Pdl-1/pdl-3 (programmed death ligand-1/3) tissue expression and response to treatment with IL2 and antiangiogenic therapies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4521-4521 ◽  
Author(s):  
Alexandra S. Bailey ◽  
SuChun Cheng ◽  
Eugene D. Kwon ◽  
Bradley C. Leibovich ◽  
Sabina Signoretti ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Tissue Expression ◽  
Current Data ◽  
Response To Treatment ◽  
Antiangiogenic Therapies ◽  
Programmed Death ◽  
Immune Therapies ◽  
Aggressive Histology ◽  
Select Trial ◽  
Background Expression

4521 Background: Expression of PDL1 by RCC has been associated with aggressive histology and poor survival. Tissue obtained from the patients enrolled in the IL-2 Select Trial, a prospective, single arm, multicenter CWG study, was analyzed by IHC to determine if PDL1or PDL3 expression predicted for response to initial or subsequent therapy. Methods: Paraffin embedded tumor tissue was stained for PDL1 and PDL3 expression, and results were correlated with RECIST defined response to IL2 treatment. Tumor tissue was considered positive for PDL1 if >5% of the tumor membranes stained for the marker. A cutoff of 10% was used for PDL3. Duration of subsequent VEGFR/mTOR inhibitor therapy was also correlated with tissue PDL1/3 expression. Results: 120 eligible pts were enrolled; 115 had clear cell histology. The overall response rate (ORR) to IL2 was 25% (30/120) with a median OS of 40.6 months. 113 tumors were stained. 18 (16%) were PDL1+. ORR was 19% and 50% in the patients PDL1- and PDL1+ tumors, respectively (p=0.012). 85 (75%) tumors were PDL3+. ORR was 10.7% and 29.4% in the PDL3- and PDL3+ tumors, respectively (p=0.075). In the 17 patients who were positive for both PDL1 and PDL3, ORR was 52.9%. In the 27 pts who were negative for both PDL1 and PDL3, ORR was 11.1%. 69 patients received at least 1 dose of a VEGFR TKI as next therapy following IL2 treatment. 66 tumors were stained. Pts who were PDL1+/PDL3+ had a shorter duration on VEGFR TKI therapy compared to pts who were PDL1-/PDL3- (see Table). Conclusions: This small, retrospective analysis suggests that PDL1 and PDL3 tissue expression may predict for better response to IL2. PDL1 expression has been suggested as a possible predictor of response to anti-PD1 therapy. The current data suggests that its expression may predict for benefit to other immune therapies. PDL3 (+/- PDL1) expression appears to correlate to less benefit from subsequent VEGFR TKI therapy. Funded by NCI SPORE Grant # 5 P50 CA101942-08. [Table: see text]

Melanoma: Prognostic Factors and Factors Predictive of Response to Therapy

2020 ◽  
Vol 27 (17) ◽  
pp. 2792-2813
Author(s):  
Martina Strudel ◽  
Lucia Festino ◽  
Vito Vanella ◽  
Massimiliano Beretta ◽  
Francesco M. Marincola ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Lactate Dehydrogenase ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Elevated Serum ◽  
Predictive Biomarkers ◽  
Response To Therapy ◽  
Response To Treatment ◽  
Prognostic Features ◽  
Programmed Death

Background: A better understanding of prognostic factors and biomarkers that predict response to treatment is required in order to further improve survival rates in patients with melanoma. Predictive Biomarkers: The most important histopathological factors prognostic of worse outcomes in melanoma are sentinel lymph node involvement, increased tumor thickness, ulceration and higher mitotic rate. Poorer survival may also be related to several clinical factors, including male gender, older age, axial location of the melanoma, elevated serum levels of lactate dehydrogenase and S100B. Predictive Biomarkers: Several biomarkers have been investigated as being predictive of response to melanoma therapies. For anti-Programmed Death-1(PD-1)/Programmed Death-Ligand 1 (PD-L1) checkpoint inhibitors, PD-L1 tumor expression was initially proposed to have a predictive role in response to anti-PD-1/PD-L1 treatment. However, patients without PD-L1 expression also have a survival benefit with anti-PD-1/PD-L1 therapy, meaning it cannot be used alone to select patients for treatment, in order to affirm that it could be considered a correlative, but not a predictive marker. A range of other factors have shown an association with treatment outcomes and offer potential as predictive biomarkers for immunotherapy, including immune infiltration, chemokine signatures, and tumor mutational load. However, none of these have been clinically validated as a factor for patient selection. For combined targeted therapy (BRAF and MEK inhibition), lactate dehydrogenase level and tumor burden seem to have a role in patient outcomes. Conclusions: With increasing knowledge, the understanding of melanoma stage-specific prognostic features should further improve. Moreover, ongoing trials should provide increasing evidence on the best use of biomarkers to help select the most appropriate patients for tailored treatment with immunotherapies and targeted therapies.

