Markers of response to PD-1 inhibition.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14505-e14505 ◽  
Author(s):  
Thijo Jeroen Nicolaas Hiltermann ◽  
Lucie Hijmering-Kappelle ◽  
Harry J.M. Groen
Keyword(s):  
Survival Data ◽  
Lymphocyte Count ◽  
Cox Regression ◽  
Tumour Response ◽  
Absolute Lymphocyte Count ◽  
Patient Characteristics ◽  
Predictive Biomarker ◽  
Response To Treatment ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps

e14505 Background: Nivolumab (Nivo) has a durable tumour response in 20 % of patients. While a PD-L1 IHC complementary diagnostic has been approved, there is a need to identify a predictive biomarker with greater diagnostic accuracy. Serum biomarkers predicted by the cancer immunogram (Blake Science 2016) and response to Nivo defined by a clinical benefit ≥6 month (DR) and response by CR, PR or SD according to RECIST v1.1 are shown. Methods: Advanced NSCLC pts progressing after 1L platinum-based chemotherapy were treated with Nivo. Baseline blood markers drawn: CRP, absolute lymphocyte count, plasma glucose and LDH. Kaplan-Meier used to estimate survival data. Cox regression was used to predict associations with possible (bio-) markers and survival (age, gender, ECOG PS, histology, presence of brain metastasis, CRP, LDH, glucose, lymphocyte count). Results: Patient characteristics see table. 20% showed a DR with CR (n = 3), PR (n = 31 of 33) and SD (n = 9 of 20). Only ECOG PS was associated with OS and PFS. Soluble biomarkers were not. When tumour response (RECIST or DR) was added to the regression model ECOG PS was no longer significant but responses were. HR for PFS for DR was 0.07 (0.03-0.14) and HR according to the classical RECIST1.1 was 0.22 (0.16-0.32). HR for OS for DR 0.09 (0.03-0.21) and for classical RECIST1.1 0.26 (0.17-0.40). Conclusions: Serum blood markers at baseline were not associated with survival. Response to treatment as DR seems a stronger predictor for survival than RECIST. 45% of pts with SD had a DR. [Table: see text]

SIGNIFICANCE of ABSOLUTE LYMPHOCYTE COUNT at RELAPSE as a PROGNOSTIC FACTOR in PATIENTS with T-CELL NON-HODGKIN'S LYMPHOMA.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2939-2939
Author(s):  
Dae Ro Choi ◽  
Dok Hyun Yoon ◽  
Heui June Ahn ◽  
Yoojin Cho ◽  
Eun Kyoung Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Lymphocyte Count ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
Absolute Lymphocyte Count ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
First Relapse ◽  
Ecog Ps

Abstract Abstract 2939 Poster Board II-915 Introduction: Peripheral blood absolute lymphocyte count (ALC) at the time of diagnosis is a prognostic indicator in hematologic malignancies. However, no reports have addressed whether ALC at the time of first relapse (ALC-R) has a prognostic significance in the patients with relapsed T-cell Non-Hodgkin's lymphoma (NHL). We retrospectively studied the prognostic significance of ALC-R in these patients. Patients and Methods: We identified 63 patients who had a documented relapsed disease after having reached a complete response, including at least an unconfirmed complete response between 1993 and 2007 and we analyzed their ALC-R and following variables at the time of first relapse; age, gender, the number of extranodal sites, lactate dehydrogenase, ECOG performance status, stage and international prognostic index. Results: Out of the 63 patients, 23 (36.5%) had a peripheral T-cell lymphoma, not otherwise characterized, while 15 (23.8%) had an extranodal NK/T-cell lymphoma, nasal type, 6 (9.5%) anaplastic large-cell lymphoma, 5 (7.9%) angioimmunoblastic T-cell lymphoma, 2 (3.2%) primary cutaneous T cell lymphoma and 12 (19%) other types. Among them, 32 (50.8%) had an ALC-R ≥ 1.25 × 109/L, 47 (74.6%) had an ECOG PS 0 or 1 and by IPI at relapse, 0, 1, 2, 3, 4, and 5 were 20.6%, 25.4%, 23.8%, 23.8%, 4.8%, and 1.6%, respectively. Univariate analyses showed that good ECOG PS (HR, 0.408; 95% CI 0.190-0.876; p=0.022) and high ALC at relapse (HR, 0.394; 95% CI 0.210-0.740; p=0.004) were associated with longer survival from relapse (Table 1). Multivariate analysis also showed that high ALC at relapse (HR, 0.369; 95% CI 0.187-0.726; p=0.004) and good ECOG PS (HR, 0.295; 95% CI 0.131-0.666; p=0.003) were still associated with longer survival outcome (Table 2). Conclusions: The high ALC-R predicted a better prognosis in patients with relapsed T-cell NHL, suggesting that the host immune system might have a crucial role. Disclosures: No relevant conflicts of interest to declare.

