met criteria for HPD. All 4 treated with monotherapy PD1 inhibitor and received at least 2 further lines of therapy post-trial; 1 patient treated with IO as first-line therapy, 3 in the second or later lines. There was no significant difference in the overall OS of patients with HPD and patients who did not meet definition for HPD HR 0.89, (95% CI: 0.26-3.01; p = 0.41). Univariable analysis did not identify factors associated with HPD. Conclusions: HPD was observed in 10% of aTNBC treated on IO clinical trials. HPD was not associated with worse survival outcomes or known prognostic factors in our analysis.

Sign in / Sign up

Export Citation Format

Share Document