Evaluation of CD44 and CD44v6 in Colorectal Carcinoma Patients: Soluble Forms in Relation to Tumor Tissue Expression and Metastasis

2008 ◽  
Vol 39 (1-4) ◽  
pp. 73-78 ◽  
Author(s):  
Zahra Amirghofran ◽  
Seyed Amir Jalali ◽  
Seyed Vahid Hosseini ◽  
Mohammad Vasei ◽  
Behnam Sabayan ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Tumor Tissue ◽  
Tissue Expression

Value and Limitations of Measuring HER-2 Extracellular Domain in the Serum of Breast Cancer Patients

2009 ◽  
Vol 27 (10) ◽  
pp. 1694-1705 ◽  
Author(s):  
Alexandra F. Leary ◽  
Wedad M. Hanna ◽  
Marc J. van de Vijver ◽  
Frederique Penault-Llorca ◽  
Josef Rüschoff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Tissue ◽  
Extracellular Domain ◽  
Prognostic Indicator ◽  
Early Recurrence ◽  
Response To Treatment ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her 2 ◽  
American Society

The human epidermal receptor-2 (HER-2) is overexpressed or amplified in 15% to 25% of breast cancers. Determination of HER-2 tumor status offers clinically useful information, as it selects patients who may benefit from treatment with trastuzumab, the monoclonal antibody against HER-2. Currently approved methods for HER-2 testing include immunohistochemistry or fluorescent in situ hybridization using tumor tissue. A fragment of HER-2 composed of its extracellular domain (ECD) can also be detected in the serum of some patients with breast cancer. As an easily accessible tumor marker, it could offer additional useful prognostic or predictive information. This review will briefly address the biology of the circulating HER-2 ECD and discuss the evidence to support the role, if any, for measuring HER-2 ECD levels in women with breast cancer. In particular, we focus on the value and limitations of serum ECD in both early and advanced breast cancer in the following clinical contexts: as a marker of HER-2 tumor tissue status; clinical implications of raised levels in women who have a tumor not overexpressing HER-2; as a prognostic indicator and as a predictor of response to treatment; and as a monitoring tool for early recurrence. On the basis of our review of the literature, we conclude that there is currently insufficient evidence to support the use of serum HER-2 ECD in the routine management of individual patients with breast cancer. This conclusion is in agreement with the 2007 American Society of Clinical Oncology guidelines on the use of biomarkers in breast cancer.

scholarly journals Major hyperghrelinemia in advanced well-differentiated neuroendocrine carcinomas: report of three cases

2009 ◽  
Vol 161 (4) ◽  
pp. 639-645 ◽  
Author(s):  
Thomas Walter ◽  
Laurence Chardon ◽  
Valérie Hervieu ◽  
Richard Cohen ◽  
Jean-Alain Chayvialle ◽  
...  
Keyword(s):  
Tumor Tissue ◽  
Tissue Expression ◽  
Primary Tumors ◽  
Disease Characteristics ◽  
Total Ghrelin ◽  
Functional Consequences ◽  
Acyl Ghrelin ◽  
Well Differentiated ◽  
Serum Ghrelin ◽  
Neuroendocrine Carcinomas