Survival of advanced melanoma patients with normal LDH treated with oblimersen, temozolomide, and nab-paclitaxel

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9080-9080
Author(s):  
A. C. Pavlick ◽  
P. Ott ◽  
J. Escalon ◽  
K. Madden ◽  
E. Yepes ◽  
...  
Keyword(s):  
Survival Data ◽  
Caspase 3 ◽  
Subcutaneous Tissue ◽  
Tumor Biology ◽  
Metastatic Tumor ◽  
Advanced Melanoma ◽  
Response To Treatment ◽  
Antisense Therapy ◽  
Melanoma Patients ◽  
Ecog Ps

9080 Background: Oblimersen (OBL), temozolomide (TMZ), and abraxane (ABX) act synergistically in preclinical studies with melanoma cell lines. Bcl-2 antisense therapy in combination with dacarbazine was encouraging in advanced melanoma patients(pts) with normal LDH. Methods: Chemotherapy-naïve advanced melanoma pts (ECOG PS ≤ 2, baseline LDH ≤1.1 × ULN, measurable disease per RECIST) were enrolled on a phase I/II protocol. The treatment regimen consisted of 56-day cycles of OBL (7 mg/kg/d continuous IV infusion, d 1–7 and 22–28), TMZ (75 mg/m2/d, d 1–42), and ABX (175 mg/m2 in Cohort 1, 260 mg/m2 in Cohort 2, d 7 and 28). Immunohistochemical (IHC) staining for Bcl-2, Bcl-XL, BAK and caspase 3 was performed in pre- and post-therapy tumor samples. Serum shed collagen cryptic epitope levels were monitored. Results: 18 pts were treated (Cohort 1 = 14 pts [1–6 cycles];Cohort 2 = 4 pts [2–3 cycles]). Median age was 58 years (range: 34–78). Disease sites included liver (6), other visceral sites (10), skin, subcutaneous tissue, and lymph nodes (2). The overall survival (OS) was 14.7 months and showed a trend towards superiority when compared to both arms of the prior oblimersen trial (DTIC, OS 9.7 months, p = 0.078 and DTIC-OBL, OS 11.4 months, p = 0.31) in pts with the same LDH cut-off (Bedikian et al. JCO. 2006). 50% of pts survived > 1 year. One CR lasted 25+ mo, five PR (>50% tumor reduction) lasted > 2 cycles, and 7 SD lasted > 3 cycles. Five PD after 1 cycle were seen. One ocular melanoma pt survived 15 mo despite PD. Shed cryptic epitopes correlated with clinical response versus disease progression. Alteration of the tumor biology based on phenotypic changes in Bcl-2, Bcl-xL, BAK and caspase 3 correlated with response to treatment. Conclusions: Our data suggest that the combination of OBL, TMZ, and ABX is synergistic in advanced melanoma pts with normal LDH, possibly translating into improved OS compared to prior regimens with dacarbazine ± OBL. Biomarker studies support the rationale that Bcl-2 antisense therapy specifically impacts apoptotic signaling pathways in melanoma cells from metastatic tumor. The survival data in the limited number of pts enrolled in cohort 1 and 2 of this trial are encouraging; further exploration with this combination is underway using 1-hour infusions of OBL. No significant financial relationships to disclose.

High baseline lymphocyte count is a predictive biomarker of prolonged time to progression in patients with advanced solid tumors receiving checkpoint inhibitors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14532-e14532
Author(s):  
Mariangela Maltese ◽  
Stefano Panni ◽  
Silvia Lazzarelli ◽  
Matteo Brighenti ◽  
Federica Negri ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Lymphocyte Count ◽  
Checkpoint Inhibitors ◽  
Absolute Lymphocyte Count ◽  
Predictive Biomarker ◽  
Rank Test ◽  
Advanced Solid Tumors ◽  
Time To Progression ◽  
Neutrophil Lymphocyte Ratio ◽  
Kaplan Meier

e14532 Background: Biomarkers predicting response to checkpoint inhibitor are needed to better select patients most likely to benefit from treatment. We observed that baseline absolute lymphocyte count (ALC) can predict durable responses to anti-PD-1 antibodies in various malignancies. Methods: This is a retrospective analysis of patients with advanced solid tumors treated with anti-PD-1 antibodies. Pembrolizumab was given at 2 mg/kg every 3 weeks, Nivolumab at 3 mg/kg every 2 weeks. Peripheral ALC and absolute neutrophil count (ANC) from routine safety labs were collected at baseline, cycle 4 and cycle 8. Evaluation of response was based on irRECIST. Neutrophil lymphocyte ratio [NLR = ANC/ALC] was stratified by ≤4 or > 4. The lymphocyte count cutoff was 1000/mm3. Time to progression (TTP) and overall survival (OS) were estimated with the Kaplan-Meier method. Differences between groups were estimated with the log rank test. Results: We have retrospectively evaluated 40 patients with unresectable stage III/IV Non Small Cell Lung Cancer (squamous n. 17; 42.5%, adenocarcinoma n. 7; 17.5%), Malignant Melanoma (n.11; 27.5%), Renal Cell Carcinoma (n.5; 12.5%) treated with anti-PD-1 antibodies. 6 pts (15%) received treatment as 1st line, 14 pts (35%) as 2nd line, 20 pts (15%) as ≥ 3rd line. We observed a 29% partial response (PR), 31% stable disease (SD) and 40% progressive disease (PD). The overall response rate (ORR) was 29% [I.C. 95% 13-42]. Median TTP was 5.5 months [IC 95% 3.3-NR]. Median OS was not reached. Pts with baseline ALC ≥1000/mm3 had significantly longer TTP (median value not reached), compared with those who had ALC < 1000/mm3 (median TTP 2.8 months), p = 0.01. There was also a trend for longer TTP in patients with NLR < 4 vs ≥4 (4.9 vs 10.5 months, p 0.44). Conclusions: In our observation baseline ALC ≥1000/mm3 is a predictive biomarker of prolonged TTP in patients treated with anti-PD-1 antibodies. The potential predictive value of this test should be prospectively validated.

MACC1 expression as a candidate prognostic biomarker in colorectal cancer patients receiving adjuvant oxaliplatin-based therapy.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 567-567 ◽  
Author(s):  
Lynn Katherine Symonds ◽  
Kelsey K. Baker ◽  
Mary Weber Redman ◽  
Lisa Koch ◽  
Kelly Carter ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Patient Characteristics ◽  
Hazard Ratios ◽  
Platinum Based Chemotherapy ◽  
Tumor Mutational Burden ◽  
Colorectal Cancer Patients

567 Background: MACC1, part of the HGF-MET pathway, drives proliferation and regulation of MET expression in vitro. In vivo, MACC1 is associated with tumor progression and studies suggest greater MACC1 expression is associated with resistance to platinum-based chemotherapy. We hypothesized that MACC1 may be a prognostic biomarker in colorectal cancer (CRC). Methods: MACC1 expression was evaluated by immunohistochemistry on tumor microarrays (N = 428). Patients were stage I-III CRC who received an oxaliplatin-based regimen (either with 5-FU (FOLFOX) or capecitabine (XELOX)) within the HeCOG 6C/08 observational study. MACC1 expression was assessed by a blinded GI pathologist using a scale ranging from 0 (no staining) to 3+ (strong expression). Each patient had at least 3 samples and the strongest result was used for the final score. MACC1 positivity was defined as ≥2+ expression and 0-1+ as MACC1-. Cox regression models were used to estimate hazard ratios (HR) for the association of MACC1 expression with patient characteristics, disease-free (DFS), and overall survival (OS). Results: 400/428 CRC tumors were evaluable: 322 (80.5%) were MACC1+ and 78 (19.5%) MACC1-. Mucinous features were less likely in MACC1+ patients (24% vs. 38%, p = 0.02). Other unfavorable features including grade, lymphovascular invasion, perineural invasion, and tumor mutational burden were not significantly different. There was no difference for stage, microsatellite instability, BRAF, KRAS, or NRASstatus between MACC1+/- cancers. There was a trend towards worse survival in MACC1+ patients regardless of treatment (DFS HR 1.55 [95% CI: 0.87, 2.76], OS HR 1.59 [95% CI 0.74, 3.4]). This difference was not statistically significant for OS (p = 0.26) or DFS (p = 0.08) even when stratified by clinicopathologic variables. Conclusions: Patients with MACC1+ CRC tumors who received adjuvant oxaliplatin-based therapy were less likely to have mucinous histology. They had a trend toward independently worse survival that was not significant when accounting for stage and clinicopathologic variables. Studies focused on the predictive role of MACC1 and oxaliplatin in stage III CRC are in progress.