ObjectiveWe aimed to gain insight into the functional consequences of ghrelin overproduction in patients with neuroendocrine tumors and its relations with disease characteristics and evolution.DesignWe retrospectively analyzed three cases of neuroendocrine carcinomas associated with very high levels of circulating ghrelin.MethodsBetween February and October 2007, serum ghrelin levels were determined in all patients with well-differentiated endocrine carcinoma referred to our center (n=72). Three patients were found to have circulating ghrelin levels >10-fold the upper limit of normal. The clinical, biochemical, and pathological characteristics of these three patients were reviewed. The ratio between circulating acyl and total ghrelin was determined, and tumor tissue expression of ghrelin was assayed by immunohistochemistry.ResultsThe three patients had massive hyperghrelinemia (respectively 49 028, 63 711, and 101 996 pg/ml), with <10% of acyl ghrelin. The corresponding primary tumors were located in the pancreas, rectum, and gallbladder; all were metastatic. There was no acromegaly; there was a decrease in appetite; and body mass index was low. Serum GH levels were only slightly increased and serum IGF1 levels were normal. Immunoreactive ghrelin was detected in the tumor tissue in the two cases in which tissue material was available. All three patients died before 12 months after the diagnosis of hyperghrelinemia.ConclusionWell-differentiated neuroendocrine carcinomas of various origins may produce markedly high levels of circulating ghrelin, without evidence of clinical or functional consequences.

The significance of p53 and Ki-67 expression rate in adenoma and adenocarcinoma of the stomach.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 32-32
Author(s):  
I. Baek
Keyword(s):  
Gastric Cancer ◽  
Early Gastric Cancer ◽  
Tumor Tissue ◽  
Subtotal Gastrectomy ◽  
Tissue Expression ◽  
Endoscopic Biopsy ◽  
Low Grade ◽  
Gastric Adenoma ◽  
Ki 67 ◽  
Low Grade Dysplasia

32 Background: Endoscopic submucosal dissection (ESD) is used for the treatment of gastric adenoma as well as early gastric cancer. Gastric adenoma is a well-known precursor of gastric cancer. The aim of this study is to investigate the expression degree of p53 and Ki-67 in gastric adenoma can predict progression to gastric cancer. Methods: We analyzed p53 and Ki-67 expression degree in the tumor tissue of 16 gastric adenoma patients treated by ESD and 11 early gastric cancer patients treated by subtotal gastrectomy at Kangnam Sacred Heart Hospital of Hallym University between November 2008 and May 2009. According to the fraction of stained nuclei in tumor tissue, expression degree was classified as < 10% = negative, 10%∼33% = 1+, 34%∼66% = 2+, > 66% = 3+. Results: Mean age was 65.1 ± 11.5 years and mean tumor size was 33.7 ± 20.2mm. Among 16 gastric adenoma patients, low-grade dysplasia were 11 and high grade dysplasia were 5. p53 positivity was not different between gastric adenoma and gastric cancer, but Ki-67 positivity was significantly different between adenoma and cancer (p < 0.05). In addition, Ki-67 positivity was increasing tendency as the pathology progress from low grade dysplasia to cancer. Conclusions: Ki-67 positivity grade seems to be correlated with malignancy. High Ki-67 positivity in gastric adenoma can predict progression to gastric cancer. Even if endoscopic biopsy showed low grade dysplasia, additional ESD should be preferentially considered in lesions with high Ki-67 positivity. No significant financial relationships to disclose.

Immunotherapy discontinuation and outcome: A multicenter real-life experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14075-e14075
Author(s):  
Maria Bassanelli ◽  
Diana Giannarelli ◽  
Maria RITA Migliorino ◽  
Marco Russano ◽  
Alain Gelibter ◽  
...  
Keyword(s):  
Advanced Cancer ◽  
Progressive Disease ◽  
Life Experience ◽  
Checkpoint Inhibitors ◽  
Real Life ◽  
Progression Free Survival ◽  
Complete Response ◽  
Response To Treatment ◽  
Best Response ◽  
Programmed Death