Evaluation of the absolute lymphocyte count as a biomarker for melanoma patients treated with the commercially available dose of ipilimumab (3mg/kg).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8575-8575 ◽  
Author(s):  
Michael Andrew Postow ◽  
Jianda Yuan ◽  
Katherine Panageas ◽  
Kita Bogatch ◽  
Margaret Callahan ◽  
...  
Keyword(s):  
Survival Data ◽  
Lymphocyte Count ◽  
Preliminary Finding ◽  
Absolute Lymphocyte Count ◽  
Phase Iii ◽  
Cancer Center ◽  
Karnofsky Performance Score ◽  
Phase Iii Trials ◽  
Pre Treatment

8575 Background: Ipilimumab (ipi) has demonstrated an overall survival (OS) benefit in 2 phase III trials. Only ~30% of patients (pts) achieve clinical benefit, and factors that determine which pts benefit are unclear. For pts treated with 10mg/kg of ipi, we previously reported that an absolute lymphocyte count (ALC) ≥1000/μL prior to dose 3 [week (wk) 7] was associated with improved OS. Since the mean increase in ALC during ipi treatment correlates with dose, we investigated if ALC is also associated with improved OS at 3mg/kg, the currently FDA approved, commercially available dose. Methods: In an IRB-approved analysis, we evaluated landmark survival data from 137 pts treated with 3mg/kg of ipi at Memorial Sloan-Kettering Cancer Center. 67 pts were treated on an expanded access protocol (CA 184-045). 70 pts were treated per FDA approval (commercial ipi) with 4 standard induction doses. These 2 groups were analyzed separately because some pts in CA 184-045 received re-induction ipi. ALC was determined at first ipi dose (baseline, wk 1) and at subsequent doses (wks 4, 7, and 10). Results: Pts treated with 3mg/kg on CA 184-045 with a wk 7 (prior to dose 3) ALC ≥1000/µL had significantly improved OS compared to pts with an ALC at wk 7 <1000/μL (Median OS: not reached vs. 4.24 mos, p<0.001). This OS difference was also seen for pts treated with commercial ipi (Median OS: not reached vs. 4.44 mos, p<0.01). This difference remained significant in a multivariable model accounting for Karnofsky performance score, LDH, M-stage, and number of prior therapies for pts in the CA 184-045 group and commercial ipi group (p=0.01 and p=0.05, respectively). Baseline ALC ≥1000/µL was associated with improved OS (p=0.02) for pts in the commercial ipi group, though follow-up is limited. Conclusions: At the FDA approved dose of ipi, 3mg/kg, ALC at wk 7 remains significantly associated with improved OS. Our preliminary finding of improved OS for pts treated with commercial ipi whose pre-treatment baseline ALC ≥1000/µL deserves confirmation with longer follow-up and prospective validation. Baseline or on treatment ALC may be a marker of overall prognosis, regardless of therapy.

SLFN11 expression (exp) in castration-resistant prostate cancer (CRPC) patients (pts) to predict response to platinum-based chemotherapy (PLT).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5065-5065
Author(s):  
Vincenza Conteduca ◽  
Loredana Puca ◽  
Sheng-Yu Ku ◽  
Judy Hess ◽  
Megan Kearney ◽  
...  
Keyword(s):  
Cox Regression ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Median Number ◽  
Parp Inhibitors ◽  
Castration Resistant Prostate Cancer ◽  
Cox Regression Analysis ◽  
Platinum Based Chemotherapy

5065 Background: Schlafen family member 11 (SLFN11) sensitizes tumor cells to DNA-damaging agents and has been investigated as a potential predictive biomarker of response to PLT and PARP inhibitors, especially in small cell lung cancer (Lok, CCR 2017; Pietanza, JCO 2018). We aimed to explore the predictive/prognostic role of SLFN11 in PLT-treated CRPC. Methods: We assessed tumor exp of SLFN11 in PLT-treated, metastatic CRPC pts by RNAseq (N=27) and/or CTCs (N=20) (via the Epic Sciences platform). In addition, tumor morphology for neuroendocrine (NE) features and genomic status of select genes (ie, AR, TP53, RB1, BRCA2, BRCA1, ATM) by whole exome sequencing were evaluated. Statistical comparisons used Cox regression analysis and Kaplan Meier method for the association with overall/radiographic progression free survival (OS/rPFS). A dose response curve with PLT was performed in patient-derived organoids using Cell Title Glo according to the manufacturer’s protocol. Results: 41 CRPC (including 20 CRPC-NE) treated with PLT monotherapy (N=3) or PLT combination therapy (N=38) between August 2013 and December 2017 were evaluated. Median age was 67.1 years (range 51-91). Median number of prior therapies was 2 (range 1-7). A longer median rPFS was observed in all SLFN11+ pts treated with PLT (regardless of histology, RB1, TP53, PTEN, or DNA repair status) compared to SLFN11- [5.2 vs 2.3 months, HR 3.5, 95%CI 1.6-7.7, P<0.0001]. No association was reported for OS. On multivariable analysis (Table), SLFN11 was an independent factor associated with rPFS. Organoids derived from patient tumors expressing SLFN11 showed sensitivity to PLT in vitro. Conclusions: SLFN11 exp identifies both CRPC and CRPC-NE pts with a better response to PLT. Patient-derived organoids expressing SLFN11 confirmed increased sensitivity to PLT. Larger prospective evaluation of therapy decisions based on SLFN11 exp is now required. [Table: see text]

scholarly journals Comparative Analysis of Acral Melanoma in Chinese and Caucasian Patients

2020 ◽  
Author(s):  
Kai Huang ◽  
Yu Xu ◽  
Emmanuel M. Gabriel ◽  
Subhasis Misra ◽  
Yong Chen ◽  
...  
Keyword(s):  
Survival Data ◽  
Cox Regression ◽  
Patient Characteristics ◽  
Chinese Patients ◽  
Cancer Center ◽  
Cox Regression Analysis ◽  
Acral Melanoma ◽  
Significant Difference ◽  
Positive Rate ◽  
Caucasian Patients

Abstract Background Acral melanoma is the most common subtype of melanoma in Chinese patients and one of the least common in Caucasian patients. It has been unclear if outcomes differ between Chinese and Caucasian patients diagnosed with Acral Melanoma. This study investigated patient characteristics and survival differences between Chinese and Caucasian Acral Melanoma patients. Methods Two large institutional melanoma databases from Fudan University Shanghai Cancer Center (FUSCC) and Mayo Clinic enterprise, were retrospectively reviewed from 2009 to 2015. Clinicopathologic and survival data were collected and analyzed between the two groups. The primary outcome was disease-specific survival (DSS) and was calculated using the Kaplan Meier (KM) method. Results The Chinese group presented with more advanced disease compared with Caucasians: thicker Breslow depth (median 3.0 mm vs. 1.2 mm, p=0.003), more ulcerated disease (66.1% vs 29%; p<0.001), and advanced stages (stage II/III 84.3% vs. 37.1%; p<0.001). No significant difference was identified in terms of age at diagnosis, location, histologic subtypes, or node positive rate. The 5-year DSS rate was 68.4% and 73% (p=0.56) for Chinese and Caucasians, respectively. Male gender, Breslow thickness, ulceration, and positive sentinel lymph nodes predicted worse DSS on multivariate Cox regression analysis. Conclusions There appears to be no difference in stage-stratified survival between Chinese and Caucasians, supporting the implementation of clinical trials of AM that could include both Chinese and Caucasian patients.

The predictive role of plasma mutant allele fraction to antiangiogenic drugs in patients with mCRC: An expanded analysis of surrogate biomarkers of response to first-line treatment with bevacizumab.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3541-3541
Author(s):  
Giulia Martini ◽  
Elena Elez ◽  
Francesco M Mancuso ◽  
Maria Auxiliadora Gomez ◽  
Ginevra Caratu ◽  
...  
Keyword(s):  
Survival Data ◽  
Mutant Allele ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Digital Pcr ◽  
Score Distribution ◽  
Treatment Benefit ◽  
Clinicopathological Variables ◽  
Allele Fraction