e14075 Background: Unlike chemotherapy, the optimum treatment duration with Immune checkpoint inhibitors (ICIs) is not clearly established. The aim of this study was to assess the outcome of patients (pts) who discontinued immune-based therapies for any reason except progressive disease. Methods: We conducted an observational, retrospective analysis of 46 consecutive pts with advanced cancer who received ICIs as clinically indicated, at eight Italian institutions. Tumor response to treatment was defined according to RECIST. Median overall survival (OS) and the 95% confidence interval (CI) were estimated with the Kaplan -Meier method. Results: 46 pts (median age 68 years [range 41-86]; male: 65.2%) with advanced cancer (n.39 non-small-cell lung cancer, n.15 renal cell carcinoma and n.2 melanoma) were treated with ICIs: 44 pts received programmed death 1 (PD-1) inhibitors (n.31 nivolumab, n.13 pembrolizumab) and 2 pts programmed death ligand 1 (PD-L1) (n.1 durvalumab, n.1 atezolizumab). A median of 8 cycles were administered [range 1 to 52]. 36 pts discontinued ICIs due to toxicities (diarrhoea, pneumonitis, hepatotoxicity) and 10 pts for reasons non immune-related. The median progression free survival (PFS) from the beginning of ICIs was 12.4 months (mo) [95% CI: 8.2-16.6] and the median OS was 20.0 mo (95% CI: 11.8-28.2). Median PFS from discontinuation of therapy was 5.0 mo [95% CI: 2.7-7.3] and median OS was 16.1 mo (95% CI: 5.4-26.8). Best response achieved according RECIST criteria were: 1 complete response (CR), 18 partial response, 21 stable disease (SD), 2 progressive disease (PR) and 3 non evaluable (NE). During interruption of ICIs 1 pts achieved a PR. Conclusions: This study shows the activity of ICIs, in terms of outcome and durable immune-response, in pts with advanced cancer even after treatment discontinuation.

Results from the safety lead-in for a phase II study of pembrolizumab in combination with binimetinib and bevacizumab in patients with refractory metastatic colorectal cancer (mCRC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4031-4031
Author(s):  
Christopher Hanyoung Lieu ◽  
Sarah Lindsey Davis ◽  
Stephen Leong ◽  
Alexis Diane Leal ◽  
Patrick Jud Blatchford ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Progression Free Survival ◽  
Median Number ◽  
Response To Treatment ◽  
Clinical Activity ◽  
Clinical Benefit Rate ◽  
T Cell Infiltration ◽  
Immune Biomarkers ◽  
Best Response ◽  
Immune Therapies

4031 Background: The majority of pts with mCRC have microsatellite stable (MSS) tumors with minimal response to PD-L1/PD-1 blockade. MEK inhibition and VEGF inhibition have immunomodulatory effects (upregulation of tumor major histocompatibility complex-I expression, enhanced T-cell infiltration, reduced MDSCs and Tregs in tumors) supporting clinical evaluation of combined MEKi (B), anti–PD-1 (P), and anti-VEGF (BV) in pts with mCRC. We hypothesize that the combination of binimetinib, pembrolizumab, and bevacizumab (BPBV) will result in greater clinical benefit than pembrolizumab alone. Methods: Patients with chemotherapy-refractory mCRC were evaluated (20 planned in the safety lead-in and 50 planned for total accrual). B was dosed at 45mg PO BID, P was administered at 200mg IV Q21 days, and BV was administered at 7.5mg/kg IV Q21 days. Primary objectives were safety, tolerability, and investigator-assessed ORR by RECIST 1.1. Clinical benefit rate (CR+PR+SD) and progression-free survival were secondary endpoints. Descriptive statistics were used to summarize safety and clinical activity. Results: As of January 9, 2020, 21 pts (10 KRAS/NRASmt, 11 RASwt, 21 MSS) were enrolled into the safety lead-in and were evaluable. The median number of prior therapies was 6. The BPBV combination was tolerable. Treatment-related Gr 1-2 and Gr 3-4 AEs occurred at 60% and 38%, respectively. The most frequent related Gr 3-4 AEs were aceniform rash, diarrhea, and hypertension (19%, 14%, 14% respectively). No treatment-related Gr 5 AEs occurred. A total of 17 patients were evaluable for response. Confirmed PR was observed in 2 pts (12%). SD was noted in 14 patients (82%) leading to a clinical benefit rate of 94%. 1 patient had PD as the best response to treatment. Median PFS was 6.4 months (95% CI 4.2-8.9). Molecular determinants, immune biomarkers, and updated tumor assessments of response will be presented. Conclusions: B + P + BV demonstrated a tolerable safety profile and improvements in ORR and clinical benefit rate compared to those reported with SOC in heavily pretreated pts with mCRC. Objective responses observed in pts were durable, suggesting benefit of this novel combination in a patient population refractory to immune therapies. Clinical trial information: NCT03475004 .

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