3541 Background: So far, no biomarkers of response to anti-angiogenic drugs are available in colorectal cancer (CRC) treatment. Liquid biopsy tracks dynamic mutational changes in CRC patients (pts). RAS mutant allele fraction in plasma (plMAF) is an independent prognostic marker in metastatic CRC (mCRC). We explored the predictive value of plMAF in RAS mutant pts treated in 1st line with chemotherapy +/- bevacizumab (bev). Methods: A multicentric prospective/retrospective analysis was conducted. We collected data from 226 mCRC pts and selected the subset not eligible for metastasis resection with basal plMAF sample evaluable for RAS mutant MAF quantification with digital PCR (BEAMing). Pts were stratified as high (≥ 5.8%) or low ( < 5.8%) plMAF. We investigated associations between clinicopathological variables and progression-free survival (PFS) stratified by plMAF RAS levels using Cox regression models and survival data were calculated by Kaplan-Meier method. Computational analysis of baseline CT scan data extracted 93 radiomics features of all the lesions per patient including 1) 1st class from density histogram distribution and texture analysis by 2) 2nd order and 3) higher order feature classes. The radiomic features distribution between pts with high and low pIMAF was assessed with Student’s t-test analysis. Results: From October 17 to May 19, 63 basal plasma samples were analysed with BEAMing. 42 pts (67.7%) were classified as high and 21 pts (32,3%) as low plMAF. In high plMAF subgroup, a statistically significant longer PFS favouring FOLFOX+bev was observed, compared to FOLFOX alone (10.7 vs 6.9 mts; HR: 0.30; p = 0.002). In low RAS plMAF subgroup, no differences in terms of PFS were observed in either arm (8.9 vs 8.7 mts; HR: 0.7; p = 0.6). Multivariate PFS model showed no association between RAS plMAF and clinicopathological variables, except for high RAS plMAF and treatment benefit with FOLFOX+bev. The CT-radiomics signature, that may translate tumor vascularization, differentiated patients with high vs low pIMAF (p = 0.002). 58 patients (92%) had similar radiomic score; 5 patients with high plMAF (8%) presented very heterogeneous radiomic score distribution. Conclusions: Tumor-borne RAS plMAFs may constitute a potential predictive biomarker of efficacy for anti-angiogenic drugs in mCRC. Next steps will include the identification of -histological, transcriptomic and radiomic- surrogate biomarkers of response that reflect tumor irrigational status.

83 The prognostic significance of peripheral blood biomarkers in patients with advanced non-small cell lung cancer treated with pembrolizumab: a clinical study

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A91-A91
Author(s):  
Kira MacDougall ◽  
Muhammad Niazi ◽  
Jeff Hosry ◽  
Sylvester Homsy ◽  
Alexander Bershadskiy
Keyword(s):  
Peripheral Blood ◽  
Lymphocyte Count ◽  
Advanced Nsclc ◽  
Cox Regression ◽  
Absolute Lymphocyte Count ◽  
Blood Biomarkers ◽  
Cox Regression Analysis ◽  
Start Date ◽  
Kaplan Meier ◽  
Significant Difference

BackgroundPembrolizumab is an anti-programmed cell death protein 1 (PD-1) antibody used for the treatment of advanced non-small cell lung carcinoma (NSCLC). Systemic inflammation has long been associated with poor outcomes in many types of solid tumors.1 Peripheral blood biomarkers such as absolute lymphocyte count (ALC) and absolute neutrophil count to absolute lymphocyte count ratio (ANC/ALC) serve as surrogate markers of inflammation. The aim of this study is to investigate ALC and ANC/ALC in patients with advanced NSCLC receiving pembrolizumab and determine if there is a correlation between these biomarkers and overall survival (OS).MethodsA total of 240 patients with advanced NSCLC treated with pembrolizumab at Northwell Health hospital centers were included. The ALC and ANC/ALC were examined at initiation of pembrolizumab and after 6 weeks on treatment. The prognostic role of these peripheral blood biomarkers on OS were examined with Kaplan-Meier curves and a multivariable cox regression analysis.ResultsOf the 240 patients, the majority were male (52%), with a median age of 67 years (interquartile range [IQR] 59–73 years), had a diagnosis of adenocarcinoma (76%), with stage IV disease (82%). PDL-1 expression was >50% in 44% of the patients. The median time on treatment with pembrolizumab was 5.7 months [IQR: 2.7–12.5]. The median ALC and ANC/ALC were significantly lower at 6 weeks of pembrolizumab compared to the start date of treatment (1.38 vs. 1.4, p<0.001) and (3.6 vs. 4.6, p<0.001) respectively. An ALC greater than 1.4 was associated with an increased OS (figure 1), at 6 weeks after initiation of pembrolizumab (p=0.046), but not at the start of treatment (p=0.095). An ANC/ALC less than 5 was associated with improved OS (figure 2), both at initiation of pembrolizumab (p=0.003) and at 6 weeks after initiation of treatment (p = 0.028). Likewise, after adjusting for potential cofounders with a multivariate analysis (table 1), a baseline ANC/ALC of 5 or higher had a significantly increased risk of death (hazards ratio (HR)=1.84; 95% confidence interval (CI), 1.21–2.79; p=0.004), compared with patients with a lower ratio.ConclusionsHigh ALC at time of diagnosis as well as low ANC/ALC at baseline and at 6 weeks on treatment correlated with an increased OS in patients with advanced NSCLC treated with pembrolizumab. These findings represent a readily available predictive biomarker for oncologists and may help with risk stratification and strategizing treatment plans.Abstract 83 Figure 1Kaplan-Meier survival estimates between groups with different ALC at the start date of pembrolizumab and at 6 weeks after initiation of pembrolizumab. There is a statistically significant difference in OS between patients with ALC < 1.4 and patients with ALC ≥ 1.4 at 6 weeks after initiation of pembrolizumab (p = 0.046), but not at the start of treatment (p = 0.095).Abstract 83 Figure 2Kaplan-Meier survival estimates between groups with different ANC/ALC ratio at the start date of pembrolizumab and at 6 weeks after initiation of pembrolizumab. There is a statistically significant difference in OS between patients with ANC/ALC < 5 and patients with ALC ≥ 5, both at the start date of pembrolizumab (p = 0.003) and at 6 weeks after initiation of pembrolizumab (p = 0.028).Abstract 83 Table 1Multivariable cox regression analysis for association of baseline peripheral blood biomarkers and overall survival.Legend: HR, hazards ratio; CI, confidence interval; CNS, central nervous system, ANC/ALC, absolute neutrophil count to absolute lymphocyte count ratio; PDL-1, programmed death-1 ligand 1; ECOG, Eastern Cooperative Oncology Group performance scale.Ethics ApprovalThe study was approved by Zucker School of Medicine at Hofstra/Northwell at Staten Island University Hospital’s IRB #: 19–0922ReferenceMantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.

scholarly journals Upregulation of Twist2 in Non-Muscle Invasive Urothelial Carcinoma of the Bladder Correlate with Response to Treatment and Progression

2018 ◽  
Vol 6 (6) ◽  
pp. 1017-1022 ◽  
Author(s):  
Mohamed Wishahi ◽  
Heba Khalil ◽  
Mohamed H. Badawy ◽  
Amr Elkholy ◽  
Khaled Eseily ◽  
...  
Keyword(s):  
Cox Regression ◽  
Tumour Response ◽  
Initial Diagnosis ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Bcg Therapy ◽  
Muscle Invasive

BACKGROUND: Twist2 is a transcription factor and an epithelial-to-mesenchymal transition that plays an important role in cell polarity, cell adhesion, and has a role in tumour invasion and metastases.AIM: In this study, we examined the expression of Twist2 in non-muscle invasive bladder carcinoma (NMIBC) and correlated the expression with response to treatment and tumour progression.METHODS: Data of 305 patients with NMIBC of Ta, T1 were retrieved from hospitals archives. Twist2 expression was examined in tissue samples by immunohistochemistry at initial diagnosis and final follow-up, normal control was 10 normal urothelium, 10 patients with muscle-invasive bladder cancer (MIBC) were a positive control. Treatment of NMIBC was implemented according to the European Association of Urology guidelines on NMIBC. The descriptive statistical analysis included means, standard deviation, p-value; Univariate and multivariate Cox regression analyses.RESULTS: Twist2 expression score was identified as negative, low (1-15%); medium (15-40%); and high (40-100%). Patients who had low or low medium scores at the initial diagnosis had a good response and a favourable prognosis. Expression of a high score of Twist2 in patients having high-grade T1 tumours showed non-responsiveness to repeated courses of intravesical bacillus Calmette Guerin (BCG) therapy and was upstaged to MIBC.CONCLUSION: Twist2 expression in tissue samples of NMIBC would indicate the tumour response to therapy, upgrading and upstaging in the follow up after intravesical BCG therapy.

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